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For the proper functioning of the Immunohematology Area, an External Quality Control was established since 1973 through a program that evaluates the performance of the laboratories of the Blood Bank and transfusion services that carry out immunohematology tests. This program consists of sending panel cells to participating blood banks or services, which are phenotyped erythrocyte samples previously studied as problem cases but whose results are unknown by the participating laboratories. The processes in which the program is of most importance are determination of the ABO group, determination of Rh, performance of the direct and indirect Coombs test, and pre-transfusion compatibility tests. It was carried out an observational and retrospective study of the results obtained in the 2020 period from 104 units participating in the Immunohematology Quality Control Program of the National Medical Center's Blood Bank. A panel of cells was sent for external quality control of immunohematology every 45 days, resulting in 9 panels for each unit in the studied period. Compliance with the program was observed in the general result (79.6%), i.e., there was a decrease in the participation of the registered units. Of a maximum score of 100% to be obtained, it was observed a general result of 95.3% compliance of the participating units. The results obtained confirm the good general training of the immunohematology laboratories of the participating units. Yet, as in any external control program, it becomes clear that obtaining an erroneous result is a risk that can occur in any laboratory.Para el buen funcionamiento del Área de Inmunohematología, desde 1973 se instauró el Control de Calidad Externo con un programa que evalúa los laboratorios del Banco de Sangre y los servicios de transfusión que hacen pruebas de inmunohematología. El programa consiste en enviar a los bancos de sangre, o servicios participantes, células panel, que son muestras de eritrocitos fenotipados y previamente estudiados como casos problema, pero cuyos resultados son desconocidos por los laboratorios participantes. Los procesos en los que el programa es de suma importancia son determinación del grupo ABO, determinación del Rh, realización de la prueba de Coombs directa e indirecta y las pruebas de compatibilidad pretransfusionales. Se hizo un estudio observacional y retrospectivo de los resultados de 2020 de 104 unidades participantes en el Programa de Control de Calidad de Inmunohematología del Banco de Sangre del Centro Médico Nacional Siglo XXI. Se envió un panel de células para el control de calidad externo de inmunohematología cada 45 días y dio como resultado nueve paneles para cada unidad. El cumplimiento del programa se observó en el resultado general (79.6%), es decir, disminuyó la participación de las unidades inscritas. De una calificación máxima de 100%, hubo un resultado general de las unidades participantes del 95.3% de cumplimiento. Los resultados confirman la buena capacitación general de los laboratorios de inmunohematología de las unidades participantes. Aun así, como en cualquier programa de control externo, obtener un resultado erróneo es un riesgo que puede presentarse en cualquier laboratorio.

Sickle cell disease (SCD) is a common hemoglobinopathy, secondary to alterations in the β globin chain, resulting in an abnormal hemoglobin variant named as hemoglobin S. These disorders show a wide phenotypical spectrum, and the prevalence of these disorders has significantly changed over the time because of multiple factors such as migration. We report a case of a 17-year-old black male, born in Gambia, diagnosed with sickle cell disease, who presented an associated mutation only described in a Japanese family (Oshima et al., 1996).

Hereditary anemia (HA) encloses a wide group of rare inherited disorders with clinical and hematologic overlaps that complicate diagnosis.A 48-gene panel was developed to diagnose HA by Next Generation Sequencing (NGS) in a large cohort of 165 patients from 160 unrelated families.Patients were divided in: A) patients who had a suspicion of a specific type of HA (n = 109), and B) patients who had a suspicion of HA but with no clear type (n = 56). Diagnostic performance was 83.5% in group A and a change of the initial diagnosis occurred in 11% of these patients. In group B, 35.7% of patients achieved a genetic diagnosis. NGS identified 6 cases of xerocytosis, 6 of pyruvate kinase (PK) deficiency, 4 of G6PD, and 1 case of phytosterolemia with no initial suspicion of these pathologies, which is clinically relevant since they have specific treatment. Five patients were found to carry variants associated to two different pathologies (4 of them combining a metabolic deficiency and a membrane defect), and 44 new variants were identified in 41 patients.The use of NGS is a sensitive technique to diagnose HA and it shows better performance when patients are better characterized.

