Tuberculosis disease in immunocompromised children and adolescents: a pTBnet multi-centre case-control study.

BACKGROUND: In high-resource settings the survival of immunocompromised (IC) children has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools and outcome of IC children with TB in Europe. METHODS: Multicentre, matched case-control study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), capturing TB cases <18 years diagnosed 2000-2020. RESULTS: 417 TB cases were included, comprising 139 children with IC (HIV, inborn errors of immunity, drug-induced immunosuppression and other immunocompromising conditions) and 278 non-IC children as controls. Non-respiratory TB was more frequent among cases than controls (32.4% vs. 21.2%; p = 0.013). IC patients had an increased likelihood of presenting with severe disease (57.6% vs. 38.5%; p < 0.001; OR [95% CI]: 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs. 6.0%; p < 0.001) and QuantiFERON-TB Gold assay (30.0% vs. 7.3%; p < 0.001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs. 49.3%; p = 0.083). Although the mortality in IC children was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs. 6.1%; p = 0.004). CONCLUSIONS: IC children with TB disease in Europe have increased rates of non-respiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in IC patients, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies.

Sudden Infant Death Syndrome (SIDS): State of the Art and Future Directions.

Sudden infant death syndrome (SIDS) is a type of death that occurs suddenly and without any apparent explanation, affecting infants between 28 days of life and up to a year. Recognition of this entity includes performing an autopsy to determine if there is another explanation for the event and performing both an external and internal examination of the different tissues to search for possible histopathological findings. Despite the relative success of awareness campaigns and the implementation of prevention measures, SIDS still represents one of the leading causes of death among infants worldwide. In addition, although the development of different techniques has made it possible to make significant progress in the characterization of the etiopathogenic mechanisms underlying SIDS, there are still many unknowns to be resolved in this regard and the integrative consideration of this syndrome represents an enormous challenge to face both from a point of view scientific and medical view as humanitarian. For all these reasons, this paper aims to summarize the most relevant current knowledge of SIDS, exploring from the base the characterization and recognition of this condition, its forensic findings, its risk factors, and the main prevention measures to be implemented. Likewise, an attempt will be made to analyze the causes and pathological mechanisms associated with SIDS, as well as potential approaches and future paths that must be followed to reduce the impact of this condition.

The Use of Prebiotics from Pregnancy and Its Complications: Health for Mother and Offspring-A Narrative Review.

Pregnancy involves a metabolic reprogramming that includes changes in the gut microbiota composition in women. Evidence shows that maternal dysbiosis is linked to neonatal dysbiosis, and this factor can determine health status in adulthood. Although there is little literature available on this topic, high heterogeneity is a limitation when examining nutritional interventions. Information has been gathered to contrast the benefits of prebiotic usage, specifically in pregnancy, in its possible complications and in newborns' gut microbiota development. The objective pursued in this brief narrative review is to provide a clear summary of relevant content when searching with regard to the use of prebiotics in pregnancy, the effects in prenatal and postnatal periods, and to help in clinical decision-making in pregnancy management and lactation. A search has found that the nutritional status of the pregnant mother is key for the earliest microbial colonization in newborns, and thus intervention programs from pregnancy could assure better outcomes in both the mother and offspring. In this sense, prebiotics (administered to mothers who breastfeed or provided in formula milk) are feasible and cost-effective elements that can prevent allergies, colic, and other maladies in newborns.

Women with psychotic episodes during pregnancy show increased markers of placental damage with Tenney-Parker changes.

