Bilateral tractional retinal detachment in hemoglobin SC disease patient / Descolamento tracional de retina bilateral em hemoglobinopatia S-C

ABSTRACT A 36-year-old black male presented with a progressive loss of visual acuity in both eyes for 7 years. He had a history of tractional retinal detachment in the right eye and vitreous hemorrhage followed by retinal detachment in the left eye. He denied any systemic illness, trauma, or drug abuse. After clinical investigation, he was diagnosed with SC hemoglobinopathy and proliferative sickle cell retinopathy stage V in both eyes.

RESUMO Paciente do sexo masculino, 36 anos, negro, apresentou baixa acuidade visual progressiva em ambos os olhos por 7 anos. Possuía antecedentes de descolamento tracional de retina no olho direito e hemorragia vítrea, seguida de descolamento de retina no olho esquerdo. Negava doenças sistêmicas, trauma ou abuso de drogas. Após investigação clínica, foi diagnosticado com hemoglobinopatia S-C e retinopatia falciforme proliferativa estágio V em ambos os olhos.

Antagonistic effect of SC79 on high glucose-induced apoptosis of RPE cells and its regulatory mechanism on AKT-XIAP signaling pathway / 中华实验眼科杂志

Objective:To investigate the antagonistic effect and potential mechanism of specific AKT activator SC79 on the apoptosis of human retinal pigment epithelial (ARPE)-19 cells induced by high glucose in vitro. Methods:The ARPE-19 cells were cultured in high glucose medium (containing 30 mmol/L glucose) plus 5, 10 or 20 μg/ml SC79, respectively.After 6-, 12- and 24-hour culture, the optimal experimental concentration and timing were determined according to cell proliferation rate.Then ARPE-19 cells were divided into four groups, normal control group cultured in normal medium containing 5.6 mmol/L glucose for 48 hours, mannitol group cultured in medium containing 5.6 mmol/L glucose and 24.4 mmol/L mannitol for 48 hours, high glucose group cultured in high glucose medium for 48 hours, and high glucose+ SC79 group cultured in normal medium containing 10 μg/ml SC79 for 12 hours plus in high glucose medium for 36 hours.The proliferation rate of APRE-19 cells was detected by MTS assay.The apoptosis rate was measured by flow cytometry.The relative expression levels of phosphorylated protein kinase B (p-Akt), X-linked inhibitor of apoptosis protein (XIAP), caspase-9, caspase-3 and its active fragments (active-caspase-3) were assayed by Western blot.The ARPE-19 cells were divided into Neg-shRNA group, AKT shRNA group and blank control group and were treated with the corresponding transfection complex and serum-free medium.The AKT mRNA expression was detected by real-time PCR.The transfected ARPE-19 cells were divided into Neg-shRNA+ SC79 group and AKT shRNA+ SC79 group and were cultured according to the culturing method of high-glucose+ SC79 group.The apoptosis rate of the two groups was tested by flow cytometry.Results:Among different concentrations of SC79 and treatment times, the proliferation rate of cells treated with 10 μg/ml SC79 for 12 hours was the highest.The proliferation rate of ARPE-19 cells in high-glucose group was significantly lower than that in normal control group, mannitol group and high-glucose+ SC79 group, and the differences were statistically significant (all at P<0.01). The apoptosis rate of cells in the high-glucose group was (52.27±3.21)%, which was significantly higher than (3.90±0.71)% in normal control group and (20.70±3.62)% in high-glucose+ SC79 group (both at P<0.01). The relative expression levels of p-Akt, XIAP, caspase-9 and caspase-3 were significantly lower and the relative expression level of active-caspase-3 was significantly higher in high glucose group than those in normal control group and high-glucose+ SC79 group (all at P<0.05). The relative expression level of AKT mRNA in normal control group, Neg-shRNA group and AKT shRNA group was 0.60±0.07, 0.59±0.03 and 0.11±0.10, respectively, showing a statistically significant difference among the groups ( F=30.44, P<0.01). The apoptosis rate of cells in the AKT shRNA+ SC79 group was significantly higher than that in high-glucose+ SC79 group and Neg-shRNA+ SC79 group (both at P<0.001). Conclusions:SC79 can partially antagonize the apoptosis of ARPE-19 cells induced by high glucose, which is related to the activation of AKT/XIAP pathway and the inhibition of the caspase family.

Anti-tyrosinase, anti-skin pathogenic bacterial, and antioxidant activities and phytochemical constituents of Dracaena cochinchinensis (Lour.) S.C. Chen extract

Dracaena cochinchinensis (Lour.) S.C. Chen (Chandaeng) is an important traditional medicinal plant used in ancient Thai household remedies. This research focused on investigating the biological properties, including the antibacterial, anti-tyrosinase, antioxidant activities, and phytochemical characteristics of crude Chandaeng extracts. Dried Chandaeng heartwood powder was extracted using ethanol, methanol, and deionized water. The antibacterial activities of the extracts were then tested against skin pathogens, including Cutibacterium acnes (DMST14916), Staphylococcus epidermidis (TISTR518), and Staphylococcus aureus (TISTR321). The ethanolic extract showed antibacterial activity. In a time-kill assay, all bacteria were completely killed after being exposed to it, while the cell membranes were found to have leaked when viewed under a scanning electron microscope. Antioxidant potential was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2¢-azino-bis -3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. According to the findings, the crude ethanolic extract of Chandaeng showed the highest level of antioxidant activity. Furthermore, the potential of the extract to treat skin hyperpigmentation by inhibiting tyrosinase, an important melanin synthesis enzyme, was determined and the ethanolic extract was found to be an anti-tyrosinase agent. Finally, the crude ethanolic extract showed the highest total phenolic compound and flavonoid content. In conclusion, crude Chandaeng extract showed significant potential in activity against skin pathogenic bacteria, antioxidant activity, and tyrosinase inhibition. These properties of the extract could be applied to skincare cosmetics.