Purpose: There is scarce evidence of effective treatments for the chronic phase of Febrile infection-related epilepsy syndrome (FIRES). This study aimed to analyze the outcomes of treatment with anakinra and tocilizumab. Methods: Retrospective study including patients receiving either anti-interleukin-1 (anti-IL-1, anakinra) or anti IL-6 (tocilizumab) during the chronic phase of FIRES. We evaluated seizure outcomes, non-seizure comorbidities, and adverse events. Additionally, an indirect control group including patients during the chronic phase of FIRES non-treated with-IL therapies was evaluated. Results: Five patients were included; three females. Median age at FIRES: 8 years (IQR: 6???10). Five patients received anakinra; one patient switched to tocilizumab after ineffectiveness. Median treatment duration was 9months (IQR: 7???20). While no patients became seizure-free, 20???50% reduction in seizure frequency was reported in 3/5 patients after 6 months with anakinra. Retention rate was 100% at 6 months and 40% at 12months. Three patients reported reduced seizure intensity and rescue medication needed, and better behavior/communication. Similar improvement was reported for the patient switching to tocilizumab. Patients with the best response received anti-IL a median of 9 years after acute phase. All discontinuations were due to ineffectiveness. There were none relevant adverse events apart from one patient presenting transient seizure aggravation. Nine patients were included in the control group; none of them showed relevant improvement in seizure outcomes or cognitive/behavioral comorbidities. Only one presented mild improvement in seizure frequency during the 6 months follow-up. Conclusion: This study provides promising data on effectiveness/safety of anakinra and tocilizumab in the chronic phase of FIRES. These findings warrant prospective/larger studies.

Objective The aim of this study was to determine the possible relationship between the Sp1 polymorphism of gene COL1A1 and bone metabolism disorder in individuals with epilepsy. Methods To this end, we carried out an observational cross-sectional study on 64 patients in monotherapy with an antiepileptic drug. The patients were classified on the basis of the presence of the 's' allele of the COL1A1 Sp1 polymorphism. Results In the patients with SS, the standardized bone mineral density (sBMD) in the left femoral neck was 1024.9±206.1 mg/cm, whereas in the patients with Ss or ss, the density was significantly lower, 917±141.4 mg/cm (P=0.027), as was the femoral t-score (0.72±1.67 vs. -0.29±1.15, P=0.01). The values in the lumbar spine were equally greater in those with SS: 1219.1±236.3 versus 1090.5±142.7 mg/cm for the sBMD (P=0.018) and 0.67±1.98 versus -0.34±1.16 for the lumbar t-score (P=0.023). The bone biomarkers showed no significant differences nor did the 25-OH vitamin D and parathormone values. In the patient group treated with valproic acid (VPA), the densitometric values were significantly lower in the Ss or ss patients compared with SS homozygotes: 887.1±142.6 versus 1120.6±198.2 mg/cm for femoral sBMD (P=0.02), 990±98.1 versus 1417±251.2 mg/cm for lumbar sBMD (P=0.001). Of the patients who were carriers of the 's' allele and who were treated with VPA, 86% achieved osteopenia values. Conclusion In our study, the presence of the 's' allele of the COL1A1 Sp1 polymorphism in individuals with epilepsy was related to lower bone BMD (lumbar and femoral). This relationship seemed to be further apparent in the patients undergoing treatment with VPA.

The alternative pathway (AP) is critical for the efficient activation of complement regardless of the trigger. It is also a major player in pathogenesis, as illustrated by the long list of diseases in which AP activation contributes to pathology. Its relevance to human disease is further emphasized by the high prevalence of pathogenic inherited defects and acquired autoantibodies disrupting components and regulators of the AP C3-convertase. Because pharmacological downmodulation of the AP emerges as a broad-spectrum treatment alternative, there is a powerful interest in developing new molecules to block formation and/or activity of the AP C3-convertase. In this paper, we describe the generation of a novel mAb targeting human factor B (FB). mAb FB48.4.2, recognizing with high affinity an evolutionary-conserved epitope in the Ba fragment of FB, very efficiently inhibited formation of the AP C3-proconvertase by blocking the interaction between FB and C3b. In vitro assays using rabbit and sheep erythrocytes demonstrated that FB28.4.2 was a potent AP inhibitor that blocked complement-mediated hemolysis in several species. Using ex vivo models of disease we demonstrated that FB28.4.2 protected paroxysmal nocturnal hemoglobinuria erythrocytes from complement-mediated hemolysis and inhibited both C3 fragment and C5b-9 deposition on ADP-activated HMEC-1 cells, an experimental model for atypical hemolytic uremic syndrome. Moreover, i.v. injection of FB28.4.2 in rats blocked complement activation in rat serum and prevented the passive induction of experimental autoimmune Myasthenia gravis. As a whole, these data demonstrate the potential value of FB28.4.2 for the treatment of disorders associated with AP complement dysregulation in man and animal models.

