Stem-cell transplantation for children with primary immune deficiencies: A retrospective study of 19 patients from one centre in Mexico.

INTRODUCTION: For many patients with primary immune deficiency (PID), stem-cell transplantation (SCT) may be life-saving. OBJECTIVE: To review our experience of 11 years transplanting children with PID in Mexico. METHODS: Chart review of patients who underwent SCT from 2008 to 2018, to describe their diagnoses, time to transplant, conditioning regime, survival rate and outcomes. All patients received post-transplant cyclophosphamide as graft-versus-host-disease (GVHD) prophylaxis. RESULTS: 19 patients with combined, phagocytic or syndromic PID from 5 states. Twelve of them were male (58%) and 14 survive (79%). Mean age at HSCT was 41.9 months; mean time from diagnosis was 31.2 months. Seven grafts were umbilical cord and 12 haploidentical. The conditioning regime was myeloablative, with five primary graft failures. Two patients had partial and 10 full chimerism. Five patients died within 2 months after transplant. Immune reconstitution was complete in 11 of 19 patients. We found a prevalence of 21% GVHD. DISCUSSION: We describe 19 patients from Mexico with 8 PID diagnoses who underwent allogenic HSCT over a period of 11 years. Survival rate and other outcomes compare well with industrialized countries. We recommend the use of post-transplant cyclophosphamide to prevent GVHD in scenarios of resource scarcity and a lack of HLA-identical donors.

COVID-19 in the Context of Inborn Errors of Immunity: a Case Series of 31 Patients from Mexico.

INTRODUCTION: Patients with inborn errors of immunity (IEI) have a compromised or inappropriate immune response. Although they might be considered a high-risk group for severe SARS-CoV-2 infection, the reported impact of COVID-19 in these patients has been reassuring, while the differential susceptibility of distinct types of IEI remains unclear. OBJECTIVE: We aimed to describe the findings and outcomes of our known patients with IEI who were diagnosed with COVID-19. METHODS: In a retrospective study from March 2020 to February 2021, four centers in Mexico collected clinical, laboratory, and genetic data from pediatric and adult patients with known diagnoses of IEI who presented with COVID-19, based on compatible symptoms and positive SARS-CoV-2 testing or known household exposure. RESULTS: We report 31 patients with known IEI from Mexico who presented with SARS-CoV-2 infection. Seventy-four percent were male, 52% were pediatric, and 81% survived. Their ages ranged from 5 months to 56 years, with a median of 17 years. Sixty-five percent had predominant antibody deficiencies, 48% were hospitalized, and 26% required ICU. Pediatric patients had a higher hospital admission rate than adults. Inpatient mortality was 40%, and ICU mortality rate was 63%. Forty-eight percent developed pneumonia, while 36% had evidence of hyperinflammation (4 adults and 7 children). Predominant laboratory features were lymphopenia and thrombocytopenia, seen in 70 and 44% of patients, respectively. The serum D-dimer median value was 2.6 (0.5-20.6) µg/mL, and the median highest ferritin value was 1015 (32-10,303) ng/mL. Intravenous immunoglobulin was used in 80% of patients. Other treatments included macrolides (39%) and corticosteroids (29%). Six patients died from secondary infection or uncontrolled systemic inflammation. DISCUSSION: Although impaired immunity due to IEI may be a predisposing factor for severe COVID-19, most of our patients with IEI who acquired the SARS-CoV-2 infection developed a well-tolerated infection and survived, as have more than 80% of worldwide reported patients to date. An impaired immune or inflammatory response may be a predisposing factor for some and a protective factor for others. A systematic review of the literature could help identify those patients at risk of severe disease and complications. Healthcare-associated infections should be aggressively prevented.

Parametric Study of the Factors Influencing Liposome Physicochemical Characteristics in a Periodic Disturbance Mixer.

