A Survey of the Course: 'How to Successfully Write a Scientific Article'.

BACKGROUND: The aim of the present survey was to analyze the knowledge and skills in medical paper writing of physicians who attended the course "how to write successfully a scientific paper." METHODS: A blind survey was used to analyze participants' knowledge on the topic of the course "how to write successfully a scientific paper." Before starting the workshop, participants anonymously filled out the input questionnaire containing 12 preliminary data questions. The three-hour course included a lecture on the steps of creating and writing a scientific article with examples. At the end, all participants anonymously completed the exit questionnaire consisting of 18 questions. Differences and associations between the collected data were analyzed using appropriate statistical tests. RESULTS: The survey included 22 participants, most of whom were women (16, 72.7%). The participants' educational level was proportional to their age. 12 of the participants had an intermediate level, while the others reported higher English proficiency. Half of the participants had never published an article. A significant difference was observed between English level and being the first author of an article published in a scientific journal (p = 0.044). Before class, only 13.6% of participants knew that guidelines are mandatory for making clinical decisions according to evidence- based medicine. There was a significant positive correlation between sex and current affiliation (p = 0.038). A negative correlation was observed between sex and article publication (p = 0.037). A positive correlation was observed between English level and current affiliation (p = 0.020). There was a negative correlation observed between previous sources of learning scientific article writing and having already published an article (p = 0.025). A positive correlation was found between reading an article and publishing it (p = 0.046). Statistical analysis showed a significant difference between reading frequency, number of published articles, being the first author, and knowing the title of a scientific article (p = 0.036, p = 0.027, and p = 0.030, respectively). CONCLUSION: The results of the questionnaires revealed discrepancies in prior research engagement and understanding of scientific concepts and rules. This survey highlights the importance of the course "how to successfully write a scientific article" in improving participants' knowledge of scientific work and the process of creating an article for submission to medical journals.

Association between innate immunity gene polymorphisms and neonatal sepsis development: a systematic review and meta-analysis.

BACKGROUND: The aim of this meta-analysis was to analyze all available data from studies investigating associations between polymorphisms in genes responsible for innate immunity and neonatal sepsis development. METHODS: A comprehensive literature search, reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-S guidelines, was performed with no language restriction. Studies derived using the PICO (population, intervention, comparison and outcomes) strategy, with data on the genotype distribution for innate immunity gene polymorphisms in newborns with and without sepsis. Data were analyzed using Review Manager. The Cochran-Mantel-Haenszel test was used to calculate odds ratios with 95% confidence intervals. Heterogeneity was tested using the I2 index. RESULTS: From a total of 9428 possibly relevant articles, 33 qualified for inclusion in this systematic review. According to the STrengthening the REporting of Genetic Association Studies, 23 studies were found to be of moderate quality, while 10 were of low quality. The results showed an association of the mannose-binding lectin (MBL) exon 1 genetic polymorphism with the risk of culture-proven sepsis. Toll-like receptor (TLR) 4 rs4986791 genotype distribution suggests its association with the increased risk of culture-proven sepsis. The certainty of evidence per GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) varied from very low to low. Publication bias was not detected. CONCLUSIONS: Out of the 11 investigated single-nucleotide polymorphisms, this meta-analysis found a possible association between the risk for culture-proven sepsis and MBL exon 1 and TLR4 rs4986791 polymorphisms. There is an evident need for larger well-designed, multicentric observational studies investigating inflammatory gene polymorphisms in neonatal sepsis.

Colonization with Multidrug-Resistant Bacteria in the First Week of Life among Hospitalized Preterm Neonates in Serbia: Risk Factors and Outcomes.