Función biológica de AMPK- ß2 en músculo esquelético y su dinámica estructural después de la activación por SC4 / Biological role of AMPK- ß2 in skeletal muscle and its structural dynamics after activation by SC4

INTRODUCCIÓN: la Proteína Quinasa Activada por AMP (AMPK), es una enzima monitora y reguladora central del estado energético celular, por tanto, es responsable de la respuesta celular al suministro y demanda de energía. El AMP actúa como activador en condiciones de déficit energético, mientras que el ATP la inactiva cuando las condiciones energéticas son más favorables. Debido a su función central en el metabolismo, la AMPK surge como un blanco proteico prometedor para el tratamiento de diferentes enfermedades como la Diabetes Mellitus tipo 2 (DM2), Síndrome Metabólico (SM), Cáncer, entre otros. Existen múltiples isoformas de AMPK que se regulan y expresan diferencialmente en todo el organismo. La isoforma AMPK­ß2 se expresa casi exclusivamente en músculo esquelético y dado que este es el órgano primario para el almacenamiento y eliminación de Glucosa, AMPK­ß2 puede dirigir su homeostasis por una ruta independiente a la Insulina. La molécula activadora SC4 tiene una gran selectividad por AMPK­ß2 y debido a su función biológica, podría servir como modelo farmacológico para coadyuvar el tratamiento de enfermedades metabólicas. OBJETIVO: análisis de la dinámica molecular de activación de la AMPK­ß2. METODOLOGÍA: en el presente estudio, se emplean herramientas bioinformáticas como Chimera 1.15 y Phyton Molecular Viewer. RESULTADOS: el análisis in silico permitió comprender varios aspectos estructurales relacionados con la acción de SC4 sobre la estructura trimérica de la AMPK, los aminoácidos con los que interacciona y cómo su estructura química le otorga gran selectividad. También fue útil para en un futuro, ampliar los criterios de extracción, identificación y/o diseño de compuestos activos a partir de fuentes naturales, con propiedades funcionales similares o aún mejores a SC4, para así poder emplearlos con un enfoque terapéutico que beneficie a nuestra población.

INTRODUCTION: protein Kinase Activated by AMP (AMPK), is a monitor enzyme and a central regulator of the energetic cellular state, therefore, it is responsible for the cellular response to the supply and demand of energy. AMP acts as an activator in conditions of energy deficit, while ATP inactivates it when energy conditions are more favorable. Due to its central role in metabolism, AMPK appears as a promising protein target for the treatment of different diseases such as Diabetes Mellitus type 2 (DM2), Metabolic Syndrome (SM), and Cancer among others. There are multiple isoforms of AMPK that are regulated and differentially expressed throughout the body. The ß2-AMPK isoform is expressed almost exclusively in skeletal muscle and since this is the primary organ for Glucose disposal and storage, ß2-AMPK has an established role as a driver of insulin-independent Glucose clearance. The activator SC4 has a high selectivity for ß2-AMPK and due to its biological function; it could serve as a pharmacological model to aid the treatment of metabolic diseases. OBJETIVE: to analize the molecular dinamic of AMPK- ß2 activation. METHODOLOGY: in the present work we employed bioinformatics, Chimera 1.15 and Phyton Molecular Viewer. RESULTS: the in silico analysis allow us to understand many many structural features related to the action of SC4 on the trimeric structure of AMPK, the specific amino acids involved in the interaction and how its chemical structure gives it high selectivity. Thus, this structural analysis will be useful in order to broaden the criteria for extraction, identification and/or design of active compounds from natural sources, with similar or even better properties than SC4, to use them in a future, with a therapeutic approach that benefits our population.

Impacto del diagnóstico prenatal del Programa Nacional para la Prevención de Anemia Falciforme en la incidencia de hemoglobinopatías en Santiago de Cuba / Impact of the prenatal diagnosis of the National Program for the prevention of sickle-cell anemia in the incidence of hempoglobimopathies in Santiago de Cuba

Introducción: El nacimiento de personas con hemoglobinas SS y SC promovió la creación en Cuba de un programa de prevención que incluye el diagnóstico prenatal de estas hemoglobinopatías. Objetivo: Mostrar el impacto del diagnóstico prenatal en la incidencia de anemia drepanocítica y de enfermedad heterocigótica compuesta SC. Métodos: Se realizó un estudio descriptivo, retrospectivo, de corte transversal, en el Departamento Provincial de Genética Médica del Hospital Docente Infantil Sur Dr. Antonio María Béguez César en Santiago de Cuba, que abarcó un período de tres decenios más un sexenio (de 1984 a 2019), de los 713 fetos y niños en los que se detectó anemia de células falciformes. Para establecer el diagnóstico prenatal se realizó electroforesis de hemoglobina a las embarazadas -durante los primeros años con el equipo Habana y a partir del 2012 con la tecnología Hydrasys-. Resultados: Del total de casos diagnosticados, se interrumpió el embarazo en 44,3 %, con un incremento significativo de los abortos provocados por esta causa al transcurrir los años, a saber: 23,7 % en el primer decenio, 46,1 % en el segundo y 68,1 % en el tercero; mientras que en el período 2014-2019 fue de 59,3 %. Por consiguiente, disminuyó el nacimiento de niños enfermos de 76,3 % en los inicios del estudio a 53,9 y 31,9 % en el segundo y tercero decenios, respectivamente, y por último a 40,7 % en el sexenio. Conclusiones: El diagnóstico prenatal de la anemia de células falciformes SS y la enfermedad heterocigótica compuesta SC constituye el pilar fundamental para la prevención de estas hemoglobinopatías.