Liposomes encapsulate different substances ranging from drugs to genes. Control over the average size and size distribution of these nanoparticles is vital for biomedical applications since these characteristics determine to a high degree where liposomes will accumulate in the human body. Micromixers enable the continuous flow synthesis of liposomes, improving size control and reproducibility. Recently, Dean flow dynamics-based micromixers, such as the periodic disturbance mixer (PDM), have been shown to produce controlled-size liposomes in a scalable and reproducible way. However, contrary to micromixers based on molecular diffusion or chaotic advection, their production factors and their influence over liposome properties have not yet been addressed thoroughly. In this work, we present a comprehensive parametric study of the effects of flow conditions and molecular changing factors such as concentration, lipid type, and temperature on the physicochemical characteristics of liposomes. Numerical models and confocal images are used to quantitatively and qualitatively evaluate mixing performance under different liposome production conditions and their relationship with vesicle properties. The total flow rate (TFR) and, to a lesser extent, the flow rate ratio (FRR) control the liposome size and size distribution. Effects on liposome size are also observed by changing the molecular factors. Moreover, the liposome ζ potential is independent of the factors studied here. The micromixer presented in this work enables the production of liposomes as small as 24 nm, with monodispersed to low or close to low polydispersed liposome populations as well as a production rate as high as 41 mg/h.

Attitude of the medical personnel of a pediatrics department towards patient death. / Actitud del personal médico de un servicio de pediatría ante la muerte de los pacientes.

Introduction: Tertiary care hospitals' physicians require high emotional competence, since they are faced with the demands of terminally ill patients and their families. Objective: to assess the attitude of physicians of a pediatrics department towards patient death. Method: Pediatrics staff and resident physicians anonymously answered the Attitudes Towards Death (ATD) questionnaire. Absolute frequencies, percentages, means, standard deviations, Student's t-test and the chi-square test were used. Statistical significance was considered with p < 0.05. Results: The questionnaire was answered by 38 physicians, 26 (68.4%) were residents and 12 (37.6%) staff physicians; 15 (39.4%) were males and 23 (60.6%) females. Four residents (15.4%) had a positive attitude versus 2 staff physicians (16.7%) (p = 0.920). Statistical significance was found in items 1 (69.2% of residents versus 100% of staff physicians, p = 0.03), 16 (23% of residents versus 100% of staff physicians, p = 0.001) and 19 (92.3% of residents versus 58.3% of staff physicians, p = 0.01), corresponding to the avoidance, acceptance and professional perspective dimensions. Conclusion: Less than 20% of pediatric physicians have a positive attitude towards death. Most didn't value death as a passage or transition to a better life, or as a solution to life's problems.

Introducción: Los médicos de hospitales de tercer nivel requie-ren alta competencia emocional, ya que enfrentan las de-mandas de enfermos terminales y sus fami-liares. Objetivo: Evaluar la actitud de médicos de un servicio de pediatría ante la muerte de los pacientes. Método: Médicos adscritos y residentes de pediatría contestaron anónimamente el Cuestionario de Actitudes ante la Muerte (CAM). Se utilizaron frecuencias absolutas, porcentajes, medias, desviaciones estándar, t de Student y chi cuadrado. Se consideró significación estadística con p < 0.05. Resultados: Contestaron el cuestionario 38 médicos, 26 (68.4 %) residentes y 12 (37.6 %) adscritos; 15 (39.4 %) hombres y 23 (60.6 %) mujeres. Cuatro residentes (15.4 %) tuvieron actitud positiva versus dos médicos adscritos (16.7 %) (p = 0.920). Se encontró significación estadística en los ítems 1 (69.2 % de residentes versus 100 % de adscritos, p = 0.03), 16 (23 % de residentes versus 100 % de adscritos, p = 0.001) y 19 (92.3 % de residentes versus 58.3 % de adscritos, p = 0.01), correspondientes a las dimensiones evitación, aceptación y perspectiva profesional. Conclusión: Menos de 20 % de los médicos de pediatría tiene una actitud positiva ante la muerte. La mayoría no valoró la muerte como un pasaje o tránsito hacia una vida mejor, ni como una salida a los problemas de la vida.

