Approach and Management of Pregnancies with Risk Identified by Non-Invasive Prenatal Testing.

This study represents our second investigation into NIPT, involving a more extensive patient cohort with a specific emphasis on the high-risk group. The high-risk group was subsequently divided into two further groups to compare confirmed cases versus unconfirmed via direct methods. The methodology encompassed the analysis of 1400 consecutive cases from a single genetic center in western Romania, where NIPT was used to assess the risk of specific fetal chromosomal abnormalities. All high-risk cases underwent validation through direct analysis of fetal cells obtained via invasive methods, including chorionic villus sampling and amniocentesis. The confirmation process utilized QF-PCR, karyotyping, and SNP-Array methods customized to each case. Results: A high risk of aneuploidy at NIPT was identified in 36 out of 1400 (2.57%) cases and confirmed in 28 cases. The study also detected an increased risk for copy number variations (CNVs) in 1% of cases, confirmed in two instances involving one large microdeletion and one large microduplication. Trisomy 21 was the exclusive anomaly where NIPT confirmed all cases with identified risk. High-risk NIPT results which were not validated by invasive methods, were classified as false positives; parents in these cases determined to continue the pregnancy. In conclusion, NIPT can serve as a screening method for all pregnancies; however, in high-risk cases, an invasive confirmation test is strongly recommended.

The Implications of Cytochrome P450 2D6/CYP2D6 Polymorphism in the Therapeutic Response of Atypical Antipsychotics in Adolescents with Psychosis-A Prospective Study.

BACKGROUND: The plasma level of antipsychotics and their metabolites depends on the activity of the cytochrome P450 (CYP) system in the liver. This research aims to test the individual response variability to atypical antipsychotic drugs, depending on the activity of the CYP2D6 enzyme. METHODS: In a prospective, noninterventional study, we included 56 adolescents, 51.79% male, diagnosed with schizophrenia. The patients underwent DNA sampling for genotyping SNP by RT-PCR and CYP* allelic variants using Applied Bio-systems™ TaqMan® Assays Foster City, CA, USA). and clinical and paraclinical assessments. The effectiveness of the therapy was evaluated with the PANSS scores at baseline and 3, 6, and 12 months after the initiation of an atypical antipsychotic treatment. RESULTS: Based on the genotyping results, the patients were divided into slow metabolizers (Group 1), extensive metabolizers (Group 2), and intermediate metabolizers (Group 3). The PANSS score showed a significant decrease in Group 2, compared to Group 3 after 3 (p = 0.02), 6 (p = 0.0009), and 12 months (p < 0.0001). The patients in Group 1 showed high PANSS scores, and those in Group 2 had fewer adverse reactions than the other groups. CONCLUSIONS: Assessing the CYP2D6 polymorphism may be useful in clinical pediatric psychiatric practice towards improving clinical results and patients' quality of life.

Genetic Characterization of Dilated Cardiomyopathy in Romanian Adult Patients.

Dilated cardiomyopathy (DCM) represents a group of disorders affecting the structure and function of the heart muscle, leading to a high risk of heart failure and sudden cardiac death (SCD). DCM frequently involves an underlying genetic etiology. Genetic testing is valuable for risk stratification, treatment decisions, and family screening. Romanian population data on the genetic etiology of DCM are lacking. We aimed to investigate the genetic causes for DCM among Romanian adult patients at tertiary referral centers across the country. Clinical and genetic investigations were performed on adult patients presenting to tertiary hospitals in Romania. The genetic investigations used next-generation sequencing panels of disease-associated DCM genes. A total of 122 patients with DCM underwent genetic testing. The mean age at DCM diagnosis was 41.6 ± 12.4 years. The genetic investigations identified pathogenic or likely pathogenic variants in 50.8% of participants, while 25.4% had variants of unknown significance. Disease-causing variants in 15 genes were identified in people with DCM, with 31 previously unreported variants. Variants in TTN, LMNA, and DSP explained 75% of genetic causes for DCM. In total, 52.4% of patients had a family history of DCM/SCD. Left ventricular ejection fraction of <35% was observed in 41.9% of patients with disease-causing variants and 55% with negative or uncertain findings. Further genotype-phenotype correlations were explored in this study population. The substantial percentage (50.8%) of disease-causing variants identified in patients with DCM acknowledges the importance of genetic investigations. This study highlights the genetic landscape in genes associated with DCM in the Romanian population.