The aim of this prospective cohort study was to determine the prevalence of gut colonization with multidrug-resistant (MDR) bacteria, risk factors for colonization, infection risk, and outcomes among preterm neonates hospitalized at a tertiary-care center in Serbia. During the period from December 2017 to April 2018, 103 neonates were screened for rectal carriage at admission and on the seventh day of life. Characterization of MDR strains was done by conventional microbiology and molecular methods. Out of 61 (59.2%) colonized neonates, 12 (11.6%) were found colonized at admission, while 49 (47.6%) became colonized at the study site. Among a total of 72 MDR isolates, extended-spectrum beta-lactamase (ESBL)-producing enterobacteria prevailed (56/72, 77%), followed by Acinetobacter baumannii (14/72, 19%). The majority of ESBL-producing strains carried multiple genes (blaTEM/blaCTX-M-15 or blaTEM/blaSHV). Longer previous hospitalization and delivery by cesarean section were associated with MDR colonization, while mechanical ventilation was a risk factor for colonization at the study site. Infections due to MDR bacteria were more frequent among colonized than non-colonized neonates, but not significantly, and mortality was low (1%) in the studied neonates. These results indicate that hospitalized preterm neonates in Serbia are rapidly colonized with a diversity of MDR species and resistance phenotypes/genotypes.

Clinical and genetic characteristics of patients with congenital hyperinsulinism in 21 non-consanguineous families from Serbia.

Persistent hypoglycaemia in newborns and infants is most commonly caused by congenital hyperinsulinism (CHI). Most CHI studies report outcomes in children from both consanguineous and non-consanguineous families which can affect the phenotype-genotype analysis. The aim of this study was to analyze characteristics of patients with CHI in 21 non-consanguineous families from Serbia. This retrospective cohort study included a total of 21 patients with CHI treated in the Mother and Child Healthcare Institute of Serbia during the past 20 years. The prevalence of macrosomia at birth was very low in our cohort (4.8%). Median age at presentation was 6 days, with seizures as the presenting symptom in 76% of patients. Only four patients (19%) were diazoxide unresponsive, and eventually underwent pancreatectomy. Genetic testing was performed in 15 patients and genetic diagnosis was confirmed in 60%, with all patients being heterozygous for detected mutations. The ABCC8 gene mutations were detected in 55.6%, GLUD1 in three patients (33.3%) with HIHA syndrome and one patient had HNF4A gene mutation and unusual prolonged hyperglycaemia lasting 6 days after diazoxide cessation. Neurodevelopmental deficits persisted in 33% of patients.Conclusion: This is the first study regarding CHI patients in Serbia. It suggests that in countries with low consanguinity rate, majority of CHI patients are diazoxide responsive. The most common mutations were heterozygous ABCC8, followed by GLUD1 and HNF4A mutations, suggesting the potential benefit of population-tailored genetic analysis approach, targeting the mutations causing CHI via dominant inheritance model in regions with low consanguinity rates. What is Known: • Persistent hypoglycaemia during infancy and early childhood is most commonly caused by congenital hyperinsulinism (CHI). • Consanguinity is a very important factor regarding the genetics and phenotype of CHI, increasing the risk of autosomal recessive genetic disorders, including the severe, diazoxide-unresponsive forms caused by recessive inactivating mutations in ABCC8 and KCNJ11. What is New: • Results of the present study which included CHI patients from 21 non-consanguineous families suggest that in countries with low consanguinity rates, majority of CHI patients can be diazoxide responsive, with most common mutations being heterozygous ABCC8, followed by GLUD1 and HNF4A mutations. • Unusually prolonged hyperglycaemic reaction to diazoxide treatment in a patient with HNF4A mutation was also described in the present study.

The features of neonatal seizures as predictors of drug-resistant epilepsy in children.

PURPOSE: The aim of this study was to evaluate the predictive value of the features of neonatal seizures for pharmacoresistant epilepsy in children. METHOD: This is a retrospective study that involved all children diagnosed as having epilepsy who had neonatal seizures and who were hospitalized at the Neurology Department of the Mother and Child Healthcare Institute in Belgrade from January the 1st 2017 until December 31st 2017. The following parameters and their impact on the outcome were investigated: perinatal data, the characteristics of epileptic seizures in the neonatal period, and the response to anticonvulsant treatment. The presence of pharmacoresistance was observed as an outcome parameter. Univariate and multivariate logistic regression analyses were used to define predictors of drug-resistant epilepsy. RESULTS: The study involved 55 children, 35 (63.6%) male and 20 (36.4%) female. The average age of the children at the end of the observation period was 5.17 years (min: 0.25, max: 17.75, iqr (interquartile range): 6.92). Pharmacoresistant epilepsy was found in 36 (65.5%) children. The most common type of epilepsy was focal, which affected 30 patients (54.5%), than generalized, which affected 15 patients (27.3%), and combined generalized and focal, which affected 8 patients (14.5%). At the end of the observation period, 28 patients (50.9%) had no seizures, while 14 (25.5%) had daily seizures. It was found that the pharmacoresistant neonatal seizures and metabolic-genetic disorders were predictive factors of the occurrence of pharmacoresistant epilepsy. CONCLUSION: Patients prone to developing pharmacoresistant epilepsy might be identified as early as the neonatal and early infant period. High incidence of asphyxia cooccurring with established genetic-metabolic disease further emphasizes need for genetic testing in infants with neonatal seizures including in the presence of hypoxic-ischemic injury.