Alteraciones puberales en adolescentes con leucemia en fase de vigilancia.

OBJECTIVE: To evaluate which factors are associated with alterations in pubertal development in pediatric patients with leukemia in the surveillance phase. METHOD: A case-control study was carried out, including patients aged 8-14 years with diagnosis of acute lymphoblastic leukemia under surveillance. Demographic data were collected, age at diagnosis, type of leukemia, risk of leukemia, duration and type of treatment received, time of surveillance phase; and pubertal development was assessed by Tanner stage, bone age, pelvic ultrasound for women, and LH levels. Fisher's exact test and Mann-Whitney U-test were used. RESULTS: Twenty-five pediatric patients with a diagnosis of acute lymphoblastic leukemia between 8 and 14 years of age with a median of 8 were included, only 4 (16%) presented pubertal alterations, 1 had pubertal delay and 3 advanced puberty. The history of radiotherapy was related to pubertal alterations (p = 0.03). CONCLUSIONS: The antecedent of having received radiotherapy as part of the treatment in patients with acute lymphoblastic leukemia is a risk factor for developing pubertal abnormalities.

Zoledronate as effective treatment for minimal trauma fractures in a child with STAT3 deficiency and osteonecrosis of the hip.

Signal transducer and activator of transcription 3 (STAT3) deficiency is a primary immunodeficiency characterized by eczema, complicated recurrent infections, elevated serum immunoglobulin E (IgE), osteopenia, and minimal trauma fractures. Zoledronic acid (ZA) is a long-acting bisphosphonate that has been successfully used in children with secondary osteoporosis and osteogenesis imperfecta. We describe the case of a 7-year-old male with STAT3 deficiency and minimal trauma fractures, who also developed osteonecrosis of the hip. He responded well to intravenous ZA every 6 months for 18 months. Three years later, he walks independently and unaided, and has not suffered any other fractures. Although more studies are needed, ZA might help reduce minimal trauma fractures in patients with STAT3 deficiency.

[Clinical presentation of supratentorial and infratentorial intracranial tumors in pediatric patients]. / Presentación clínica de tumores intracraneales supratentoriales (ST) e infratentoriales (IT) en pacientes pediátricos.

BACKGROUND: Brain tumors are the second most common malignancy in childhood and they are also the most common solid tumors in children and the most frequent cause of morbidity and mortality associated with cancer in this age. OBJECTIVE: To determine the clinical presentation of supratentorial and infratentorial intracranial tumors in pediatric patients. MATERIAL AND METHODS: An observational, retrospective, cross-sectional comparative study in which records the clinical manifestations of 51 pediatric patients diagnosed with intracranial tumor, according with its location, supra- or infratentorial. RESULTS: 51 patients were analyzed. Tumor location was infratentorial in 32 patients (62.7%) and supratentorial in 19 (37.3%). Cerebellar syndrome occurred in 21 patients (65.6 %) with infratentorial tumor compared with six (31.5 %) with supratentorial tumor (p = 0.04; OR: 3.2; 95% CI: 1.1-12.8). Nystagmus was significantly more common in patients with infratentorial tumors (p = 0.029). Endocrine manifestations were present in four patients (21%) with supratentorial tumor and none of the infratentorial group (p = 0.03). CONCLUSIONS: Cerebellar syndrome was statistically significantly more common in patients with infratentorial when compared with patients with supratentorial. Nystagmus is one of the most common visual impairments in patients with infratentorial tumor. Endocrine disorders are significantly more frequent in patients with supratentorial tumor. The interval between onset of symptoms and diagnosis of intracranial tumor is significantly longer in children with supratentorial tumor because the symptoms are more insidious in onset and are mistaken for other benign conditions.

