Acute myocardial infarction due to giant coronary artery aneurysm and arteriovenous fistula: a challenging case report and review of the literature.

BACKGROUND: A coronary artery aneurysm (CAA) is an abnormal dilation of a coronary artery segment often accompanied by coronary artery fistula (CAF), leading to communication between a coronary artery and a cardiac chamber or a part of the coronary venous system. Both CAAs and CAFs can present with symptoms and signs of myocardial ischemia and infarction. CASE PRESENTATION: We describe the case of a 46-year-old woman with non-ST-elevation myocardial infarction (NSTEMI) caused by a "giant" CAA. Various imaging modalities revealed a thrombus-containing aneurysm located at the right-posterior cardiac border, with established arteriovenous communication with the distal part of left circumflex artery (LCx). After initial treatment with dual antiplatelet therapy, a relapse of pain was reported along with a new increase in troponin levels, electrocardiographic abnormalities, reduced left ventricular ejection fraction (LVEF) and thrombus enlargement. Surgical excision of the aneurysm was favored, revealing its true size of 6 cm in diameter. Τhe aneurysm was excised without complications. The patient remained asymptomatic during follow-up. CONCLUSIONS: Management of rare entities such as "giant" CAAs and CAFs can be challenging. Cases such as this can serve as precedents to facilitate treatment plans and develop consistent recommendations, emphasizing the importance of personalized strategies for future patients.

Effectiveness of a Robot-Assisted Psychological Intervention for Children with Autism Spectrum Disorder.

Difficulties with social interaction characterise children with Autism Spectrum Disorders and have a negative impact in their everyday life. Integrating a social-humanoid robot within the standard clinical treatment has been proven promising. The main aim of this randomised controlled study was to evaluate the effectiveness of a robot-assisted psychosocial intervention and the secondary aim was to investigate potential differences between a robot-assisted intervention group and a control group receiving intervention by humans only. The analysis of the results showed that robot-assisted intervention could be beneficial by improving children's psychosocial skills. This improvement was highlighted by neuropsychological testing and parent reporting. Group comparison only presented minimal statistically significant differences. The study underpins the potential of robot-assisted interventions to augment standard care.

Acute aortic dissection type A: case series and insights on incidence, management and outcomes.

BACKGROUND: Acute aortic dissection (AAD) is a life-threatening condition with high mortality rates, despite significant advances in surgical approaches. The understanding of the clinical presentation and outcomes is crucial in order to upgrade management strategies. However, epidemiological data regarding AAD occurrence are scarce in Europe, highlighting the gap of evidence in the existing guidelines. CASE SERIES: We investigated 197 consecutive patients admitted to our institution from January 2018 to December 2019 with suspicion of type A AAD, conducting a retrospective case series. All demographic characteristics, as well as the outcomes of these patients, were recorded and further analyzed to deliver data on the epidemiology of AAD. A total of 197 patients were admitted to our hospital with a suspected AAD. Forty-one (25.9 %) patients presented with a dilated aortic lumen or with a previously repaired aortic dissection, while 28 patients (14.2 %) were diagnosed with AAD (14 patients with type A AAD, 13 with type B AAD and 1 with intramural hematoma). Among 14 patients with type A AAD, nine patients (64.0 %) were treated surgically, while the rest were managed conservatively due to futile clinical status or inability for immediate transportation to a surgical facility. The most frequent initial symptom was chest pain in 86.0 % of patients, followed by dyspnea in 42.9 %. Post-surgical mortality was 33.0 %, while all patients that were managed conservatively did not survive. D-dimers on arrival were significantly lower among patients who survived compared to those who did not. CONCLUSION: The incidence of type A AAD in our case series was consistent with the one demonstrated in other international cohorts; however, the mortality in our patient group was higher. Our results encourage surgical treatment due to a lower in-hospital mortality rate when compared to conservative treatment. HIPPOKRATIA 2021, 25 (1):42-46.

Atypical Presentation of Sjögren-Larsson Syndrome.

Sjögren-Larsson syndrome is a rare neurocutaneous disorder characterized by ichthyosis, spastic diplegia or tetraplegia, and intellectual disability. Herein, we describe a case of a Greek patient with ichthyosis and spasticity of the legs but with normal intelligence (IQ 95). This syndrome should be suspected when a child presents with ichthyosis and spastic diplegia or tetraplegia, even if intelligence is normal.

