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The early childhood period, encompassing prenatal and early stages, assumes a pivotal role in shaping cardiovascular risk factors. We conducted a narrative review, presenting a non-systematic summation and analysis of the available literature, focusing on cardiovascular risk from prenatal development to the first 1000 days of life. Elements such as maternal health, genetic predisposition, inadequate fetal nutrition, and rapid postnatal growth contribute to this risk. Specifically, maternal obesity and antibiotic use during pregnancy can influence transgenerational risk factors. Conditions at birth, such as fetal growth restriction and low birth weight, set the stage for potential cardiovascular challenges. To consider cardiovascular risk in early childhood as a dynamic process is useful when adopting a personalized prevention for future healthcare and providing recommendations for management throughout their journey from infancy to early adulthood. A comprehensive approach is paramount in addressing early childhood cardiovascular risks. By targeting critical periods and implementing preventive strategies, healthcare professionals and policymakers can pave the way for improved cardiovascular outcomes. Investing in children’s health during their early years holds the key to alleviating the burden of cardiovascular diseases for future generations.

Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterised by abnormal cell proliferation and differentiation that affects multiple organs and can lead to the growth of hamartomas. Tuberous sclerosis complex is caused by the disinhibition of the protein mTOR (mammalian target of rapamycin). In the past, various therapeutic approaches, even if only symptomatic, have been attempted to improve the clinical effects of this disease. While all of these therapeutic strategies are useful and are still used and indicated, they are symptomatic therapies based on the individual symptoms of the disease and therefore not fully effective in modifying long-term outcomes. A new therapeutic approach is the introduction of allosteric inhibitors of mTORC1, which allow restoration of metabolic homeostasis in mutant cells, potentially eliminating most of the clinical manifestations associated with Tuberous sclerosis complex. Everolimus, a mammalian target of the rapamycin inhibitor, is able to reduce hamartomas, correcting the specific molecular defect that causes Tuberous sclerosis complex. In this review, we report the findings from the literature on the use of everolimus as an effective and safe drug in the treatment of TSC manifestations affecting various organs, from the central nervous system to the heart.

We previously published that in patients with infantile hemangioma (IH) at the onset (T0) colony forming unit-fibroblasts (CFU-Fs) are present in in vitro cultures from PB. Herein, we characterize these CFU-Fs and investigate their potential role in IH pathogenesis, before and after propranolol therapy. The CFU-F phenotype (by flow cytometry), their differentiation capacity and ability to support angiogenesis (by in vitro cultures) and their gene expression (by RT-PCR) were evaluated. We found that CFU-Fs are actual circulating MSCs (cMSCs). In patients at T0, cMSCs had reduced adipogenic potential, supported the formation of tube-like structures in vitro and showed either inflammatory (IL1β and ESM1) or angiogenic (F3) gene expression higher than that of cMSCs from CTRLs. In patients receiving one-year propranolol therapy, the cMSC differentiation in adipocytes improved, while their support in in vitro tube-like formation was lost; no difference was found between patient and CTRL cMSC gene expressions. In conclusion, in patients with IH at T0 the cMSC reduced adipogenic potential, their support in angiogenic activity and the inflammatory/angiogenic gene expression may fuel the tumor growth. One-year propranolol therapy modifies this picture, suggesting cMSCs as one of the drug targets.

Abstract Background Multisystem inflammatory syndrome in children (MIS-C) is a novel condition temporally associated with SARS-CoV2 infection. Cardiovascular involvement is mainly evident as acute myocardial dysfunction in MIS-C. The aim of this study was to describe the cardiac dysfunction in patients with MIS-C, defining the role of severity in the clinical presentations and outcomes in a single cohort of pediatric patients. Methods A single-center retrospective study on patients diagnosed with MIS-C, according to the Center for Disease Control and Prevention (CDC) definition, and referred to Vittore Buzzi Children’s Hospital in Milan from November 2020 to February 2021. Patients were managed according to a local approved protocol. According to the admission cardiac left ventricular ejection fraction (LVEF), the patients were divided into group A (LVEF

