Frequency Of Abnormalities Research Articles

C.3 Retrospective study of sulthiame in treatment of pediatric epilepsy

Background: This retrospective study assessed the efficacy and tolerability of sulthiame as a treatment in children with epilepsy. In Canada, sulthiame is only available through Health Canada’s Special Access Program. Methods: Patients who received sulthiame at the Montreal Children’s Hospital from April 2012 to March 2023 were included. Patients’ medical charts were reviewed, and clinical data was extracted from neurology clinic notes and electroencephalogram (EEG) reports. Efficacy was assessed by comparing seizure frequency and frequency of EEG epileptiform abnormalities before and after initiating sulthiame, while also noting any reported changes in cognition or behaviour. Results: Sixteen patients were included (10 males, 6 females), all of whom had drug-resistant epilepsy and continuous spike-wave in sleep (CSWS) on EEG. Sulthiame starting dose ranged from 0.74 to 6.75 mg/kg/day. Improvement, either in terms of seizure control, cognition, or reduction in EEG epileptiform abnormalities, was reported in 8/16 children (50%). Two patients (13%) became seizure free, while three more (19%) had reduced seizure frequency. Three other patients (19%) had reported improvements in concentration, learning abilities or behaviour. No serious adverse event was reported. Conclusions: These data indicate that sulthiame is effective and well-tolerated in children with CSWS, regardless of the etiology and type of epilepsy.

Assessment of shoulder joint derangements with magnetic resonance imaging in adult Nigerians.

Shoulder pain secondary to various aetiologies is a common musculoskeletal complaint worldwide, and Magnetic Resonance Imaging (MRI) is the most accurate imaging method for evaluating shoulder pain in all age groups. While the patterns of shoulder MRI abnormalities in various demographics have been reported, data on sub-Sahara African populations are still sparse. This study aims to describe the imaging features and spectrum of shoulder joint pathologies on MRI in adult Nigerians. This was a retrospective review of the shoulder MRI of 100 adult Nigerians (with and without trauma) from September 2020 to December 2021. Their clinical data and shoulder MRI findings were extracted and analysed. Statistical significance was set at P ≤ 0.05. There were 64 males and 36 females aged 18-82 years. Right shoulder MRI was done in 53 subjects (53%), while the left shoulder was studied in 47 (47%). Supraspinatus tendinopathy (73%), acromioclavicular joint arthropathy (68%), and subacromial-subdeltoid (SASD) bursitis (64%) were the most frequently detected pathologies. Other demonstrated derangements include glenohumeral joint effusion (24%), long head of biceps tendon sheath effusion (18%), labral abnormalities (16%), subcoracoid bursitis (4%), Hill Sach's deformity (3%), anterior glenohumeral dislocation (2%), fatty degeneration of the supraspinatus/infraspinatus muscles (2%), adhesive capsulitis (1%), and other bony abnormalities (contusion, erosion, subchondral cysts). There was no significant difference in the frequency of shoulder abnormalities between the male and female subjects. Acromioclavicular joint arthropathy, SASD bursitis, and rotator cuff disorders were the dominant pathologies in the participants' shoulders.

Abnormal Electroencephalogram Findings and Its Correlation With Clinical Features From Pediatric Patients in Psychiatric Clinic.

