Ablation of accessory pathways in different anatomic locations using focal pulsed field ablation.

BACKGROUND: Ablation of accessory pathways (APs) is the cornerstone for treatment of patients with Wolff-Parkinson-White syndrome and manifestation of atrioventricular reentrant tachycardia. Pulsed field ablation (PFA) is a new type of nonthermal energy source delivered to the underlying tissue via the ablation catheter and used for ablation of arrhythmic substrates. OBJECTIVE: The purpose of this study was to determine the efficiency and long-term outcome of ablation of APs of different localizations using a focal pulsed electrical field. METHODS: Electrophysiological study was performed in patients with indication for AP ablation. An ablation catheter was used to map the position of AP insertion. Pulsed electric field was delivered through a standard ablation catheter. In left-sided APs, the first ablation attempt was within the coronary sinus (CS). Patient follow-up was scheduled 1-3 months after the ablation. Additional check-up was performed after 6 and 12 months. RESULTS: Fourteen 14 patients (3 pediatric) were treated. Termination of AP conduction was achieved in all procedures. The cohort consisted of 3 right free wall, 3 posteroseptal, and 8 left-sided APs. Ablation through CS was successfully used in 7 of 8 patients with left-sided APs. No complications were reported. Median follow-up was 5.5 months. Conduction recurrence through AP was documented in 1 patient. CONCLUSION: Focal PFA for AP shows promising results in terms of efficacy and safety. A high rate of successful termination of left-sided APs by ablation within CS may represent a new standard approach. The safety and efficacy profile of PFA seems to be transferable to the pediatric population.

Three Cases of Joubert Syndrome in a Consanguineous Syrian Family and a Interesting Case of Multinational Collaboration.

Joubert syndrome (JS) is a rare congenital, autosomal recessive disorder characterized by a distinctive brain malformation, developmental delay, ocular motor apraxia, breathing abnormalities, and high clinical and genetic heterogeneity. We are reporting three siblings with JS from consanguineous parents in Syria. Two of them had the same homozygous c.2172delA (p.Trp725Glyfs*) AHI1 mutation and the third was diagnosed prenatally with magnetic resonance imaging. This pathogenic variant is very rare and described in only a few cases in the literature. Multinational collaboration could be of benefit for the patients from undeveloped, low-income countries that have a low-quality health care system, especially for the diagnosis of rare diseases.

Incidence and Clinical Phenotype of Multisystem Inflammatory Syndrome in Children After Two SARS-CoV-2 Pandemic Waves: A Croatian Prospective Nationwide Study.

This prospective nationwide study in Croatia (March 1, 2020-December 31, 2021) embraced 121 children with multisystem inflammatory syndrome. Incidence rates, disease course and outcomes were similar to those reported from other European countries. The severe acute respiratory syndrome coronavirus 2 virus Alpha strain appeared associated with a higher propensity to result in multisystem inflammatory syndrome in children than the Delta strain but did not appear related to disease severity.

The Impact of Vitamin D Levels on Clinical Manifestations of Multisystem Inflammatory Syndrome in Children: A Cross-Sectional Study.

BACKGROUND: Hyperinflammatory response that resembles Kawasaki disease may develop in children after COVID-19 disease, and it is called multisystem inflammatory syndrome in children. The cause of MIS-C is dysregulated innate immune response and a subsequent cytokine storm that results in endothelial damage. It has been determined that low levels of serum 25(OH)D increase the risk of developing immune-related diseases and disorders. METHODS: To determine the incidence of hypovitaminosis D, and a possible correlation between 25(OH)D levels and the clinical severity of MIS-C, 21 patients hospitalized in the University Hospital of Split due to MIS-C were evaluated. RESULTS: Hypovitaminosis D was detected in 95% of MIS-C patients. We found a significant relationship between the severity of MIS-C and 25(OH)D levels, as patients with more severe MIS-C had lower 25(OH)D. MIS-C patients with lower vitamin D levels had worse systolic and diastolic function of the left ventricle according to echocardiograms. There was no relationship between 25(OH)D levels and the tested laboratory inflammatory and cardiac markers. CONCLUSION: Hypovitaminosis D is very common in children with MIS-C and influences the severity of the disease. VD could be a new potential biomarker in MIS-C, and VD replacement therapy should be considered early on in the treatment of MIS-C.