Benign epilepsy with centro-temporal spikes (BECTS): relationship between unilateral or bilateral localization of interictal stereotyped focal spikes on EEG and the effectiveness of anti-epileptic medication.

BACKGROUND AND AIM: Benign epilepsy with centro-temporal spikes (BECTS) is one of the most frequent epileptic syndromes in children. It is placed among the idiopathic localization-related epilepsies. However, the relationship between unilateral or bilateral localization of interictal stereotyped focal spikes on electroencephalogram (EEG) and the effectiveness of anti-epileptic drugs has not been studied yet. PATIENTS AND METHODS: We studied 55 neurodevelopmentally normal children who had been diagnosed with BECTS. Children were subdivided into two groups, based on EEG findings: Group A comprised 30 children with unilateral findings on EEG and Group B 25 children with bilateral findings on EEG. All patients in the present study were started on an anti-epileptic medication after the third seizure (Sodium Valproate, Carbamazepine, Oxcarbazepine) and we studied the response to medications. RESULTS: Children with bilateral findings on EEG had the same response to treatment with either Sodium Valproate or Carbamazepine or Oxcarbazepine. Other side, children with unilateral findings on EEG corresponded best to Carbamazepine or Oxcarbazepine. CONCLUSIONS: Children diagnosed with BECTS and bilateral discharges on EEG have good response to treatment with either Sodium Valproate or Carbamazepine or Oxcarbazepine.

Idiopathic acute transverse myelitis: Complete recovery after intravenous immunoglobulin.

Idiopathic acute transverse myelitis is a focal inflammatory disorder of the spinal cord of unknown etiology diagnosed according to established criteria. As it occurs rarely in children herein we report a case of a 4 year old boy who developed clinical and radiological manifestations of myelitis, 10 days after a recent respiratory tract infection. Diagnostic workup failed to reveal a causative factor. After the administration of corticosteroids a clinical deterioration was observed and intravenous immunoglobulin was administered. Symptoms resolved within a 48-hour period, suggesting an immune-mediated pathogenetic mechanism.

Carnitine status and lactate increase in patients with type I juvenile diabetes.

AIM: In 32 juvenile patients suffering from insulin dependent diabetes we observed a carnitine imbalance (increase in acylcarnitine and reduction of free carnitine), which was higher in patients with the highest levels of glycosylated hemoglobin. Parallel to that, in patients with the most prominent carnitine imbalance, there was the highest increase in the postprandial lactic acid level and the highest increase in the lactate/pyruvate ratio, without relating to ketosis. In addition, we observed a decrease in free carnitine related to the length of time after appearance of diabetes. METHODS: This was a prospective study of a cohort of 32 children and young adolescents with insulin dependent diabetes mellitus. All patients were on insulin treatment. Plasma concentrations of total, free and acyl-Carnitine were evaluated in 12 hours fasting blood samples and before the morning administration of insulin. Blood glucose, cholesterol, triglycerides, and lactate, pyruvate, beta-hydroxybutyrate and free fatty acid levels were measured. RESULTS: The postprandial highest increase of the lactate and lactate/pyruvate ratio observed in patients with the highest degree of carnitine imbalance, namely with poorliest regulated diabetes, raises the question of a coincidental mitochondrial dysfunction. On the ground of our own data, such a claim cannot be substantiated for our patients. In contrast we suggest that the role of other factors like increased gluconeogenesis, degree of ketosis need to be sought. CONCLUSION: In order to clarify the role of carnitine in the pathophysiology of disease we need also data from other tissues. Carnitine in the peripheral blood reflects only the 1% of the total body carnitine ; furthermore, patients with diabetes exhibit changes in carnitine status not only in the peripheral blood but also in other body tissues, mainly in muscles.

Cardiac manifestations of inborn errors of metabolism.