Objective: We aimed to evaluate the occurrence of electroencephalogram (EEG) abnormalities in pediatric patients attending an outpatient psychiatry clinic at a tertiary center. We examined the rates of abnormalities and specific findings based on demographics, specific diagnoses, and clinical severity. Methods: This study included pediatric patients who underwent EEG at the outpatient psychiatry clinic. Patient demographics, psychiatric diagnosis, intellectual disability, intelligent quotient (IQ) score, family history of psychiatric disorders, and Clinical Global Impression-Severity (CGI-S) score were obtained through retrospective electronic health record analysis. The rate of EEG abnormalities was calculated, and specific abnormal findings were reviewed. Relationships between the rate of EEG abnormalities and diagnosis, severity, IQ, and age at EEG examination were analyzed. Results: Of 319 patients who underwent EEG, 21.3% (68 patients) of patients exhibited abnormalities, including background abnormalities (14.7%, 47 patients), interictal epileptiform discharges (IEDs) (10.3%, 33 patients), and a slow posterior dominant rhythm (3.8%, 10 patients). The frontal region was the most commonly affected area. Neurodevelopmental disorders (NDDs) had the most frequent abnormalities (29.8%), followed by anxiety (16.7%), sleep (14.3%), mood (11.7%), psychotic (5%), and conduct disorders (0%). Disease severity did not correlate with the rate of EEG abnormalities. Adjusted for age, sex, severity, and family history, patients with EEG abnormalities exhibited lower IQ scores. Conclusion: EEG abnormalities were common in pediatric patients with psychiatric disorders, with background abnormalities detected as frequently as IEDs. Disease severity was not associated with EEG abnormality, while IQ scores showed a negative correlation.

#817 Genetic analysis in a group of patients with persistent isolated microscopic hematuria

Abstract Background and Aims Autosomal dominant Alport syndrome (ADAS) is a genetic disease caused by pathogenic variants in COL4A3 and COL4A4 genes. ADAS is the main cause of isolated persistent microscopic hematuria (PMH). However, other diseases like IgA nephropathy (IgAN) can present with PMH. Establishing a precise genetic diagnosis in this type of patients would avoid invasive studies like kidney biopsies. In this study we performed a comprehensive genetic test in a cohort of patients with isolated PMH to evaluate the frequency of ADAS or other genetic abnormalities and compare the clinical characteristics of patients with or without ADAS Method Fifty-two patients with PMH were included in the study. PMH was defined by the presence of 3 or more dysmorphic red blood cells per field in at least 5 consecutive urine sediments and a time-averaged proteinuria <1 gr/day. Average proteinuria was determined for every 6 months of follow-up and time-averaged (TA) proteinuria represented an average of the mean proteinuria measurements in each 6-month period. A comprehensive genetic study using whole exome next-generation sequencing was performed. One hundred and one genes related to familial hematuria, focal segmental glomerulosclerosis and cystic kidney diseases were analyzed. Patients with known secondary causes of hematuria were excluded. The baseline clinical characteristics of patients with and without ADAS were compared. Patients with pathogenic variants in COL4A5 gene were excluded of this analysis. Results Thirty-one (60%) patients were diagnosed with ADAS (16 patients with pathogenic variants in COL4A3, 15 in COL4A4), 3 (6%) patients (2 women, 1 man) presented pathogenic variant in COL4A5 gene, and the genetic study was negative in the remaining 18 patients (variants of unknown significance in COL4A3 or COL4A4 were found in 3 of the latter). No other genetic abnormalities were detected in the panel of 101 genes. Table 1 shows the baseline clinical characteristics of patients with and without ADAS. Patients with ADAS presented a higher TA proteinuria [0.23 (0.11-0.6) vs 0.08 (0.05-0.16), p = 0.01], and a more frequent familial history of isolated microscopic hematuria (76% vs 40%, p = 0.01) chronic kidney disease (CKD) (44% vs 0%, p = 0.01) or end stage kidney disease (32% vs 0%, p = 0.02). In the multivariate analysis, only a family history of microscopic hematuria was associated with ADAS: OR 5.62 (1.25-25.49, p = 0.02). Conclusion ADAS is the most common cause of PMH. A genetic study should be the first diagnostic step in order to obtain a precise cause of the disease and avoid invasive procedures. A family history of microscopic hematuria and of CKD increases the likelihood of ADAS prior to the performance of genetic test.

