RESUMEN

Hypoxic-ischemic encephalopathy (HIE) is a common condition occurring at birth, impairing central nervous system function. Therapeutic hypothermia is beneficial for suspected HIE as it reduces mortality and disability in survivors but not for other types of encephalopathy (e.g., metabolic). Amplitude-integrated electroencephalography (aEEG) complements limited resource Neonatal Intensive Care Units as a screening tool that can provide information regarding the degree of encephalopathy and electrographic seizures. Patients with HIE are at increased risk for seizures, which are subclinical in half of the cases. The aEEG emphasizes electroencephalographic amplitude differences, whereas continuous video electroencephalography (cEEG) provides a high-resolution picture of cerebral electrical activity, making it the most accurate method for detecting subclinical seizures. Still, its interpretation demands extensive training beyond the scope of neonatologists. Any infant in whom aEEG is suspicious for seizures should undergo cEEG to confirm the findings because even very low-amplitude artifacts might be misdiagnosed as seizures. We report a case and review the utility of aEEG in detecting subclinical seizures in neonates with HIE during therapeutic hypothermia while cEEG is not available.

RESUMEN

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is a condition causing brain injury in newborns with unclear pathogenesis. Cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway and NOD-like receptor protein 3 (NLRP3) mediated pyroptosis are thought to be involved in the pathological process of HIE, but whether these two mechanisms act independently is still unknown. Therefore, we aim to clarify whether there is any interaction between these two pathways and thus synergistically affects the progression of HIE. Methods: The HIE model of neonatal rats was established using the Rice-Vannucci method. The potential therapeutic effect of RU.521 targeting cGAS on HIE was explored through rescue experiment. Twenty-four hours after modeling was selected as observation point, sham + vehicle group, HIE + vehicle group and HIE + RU.521 group were established. A complete medium of BV2 cells was adjusted to a glucose-free medium, and the oxygen-glucose deprivation model was established after continuous hypoxia for 4 hours and reoxygenation for 12 to 24 hours. 2,3,5-triphenyl tetrazolium chloride staining was employed to detect ischemic cerebral infarction in rat brain tissue, and hematoxylin and eosin staining was used to observe tissue injury. Immunofluorescence was applied to monitor the expression of cGAS. Real-time quantitative polymerase chain reaction and western blot were utilized to detect the expression of messenger RNA and protein. Results: cGAS expression was increased in brain tissues of neonatal rats with HIE, and mainly localized in microglia. RU.521 administration reduced infarct size and pathological damage in rat HIE. Moreover, blocking cGAS with RU.521 significantly reduced inflammatory conditions in the brain by down-regulating STING expression, decreasing NLRP3 inflammasome activation and reducing microglial pyroptosis both in vivo and in vitro. Besides, RU.521 promoted the switching of BV2 cells towards the M2 phenotype. Conclusions: This study revealed a link between the cGAS/STING pathway and the NLRP3/GSDMD/pyroptosis pathway in neonatal HIE. Furthermore, the small molecule compound RU.521 can negatively regulate cGAS/STING/NLRP3/pyroptosis axis and promote M2 polarization in microglia, which provides a potential therapeutic strategy for the treatment of neuroinflammation in HIE.

RESUMEN

BACKGROUND: This retrospective study aims to assess the added diagnostic utility and clinical value of a 3-Tesla neonatal brain magnetic resonance imaging after obtaining a 1-Tesla magnetic resonance imaging within the neonatal intensive care unit. METHODS: A cohort of 34 infants had an initial 1-Tesla magnetic resonance imaging and repeat imaging within 14 days in a 3-Tesla scanner. All infants were admitted to the level III neonatal intensive care unit at Brigham and Women's Hospital, and all images were interpreted by pediatric neuroradiologists. RESULTS: For 31 infants (91%), the 3-Tesla magnetic resonance imaging showed similar or expected evolution of known findings found on 1 Tesla. For infants with change between the 1-Tesla and 3-Tesla imaging results, there was no clinical impact. CONCLUSION: Images from 1-Tesla magnetic resonance imaging were sufficient for characterizing a wide range of neonatal brain injuries and abnormalities and repeated 3-Tesla magnetic resonance imaging did not yield further clinical benefit.

