URB447 Is Neuroprotective in Both Male and Female Rats after Neonatal Hypoxia-Ischemia and Enhances Neurogenesis in Females.

The need for new and effective treatments for neonates suffering from hypoxia-ischemia is urgent, as the only implemented therapy in clinics is therapeutic hypothermia, only effective in 50% of cases. Cannabinoids may modulate neuronal development and brain plasticity, but further investigation is needed to better describe their implication as a neurorestorative therapy after neonatal HI. The cannabinoid URB447, a CB1 antagonist/CB2 agonist, has previously been shown to reduce brain injury after HI, but it is not clear whether sex may affect its neuroprotective and/or neurorestorative effect. Here, URB447 strongly reduced brain infarct, improved neuropathological score, and augmented proliferative capacity and neurogenic response in the damaged hemisphere. When analyzing these effects by sex, URB447 ameliorated brain damage in both males and females, and enhanced cell proliferation and the number of neuroblasts only in females, thus suggesting a neuroprotective effect in males and a double neuroprotective/neurorestorative effect in females.

[Feasibility of using artificial intelligence for screening COVID-19 patients in ParaguayViabilidade do uso de inteligência artificial na triagem de pacientes com COVID-19 no Paraguai]. / Factibilidad de la utilización de la inteligencia artificial para el cribado de pacientes con COVID-19 en Paraguay.

Objective: Study the feasibility of using artificial intelligence as a sensitive and specific method for COVID-19 screening in patients with respiratory conditions, using chest CT scan images and a telemedicine platform. Methods: From March 2020 to June 2021, the authors conducted an observational descriptive multicenter feasibility study based on artificial intelligence (AI) for COVID-19 screening using chest images of patients with respiratory conditions who presented at public hospitals. The AI platform was used to diagnose chest CT scan images; this was then compared with molecular diagnosis (RT-PCR) to determine whether they matched and to analyze the feasibility of AI for screening patients with suspected COVID-19. A telemedicine platform was used to send images and diagnostic results. Results: Screening of 3 514 patients with a suspected COVID-19 diagnosis was performed in 14 hospitals around the country. Most patients were aged 27 to 59 years, followed by those over 60. The average age was 48.6 years; 52.8% were male. The most frequent findings were severe pneumonia, bilateral pneumonia with pleural effusion, bilateral pulmonary emphysema, and diffuse ground glass opacity, among others. There was an average of 93% matching and 7% mismatching between images analyzed by AI and RT-PCR. Sensitivity and specificity of the AI system, obtained by comparing AI and RT-PCR screening results, were 93% and 80% respectively. Conclusions: The use of sensitive and specific AI for stratified rapid detection of COVID-19 in patients with respiratory conditions by using chest CT scan images and a telemedicine platform in public hospitals in Paraguay is feasible.

Objetivo: Examinar a viabilidade do uso de inteligência artificial como um método sensível e específico de triagem de COVID-19 em pacientes com afecções respiratórias, empregando imagens obtidas por exame de tomografia do tórax e uma plataforma de telemedicina. Métodos: Entre março de 2020 e junho de 2021, foi realizado um estudo observacional descritivo multicêntrico sobre a viabilidade do uso de inteligência artificial (IA) para a triagem de COVID-19, empregando imagens do tórax de pacientes com afecções respiratórias atendidos em hospitais da rede pública. O diagnóstico das imagens obtidas em tomografia do tórax foi realizado por meio de uma plataforma de IA e, em seguida, cotejado com o diagnóstico molecular (RT-PCR) para determinar a concordância entre os métodos utilizados e analisar a viabilidade deste processo para a triagem de pacientes com suspeita de COVID-19. As imagens e os resultados do exame diagnóstico foram disponibilizados em uma plataforma de telemedicina. Resultados: Foi realizada a triagem de 3 514 pacientes com suspeita de COVID-19 atendidos em 14 hospitais de todo o país. Os pacientes, na sua maioria, tinham entre 27 e 59 anos de idade ou pertenciam à faixa etária acima de 60 anos, com média de idade de 48,6 anos, sendo que 52,8% eram do sexo masculino. Os achados mais comuns foram pneumonia grave, pneumonia bilateral com derrame pleural, enfisema pulmonar bilateral e opacidade difusa em vidro fosco, entre outros. Verificou-se, em média, 93% de concordância e 7% de discordância entre as imagens analisadas com uso de IA e os resultados do exame de RT-PCR, com uma sensibilidade de 93% e especificidade de 80% desse sistema de triagem. Conclusões: Demonstrou-se que o uso de um sistema de IA sensível e específico é viável nos hospitais públicos do Paraguai para a detecção rápida estratificada de COVID-19 em pacientes com afecções respiratórias, empregando imagens de exame de tomografia do tórax e uma plataforma de telemedicina.