Maternal Risk Factors Associated with Congenital Abnormalities in Infants Born in Yazd from 2018 to 2021

Background: Maternal factors like age, existing medical conditions, and exposure to medications/substances during pregnancy are crucial in the development of congenital anomalies. This study aims to investigate maternal risk factors associated with congenital anomalies in newborns in Yazd from 2018 to 2021. Methods: This particular research entails a cross-sectional descriptive analysis where the data concerning all live births and their respective mothers from the years 2018 to 2021 in the hospitals situated in Yazd were culled from the database of the National Mother and Newborn Health Registration System affiliated with Shahid Sadoughi University of Medical Sciences. Results: Over four years, approximately 122,098 mothers' information was recorded in the mother's information registration system. The outcomes about social factors indicated that 1.3% of mothers with limited educational background and 0.62% of educated mothers had newborns with abnormal conditions. The heightened occurrence of newborns with congenital anomalies among mothers with lower educational attainment in comparison to their educated counterparts was deemed statistically significant (P < 0.001). Moreover, mothers under the age of 19 exhibited a 1.2% frequency of abnormalities, a rate significantly surpassing that of other age brackets. Conclusion: The discernment that very young mothers and those with limited education exhibit a higher frequency of abnormalities underscores the necessity for enhanced medical attention and awareness within these specific demographic segments. Nevertheless, further comprehensive inquiries regarding risk factors among mothers and high-risk cohorts are imperative.

Hematological and genotoxic biomarkers in a natural population of freshwater turtles Trachemys dorbigni (Duméril & Bibron, 1835) (Testudines: Emydidae) living in an urban area in Southern Brazil.

The present study aimed to report the morphometric and hematological indices and genotoxicity of a free-life population of D'Orbigny's slider turtles (Trachemys dorbigni) living in an urban area in Southern Brazil. For that, 16 specimens were randomly captured in an urban canal that receives irregular releases of wastewater. Biometrics and external visual changes were analyzed, such as turtle shell deformities, and the presence of parasites. Blood samples were collected to evaluate the hematological profile and the presence of micronuclei and other erythrocyte nuclear abnormalities as potential mutagenic and genotoxic effects. Water physicochemical parameters were also measured. Organisms with ectoparasites (31.25%) and small carapace deformations (56.25%) were observed, but maximum carapace length and weight were considered normal for the species according to the literature. The blood profile indicated low hemoglobin and hematocrit and a high number of total leukocytes, particularly eosinophils which characterize parasitic infections. A frequency of 0.12% for the micronucleus was considered basal, but the frequency of other erythrocyte abnormalities was evident, mainly of blebbed nuclei (63.79%), indicating chromosomal damage in the early stage. The results of this study suggest that natural populations of chelonian inhabiting urbanized areas are impacted by anthropogenic activities in the surrounding environment. Furthermore, it provides comprehensive data which can serve as a comparative model for environmental monitoring studies involving turtles.

Safety and prescribing recommendations for verapamil in newly diagnosed pediatric type 1 diabetes (T1D): The CLVer experience

ObjectivesTo report the safety and side effects associated with taking verapamil for beta-cell preservation in children with newly-diagnosed T1D. Research Design and MethodsEighty-eight participants aged 8.5 to 17.9 years weighing ≥ 30 kg were randomly assigned to verapamil (N = 47) or placebo (N = 41) within 31 days of T1D diagnosis and followed for 12 months from diagnosis, main CLVer study. Drug dosing was weight-based with incremental increases to full dosage. Side effect monitoring included serial measurements of pulse, blood pressure, liver enzymes, and electrocardiograms (ECGs). At study end, participants were enrolled in an observational extension study (CLVerEx), which is ongoing. No study drug is provided during the extension, but participants may use verapamil if prescribed by their diabetes care team. ResultsOverall rates of adverse events were low and comparable between verapamil and placebo groups. There was no difference in the frequency of liver function abnormalities. Three CLVer participants reduced or discontinued medication due to asymptomatic ECG changes. One CLVerEx participant (18 years old), treated with placebo during CLVer, who had not had a monitoring ECG, experienced complete AV block with a severe hypotensive episode 6 weeks after reaching his maximum verapamil dose following an inadvertent double dose on the day of the event. ConclusionsThe use of verapamil in youth newly-diagnosed with T1D appears generally safe and well tolerated with appropriate monitoring. We strongly recommend monitoring for potential side effects including an ECG at screening and an additional ECG once full dosage is reached.ClinicalTrials.gov number: NCT04233034.

