Hyperbilirubinemia and retinopathy of prematurity: a retrospective cohort study.

Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease in preterm infants. Oxidative stress plays a key role in the pathogenesis of ROP. Due to its antioxidant effects, bilirubin has been proposed to be protective against ROP. This study explored the association between hyperbilirubinemia and ROP. We analyzed a 10-year cohort from a neonatal intensive care unit in Milan, Italy, including 1606 infants born under 32 weeks and/or < 1500 g. Data from 1606 infants meeting specific inclusion criteria were reviewed. Eighty infants were excluded due to lack of data, 1526 were deemed eligible for analysis, and 1269 had hyperbilirubinemia requiring phototherapy. There was a higher incidence of ROP among infants with hyperbilirubinemia (13.8%) versus those without (7.8%, p<0.01). Infants with any ROP, non-severe or severe ROP, were exposed to hyperbilirubinemia for a significantly higher number of days compared with those without ROP. Each additional day of exposure increases the risk of developing any ROP by 5%, non-severe ROP by 4%, and severe ROP by 6%. However, this correlation was not observed in infants with gestational age less than 27 weeks and/or body weight less than 1000 g.    Conclusion: Our data show that hyperbilirubinemia requiring phototherapy is associated with an increased risk of developing ROP. However, severe hyperbilirubinemia and ROP share many of their risk factors. Therefore, rather than being a risk factor itself, hyperbilirubinemia may be a surrogate for other risk factors for ROP.    Clinical Trial Registration: NCT05806684. What is Known: • The development of retinopathy of prematurity (ROP) is influenced by several critical risk factors, including low gestational age, low birth weight, supplemental oxygen use, and increased oxidative stress. • In vitro, unconjugated bilirubin is an effective scavenger of harmful oxygen species and a reducing agent, highlighting its potential protective role against oxidative stress. What is New: • Hyperbilirubinemia requiring phototherapy was associated with an increased risk of developing ROP, but this association was not observed in the most vulnerable population of extremely preterm infants. • Every additional day of phototherapy for hyperbilirubinemia increases the risk of ROP by 5% for any ROP, 4% for non-severe ROP, and 6% for severe ROP.

Direct separation of the enantiomers of ramosetron on a chlorinated cellulose-based chiral stationary phase in hydrophilic interaction liquid chromatography mode.

Ramosetron is an enantiopure active pharmaceutical ingredient marketed in Japan since 1996 and later in a few Southeast Asian countries predominantly as an antiemetic for patients receiving chemotherapy. In this study, a simple and rapid high-performance liquid chromoatography method for the separation of ramosetron and its related enantiomeric impurity by using hydrophilic interaction liquid chromatography mode is presented. Chiral resolution was performed on an analytical column (100 mm × 4.6 mm id) packed with 3 µm particles of cellulose-based Chiralpak IC-3 chiral stationary phase. Using a mobile phase containing acetonitrile-water-diethylamine (100:10:0.1, v/v/v) and setting the column temperature at 35°C, the resolution value was 7.35. At a flow rate of 1 mL/min, the enantioseparation was completed within 5 min. The proposed method was partially validated and it has proven to be sensitive with limit of detection and limit of quantitation of the (S)-enantiomer impurity of 44.5 and 133.6 ng/mL.

Hip arthrodesis conversion to dual mobility total hip arthroplasty in a young adult using a custom-made highly-porous titanium monobloc cup: A case report.

INTRODUCTION: Conversion of hip arthrodesis to total hip arthroplasty (THA) is an effective but challenging procedure to restore hip functionality and improve quality of life. Herein, a case of arthrodesis takedown to a dual mobility THA with a custom-made 3D-printed cup. PRESENTATION OF CASE: Due to higher risk of instability and loosening for the altered and atrophic anatomy, a custom-made highly-porous titanium dual mobility monobloc cup has been used for a cementless conversion THA in 31-year-old patient with hip arthrodesis. At 3-year follow-up clinical and radiographic results were excellent with the custom-made implant found stable and well osseointegrated. DISCUSSION: To the best of our knowledge, this is the first case of arthrodesis conversion to THA with custom-made highly-porous dual mobility cup in a young adult. The dual mobility construct helped reducing the risk of dislocation, while the highly-porous structure reduced the risk of aseptic loosening. CONCLUSION: The use of cementless highly-porous dual mobility implant in complex cases young patients is supported.