Antiepileptic drugs have been known to worsen myasthenia gravis (MG) symptoms, and therefore, in patients who suffer both conditions (myasthenia and epilepsy), treatment selection is difficult. We report 2 cases of patients with MG who were safely treated with lacosamide. Evidence about antiepileptic drug treatment and adverse effects in MG is reviewed.

The aim of this study was to determine the bacteriological quality of bottled water samples obtained from small purification plants located in Mexico City and to identify potentially pathogenic nontuberculous mycobacteria (NTM) species found in these samples. All 111 samples analyzed were positive for aerobic mesophilic bacteria (AMB) and 46 (41.4%) did not comply with Mexico's Official Guidelines. Sixty-nine (62.1%) and 23 (20.7%) water samples were positive for total coliforms (TC) and fecal coliforms (FC), respectively. A total of 81 (72.9%) of the water samples exceeded the maximum allowed limit stipulated in the guideline. Thirty-three (29.7%) of the purified water samples were positive for NTM, being recovered a total of 40 isolates. These NTM isolates were identified using three molecular markers (hsp65, rrs and rpoB genes) which corresponded to the fast-growing mycobacteria M. chelonae (n = 12), M. porcinum (n = 8), M. senegalense (n = 5), M. abscessus (n = 4), M. septicum (n = 4), M. wolinskyi (n = 3), M. mucogenicum (n = 2), M. fortuitum (n = 1) and M. sp. (n = 1). In seven purified water samples, two different NTM species were isolated simultaneously. Overall, these results showed that most of the purified bottled water samples analyzed in this study had unsatisfactory microbiological quality and some harbored NTM associated with illness. Our data could hasten health authorities to intensify efforts in the routine monitoring of activities in the purified bottled water industry in order to supply safe and healthy water to the public.

Oxidative stress is a biochemical state in which reactive oxygen species are generated and it has been associated with pathological states including epilepsy. Therein, neuroprostanes (NeuroPs) and dihomo-isoprostanes (Dihomo-IsoPs)-a series of compounds formed nonenzymatically through free radical-induced DHA, n-6 DPA, and AdA peroxidation-are implicated in the pathophysiological status of various human neurological diseases. A new, robust, and selective analytical method for the determination of 10 NeuroPs/Dihomo-IsoPs in human urine, using solid-phase extraction and UHPLC-QqQ-MS/MS in the multiple reaction monitoring mode (using a negative electrospray ionization interface), was developed. Nine NeuroPs/Dihomo-IsoPs were identified in 15 epileptic patients, matched with healthy volunteers. Among them, 17-F2t-Dihomo-IsoP, Ent-7(R)-7-F2t-Dihomo-IsoP, and Ent-7-epi-7-F2t-Dihomo-IsoP, derived from adrenic acid (AdA), were significantly higher in epileptic patients than in healthy volunteers. The validated method provided a high-throughput assay with a limit of detection and limit of quantification for each analyte of 0.10-5.90ngmL(-1) and 0.15-11.81ngmL(-1), respectively. The intra- and interday variations were lower than 14%. Dihomo-IsoPs have been considered as potential markers of epilepsy for the first time and their measurement may increase the understanding of the role of oxidative stress in neurological diseases, in intra vitam studies. The present study highlights a potential role of Dihomo-IsoPs as biomarkers in persons with epilepsy, though its mechanisms and possible implications should be the subject of further investigations.

The alpha thalassaemia diseases in most cases are caused by deletions that affect one or two of the alpha genes, being less frequent the cases due to punctual mutations, insertions or deletions of a few pairs of bases, which have been denominated no deletion a thalassaemias. The objective of this investigation was to determine the incidence of the no deletion alpha thalassaemia in patients with a thalassaemia using molecular biology techniques. We studied 517 individuals of the San Carlos Hospital (Thalassemia Molecular Research Center, Madrid-Spain) between January 2001 and December 2003, in whom iron deficiency anemia had been ruled out, that presented microcytosis and hypochromia and that presented normal HbA2, HbF and EEF from normal Hbs. The two types of no deletion a thalassaemia most frequently described in the Mediterranean were studied: 1) alpha Hph due to deletion of 5bp in the IVS I and 2) alphaNco due to a change in the initiation codon of the gene. Of the 517 cases studied, 40 (7.7% of the cases) represented a no deletion alpha thalassaemia. Of these cases, 28 were positive for alphaHph of the alpha2 gene, 24 in the heterozygote state, one homozygote and three double heterozygotes associated with the 3,7 kb deletion. The remaining 12 cases were positive for the alphaNco of the alpha2 gene, 10 heterozygotes, one homozygote and one double heterozygote associated with the 4,2 kb deletion. The no deletion alpha thalassaemias represent8% from the cases in our environment. The alphaHph is the most frequent type of no deletion a thalassaemia and its haematological abnormalities are more manifest that the ones present in the cases of alphaNco.