Earthworm, Perionyx excavatus as an alternate protein source for Nile tilapia: Effects on growth performance, blood biochemistry, erythrocyte morphology and intestinal health

Recently, an increasing disparity has emerged in the need for raw fish meal (FM) and its supply, along with the environmental and financial obstacles associated with its use. Therefore, increasing and elevating the diversity of alternative protein sources for aquaculture nutrition is imperative. The study investigated the impact of substituting FM protein with EW meal on the growth, haemato-biochemical response and intestinal histomorphology of Nile tilapia. Up to 20% fishmeal replacement with EW meal had no adverse effects on fish growth performance. A quadratic analysis of the final body weight and EW meal level indicated the best growth performance at 17.5% replacement. Fish fed the 40% replacement level had significantly decreased height and width of intestinal folds and number of mucosal goblet cells compared to the control. Although red and white blood cell counts were found unchanged between the control, the 10% and 20% replacement groups, a significantly higher number of white blood cells and a lower number of red blood cells were found in the 40% group compared to the control. Blood glucose level was the highest, while haemoglobin level was the lowest in the 40% group. In the same group, significantly higher frequencies of erythrocyte cellular and nuclear abnormalities were noted. Lipid droplet accumulation in the liver was significantly higher in the 40% group, whilst the 10% and 20% groups showed no significant difference compared to the control.

Prevalence of abnormal electrocardiographic findings and associated factors among patients with epilepsy at Jimma Medical Center, Ethiopia; Hospital-based cross-sectional study.

A person with epilepsy experiences recurrent seizures as a result of a persistent underlying disorder. About 50 million people globally are impacted by it, with 4 million of those being in Sub-Saharan Africa. One of the most frequent comorbidities that raise the mortality and morbidity rates of epileptic patients is abnormal Electrocardiographic (ECG) findings. Thus, the purpose of this study is to evaluate the prevalence of abnormal ECG findings in epileptic patients that might lead to increased risk of sudden cardiac death. A hospital based cross-sectional study was at Jimma Medical Center of Ethiopia on epileptic patients who were on follow-up at neurologic clinics during the data collection period. The malignant ECG characteristics and was identified using the ECG abnormality tool. To facilitate analysis, the gathered data was imported into Epidata version 3.1 and exported to the SPSS version 26. The factors of abnormal ECG and sudden death risk were examined using bivariate logistic regression. The study comprised 190 epileptic patients, with a mean age of 32 years. There were more men than women, making up 60.2%. A 43.2% (n = 80) frequency of ECG abnormalities was identified. According to the study, early repolarization abnormalities were the most common ECG abnormalities and increased with male sex and the length of time a person had seizures (AOR) of 4.751 and 95% CI (.273,.933), p = 0.029, compared to their female counterparts. The frequency of malignant ECG alterations in epileptic patients on follow-up at Jimma Medical Center in Ethiopia is described in the study. According to the study, there were significant ECG alterations in epileptic individuals. Male gender and longer duration of epilepsy raise the risk of abnormal ECG findings that could result in sudden cardiac death.

Cold-evoked potentials in Fabry disease and polyneuropathy.

Fabry disease (FD) causes cold-evoked pain and impaired cold perception through small fiber damage, which also occurs in polyneuropathies (PNP) of other origins. The integrity of thinly myelinated fibers and the spinothalamic tract is assessable by cold-evoked potentials (CEPs). In this study, we aimed to assess the clinical value of CEP by investigating its associations with pain, autonomic measures, sensory loss, and neuropathic signs. CEPs were examined at the hand and foot dorsum of patients with FD (n = 16) and PNP (n = 21) and healthy controls (n = 23). Sensory phenotyping was performed using quantitative sensory testing (QST). The painDETECT questionnaire (PDQ), FabryScan, and measures for the autonomic nervous system were applied. Group comparisons and correlation analyses were performed. CEPs of 87.5% of the FD and 85.7% of the PNP patients were eligible for statistical analysis. In all patients combined, CEP data correlated significantly with cold detection loss, PDQ items, pain, and autonomic measures. Abnormal CEP latency in FD patients was associated with an abnormal heart frequency variability item (r = -0.684; adjusted p = 0.04). In PNP patients, CEP latency correlated significantly with PDQ items, and CEP amplitude correlated with autonomic measures (r = 0.688, adjusted p = 0.008; r = 0.619, adjusted p = 0.024). Furthermore, mechanical pain thresholds differed significantly between FD (gain range) and PNP patients (loss range) (p = 0.01). Abnormal CEPs were associated with current pain, neuropathic signs and symptoms, and an abnormal function of the autonomic nervous system. The latter has not been mirrored by QST parameters. Therefore, CEPs appear to deliver a wider spectrum of information on the sensory nervous system than QST alone.