Acute total hip arthroplasty with a highly-porous multi-holes cup in elderly patients after traumatic acetabular fracture: A case series and literature review.

There are no general guidelines for the treatment of acetabular fractures. Open reduction and internal fixation is advised in young and active patients, while acute total hip arthroplasty (THA) is recommended for elderly patients in order to allow immediate weight bearing. Various THA systems have been reported. We present four cases, mean age 79 years (range 67-92), of closed acetabular fractures managed with acute cementless THA, comprising a highly-porous multi-hole acetabular cup and a CLS-type femoral stem. After extensive pre-operative planning, autograft was used to fill in the acetabulum defects left by the trauma and the press-fit acetabular cup were implanted. One or more screws were used to improve primary stability and secure bone fragments. Patients were follow-up for mean 1.5 years (range 1.1-2.0). A Brooker III heterotopic ossification was the only complication occurred postoperatively. All the patients were satisfied, with a mean Harris Hip Score of 90 and Postel Merle D'Aubigné score of 16.3. There were no radiolucency lines nor osteolysis, showing that the cups were well osteointegrated and fractures united. As the bone bed after acetabular fracture might be highly compromised, whenever acute THA is indicated, a highly-porous multi-hole cup could be used to limit radiolucency lines and aseptic loosening. The series is limited by the small number of cases but is significant for the promising results.

Viscoelastic coagulation testing in Neonatal Intensive Care Units: advantages and pitfalls in clinical practice.

The expression "developmental hemostasis" indicates the age-related physiological changes occurring during the maturational process of the hemostatic system. Despite the quantitative and qualitative alterations, the neonatal hemostatic system is competent and well-balanced. Conventional coagulation tests do not provide reliable information as they only explore the procoagulants during the neonatal period. In contrast, viscoelastic coagulation tests (VCTs), such as viscoelastic coagulation monitoring (VCM), thromboelastography (TEG or ClotPro), and rotational thromboelastometry (ROTEM), are point-of-care assays that provide a quick, dynamic and global view of the hemostatic process, allowing prompt and individualized therapeutic intervention when necessary. Their use in neonatal care is on the increase and they could help monitor patients at risk of hemostatic derangement. In addition, they are crucial for anticoagulation monitoring during extracorporeal membrane oxygenation. Moreover, implementing VCT-based monitoring could optimize blood product use.

Hemostasis in neonatal ECMO.

Extracorporeal membrane oxygenation (ECMO) is a life-saving support for cardio-respiratory function. Over the last 50 years, the extracorporeal field has faced huge technological progress. However, despite the improvements in technique and materials, coagulation problems are still the main contributor to morbidity and mortality of ECMO patients. Indeed, the incidence and survival rates of the main hemorrhagic and thrombotic complications in neonatal respiratory ECMO are relevant. The main culprit is related to the intrinsic nature of ECMO: the contact phase activation. The exposure of the human blood to the non-endothelial surface triggers a systemic inflammatory response syndrome, which chronically activates the thrombin generation and ultimately leads to coagulative derangements. Pre-existing illness-related hemostatic dysfunction and the peculiarity of the neonatal clotting balance further complicate the picture. Systemic anticoagulation is the management's mainstay, aiming to prevent thrombosis within the circuit and bleeding complications in the patient. Although other agents (i.e., direct thrombin inhibitors) have been recently introduced, unfractionated heparin (UFH) is the standard of care worldwide. Currently, there are multiple tests exploring ECMO-induced coagulopathy. A combination of the parameters mentioned above and the evaluation of the patient's underlying clinical context should be used to provide a goal-directed antithrombotic strategy. However, the ideal algorithm for monitoring anticoagulation is currently unknown, resulting in a large inter-institutional diagnostic variability. In this review, we face the features of the available monitoring tests and approaches, mainly focusing on the role of point-of-care (POC) viscoelastic assays in neonatal ECMO. Current gaps in knowledge and areas that warrant further study will also be addressed.