AIM: The aim of the study was to investigate the frequency and type of cardiac manifestations in a defined group of patients with inborn errors of metabolism. This paper also explores the key role of cardiac manifestations in the diagnosis of inborn errors of metabolism in daily practice. METHODS: Out of the 287 patients with the potential for inborn errors of metabolism who had been referred to the University Hospital of Heraklion (202 children and adolescents and 85 adults), 41 were found to have a variety of cardiac manifestations, including cardiomyopathy, cardiomegaly, atrioventricular conduction disorders and coronary artery disease. RESULTS: In 15 out of the 41 patients a diagnosis of inborn errors of metabolism was established, while the total number of patients with inborn errors of metabolism was 60 out of the 287. In 6 out of the 15 patients the major symptoms were from the cardiovascular system and 7 of them were adults with symptoms initiating in childhood. CONCLUSION: The cardiac findings consist of a neglected area in the diagnosis of the inborn errors of metabolism. Neurologists, pediatricians and internists should cooperate with cardiologists in managing people with unexplained cardiac symptoms and signs and be aware that several inborn errors of metabolism are associated with cardiac abnormalities and mild neurologic findings.

Prevention of complications related to traumatic brain injury in children and adolescents with creatine administration: an open label randomized pilot study.

BACKGROUND: There has been an enormous focus on the discovery and development of neuroprotective agents that might have clinical relevance after traumatic brain injury (TBI). Based on experimental facts, we studied administration of creatine to patients with TBI. METHODS: A prospective, randomized, comparative, open-labeled pilot study of the possible neuroprotective effect of creatine was performed on 39 children and adolescents, aged between 1 to 18 years old, with TBI. The creatine was administered for 6 months, at a dose of 0.4 gr/kg in an oral suspension form every day. For categorical variables, we used the chi test to identify differences between controls and cases. Statistical significance was defined as a p value <0.05 and not statistically significant if p value >0.1. RESULTS: The administration of creatine to children with TBI improved results in several parameters, including duration of post-traumatic amnesia (PTA), duration of intubation, intensive care unit (ICU) stay, disability, good recovery, self care, communication, locomotion, sociability, personality/behavior and neurophysical, and cognitive function. Significant improvement was recorded in the categories of Cognitive (p < 0.001), personality/behavior (p < 0.001), Self Care (p = 0.029), and communication (p = 0.018) aspects in all patients. No side effects were seen because of creatine administration. CONCLUSION: Preliminary data suggest that the administration of creatine may be beneficial to patients with traumatic brain injury.

Constitutive or induced elevated levels of L-carnitine correlate with the cytokine and cellular profile of endometriosis.

During the past decade, accumulated evidence indicates an association between endometriosis and an alteration of humoral and cell-mediated immunity. While the role of L-carnitine in the regulation of energy metabolism is well established, it is only recently that L-carnitine has been recognized to modify the immune response in mice after in vitro or in vivo treatment. The present study has examined whether administration of L-carnitine to young female mice alters the percentage of immune cells in peritoneal exudates and the uterus as well as the levels of IFN-gamma, TNF-alpha, IL-2, IL-4, IL-6, VEGF, GM-CSF and IGF-I in blood serum, peritoneal fluid and supernatants of uterine cultured cells as tested by immunofluorescence or ELISA techniques, respectively, leading to a pathological disorder resembling human endometriosis. The results showed that, except from infertility, L-carnitine treatment resulted in a significant increase of macrophages and to a lesser degree an increase of T-cells, while elevated levels of IFN-gamma and TNF-alpha were detected in both serum and peritoneal fluid compared to controls. Although levels of L-carnitine measured in mouse serum samples using a radioisotopic method showed an increase as compared to controls, levels of acyl-L-carnitine measured in the murine peritoneal fluid samples showed a decrease similar to that measured in peritoneal fluid samples from patients with endometriosis in stage IV of the disease. These results indicate that L-carnitine administration to female mice alters the cellular and growth factor profile in the uterus and peritoneum towards a phenotypical pathology similar to that of clinical endometriosis.

Carnitine metabolism and deficit--when supplementation is necessary?