Knowledge and Practice of Pediatricians Regarding Hypovitaminosis D-A Survey across 33 European Countries.

Hypovitaminosis D has been recognized as a worldwide pandemic, but there are disagreements regarding its diagnosis and treatment. This study aimed to evaluate the knowledge and practice of European pediatricians concerning vitamin D (VD) and hypovitaminosis D and their adherence to relevant guidelines. A cross-sectional study was conducted through an anonymous survey via SurveyMonkey on 304 European pediatricians. Most of the participants were general pediatricians, followed by endocrinologists and neonatologists. ESPGHAN's and the national guidelines were the most frequently used. VD testing was mostly performed in patients with skeletal, chronic kidney, and autoimmune diseases. Participants predominantly answered the questions regarding the definition of hypovitaminosis D and VD supplementation correctly, especially in children younger than 12 months. They showed the least knowledge regarding the cut off-point for the initiation of the therapy and therapeutic doses used to treat confirmed hypovitaminosis D. Participants' conflicting answers could be related to the differences between the guidelines. We consider that experts in this field should create uniform guidelines, and that those guidelines should also be promoted by national or local pediatric associations.

A suicide attempt by ingestion of oleander leaves and treatment with digoxin-specific Fab antibody fragments.

Natural cardiac glycosides have positive inotropic heart effects but at high, toxic doses they can cause life-threatening cardiac arrhythmias. Here we present the first Croatian case of a 16-year-old girl who attempted suicide by eating dried oleander leaves, which contain natural cardiac glycosides, and her treatment with a specific antidote. The girl presented with an oedema of the uvula indicating local toxicity, severe bradycardia, first-degree atrioventricular block, drowsiness, and vomiting. Having taken her medical history, we started treatment with atropine, intravenous infusion of dextrose-saline solution and gastroprotection, but it was not successful. Then we introduced digoxin-specific Fab antibody fragments and within two hours, the patient's sinus rhythm returned to normal. Cases of self-poisoning with this oleander are common in South-East Asia, because it is often used as a medicinal herb, and digoxin-specific Fab fragments have already been reported as effective antidote against oleander poisoning there. Our case has taught us that it is important to have this drug in the hospital pharmacy both for digitalis and oleander poisoning.

Hypovitaminosis D Influences the Clinical Presentation of Immune Thrombocytopenia in Children with Newly Diagnosed Disease.

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia defined as platelet count in peripheral blood <100 × 109/L. Hypovitaminosis D is very common in children with autoimmune diseases. To analyze whether hypovitaminosis D is associated with the clinical presentation of ITP in children, medical records of 45 pediatric patients with newly diagnosed immune thrombocytopenia in the coastal region of Croatia were evaluated. The severity of bleeding was assessed using two bleeding scores. Children with lower 25-hydroxyvitamin D (25(OH)D) values had higher values of the skin-mucosa-organ-gradation (SMOG) bleeding score and respectively more severe bleeding on diagnosis of ITP. With further analysis of the main domains of that score, we found that patients with a lower 25(OH)D value had more severe bleeding in the skin and organs. When 25(OH)D and ITP Bleeding Scale (IBLS) score were analyzed, a negative correlation was found, but it was not significant. Our findings suggest that hypovitaminosis D influences the severity of the clinical presentation of ITP in children on initial diagnosis of the disease. Therefore, therapy with 25(OH)D could be a new potential option for treatment of ITP. To investigate the connection between 25(OH)D and the incidence and severity of ITP, further studies, especially randomized controlled studies, are needed.

Distal arthrogryposis with variable clinical expression caused by TNNI2 mutation.

Distal arthrogryposis (DA) is a clinically and genetically heterogeneous disorder with multiple joint contractures. We describe a female DA patient with hand and foot deformities, and right-sided torticollis. Using exome sequencing, we identified a novel TNNI2 mutation (c.485>A, p.Arg162Lys) in the patient and her father. The father has no typical DA but hip dysplasia. This may explain the clinical features of DA2B in this family, but with variable clinical expression.