BackgroundA severe multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 has been described after infection. A limited number of reports have analyzed the long-term complications related to pro-inflammatory status in MIS-C. We evaluated multiorgan impairment at the 6-month follow-up in MIS-C.MethodsWe enrolled 33 pediatric patients consecutively hospitalized for MIS-C and monitored for almost 6 months. The inter-relationship of patient's features and disease severity at admission with long term complications was studied by multivariate analysis.ResultsEndo-metabolic derangement, cardiac injury, respiratory, renal and gastrointestinal manifestations and neurological involvement are part of the initial presentation. The most abnormalities appear to resolve within the first few weeks, without significant long term dysfunction at the 6-months follow-up, except for endocrine (non-thyroidal illness syndrome in 12.1%, insulin resistance in 21.2%) and neurological system (27.3% cognitive or psychological, behavioral, adaptive difficulties). Endocrine and heart involvement at admission represent a significant factor on the long term sequelae; however no association between severity score and long-term outcome was noted.ConclusionsThe severity of initial clinical presentation may be associated to organ domain, however it is not related to long term sequelae. The prevalent organ restoration supports a predominant indirect immune-mediated injury triggered by a systemic inflammatory response; however a direct damage due to the viral entry could be not excluded. Eventhought our preliminary results seem to suggest that MIS-C is not a long-term risk condition for children health, a longer follow-up is mandatory to confirm this hypothesis.

Background: Cardiac rhabdomyomas (CRs) are the most common cardiac tumors in newborns. Approximately 80–90% of cases are associated with tuberous sclerosis complex (TSC). In selective cases, Everolimus has resulted in a remarkable tumoral regression effect in children with TS. The optimal dosage for neonates is still unknown. Case presentation: We describe the use of Everolimus in a neonate with multiple biventricular CRs, causing subaortic obstruction, in which a low-dose treatment (0.1 mg/die), in an effort to maintain serum trough levels of 3–7 ng/mL, was successfully used off-label, without adverse effects. Conclusions: We showed that a low-dose Everolimus regimen may be an effective and safe treatment for CR regression in TS neonates, when the minimum therapeutic range was maintained.

Abstract Prenatal DA closure due to early maternal intake of high‐dose paracetamol and selective serotonin reuptake inhibitors. MC twin pregnancy uncomplicated by TTTS with discordant prenatal DA closure.

Congenital or acquired atrioventricular block (AVB) is a rare disorder in the pediatric population, while celiac disease (CeD) is a common multisystemic autoimmune disorder that is characterized by intestinal manifestations as they are the typical clinical presentation. Sometimes CeD presents more complex multisystemic involvement which includes the heart. Cardiac involvement, such as dilated cardiomyopathy, myocarditis or conduction disease, have been mainly described in untreated adult patients with or without gastro-intestinal symptoms; rare cases of AVB and CeD have been also reported, particularly in association with extra-cardiac manifestations. We describe a case of a progressive acquired AVB block in a 4-year-old child, in which CeD was later diagnosed. A rapid and significantly improvement of the AVB grade has been obtained after the child started a strict gluten-free diet, and so we suggest including diagnostic exams for CeD in all of the children with acquired AVB.

Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory disease related to SARS-CoV2 infection, with frequent cardiovascular involvement in the acute setting. The aim of the study was to evaluate the cardiac function at 6 months. Thirty-two patients diagnosed with MIS-C were enrolled and underwent advanced echocardiogram at discharge and at 6 months. According to the left ventricular ejection fraction (LVEF) at admission, the patients were divided into group A (LVEF < 45%) and group B (LVEF ≥ 45%) and the follow-up results were compared. At discharge, all patients had normal LV and RV systolic function (LVEF 61 ± 4.4%, LV global longitudinal strain −22.1%, TAPSE 20.1mm, s’ wave 0.13m/s, RV free wall longitudinal strain −27.8%) with normal LV diastolic function (E/A 1.5, E/e’ 5.7, and left atrial strain 46.5%) and no significant differences at 6 months. Compared to group B, the group A patients showed a reduced, even if normal, LV global longitudinal strain at discharge (−21.1% vs. −22.6%, p-value 0.02), but the difference was no longer significant at the follow-up. Patients with MIS-C can present with depressed cardiac function, but if treated, the cardiac function recovered without late onset of cardiac disease. This favorable result was independent of the severity of acute LV dysfunction.