Carnitine is an ammo acid derivative found in high energy demanding tissues (skeletal muscles, myocardium, the liver and the suprarenal glands). It is essential for the intermediary metabolism of fatty acids. Carnitine is indispensable for beta-oxidation of long-chain fatty acids in the mitochondria but also regulates CoA concentration and removal of the produced acyl groups. AcylCoAs act as restraining factor for several enzymes participating in intermediary metabolism. Transformation of AcylCoA into acylcarnitine is an important system for removing the toxic acyl groups. Although primary deficiency is unusual, depletion due to secondary causes, such as a disease or a medication side effect, can occur. Primary carnitine deficiency is caused by a defect in plasma membrane carnitine transporter in muscle and kidneys. Secondary carnitine deficiency is associated with several inborn errors of metabolism and acquired medical or iatrogenic conditions, for example in patients under valproate and zidovuline treatment. In cirrhosis and chronic renal failure, carnitine biosynthesis is impaired or carnitine is lost during hemodialysis. Other chronic conditions like diabetes mellitus, heart failure, Alzheimer disease may cause carnitine deficiency also observed in conditions with increased catabolism as in critical illness. Preterm neonates develop carnitine deficiency due to impaired proximal renal tubule carnitine re-absorption and immature carnitine biosynthesis. Carnitine stabilizes the cellular membrane and raises red blood cell osmotic resistance but has no metabolic influence on lipids in dialysis patients. L-Carnitine has been administered in senile dementia, metabolic nerve diseases, in HIV infection, tuberculosis, myopathies, cardiomyopathies, renal failure anemia and included in baby foods and milk.

L-carnitine accelerates the in vitro regeneration of neural network from adult murine brain cells.

The development, growth and regeneration of nerve cells remain an unresolved issue. The up-to-date reported brain repair mechanisms are numerous and evidence suggests that, apart from the required trophism, tropism, microenvironment and specificity of the brain, a plethora of chemical, physiological and immunological compounds can contribute to such events. Among these compounds, we concentrated our interest on L-carnitine (L-Cn), which regulates the beta-oxidation of long chain fatty acids necessary for brain development, myelinization and growth. In contrast to fetal brain cells that grow easily in culture, adult brain cells show limited neurogenesis. Here, using adult brain cells from experimental mice, we show that although L-Cn does not improve their proliferative activity in short-term cultures, it accelerates the growth and differentiation of neurons, astrocytes, oligodendrocytes and ependymal cells from neurospheres in long-term cultures. Thus, the formation of a confluent neural network requires a 2-month period in culture. These observations provide new insights for in vivo use of L-Cn to support brain cell development in cases of injury or brain degenerative diseases.

The role of L-carnitine on a restricted number of myeloid leukemia progenitor cells: generation of atypical cell types.

AIM: Since cellular maturation largely depends on lipid metabolism, we examined whether L-carnitine (L-C), a substance involved in these biochemical pathways, is able to promote differentiation of the promyelocytic cell line HL-60. METHODS: Differentiation was assessed by marker analysis, morphology, immunohistochemistry, proliferation and cellular activity assays. RESULTS: L-C increases HLA-DR and CD14 surface antigens, while morphologic and marker analysis of the treated cells reveals the presence of monocytes, neutrophiles and few dendritic cells. What is important, however, is the induction of cells that have an atypical to this pathway allure staining positive for the neurofilament 3A10 monoclonal antibody, specific for nerve cells and the anti-p75 (Nerve Growth Factor Receptor) monoclonal antibody. The events described concern active and, at the same time, not proliferative senescent cells. CONCLUSIONS: L-C exerts its differentiation action on a certain fraction of the leukemic population yielding a non-negligible number of atypical for the myeloid lineage cells. These findings complement earlier and recent reports that describe the generation of cells of a different lineage irrelevant to their parent line of differentiation indicating that the hemopoietic pool appears to be the source of any kind of cell types according to the stimulus provided. Thus, in the context of the plasticity theory it appears that the HL-60 cell line also possess the potential to differentiate towards unexpected pathways.

L-carnitine modifies the humoral immune response in mice after in vitro or in vivo treatment.