Serum vitamin D levels in children with newly diagnosed and chronic immune thrombocytopenia.

The primary objective of the study was to assess the vitamin D (VD) status of patients suffering from ITP. Children from the case cohort (total 21) were recruited from chronic ITP patients (followed as outpatients) and newly diagnosed ITP (prospective study) patients. VD deficiency (values <75 nmol/L) was detected in 11 patients with newly diagnosed ITP, and seven patients with chronic ITP. Only three patients with newly diagnosed, and none with chronic ITP had normal VD values. Newly diagnosed ITP patients had statistically significantly higher values (P <.044) of VD than the patients with chronic type of ITP. Platelets values did not follow VD level. VD deficiency is very common in children with either newly diagnosed or chronic ITP form. Therefore there is a utility supplementing VD in these patients. To investigate the role of VD as an immune modulating drug for patients with ITP, a prospective randomized placebo-controlled trial needs to be performed.

A surgical approach to giant condyloma (Buschke-Löwenstein tumour) with underlying superficial vulvar carcinoma: A case report.

Anogenital warts (condyloma acuminatum or venereal warts) are a common sexually transmitted disease in males and females. Common clinical treatment of anogenital warts is conservative, however, in extreme cases conservative therapy is insufficient and surgical excision is required. Giant condyloma acuminata (Buschke-Löwenstein tumour) is an extremely rare clinical type of genital wart, characterised by aggressive down growth into underlying dermal structures. A 55-year-old female presented with cauliflower-like growth over the anogenital and sacral region, earlier diagnosed as condyloma acuminatum which was resistant to conservative therapy. During the period between 2005 and 2008 the patient underwent five surgical procedures. Due to the size and location of the tumour, gynaecological and plastic surgeons were involved in the procedures. In addition, definitive histology examination identified a superficial vulvar carcinoma.

Human fetal tau protein isoform: possibilities for Alzheimer's disease treatment.

While early 1990s reports showed the phosphorylation pattern of fetal tau protein to be similar to that of tau in paired helical filaments (PHF) in Alzheimer's disease (AD), neither the molecular mechanisms of the transient developmental hyperphosphorylation of tau nor reactivation of the fetal plasticity due to re-expression of fetal protein kinases in the aging and AD human brain have been sufficiently investigated. Here, we summarize the current knowledge on fetal tau, adding new data on the specific patterns of tau protein and mRNA expression in the developing human brain as well as on change in tau phosphorylation in the perforant pathway after entorhinal cortex lesion in mice. As fetal tau isoform does not form PHF even in a highly phosphorylated state, understanding its expression and post-translational modifications represents an important avenue for future research towards the development of AD treatment and prevention.

Reliability of sentinel node assay in vulvar cancer: the first Croatian validation trial.

OBJECTIVE: To evaluate the reliability of sentinel node assay in early stage vulvar cancer patients by using preoperative lymphoscintigraphy. METHODS: Technetium-99m colloid albumin was injected intradermally around the tumor for lymphoscintigraphic mapping and intraoperative hand-held gamma probe detection of sentinel nodes. For all patients, sentinel node biopsy was followed by inguinofemoral lymphadenectomy, regardless of the sentinel lymph node status. RESULTS: From December 2008 until May 2011, 25 consecutive patients with T1 or T2 stage of vulvar squamous cell cancer were enrolled. The median age of patients was 69 years (range, 48-79). The detection of sentinel lymph node was successful in all 25 patients. A total of 36 sentinel lymph nodes were harvested and metastatic carcinoma was identified in 12 sentinel nodes from 8 patients. There was 1 patient with metastatic non-sentinel lymph node despite the negative sentinel node. Two patients with negative sentinel nodes proven by routine histopathological examination were positive by immunohistochemical staining. The sensitivity, specificity and negative predictive value of sentinel node assay with immunohistochemistry included were 89%, 100%, and 94%, respectively. CONCLUSIONS: Lymphoscintigraphy and sentinel lymph node biopsy under gamma-detecting probe guidance proved to be an easy and reliable method for the detection of sentinel node in early vulvar cancer. Immunohistochemical analysis improves the sensitivity for the detection of regional micrometastases. The sentinel node assay is highly accurate in predicting the status of the remaining inguinofemoral lymph nodes. Our results indicate that patients best suited to SLN assay have had a simple punch biopsy to confirm the diagnosis rather than a previous tumor excision. This technique represents a true advance in the selection of patients for less radical surgery.