Cannabinoid-mediated Modulation of Oxidative Stress and Early Inflammatory Response after Hypoxia-Ischemia.

In the process of neonatal encephalopathy, oxidative stress and neuroinflammation have a prominent role after perinatal asphyxia. With the exception of therapeutic hypothermia, no therapeutic interventions are available in the clinical setting to target either the oxidative stress or inflammation, despite the high prevalence of neurological sequelae of this devastating condition. The endocannabinoid system (ECS), recently recognized as a widespread neuromodulatory system, plays an important role in the development of the central nervous system (CNS). This study aims to evaluate the potential effect of the cannabinoid (CB) agonist WIN 55,212-2 (WIN) on reactive oxygen species (ROS) and early inflammatory cytokine production after hypoxia-ischemia (HI) in fetal lambs. Hypoxic-ischemic animals were subjected to 60 min of HI by partial occlusion of the umbilical cord. A group of lambs received a single dose of 0.01 µg/kg WIN, whereas non-asphyctic animals served as controls. WIN reduced the widespread and notorious increase in inflammatory markers tumor necrosis factor (TNF)-α and interleukin (IL)-1ß and IL-6 induced by HI, a modulatory effect not observed for oxidative stress. Our study suggests that treatment with a low dose of WIN can alter the profile of pro-inflammatory cytokines 3 h after HI.

[Public health impact of a remote diagnosis system implemented in regional and district hospitals in Paraguay]. / Impacto en la salud pública del sistema de telediagnóstico implementado en Paraguay.

OBJECTIVE: Determine the viability of a remote diagnosis system implemented to provide health care to remote and scattered populations in Paraguay. METHODS: The study was conducted in all regional and general hospitals in Paraguay, and in the main district hospitals in the country's 18 health regions. Clinical data, tomographic images, sonography, and electrocardiograms (ECGs) of patients who needed a diagnosis by a specialized physician were entered into the system. This information was sent to specialists in diagnostic imaging and in cardiology for remote diagnosis and the report was then forwarded to the hospitals connected to the system. The cost-benefit and impact of the remote diagnosis tool was analyzed from the perspective of the National Health System. RESULTS: Between January 2014 and May 2015, a total of 34 096 remote diagnoses were made in 25 hospitals in the Ministry of Health's telemedicine system. The average unit cost of remote diagnosis was US$2.6 per ECG, tomography, and sonography, while the unit cost of "face-to-face" diagnosis was US$11.8 per ECG, US$68.6 per tomography, and US$21.5 per sonography. As a result of remote diagnosis, unit costs were 4.5 times lower for ECGs; 26.4 times lower for tomography, and 8.3 times lower for sonography. In monetary terms, implementation of the remote diagnosis system during the 16 months of the study led to average savings of US$2 420 037. CONCLUSION: Paraguay has a remote diagnosis system for electrocardiography, tomography, and sonography, using low-cost information and communications technologies (ICTs) based on free software that is scalable to other types of remote diagnostic studies of interest for public health. Implementation of remote diagnosis helped to strengthen the integrated network of health services and programs, enabling professionals to optimize their time and productivity, while improving quality, increasing access and equity, and reducing costs.

Role of Antioxidants in Neonatal Hypoxic-Ischemic Brain Injury: New Therapeutic Approaches.

Hypoxic-ischemic brain damage is an alarming health and economic problem in spite of the advances in neonatal care. It can cause mortality or detrimental neurological disorders such as cerebral palsy, motor impairment and cognitive deficits in neonates. When hypoxia-ischemia occurs, a multi-faceted cascade of events starts out, which can eventually cause cell death. Lower levels of oxygen due to reduced blood supply increase the production of reactive oxygen species, which leads to oxidative stress, a higher concentration of free cytosolic calcium and impaired mitochondrial function, triggering the activation of apoptotic pathways, DNA fragmentation and cell death. The high incidence of this type of lesion in newborns can be partly attributed to the fact that the developing brain is particularly vulnerable to oxidative stress. Since antioxidants can safely interact with free radicals and terminate that chain reaction before vital molecules are damaged, exogenous antioxidant therapy may have the potential to diminish cellular damage caused by hypoxia-ischemia. In this review, we focus on the neuroprotective effects of antioxidant treatments against perinatal hypoxic-ischemic brain injury, in the light of the most recent advances.