RESUMEN

Hypoxic ischemic encephalopathy (HIE) is the most common cause of neonatal encephalopathy and results in significant morbidity and mortality. Long-term outcomes of the condition encompass impairments across all developmental domains. While therapeutic hypothermia (TH) has improved outcomes for term and late preterm infants with moderate to severe HIE, trials are ongoing to investigate the use of TH for infants with mild or preterm HIE. There is no evidence that adjuvant therapies in combination with TH improve long-term outcomes. Numerous trials of various adjuvant therapies are underway in the quest to further improve outcomes for infants with HIE.

Asunto(s)

Hipotermia Inducida , Hipoxia-Isquemia Encefálica , Recien Nacido Prematuro , Humanos , Hipoxia-Isquemia Encefálica/terapia , Recién Nacido , Hipotermia Inducida/métodos , Resultado del Tratamiento

RESUMEN

The authors summarize the methodology for a new pragmatic comparative effectiveness research investigation, Cooling Prospectively Infants with Mild Encephalopathy (COOLPRIME), which uses sites' existing mild hypoxic-ischemic encephalopathy (HIE) treatment preference (hypothermia or normothermia) to assess hypothermia effectiveness and safety. COOLPRIME's primary aim is to determine the safety and effectiveness of hypothermia compared to normothermia in mild HIE. Engagement of Families and Community Affected by Hypoxic-Ischemic Encephalopathy strongly favored Effectiveness over Efficacy Trials leading to COOL PRIME design.

Asunto(s)

Investigación sobre la Eficacia Comparativa , Hipotermia Inducida , Hipoxia-Isquemia Encefálica , Humanos , Hipotermia Inducida/métodos , Hipoxia-Isquemia Encefálica/terapia , Recién Nacido , Estudios Prospectivos , Lactante , Resultado del Tratamiento

RESUMEN

Hypoxic ischemic encephalopathy (HIE) in neonates can cause severe, life-long functional impairments or death. Treatment of these neonates can involve ethically challenging questions about if, when, and how it may be appropriate to limit life-sustaining medical therapy. Further, parents whose infants suffer severe neurologic damage may seek recourse in the form of a medical malpractice lawsuit. This study uses several hypothetical cases to highlight important ethical and legal considerations in the care of infants with HIE.

Asunto(s)

Hipoxia-Isquemia Encefálica , Humanos , Hipoxia-Isquemia Encefálica/terapia , Recién Nacido , Mala Praxis/legislación & jurisprudencia , Privación de Tratamiento/legislación & jurisprudencia , Privación de Tratamiento/ética , Padres , Hipotermia Inducida/ética , Hipotermia Inducida/métodos

RESUMEN

OBJECTIVE: This scoping review aims to explore the current state of encounter notification systems (ENS) between emergency departments (EDs) and primary care providers (PCPs), focusing on their mechanisms, effectiveness, impacts, and challenges in healthcare settings. METHODS: A systematic search was conducted using PubMed/MEDLINE and Google Scholar to identify relevant literature on ENS between EDs and PCPs. Eligible studies were selected based on predefined criteria, and data were synthesized narratively. RESULTS: The initial search yielded 1,396 articles, with 29 included in the review. Studies highlighted the significance of encounter notifications in improving communication and care coordination between EDs and PCPs, leading to enhanced patient outcomes. However, challenges such as technological barriers, privacy concerns, and variations in healthcare settings were identified. CONCLUSION: ENS play a crucial role in enhancing communication and care coordination between EDs and PCPs. Despite challenges, these systems offer substantial benefits and opportunities for improving patient care in the ED-primary care continuum. Future research should focus on addressing implementation barriers and evaluating long-term impacts to optimize the effectiveness of ENS in this context.

Asunto(s)

Servicio de Urgencia en Hospital , Atención Primaria de Salud , Humanos , Servicio de Urgencia en Hospital/organización & administración , Comunicación , Continuidad de la Atención al Paciente

RESUMEN

OBJECTIVE: The study aimed to address the challenge of early assessment of neonatal hypoxic-ischemic encephalopathy (HIE) severity to identify candidates for therapeutic hypothermia (TH). The objective was to develop an automated classification model for neonatal EEGs, enabling accurate HIE severity assessment 24/7. METHODS: EEGs recorded within 6 h of life after perinatal anoxia were visually graded into 3 severity groups (HIE French Classification) and quantified using 6 qEEG markers measuring amplitude, continuity and frequency content. Machine learning models were developed on a dataset of 90 EEGs and validated on an independent dataset of 60 EEGs. RESULTS: The selected model achieved an overall accuracy of 80.6% in the development phase and 80% in the validation phase. Notably, the model accurately identified 28 out of 30 children for whom TH was indicated after visual EEG analysis, with only 2 cases (moderate EEG abnormalities) not recommended for cooling. CONCLUSIONS: The combination of clinically relevant qEEG markers led to the development of an effective automated EEG classification model, particularly suited for the post-anoxic latency phase. This model successfully discriminated neonates requiring TH. SIGNIFICANCE: The proposed model has potential as a bedside clinical decision support tool for TH.

