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.

Assessing the Outcomes of Patients with Severe SARS-CoV-2 Infection after Therapeutic Plasma Exchange by Number of TPE Sessions.

The high mortality risk in severe SARS-CoV-2 infections is tightly correlated to the extreme elevation of inflammatory markers. This acute accumulation of inflammatory proteins can be cleared using plasma exchange (TPE), commonly known as plasmapheresis, although the available data on performing TPE in COVID-19 patients is limited regarding the optimal treatment protocol. The purpose for this study was to examine the efficacy and outcomes of TPE based on different treatment methods. A thorough database search was performed to identify patients from the Intensive Care Unit (ICU) of the Clinical Hospital of Infectious Diseases and Pneumology between March 2020 and March 2022 with severe COVID-19 that underwent at least one session of TPE. A total of 65 patients satisfied the inclusion criteria and were eligible for TPE as a last resort therapy. Of these, 41 patients received 1 TPE session, 13 received 2 TPE sessions, and the remaining 11 received more than 2 TPE sessions. It was observed that IL-6, CRP, and ESR decreased significantly after all sessions were performed in all three groups, with the highest decrease of IL-6 in those who received >2 TPE sessions (from 305.5 pg/mL to 156.0 pg/mL). Interestingly, there was a significant increase in leucocyte levels after TPE, but there was no significant difference in MAP changes, SOFA score, APACHE 2 score, or the PaO2/FiO2 ratio. The ROX index was significantly higher among the patients who underwent more than two TPE sessions, with an average of 11.4, compared to 6.5 in group 1 and 7.4 in group 2, which increased significantly after TPE. Nevertheless, the mortality rate was very high (72.3%), and the Kaplan-Meier analysis identified no significant difference in survival according to the number of TPE sessions. TPE can be used as last resort salvage therapy that can be regarded as an alternative treatment method when the standard management of these patients fails. It significantly decreases the inflammatory status measured via IL-6, CRP, and WBC, as well as demonstrating an improvement of the clinical status measured via PaO2/FiO2, and duration of hospitalization. However, the survival rate does not seem to change with the number of TPE sessions. Based on the survival analysis, one session of TPE as last resort treatment in patients with severe COVID-19 proved to have the same effect as repeated TPE sessions of 2 or more.

Efficacy of Therapeutic Plasma Exchange in Severe Acute Respiratory Distress Syndrome in COVID-19 Patients from the Western Part of Romania.

Background and Objectives: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has surprised the medical world with its devastating effects such as severe acute respiratory distress syndrome (ARDS) and cytokine storm, but also with the scant therapeutic solutions which have proven to be effective against the disease. Therapeutic plasma exchange (TPE) has been proposed from the very beginning as a possible adjuvant treatment in severe cases. Our objective was to analyze the evolution of specific biological markers of the COVID-19 disease before and one day after a therapeutic plasma exchange session, how a change in these parameters influences the patient's respiratory status, as well as the impact of TPE on the survival rate. Materials and Methods: In this retrospective study, we include 65 patients with COVID-19 admitted to the intensive care unit department of our hospital between March 2020 and December 2021, and who received a total of 120 sessions of TPE. Results: TPE significantly reduced the following inflammation markers (p < 0.001): interleukin-6 (IL-6), C-reactive protein (CRP), lactate dehydrogenase (LDH), fibrinogen, ferritin, and erythrocyte sedimentation rate. This procedure significantly increased the number of lymphocytes and decreased D-dimers levels (p = 0.0024). TPE significantly improved the PaO2/FiO2 ratio (p < 0.001) in patients with severe acute respiratory distress syndrome (PaO2/FiO2 < 100). Survival was improved in intubated patients who received TPE. Conclusions: TPE involved the reduction in inflammatory markers in critical patients with COVID-19 disease and the improvement of the PaO2/FiO2 ratio in patients with severe ARDS and had a potential benefit on the survival of patients with extremely severe COVID-19 disease.

The role of personality dimensions and trait anxiety in increasing the likelihood of suicide ideation in women during the perinatal period.