The Role of Circular RNA for Early Diagnosis and Improved Management of Patients with Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are responsible for approximately 17.9 million deaths every year. There is growing evidence that circular RNAs (circRNAs) may play a significant role in the early diagnosis and treatment of cardiovascular diseases. As regulatory molecules, circular RNAs regulate gene expression, interact with proteins and miRNAs, and are translated into proteins that play a key role in a wide variety of biological processes, including the division and proliferation of cells, as well as the growth and development of individuals. An overview of the properties, expression profiles, classification, and functions of circRNAs is presented here, along with an explanation of their implications in cardiovascular diseases including heart failure, hypertension, ischemia/reperfusion injury, myocardial infarction, cardiomyopathies, atherosclerosis, and arrhythmia.

Latent Tuberculosis in Psoriasis Patients on Biologic Therapies: Real-World Data from a Care Center in Romania.

Background and Objectives: Psoriasis is a chronic and inflammatory condition that has a huge impact on the patient's quality of life. Biological treatment improved psoriasis therapy, with impressive results seen in the evolution of the disease and the patient's quality of life. However, the risk of mycobacterium tuberculosis (MTB) infection reactivation is well-known to biological therapy, which raises problems especially in an endemic country. Materials and Methods: In this study, we followed moderate to severe psoriasis patients who had latent tuberculosis infection (LTBI) following treatment with a biological therapy approved in Romania. Results: The patients were evaluated at baseline and then followed-up with Mantoux tests and chest X-rays every year, resulting in 54 patients being diagnosed with LTBI. At the initial evaluation, 30 patients with LTBI were identified, and 24 more were identified during biological therapy. These patients were given prophylactic treatment. Out of the 97 participants in this retrospective study, 25 required association of methotrexate (MTX) alongside biological therapy. We compared the prevalence of positive Mantoux tests in patients with combined therapy with that of patients only on biological treatment, and the results were higher in the combined therapy group. Conclusion: All the patients in the study were vaccinated against tuberculosis (TB) after birth, and none were diagnosed with active tuberculosis (aTB) before or after the start of therapy according to the pulmonologist.

Primary Cutaneous B-Cell Lymphoma Co-Existing with Mycosis Fungoides-A Case Report and Overview of the Literature.

The existence of two sequential lymphomas, one localized and one systemic, either both with B or T lymphocytes, or one with B cells and one with T cells, with the same patient, is a known possibility. The second lymphoma is often induced by immunodepression or by the initial treatment. However, the existence of two cutaneous lymphomas with different cell lines, without systemic involvement, represents an uncommon situation. In this report, we describe the case of a 37-year-old man with an initial diagnosis of PMZBCL that over 10 months also developed a MF patch/plaque on the left leg.

Cardiofaciocutaneous syndrome - a longitudinal study of a case over 33 years: case report and review of the literature.

Cardiofaciocutaneous (CFC) syndrome [Online Mendelian Inheritance in Man (OMIM) #115150] is characterized by craniofacial dysmorphism, heart malformation, ectodermal abnormalities, neuromotor delay and intellectual disability. It is not a frequent disease, about 300 cases have been reported in the medical literature. We describe the case of a 34-year-old patient presenting with CFC syndrome phenotype, monitored since the age of 1 1∕2 years. Clinical findings included craniofacial dysmorphism, development delay, heart malformation and severe intellectual disability. The evolution was with progressive intellectual disability, hypogonadism, hypertrophic cardiomyopathy, wrinkled palms and soles. Molecular analysis showed a heterozygous variant in the B-Raf proto-oncogene, serine∕threonine kinase (BRAF) gene (7q34): NM_001354609.2:c.1502A>G, with pathogenic significance. We report this case, observed along a period of 33 years, for illustration of clinical evolutive particularities, and for difficulties in establishing the positive diagnosis.