Asunto(s)

Electroencefalografía , Hipotermia Inducida , Hipoxia-Isquemia Encefálica , Humanos , Hipoxia-Isquemia Encefálica/terapia , Hipoxia-Isquemia Encefálica/fisiopatología , Hipoxia-Isquemia Encefálica/clasificación , Hipoxia-Isquemia Encefálica/diagnóstico , Hipotermia Inducida/métodos , Recién Nacido , Electroencefalografía/métodos , Femenino , Masculino , Aprendizaje Automático

RESUMEN

Background Acidosis, hypoxemia, and hypercarbia are symptoms of a syndrome known as perinatal asphyxia that occurs during the first and second stages of labor and shortly after delivery due to poor gas exchange. The Doppler technique is a non-invasive way to assess the risk of neurodevelopment damage in hypoxic-ischemic encephalopathy (HIE) that may be done at the patient's bedside without disturbing them. The study aims to evaluate cranial ultrasound findings in HIE and investigate the role of resistive index (RI) values assessed by color Doppler transcranial ultrasonography in predicting early morbidities in neonates with HIE within 72 hours of life. Methodology Prospective observational research was carried out at the north Karnataka region's tertiary newborn critical care unit. The study included 54 infants with HIE in total. The male-to-female ratio was 1.7:1, with 34 (63%) male and 20 (37%) female newborns. Results About 32 instances had grade I HIE, 8 had grade II HIE, and 14 had grade III HIE. In 35 instances (64.81%), the RI was normal; in 19 cases (35.19%), it was abnormal. Increased periventricular density and cerebral parenchyma echo density were common Doppler ultrasonography findings. Roughly 93% of people survived, and 7% of people died from HIE. Seizures (12.96%) and acute renal damage (33.33%) were the most frequent consequences. Conclusion In instances of HIE, the RI was revealed to be a favorable predictive indicator for newborn prognosis. Counseling and educating parents about early morbidities, anticipated long-term consequences, and the need for follow-up will all benefit from it. Additionally, color Doppler is a practical and secure diagnostic method for determining a newborn's level of HIE.

RESUMEN

Herein, we demonstrate an efficient method for multi-deuterium labelling of pirtobrutinib-a Bruton's tyrosine kinase inhibitor recently approved by the FDA-using a straightforward hydrogen isotope exchange (HIE) reaction. A remarkably high level of deuterium incorporation was achieved using an excess of a Kerr-type iridium catalyst. The key factor in the significant deuterium labelling was the decision to employ a deuterium uniformly labelled solvent, chlorobenzene-d5, at an elevated temperature. Virtually, no d0-d3 species were detected, with only traces of d4-d5 isotopomers (< 5%) observable in the mass spectrum of pirtobrutinib-d8, fulfilling requirements for stable isotope-labelled internal standard. The labelled compound-mainly consisting of isotopomers d6-d9 at 82.4% of the total abundance-was isolated in a high yield (73%) and purity (99%). Noteworthy, fluorine group acting as a directing group was observed for the first time. Significant incorporation of deuterium in ortho-positions, exceeding 87%, was observed. Interestingly, chlorinated solvent used in the HIE reactions was non-specifically deuterated yielding up to 0.42 deuterium per chlorobenzene molecule even at an exceptionally low iridium catalyst loading of 4.17 × 10-2 mol%.

Asunto(s)

Deuterio , Marcaje Isotópico , Deuterio/química , Pirimidinas/química , Piperidinas/química

RESUMEN

Hypoxic-ischemic encephalopathy (HIE) is a brain lesion caused by inadequate blood supply and oxygen deprivation, often occurring in neonates. It has emerged as a grave complication of neonatal asphyxia, leading to chronic neurological damage. Nevertheless, the precise pathophysiological mechanisms underlying HIE are not entirely understood. This paper aims to comprehensively elucidate the contributions of hypoxia-ischemia, reperfusion injury, inflammation, oxidative stress, mitochondrial dysfunction, excitotoxicity, ferroptosis, endoplasmic reticulum stress, and apoptosis to the onset and progression of HIE. Currently, hypothermia therapy stands as the sole standard treatment for neonatal HIE, albeit providing only partial neuroprotection. Drug therapy and stem cell therapy have been explored in the treatment of HIE, exhibiting certain neuroprotective effects. Employing drug therapy or stem cell therapy as adjunctive treatments to hypothermia therapy holds great significance. This article presents a systematic review of the pathogenesis and treatment strategies of HIE, with the goal of enhancing the effect of treatment and improving the quality of life for HIE patients.