Behavioral pattern of overweight and obese school children.

The aim of this study was to determine socio economic, health status, nutritional and behavioral differences in obese, overweight and normal weight children attending first grade elementary school. In overweight group there is 13.8% of boys and 12.6% of girls, in obese group 8.3% of boys and 6.9% of girls. In factor analysis 12 factors was excluded with cumulative loading of 60% variability. Discriminant analysis was performed with 12 factors as predictive variables and discriminant variables were three BMI groups: normal weight, overweight and obese. Function 1 discriminate well normal weight group from overweight and obese group. Overweight and obese groups is described with lower number of children in the family and lower order of birth, higher education of parents, they eat less vegetables and fruits, spend more time playing computer games, have less physical activity, drink more alcohol with their meals, exactly opposite to normal weight group.

Morphology, molecular phenotypes and distribution of neurons in developing human corpus callosum.

The aim of this study was to investigate the morphology, molecular phenotypes, distribution and developmental history of interstitial neurons in the human corpus callosum, here defined as intracallosal neurons. We analysed 26 fetuses, three newborns, five infants and children, and eight adults [age range - 15 weeks postconception (PCW) to 59 years] by means of acetylcholinesterase (AChE) histochemistry and immunohistochemistry for neuron markers (MAP2, NeuN, NPY, calretinin and calbindin). We found a heterogeneous neuron population, positioned within the callosal trunk itself (aside from neurons present in the transient midline structures such as callosal sling, septa or subcallosal zone), which was most numerous during the second half of gestation and early postnatal years. We named these cells intracallosal neurons. At 15 PCW, the intracallosal neuron population consisted of poorly differentiated, small fusiform or bipolar, migratory-like MAP2- or calretinin-positive neurons which could be observed until mid-gestation. Later the population comprised morphologically diverse, predominantly well-differentiated MAP2-, NPY-, calbindin- and AChE-positive neurons. The morphological differentiation of intracallosal neurons culminated in the newborns and remained pronounced in infants and children. In the adult brain, the intracallosal neurons were found only sporadically, with small somata and poorly stained dendrites. Thus, intracallosal neurons form part of a transitory neuron population with a developmental peak contemporaneous to the critical period of callosal formation. Therefore, they may be involved in processes such as axon guiding or elongation, withdrawal of exuberant axons, fasciculation, or functional tuning, which occur at that time.

Expression of Ki-67, P53 and progesterone receptors in uterine smooth muscle tumors. Diagnostic value.

Aim was to investigate expression of Ki-67, P53 and progesterone receptors (PR) in leiomyomas (LM), smooth muscle tumors of uncertain malignant potential (STUMP) and leiomyosarcomas (LMS) and to establish possible usefulness of these three parameters in distinguishing between LM and STUMP and STUMP and LMS. Retrospective study of 51 uterine smooth muscle neoplasm (16 LM, 18 STUMP, 17 LMS) technically acceptable for analyses from years 2002-2007 from Department of Gynecological and Prenatal Pathology, University Hospital Center Zagreb, Croatia. Immunohistochemical analysis of Ki-67, P53 and PR expression was performed. Every nuclei stained brown, regardless of shade intensivity, was considered positive. The interpretation of immunohistochemical staining was expressed as number of positive cells in 100 cell count in most active area of the slide. Non-parametric analysis of variance Kruskal-Walis test was performed. Ki-67 expression was negative in all LM and higher than 5% in 12/18 STUMP and 10/17 LMS. Significant differences were observed between LM and STUMP expression for Ki-67 (p = 0.000), and LM and LMS expression for Ki-67 (p = 0.000). There was no expression of P53 in LM, expression of P53 was found in 7/17 LMS and 5/18 STUMP Expression of P53 was significant between LM and LMS (p = 0.002), and between LM and STUMP (p = 0.006). Expression of PR was found in 16/16 LM and 18/18 STUMP 10/17 LMS did not show PR expression. Expression of PR was significant between LM and LMS (p = 0.018) and STUMP and LMS (p = 0.004). The findings of our study in concordance with other study results are helpful information establishing more diagnostic criteria and parameters for diagnosis in doubtful cases between three entities. Immunoassaying for Ki-67, P53 and PR are such parameters. The panel of their expression in specific case eases diagnosis.