Introduction: The birth of people with SS and SC hemoglobine justified the creation of a prevention program in Cuba which includes the antenatal diagnosis of these hemoglobinopathies. Objective: To show the impact of the antenatal diagnosis in the incidence of sickle-cell anemia and of the composed heterocigotic disease SC. Methods: A descriptive restrospective and cross-sectional study was carried out in the Provincial Department of the Teaching Southern Pediatric Hospital Antonio María Béguez César in Santiago de Cuba, which included three decades and a sexennium (from 1984 to 2019), of the 713 fetuses and children in whom sickell-cell anemia was diagnosed. To establish the prenatal diagnosis, hemoglobine electrophoresis to all pregnant women, -During the first years with Havana equipment and from 2012 on, with the technology Hydrasys-. Results: From the total of diagnosed cases, pregnancy was interrupted in 44,3 %, with a significant increase of aborptions provoked due to this cause with the passing of years: 23.7 % in the first decenium, 46.1 in the second and 68.1 % in the third, while in the period 2014-2019 it was 59.3 %. Due to this, the births of sick children to from 76.3 % at the beggining of the study to 53.9 and 31.9 respectively, and finally to 40.7 % in the sexenium 2014-2019. Conclusions: The prenatal diagnosis of sickel-cell anemia SS and SC constitutes the key stone for the prevention of these hemoglobinopathies.

Perda auditiva na hemoglobinopatia SC (HbSC): relato de caso / Hearing loss in SC hemoglobinopathy (HbSC): case report

Introdução: Doença falciforme (DF) engloba um conjunto de hemoglobinopatias marcadas pela hemoglobina (Hb) anormal S (HbS). A HbS possui um formato de foice e aumento de rigidez, culminando em hemólise. Além disso, dificulta a passagem pela microcirculação sanguínea, causando vaso-oclusão e lesão isquêmica em diversos órgãos e tecidos. Na orelha interna, tem sido descrita como os responsável por danos auditivos. Objetivo: apresentar um relato de caso de paciente do sexo feminino com doença falciforme, acometida de perda auditiva sensorioneural (PASN) bilateral assimétrica. Relato do caso: paciente do sexo feminino, destra, 45 anos, compareceu para avaliação, queixando se de diminuição da audição e zumbido na orelha esquerda. Foi submetida à avaliação audiológica, constituída por audiometria tonal limiar, logoaudiometria, imitanciometria, emissões otoacústicas por produto de distorção (EOAPD) e potencial evocado auditivo do tronco encefálico (PEATE). Resultados: constatou-se: perda auditiva sensorioneural bilateral de grau leve na orelha direita e severo na orelha esquerda; presença dos reflexos estapedianos contralaterais na orelha direita e ausência na orelha esquerda; curvas timpanométricas tipo A; ausência de emissões otoacústicas bilateralmente; e os potenciais auditivos evocados do tronco encefálico dentro dos padrões de normalidade. Discussão: diversos mecanismos estão envolvidos na relação DF e PASN, como a falta de oxigenação e infarto do órgão de Corti, hemorragia labiríntica e labirintite ossificante, bem como uma associação entre o nível de viscosidade sanguínea, disfunção endotelial e hipertensão sistêmica. E ainda deve ser considerada a questão de dominância hemisférica na assimetria da perda. Conclusão: os conhecimentos sobre as características dos danos auditivos na HbSC ainda não são conclusivos e merecem mais investigações. A implementação de avaliações periódicas da função auditiva tem contribuído para prevenir a progressão dos danos e auxiliado no tratamento precoce.

Introduction: Sickle cell disease (SCD) comprises a set of hemoglobinopathies marked by abnormal hemoglobin (Hb) S (HbS). HbS has a sickle shape and increased stiffness culminating in hemolysis, in addition to making it difficult to pass through the blood microcirculation, causing vessel-occlusion and ischemic damage in various organs and tissues. In the inner ear, they have been described as responsible for hearing damage. Objective: describing a case report of a female patient with sickle cell disease affected by asymmetric bilateral sensorineural hearing loss (SNHL). Case report: a 45-year-old female patient, right-handed, came for evaluation, complaining of decreased hearing and tinnitus in her left ear. She underwent audiological evaluation consisting of pure tone audiometry, logoaudiometry, immittance testing, distortion product otoacoustic emissions (DPOAE) and brainstem auditory evoked potential (BAEP). Results: bilateral mild sensorineural hearing loss in the right ear and severe in the left ear, presence of contralateral stapedial reflexes in the right ear and absence in the left ear, type A tympanometric curves, absence of bilateral otoacoustic emissions and the brainstem auditory evoked potentials within the normality patterns. Discussion: Several mechanisms are involved in the SCD and SNHL relationship, such as the lack of oxygen and infarction of the Organ of Corti, labyrinthine hemorrhage and ossifying labyrinthitis, as well as an association between the level of blood viscosity, endothelial dysfunction and systemic hypertension. And the question of hemispheric dominance in the loss asymmetry must still be considered. Conclusion: knowledge about the characteristics of hearing damage in HbSC is not yet conclusive and deserves further investigation. Implementation of periodic auditory function assessments has helped to prevent the progression of damage and has helped in early treatment.