Abstract The primary purpose of these practical guidelines related to Kawasaki disease (KD) is to contribute to prompt diagnosis and appropriate treatment on the basis of different specialists’ contributions in the field. A set of 40 recommendations is provided, divided in two parts: the first describes the definition of KD, its epidemiology, etiopathogenetic hints, presentation, clinical course and general management, including treatment of the acute phase, through specific 23 recommendations. Their application is aimed at improving the rate of treatment with intravenous immunoglobulin and the overall potential development of coronary artery abnormalities in KD. Guidelines, however, should not be considered a norm that limits treatment options of pediatricians and practitioners, as treatment modalities other than those recommended may be required as a result of peculiar medical circumstances, patient’s condition, and disease severity or complications.

Abstract This second part of practical Guidelines related to Kawasaki disease (KD) has the goal of contributing to prompt diagnosis and most appropriate treatment of KD resistant forms and cardiovascular complications, including non-pharmacologic treatments, follow-up, lifestyle and prevention of cardiovascular risks in the long-term through a set of 17 recommendations. Guidelines, however, should not be considered a norm that limits the treatment options of pediatricians and practitioners, as treatment modalities other than those recommended may be required as a result of peculiar medical circumstances, patient’s condition, and disease severity or individual complications.

MIS-C (multisystem inflammatory syndrome in children) linked to SARS-CoV-2 infection, is a pathological state observed in subjects younger than 21 years old with evidence of either current SARS-CoV-2 infection or exposure within the 4 weeks prior to the onset of symptoms, the presence of documented fever, elevated markers of inflammation, at least two signs of multisystem involvement, and, finally, lack of an alternative diagnosis. They share with adult COVID-19 patients the presence of altered markers of inflammation, but unlike most adults the symptoms are not pulmonary but are affecting several organs. Lipid mediators arising from polyunsaturated fatty acids (PUFA) play an important role in the inflammatory response, with arachidonic acid-derived compounds, such as prostaglandins and leukotrienes, mainly pro-inflammatory and ω3 PUFA metabolites such as resolvins and protectins, showing anti-inflammatory and pro-resolution activities. In order to assess potential alterations of these FA, we evaluated the blood fatty acid profile of MIS-C children at admission to the hospital, together with biochemical, metabolic and clinical assessment. All the patients enrolled showed altered inflammatory parameters with fibrinogen, D-dimer, NT-proBNP, ferritin, aspartate aminotransferase (AST), C-reactive protein (CRP) and TrygIndex levels over the reference values in all the subjects under observation, while albumin and HDL-cholesterol resulted below the normal range. Interestingly, linoleic acid (LA), arachidonic acid (AA) and the ω3 PUFA docosahexaenoic acid (DHA) results were lower in our study when compared to relative amounts reported in the other studies, including from our own laboratory. This significant alteration is pointing out to a potential depletion of these PUFA as a result of the systemic inflammatory condition typical of these patients, suggesting that LA- and AA-derived metabolites may play a critical role in this pathological state, while ω3 PUFA-derived pro-resolution metabolites in these subjects may not be able to provide a timely, physiological counterbalance to the formation of pro-inflammatory lipid mediators. In conclusion, this observational study provides evidence of FA alterations in MIS-C children, suggesting a significant contribution of ω6 FA to the observed inflammatory state, and supporting a potential dietary intervention to restore an appropriate balance among the FAs capable of promoting the resolution of the observed inflammatory condition.