[Left ventricular adaptive response after surgery of aortic valve replacement for severe valvular stenosis]. / Respuesta adaptativa ventricular izquierda posterior a la cirugía de reemplazo valvular aórtico por estenosis valvular severa.

BACKGROUND: Myocardial hypertrophy is a compensatory mechanism in patients with severe aortic stenosis. The left ventricle fits the systolic pressure through a hypertrophic process with increased wall thickness. The effects of elevated ventricular afterload reduce ventricular myocardial elasticity and decrease coronary flow with increased myocardial work, oxygen consumption, and mortality. Aortic valve replacement surgery can cause regression of left ventricular hypertrophy and improve patient survival. The aim of this study was to evaluate left ventricular adaptive response after surgery of aortic valve replacement for severe valvular stenosis. MATERIAL AND METHODS: An observational, analytical, longitudinal study that included patients with diagnosis of aortic stenosis with evidence of left ventricular hypertrophy undergoing valve replacement during the period January 2013 to September 2014. Echocardiographic studies were performed before surgery and six months thereafter. Pre- and postoperative means were compared with Student t test for related samples. Statistical significance was considered at p ≤ 0.05. RESULTS: 24 patients were included, with an average age of 57.5 years, with no gender predominance, of which 87.5% had history of smoking and 50% with hypertension. There was no statistically significant difference in diastolic and systolic diameter before and after surgery. The interventricular septum was 14.9 ± 2.3 mm preoperative and 12.8 ± 2.2 mm postoperative (p = 0.001). The back wall was 14.2 ± 1.8 mm preoperative and 12.5 ± 2.2 mm postoperative (p = 0.002). The ventricular mass before surgery was 154.8 ± 54.3 g/m(2) and then 123.2 ± 41.4 g/m(2) (p = 0.000). The maximum preoperative transvalvular gradient was 93 ± 35 mmHg and postoperative was 32.2 ± 14.4 mmHg (p = 0.00). The average preoperative transvalvular gradient was 56.3 ± 19 mmHg and postoperative was 7.5 ± 16.49 mmHg (p = 0.00). CONCLUSIONS: The interventricular septum, posterior wall, and left ventricular mass decreased significantly after aortic valve replacement. The maximum and mean transvalvular gradient decreased significantly after surgery for aortic valve replacement.

[Zoledronic acid (zoledronate) in children with osteogenesis imperfecta]. / Ácido zoledrónico (zolendronato) en niños con osteogénesis imperfecta.

INTRODUCTION: Zoledronic acid or zo/edronate is a potent bisphosphonate that recently has been used in children with osteoporosis and osteogenesis imperfecta (01), so it could be an option in the treatment of children with this terrible disease that virtually condemns them to a life of pain and prostration. The aim of this study was to evaluate the clinical and biochemical conditions of pediatric patients with 01 before and after treatment with zo /edronate. RESULTS: We included 14 patients, median age six years (6 months to 14 years), eight (57.1 %) males and six (42 .9%) females, weight 19 kg (5.8-45 kg). According to the type of 01, six (42.9%) were type I, six (42.9%) type Ill, and two (14.2%) type IV The functional score (Bleck) previous to treatment was 4 (1-9) and 6 (2-9) after treatment (p = 0.001). Pain intensity prior to zo/edronate was 2 (1-9) and 0 (0-2) after (p = 0.008). Previous fractures five (1-15) and post-treatment one (0-2) (p = 0.001 ). There were no significant differences in calcium, phosphorus, alkaline phosphatase, and parathyroid hormone. CONCLUSIONS: Zoledronic acid decreases the number of bone fractures and pain in children with osteogenesis imperfect and improves functional status. The most common side effects were fever and bone pain within five days after the infusion,which disappear paracetamol. No adverse long-term effects such as hypocalcemia or hypoparathyroidism were reported.

[Pulmonary complications in pediatric patients with primary immunodeficiency]. / Complicaciones pulmonares en pacientes pediátricos con inmunodeficiencias primarias.