Rasgo falciforme e infarto esplénico: una entidad no ajena en población antioqueña / Sickle trait and splenic infarction, a non-foreign entity in Antioquia population

Resumen Generalmente, los pacientes con rasgo falciforme sufren pocas manifestaciones del espectro de la anemia de células falciformes. El infarto esplénico es raro, pero es una complicación documentada del rasgo falciforme y, usualmente, se presenta en condiciones de disminución de la presión parcial de oxígeno, como ocurre en grandes alturas. Se presenta el caso de un joven sin antecedentes, quien presentó dolor súbito en hipocondrio izquierdo luego de viaje a zona de gran altura y en quien se documentó infarto esplénico y posteriormente se confirmó como etiología del cuadro, rasgo falciforme mediante electroforesis de hemoglobina. La mayoría de los pacientes desconocen su rasgo falciforme, lo que hace desafiante su enfoque, retrasa el diagnóstico y resulta en manejos inadecuados que pueden aumentar la extensión del infarto esplénico y requerir finalmente esplenectomía.

Abstract Generally, patients with sickle cell trait have few manifestations of the sickle cell spectrum. Splenic infarction is rare, but is a documented complication of sickle cell trait and usually occurs under conditions of decreased partial pressure of oxygen, such as at high altitudes. We present the case of a young man with no previous history who presented sudden pain in the left hypochondrium after traveling to a high-altitude area. Splenic infarction was documented and sickle cell trait was later confirmed with hemoglobin electrophoresis as the etiology of the condition. Most patients remain ignorant of their sickle cell trait, which makes their approach challenging, delays diagnosis, and results in inappropriate management that may increase the extent of splenic infarction and eventually require splenectomy.

Recent advances in using of stem cell-derived extracellular vesicles in treating central nervous system diseases / 上海交通大学学报（医学版）

Stem cell-derived extracellular vesicles can regulate functions of targeting cells in lesions and have fewer risks in treating diseases. In central nervous injury lesions, stem cell-derived extracellular vesicles can promote neurogenesis and angiogenesis and regulate nervous inflammation, which promotes the recovery of the nerve injury. Stem cell-derived extracellular vesicles can ease Aβ protein-related neuron damage in Alzheimer's disease. Stem cell-derived extracellular vesicles also can deliver microRNA and chemotherapeutic agents to neuroglioma cells. This review introduces recent advances in using stem cell-derived extracellular vesicles in treating central nervous system diseases.

Cloning and expression analysis of 2-oxoglutarate-dependent dioxygenase from Schisandra chinensis / 药学学报

The 2-oxoglutarate-dependent dioxygenase (2-ODD) gene is regarded as the key enzyme gene involved with aryl naphthalene lignan-podophyllotoxin synthesis. To study the expression pattern and function of the Sc2-ODD gene, a full-length cDNA of the gene was cloned. Bioinformatic analysis, the expression pattern, and prokaryotic expression and purification were implemented. The open reading frame of Sc2-ODD gene was 1 077 bp and encoded 358 amino acids with a molecular weight of 40.16 kD. The Sc2-ODD protein contained the conserved 2OG-FeII-oxy sequence of the 2-ODD protein. The results of phylogenetic analysis revealed that Sc2-ODD is most closely related to Corchorus olitorius 2-ODD. qRT-PCR results showed that Sc2-ODD expression displayed obvious up-regulation at the fruit-swelling stage, then down-regulation in the fruit-coloring period. The Sc2-ODD gene was cloned into the bacterial expression vector pGS21T, the recombinant Sc2-ODD protein was expressed in Escherichia coli Rosetta (DE3) cells and the fusion protein was obtained and purified by GST fusion protein purification technology. This study will lay a foundation for further research on the function and expressional regulation of the Sc2-ODD gene in the aryl naphthalene lignans biosynthesis pathway, and also provides a scientific basis for improving the lignan content and the medicinal quality of Schisandra chinensis using plant genetic engineering.

Use of subcutaneous tocilizumab to prepare intravenous solutions for COVID-19 emergency shortage: Comparative analytical study of physicochemical quality attributes / 药物分析学报

COVID-19, a disease caused by the novel coronavirus SARS-CoV-2, has produced a serious emergency for global public health, placing enormous stress on national health systems in many countries. Several studies suggest that cytokine storms (interleukins) may play an important role in severe cases of COVID-19. Neutralizing key inflammatory factors in cytokine release syndrome (CRS) could therefore be of great value in reducing the mortality rate. Tocilizumab (TCZ) in its intravenous (IV) form of administration-RoActemra? 20 mg/mL (Roche)-is indicated for treatment of severe CRS patients. Preliminary in-vestigations have concluded that inhibition of IL-6 with TCZ appears to be efficacious and safe, with several ongoing clinical trials. This has led to a huge increase in demand for IV TCZ for treating severe COVID-19 patients in hospitals, which has resulted in drug shortages. Here, we present a comparability study assessing the main critical physicochemical attributes of TCZ solutions used for infusion, at 6 mg/mL and 4 mg/mL, prepared from RoActemra? 20 mg/mL (IV form) and from RoActemra? 162 mg (0.9 mL solution pre-filled syringe, subcutaneous(SC) form), to evaluate the use of the latter for preparing clinical solutions required for IV administration, so that in a situation of shortage of the IV medicine, the SC form could be used to prepare the solutions for IV delivery of TCZ. It is important to remember that during the current pandemic all the medicines are used off-label, since none of them has yet been approved for the treatment of COVID-19.