[Implementation of a community tele-epidemiological surveillance system using information and communication technologies in Paraguay]. / Implementación de un sistema de televigilancia epidemiológica comunitaria mediante tecnologías de la información y la comunicación en Paraguay.

OBJECTIVE: Report preliminary results of the application of the BONIS system in community tele-epidemiological surveillance in Paraguay. METHODS: A study of viability and implementation carried out in the Family Health Unit located in Bañado Sur in the city of Asunción by the Paraguay River. The system automatically records personal data and symptoms of individuals who make telephone reports, and suspected cases of dengue are classified and prioritized. This information goes to community agents for follow-up and to specialists in charge of epidemiological surveillance. RESULTS: From April 2010 to August 2011, 1 028 calls to the system were logged. Of 157 reported cases of fever, home visits were made to 140 (89.2%); of these, fever and headache or body ache were confirmed in 52 (37.1%) cases, and headache or body ache without fever in 58 (41.4%) cases. Community agents referred 49 (35.0%) of them for medical consultation and blood tests, and they took blood samples in the homes of 19; of these, 56 (82.3%) were positive for dengue and 12 (17.4%) for influenza. CONCLUSIONS: Paraguay has a low-cost community tele-epidemiological surveillance system based on information and communication technologies and open-source software, which is scalable to other health symptoms and disorders of interest. To enable its acceptance and application, education programs should be developed to strengthen the management and promotion of community health.

Neuroprotective effect of melatonin: a novel therapy against perinatal hypoxia-ischemia.

One of the most common causes of mortality and morbidity in children is perinatal hypoxia-ischemia (HI). In spite of the advances in neonatology, its incidence is not diminishing, generating a pediatric population that will require an extended amount of chronic care throughout their lifetime. For this reason, new and more effective neuroprotective strategies are urgently required, in order to minimize as much as possible the neurological consequences of this encephalopathy. In this sense, interest has grown in the neuroprotective possibilities of melatonin, as this hormone may help to maintain cell survival through the modulation of a wide range of physiological functions. Although some of the mechanisms by which melatonin is neuroprotective after neonatal asphyxia remain a subject of investigation, this review tries to summarize some of the most recent advances related with its use as a therapeutic drug against perinatal hypoxic-ischemic brain injury, supporting the high interest in this indoleamine as a future feasible strategy for cerebral asphyctic events.

The Long-Term Neuroprotective Effect of the Endocannabinoid 2-AG and Modulation of the SGZ's Neurogenic Response after Neonatal Hypoxia-Ischemia.

Neonatal hypoxia-ischemia (HI) often causes hypoxic-ischemic encephalopathy (HIE), a neurological condition that can lead to overall disability in newborns. The only treatment available for affected neonates is therapeutic hypothermia; however, cooling is not always effective to prevent the deleterious effects of HI, so compounds such as cannabinoids are currently under research as new therapies. Modulating the endocannabinoid system (ECS) may reduce brain damage and/or stimulate cell proliferation at the neurogenic niches. Further, the long-term effects of cannabinoid treatment are not so clear. Here, we studied the middle- and long-term effects of 2-AG, the most abundant endocannabinoid in the perinatal period after HI in neonatal rats. At middle-term (postnatal day 14), 2-AG reduced brain injury and increased SGZ's cell proliferation and the number of neuroblasts. At post-natal day 90, the treatment with the endocannabinoid showed global and local protection, suggesting long-lasting neuroprotective effects of 2-AG after neonatal HI in rats.

Effects of Cannabidiol, Hypothermia, and Their Combination in Newborn Rats with Hypoxic-Ischemic Encephalopathy.