INTRODUCTION: Primary immunodeficiencies comprise diseases that impair the immune system. Clinical manifestations are characterized by recurrent respiratory infections, which may be complicated by bronchiectasis, peribronchial thickening, abscesses, bullae, and pulmonary fibrosis. The aim of this study was to determine pulmonary complications in pediatric primary immunodeficiency by type. RESULTS. We included 65 patients, 28 patients with humoral immunodeficiency, four with cellular immunodeficiency, 13 with well-defined syndromes, and 20 with phagocytic defects. Patients with cellular immunodeficiency with symptoms began at an early age, and were diagnosed before one year of age (p = 0.01 ). Patients with humoral immunodeficiency had more frequent and early respiratory symptoms (p = 0.01 ). The most common respiratory diseases were acute suppurative otitis media, with sinusitis and pneumonia more common in humoral immunodeficiencies and phagocytic defects. The most common pulmonary complications were bronchiectasis and pulmonary fibrosis interstitial damage, with no statistical difference between primary immunodeficiency type. Pulmonary function tests showed greater impairment in patients with phagocyte defects, but no statistical difference (p = 0.28). The presence of pulmonary complications showed no difference when compared by type of immunodeficiency, agammaglobulinemia only (p = 0.02). CONCLUSIONS: Cell immunodeficiencies are diagnosed as early as the onset of symptoms before the patient is one year old. Humoral immunodeficiencies present maximum upper and lower respiratory infections and increased risk of pulmonary complications, especially agammaglobulinemia.

[Factors associated with advanced thyroid cancer in pediatric patients in a high specialty medical unit in Northeast Mexico]. / Factores asociados a estadios avanzados de cáncer tiroideo en pacientes pediátricos de una UMAE del noreste de México.

INTRODUCTION: Thyroid cancer represents 2% of all childhood malignances. Its incidence rises 1.1% per year. In comparison with adults, childhood thyroid cancer is detected in a more advanced stage, but with a survival rate above 95%. The objective of this study was to evaluate whether there are factors associated with advanced stages of thyroid cancer in pediatric patients. RESULTS: Nineteen patients were included, 13 (68.4%) were female and six male, all between 7-15 years, with a median of 11 years. Fifteen in advanced and four in early stage. The median age of patients in advanced stage at time of diagnosis was 10.6 years (7-15) and 13.2 (12-14) were in early stage (p=0.075). There was a delay of nine months to get a diagnosis in advanced stage, and 7.2 in early stage (p=0.931). Three of the patients with advanced stage and two with early stage were from Nuevo León (Mexico) and the rest were foreign (p=0.567). In the group with advanced stage, two had thyroid cancer familiar history, and none in the early stage group (p=0.452). Nine patients in advanced stage and three in early stage presented thyroid nodule as the first sign of illness. Six patients in advanced stage and one in early stage presented goiter (p=0.590). None of the studied patients had radiation history. Six patients in advanced stage and one in early stage suffered from Hashimoto's Thyroiditis (p=0.590). Eleven in advanced stage and one in early stage had papillary histologic variety. Four in advanced stage and three in early stage had papillary histologic variety with a follicular patter (p=0.083). Eight patients presented lung metastasis at time of diagnosis (p=0.061). CONCLUSIONS: There are no factors associated with advanced stage thyroid cancer in pediatric populations. Although half of studied patients presented lung metastasis, treatment response and survival is satisfactory.

[Genetic mutations and the relationship with clinical phenotype in patients with mucopolysaccharidosis type I in northeast Mexico]. / Mutaciones genéticas y su relación con el fenotipo clínico en pacientes con mucopolisacaridosis de tipo I en el noreste de México.