Genotoxic Assessment of the Metabolite M-11 of Mepanipyrim, the Active Ingredient in the Plant Protection Product FRUPICA SC

The VKM Panel for plant protection products considered Frupica SC in a meeting on 25.11.2010, and found the active ingredient problematic with regard to carcinogenic effects and possible genotoxicity. M11 is a metabolite of mepanipyrim which is the active ingredient the plant protection product Frupica SC. The Norwegian Food Safety Authority has asked the applicant for further assessment of the genotoxic potential of the metabolite M11. The applicant has submitted a rat liver in vivo Comet assay of the metabolite, and the panel has been requested to consider if the genotoxic properties of mepanipyrim and the metabolite M11 is adequately documented. The metabolite M11 caused positive findings in in vitro studies for bacterial mutation and chromosomal aberrations. Three in vivo studies (Micronucleus, unscheduled DNA synthesis and Comet assay) did not show evidence of genotoxicity. Based on the documentation available, VKMs Panel on Plant Protection Products concludes that mepanipyrim and the metabolite M11 should not be considered genotoxic in vivo. The lack of demonstrated in vivo genotoxicity makes it likely that mepanipyrim induces liver tumors in rats and mice by a mechanism that involves a threshold below which tumors are not expected to develop. This conclusion is strengthened by the finding of a promoter-like behavior of mepanipyrim for induction of gamma-glutamyl-transpeptidase positive foci in rat liver.

Anemia hemolítica autoinmune por crioaglutininas y crisis aplásica en una paciente con hemoglobinopatía SC / Autoimmune hemolytic anemia with cryoagglutinins and aplastic crisis in a patient with SC hemoglobinopathy

La infección por parvovirus B19 humano, es la causa de la mayor parte de los casos de crisis aplásica transitoria que aparecen de forma brusca en pacientes con enfermedades hemolíticas crónicas, como es el caso de la drepanocitosis. Por otra parte, se han descrito unos pocos casos de infección aguda, por parvovirus B19 humano como causa de anemia hemolítica autoinmune, por medio de la formación de anticuerpos dirigidos contra los glóbulos rojos. La asociación entre drepanocitosis y anemias hemolíticas autoinmunes es poco frecuente. Se reporta un caso poco usual de una paciente adulta, con antecedentes de hemoglobinopatía S/C que presentó una crisis aplásica y posteriormente apareció una anemia hemolítica autoinmune diagnosticada en el Instituto de Hematología e Inmunología. Se trató con dosis inmunosupresoras de esteroide, con lo que se alcanzó la remisión de la anemia hemolítica autoinmune(AU)

Infection with human B19 parvovirus is the cause of most cases of transient aplastic crisis that appear in patients with chronic hemolytic diseases, as in the case of sickle cell disease. On the other hand, a few cases of acute infection by human parvovirus B19 have been described as a cause of autoimmune hemolytic anemia, through the formation of antibodies directed against red blood cells. The association between sickle cell disease and autoimmune hemolytic anemia is rare. We report an unusual case of an adult patient, with a history of S C hemoglobinopathy who presented an aplastic crisis and subsequently an autoimmune hemolytic anemia diagnosed at the Institute of Hematology and Immunology, treated with high steroids doses, reaching the remission of autoimmune hemolytic anemia and constitutes the first report in Cuba(AU)

Evolutionary profile of patients with hemoglobin SC disease regularly followed in Côte d'Ivoire

Background: West Africa is recognized as the elective focus of hemoglobin C. The S and C combination in the same patient gives a major sickle cell syndrome. In our country, very few series dealing with the evolutionary features of this SC form have been published contrary to the homozygous SS form. The aim of this study was to describe the evolutionary profile of double heterozygous SC sickle cell patients.Methods: This was a retrospective and prospective study with descriptive and analytical purpose of 174 SC sickle cell patients.Results: The median age was 26 years with extremes of 6 years and 57 years. 96% of patients had less than 4 vaso-occlusive seizures per year. The evolutionary complications were mainly ischemic (56.30%) and infectious (39.10%). Among ischemic complications, sickle cell retinopathies and aseptic osteonecrosis are the most common with 59.20% and 31.63% respectively. Infectious complications were dominated by ENT (36.76%) and osteoarticular (35.29%) infections. Only age had an influence on the occurrence of ischemic complications (p = 0.0001). The probability of survival at 5 years was 99.38% and that at 20 years was 91.57%. The overall survival was not influenced by evolutionary complications.Conclusions: Infectious and ischemic evolutionary complications show the importance of vaccination and an early screening program.