Massive fetomaternal hemorrhage as a cause of severe fetal anemia.

Introduction: Fetomaternal hemorrhage (FMH) is a transfu-sion of fetal blood into the maternal circulation. A volume of transfused fetal blood required to cause severe, life-threatening fetal anemia, is not clearly defined. Some authors suggest vol-umes of 80 mL and 150 mL as a threshold which defines mas-sive FMH. Therefore, a rate of massive FMH is 1 : 1,000 and 1 : 5,000 births, respectively. Fetal and neonatal anemia is one of the most serious complications of the FMH. Clinical manifesta-tions of FMH are nonspecific, and mostly it presented as re-duced fetal movements and changes in cardiotocography (CTG). The standard for diagnosing FMH is Kleihaurer-Betke test. Case report: A 34-year-old gravida (G) 1, para (P) 1 was hospitalized due to uterine contractions at 39 weeks of gesta-tion. CTG monitoring revealed sinusoidal fetal heart rate and clinical examination showed complete cervical dilatation. Im-mediately after admission, the women delivered vaginally. Ap-gar scores were 1 and 2 at the first and fifth minute, respec-tively. Immediately baby was intubated and mechanical ventila-tion started. Initial analysis revealed pronounced acidosis and severe anemia. The patient received intravenous fluid therapy with sodium-bicarbonate as well as red cell transfusion. With all measures, the condition of the baby improved with normaliza-tion of hemoglobin level and blood pH. Kleihaurer-Betke test revealed the presence of fetal red cells in maternal circulation, equivalent to 531 mL blood loss. The level of maternal fetal hemoglobin (HbF) and elevated alpha fetoprotein also con-firmed the diagnosis of massive FMH. Conclusion: For the successful diagnosis and management of FMH direct commu-nication between the obstetrician and the pediatrician is neces-sary as presented in this report.

Use of intravenous immunoglobulin in neonates with haemolytic disease and immune thrombocytopenia.

BACKGROUND/AIM: Intravenous immunoglobulin is a blood product made of human polyclonal immunoglobulin G. The mode of action of intravenous immunoglobulin is very complex. It is indicated in treatment of neonatal immune thrombocytopenia and haemolytic disease of the newborn. The aim of the study was to present our experience in the use of intravenous immunoglobulin in a group of term neonates. METHODS: We analysed all relevant clinical and laboratory data of 23 neonates who recieved intravenous immunoglobulin during their hospitalization in Neonatal Intensive Care Unit of Mother and Child Health Care Institute over a five year period, from 2006. to 2010. RESULTS: There were 11 patients with haemolytic disease of the newborn and 12 neonates with immune thrombocytopenia. All of them recieved 1-2 g/kg intravenous immunoglobulin in the course of their treatment. There was no adverse effects of intravenous immunoglobulin use. The use of intravenous immunoglobulin led to an increase in platelet number in thrombocytopenic patients, whereas in those with haemolytic disease serum bilirubin level decreased significantly, so that some patients whose bilirubin level was very close to the exchange transfusion criterion, avoided this procedure. CONCLUSION: The use of intravenous immunoglobulin was shown to be an effective treatment in reducing the need for exchange transfusion, duration of phototherapy and the length of hospital stay in neonates with haemolytic disease. When used in treatment of neonatal immune thrombocytopenia, it leads to an increase in the platelet number, thus decreasing the risk of serious complications of thrombocytopenia.

Two seasons' experience with pandemic A H1N1 influenza infection in neonates.