Therapeutic hypothermia is well established as a standard treatment for infants with hypoxic-ischemic (HI) encephalopathy but it is only partially effective. The potential for combination treatments to augment hypothermic neuroprotection has major relevance. Our aim was to assess the effects of treating newborn rats following HI injury with cannabidiol (CBD) at 0.1 or 1 mg/kg, i.p., in normothermic (37.5°C) and hypothermic (32.0°C) conditions, from 7 d of age (neonatal phase) to 37 d of age (juvenile phase). Placebo or CBD was administered at 0.5, 24, and 48 h after HI injury. Two sensorimotor (rotarod and cylinder rearing) and two cognitive (novel object recognition and T-maze) tests were conducted 30 d after HI. The extent of brain damage was determined by magnetic resonance imaging, histologic evaluation, magnetic resonance spectroscopy, amplitude-integrated electroencephalography, and Western blotting. At 37 d, the HI insult produced impairments in all neurobehavioral scores (cognitive and sensorimotor tests), brain activity (electroencephalography), neuropathological score (temporoparietal cortexes and CA1 layer of hippocampus), lesion volume, magnetic resonance biomarkers of brain injury (metabolic dysfunction, excitotoxicity, neural damage, and mitochondrial impairment), oxidative stress, and inflammation (TNFα). We observed that CBD or hypothermia (to a lesser extent than CBD) alone improved cognitive and motor functions, as well as brain activity. When used together, CBD and hypothermia ameliorated brain excitotoxicity, oxidative stress, and inflammation, reduced brain infarct volume, lessened the extent of histologic damage, and demonstrated additivity in some parameters. Thus, coadministration of CBD and hypothermia could complement each other in their specific mechanisms to provide neuroprotection.

Magnesium sulfate treatment decreases the initial brain damage alterations produced after perinatal asphyxia in fetal lambs.

The aim of this work was to analyze the effect of MgSO(4) treatment in the brain after hypoxic-ischemic (HI) injury in premature fetal lambs. Injury was induced by partial occlusion of umbilical cord for 60 min, and then the preterm lambs (80-90% of gestation) were randomly assigned to one of the following groups: control group, in which the animals were managed by conventional mechanical ventilation for 3 hr; 3 hr postpartial cord occlusion (3-hr-PCO) group, in which injured animals were managed by ventilation and then sacrificed 3 hr after HI; and MgSO(4) group, in which animals received 400 mg/kg MgSO(4) for 20 min soon after HI was induced and were managed by ventilation for 3 hr. Brains were analyzed for apoptosis by TUNEL assay. Cell viability and intracellular state studies were assessed by flow cytometry. The delayed death index was significantly increased in the 3-hr-PCO group in comparison with control. Administration of MgSO(4) elicited a delay in cell death that was similar to that in the control group. The 3-hr-PCO group showed a significantly higher concentration of reactive oxygen species, mitochondrial damage, and intracellular calcium in comparison with control and MgSO(4) - treated groups. Our results suggest that MgSO(4) treatment might have potential therapeutic benefits after the HI event.

Pretreatment with the monoacylglycerol lipase inhibitor URB602 protects from the long-term consequences of neonatal hypoxic-ischemic brain injury in rats.

BACKGROUND: The endocannabinoids are emerging as natural brain protective substances that exert potentially beneficial effects in several neurological disorders by virtue of their hypothermic, immunomodulatory, vascular, antioxidant, and antiapoptotic actions. This study was undertaken to assess whether preventing the deactivation of the endocannabinoid 2-arachidonoylglycerol (2-AG) with the monoacylglycerol lipase (MAGL) inhibitor URB602 can provide neuroprotective effects in hypoxia-ischemia (HI)-induced brain injury. METHODS: URB602 was administered into the right lateral ventricle 30 min before 7-day-old pup rats were subjected to HI. The neuroprotective effect was evaluated on postnatal day (PN) 14 or at adulthood (PN80) using behavioral and histological analyses. Activated caspase-3 expression and propidium iodide labeling were assessed as indexes of apoptotic and necrotic cell death, respectively. RESULTS: Pretreatment with URB602 reduced apoptotic and necrotic cell death, as well as the infarct volume measured at PN14. At adulthood, URB602-treated HI animals performed better at the T-maze and the Morris maze, and also showed a significant reduction of brain damage. CONCLUSION: These results demonstrate that a pretreatment with URB602 significantly reduces brain damage and improves functional outcome, indicating that endocannabinoid-degrading enzymes may represent an important target for neuroprotection in neonatal ischemic brain injury.

Neonatal multiple organ failure after perinatal asphyxia.