Psychotherapy and psychological counseling in narcology are an important component of the therapeutic and prophylactic process and are used in the complex of rehabilitation measures. Is inseparable from medication, physiotherapy and psychosocial effects, begins at the earliest stages of treatment. The use of psychotherapy in the rehabilitation phase of chemically dependent persons is necessary and promising. Effective psychotherapeutic programs involve the use of a whole range of psychotherapeutic approaches that include various methods and forms of psychotherapy that are used by the community of specialists in unison with the complex of psychopharmacotherapy and other non-drug therapies. Each separate strategic stage of rehabilitation of substance addicts corresponds to a specific psychotherapeutic method. Psychotherapeutic rehabilitation measures in narcology should be personality-oriented, differentiated and comprehensive, including both psychotherapeutic rehabilitation measures and drug-centered rehabilitation approaches. In stages, the introduction of elements of the psychotherapy-rehabilitation approach, which is necessary from the very beginning, at the stage of acute conditions. If successful psychotherapy optimizes the totality of personal statuses seeking their harmonious disclosure and fixing the position of the individual in the desired statuses. The basic principles of psychotherapy abusing on surfactants are considered in unison with the modern concepts of treatment in general and include volunteering, individuality, complexity and refusal to use psychoactive substance.

An interaction between metabolic glucose impairment and coronavirus disease 2019 is reported. The development of a severe multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection has been described. We evaluated the impact of MIS-C on glycemic patterns in pediatric patients. A group of 30 children and adolescents affected by MIS-C were considered; all patients were normal weight. Clinical and biochemical assessments, including surrogate markers of insulin resistance (IR) such as homeostasis model analysis-IR (HOMA-IR) and triglyceride–glucose (TyG) indexes, were recorded. Patients were also invited to undergo an intermittently scanned continuous glucose monitoring (isCGM). HOMA-IR index was calculated in 18 patients (60%), of which 17 (94%) revealed a pathological value. TyG index was computed for all patients and pathological values were detected in all cases. In 15 patients, isCGM data were recorded on average for 9 days (±3 days). Overall, average glucose was 105 mg/dL (±16 mg/dL) and average time spent in the 70–180 mg/dL range (TIR) was 93.76%, with nearly 10% of glucose readings in the 141–180 mg/dL range; glycemic fluctuations over the hyperglycemic threshold were detected in four patients. Regular glucose monitoring may be useful to prevent metabolic imbalance and obtain a better outcome.

A combination of information from blood glucose (BG) and heart rate (HR) measurements has been proposed to investigate the HR changes related to nocturnal hypoglycemia (NH) episodes in pediatric subjects with type 1 diabetes (T1D), examining whether they could improve hypoglycemia prediction. We enrolled seventeen children and adolescents with T1D, monitored on average for 194 days. BG was detected by flash glucose monitoring devices, and HR was measured by wrist-worn fitness trackers. For each subject, we compared HR values recorded in the hour before NH episodes (before-hypoglycemia) with HR values recorded during sleep intervals without hypoglycemia (no-hypoglycemia). Furthermore, we investigated the behavior after the end of NH. Nine participants (53%) experienced at least three NH. Among these nine subjects, six (67%) showed a statistically significant difference between the before-hypoglycemia HR distribution and the no-hypoglycemia HR distribution. In all these six cases, the before-hypoglycemia HR median value was higher than the no-hypoglycemia HR median value. In almost all cases, HR values after the end of hypoglycemia remained higher compared to no-hypoglycemia sleep intervals. This exploratory study support that HR modifications occur during NH in T1D subjects. The identification of specific HR patterns can be helpful to improve NH detection and prevent fatal events.