Expanded Newborn Screening and Genomic Sequencing in Latin America and the Resulting Social Justice and Ethical Considerations.

Newborn screening (NBS) has widely been utilized in developed countries as a cost-effective public health strategy that reduces morbidity and mortality. Developing countries, however, are new to the NBS scene and have their own unique challenges, both in instituting the program as well as effectively acting on the results. NBS offers numerous ethical issues on a global scale, however, here we argue that there are unique ethical issues surrounding the development and expansion of newborn screening in Latin America given its highly heterogenous population. Once a NBS program is effectively instated, ethical considerations continue when pursuing expansion of screening to include further conditions. While Latin America grapples with the ethics of expanded newborn screening (ENBS), some developed countries discuss utility of genomic sequencing technologies in the newborn population. When the ability to detect further pathology is expanded, one must know what to do with this information. As rare diseases are identified either on ENBS or via genome sequencing, access to treatments for these rare diseases can be a real challenge. If we consider newborn screening as a global initiative, then we need more than a deontology approach to analyze these challenges; we need an approach that considers the unique characteristics of each territory and tremendous heterogeneity that exists prior to the implementation of these programs. As genomic technology advances further in the developed world, while some developing countries still lack even basic newborn screening, there is a further widening of the gap in global health disparities. The question is posed as to who has responsibility for these newborns' lives on an international level. Without an approach towards newborn screening that accounts for the diverse global population, we believe optimal outcomes for newborns and families across the world will not be achieved.

A 3D microfluidic model for preclinical evaluation of TCR-engineered T cells against solid tumors.

The tumor microenvironment imposes physical and functional constraints on the antitumor efficacy of adoptive T cell immunotherapy. Preclinical testing of different T cell preparations can help in the selection of efficient immune therapies, but in vivo models are expensive and cumbersome to develop, while classical in vitro 2D models cannot recapitulate the spatiotemporal dynamics experienced by T cells targeting cancer. Here, we describe an easily customizable 3D model, in which the tumor microenvironment conditions are modulated and the functionality of different T cell preparations is tested. We incorporate human cancer hepatocytes as a single cell or as tumor cell aggregates in a 3D collagen gel region of a microfluidic device. Human T cells engineered to express tumor-specific T cell receptors (TCR-T cells) are then added in adjacent channels. The TCR-T cells' ability to migrate and kill the tumor target and the profile of soluble factors were investigated under conditions of varying oxygen levels and in the presence of inflammatory cytokines. We show that only the 3D model detects the effect that oxygen levels and the inflammatory environment impose on engineered TCR-T cell function, and we also used the 3D microdevice to analyze the TCR-T cell efficacy in an immunosuppressive scenario. Hence, we show that our microdevice platform enables us to decipher the factors that can alter T cell function in 3D and can serve as a preclinical assay to tailor the most efficient immunotherapy configuration for a specific therapeutic goal.

[Glucose transponer type 1 deficiency síndrome (GLUT-1 SD) treated with ketogenic diet. Report of one case]. / Síndrome de deficiencia del transportador de glucosa tipo 1 (SDGLUT-1) tratado con dieta cetogénica. Caso clínico.

The glucose transporter type 1 deficiency syndrome (GLUT-1 SD) (OMIM 606777) is an inborn error of metabolism of brain glucose transport. The characteristic clinical manifestations are seizures, hypotonia, developmental delay, microcephaly and hypoglycorrhachia. We report a girl with normal weight and height at birth. At 6 weeks of age she started with convulsions reaching up to 20 myoclonic seizures a day. She was treated with valproate, phenobarbital and carbamazepine without response. Blood analysis including aminoacids and acylcarnitines were all normal. The brain MRI showed frontal atrophy with an increased subarachnoidal space and Electroencephalography was abnormal. Blood glucose was 84 mg/dl and spinal fluid glucose 26 mg/dl with a ratio of 0.31 (Normal Ratio >0.65+/-00.1). These results suggested the diagnosis of GLUT-1 SD, and was confirmed with erythrocyte glucose uptake of 44% (Normal range 80-100%). A molecular study found the mutation 969del, C971T in exon 6 of the gene Glut-1. Treatment with a ketogenic diet was started immediately and after 7 days with this diet seizures ceased. Anticonvulsants were progressively suspended. At present, the patient is 6 years old, she continues on a ketogenic diet and supplements with L-carnitine, lipoic acid, vitamins and minerals. Growth and development are normal with an intelligence quotient of 103. It is concluded that it is necessary to include GLUT-1 SD in the differential diagnosis of children with early seizures that are non responsive to pharmacological treatment.