INTRODUCTION: The mutations found in the IDUA gene depend on racial and genetic background. The aim of this paper is to determine the mutations of the IDUA gene in patients with MPS I in the Northeast of Mexico and the relationship with phenotype. RESULTS: Molecular studies were performed in seven patients from Nuevo Leon with MPS I. Five patients had Hurler-Scheie phenotype and two had Hurler phenotype. Four patients (57.1%) had the mutation p.W402X, and two patients (28.5%) had the mutation p.533R, which are both common mutations found in MPS I. Three patients had a novel mutation p.180Ser, so the relationship phenotype/genotype is unknown. Six patients (85.7%) were heterozygotes and one (14.2%) was homozygote. There was a good phenotype/genotype relationship in patients with previously described mutations and only in one patient the genotype had no correlation with the expected phenotype. CONCLUSIONS: The most common mutation in these patients was p.W402X. The mutation p.180Ser has not been listed as a pathogenic mutation or as polymorphism in the data base of the IDUA gene. There was a good phenotype/genotype relationship.

IFITM5-related (type V) osteogenesis imperfecta with evidence of perinatal involvement: A case report.

Osteogenesis imperfecta (OI) is a rare hereditary disorder characterized by bone fragility and frequent fractures. While most cases are attributed to variations in collagen-coding genes COL1A1 and COL1A2, other genes such as IFITM5 have also been associated with the disease, accounting for up to 5 % of cases. Here, we report a case of a 3-month-old female with a femur fracture and limb deformity. X-rays revealed evidence of osteopenia and previous fractures in the arms, clavicle, ribs, and left limb, alongside prenatal bone deformities detected by ultrasound. Initial clinical evaluation suggested progressively deforming (Sillence's type III) osteogenesis imperfecta (OI). Molecular testing led to the diagnosis of IFITM5-related OI, identifying the c.-14C>T (rs587776916) variant. Although this variant has been previously reported in patients with IFITM5-related OI, prenatal involvement had not been associated with this variant.

Mutational spectrum and genotype-phenotype correlation in Mexican patients with infantile-onset and late-onset Pompe disease.

BACKGROUND: Pompe Disease (PD) is a metabolic myopathy caused by variants in the GAA gene, resulting in deficient enzymatic activity. We aimed to characterize the clinical features and related genetic variants in a series of Mexican patients. METHODS: We performed a retrospective study of clinical records of patients diagnosed with LOPD, IOPD or pseudodeficiency. RESULTS: Twenty-nine patients were included in the study, comprising these three forms. Overall, age of symptom onset was 0.1 to 43 years old. The most frequent variant identified was c.-32-13T>G, which was detected in 14 alleles. Among the 23 different variants identified in the GAA gene, 14 were classified as pathogenic, 5 were likely pathogenic, and 1 was a variant of uncertain significance. Two variants were inherited in cis arrangement and 2 were pseudodeficiency-related benign alleles. We identified two novel variants (c.1615 G>A and c.1076-20_1076-4delAAGTCGGCGTTGGCCTG). CONCLUSION: To the best of our knowledge, this series represent the largest phenotypic and genotypic characterization of patients with PD in Mexico. Patients within our series exhibited a combination of LOPD and IOPD associated variants, which may be related to genetic diversity within Mexican population. Further population-wide studies are required to better characterize the incidence of this disease in Mexican population.

[Rituximab in pediatric patients with systemic lupus erythematosus]. / Evolución de los pacientes pediátricos con lupus eritematoso sistémico tratados con rituximab.