Perinatal asphyxia is an event with far-reaching consequences that can lead not only to the development of neonatal encephalopathy, but also to multiple organ failure (MOF). This ailment may result from the redistribution of blood flow, which would preserve the perfusion of vital organs such as the heart, brain and adrenal glands at the expense of other organs. The objective of the study was to determine the incidence and aetiopathogenesis of failure in the organs most frequently involved in neonatal MOF following perinatal asphyxia. We conducted a systematic literature search in the PubMed, Scopus and Cochrane Library databases using the MeSH terms (ischemia AND hypoxia AND multiorgan dysfunction AND neonat*), (asphyxia AND multiorgan dysfunction AND neonat*) and (liver/kidney/digestive OR gastrointestinal/heart injury AND ischemia AND hypoxia AND neonat*). We selected clinical and preclinical studies published after 2000 and excluded case series, letters to the editor, cohort studies without comparison groups and abstracts. In this study, we found that MOF associated with perinatal asphyxia is a frequent phenomenon with a relevant impact on neonatal morbidity and mortality, as it can cause changes not only in the kidney, liver and gastrointestinal tract, but also cardiomyopathy if the ailment is protracted or severe.

Cannabidiol reduces brain damage and improves functional recovery after acute hypoxia-ischemia in newborn pigs.

Newborn piglets exposed to acute hypoxia-ischemia (HI) received i.v. cannabidiol (HI + CBD) or vehicle (HI + VEH). In HI + VEH, 72 h post-HI brain activity as assessed by amplitude-integrated EEG (aEEG) had only recovered to 42 ± 9% of baseline, near-infrared spectroscopy (NIRS) parameters remained lower than normal, and neurobehavioral performance was abnormal (27.8 ± 2.3 points, normal 36). In the brain, there were fewer normal and more pyknotic neurons, while astrocytes were less numerous and swollen. Cerebrospinal fluid concentration of neuronal-specific enolase (NSE) and S100ß protein and brain tissue percentage of TNFα(+) cells were all higher. In contrast, in HI + CBD, aEEG had recovered to 86 ± 5%, NIRS parameters increased, and the neurobehavioral score normalized (34.3 ± 1.4 points). HI induced histological changes, and NSE and S100ß concentration and TNFα(+) cell increases were suppressed by CBD. In conclusion, post-HI administration of CBD protects neurons and astrocytes, leading to histological, functional, biochemical, and neurobehavioral improvements.

Rapid screening for COVID-19 by applying artificial intelligence to chest computed tomography images: A feasibility study.

Aim: The aim of the study was to present the results and impact of the application of artificial intelligence (AI) in the rapid diagnosis of COVID-19 by telemedicine in public health in Paraguay. Methods: This is a descriptive, multi-centered, observational design feasibility study based on an AI tool for the rapid detection of COVID-19 in chest computed tomography (CT) images of patients with respiratory difficulties attending the country's public hospitals. The patients' digital CT images were transmitted to the AI diagnostic platform, and after a few minutes, radiologists and pneumologists specialized in COVID-19 downloaded the images for evaluation, confirmation of diagnosis, and comparison with the genetic diagnosis (reverse transcription polymerase chain reaction (RT-PCR)). It was also determined the percentage of agreement between two similar AI systems applied in parallel to study the viability of using it as an alternative method of screening patients with COVID-19 through telemedicine. Results: Between March and August 2020, 911 rapid diagnostic tests were carried out on patients with respiratory disorders to rule out COVID-19 in 14 hospitals nationwide. The average age of patients was 50.7 years, 62.6% were male and 37.4% female. Most of the diagnosed respiratory conditions corresponded to the age group of 27-59 years (252 studies), the second most frequent corresponded to the group over 60 years, and the third to the group of 19-26 years. The most frequent findings of the radiologists/pneumologists were severe pneumonia, bilateral pneumonia with pleural effusion, bilateral pulmonary emphysema, diffuse ground glass opacity, hemidiaphragmatic paresis, calcified granuloma in the lower right lobe, bilateral pleural effusion, sequelae of tuberculosis, bilateral emphysema, and fibrotic changes, among others. Overall, an average of 86% agreement and 14% diagnostic discordance was determined between the two AI systems. The sensitivity of the AI system was 93% and the specificity 80% compared with RT-PCR. Conclusion: Paraguay has an AI-based telemedicine screening system for the rapid stratified detection of COVID-19 from chest CT images of patients with respiratory conditions. This application strengthens the integrated network of health services, rationalizing the use of specialized human resources, equipment, and inputs for laboratory diagnosis.