Biallelic variants in BRCA1 gene cause a recognisable phenotype within chromosomal instability syndromes reframed as BRCA1 deficiency.

Pathogenic variants in BRCA1 gene in heterozygous state are known to be associated with breast-ovarian cancer susceptibility; however, biallelic variants cause a phenotype recognised as Fanconi anaemia complementation group S. Due to its rarity, medical management and preventive screening measures are insufficiently understood. Here, we present nine individuals (one new and eight previously presented) with biallelic variants in BRCA1 gene, to delineate clinical features in comparison with other chromosome instability syndromes and understand the patients' health risk. Features seen in these 9 individuals (7 females/2 males) include prenatal and postnatal growth failure (9/9), microcephaly (9/9), hypo/hyperpigmented lesions (9/9), facial dysmorphism (9/9), mild developmental delay (8/9) and early-onset solid tumours (5/9). None presented bone marrow failure or immunodeficiency. Individuals with biallelic variants in BRCA1 also showed chromosomal instability by mitomycin and diepoxybutane test. The phenotype caused by biallelic BRCA1 variants is best framed between Fanconi anaemia and Nijmegen syndrome, yet distinct due to lack of bone marrow failure and immunodeficiency. We hypothesise that disease class should be reframed and medical management in people with biallelic variants in BRCA1 should emphasise on detection of solid tumour development and avoiding exposure to ionising radiation.

CHDH-PNPLA3 Gene-Gene Interactions Predict Insulin Resistance in Children with Obesity.

INTRODUCTION: Insulin resistance plays a major role in metabolic syndrome and is recognized as the most common risk factor for non-alcoholic fatty liver disease (NAFLD). Identifying predictors for insulin resistance could optimize screening and prevention. PURPOSE: To evaluate the contribution of multiple single nucleotide polymorphisms across genes related to NAFLD and choline metabolism, in predicting insulin resistance in children with obesity. METHODS: One hundred fifty-three children with obesity (73 girls), aged 7-18 years, were evaluated within the NutriGen Study (ClinicalTrials.gov-NCT02837367). Insulin resistance was defined by Homeostatic Model Assessment for insulin-resistance cut-offs that accommodated pubertal and gender differences. Anthropometric, metabolic, intake-related variables, and 55 single nucleotide polymorphisms related to NAFLD and choline metabolism were evaluated. Gene-gene interaction effects were assessed using Multiple Data Reduction Software. RESULTS: Sixty percent (93/153) of participants showed insulin resistance (58.7% of boys, 63% of girls). Children with insulin resistance presented significantly higher values for standardized body mass index, triglycerides, transaminases and plasma choline when compared to those without insulin resistance. Out of 52 single nucleotide polymorphisms analysed, the interaction between genotypes CHDH(rs12676) and PNPLA3(rs738409) predicted insulin resistance. The model presented a 6/10 cross-validation consistency and 0.58 testing accuracy. Plasma choline levels and alanine aminotransferase modulated the gene interaction effect, significantly improving the model. CONCLUSION: The interaction between genotypes in CHDH and PNPLA3 genes, modulated by choline and alanine aminotransferase levels, predicted insulin-resistance status in children with obesity. If replicated in larger cohorts, these findings could help identify metabolic risk in children with obesity.

Challenges in reporting pathogenic/potentially pathogenic variants in 94 cancer predisposing genes - in pediatric patients screened with NGS panels.