INTRODUCTION: Increasing amount of data reveal that suicide risk is a real phenomenon among perinatal women, determined by several other psychopathological conditions with depression being just one of them. This study aimed to investigate the role of personality dimensions on the occurrence of suicide ideation during the perinatal period. METHODS: A longitudinal prospective study was performed in pregnant women who were monitored at university-based obstetrical care units in our county. Recruited women were reassessed between 6 and 8 weeks into their postnatal period. Trait and state anxiety, five-factor based dimensions of personality, and depressive symptoms were assessed using established psychometric measures. Appropriate statistical analyses were conducted, depending on the distribution of variables. RESULTS: Significant levels of state anxiety (33.7% vs. 15.5%), depressive symptoms (19.8% vs. 8.5%), and suicide risk (13.9% vs. 6.3%) have halved in the postnatal period compared to the antenatal assessment. A lower level of education was associated with the presence of postnatal suicide ideation (p = .041), while an unemployed professional status was more frequent in pregnant women presenting antenatal suicide ideation (p = .021). Trait anxiety was predictive for the appearance of suicide ideation within the entire perinatal period assessed (p < .001 and p = .007, respectively). Agreeableness and conscientiousness predicted antenatal suicide ideation (p = .033 and p = .032, respectively). DISCUSSIONS: Different dimensions of personality may play a contributing role in the development of suicide ideation in perinatal women. Consequently, personality dimensions and trait anxiety, not only depressive symptoms, should be investigated when attempting to identify perinatal women at risk of suicide.

The utility of indirect imagistic signs in the diagnosis of anterior cruciate ligament ruptures.

We conducted a retrospective study, between 2013 and 2018. The study was conducted by analyzing the comparative imaging of two groups of patients. The two groups comprise 42 patients, 14 women and 28 men aged between 17 and 70 years old, to whom objective variables of statistical relevance were tracked. The results of this study show that there is a significant correlation between an angle value of less than 45° and the rupture of the anterior crossed ligament.

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.

Integrative clinico-biological, pharmacogenetic, neuroimagistic, neuroendocrinological and psychological correlations in depressive and anxiety disorders.

We approach the theme of modern treatment strategies, based on clinico-biological, pharmacogenetic, neuroimagistic, neuroendocrinological and psychological integrative correlations in the management of depressive and comorbid anxiety disorders. We target to evaluate the efficacy of the pharmacogenetic testing and the evolution, functioning of patients in correlation with specific neurobiological, neuroimagistic and neuroendocrinological markers. Our research was conducted between 2010-2016 on 80 children and adolescents with depressive and comorbid anxiety disorders - 40 children (G1 group), who benefited in choosing the pharmacotherapy from pharmacogenetic testing and 40 children without testing (G2 group). Also, the patients were evaluated through magnetic resonance (MR) spectroscopy at baseline and after pharmacotherapy. The efficacy of the chosen therapy in correlation with the pharmacogenetic testing was evaluated through the mean change in the CDRS (Children's Depression Rating Scale) total scores, in the CGI-S÷I (Clinical Global Impression - Severity÷Improvement), CGAS (Children's Global Assessment Scale) and through the change of the relevant neurobiological markers and MR spectroscopy metabolites. We evaluated the side effects through the PAERS (Pediatric Adverse Events Rating Scale)-Clinician. Our results show statistically significant differences of the clinical scores between the studied groups: for those subjects who benefited of pharmacogenetic testing, the CDRS, the global functioning scores prove a higher clinical improvement, a better compliance and lower PAERS side effects scores and also improvement concerning the MR spectroscopy dosed metabolites values. Our research was a proof sustaining the use of the pharmacogenetic testing in clinical practice and the value of investigating relevant neurobiological, neuroimagistic and neuroendocrinological markers for a personalized therapy in depressive disorders.

A rare case of Meckel-Gruber syndrome.

Meckel-Gruber syndrome (MKS) is a lethal, autosomal recessive transmitted anomaly, characterized by the ultrasound triad: occipital meningoencephalocele, bilateral polycystic kidney, postaxial polydactyly. The incidence is between 1÷13 250 and 1÷140 000 live births, being a rare anomaly. We report a MKS case of feminine gender diagnosed on two ultrasound findings (bilateral polycystic kidney, occipital meningoencephalocele). This case highlights the presence of MKS in a young female without family history.