Perfil epidemiológico do trauma dentário e facial em Curitiba / Epidemiological profile of dental and facial trauma in Curitiba

Introdução: Trauma é uma lesão produzida por ação violenta, em geral de natureza física externa ao organismo.O atendimento é de urgência e alta complexidade. O trauma, além de sequelas físicas, traz também sequelas psicológicas graves. Os traumas faciais e dentários causam grandes conflitos psicológicos em virtude do comprometimento da estética. Objetivos: Analisar o perfil epidemiológico do trauma dentofacial nos pacientes atendidos no ano de 2009, no Pronto-Socorro Geral e Odontológico do Hospital Universitário Cajuru, na cidade de Curitiba (PR). Materiais e métodos: O estudo foi realizado por meio da análise retrospectiva de 1.380 prontuários de pacientes vítimas de trauma dentofacial atendidos no Hospital Universitário Cajuru no ano de 2009. Resultados: O sexo masculino compreendeu 66,37% dos pacientes traumatizados.A faixa etária de zero aos 10 anos foi a mais afetada, com 38,47%. As quedas foram o principal motivo dos traumas (53,92%). Os domingos (17,39%) e o período noturno (35,90%) foram os momentos mais frequentes dos traumatismos. O trauma dentário mais frequente foi a fratura coronária (30,25%) e os dentes mais acometidos foram os incisivos centrais (45,64%) Conclusão: As crianças foram as principais vítimas.O sexo masculino foi o mais acometido. Os traumas ocorrem, em sua maioria, durante a noite, sendo que no domingo a ocorrência desse tipo de trauma foi maior. A etiologia da maioria dos traumas são as quedas.O trauma dentário mais frequente foi a fratura coronária sendo que os dentes incisivos centrais são os mais frequentemente afetados. A maioria dos pacientes não sofreu fraturas ósseas associadas.

Introduction: Trauma is a lesion produced by a violent action, usually from outside the body. The service isurgent and of high complexity. The facial trauma brings high physiological conflict due to the impairment ofaesthetics. Objectives: The aim of the study was to analyze the epidemiological profile of dentofacial traumaof patients treated during the year 2009 in the Dental Emergency Service of the Cajuru Hospital, located inthe city of Curitiba (PR, Brazil). Materials and methods: The study was carried out through the retrospectiveanalysis of 1,380 medical records of patients victims of dentofacial trauma taken care in CajuruHospital duringthe year of 2009. Results: It was observed that 66,37% from the affected patients were men. Children (0 to 10years old) were the most affected age group, with 38,47%. The falls were the main cause of traumas (53,92%).Sundays (17,39%) and the nighttime (35,90%) were the most frequentperiod of time that traumas occurred.The most frequent type of trauma was the coronary fracture (30,25%) and the most affected teeth were centralincisors (45,64%). Conclusions: The children were the main victims of dentofacial trauma. The male sex wasthe most affected. It was noticed that traumas occur mostly during the night and on Sundays. The most frequentlyreported etiology of trauma was fall. The coronal fracture was the most frequent type of fracture andthe central incisor was the most affected tooth. Most of the patients did notreport associated bone fractures.

[Diagnosis and follow up of 23 children with organic acidurias]. / Diagnóstico y seguimiento de 23 niños con acidurias orgánicas.