Williams-Beuren syndrome (WBS) is a genetic disorder caused by elastin gene deletions, and is characterized by cardiovascular malformations, primarily including supravalvular aortic stenosis and peripheral pulmonary stenosis. We report a case of a neonate who developed severe discrete aortic coarctation, underwent multiple surgical interventions, and was subsequently diagnosed with WBS. Severe discrete aortic coarctation is a rare event in WBS newborns. An abnormally thick aortic wall is present in these patients and is the basis of the failure of the classical approach towards coarctation repair, which consists of end-to-end anastomosis as first surgical choice. Our case, and a very few similar previously documented cases, have all demonstrated recoarctation, which only aortic patch implantation was able to successfully repair. In light of this, we would also like to underline the importance of early WBS diagnosis. Therefore, even in mild syndromic phenotype such as low birth weight or facial dysmorphism that raise the suspicion of a genetic syndrome, it is advisable to perform fluorescent in situ hybridization analysis rather than merely karyotypic one.

Postoperative effect of music listening has not been established in pediatric age. Response on postoperative distress and pain in pediatric day care surgery has been evaluated. Forty-two children were enrolled. Patients were randomly assigned to the music-group (music intervention during awakening period) or the non-music group (standard postoperative care). Slow and fast classical music and pauses were recorded and played via ambient speakers. Heart rate, blood pressure, oxygen saturation, glucose and cortisol levels, faces pain scale and Face, Legs, Activity, Cry, Consolability (FLACC) Pain Scale were considered as indicators of response to stress and pain experience. Music during awakening induced lower increase of systolic and diastolic blood pressure levels. The non-music group showed progressive increasing values of glycemia; in music-group the curve of glycemia presented a plateau pattern (P

OBJECTIVE: Early diagnosis of significant patent ductus arteriosus reduces the risk of clinical worsening in very low birth weight infants. Echocardiographic patent ductus arteriosus shunt flow pattern can be used to predict significant patent ductus arteriosus. Pulmonary venous flow, expressed as vein velocity time integral, is correlated to ductus arteriosus closure. The aim of this study is to investigate the relationship between significant reductions in vein velocity time integral and non-significant patent ductus arteriosus in the first week of life. METHODS: A multicenter, prospective, observational study was conducted to evaluate very low birth weight infants (

The review discusses cognitive functions in late-onset schizophrenia and very late-onset schizophrenia-like psychosis compared to cognition in normal aging, early-onset schizophrenia, and neurodegenerative diseases. The problem of the dynamics of the state of the cognitive functions in patients with late-onset schizophrenic psychoses is highlighted, and prospects for further research are discussed. Patients with late-onset schizophrenic psychosis are characterized by more pronounced cognitive deficits compared to normal aging, but less severe than cognitive changes observed in early-onset schizophrenia. Late-onset schizophrenia may be a heterogeneous condition in terms of cognitive dysfunction.

This review considers the issues of clinical typology of delirium (mental confusion), its etiology and pathogenesis. Based on these data, the peculiarities of treatment, prevention and rehabilitation of delirium are discussed. Attention is drawn to the risk factors of this disorder (potentially modifiable or non-modifiable), which are most important in treatment and prevention of delirium. The questions of rehabilitation measures are regarded. Section "Treatment" presents pharmacological and non-pharmacological approaches to treatment of delirium.

Authors studied 198 patients with first-ever cerebral stroke. Affective disorders, including depression, generalized anxiety disorder (GAD) and phobias, were identified in 71.2% of patients. The study demonstrated that the anxiety syndrome developed in the post-stroke period may be regarded as relatively independent. Some post-stroke anxiety disorders had different risk and pathogenetic factors. GAD is associated with young age and phobias are associated with female sex and inherited predisposition. In contrast to post stroke depression, anxiety-phobic disorders develop more frequently in patients with mild stroke.

An aim of the study was to evaluate clinical features and risk factors of post stroke apathy. The study included 209 patients with first-time stroke. Assessments of neurological and mental status were carried out on the 1st, 7th day, after 2 weeks, 1 month, 3, 6 and 12 months after stroke. The frequency of apathy was 28.2%. Three types of apathy were singled out: classical, depressive, and combined. Apathy was significantly associated with the older age of patients, right-sided brain lesion and worst recovery of neurological deficit. Patients with depressive apathy were significantly older than patients without apathy, classic apathy was more common in men, and depressive apathy - in women. Depressive apathy was significantly associated with small lesions, while classic or combined apathy was significantly associated with the average volume of lesions.