There are only a few reports on influenza A H1N1 infection in neonates. In this paper, we present our additional experience on the clinical characteristics, epidemiology and treatment of influenza A H1N1 (2009) infection in 10 newborn infants (aged 9-24 days). Influenza A H1N1 infection was confirmed by real-time reverse transcription-polymerase chain reaction of the nasopharyngeal swab specimens. The majority of neonates presented with fever, respiratory symptoms and lethargy. The respiratory illness ranged from mild symptoms to severe pneumonia requiring mechanical ventilation. Antiviral treatment with oseltamivir was started in five patients (50%). One lethal outcome was observed, while nine patients (90%) had complete recovery. To our knowledge, this is the largest presented series of neonatal cases with different clinical symptoms. We discuss the necessity of initiation of oseltamivir in infants with different clinical features.

[Non-immune hydrops fetalis--clinical experience in newborn infants].

INTRODUCTION: Non-immune hydrops fetalis is a condition of excessive accumulation of extravascular fluid without identifiable circulating antibody to erythrocytes membrane antigens. In newborn infants it is characterized by skin oedema and pleural, pericardial or peritoneal effusion. In the era of routine Rh immunization for the prevention of foetal erythroblastosis, non-immune pathophysiologic mechanisms are presented in 76-87% of all hydropic newborns. Non-immune hydrops fetalis can be associated with numerous and various disorders. The mortality rate may exceed 50%. This study was aimed at presenting our clinical experience in treating newborn infants with non-immune hydrops fetalis. MATERIAL AND METHODS: A retrospective-prospective study included newborn infants with non-immune hydrops fetalis, who were treated in the Neonatal Intensive Care Unit of Mother and Child Health Institute of Serbia between January 1, 2001 and October 31, 2010. All valid data about aetiology, diagnosis, clinical course and outcome were recorded. RESULTS: The diagnosis of non-immune hydrops fetalis was made in 11 newborns. The etiologic diagnosis was established in 8 patients: anaemia due to fetomaternal transfusion in 4 patients and conatal cytomegalovirus infection, intracranial haemorrhage, isolated pulmonary lymphangiectasia and diffuse skin and mediastinal lymphangiomatosis in the remaining 4 patients. CONCLUSION: Non-immune hydrops of newborn infant is associated with a high mortality rate and requires complex diagnostic and therapeutic procedures. An optimal management of neonates with non-immune hydrops fetalis demands a multidisciplinary approach to the treatment in a neonatal intensive care unit.

The efficacy of bromides, stiripentol and levetiracetam in two patients with malignant migrating partial seizures in infancy.

The syndrome of malignant migrating partial seizures in infancy is a devastating, age-specific, epileptic encephalopathy, which still presents an aetiological, pathophysiological and therapeutic problem. In this study, we present two patients who were diagnosed with the disease, based on electroclinical symptoms. The patients were treated with a combination of sodium bromide, stiripentol and levetiracetam. The first patient unequivocally responded, following a course of ineffective conventional drugs, and the second, who was diagnosed and treated immediately, showed a more significant therapeutic response. Antiepileptic drugs, previously reported to be beneficial in case reports, when given concomitantly, may substantially reduce the number and severity of seizures, without influence on psychomotor development. [Published with video sequences].

Hemophilia in the newborn without family history--pattern of clinical presentation of three patients.

INTRODUCTION: Hemophilia is the most frequently diagnosed inborn clotting factor deficiency in the newborn. In about half of the cases diagnosis is made during neonatal period. However, due to different clinical presentation comparing to older children, hemophilia in the newborn could be misdiagnosed, especially in the setting of negative family history. CASE REPORT: Clinical features of three newborns with negative family history for hemophilia are described. All three newborns were the first born children with uneventful perinatal history, and they were referred for investigation of convulsions, soft tissue tumorous mass and sepsis, respectively. Prompt diagnosis of underlying bleeding disorder and adequate substitution therapy lead to the good outcome in all three boys. CONCLUSION: Symptoms and signs of hemophilia in the newborn could be at time misleading and contribute to delayed treatment. High index of suspicion on inherited bleeding disorder is warranted in every neonate with intracranial bleeding.

Neonatal cellulitis and sepsis caused by group A streptococcus.