RESUMEN

Hypoxic ischemic encephalopathy (HIE) is a primary cause of neonatal death and disabilities. The pathogenetic process of HIE is closely associated with neuroinflammation. Therefore, targeting and suppressing inflammatory pathways presents a promising therapeutic strategy for the treatment of HIE. Echinatin is an active component of glycyrrhiza, with anti-inflammatory and anti-oxidative properties. It is commonly combined with other traditional Chinese herbs to exert heat-clearing and detoxifying effects. This study aimed to investigate the anti-inflammatory and neuroprotective effects of Echinatin in neonatal rats with hypoxic-ischemic brain damage, as well as in PC12 cells exposed to oxygen-glucose deprivation (OGD). In vivo, Echinatin effectively reduced cerebral edema and infarct volume, protected brain tissue morphology, improved long-term behavioral functions, and inhibited microglia activation. These effects were accompanied by the downregulation of inflammatory factors and pyroptosis markers. The RNA sequencing analysis revealed an enrichment of inflammatory genes in rats with hypoxic-ischemic brain damage, and Protein-protein interaction (PPI) network analysis identified TLR4, MyD88, and NF-κB as the key regulators. In vitro, Echinatin reduced the levels of TLR4 relevant proteins, inhibited nuclear translocation of NF-κB, reduced the expression of downstreams inflammatory cytokines and pyroptosis proteins, and prevented cell membrane destructions. These findings demonstrated that Echinatin could inhibit the TLR4/NF-κB pathway, thereby alleviating neuroinflammation and pyroptosis. This suggests that Echinatin could be a potential candidate for the treatment of HIE.

Asunto(s)

Hipoxia-Isquemia Encefálica , FN-kappa B , Fármacos Neuroprotectores , Piroptosis , Ratas Sprague-Dawley , Transducción de Señal , Receptor Toll-Like 4 , Animales , Masculino , Ratas , Animales Recién Nacidos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/patología , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/patología , Inflamación/tratamiento farmacológico , Microglía/efectos de los fármacos , Microglía/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , FN-kappa B/metabolismo , Células PC12 , Piroptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Subunidad p50 de NF-kappa B/metabolismo

RESUMEN

Background: This study investigates the association between the mean arterial blood pressure (MAP), vasopressor requirement, and severity of hypoxic-ischemic encephalopathy (HIE) after cardiac arrest (CA). Methods: Between 2008 and 2017, we retrospectively analyzed the MAP 200 h after CA and quantified the vasopressor requirements using the cumulative vasopressor index (CVI). Through a postmortem brain autopsy in non-survivors, the severity of the HIE was histopathologically dichotomized into no/mild and severe HIE. In survivors, we dichotomized the severity of HIE into no/mild cerebral performance category (CPC) 1 and severe HIE (CPC 4). We investigated the regain of consciousness, causes of death, and 5-day survival as hemodynamic confounders. Results: Among the 350 non-survivors, 117 had histopathologically severe HIE while 233 had no/mild HIE, without differences observed in the MAP (73.1 vs. 72.0 mmHg, pgroup = 0.639). Compared to the non-survivors, 211 patients with CPC 1 and 57 patients with CPC 4 had higher MAP values that showed significant, but clinically non-relevant, MAP differences (81.2 vs. 82.3 mmHg, pgroup < 0.001). The no/mild HIE non-survivors (n = 54), who regained consciousness before death, had higher MAP values compared to those with no/mild HIE (n = 179), who remained persistently comatose (74.7 vs. 69.3 mmHg, pgroup < 0.001). The no/mild HIE non-survivors, who regained consciousness, required fewer vasopressors (CVI 2.1 vs. 3.6, pgroup < 0.001). Independent of the severity of HIE, the survivors were weaned faster from vasopressors (CVI 1.0). Conclusions: Although a higher MAP was associated with survival in CA patients treated with a vasopressor-supported MAP target above 65 mmHg, the severity of HIE was not. Awakening from coma was associated with less vasopressor requirements. Our results provide no evidence for a MAP target above the current guideline recommendations that can decrease the severity of HIE.