Clinical and hematological profile in a newborn cohort with hemoglobin SC / Perfil clínico e hematológico em uma coorte neonatal com hemoglobina SC

Abstract Objectives: Hemoglobin SC is the second most common variant of sickle-cell disease worldwide, after hemoglobin SS. The objectives of the study were to describe the clinical and laboratory characteristics of hemoglobin SC disease in children from a newborn screening program and treated at a blood center. Methodology: This study assessed a cohort of 461 infants born between 01/01/1999 and 12/31/2012 and followed-up until 12/31/2014. Clinical events were expressed as rates for 100 patient-years, with 95% confidence intervals. Kaplan-Meier survival curves were created. Results: The median age of patients was 9.2 years; 47.5% were female. Mean values of blood tests were: hemoglobin, 10.5 g/dL; reticulocytes, 3.4%; white blood cells, 11.24 × 109/L; platelets, 337.1 × 109/L; and fetal hemoglobin, 6.3%. Clinical events: acute splenic sequestration in 14.8%, blood transfusion 23.4%, overt stroke in 0.2%. The incidence of painful vaso-occlusive episodes was 51 (48.9-53.4) per 100 patient-years and that of infections, 62.2 episodes (59.8-64.8) per 100 patient-years. Transcranial Doppler ultrasonography (n = 71) was normal given the current reference values for SS patients. Hydroxyurea was given to ten children, all of whom improvement of painful crises. Retinopathy was observed in 20.3% of 59 children who underwent ophthalmoscopy. Avascular necrosis was detected in seven of 12 patients evaluated, predominantly in the left femur. Echocardiogram compatible with pulmonary hypertension was recorded in 4.6% of 130 children, with an estimated average systolic pulmonary artery pressure of 33.5 mmHg. The mortality rate from all causes was 4.3%. Conclusions: Clinical severity is variable in SC hemoglobinopathy. Several children have severe manifestations similar to those with SS disease.

Resumo Objetivos: A hemoglobinopatia SC é a segunda variante mais comum da doença falciforme no mundo, após a hemoglobinopatia SS. Os objetivos do estudo foram descrever as características clínicas e laboratoriais da hemoglobinopatia SC em recém-nascidos diagnosticados por programa de triagem neonatal e encaminhados para acompanhamento em hemocentro. Metodologia: Coorte de 461 recém-nascidos SC nascidos entre 01/01/1999 e 31/12/2012 e seguidos até 31/12/2014. A incidência de eventos clínicos foi expressa por taxas relativas a 100 pacientes-ano, com limites de confiança a 95%. Curvas de sobrevida foram construídas segundo Kaplan-Meier. Resultados: Mediana de idade, 9,2 anos; 47,5%, feminino. Médias dos valores hematológicos: hemoglobina 10,5 g/dL; reticulócitos 3,4%; leucometria 11,24 x 109/L; plaquetometria 337,1x109/L; hemoglobina fetal 6,3%. Eventos clínicos: sequestro esplênico agudo em 14,8%, hemotransfusão 23,4%, AVC isquêmico 0,2%. A incidência de episódios vaso-oclusivos dolorosos foi de 51 (48,9-53,4) por 100 pacientes-ano; a de infecções, 62,2 episódios (59,8-64,8) por 100 pacientes-ano. Doppler transcraniano (n = 71) foi normal, se usados os valores de referência de crianças SS. Dez pacientes usaram hidroxiureia, todos com melhoria das crises dolorosas. Retinopatia foi observada em 20,3% das 59 crianças que fizeram fundoscopia. Necrose avascular foi detectada em 7 de 12 pacientes avaliados, com predomínio no fêmur esquerdo. Ecocardiograma compatível com hipertensão pulmonar foi registrado em 4,6% de 130 crianças, com média estimada de 33,5 mm Hg de pressão arterial pulmonar. A taxa de mortalidade por todas as causas foi de 4,3%. Conclusões: A hemoglobinopatia SC tem gravidade variável; várias crianças apresentam manifestações clínicas intensas, semelhantes às da hemoglobinopatia SS.

Caracterização clínica dos pacientes com hemoglobinopatia atendidos no Hemocentro de Sergipe / Clinical characterization of patients with hemoglobinopathy at Sergipe's Hemocentro

Descrever as características clínicas dos pacientes com hemoglobinopatias do Hemocentro de Sergipe. Neste estudo transversal foram coletados dados clínicos dos pacientes portadores de hemoglobinopatias através da leitura dos prontuários. Realizou-se estatística descritiva e análise de variáveis utilizando-se o teste ANOVA para comparação de médias e o teste exato de Fisher para associação, utilizando em ambos uma significância com p<0,05. Foram coletados os dados de 96 pacientes. A principal hemoglobinopatia encontrada foi a SS (85,4%), seguida da SC (11,5%) e ßtalassemia (3,1%). A principal complicação encontrada foi a hiperferritinemia (50,7%), que teve uma relação direta com a hemotransfusão (p=0,039) e os pacientes com mais complicações tinham uma maior idade (p=0,026). A hemotransfusão foi necessária em 71,9% dos pacientes, enquanto que a hidroxiureia e o deserafirox em 40,6% e 13,5%, respectivamente. A principal hemoglobinopatia encontrada foi SS, teve como principal complicação a hiperferritinemia e o principal tratamento realizado foi a hemotransfusão.

To describe the clinical characteristics of patients with hemoglobinopathies at the Blood Center of Sergipe. In this cross-sectional study, clinical data were collected from patients with hemoglobinopathies by reading the medical records. Descriptive statistics and variable analysis were performed using the ANOVA test for comparison of means and Fisher's exact test for association, using a significance level of p<0.05. Data were collected from 96 patients. The main hemoglobinopathy found was SS (85.4%), followed by SC (11.5%) and ß-thalassemia (3.1%). The main complication was hyperferritinemia (50.7%), which had a direct relationship with blood transfusion (p=0.039) and patients with more complications had an older age (p=0.026). Hemotransfusion was required in 71.9% of the patients, whereas hydroxyurea and deserafirox in 40.6% and 13.5%, respectively. The main hemoglobinopathy found was SS, the main complication was hyperferritinemia and the main treatment was hemotransfusion.