Psychosis is a hazardous and functionally disruptive psychiatric condition which may affect women in pregnancy, entailing negative consequences for maternofetal well-being. The precise pathophysiological basis and consequences of a psychotic episode in pregnancy remain to be further elucidated. The placenta is a pivotal tissue with many functions in the gestational period, critically influencing the fate and development of pregnancy. Although detrimental alterations have been observed in women undergoing severe psychiatric disorders in pregnancy, there are little studies evaluating the consequences of suffering from a psychotic episode in the placental tissue In this work, we have evaluated the histopathological consequences of a first episode of psychosis in pregnancy (FE-PW; N=22) and compare them with healthy pregnant women (HC-PW; N=20) by using histological, immunohistochemical and gene expression techniques. Our results define that the placental tissue of FE-PW display an increase in the number of placental villi, bridges, syncytial knots and syncytial knots/villi. Besides, we have also observed an enhanced gene and protein expression in FE-PW of the hypoxic marker HIF-1α, together with the apoptotic markers BAX and Bcl-2. To our knowledge, this is the first study demonstrating significant histopathological changes in the placenta of women suffering a new-onset psychotic episode in pregnancy. Further studies should be aimed at deepening the knowledge about the pernicious effects of psychosis in the maternofetal tissues, as well as the potential implications of these alterations.

Evidence of Increased Oxidative Stress in the Placental Tissue of Women Who Suffered an Episode of Psychosis during Pregnancy.

Psychosis is a complex clinical syndrome resulting in a loss of contact with reality and alterations in behavior and sensorial and motor functions. Although the onset of psychosis can be related to any medical condition, most cases of psychosis are not fully understood. Psychosis may manifest for the first time during pregnancy, which is detrimental to maternofetal well-being. The impact of having a first episode of psychosis during pregnancy on the placenta has not yet been explored. Oxidative stress is thought to take part in the etiopathogenesis of this complex disorder, and this condition can also affect the placenta as it is highly sensitive to changes in the maternal environment. In this sense, the aim of the present work was to study the gene and protein expression through RT-qPCR and immunohistochemistry, respectively, of oxidative stress markers (NOX-1, NOX-2, iNOS, eNOS and PARP) in the placental tissue of women who underwent a first episode of psychosis during pregnancy (FE-PW) in comparison to healthy pregnant women. Our results showed augmented gene and protein expression of NOX-1, NOX-2, iNOS and PARP in the placental tissue of FE-PW. For the first time, we demonstrated that oxidative stress may have an important pathophysiological role in this tissue, aiding in explaining the impact of psychosis on pregnancy and the need for future studies in this field to guide better clinical management of these patients.

The Placentas of Women Who Suffer an Episode of Psychosis during Pregnancy Have Increased Lipid Peroxidation with Evidence of Ferroptosis.

Psychosis is a complex entity characterized by psychological, behavioral, and motor alterations resulting in a loss of contact with reality. Although it is not common, pregnancy can be a period in which a first episode of psychosis can manifest, entailing detrimental consequences for both the fetus and the mother. The pathophysiological basis and study of maternofetal wellbeing need to be further elucidated. Lipid peroxidation and ferroptosis are two phenomena that are tightly linked to the placental dysfunction commonly observed in different complications of pregnancy. In the present study, we aim to explore the histopathological and gene expression of different markers of lipid peroxidation and ferroptosis in the placentas of women who underwent a first episode of psychosis during their pregnancy (n = 22). The aim is to then compare them with healthy pregnant women (n = 20). In order to achieve this goal, iron deposits were studied using Prussian Blue staining. In addition, the protein/gene expression of a transferrin receptor (TFRC), as well as an acyl-CoA synthetase long-chain family member 4 (ACSL-4), arachidonate lipoxygenase-5 (ALOX-5), malondialdehyde (MDA), and glutathione peroxidase 4 (GPX4) were all analyzed through gene expression (RT-qPCR) and immunohistochemical procedures. Our results demonstrate an increased presence of iron deposits that are accompanied by a further expression of TFRC, ACSL-4, ALOX-5, MDA, and GPX4-all of which are observed in the placenta tissue of women who have suffered from a first episode of psychosis. Therefore, in our study, a histopathological increase in lipid peroxidation and ferroptosis markers in the affected women is suggested. However, further studies are needed in order to validate our results and to establish possible consequences for the reported alterations.