We have studied 198 patients with first-ever stroke. The spectrum of affective disorders included depressions, generalized anxiety disorder, phobias. The study has demonstrated that mentioned post stroke affective disorders have different risk and pathogenetic factors. In stroke patients, affective disorders were caused by the damage of different brain areas. Depression was associated with the damage of left frontal/temporal cortical areas and left subcortical structures. On the contrary, anxiety disorders were associated with the damage of these structures in the right hemisphere.

Platelet serotonin content in patients in the acute period of stroke is an important index of clinical changes during the post stroke period as well as a predictor of development of mental disorders. We studied the association between two polymorphisms (5-HTTLPR and Val66Met BDNF) and the platelet serotonin content in 47 patients with stroke. We also investigated the moderating effect of genetic variants on the association between platelet serotonin content and development of affective and anxiety disorders in stroke patients in the acute period of stroke. The interaction effect of two polymorphisms on levels of platelet serotonin was found. The lowest level was observed in patients with the diplotype LL*ValVal, the highest level--in the group of patients with the LL genotype and genotypes containing at least one copy of a Met allele. No moderating effect of genetic variants on the relationship between serotonin content and affective or anxiety disorder was found.

Fifty patients with affective disorders developed after first cerebral stroke were studied. A spectrum of affective disorders included post-stroke depressions, generalized anxiety disorders, anxiety-depressive disorders and pseudo post-stroke depressions. Platelet serotonin (PS) levels were measured in these patients as well. The levels of PS at the first three days after stroke and their changes towards the 28th day are associated with the development of post-stroke affective disorders. The development of anxiety-depressive disorders in the acute period of stroke is related to the localization of brain lesion focus. The low levels of PS in patients at the first three days after stroke may be the risk factor of delayed affective disorders development.

One hundred and forty-nine patients with ischemic stroke who had different affective disorders developed one year after stroke (depression, anxiety, depression-anxiety disorders) were included in the study. Based on the computer data analysis of EEG, we singled out the characteristics of bioelectrical brain activity in patients with different types of poststroke affective disorders in acute, early and late restorative periods.

Antibodies against a new allotype, Ld2, of mink low-density lipoprotein (LDL) were obtained by alloimmunization with a preparation of this lipoprotein. The two known allotypes of LDL, designated Ld1 and Ld2, are coded for by codominant alleles of the autosomal Ld locus. This locus is probably involved in the genetic control of the whole serum pool of LDL molecules. In Ld1/Ld2 heterozygotes, LDL is represented by two homozygous types of molecules, Ld1 and Ld2; it has no hybrid molecules bearing both allotypic specificities together. The results suggest that the Ld locus has, presumably, only two alleles in the mink populations studies. Mink LDL having allotypes Ld1 and Ld2 was found to be homologous to human and pig LDLs. Antigenic specificity of Ld1 allotype was established in the sera of a wide phylogenetic range of mammals and in the human LDL. The parallelism between the phylogenetic antiquity of the Ld1 gene and its high frequency in mink and other species may be attributed to the selective value of this gene, which has been retained unaltered during macroevolution.

Mink Ldl antigen of serum low-density lipoprotein was demonstrated by alloantibodies. No genetic relation was found between Ldl and the Lpm system of very-high-density lipoprotein. The existence of an autosomal dominant gene, coding for the new alloantigenic marker, is postulated on the basis of mink breeding data.

Five allotypes, Lpm 1, Lpm 2, Lpm 3, Lpm 4, and Lpm 5, were detected by isoimmunization in mink sera. Immunoelectrophoresis, preparative ultracentrifugation, and histochemical tests for lipids and esterase permitted reference of these alloantigenic markers to a very high density alpha2-lipoprotein. Based on population analysis and breeding tests, five genetic units are postulated: Lpm1, Lpm4, Lpm3,4, Lpm1,2, and Lpm2,4,5. These units determine the polymorphism of the Lpm system and behave as Mendelian alleles.