We report a case of late onset neonatal invasive group A streptococcal disease characterized with rapidly progressing cellulitis and development of sepsis. The infection was acquired from benign and mild skin infection of the child's mother. The causative agent was group A streptococcus, belonging to the emm type 53.2, which usually causes mild skin disease.

[Use of mechanical ventilation in pediatric patients].

BACKGROUND/AIM: Major aims of mechanical ventilation (MV) in pediatrics mean the contribution to complete recovery of acute disorder or to establishing stability of previously long-term changed health condition. MV is used today in 16-46% of patients treated in pediatric intensive care units. The aim of this paper was to get insight into the presence of the disease and pathologic conditions and outcome of MV regarding previous health condition of pediatric patients. METHODS: This retrospective study included 476 pediatric patients (beyond neonatal age) who underwent mechanical ventilation (MV). On the basis of previous health status the patients were classified in two groups: the group A consisted of 157 children with no previous chronic disease leading to MV and the group H comprised of 319 children who received MV due to worsening ofprevious chronic disease. RESULTS: In both groups of pediatric patients there was significant predominance of younger age patients. Acute and chronic neurological disorders were the most frequent conditions requiring use of MV. Out of a total number (476) of the patients, 178 patients (37.40%) died. In the group A 17 patients (10.9%) died, while in the group H mortality rate was significantly higher (161 or 50.5% patients died; p < 0.01; RR 4.85; CI 3.1-7.6). Total duration time of MV in all the patients was 7 525 days, with 1 345 days (15%) accounted for the group A and 4 567 days (85%) for the group H. Mean MV duration was 7.48 (+/- 9.23) days for the patients in the group A which is significantly shorter in comparison to mean 21.8 (+/- 57.96) days for the group H patients (p < 0.001). CONCLUSION: These results point out significant contribution of MV to better outcome in pediatric patients with different acute disorders. Clear dominance of chronically ill children requiring mechanical ventilation due to acute worsening of their condition implies new complexity of problems regarding organization of pediatric intensive care and treatment.

Disseminated neonatal herpes caused by herpes simplex virus types 1 and 2.

Disseminated neonatal herpes simplex virus (HSV) infection is characterized by progressive multiple organ failure and high mortality rates. It can result from infection with either HSV-1 or HSV-2. We report a case of disseminated neonatal herpes that was caused by HSV-1 and HSV-2.

Transient neonatal diabetes mellitus in an infant with paternal uniparental disomy of chromosome 6 including heterodisomy for 6q24.

We describe a female infant who developed transient neonatal diabetes mellitus (TNDM) (MIM 601410). At birth she presented with growth retardation and macroglossia. Diabetes was diagnosed on the fourth day of life and it resolved after two months of insulin therapy. Genetic testing revealed the presence of paternal uniparental disomy of chromosome 6 (UPD6) including heterodisomy of 6q24. This is the first documented case of uniparental heterodisomy for chromosome 6.

[C-reactive protein and cytokines in the diagnosis of neonatal sepsis].

INTRODUCTION: Accurate evaluation and correct treatment of neonates for possible sepsis still represent the most challenging clinical tasks. Early diagnosis of neonatal sepsis is largely based on the measurement of serum concentrations of different mediators of systemic inflammation, as well as, on a group of proteins named acute phase reactants. Among acute phase reactants, C-reactive protein (CRP) has been the most extensively used and investigated so far. SYNTHESIS AND BIOLOGICAL ROLE OF CRP: This article reviews current knowledge on the synthesis, structure and biologic roles of CRP. Also, we present our original results in regard to the kinetics of serum CRP concentration during the first 24 hours of systemic injection, as well as different patterns of CRP dynamics associated with the initial choice of antibiotics, complications and the final outcome of systemic injection. INTERLEUKINS AND PROCALCITONIN IN DIAGNOSIS OF SEPSIS: Because CRP is specific, but somewhat late marker of neonatal sepsis, possible diagnostic use of other indicators of inflammation, i.e. interleukins 6 and 8, and procalcitonin during neonatal sepsis is also considered. The theoretical advantage of these early indicators is discussed in comparative analysis of the time of their activation after initial infections stimuli. CONCLUSION: In conclusion, we point to the diagnostic accuracy of serial measurements of serum CRP levels. As an alternative, simultaneous measurement of CRP and serum levels using a faster marker, such as procalcitonin, is recommended.