RESUMEN

Hypoxic-ischemic encephalopathy (HIE) is a prominent cause of neonatal mortality and neurodevelopmental disorders; however, effective therapeutic interventions remain limited. During neonatal hypoxic-ischemic injury events, increased reactive oxygen species (ROS) production and decreased antioxidant levels lead to the induction of oxidative stress, which plays a pivotal role in the pathological process of neonatal HIE. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key endogenous antioxidant transcription factor that protects against oxidative stress by promoting the transcription of various antioxidant genes. It has been demonstrated that Nrf2 signaling pathway activation by different compounds may protect against neonatal HIE. This review outlines the role of oxidative stress in neonatal HIE and summarizes the impact of antioxidants on neonatal HIE via activation of the Nrf2 signaling pathway. In conclusion, Nrf2 signaling pathway potentially exerts antioxidant, anti-inflammatory, antiapoptotic and antiferroptotic effects, thereby emerging as a focal point for future neonatal HIE treatment strategies.

Asunto(s)

Hipoxia-Isquemia Encefálica , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Recién Nacido , Animales , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Antioxidantes/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología

RESUMEN

BACKGROUND: To investigate the prevalence and associated outcomes of glucose abnormalities in infants with hypoxic ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). METHODS: Glucose values were reviewed in all HIE infants. Pearson's correlation was used to assess the association of hypo- and hyperglycemic episodes with neonatal brain MRI and neurodevelopmental outcomes (NDO) at 12 & 24 months. RESULTS: Of 153 infants included, 31, 56 and 43 had episodes of hypo-, hyperglycemia and combined, respectively. Hyperglycemia and combined hypo/hyper had higher mortality (p = 0.035), seizures (p = 0.009), and longer hospitalization (p = 0.023). Hypo- and hyperglycemia were associated with parenchymal hemorrhages (p = 0.028 & p = 0.027, respectively). Hypoglycemia was associated with restricted diffusion (p = 0.014), while hyperglycemia was associated with cortical injuries (p = 0.045). Each hour of hyper- or hypoglycemia was associated with 5.2-5.8 times unfavorable outcomes (p < 0.001). CONCLUSION: Blood glucose aberrations were detrimental in HIE infants treated with TH. Optimizing glucose management is crucial in this setting.

Asunto(s)

Glucemia , Hiperglucemia , Hipoglucemia , Hipotermia Inducida , Hipoxia-Isquemia Encefálica , Humanos , Hipoxia-Isquemia Encefálica/terapia , Hipotermia Inducida/métodos , Masculino , Recién Nacido , Femenino , Glucemia/metabolismo , Lactante , Imagen por Resonancia Magnética , Estudios Retrospectivos , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Resultado del Tratamiento

RESUMEN

Neonatal Encephalopathy (NE) is a major cause of lifelong disability and neurological complications in affected infants. Identifying novel diagnostic biomarkers in this population may assist in predicting MRI injury and differentiate neonates with NE from those with low-cord pH or healthy neonates and may help clinicians make real-time decisions. To compare the microRNA (miRNA) profiles between neonates with NE, healthy controls, and neonates with low cord pH. Moreover, miRNA concentrations were compared to brain injury severity in neonates with NE. This is a retrospective analysis of miRNA profiles from select samples in the biorepository and data registry at the University of Florida Health Gainesville. The Firefly miRNA assay was used to screen a total of 65 neurological miRNA targets in neonates with NE (n = 36), low cord pH (n = 18) and healthy controls (n = 37). Multivariate statistical techniques, including principal component analysis and orthogonal partial least squares discriminant analysis, and miRNA Enrichment Analysis and Annotation were used to identify miRNA markers and their pathobiological relevance. A set of 10 highly influential miRNAs were identified, which were significantly upregulated in the NE group compared to healthy controls. Of these, miR-323a-3p and mir-30e-5p displayed the highest fold change in expression levels. Moreover, miR-34c-5p, miR-491-5p, and miR-346 were significantly higher in the NE group compared to the low cord pH group. Furthermore, several miRNAs were identified that can differentiate between no/mild and moderate/severe injury in the NE group as measured by MRI. MiRNAs represent promising diagnostic and prognostic tools for improving the management of NE.