Health-related quality of life in patients with hallux valgus.

BACKGROUND AND AIMS: No deformity of the forefoot occurs more frequently than hallux valgus (HV), which is considered to be medial deviation of the first metatarsal and lateral deviation and rotation of the hallux, either with or without medial soft tissue enlargement of the metatarsal head. The HV deformity can lead to painful motion of the joint or difficulty in daily joint activity that often requires surgical correction. The aims of this study were to investigate the levels of foot pain and quality of life of patients with HV before and after surgery. Our study is focusing on imagistic investigations in HV, clinical aspects, specific treatment, foot pain levels, quality of life and general health before and after surgery. PATIENTS, MATERIALS AND METHODS: Our research was conducted in the period 2010-2015. We recruited 56 patients, 35 women and 21 men, age range 20 to 76 years, mean age 44.4 years, with HV (radiographic HV angle 25-40 and >40). We applied Visual Analogue Scales (VAS) for the foot pain and the Euro Quality of Life - five dimensions health questionnaire (EQ-5D). RESULTS: The results show statistically significant differences concerning the foot pain levels in VAS and also pain/discomfort, mobility and anxiety÷depression in the EQ-5D subscale in HV before and after surgery. The results prove high improvement of the scores of foot pain, discomfort, mobility and anxiety÷depression after surgery. Concerning the participation in usual activities and the self-care, the obtained results were not statistically significant. CONCLUSIONS: Our research was a proof that the surgery in HV represents a fruitful pathway of intervention and care and shows a high rate of success, favorable outcomes and improvement in quality of life of the patients.

The effect of neurobiological changes in the brain of children with schizophrenia, ultra high-risk for psychosis and epilepsy: clinical correlations with EEG and neuroimagistic abnormalities.

Relatively little research has been conducted on quantitative electroencephalography (QEEG) activity in patients with psychosis÷schizophrenia, especially in populations at-risk for the illness. Further studies are needed, in order to offer a possible endophenotypic marker of the cerebral functioning, associated with psychosis÷schizophrenia, in correlation with the neuroimaging, the neurocognitive, biochemical, molecular genetic tests, clinical aspects and the EEG activity from the same subjects. The aim was to investigate the role the QEEG abnormalities play in the etiology of psychosis÷schizophrenia, whether it can provide an endophenotype for psychosis and to make some correlations with the results obtained through magnetic resonance (MR) spectroscopy, for proper early detection and intervention. The prospective research was performed in the University Clinic of Child and Adolescent Psychiatry, Timisoara, Romania, involving 55 children with schizophrenia or ultra high-risk (UHR) for psychosis (groups 1, 2, 3 and 4) and 55 children as healthy controls (group 5). Groups 1 and 2 (28 children) are diagnosed with schizophrenia, groups 3 and 4 are UHR for psychosis (27 children), and group 5 represents healthy controls. Groups 1 and 3 had convulsive seizures in their personal history. We noticed: through the QEEG, numerous patterns of theta and delta activity, the diminished amplitude of the alpha band waves and the diminished alpha activity; also, the onset of psychosis was earlier at those presenting convulsive seizures in their personal history (groups 1 and 3); also, specific neuroimagistic abnormalities and modifications. The cerebral lesions, appearing during the development, raise the liability for schizophrenia. The high-risk for schizophrenia is correlated with the personal history of epilepsy, as well as with the family risk for psychosis.

The prognostic and clinical significance of neuroimagistic and neurobiological vulnerability markers in correlation with the molecular pharmacogenetic testing in psychoses and ultra high-risk categories.