The benefit of reporting unsolicited findings in Next Generation Sequencing (NGS) related to cancer genes in children may have implications for family members, nevertheless, could also cause distress. We aimed to retrospectively investigate germline variants in 94 genes implicated in oncogenesis, in patients referred to NGS testing for various rare genetic diseases and reevaluate the utility of reporting different classes of pathogenicity. We used in silico prediction software to classify variants and conducted manual review to examine unsolicited findings frequencies in 145 children with rare diseases, that underwent sequencing - using a 4813 gene panel. The anonymized reanalysis revealed 18250 variants, of which 126 were considered after filtering. Six pathogenic variants (in BRCA1,BMPR1A,FANCA,FANCC,NBN genes) with cancer related phenotype and three unsolicited variants (in BRCA2,PALB2,RAD50 genes) were reported to patients. Additionally, three unsolicited variants in ATR, BLM (in two individuals), and FANCB genes presented potential cancer susceptibility, were not reported to patients. In retrospect, 4.8% (7/145) of individuals in our cohort had unsolicited NGS findings related to cancer. More efforts are needed to create an updatable consensus in reporting variants in cancer predisposing genes, especially for children. Consent process is crucial to inform of both value and risk of additional genetic information.

Oral cancer histopathological subtypes in association with risk factors: a 5-year retrospective study.

BACKGROUND: Oral cancer is a worldwide public health problem, being the sixth most common neoplasm. The high mortality rate of this type of cancer is due to a delayed diagnosis, a fast evolution and metastasis, no primary symptomatology, the multitude of risk factors and the lack of awareness among the population concerning oral malignancy. AIM: The aim of this 5-year retrospective study was to evaluate the incidence of oral cancer patients in the Clinic of Maxillo-Facial Surgery, Emergency County Hospital, Timisoara, Romania and quantify the histopathological (HP) subtypes, localization, age, gender, tumor staging and differentiation, positive loco-regional lymph nodes and risk factors. PATIENTS, MATERIALS AND METHODS: A number of 129 patients diagnosed with oral cancer were included in the study and their medical records were analyzed. A statistical analysis was performed that included the variables gender, age, tumor staging, differentiation grade, HP subtype, lymph nodes, localization, and risk factors. RESULTS: Our results outlined a high prevalence of oral cancer among males (65.9%), squamous cell carcinoma (SCC) being the most common HP subtype. Tumor staging revealed the fact that the majority of were T3 and T4 tumors with dissemination in the loco-regional lymph nodes. In 52% of the cases, tobacco was identified as a risk factor, and the association of tobacco and alcohol was present in 28.3% of the cases. CONCLUSIONS: The early diagnosis is crucial for the improvement of oral cancer survival rate. The oral cavity is permanently exposed to carcinogenic substances that associated with other risk factors have an influence upon the incidence of oral malignancies.

Single Nucleotide Polymorphisms in PEMT and MTHFR Genes are Associated with Omega 3 and 6 Fatty Acid Levels in the Red Blood Cells of Children with Obesity.

Polyunsaturated fatty acids (PUFAs) play important roles in health and disease. PUFA levels are influenced by nutrition and genetic factors. The relationship between PUFA composition in red blood cells (RBCs) and genetic variations involved in PUFA metabolism has not been investigated in children with obesity. This study evaluated the association between several genetic variations and PUFA levels in RBCs in children with obesity. One hundred ninety-six children with obesity (101 females, 95 males) were evaluated using anthropometric measurements, dietary intakes, plasma and RBC PUFA quantification, blood biochemistry, and 55 single nucleotide polymorphisms within 14 genes. phosphatidylethanolamine N-methyltransferase (PEMT) rs1109859 and methylenetetrahydrofolate reductase gene (MTHFR) rs4846052 genotypes were associated with PUFA levels in RBCs. PUFA intake did not influence the RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels. Higher RBC DHA and EPA levels were observed for PEMT rs1109859 GG and GA genotypes versus the AA genotype. Higher levels of RBC DHA, EPA, arachidonic acid (ARA), and linoleic acid (LA) and were observed for MTHFR rs4846052 TT genotype versus TC and CC genotypes. Genetic variations in PEMT rs1109859 and MTHFR rs4846052 were associated with different PUFA levels in RBC membranes and are estimators for PUFA species in RBCs. Further research is needed to establish whether these genotype-specific alterations are specific to overweight children.