A Review: Integrative Perspectives on the Features and Clinical Management of Psychotic Episodes in Pregnancy.

Psychotic episodes represent one of the most complex manifestations of various mental illnesses, and these encompass a wide variety of clinical manifestations that together lead to high morbidity in the general population. Various mental illnesses are associated with psychotic episodes; in addition, although their incidence and prevalence rates have been widely described in the general population, their correct identification and treatment is a challenge for health professionals in relation to pregnancy. In pregnant women, psychotic episodes can be the consequence of the manifestation of a previous psychiatric illness or may begin during the pregnancy itself, placing not only the mother, but also the fetus at risk during the psychotic episode. In addition, we cannot forget that both pharmacological and nonpharmacological management are complex given the different teratogenic effects of various neuroleptic drugs or mood stabilizers; moreover, the recommendation is that patients should be followed together with different specialists to maintain close contact during puerperium given the high incidence of recurrence of psychotic episodes. In addition, we cannot forget that a large portion of these patients for whom the onset times of such episodes are during pregnancy have a greater probability of an unpredictable psychiatric illness that requires a postpartum follow up, in addition to the postpartum psychotic episodes, at some point in their lives. Therefore, the purpose of this review is to summarize the epidemiology of psychotic breaks during pregnancy related to the main mental illnesses that affect this population and to summarize the main pharmacological treatments available for their clinical management.

Unfolding the role of placental-derived Extracellular Vesicles in Pregnancy: From homeostasis to pathophysiology.

The human placenta is a critical structure with multiple roles in pregnancy, including fetal nutrition and support, immunological, mechanical and chemical barrier as well as an endocrine activity. Besides, a growing body of evidence highlight the relevance of this organ on the maternofetal wellbeing not only during gestation, but also from birth onwards. Extracellular vesicles (EVs) are complex macromolecular structures of different size and content, acting as carriers of a diverse set of molecules and information from donor to recipient cells. Since its early development, the production and function of placental-derived EVs are essential to ensure an adequate progress of pregnancy. In turn, the fetus receives and produce their own EVs, highlighting the importance of these components in the maternofetal communication. Moreover, several studies have shown the clinical relevance of EVs in different obstetric pathologies such as preeclampsia, infectious diseases or gestational diabetes, among others, suggesting that they could be used as pathophysiological biomarkers of these diseases. Overall, the aim of this article is to present an updated review of the published basic and translational knowledge focusing on the role of placental-derived EVs in normal and pathological pregnancies. We suggest as well future lines of research to take in this novel and promising field.

Irregular Expression of Cellular Stress Response Markers in the Placenta of Women with Chronic Venous Disease.

Pregnancy comprises a period in a woman's life in which the circulatory system is subjected to hemodynamical and biochemical changes. During this period, while restructuring blood vessels and exchanging maternal-fetal products there is an increased risk of developing chronic venous disease (CVD), which may have an echo in life after childbirth for both mother and child. Previously, we investigated that pregnancy-associated CVD involves changes in placental architecture at angiogenesis, lymphangiogenesis and villi morphology compared with healthy controls (HC) with no history of CVD. We aimed to more deeply investigate the oxidative stress response in placenta from women with CVD versus HC through several markers (NRF2, KEAP1, CUL3, GSK-3ß). An observational, analytical, and prospective cohort study was conducted on 114 women in their third trimester of pregnancy (32 weeks). A total of 62 participants were clinically diagnosed with CVD. In parallel, 52 controls with no history of CVD (HC) were studied. Gene and protein expressions of NRF2, KEAP1, CUL3, GSK-3ß were analyzed by real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry. Nrf2 gene and protein expression was significantly greater in placental villi of women with CVD, while Keap1, CUL-3 and GSK-3ß gene and protein expressions were significantly lower. Our results defined an aberrant gene and protein expression of Nrf2 and some of their main regulators Keap1, CUL-3 and GSK-3 ß in the placenta of women with CVD, which could be an indicator of an oxidative environment observed in this tissue.