UNLABELLED: Systemic lupus erythematosus (SLE) is an autoimmune disease that is more severe in pediatric population than in adults. Biological therapy with anti-CD20 (rituximab) in children with SLE was begun to use only a few years ago, in patients that do not respond to conventional therapy. The aim of this study is to determine the clinical response in pediatric patients with SLE that received treatment with rituximab in a third level hospital. RESULTS: Eight pediatric patients with SLE treated with rituximab were included. Female gender predominated with six (75%). The age at diagnosis of SLE was a mean of 11.3 ± 1.03 years. The mean time between the onset of symptoms and diagnosis was 4.12 ± 1.01 months, and the application of rituximab was 20.7 ± 6.2 months after diagnosis. The most common diagnostic criteria were: malar erythema, hematologic disease, arthritis and kidney disease. Positive ANA title was found in 62.5% of the patients. The clinical activity index MEX-SLEDAI before rituximab was 11.63 ± 6.8 points. Four patients (50%) died, they had activity index before rituximab of 23 ± 1.7 and the survivors of 12.2 ± 3.2 (p = 0.002). After treatment with rituximab the patients that died had 17.6 ± 8.5 points and the survivors 8 ± 2.1 (p = 0.038). In laboratory findings, only C3 and C4 had a significant change after treatment (p = 0.048 and 0.032). CONCLUSIONS: Rituximab reduces lupus activity index and increases complement levels in children with LES that don't respond to conventional therapy.

[Clinical and immunological characteristics in pediatric patients with coccidioidomycosis in northeastern Mexico]. / Características clínicas e inmunológicas en pacientes pediátricos con coccidioidomicosis del noreste de México.

BACKGROUND: Coccidioidomycosis is a systemic fungal disease caused by Coccidioides spp. Patients with phagocytic, cellular, or humoral immunodeficiencies exhibit immunodeficiencies that confer increased susceptibility to fungal infections. In Mexico there is an underreporting of this disease and no studies currently describe the immune status of these patients in an endemic area. OBJECTIVE: To describe the clinical and immunological characteristics of pediatric patients with coccidioidomycosis. MATERIALS AND METHODS: Pediatric patients with diagnosis of coccidioidomycosis from two tertiary level hospitals of northeastern Mexico were included, from the period 2008-2012; immune status was assessed by clinical history, immunoglobulins levels, levels of lymphocytes T, B, and NK (natural killer), and the nitroblue tetrazolium test. RESULTS: Thirty patients were included, 18 male (60%). The age at diagnosis was five years (median, range 0.25-13). Twelve were from Coahuila (40%). Residual pulmonary coccidioidomycosis was the clinical type presentation found in 16 patients (53%). A primary humoral immunodeficiency was found in three patients (10%) and a secondary immunodeficiency in another three (10%). Case fatality rate was 16%. CONCLUSIONS: . The disease predominated in male patients. In 33% of patients, levels of IgG were elevated, probably due to stimulation by chronic fungal infection. In 20% of patients, immunodeficiency was documented. There was a high mortality rate.

[Tezepelumab: a new option for the treatment of severe asthma]. / Tezepelumab: una nueva opción para el tratamiento del asma grave.

In Latin America, asthma is a public health problem with a significant impact on both patients and health systems. The greater understanding of the pathophysiology and the recognition of the central role that inflammation has in the severity of asthma has favored the development of monoclonal antibodies that have IL-5, IL-4, IL-13 and IgE as therapeutic targets. Although these therapeutic alternatives promote better control of the disease, not all patients respond favorably to these treatments. Therefore, it is of particular interest to explore monoclonal antibodies such as Tezepelumab, directed against thymic stromal lymphopoietin (TSLP), an alarmin (epithelial cytokine) that participates in the initiation and perpetuation of inflammation in Asthma. Therefore, in this review, we will show the clinical efficacy of tezepelumab in reducing the annual rate of exacerbations, improving lung function, and reducing bronchial hyperreactivity, regardless of the patient's baseline biomarker levels. Therefore, this new molecule is a highly effective therapeutic option for patients with severe asthma.