Synthesis and preliminary characterization of polyurethane nanoparticles with ginger extract as a possible cardiovascular protector.

Background and aim: The extract of ginger, obtained from the rhizome of Zingiber officinale, contains 6-gingerol, 6-shogaol, 8-gingerol, and 10-gingerol. It has many therapeutic effects such as being chemopreventive against stroke and heart diseases, malabsorption, bacterial infections, indigestion, and nausea, which have been observed since ancient times. The main aim of this study is to evaluate the polyurethane (PU) as a proper material for the hollow nanoparticles' preparation. Methods: The PU nanoparticles were obtained by a spontaneous emulsification, in the presence of a nonionic surfactant, combined with an interfacial polyaddition process between an aliphatic diisocyanate and different mixtures of etheric and esteric polyols. The synthesis was done without any PU additives, such as catalysts, blowing agents, chains promoters, cross-linking agents, and stabilizers. Results: The particles present almost neutral pH values and low water solubility. They are heat resistant up to 280°C. Decreased irritation level was found in the assay of PU nanoparticles loaded with pure ginger extract (GE) on the murine skin tests than the irritation level recorded for pure GE. Conclusion: This research shows the reduced noxiousness of these PU nanoparticles and consequently the possibility of their use as a possible cardiovascular protector.

No clinical utility of common polymorphisms in IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 genes previously associated with insulin resistance in overweight children from Romania and Moldova.

Background Previous genome-wide association studies (GWAS) identified IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 as candidate genes for insulin resistance and type 2 diabetes (T2D). We investigated the associations of these previously reported common variants in these genes with insulin resistance in overweight children from Romania and Moldova. Methods Six single nucleotide polymorphisms (SNPs), IGF1 (rs35767), IRS1 (rs2943634), GCKR (rs780094), PPARG (rs1801282), GCK1 (rs1799884) and KCTD15 (rs29941), were genotyped in 100 overweight children along with clinical and metabolic parameters. Homeostatic model assessment of insulin resistance (HOMA-IR) above 3.4 (defining insulin resistance) was used as the outcome. Results Children differed in insulin resistance status despite having similar body mass index (BMI) standard deviation scores (SDS) (World Health Organization, [WHO] reference). The identified predictors for altered insulin metabolism were higher cholesterol levels, higher diastolic blood pressure and higher waist-to-hip-ratio (as a marker for increased abdominal fat). None of the SNPs showed significant association with increase in the risk for insulin resistance in children (p range=0.478-0.724; odds ratio [OR] range=1.924-4.842); however, the risk allele in GCKR (rs780094, p=0.06, OR=6.871) demonstrated near statistical significance. Conclusions The interrogated risk alleles did not show any significant association with insulin resistance in children in our cohort; however, the GCKR (rs780094) might be a viable candidate in larger cohorts. The lack of replication of the proposed association may point to differences in linkage disequilibrium or effect modifiers across studies.

Impact of the CYP2D6 phenotype on hyperprolactinemia development as an adverse event of treatment with atypical antipsychotic agents in pediatric patients.

BACKGROUND: Treatment with atypical antipsychotics is today the election therapy for different types of psychosis, but there is a high incidence of endocrine and metabolic disturbances. One of the major enzymes involved in the metabolism of antipsychotics is CYP2D6. Depending on the existing CYP2D6 alleles, the metabolic capacity of the enzyme may vary from very low to very high, so that patients can be grouped into four phenotypic groups: slow, intermediate, extensive (normal), and fast metabolizers. AIM OF THE STUDY: The aim of the study is to find a relationship between the individual intervariability of CYP2D6 and the incidence of hyperprolactinemia as side effect of atypical antipsychotics. RESULTS: A total of 81 patients with schizophrenia or bipolar disorders, median age 15.74 ± 4 years, were enrolled in the study and prescribed the following atypical antipsychotics: risperidone, aripiprazole, and olanzapine. They were evaluated at 6, 12, and 18 months after the initiation of treatment. Using the TaqMan Genotyping Assay, it has been identified the presence of the CYP2D6*4 allele in 28 patients, representing 34.56% of the total of 81 patients in the study, and CYP2D6*3 allele was identified in 15 patients and the presence of CYP2D6*41 to 11 patients. The allele CYP2D6*5 has not been present to the study patients. The study group has 44 patients which are extensive metabolizers (54%), 34 intermediate metabolizers (42%), and 3 poor (slow) metabolizers (4%). CONCLUSIONS: For the slow and intermediate metabolizers, atypical antipsychotics determined a significant increase of prolactinemia with high risk of adverse events.