GABA attenuates neurotoxicity of zinc oxide nanoparticles due to oxidative stress via DAF-16/FoxO and SKN-1/Nrf2 pathways

Zinc oxide nanoparticles (ZnO-NPs) are one of the most widely used metal oxide nanomaterials. The increased use of ZnO-NPs has exacerbated environmental pollution and raised the risk of neurological disorders in organisms through food chains, and it is urgent to look for detoxification strategies. γ-Aminobutyric acid (GABA) is an inhibitory neurotransmitter that has been shown to have anxiolytic, anti-aging and inhibitory effects on nervous system excitability. However, there are few reports on the prevention and control of the toxicity of nano-metal ions by GABA. In zebrafish, ZnO-NPs exposure led to increased mortality and behavioral abnormalities of larva, which could be moderated by GABA intervention. Similar results were investigated in Caenorhabditis elegans, showing lifespan extension, abnormal locomotor frequency and behavior recovery when worms fed with GABA under ZnO-NPs exposure. Moreover, GABA enhanced antioxidant enzyme activities by upregulating the expression of antioxidant-related genes and thus scavenged excessive O2−. In the case of ZnO-NPs exposure, inhibition of nuclear translocation of DAF-16 and SKN-1 was restored by GABA. Meanwhile, the protective effect of GABA was blocked in daf-16 (−) and skn-1 (−) mutant, suggesting that DAF-16/FoxO and SKN-1/Nrf2 pathways is the key targets of GABA. This study provides a new solution for the application of GABA and mitigation of metal nanoparticle neurotoxicity.

Abstract PO2-20-04: TACTIVE-U: phase 1b/2 umbrella study of vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, combined with other anticancer treatments in ER–positive advanced or metastatic breast cancer