En Latinoamérica, el asma es un problema de salud pública con un impacto importante tanto para los pacientes como para los sistemas de salud. El mayor entendimiento de la fisiopatología y el reconocimiento del papel central que tiene la inflamación en la severidad del asma ha favorecido el desarrollo de anticuerpos monoclonales que tienen como blancos terapéuticos a la IL-5, IL-4, IL-13 y la IgE. Si bien estas alternativas terapéuticas favorecen un mejor control de la enfermedad, no todos los pacientes responden favorablemente a esos tratamientos. Por lo que resulta de particular interés explorar anticuerpos monoclonales como el Tezepelumab, dirigido contra la linfopoyetina estromal tímica (TSLP) una alarmina (citocina epitelial) que participa en el inicio y la perpetuación de la inflamación en el Asma. Por lo que, en esta revisión, mostraremos la eficacia clínica del tezepelumab en la disminución de la tasa anual de exacerbaciones, mejora en la función pulmonar y en la disminución en la hiperreactividad bronquial, independientemente de los niveles de biomarcadores basales que el paciente presente. Por lo que esta nueva molécula es una opción terapéutica altamente eficaz para el paciente con asma grave.

[Mucopolysaccharidosis I: management and follow up of three patients]. / Mucopolisacaridosis I. Manejo y vigilancia de tres casos.

Mucopolysaccharidosis type I or mucopolisacaridosis type I is a rare genetic disease, with a severe and fast multiorganic damage profile and fatal prognosis in the early years of age. It belongs to the lysosomal storage diseases (LSD) group pathologies. As an LSD, mucopolisacaridosis type I is due to the lack of the α-L-iduronidase enzyme. Enzyme replacement therapy (ERT) with laronidase is an effective treatment choice. It is available in Mexico since 2005. In the Hospital UMAE 25 of the Mexican Institute of Social Security (IMSS) in Monterrey, Nuevo Leon, Mexico, three patients have been treated and followed since 2006, with a close surveillance on their clinical evolution. The ERT with laronidase is expensive, relatively new and with little experience in Mexico, so there is a real need of knowing clinical evolution as well as overall treatment efficacy from baseline pre-treatment stage to date. Data on physical, functional and biochemical changes in these patients is presented.

Numerical and Experimental Validation of Mixing Efficiency in Periodic Disturbance Mixers.

The shape and dimensions of a micromixer are key elements in the mixing process. Accurately quantifying the mixing efficiency enables the evaluation of the performance of a micromixer and the selection of the most suitable one for specific applications. In this paper, two methods are investigated to evaluate the mixing efficiency: a numerical model and an experimental model with a software image processing technique. Using two methods to calculate the mixing efficiency, in addition to corroborating the results and increasing their reliability, creates various possible approaches that can be selected depending on the circumstances, resources, amount of data to be processed and processing time. Image processing is an easy-to-implement tool, is applicable to different programming languages, is flexible, and provides a quick response that allows the calculation of the mixing efficiency using a process of filtering of images and quantifying the intensity of the color, which is associated with the percentage of mixing. The results showed high similarity between the two methods, with a difference ranging between 0 and 6% in all the evaluated points.

The effect of different organic solvents in liposome properties produced in a periodic disturbance mixer: Transcutol®, a potential organic solvent replacement.

Liposomes are versatile particles used in the biomedical field as drug delivery systems (DDS). Liposome production using micromixers have shown to yield nanoparticles for DDS in a single step with a controllable size by changing flow conditions. Nonetheless, other factors such as the organic solvent, play a crucial role in the liposome formation process. Furthermore, drug solubility and toxicity are pivotal when deciding which organic solvent to choose. In this work, liposomes were produced in a periodic disturbance mixer (PDM). We investigated three conventional organic solvents: ethanol, methanol, and isopropanol as well as Transcutol®. We assessed the organic solvent influence on liposome characteristics (size, size distribution and zeta potential). Among the four organic solvents, Transcutol® yielded the smallest liposomes, which ranged from 80 nm to 160 nm. Moreover, a more in-depth investigation showed that Transcutol® produced smaller or similar-sized particles under different temperature and lipid concentration conditions, compared with ethanol. Furthermore, we proved that particles zeta potential was not influenced by the organic solvent, production temperature, or lipid concentration. This work results show that Transcutol® could replace the conventional alcohol-based solvents and can potentially avoid filtration steps due to its low toxicity. Therefore, the present approach is appealing for DDS development.