A rare case of partial trisomy 8q24.12-q24.3 and partial monosomy of 8q24.3: Prenatal diagnosis and clinical findings.

OBJECTIVE: We describe a rare case of "pure" 8q duplication diagnosed prenatally by conventional karyotyping, that was further characterized by array comparative genomic hybridization (aCGH). CASE REPORT: A 39-year-old, primigravida woman underwent amniocentesis at 23 weeks of gestation because of an abnormal second trimester maternal serum screening for Down syndrome. Conventional cytogenetic analysis demonstrated a karyotype of 46,XX,der(8) (q24.12q24.3) and aCGH identified a duplication of approximately 27 Mb, affecting the distal region of chromosome 8q24.12-q24.3. Parenteral karyotype of both parents was normal and excluded familial translocation or other rearrangements. Although prenatal ultrasound examination showed multiple anomalies the parents decided to keep the pregnancy. The baby was born at 38 weeks of gestation, with an Apgar score of 2. The evolution was unfavorable, and he died within the first 24 h of birth. CONCLUSION: Molecular investigations contribute to a more accurate characterization of the patients with these rare duplication, but also for estimating their prognosis.

Development and Validation of a LC⁻MS/MS-Based Assay for Quantification of Free and Total Omega 3 and 6 Fatty Acids from Human Plasma.

Few high-performance liquid chromatography⁻tandem mass spectrometry (LC-MS/MS) methods have been developed for the full quantitation of fatty acids from human plasma without derivatization. Therefore, we propose a method that requires fewer sample preparation steps, which can be used for the quantitation of several polyunsaturated fatty acids in human plasma. The method offers rapid, accurate, sensitive, and simultaneous quantification of omega 3 (α-linolenic, eicosapentaenoic, and docosahexaenoic acids) and omega 6 fatty acids (arachidonic and linoleic acids) using high-performance LC-MS/MS. The selected fatty acids were analysed in lipid extracts from both free and total forms. Chromatographic separation was achieved using a reversed phase C18 column with isocratic flow using ammonium acetate for improving negative electrospray ionization (ESI) response. Mass detection was performed in multiple reaction monitoring (MRM) mode, and deuterated internal standards were used for each target compound. The limits of quantification were situated in the low nanomolar range, excepting linoleic acid, for which the limit was in the high nanomolar range. The method was validated according to the U.S. Department of Health and Human Services guidelines, and offers a fast, sensitive, and reliable quantification of selected omega 3 and 6 fatty acids in human plasma.

Effects of Dietary Nutrients on Epigenetic Changes in Cancer.

Gene-nutrient interactions are important contributors to health management and disease prevention. Nutrition can alter gene expression, as well as the susceptibility to disease, including cancer, through epigenetic changes. Nutrients can influence the epigenetic status through several mechanisms, such as DNA methylation, histone modifications, and miRNA-dependent gene silencing. These alterations were associated with either increased or decreased risk for cancer development. There is convincing evidence indicating that several foods have protective roles in cancer prevention, by inhibiting tumor progression directly or through modifying tumor's microenvironment that leads to hostile conditions favorable to tumor initiation or growth. While nutritional intakes from foods cannot be adequately controlled for dosage, the role of nutrients in the epigenetics of cancer has led to more research aimed at developing nutriceuticals and drugs as cancer therapies. Clinical studies are needed to evaluate the optimum doses of dietary compounds, the safety profile of dosages, to establish the most efficient way of administration, and bioavailability, in order to maximize the beneficial effects already discovered, and to ensure replicability. Thus, nutrition represents a promising tool to be used not only in cancer prevention, but hopefully also in cancer treatment.