Diseño y análisis psicométrico del inventario IPDP para evaluar el proceso de duelo patológico en adultos / Design and analysis of the IPDP psychometric inventory to evaluate pathological grief in adults

Resumen Se diseñó y realizó el análisis psicométrico de un instrumento para evaluar duelo patológico en adultos. El estudio es de tipo instrumental, los participantes fueron 235 hombres y mujeres mayores de 18 años. La validación de contenido se realizó con 8 jueces expertos en el tema y en psicometría, para la validez de constructo se realizó un análisis factorial exploratorio. Los ítems se agruparon en cuatro (4) factores que explican el 64.64% de la varianza. En el análisis bajo la teoría de respuesta al ítem (TRI), se encontró que el INFIT de los ítems o estadígrafo de ajuste que captura respuestas no esperadas, cerca del nivel de habilidad del evaluado osciló entre 0.6 y 1.19 y el OUTFIT estadígrafo que captura anomalías lejos de las habilidades calibradas para los evaluados, osciló entre .34 y 1.20, resultados que indican que la prueba cumple con los requerimientos psicométricos exigidos para este tipo de instrumentos. El instrumento aporta a la psicología, puesto que puede ser usado como una medida válida, fiable y útil para el objetivo y contexto para el cual fue elaborado.

Abstract We designed and analyzed an instrument to measure pathological grief in adults with 235 participants. Eight experts in grief and psychometry participated in the content validity phase, and an exploratory factor analysis was performed to assess construct validity. Items were grouped in four factors explaining 64.64% of the variance. The IRT analysis found an infit between 0.6 and 1.19 and the outfit between 0.34 and 1.20. The test fulfills the required psychometric indicators.

Anemia de células falciformes en pediatría: Revisión de la literatura / Sickle Cell Anemia in Pediatrics: Literature review / Anemia falciforme em pediatria: Revisão da literatura

Introducción: La anemia falciforme es una hemoglobinopatía estructural de origen genético, se caracteriza por la presencia de hemoglobina falciforme. La hemoglobina anormal es inestable, tiende a polimerizarse y puede ocluir la microcirculación, produciendo manifestaciones multisistémicas tanto agudas como crónicas relacionándose con mayor riesgo de contraer infecciones. Objetivo: Describir la información del tema expuesto resaltando los aspectos más relevantes como diagnóstico y tratamiento. Metodología: Se efectuó una revisión bibliográfica con búsqueda electrónica en las siguientes bases de datos: PubMed, MEDLINE, Medscape, Scopus; y se incluyó diferentes tipos de artículo (artículos originales, revisiones de temas y guías de manejo) que abordaran la anemia de células falciformes en pediatría. Resultados: Se obtuvo una revisión de 22 artículos, donde se describe el tema de anemia de células falciformes, pautas y tratamientos basados en el manejo y control de los síntomas; se evidencia que el uso de ecografía doppler transcraneal y las transfusiones demostraron ser estrategias preventivas o de tratamiento eficaces para las complicaciones relacionadas con esta patología en los niños. Conclusiones: En Colombia, la prevalencia de la patología no se encuentra establecida. Por otra parte, las principales manifestaciones se relacionan con complicaciones de vaso-oclusión en los diferentes órganos y la asplenia funcional, la cual predispone a cuadros infecciosos.[Tirado-Pérez IS, Zárate Vergara AC. Anemia de células falciformes en pediatría: Revisión de la literatura. Revisión de tema. MedUNAB 2017-2018; 20(3): 374-382].

Introduction: Sickle cell anemia is a structural hemoglobinopathy of genetic origin, characterized by the presence of sickle hemoglobin. Abnormal hemoglobin is unstable and tends to polymerize and can occlude the microcirculation. Also, it produces both acute and chronic multi system manifestations associated with an increased risk of infection. Objective: To describe the information of the exposed topic highlighting the most relevant aspects such as diagnosis and treatment. Methodology: A literature review with electronic search was carried out in the following databases: PubMed, MEDLINE, Medscape, Scopus; different types of articles were included that addressed sickle cell anemia in pediatrics such as original articles, reviews of topics and management. Results:Areview of 22 articles was obtained which describes the subject of sickle cell anemia, guidelines and treatments based on the management and control of symptoms. It is evident that the use of transcranial Doppler ultrasound and transfusions proved to be preventive strategies or effective treatments for the complications related to this pathology in children. Conclusions: In Colombia, the prevalence of the pathology is not established yet. On the other hand, the main manifestations are related to complications of vaso-occlusion in different organs and functional asplenia which predisposes to infectious conditions. [Tirado-Pérez IS, Zárate Vergara AC. Sickle Cell Anemia in Pediatrics: Literature review. MedUNAB 2017-2018; 20(3): 374-382].

Introdução: A anemia falciforme é uma hemoglobinopatia estrutural de origem genética, caracterizada pela presença de hemoglobina falciforme. A hemoglobina anormal é instável, tende a polimerizar-se e pode ocluir a microcirculação, produzindo manifestações multissistêmicas agudas e crônicas, associadas ao risco enorme das infecção graves. Objetivo: Descreva a informação do assunto exposto, destacando os aspectos mais relevantes, como o diagnóstico e seu tratamento. Metodologia: Foi realizada uma pesquisa eletrônica para a revisão bibliográfica, nos seguintes bancos de dados: PubMed, MEDLINE, Medscape, Scopus; incluindo outros tipos de artigos (artigos originais, revisões de tópicos e guias de gerenciamento), que abordam anemia falciforme em pediatria. Resultados: Foi obtida uma revisão de 22 artigos, que descreve o assunto da anemia falciforme, diretrizes e orientações baseados no tratamento e controle dos síntomas. É evidente que a identificação da doença com o uso de ultrasom Doppler transcraniana e das transfusões são estratégias preventivas ou de tratamentos eficazes para as complicações relacionadas com esta patologia nas crianças. Conclusões: Na Colômbia, a prevalência da patologia não está estabelecida. Por outro lado, as principais manifestações estão relacionadas a complicações de vaso-oclusão em diferentes órgãos e asplenia funcional, que predispõe a condições infecciosas. [Tirado-Pérez IS, Zárate Vergara AC. Anemia falciforme em pediatria: Revisão da literatura. MedUNAB 2017-2018; 20(3): 374-382].