Abstract Background: Vepdegestrant (ARV-471), an oral PROTAC ER degrader, was well tolerated and showed evidence of clinical activity in the first-in-human phase 1/2 study in heavily pretreated patients with ER+/human epidermal growth factor receptor 2–negative (HER2-) advanced breast cancer (NCT04072952). The cyclin-dependent kinase (CDK)4/6 inhibitors abemaciclib and ribociclib are approved in combination with an aromatase inhibitor or fulvestrant, or as monotherapy (abemaciclib), for ER+/HER2- advanced or metastatic breast cancer. In preclinical studies, vepdegestrant combined with abemaciclib or ribociclib showed evidence of synergistic interactions in ER+ breast cancer cells and greater tumor growth inhibition in a xenograft breast cancer model compared with fulvestrant in combination with these agents. Inhibitors targeting different CDKs, such as samuraciclib (oral CDK7 inhibitor), are in clinical development for solid tumors. The open-label, phase 1b/2 TACTIVE-U umbrella study will evaluate the safety, efficacy, and pharmacokinetics of vepdegestrant in combination with other anticancer treatments in patients with ER+ advanced or metastatic breast cancer. Vepdegestrant is being evaluated in combination with abemaciclib (sub-study A; NCT05548127), ribociclib (sub-study B; NCT05573555), and samuraciclib (sub-study C). Trial Design: Patients eligible for current sub-studies of TACTIVE-U are aged ≥18 years, have histologically or cytologically confirmed ER+/HER2- advanced or metastatic breast cancer not amenable to surgical resection, and have received prior therapy for advanced or metastatic disease, including any CDK4/6 inhibitor–based regimen in any setting. In each sub-study, patients will receive vepdegestrant orally once daily (QD) continuously in a dose escalation/de-escalation approach. Abemaciclib will be given orally twice daily continuously in sub-study A, ribociclib will be given orally QD for 21 days followed by 7 days off treatment in sub-study B, and samuraciclib will be given orally QD continuously in sub-study C. For all sub-studies, the primary endpoint of the phase 1b portion is dose-limiting toxicities to determine the recommended phase 2 dose of vepdegestrant in combination with the other anticancer treatment. Secondary endpoints of phase 1b are antitumor activity (objective response, clinical benefit rate [CBR], and duration of response [DOR]), progression-free survival (PFS), safety (type, frequency, and severity of adverse events and laboratory abnormalities), and plasma concentrations of study drugs. The phase 2 portion of each sub-study will further evaluate the antitumor activity of the combinations; the primary endpoint is objective response and secondary endpoints include antitumor activity (CBR and DOR), PFS, overall survival, safety, plasma concentration of study drugs, and changes in circulating tumor DNA. Future combination sub-studies will be included in TACTIVE-U. Citation Format: Claudine Isaacs, Katarzyna Jerzak, John Hilton, José Luiz Miranda Guimarães, Rachel Layman, Dongrui Lu, Gary Mo, Anna Maria Calella, Olga Valota, Sibyl Anderson, Cynthia Ma. TACTIVE-U: phase 1b/2 umbrella study of vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, combined with other anticancer treatments in ER–positive advanced or metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-20-04.

Aetiological Spectrum of Pancreaticobiliary Diseases in Adult Nigerians on Magnetic Resonance Cholangiopancreatography.

Imaging is vital for assessing pancreaticobiliary diseases. The aim of the study was to investigate the spectrum and pattern of pancreaticobiliary diseases in adult Nigerians using magnetic resonance cholangiopancreatography (MRCP). This was a retrospective, descriptive cross-sectional study. The electronic radiological records of 110 adult Nigerians who had undergone MRCP were reviewed. The MRCP images were evaluated for bile duct dilatation, intraluminal filling defects, strictures, calculi, and other abnormalities. There were 45 males (40.9%) and 65 females (59.1%) aged 18-83 years, with a mean age of 51.93 ± 15.22 years. Jaundice (59.1%) and right hypochondrial pain (31.8%) were the most common presenting complaints. Gallstones (32.7%), common bile duct strictures (15.5%), choledocholithiasis (11.8%), pancreatic head carcinoma (10.9%), and gallbladder carcinoma (2.7%) were the most frequent abnormalities. There was biliary obstruction in 56.4% of participants, mostly at the distal and proximal common bile duct. Other findings include hepatomegaly (23.6%), hepatic cysts (6.4%), hepatic steatosis (0.9%), duodenal wall thickening (1.8%), and ascites (5.5%). MRCP was normal in 25 (22.7%) participants. Gallstones were the predominant pathology of the various pancreaticobiliary diseases, while Pancreatic head and gallbladder carcinoma were the most common malignant diseases.

Abnormalities in pharyngeal arch-derived structures in SATB2-associated syndrome.

SATB2-associated syndrome (SAS, glass syndrome, OMIM#612313) is a neurodevelopmental autosomal dominant disorder with frequent craniofacial abnormalities including palatal and dental anomalies. To assess the role of Satb2 in craniofacial development, we analyzed mutant mice at different stages of development. Here, we show that Satb2 is broadly expressed in early embryonic mouse development including the mesenchyme of the second and third arches. Satb2-/- mutant mice exhibit microglossia, a shortened lower jaw, smaller trigeminal ganglia, and larger thyroids. We correlate these findings with the detailed clinical phenotype of four individuals with SAS and remarkable craniofacial phenotypes with one requiring mandibular distraction in childhood. We conclude that the mouse and patient data presented support less well-described phenotypic aspects of SAS including mandibular morphology and thyroid anatomical/functional issues.