Cerebral lesions after a stroke present different clinical features depending on the neurological structures affected. Complications after an injury in the respiratory center may lead to prolonged mechanical ventilation. Among these possible complications there is a rare neurological condition called "Ondine's curse" that is caused by spontaneous breathing failure. Patients who suffer this syndrome cannot breathe automatically and need to control their respiration consciously and voluntarily. We report the case of a woman who developed a syndrome of central alveolar hypoventilation secondary to an injury in respiratory center after a hemorrhagic stroke. We have reviewed the etiology, physiopathology, diagnosis and treatment of patients with Ondine's curse.

To disclose whether mutations in the HFE gene inducing liver iron overload are related to the risk of hepatocellular carcinoma (HCC) in otherwise predisposed patients.One hundred and ninety-six patients (161 males) diagnosed with HCC and 181 healthy controls were included in the study. All subjects were white Spaniards.C282Y and H63D mutations in the HFE gene were identified in leucocyte genomic DNA using a polymerase chain reaction (PCR) and specific restriction enzymes. RESULTS (CASES/CONTROLS): 1. Genotype distribution: a) C282Y mutation: homozygotes 1/0, heterozygotes 12/23, wild type 183/158 (p = 0.07, non significant); b) H63D mutation: homozygotes 9/5, heterozygotes 85/52, wild type 102/124 (0dds ratio 2.00, 95% C.I. 1.29-3.12, p = 0.002. Four cases and 6 controls were carriers of heterozygous mixed genotypes. 2. Allele frequencies: a) C282Y mutation: wild type allele 378/339, mutated allele 14/23 (p = 0.11, non significant); b) H63D mutation: wild type allele 289/300, mutated allele 103/62 (0dds ratio 1.72, 95% C.I. 1.19-2.50, p = 0.004). Age at diagnosis, gender and etiology of the underlying liver disease do not influence these findings.The C282Y mutation in the HFE gene is not related to the risk of HCC in non-hemochromatosis patients. The H63D mutation is associated with a higher risk of HCC in cirrhotic patients irrespective of their underlying liver disease.

The serum transferrin receptor (TfR) presents certain advantages over other parameters of cellular iron status because it does not vary in acute or chronic diseases.To establish reference ranges of TfR in healthy children for our laboratory, to define the distribution of this variable in children with acute illness and in those with iron deficiency, and to evaluate the diagnostic yield of TfR, the transferrin-receptor/ferritin ratio (TfR/F) and the transferrin-receptor-ferritin index (TfR-F) in distinguishing ferropenic from infectious anemia.A descriptive, cross-sectional analysis was conducted in 132 children aged from 6 months to 16 years for a period of 18 months. The subjects were classified in three groups: healthy children, children with acute illness, and children with iron deficiency. The distribution of TfR and its diagnostic yield were evaluated.Of the 132 subjects, 30 were excluded because they lacked one or more of the parameters under analysis and 19 were excluded because they showed a thalassemic trait. In the 30 healthy children, the mean TfR concentration was 1.2 mg/l (SD 0.36) and the median was 1.02 (IQR 0.7-1.7). In the 32 children with acute illness, with or without anemia, TfR values were similar to those found in healthy children (p0.05). TfR values were higher in children with iron deficiency (21 patients; mean TfR value: 1.67 mg/l SD 0:98) than in healthy children but this difference was not statistically significant (p 0.08). The highest TfR values were found in the group with ferropenic anemia (mean TfR value: 2.13 mg/l SD 1.14) with a statistically significant difference between healthy children (p 0.04) and those with iron deficiency without anemia (p 0.01). The TfR/F ratio showed an optimal diagnostic yield in distinguishing ferropenic from acute disease anemia. If this ratio is higher than 80.7 ferropenia can be suspected as the cause of the anemia with a global value of the test of 100 % (95 % CI: 75.91-99.42).TfR could be useful in evaluating intracellular iron status in children. Acute disease does not alter TfR values and, in combination with ferritin, TfR offers an optimal diagnostical yield in distinguishing ferropenic from acute illness anemia.