Asunto(s)

Lesiones Encefálicas , Enfermedades del Recién Nacido , MicroARNs , Recién Nacido , Lactante , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Estudios Retrospectivos , Biomarcadores , Estudios de Cohortes , Lesiones Encefálicas/diagnóstico , Lesiones Encefálicas/genética , Perfilación de la Expresión Génica/métodos

RESUMEN

Hypoxic-ischemic encephalopathy (HIE) occurs in up to 7 out of 1000 births and accounts for almost a quarter of neonatal deaths worldwide. Despite the name, many newborns with HIE have little evidence of perinatal hypoxia. We hypothesized that some infants with HIE have genetic disorders that resemble encephalopathy. We reviewed genetic results for newborns with HIE undergoing exome or genome sequencing at a clinical laboratory (2014-2022). Neonates were included if they had a diagnosis of HIE and were delivered ≥35 weeks. Neonates were excluded for cardiopulmonary pathology resulting in hypoxemia or if neuroimaging suggested postnatal hypoxic-ischemic injury. Of 24 patients meeting inclusion criteria, six (25%) were diagnosed with a genetic condition. Four neonates had variants at loci linked to conditions with phenotypic features resembling HIE, including KIF1A, GBE1, ACTA1, and a 15q13.3 deletion. Two additional neonates had variants in genes not previously associated with encephalopathy, including DUOX2 and PTPN11. Of the six neonates with a molecular diagnosis, two had isolated HIE without apparent comorbidities to suggest a genetic disorder. Genetic diagnoses were identified among neonates with and without sentinel labor events, abnormal umbilical cord gasses, and low Apgar scores. These results suggest that genetic evaluation is clinically relevant for patients with perinatal HIE.

Asunto(s)

Secuenciación del Exoma , Hipoxia-Isquemia Encefálica , Humanos , Hipoxia-Isquemia Encefálica/genética , Hipoxia-Isquemia Encefálica/diagnóstico , Hipoxia-Isquemia Encefálica/diagnóstico por imagen , Recién Nacido , Femenino , Masculino , Estudios Retrospectivos , Predisposición Genética a la Enfermedad , Exoma/genética , Enfermedades Genéticas Congénitas/genética , Enfermedades Genéticas Congénitas/diagnóstico

Asunto(s)

Errores Innatos del Metabolismo de los Metales , Recién Nacido , Humanos , Fenotipo , Errores Innatos del Metabolismo de los Metales/complicaciones , Errores Innatos del Metabolismo de los Metales/diagnóstico , Errores Innatos del Metabolismo de los Metales/genética

RESUMEN

Halofuginone hydrobromide has shown potent antiviral efficacy against a variety of viruses such as SARS-CoV-2, dengue, or chikungunya virus, and has, therefore, been hypothesized to have broad-spectrum antiviral activity. In this paper, we tested this broad-spectrum antiviral activity of Halofuginone hydrobomide against viruses from different families (Picornaviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, and Flaviviridae). To this end, we used relevant human models of the airway and intestinal epithelium and regionalized neural organoids. Halofuginone hydrobomide showed antiviral activity against SARS-CoV-2 in the airway epithelium with no toxicity at equivalent concentrations used in human clinical trials but not against any of the other tested viruses.

Asunto(s)

Antivirales , Piperidinas , Quinazolinonas , Virus , Humanos , Antivirales/farmacología , Antivirales/uso terapéutico , Sistemas Microfisiológicos , SARS-CoV-2 , Encéfalo

RESUMEN

Perinatal spinal cord injury is a relatively uncommon, but a frequently misdiagnosed disorder. Improvements in obstetric care have certainly led to a decrease in the incidence of birth related spinal cord trauma but unfortunately the incidence of hypoxic-ischemic encephalopathy is still very high. The exact incidence of spinal cord trauma is difficult to determine because the spinal cord is not routinely examined in far and few neonatal autopsies done in India. Here, authors present a neonate who received treatment for birth asphyxia and then had extubation failure which made the clock tick towards cervical cord injury. This baby had a hemorrhagic contusion of cervical spinal cord.

Asunto(s)

Asfixia Neonatal , Médula Cervical , Hipoxia-Isquemia Encefálica , Traumatismos de la Médula Espinal , Recién Nacido , Embarazo , Femenino , Humanos , Hipoxia-Isquemia Encefálica/complicaciones , Hipoxia-Isquemia Encefálica/diagnóstico , Médula Cervical/diagnóstico por imagen , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/diagnóstico , Asfixia Neonatal/complicaciones , Incidencia