Although the role of L-carnitine (L-Cn) as a cofactor in the oxidation of long-chain fatty acids has been well established, this agent has also been recognized to have an important role in the regulation of carbohydrate metabolism, and consequently, the maintenance of cell membrane structure and cell viability. L-Cn has been reported to reduce the apoptotic levels of CD4+ and CD8+ cells. It has also been demonstrated to interfere with cells of the monocytic lineage by regulating their ability to produce growth factors that ultimately affect both T and B lymphocytic subsets. Therefore, in this study, we examined whether this agent affects the antigenic response of immune cells and determined the relative numbers of immune cells in the murine spleen after in vitro and in vivo treatment. The results showed that L-Cn reduces the relative numbers of CD8+, CD4+ and Ly5+ cells. This observation was consistent in all systems studied including (a) in vitro inoculation of antigen (DNP-HSA) and L-Cn, (b) in vitro priming of spleen cells treated with L-Cn in vivo, and (c) in vivo immunization and L-Cn administration. In all cases, the reduction of T lymphocytes correlated with the decreased production of interleukin-2. L-Cn, however, did not affect the production of specific antibody, which indicates that the observed reduction of Ly5-positive cells is due to cell differentiation of B cells to plasma cells.

Effects of gestation age and of birth weight in the concentration of carnitine in the umbilical plasma.

To investigate the factors which affect the concentrations of the total, the free, and the acylcarnitine in neonates, blood was taken from the umbilical cord of 49 newborn infants ranging in gestation age (g. a.) from 32-40 weeks (mean g. a.: 36.8 +/- 2.6 weeks) and in birth weight (b. w.) from 1300 gr.-4300 gr. (mean b. w.: 2299 +/- 457 gr.). The carnitine and its fractions were studied in plasma. Twenty-eight of the neonates studied were premature (g. a. < or = 37 weeks) and 21 were full-term (g. a. > 37 weeks). The concentration of the total, free, and acylcarnitine in premature neonates was 28.0 +/- 2.3 mumol/L, 15.9 +/- 1.3 mumol/L, and 12.0 +/- 1.3 mumol/L, respectively. For the full-term neonates the respective concentrations were: 25.2 +/- 2.2 mumol/L, 14.6 +/- 1.5 mumol/L, and 10.7 +/- 1.5 mumol/L. These differences in concentrations between premature and full-term infants were statistically significant. For the total number of neonates studied the concentration of total, free, and of acylcarnitine was 26.8 +/- 2.6 mumol/L, 15.3 +/- 1.9 mumol/L, 11.5 +/- 1.5 mumol/L respectively. The calculation of the correlation coefficients for the total number of neonates showed the existence of a statistically significant negative correlation between the total, free and acetyl carnitine in terms of gestation age and birth weight. The comparative analysis of the correlation coefficients showed greater coefficient values between the total and the acylcarnitine in terms of birth weight. The latter finding, combined with the low rate of acylcarnitine decline, are indirect indications that the fetus uses carnitine as a source of energy, which affects the levels of total and acylcarnitine in the plasma.

Correlation between long-chain acylcarnitine in serum and myocardium after heart transplantation in humans.

The concentrations of free, short-chain, and long-chain acylcarnitine were determined in 19 right ventricular endomyocardial biopsies and in serum from 14 patients after orthotopic heart transplantation and 3 nontransplanted control patients with normal cardiac function. Coronary angiography was normal in all patients. Left ventricular ejection fraction as measured by radionuclide ventriculography was not different between heart-transplanted and control patients (60.3 +/- 6.7% and 61.7 +/- 10.7%, respectively). Myocardial and serum carnitine concentrations in heart-transplanted patients were not different from control patients (myocardium: free carnitine 11.8 +/- 4.8 vs 7.1 +/- 7.1, short-chain acylcarnitine 4.5 +/- 2.1 vs 5.8 +/- 2.0, long-chain acylcarnitine 4.9 +/- 3.8 vs 3.9 +/- 3.2 mumol/g noncollagen protein; serum: free carnitine 32.6 +/- 11.2 vs 32.0 +/- 9.9, short-chain acylcarnitine 7.3 +/- 5.2 vs 5.1 +/- 1.3, long-chain acylcarnitine 4.1 +/- 2.7 vs 4.8 +/- 4.0 mumol/L). There was a highly significant correlation between myocardial and serum long-chain acylcarnitine (r = 0.76, P < 0.001). The data suggest that carnitine metabolism is not altered after heart transplantation.