Calcium Homeostasis Abnormalities in Patients Taking Chronic Anticonvulsants Therapy – A Cross-sectional Study

Introduction: Epilepsy is a well-known disease entity that is responsible for a significant amount of morbidity. The purpose of this research is to determine the frequency of calcium homeostasis abnormalities in patients who are taking chronic anticonvulsant medication and to analyze the levels of Vitamin D in the serum of patients who are taking chronic anticonvulsant medication. Materials and Methods: The SVRRGGH general medicine department in Tirupati conducted this cross-sectional single-centered prevalence study. The study included outpatients, inpatients, and acute medical care (AMC) patients. After applying the inclusion and exclusion criteria, the study randomly selected 100 seizure disorder patients from the SVRRGH in Tirupati. Epilepsy patients who participated in the study were asked about medication, compliance, and seizure control. Anticonvulsant usage and duration were recorded. Serum calcium, Vitamin D, alkaline phosphatase (ALP), and parathormone were measured. Hypoalbuminemia caused calcium adjustments. Liver and renal function tests ruled out other major causes of hypovitaminosis D. Results: In this study, 36% were hypocalcemic and 64% were normocalcemic. There was a significant association between a number of drugs, duration of up to 12 months, normal Vitamin D levels, and good seizure levels with hypocalcemia ( P < 0.001). Around 25% had high ALP levels and 75% had normal ALP levels. High ALP levels were significantly associated with hypocalcemia ( P < 0.001). Conclusion: Chronic anticonvulsant therapy is associated with significant hypocalcemia and hypovitaminemia D, and our findings suggest that calcium and Vitamin D supplementation might be beneficial for patients experiencing these conditions.

Genetic Mechanisms Driving Uterine Leiomyoma Pathobiology, Epidemiology, and Treatment.

Uterine leiomyomas (ULs) are the most common benign tumor of the uterus. They can be associated with symptoms including abnormal uterine bleeding, pelvic pain, urinary frequency, and pregnancy complications. Despite the high prevalence of UL, its underlying pathophysiology mechanisms have historically been poorly understood. Several mechanisms of pathogenesis have been suggested, implicating various genes, growth factors, cytokines, chemokines, and microRNA aberrations. The purpose of this study is to summarize the current research on the relationship of genetics with UL. Specifically, we performed a literature review of published studies to identify how genetic aberrations drive pathophysiology, epidemiology, and therapeutic approaches of UL. With regards to pathophysiology, research has identified MED12 mutations, HMGA2 overexpression, fumarate hydratase deficiency, and cytogenetic abnormalities as contributors to the development of UL. Additionally, epigenetic modifications, such as histone acetylation and DNA methylation, have been identified as contributing to UL tumorigenesis. Specifically, UL stem cells have been found to contain a unique DNA methylation pattern compared to more differentiated UL cells, suggesting that DNA methylation has a role in tumorigenesis. On a population level, genome-wide association studies (GWASs) and epidemiologic analyses have identified 23 genetic loci associated with younger age at menarche and UL growth. Additionally, various GWASs have investigated genetic loci as potential drivers of racial disparities in UL incidence. For example, decreased expression of Cytohesin 4 in African Americans has been associated with increased UL risk. Recent studies have investigated various therapeutic options, including ten-eleven translocation proteins mediating DNA methylation, adenovirus vectors for drug delivery, and "suicide gene therapy" to induce apoptosis. Overall, improved understanding of the genetic and epigenetic drivers of UL on an individual and population level can propel the discovery of novel therapeutic options.