Desempenho de crianças e adolescentes não pacientes no Zulliger SC / Performance of non-patient children and adolescents in Zulliger SC / El rendimiento de los niños y adolescentes no pacientes en Zulliger SC

Este artigo apresenta e compara o desempenho de crianças no Zulliger Sistema Compreensivo, ZSC, de acordo com a idade. Assim, 304 crianças, de ambos os sexos, de 7 a 14 anos, que frequentavam escolas públicas e particulares, foram avaliadas pelo ZSC, considerando 70 variáveis do teste. A análise dos dados utilizou estatística descritiva, ANOVA One-Way (teste post hoc de Tukey), teste de t Student e o teste d Cohen. Os resultados mostraram diferenças significativas que permitiram dividir a amostra em três grupos. Onze variáveis mostraram diferenças significativas entre os grupos com tamanhos de efeito entre moderado e grande. O aspecto mais evidente foi a evolução cognitiva ao longo do desenvolvimento, corroborando com a literatura. Os dados levantados demonstraram que o ZSC é um instrumento que pode ser válido para avaliação psicológica da faixa etária estudada. (AU)

This article presents and compares the performance of children in the Zulliger Comprehensive System (ZSC) according to age. A sample of 304 children of both sexes, from 7 to 14 years of age, attending public and private schools, were evaluated by ZSC, considering 70 variables of the test. Data analysis incorporated descriptive statistics, One-way ANOVA (Tukey post hoc test), t Student test and Cohen's test. The results showed significant differences that allowed sample division into three groups. Eleven variables showed significant differences between groups with moderate to large effect sizes. The most evident aspect was the developmental cognitive evolution, corroborating findings in the literature. The data showed that ZSC is a valid instrument for psychological evaluation of the studied age group. (AU)

Este artículo presenta y compara el desempeño de niños en el Zulliger Sistema Comprensivo, ZSC, de acuerdo a la edad. Por lo tanto, 304 niños de ambos sexos, de 7 a 14 años, que frecuentan escuelas públicas y privadas fueron evaluados por ZSC, teniendo en cuenta 70 variables del test. El análisis de datos utilizó estadística descriptiva, ANOVA One-way (Tukey test post hoc), test de t Student y el test de Cohen. Los resultados mostraron diferencias significativas que permitieron dividir la muestra en tres grupos. Once variables mostraron diferencias significativas entre los grupos de efectos moderados y los de gran tamaño. El aspecto más evidente fue la evolución cognitiva a lo largo del desarrollo, corroborando con la literatura. Los datos obtenidos mostraron que el ZSC es un instrumento válido para la evaluación psicológica del grupo de edad estudiado. (AU)

Research progress of zoledronic acid combined with other anti-tumor methods in the treatment of tumor bone metastases / 中国医师杂志

Tumor bone metastasis is one of the common complications of advanced tumor and one of the signs of poor prognosis.There are many targeted drugs for bone metastasis in the clinic,which play a very important role in the antitumor treatment and prevention of bone related events.Among them,zoledronic acid,a representative bisphosphonate drug,has been extensively studied.It has been found that zoledronic acid combined with other anti-tumor therapies can more effectively inhibit the occurrence of tumor and bone-related events.This article reviews the latest research on zoledronic acid combined with other antitumor methods to guide clinical use and provide research ideas.

Bone marrow necrosis and fat embolism syndrome: a dreadful complication of hemoglobin sickle cell disease

Sickle cell disease encompasses a wide range of genotypic presentation with particular clinical features. The entity affects millions of people, particularly those whose ancestors came from sub-Saharan Africa and other countries in the Western Hemisphere, Saudi Arabia, and India. Currently, the high frequency of S and C genes reflects natural selection through the protection of heterozygotes against severe malaria, the high frequency of consanguineous marriages, improvement of some public health policies and the nutritional standards in the poorer countries where newborns are now living long enough to present for diagnosis and management. Although there is a high burden of the disease, in many countries, the new-born sickle cell screening test is being performed and is rendering an early diagnosis; however, it is still difficult for sickle cell patients to find proper treatment and adequate follow-up. Moreover, in many countries, patients are neither aware of their diagnosis nor the care they should receive to prevent complications; also, they do not receive adequate genetic counseling. Hemoglobin SC (HbSC) disease is the most frequent double sickle cell heterozygosis found in Brazil. The clinical course tends to be more benign with fewer hospitalizations compared with double homozygotic SS patients. However, HbSC patients may present severe complications with a fatal outcome. We report the case of a 36-year-old man who presented to the emergency care facility with symptoms consistent with the diagnosis of sickling crisis. The outcome was unfavorable and death occurred just hours after admission. The autopsy revealed a generalized vaso-occlusive crisis by sickled red cells, bone marrow necrosis, and fat embolism syndrome.