Early cell death in the brain of fetal preterm lambs after hypoxic-ischemic injury.

The objective of the present study was to evaluate using premature fetal lambs the effect of cerebral hypoxia-ischemia induced by partial occlusion of the umbilical cord on the type of cell death which occurs in different brain regions and to ascertain some of the neural pathways which may underlie the associated pathologies. Lambs were sacrificed either immediately after a 1 h hypoxic-ischemic insult or 3 h later. Brains were fixed by perfusion and blocks of the different brain territories were processed for light microscopy (hematoxylin-eosin, Nissl staining), electron transmission microscopy and quantification of apoptosis by the TUNEL method. Other fixed brains were dissociated and labeled by nonyl acridine orange to determine mitochondrial integrity. Non-fixed brains were also used for membrane asymmetry studies, in which cell suspensions were analyzed by flow cytometry to quantify apoptosis. In both hypoxic-ischemic groups, necrotic-like neurons were observed mainly in the mesencephalon, pons, deep cerebellar nuclei and basal nuclei, whereas apoptotic cells were extensively found both in white and gray matter and were not limited to regions where necrotic neurons were present. The 3 h post-partial cord occlusion group, but not the 0 h group, showed a generalized alteration of cell membrane asymmetry and mitochondrial integrity as revealed by Annexin V/PI flow cytometry and nonyl acridine orange studies, respectively. Our results show that the apoptotic/necrotic patterns of cell death occurring early after hypoxic-ischemic injury are brain-region-specific and have distinct dynamics and suggest that therapeutic strategies aimed at rescuing cells from the effects of hypoxia/ischemia should be aimed at blocking the apoptotic components of brain damage.

Fallo multiorgánico neonatal tras asfixia perinatal / Neonatal multiple organ failure after perinatal asphyxia

La asfixia perinatal es un acontecimiento con efectos de gran alcance, pudiendo conducir no solo al desarrollo de encefalopatía neonatal, sino también a un fallo multiorgánico (FMO). Esta afectación posiblemente se deba a la redistribución del flujo sanguíneo, mediante el cual se conserva la irrigación de órganos vitales como el corazón, el cerebro y las glándulas suprarrenales, a expensas de su disminución en otros órganos.El objetivo del presente trabajo fue conocer la incidencia y la etiopatogenia de los órganos más frecuentemente afectados en el FMO neonatal tras la asfixia perinatal.Se realizó una búsqueda bibliográfica sistemática en las bases de datos Pubmed, Scopus y The Cochrane Library empleando los términos MeSH (ischemia AND hypoxia AND multiorgan dysfunction AND neonat*), (asphyxia AND multiorgan dysfunction AND neonat*) y (liver / kidney / digestive OR gastrointestinal / heart injury AND ischemia AND hypoxia AND neonat*). Se incluyeron trabajos clínicos y preclínicos posteriores al año 2000 y se excluyeron series de casos, cartas al director, cohortes sin grupo comparador y abstracts.En el presente trabajo describimos que el fallo multiorgánico asociado a la asfixia perinatal es un fenómeno frecuente y relevante en la morbimortalidad del neonato, pudiendo llegar a producir no solo alteraciones en riñón, hígado y tracto gastrointestinal, sino también miocardiopatía si el fenómeno se prolonga o es de elevada gravedad. (AU)

Perinatal asphyxia is an event with far-reaching consequences that can lead not only to the development of neonatal encephalopathy, but also to multiple organ failure (MOF). This ailment may result from the redistribution of blood flow, which would preserve the perfusion of vital organs such as the heart, brain and adrenal glands at the expense of other organs.The objective of the study was to determine the incidence and aetiopathogenesis of failure in the organs most frequently involved in neonatal MOF following perinatal asphyxia.We conducted a systematic literature search in the PubMed, Scopus and Cochrane Library databases using the MeSH terms (ischemia AND hypoxia AND multiorgan dysfunction AND neonat*), (asphyxia AND multiorgan dysfunction AND neonat*) and (liver/kidney/digestive OR gastrointestinal/heart injury AND ischemia AND hypoxia AND neonat*). We selected clinical and preclinical studies published after 2000 and excluded case series, letters to the editor, cohort studies without comparison groups and abstracts.In this study, we found that MOF associated with perinatal asphyxia is a frequent phenomenon with a relevant impact on neonatal morbidity and mortality, as it can cause changes not only in the kidney, liver and gastrointestinal tract, but also cardiomyopathy if the ailment is protracted or severe. (AU)

Recent advances in cochlear hair cell regeneration-A promising opportunity for the treatment of age-related hearing loss.