Haematological abnormalities are frequently encountered in patients with systemic lupus erythematosus (SLE). Anaemia is the most common hematological abnormality in SLE, it is multifactorial. The most common form of anaemia is that of chronic disease, and it is relate with inflammatory cytokines. Other tips of anaemia are: iron deficiency anaemia, autoimmune haemolytic anaemia, pure red cell aplasia. Leucopenia is related to neutropenia and/or lymphopenia. Thrombocytopenia is common, autoimmune and associated with a decreased survival. The presence of antiphospholipid antibodies increase risk of thrombosis in patients with SLE.

To test the hypothesis that the heterozygous state for HFE gene mutations involved in the pathogenesis of hemochromatosis, that may induce an increase of hepatic iron content, may aggravate the liver damage induced by prolonged and excessive use of ethanol.C282Y and H63D mutations of HFE gene were identified through polymerase chain reaction (PCR) on leukocyte DNA, in 125 consecutive patients diagnosed of advanced alcoholic liver disease (109 men, mean age 54 years, SD 11) and 181 healthy controls. All subjects were white Spaniards. RESULTS (CASES/CONTROLS): 1. Genotype distribution: a) mutation C282Y: no homozygotes, 10/23 heterozygotes, 115/158 normal (p = 0.60); b) mutation H63D: 9/5 homozygotes, 46/52 heterozygotes, 70/124 normal (Chi square 6.51, p = 0.039). 2. Allele frequencies: a) mutation C282Y: 240/339 normal, 10/23 mutated (p = 0.21); b) mutation H63D: 186/300 normal, 64/62 mutated (odds ratio 1.66, 95% CI 1.10-2.52, p = 0.01).Our results suggest that H63D mutation of the HFE gene, but not the C282Y mutation, is associated to the risk of developing advanced liver alcoholic disease.

The results of a programme for the study of atypical familial microcytosis are analysed in this paper. The techniques used were "in vitro" synthesis of globin chains in tritiated leucine-labelled reticulocytes and genetic mapping with different restriction enzymes, plus the usual hematologic values. Of the 134 syntheses performed, 73 showed alpha/beta ratio lower than 1 (alpha-thalassaemia). The lowest values, alpha/beta ratio of 0.54 +/- 0.14, corresponded to 3 patients with Hb H disease. In general terms, our findings are similar to those reported in the literature. The genetic mapping was performed in 98 patients with alpha-thalassaemia (73 cases with decreased alpha/beta ratio, 2 cases with normal ratio, and 23 relatives). Of the 98 patients, 3 had Hb H disease, 70 corresponded to heterozygous alpha 0-thalassaemia, 11 to homozygous alpha(+)-thalassaemia, and 14 to heterozygous alpha (+)-thalassaemia. The analysis of DNA revealed the heterogeneity of the molecular alterations, the prevalent haplotypes being (--MED), in 74% of the patients, and (-3.7 alpha), in 100% of the cases. The other alpha zero-thalassaemia mutations found were the deletions (--SEA) and (--SPAN) and the "no-deletion" thalassaemias.

Almost 10 years ago we reported in this journal the characterization of Hb Hacettepe or alpha 2 beta (2)127(H5)Gln----Glu. Unfortunately, we have to conclude that the original characterization of this Turkish variant was in error. The corrected data are presented in this short communication. The variant (alpha 2 beta (2)65(E9)Lys----Met) was (re)named Hb J-Antakya, after the city where the family resides. An abnormal Hb, observed in a Spanish family and named Hb Complutense, had the beta 127 Gln----Glu substitution, erroneously assigned to the Turkish variant.

Authors present red cell indexes of 120 newborns with normal haemoglobin pattern. In the newborn there is an increase of the red cell mass with regard to the infancy and adult life. The lower limit of normality in our environment for MCV is 99.69 fl. The Hb F concentration is 74.70 +/- 10.69%. The differential aspects of the red blood cells in the umbilical cord blood are commented. The influence of several biological variables on the newborn's red cell indexes are described.

A case of Gaucher's disease, juvenile type is presented. Disease manifested with signs of hepatosplenomegaly, and thrombocytopenia. The typical Gaucher's cells were found in bone marrow aspiration. Acid phosphatase levels were 1.74 U. Bessey-Lowry/ml, 80.45% corresponding to the non-prostatic fraction. The enzymatic activity of glucosyl ceramide-beta-glucosidase was determined in a fibroblast culture, being its value of 0.42 mU/mg of protein (control: 3.2 mU/mg of protein). We comment on the existing relationship between the clinical types, as well as the therapeutic possibilities.