We approach an integrated, multidisciplinary, innovative research-action model in children and adolescents with psychosis and ultra high-risk categories. Our main focus was: to investigate the prognostic and clinical significance of neuroimagistic and neurobiological vulnerability markers in correlation with the molecular pharmacogenetic testing in psychoses and ultra high-risk categories; the dynamic evaluation of the clinical evolution for the studied groups in correlation with specific neurobiological and neuroimagistic variables and markers. Our research was conducted in the period 2009-2015 on 87 patients, children and adolescents with psychosis (42 took treatment after pharmacogenetic testing, 45 without) and 65 children with ultra high-risk (UHR) for psychosis - 32 benefited of pharmacotherapy after pharmacogenetic testing and 33 without. Also, the patients were evaluated through magnetic resonance (MR) spectroscopy at baseline and after pharmacotherapy. The efficacy of the chosen therapy in correlation with the pharmacogenetic testing was evaluated through the mean change in the Positive and Negative Syndrome Scale (PANSS) total scores, in the Clinical Global Impression of Severity and Improvement (CGI-S÷I), Children's Global Assessment Scale (CGAS) and through the change registered for the relevant neurobiological markers and MR spectroscopy metabolites, from baseline until endpoint in different timepoints. Our results, showed statistically significant differences of the clinical scores between the studied groups. Our research was a proof, sustaining the use of the pharmacogenetic testing in clinical practice and the value of investigating relevant neurobiological and neuroimagistic markers for a personalized, tailored therapy for psychotic patients and neuro-psychiatric UHR categories, as a fruitful pathway of intervention and care.

-759C÷T polymorphism of the HTR2C gene is not correlated with atypical antipsychotics-induced weight gain, among Romanian psychotic patients.

We aim to investigate whether the -759C÷T polymorphism in 5-HTR2C gene was associated with weight change and hyperinsulinemia in Romanian pediatric patients with schizophrenia and bipolar disorders. The patients under investigation were enrolled between 2009 and 2014. A total of 81 schizophrenic and bipolar-disorder patients, aged between nine to 20 years (median age 15.74±4 years), who were following an atypical antipsychotic treatment (Risperidone, Aripiprazole, Olanzapine), were enrolled from University Hospital for Child and Adolescent Psychiatry and Neurology from Timisoara, Romania. The outcomes that we measured were the changes in Body Mass Index (BMI) from baseline to different time points: three months, six months, 12 months and 18 months, and the change in insulinemia over time, after atypical antipsychotic treatment. After carrying out the 5-HTR2C 759C÷T polymorphism identification, we found that 22 patients presented the -759C÷T polymorphism in 5-HTR2C gene. Between the patients exhibiting the 5-HTR2C -759C÷T polymorphism and the patients having the wild type alleles, there was no significant statistical difference in changes of BMI from baseline to endpoints that indicates the lack of the protective effect of the T allele against atypical antipsychotics-induced weight gain. Interestingly, we found a statistically significant association between insulinemia and T alleles' carriers, after 18 months of treatment with the above-mentioned antipsychotics. Taking into consideration that atypical antipsychotics have been associated with elevated insulin levels and insulin resistance, maybe in the future the -759C÷T polymorphism would find a role in the development of a more complex algorithm for prediction of diabetes mellitus risk, in patients taking atypical antipsychotics.

Molecular study of weight gain related to atypical antipsychotics: clinical implications of the CYP2D6 genotype.

Atypical antipsychotics, especially some of them, influence cellular lipogenesis, being associated with metabolic side effects including weight gain. Due to the increasing use of atypical antipsychotics 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 atypical antipsychotics adverse effects include CYP2D6 polymorphisms. Our study, performed in 2009-2014, with a two-year enrolment period during which we recruited children and adolescents with a diagnosis of schizophrenia or bipolar disorder on treatment with the antipsychotics (Risperidone, Aripiprazole or Olanzapine), included 81 patients, aged between 9 and 20 years, median age being 15.74 years. The gender percentage was 54% girls/46% boys. The CYP2D6 genotyping was performed after enrolment of the last patient. Based on the CYP2D6 genotype, three activity groups were identified and compared and we found that the patients with wt/*4 genotype, intermediary metabolizer (carrier of one functional and one non-functional allele) have significantly higher weight gain values than the patients who did not exhibit allele *4. The CYP2D6 genotype in children and adolescents with schizophrenia and bipolar disorder, proved to be a good predictor for the response to atypical antipsychotics and the side effects registered. The significant correlations between the CYP2D6 polymorphisms and the weight gain/BMI (body mass index) increase, as major side effects induced by antipsychotics proved the fact that the pharmacogenetic screening is needed in the future clinical practice, allowing for individualized, tailored treatment, especially for at-risk individuals.