The objective of this paper is to review current information regarding the treatment of age-related hearing loss by using cochlear hair cell regeneration. Recent advances in the regeneration of the inner ear, including the usefulness of stem cells, are also presented. Based on the current literature, cochlear cell regeneration may well be possible in the short term and cochlear gene therapy may also be useful for the treatment of hearing loss associated with ageing. The present review provide further insight into the pathogenesis of Inner Ear senescence and aged-related hearing loss and facilitate the development of therapeutic strategies to repair hair cells damaged by ageing. More research will be needed in order to translate them into an effective treatment for deafness linked to cochlear senescence in humans.

Respuesta a la carta al editor: Crítica al estudio factibilidad de la utilización de la inteligencia artificial para el cribado de pacientes con COVID-19 en Paraguay

[EXTRACTO]. En respuesta a la carta al editor titulada: Critica al estudio de factibilidad de la utilización de la inteligencia artificial para el cribado de pacientes con COVID-19 en Paraguay, los autores del artículo de referencia elevan a consideración la réplica sobre el contenido de esta, con el objeto de esclarecer los cuestionamientos mencionados en la misma. Respecto al primer problema mencionado en la carta al editor; el estudio utilizó el programa de inteligencia artificial (IA) que fue desarrollado por un equipo de informáticos biomédicos, neumólogos y radiólogos (imagenólogos). El programa utilizado dispone de un método de aprendizaje profundo para realizar el diagnóstico rápido de COVID-19; es decir, cuenta con un algoritmo para detectar patologías neumológicas y un algoritmo de diagnóstico de neumopatías compatibles con COVID-19. En cuanto al segundo problema mencionado en la carta al editor; el presente estudio se realizó entre marzo del 2020 y junio del 2021 en 14 hospitales de las 18 regiones sanitarias del Ministerio de Salud Pública y Bienestar Social (MSPBS), que ya contaban con al menos un tomógrafo funcionando al momento del estudio. El informe de diagnóstico del médico radiólogo y el resultado del diagnóstico por IA fueron remitidos luego a un equipo de neumólogos para su valoración, análisis, correlación y validación; los neumólogos correlacionaron los valores porcentuales del diagnóstico por IA con el resultado de los médicos radió- logos, el resultado del análisis molecular (RT-PCR) y el cuadro clínico del paciente para determinar los grados de concordancia o discordancia entre los resultados, y llegar a un diagnóstico definitivo que permitiera informar al médico del hospital donde se trataba al paciente en cuestión. Esto permitió reducir las aglomeraciones en los centros especializados y optimizar el uso de los limitados recursos disponibles. Esta respuesta se refiere a la carta disponible en: https://doi.org/10. 26633/RPSP.2022.193

Factibilidad de la utilización de la inteligencia artificial para el cribado de pacientes con COVID-19 en Paraguay / Feasibility of using artificial intelligence for screening COVID-19 patients in Paraguay / Viabilidade do uso de inteligência artificial na triagem de pacientes com COVID-19 no Paraguai

RESUMEN Objetivo. Estudiar la factibilidad de utilización de la inteligencia artificial como método sensible y específico para el cribado de COVID-19 en pacientes con afecciones respiratorias empleando imágenes de tórax obtenidas con tomógrafo y una plataforma de telemedicina. Métodos. Entre marzo del 2020 y junio del 2021 se realizó un estudio observacional descriptivo multicéntrico de factibilidad basada en inteligencia artificial (IA) para el cribado de COVID-19 en imágenes de tórax de pacientes con afecciones respiratorias que acudieron a hospitales públicos. El diagnóstico de las imágenes tomográficas de tórax se realizó a través de la plataforma de IA; luego, se comparó con el diagnóstico molecular (RT-PCR) para determinar la concordancia entre ambos y analizar su factibilidad para el cribado de pacientes con sospecha de COVID-19. Las imágenes y los resultados diagnóstico se enviaron a través de una plataforma de telemedicina. Resultados. Se realizó el cribado de 3 514 pacientes con sospecha diagnóstica de COVID-19, en 14 hospitales a nivel nacional. La mayoría de los pacientes tenían entre 27 y 59 años, seguidos por los mayores de 60 años. La edad promedio fue de 48,6 años; el 52,8% eran de sexo masculino. Los hallazgos más frecuentes fueron neumonía grave, neumonía bilateral con derrame pleural, enfisema pulmonar bilateral y opacidad difusa en vidrio esmerilado, entre otros. Se determinó un promedio de 93% de concordancia y 7% de discordancia entre las imágenes analizadas mediante IA y la RT-PCR. La sensibilidad y especificidad del sistema de IA, obtenidas comparando el resultado del cribado obtenido por IA con la RT-PCR, fueron de 93% y 80% respectivamente. Conclusiones. Es viable la utilización de IA sensible y específica para la detección rápida estratificada de COVID-19 en pacientes con afecciones respiratorias utilizando imágenes obtenidas mediante tomografía de tórax y una plataforma de telemedicina en los hospitales públicos de Paraguay.