BACKGROUND: Propionic aciduria (PA) and Methymalonic aciduria (MMA) result from an inherited abnormality of the enzymes propionyl CoA carboxylase and methylmalonyl CoA mutase respectively. This produces marked increases in the amino acids methionine, threonine, valine and isoleucine (MTVI). Their clinical presentation can be neonatal or late onset forms. AIM: To report 23 children with organic acidurias. MATERIAL AND METHODS: Twenty three cases of organic acidurias diagnosed since 1980 (17 PA and 6 MMA) and followed at the Institute of Nutrition and Food Technology, are reported. RESULTS: The average age of diagnosis was 3.9 days for the neonatal form and 8.3 months for the late onset form. The most frequent symptoms were hypotonia, lethargy and vomiting. Neonatal PA had mean ammonemias of 1089 +/- 678.3 micrograms/dl. The figure for MMA was 933 +/- 801.9 micrograms/dl. Seven children were dialyzed and 30% died. 16 children are followed and 81.2% have normal weight for age. Seven children required gastrostomy because of anorexia and failure to thrive. The nutritional treatment is based on natural and artificial proteins without MTVI, with periodical controls, amino acid and ammonia quantification. Some patients were submitted to enzyme assays and molecular studies. CONCLUSIONS: An early diagnosis and a very strict follow up allows a normal development of children with organic acidurias. There is a relationship between prognosis and the presentation form, the nutritional status and the emergency treatment during acute episodes. The importance of the enzymatic and molecular studies is emphasized because they facilitate treatment, accurate diagnosis and allow an adequate genetic counseling.

[Phenylketonuria diagnosed during the neonatal period and breast feeding]. / Fenilquetonuria de diagnóstico neonatal y lactancia materna.

BACKGROUND: Phenylketonuria (PKU) is due to of a defect in the phenylalanine hydroxylase gene (12q22-24.1) leading to hyperphenylalaninemia. Treatment consists in a low phenylalanine (Phe) diet. AIM: To evaluate the evolution of early diagnosed PKU children, receiving direct breast feeding, and a special formula without Phe, during their first six months of life. PATIENTS AND METHODS: Nineteen PKU children diagnosed in the neonatal period (19.29 +/- 13.8 days of age), treated with breast feeding and formula without Phe since diagnosis, were studied. Intake of calories, proteins and dietary Phe were quantified. Blood Phe, nutritional status and psychomotor development were also measured. RESULTS: The diet that these children received during the 6 months period of study, had a mean of 127 +/- 19.9 Kcal/kg/day, 1.95 +/- 0.3 g protein/kg/day and 35.3 +/- 9.5 mg Phe/kg/day. Fifteen children maintained the blood level of Phe under 8 mg/dl, considered an excellent metabolic control. Only 4 cases had intermittently high levels, between 10-12 mg/dl. At 6 months of age, 74% of the children maintained breast feeding as the only source of Phe. Sixty three percent had a normal nutritional status, 5.2% were at nutritional risk and 31.6% were overweight. Eighty one percent had a normal mental development. CONCLUSIONS: The use of direct breast feeding allows a good metabolic control and improves growth and development of early diagnosed PKU children.

Efectos de la prematurez sobre el desarrollo cognitivo y la atención en etapa escolar / Effects of prematurity on cognitive development and attention at school age

Gracias a los avances tecnológicos, los niños prematuros con discapacidades físicas mayores han disminuido su prevalencia; actualmente, los defectos cognitivos son la secuela predominante. Se investigó el desarrollo cognitivo y la atención en escolares con antecedentes de haber sido recién nacidos prematuros, a través de un estudio descriptivo, de corte transversal, en que se realizaron evaluaciones neuropsicológicas mediante WISC-R y test de Gordon a niños escolares con antecedentes de prematurez (EG<33s y/o PN<1500g) y niños controles con antecedentes de ser recién nacidos de término. Se evaluó a 77 pacientes: 40 niños prematuros (EG: 30,5 s) y 37 de término, entre 6-7 años. Aunque ambos grupos obtuvieron un CIT dentro del rango normal, se observó diferencias significativas (p<0,03) en desmedro del grupo prematuro en comparación con controles. Las habilidades atencionales también fueron significativamente menores para los prematuros (p< 0,01). Los niños prematuros se encuentran en riesgo de presentar problemas cognitivos y/o de atención en la etapa escolar. Se sugiere incorporar instrumentos de pesquisa de estas dificultades durante el seguimiento, que permitan un reconocimiento precoz e intervención oportuna.