Modern molecular study of weight gain related to antidepressant treatment: clinical implications of the pharmacogenetic testing.

Antidepressant medication influences cellular lipogenesis, being associated with metabolic side effects including weight gain. Due to the increasing use of antidepressants in children and adolescents, their metabolic and endocrine adverse effects are of particular concern, especially within this pediatric population that appears to be at greater risk. Genetic factors with a possible influence on antidepressant's adverse effects include CYP [cytochrome P450 (CYP450)] polymorphisms. We target to evaluate the efficacy of the pharmacogenetic testing, when prescribing antidepressants, in correlation with the occurrence of adverse events and weight gain. Our research was performed between the years 2010 and 2016, in the University Clinic of Child and Adolescent Psychiatry, Timisoara, Romania. We recruited 80 patients, children and adolescents with depressive disorders. Our study sample was divided in two groups: G1 - 40 patients took treatment after pharmacogenetic testing, and G2 - 40 patients without pharmacogenetic testing before the treatment election. Our results show statistically significant differences concerning the weight gain for groups G1 (with pharmacogenetic testing) and G2 (without pharmacogenetic testing). The CYP genotype and the pharmacogenetic testing, for choosing the personalized antidepressant therapy in children and adolescents with depressive disorders, proved to be good predictors for the response to antidepressants and the side effects registered, especially for weight gain. The significant correlations between the CYP polymorphisms for group G2 (without pharmacogenetic testing) and the weight gain/body mass index (BMI) increase, as major side effects induced by antidepressants, proved the fact that the pharmacogenetic screening is needed in the future clinical practice, allowing for individualized, tailored treatment, especially for at-risk pediatric categories.

Clinical relevance of retinal structure in children with laser-treated retinopathy of prematurity versus controls - using optical coherence tomography.

PURPOSE: We aimed to assess the macular anatomy using spectral domain optical coherence tomography (SD-OCT), in children born preterm who had laser-treated retinopathy of prematurity (ROP), and to investigate the relationship between structural changes in macula and visual function. METHODS: Thirty-seven 3-8 years old children were included in the study in two groups: 20 children born preterm [(<34 weeks of gestation, birthweight (BW) <2000 g)] who had laser-treated ROP in the Neonatology Department, Municipal Clinical Emergency Hospital of Timisoara, Romania; and 17 controls (children born at term, without eye disease, matched for age and gender). Spectral domain optical coherence tomography (SD-OCT) imaging (Spectralis OCT) was performed at central fovea and 1 mm nasally. RESULTS: In the ROP group (total 34 eyes), we included both eyes in 14 children, and on one eye in six other children. In the control group, both eyes for all 17 children were included. Central fovea thickness (CFT) was significantly higher in children born preterm and with laser-treated ROP as compared to controls (275 ± 34.8 µm versus 224 ± 27.2 µm; p < 0.001). The laser-treated eyes with ROP had mean best-corrected visual acuity (BCVA) = 0.19 logMAR (20/31 Snellen); 35% had BCVA ≥0.3 logMAR (20/40 Snellen). In receiver operating characteristic curve (ROC) analysis, with BCVA as static variable (category 0 = BCVA ≤0.3 logMAR), the CFT cut-off was 257 µm (sensitivity: 0.917; specificity: 0.661; area under the curve: 0.810, p = 0.001). CONCLUSION: Years after the laser intervention, central fovea was significantly thicker in ROP laser-treated children born preterm when compared to controls. Central fovea thickness (CFT) correlated strongly and inversely with BW and gestational age (GA) at birth, while a CFT value above 257 µm was suggestive for suboptimal visual acuity. The proposed cut-off value needs to be validated in future larger studies.