ABSTRACT Objective. Study the feasibility of using artificial intelligence as a sensitive and specific method for COVID-19 screening in patients with respiratory conditions, using chest CT scan images and a telemedicine platform. Methods. From March 2020 to June 2021, the authors conducted an observational descriptive multicenter feasibility study based on artificial intelligence (AI) for COVID-19 screening using chest images of patients with respiratory conditions who presented at public hospitals. The AI platform was used to diagnose chest CT scan images; this was then compared with molecular diagnosis (RT-PCR) to determine whether they matched and to analyze the feasibility of AI for screening patients with suspected COVID-19. A telemedicine platform was used to send images and diagnostic results. Results. Screening of 3 514 patients with a suspected COVID-19 diagnosis was performed in 14 hospitals around the country. Most patients were aged 27 to 59 years, followed by those over 60. The average age was 48.6 years; 52.8% were male. The most frequent findings were severe pneumonia, bilateral pneumonia with pleural effusion, bilateral pulmonary emphysema, and diffuse ground glass opacity, among others. There was an average of 93% matching and 7% mismatching between images analyzed by AI and RT-PCR. Sensitivity and specificity of the AI system, obtained by comparing AI and RT-PCR screening results, were 93% and 80% respectively. Conclusions. The use of sensitive and specific AI for stratified rapid detection of COVID-19 in patients with respiratory conditions by using chest CT scan images and a telemedicine platform in public hospitals in Paraguay is feasible.

RESUMO Objetivo. Examinar a viabilidade do uso de inteligência artificial como um método sensível e específico de triagem de COVID-19 em pacientes com afecções respiratórias, empregando imagens obtidas por exame de tomografia do tórax e uma plataforma de telemedicina. Métodos. Entre março de 2020 e junho de 2021, foi realizado um estudo observacional descritivo multicêntrico sobre a viabilidade do uso de inteligência artificial (IA) para a triagem de COVID-19, empregando imagens do tórax de pacientes com afecções respiratórias atendidos em hospitais da rede pública. O diagnóstico das imagens obtidas em tomografia do tórax foi realizado por meio de uma plataforma de IA e, em seguida, cotejado com o diagnóstico molecular (RT-PCR) para determinar a concordância entre os métodos utilizados e analisar a viabilidade deste processo para a triagem de pacientes com suspeita de COVID-19. As imagens e os resultados do exame diagnóstico foram disponibilizados em uma plataforma de telemedicina. Resultados. Foi realizada a triagem de 3 514 pacientes com suspeita de COVID-19 atendidos em 14 hospitais de todo o país. Os pacientes, na sua maioria, tinham entre 27 e 59 anos de idade ou pertenciam à faixa etária acima de 60 anos, com média de idade de 48,6 anos, sendo que 52,8% eram do sexo masculino. Os achados mais comuns foram pneumonia grave, pneumonia bilateral com derrame pleural, enfisema pulmonar bilateral e opacidade difusa em vidro fosco, entre outros. Verificou-se, em média, 93% de concordância e 7% de discordância entre as imagens analisadas com uso de IA e os resultados do exame de RT-PCR, com uma sensibilidade de 93% e especificidade de 80% desse sistema de triagem. Conclusões. Demonstrou-se que o uso de um sistema de IA sensível e específico é viável nos hospitais públicos do Paraguai para a detecção rápida estratificada de COVID-19 em pacientes com afecções respiratórias, empregando imagens de exame de tomografia do tórax e uma plataforma de telemedicina.