[Thrombophilia, preeclampsia and other pregnancy complications]. / Trombofilija, preeklampsija i ostale komplikacije trudnoce.

The aim of this paper is to present the latest developments in therapy and prophylaxis of deep vein thrombosis and other pregnancy complications in women with inherited or acquired thrombophilia and in women with mechanical heart valves. The data presented in the paper have been extracted from the Current Contents database. It is well known that the hypercoagulable state in pregnant women, caused either by the physiological changes of pregnancy or by inherited thrombophilia, increases the risk of venous thromboembolism (VTE), pulmonary embolism (PE), preeclampsia, recurrent early and late fetal loss, intrauterine growth retardation (IUGR), placental abruption, and other less probable complications of pregnancy and its outcome. In women with mechanical heart valves, the risk of systemic embolism is also seen to increase during pregnancy. According to data analyzed, positive antiphospholipid antibodies (APLA) as well as anticardiolipin antibody and lupus anticoagulant (nonspecific inhibitor) positivity, homozygosity and heterozygosity for factor V Leiden mutation and heterozygosity for the prothrombin G20210A variant, MTHFR C677T variant homozygosity and hyperhomocysteinemia are in strong association with pregnancy complications and severe pregnancy outcome. The strongest association for late fetal loss was seen in women with protein S deficiency. In order to reduce such risks, anticoagulation therapy is administered throughout pregnancy. The antithrombotic agents available for the prevention and treatment of VTE during pregnancy and pregnancy complications include unfractionated heparin (UFH), low-molecular-weight heparin (LMWH) and aspirin. Vitamin K antagonists are contraindicated in pregnancy. Low-dose aspirin may have a role in the prevention of some pregnancy complications, although its safety in early pregnancy is uncertain. LMWH and UFH are quite safe and efficacious when properly selected, dosed and monitored. The efficacy and safety of LMWH have been demonstrated in the prevention and treatment of VTE in pregnancy. LMWH in association with aspirin administered throughout pregnancy have been shown to be associated with a lower risk of complications in women with APLA syndrome. Women at a high risk of preeclampsia are recommended to use low-dose aspirin throughout pregnancy. When there is a history of preeclampsia, the administration of anticoagulation therapy is not recommended as a prophylaxis in subsequent pregnancies, as the risk appears to be already decreased as compared with previous pregnancy. LMWH has probable advantages over UFH for the incidence of side effects. In pregnant women with mechanical heart valves, anticoagulant therapy during pregnancy should include assessment of additional risk factors for thromboembolism including valve type, position, and history of thromboembolism, and decision should also be strongly influenced by the patient's preferences. If the risk of thromboembolism in patients with mechanical heart valves is considered very high, and efficacy or safety of prophylaxis with UFH or LMWH is not satisfactory (older-generation prosthesis in the mitral position or history of thromboembolism), administration of vitamin K antagonists throughout pregnancy is recommended with replacement by UFH or LMWH close to delivery. It should be considered that limited effectiveness of UFH or LMWH in patients with mechanical heart valves might be due to inadequate dosing. The necessity of anticoagulation therapy in women with inherited or acquired thrombophilia is biologically plausible; nevertheless, optimum management in such cases remains unknown.

3D-ultrasound detection of fetal grasping of the umbilical cord and fetal outcome.

A case of persistent fetal palmar grasping of the umbilical cord in a 23-year-old primigravida is described. Palmar grasping was detected with three-dimensional ultrasound examination after cardiotocographically recorded fetal bradyarrhythmia. Because of acute fetal hypoxia, urgent Misgav-Ladach cesarean section was performed to deliver a hypotrophic female newborn, 2,120 g/43 cm, Apgar score 4/7, pH 7.29. No other pathology was found during the procedure. The postoperative course proceeded uneventfully and the early neonatal neurological status and neurosonographic findings were normal.