Current issues of increasing the availability of innovative therapy for the treatment of patients with non-small cell lung cancer within the Russian healthcare system

The advisory board was held to discuss he current situation with diagnosis and treatment of advanced non — small cell lung cancer with a mutation in the MET gene (aNSCLC with METex14). Lung cancer takes a leading place in the structure of oncological diseases in Russia. The frequency of molecular abnormalities in the MET gene patients with advanced lung cancer is 3%, the NGS method is the most effective in identifying this alteration.The effectiveness of capmatinib, a MET tyrosine kinase inhibitor was confirmed in the GEOMETRY mono-1 registry trial: the objective response rate in the patients with aNSCLC with METex14 who had previously received 1–2 lines of therapy was 41%, among those who had not previously received treatment — 68%. Median duration of response was 9.7 month in previously treated patients with aNSCLC with METex14 and 12.6 months in the treatment — naïve patients with aNSCLC with METex14. Intracranial response was observed in 54% of cases among patients with aNSCLC with METex14. In addition, the efficacy of capmatinib was confirmed when it is administered to the patients with aNSCLC with METex14 in real-world clinical practice. Other therapeutic options (immune-oncology therapy, chemotherapy) are less effective in case of this disease variant.Based on the data on effectiveness and tolerability of capmatinib, the expert group made a decision to recommend inclusion of capmatinib in the Russian Clinical Guidelines for the treatment of lung cancer and into the Essential Drug list.

Safety of the PCSK9 inhibitor alirocumab: insights from 47296 patient-years of observation.

The ODYSSEY OUTCOMES trial, comprising over 47000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

Polystyrene nanoplastics synergistically exacerbate diclofenac toxicity in embryonic development and the health of adult zebrafish

In this study, we investigated the possible ecotoxicological effect of co-exposure to polystyrene nanoplastics (PS-NPs) and diclofenac (DCF) in zebrafish (Danio rerio). After six days of exposure, we noticed that the co-exposure to PS-NP (100 μg/L) and DCF (at 50 and 500 μg/L) decreased the hatching rate and increased the mortality rate compared to the control group. Furthermore, we noted that larvae exposed to combined pollutants showed a higher frequency of morphological abnormalities and increased oxidative stress, apoptosis, and lipid peroxidation. In adults, superoxide dismutase and catalase activities were also impaired in the intestine, and the co-exposure groups showed more histopathological alterations. Furthermore, the TNF-α, COX-2, and IL-1β expressions were significantly upregulated in the adult zebrafish co-exposed to pollutants. Based on these findings, the co-exposure to PS-NPs and DCF has shown an adverse effect on the intestinal region, supporting the notion that PS-NPs synergistically exacerbate DCF toxicity in zebrafish.

Abnormal frequency of the memory B cell subsets and plasmablasts in patients with congenital severe hemophilia A: correlation with “Inhibitor” formation

BackgroundDevelopment of antibodies against infused Factor VIII (FVIII) or "inhibitors" represents a major challenge following FVIII replacement therapy in patients with hemophilia A (HA). Recent studies have shown that certain cellular compartments of the immune system contribute to the production of such antibodies. Herein, we determined the frequency of class-switched CD19+IgD−CD27+/non-class-switched CD19+IgD+CD27+ memory B cell subsets and CD19+CD27hiCD38hi plasmablasts in patients with severe HA and their association with the development of inhibitors in these patients.MethodsThis cross-sectional case–control study enrolled 32 patients with severe HA, including 8 with and 24 without inhibitors, and 24 healthy individuals. The frequencies of the memory B cell subsets and plasmablasts were determined using flow cytometry.ResultsThe frequency of CD19+IgD+CD27+ non-class-switched memory B cells was significantly lower in patients with HA (including both patients with and without inhibitors) than in healthy controls. The percentages of both CD19+IgD−CD27+ class-switched and CD19+IgD+CD27+ non-class-switched memory B cells did not differ significantly between patients with and without inhibitors. HA patients with inhibitors had significantly higher proportions of CD19+CD27hiCD38hi plasmablasts than the control group as well as the inhibitor (-) ones. No significant correlation was observed between the inhibitor levels with the percentages of memory B cell subsets and plasmablasts.ConclusionThis study is the first to demonstrate a dysregulated proportion of CD19+IgD+CD27+ non-class-switched memory B cells and CD19+CD27hiCD38hi plasmablasts in patients with severe HA. Therefore, strategies targeting memory B-cell/plasmablast differentiation may have promising outcomes in the management of inhibitor formation in patients with severe HA.