The prevalence of premature children with major physical disabilities has diminished over time mainly due to advances in technology. Cognitive disorders are currently the main sequels. In order to study cognitive and attentional functioning of extremely premature infants at school age, a cross sectional study was designed. Neuropsychological assessments were performed by WISC-R and Gordon test, in prematures and controls at school age. Seventy seven children, 40 preterm (GA: 30.5 w) and 37 term at birth, aged 6-7 years-old were assessed. Although both groups obtained an overall IQ within the normal range, prematures showed significantly lower scores than the control group (p< 0.03). Attentional skills were also significantly lower (p <0.01) in the premature children. Children with a history of extreme prematurity are at risk for cognitive and attention impairment at school age. We suggest to introduce screening tools during follow-up which allow early recognition and appropriate intervention.

Enfermedad de Lesch-Nyhan / Lesch-Nyhan disease

Se presenta un caso de Enfermedad de Lesch-Nyhan típico, cuyo diagnóstico fue confirmado a través de técnicas de crecimiento celular diferencial. Esta técnica permitió también establecer la condición de portadora en la madre y una de las tías en la que se realizó el diagnóstico prenatal de un nuevo caso. Se revisan algunos aspectos clínicos, metabólicos y terapéuticos de interés, enfatizando la importancia de los estudios diagnósticos específicos para el consejo genético adecuado de familias con esta rara pero grave enfermedad

Diagnóstico de fenilquetonuria en Chile / Phenylketonuria: late diagnosis

Se presentan las características clínicas y bioquímicas de 4 niños PKU diagnosticados tardíamente, a una edad promedio de 3 años 11 meses. Se enfatiza la importancia de hacer un diagnóstico y tratamiento oportuno, de modo de prevenir la aparición de retardo mental. Se plantea la necesidad de desarrollar un programa de búsqueda masiva para la detección de PKU en el período neonatal en nuestro país

Desnutrición grave precoz y desarrollo psicomotor. Efectos de un programa de rehabilitación / Early severe malnutrition and psychomotor development. Effects of a rehabilitation program

This study evaluates the psychomotor development of 228 undernourished infants submitted to an integral rehabilitation program in Nutritional Recovery Centers. At admission these children present a moderate retardation of their developmental quotient: mean 0.59 +/- 0.17, improving significantly to mean 0.79 +/- 0.4 (p < 0.001) after an average period of 178.2 +/- 63.9 days of intervention. As regards areas of development, rehabilitation only demonstrates a significant change in coordination and language, not so in the social and motor areas. Those children presenting the most severe developmental delays are also those who obtain the greater benefits from this integral rehabilitation program.

Estudio de funciones cognitivas en escolares de nivel intelectual normal con antecedentes de desnutrición grave y precoz / A study on the cognitive functions of school children with normal IQ and histories of severe and early malnutrition

El presente trabajo es un estudio de corte transversal, cuyo objetivo fue evaluar los efectos a largo plazo de la desnutrición calórica-proteica severa y precoz sobre el desarrollo de funciones cognitivas básicas. La atención, memoria y capacidad de resolver problemas fue comparada entre un grupo de 16 escolares, con antecedentes de desnutrición marásmica severa durante los dos primeros años de vida y 16 escolares con un crecimiento normal. Todos los sujetos presentaban un coeficiente intelectual normal, una edad entre 8-10 años y pertenecían al mismo nivel socieconómico. Las funciones cognitivas fueron evaluadas empleando un microcomputador. La memoria se midió mediante una modificación de la subprueba de digitos del WISC; la atención con una modificación del Continous Perfomance Task y la capacidad de resolver problemas con una adaptación de la prueba de Dominó de Anstey. El grupo con atecedentes de desnutrición presentó un rendimiento menor que el grupo control, en las mediciones de memoria (Nº de dígitos retenidos) y en la capacidad de resolver problemas (Nº de respuestas correctas). En la prueba de atención, el grupo con antecedentes de desnutrición obtuvo un rendimiento interior en la latencia de respuesta frente a las respuestas correctas. Se concluye que estas diferencias sugieren que la desnutrición temprana tendría efectos deletéreos sobre funciones cognitivas básicas