Types Of Abnormalities Research Articles

P-537 Linking genetic variation to infertility and embryonic genomic instability. Lessons from a database of whole genomes from targeted populations: challenges, and future directions

Abstract Study question Can novel genomic analysis methods be developed to identify genetic variants that predispose to specific types of infertility and genomic instability in embryos? Summary answer Whole genome analysis and the creation of a genomic variation database of highly targeted populations yielded several genomic links to human infertility and genomic instability. What is known already Infertility is a phenotypic manifestation that originates from highly variable causes, like repeated miscarriage (RM), repeated implantation failure (RIF) or various male and female factors. Specific genetic variations can predispose carriers to distinct types of infertility however quantifiable genetic risks are difficult to be established clinically due to the high amount of variables that exist in any relevant infertility studies. In addition, the combination of the maternal and paternal genetics further complicates the interpretation of genomics results especially when genetic instability in embryos are studied. Several studies have indicated multi[le risk variants however few have managed to establish causal relationships. Study design, size, duration The causes of infertility are extremely variable, which presents a challenge in the design and analysis of genome sequencing studies that involve large populations of participants with similar characteristics. In this study a targeted approach highly selected populations allows more detailed examination of the whole genome of the participants and the different subgroups that exist among them. The participants were recruited using specific selection criteria and samples were collected over a period of 5 years. Participants/materials, setting, methods Couples presenting with infertility and went through preimplantation genetic testing for aneuploidy (PGT- A) were invited to participate. Selection criteria were applied: i) referred for PGT-A after >3 assisted reproduction failed cycles, ii) Normal karyotypes, iii) Female age less than 37, iv) Embryonic instability in their subsequent PGT-A cycles in more than 40% of the produced embryos. After whole genome sequencing (WGS) and variant calling, a bespoke genomic SQL database was constructed for genomic analysis. Main results and the role of chance From 118 individuals that consented to participate 28 individuals with repeated implantation failure (RIF) and 8 individuals RIF/RM passed the selection criteria and their DNA was processed with WGS using a short read platform. In addition, WGS Validation was performed using genomes with known mutations. After the WGS quality control and validation. In total 50 genomes were processed and produced variant results. A novel MySQL database was successfully constructed and validated. Variant z scores were calculated for each participant and the significantly flagged variants were pulled and analysed and comparison with other bespoke and publicly available databases was performed. Ethnicity bias in novel variations detected and corrected. Several smaller cohorts were identified with similar genomic characteristics and accumulation of specific sets of polymorphisms, that were associated with certain types of infertility and preimplantation embryo abnormalities. Of particular interest were variants in synaptonemal complex genes associated with gamete failure, meiotic errors and instability in embryos. Structural variations were significant for male factor infertility. The WGS approach also revealed novel intronic and extragenic variants that would not be usually picked up by other methods like exome sequencing but can play a vital role in gene expression. Limitations, reasons for caution As with all genomic studies relating to infertility, association does not mean causation. Further functional analysis would be required to establish definitive causal pathways based on significant risk variants. In addition, although our study is highly targeted more genomic data can enhance to validation of these results. Wider implications of the findings This highly targeted study using a personalised approach to genome analysis combined with WGS can lead to protocols that determine the cumulative clinical risk for infertility, by revelling the accumulation of specific sets of polymorphisms, intronic and exonic, can be associated with certain types of infertility and preimplantation embryo abnormalities. Trial registration number not applicable

P-736 The therapeutic effect of hysteroscopic surgery on chronic endometritis in infertile women with intrauterine disorders

Abstract Study question Can chronic endometritis (CE) be treated by hysteroscopic surgery without antibiotic treatment in women with intrauterine disorders? Summary answer Most CE cases with intrauterine disorders were cured through hysteroscopic surgery without antibiotic therapy, regardless of the type of intrauterine abnormalities. What is known already Persistent inflammation of the local endometrium, CE, interferes with embryo implantation. CE is primarily caused by intrauterine infection; therefore, broad-spectrum antibiotic therapy is the current treatment for CE. Nevertheless, most cases with CE and endometrial polyps can be cured via hysteroscopic polypectomy without antibiotic therapy in our previous study. Study design, size, duration This study was a prospective cohort study approved by the Ethics Committee. To evaluate the therapeutic effect of hysteroscopic surgery on CE, the endometrial specimens for the immunohistochemistry analysis of the plasma cell marker CD138 were obtained to diagnose CE at surgery between November 2018 and June 2021. In the women diagnosed with CE, endometrial biopsy was performed without use of antibiotics in the subsequent menstrual cycle. Participants/materials, setting, methods The study population consisted of 337 consecutive infertile women who underwent hysteroscopic surgery. Eighty-nine consecutive patients without intrauterine disorders were also recruited as control group. CE was diagnosed as the presence of ≥ 5 CD138-positive cells in 10 nonoverlapping random stromal areas of high-power fields (HPF) in this study. Main results and the role of chance The prevalence of CE with ≥5 CD138-positive cells in women with no intrauterine disorder, endometrial polyps, myomas, intrauterine adhesion (IUA), and septate uterus were 15.7%, 85.7%, 69.0%, 78.9%, and 46.2%, respectively. Multivariate analysis revealed that CE was diagnosed significantly more often in the endometrial polyp (p < 0.0001, odds ratio [OR] 27.69, 95% confidence interval [CI] 15.01–51.08) and IUA groups (p < 0.0001, OR 8.85, 95%CI 3.26–24.05). The CE recovery rates by hysteroscopic surgery in the women with endometrial polyps, myomas, IUA, and septate uterus were 89.7%, 100%, 92.8%, and 83.3%, respectively (p = 0.45). Limitations, reasons for caution This study has limitations. First, some patients received a combination of estrogen and progestin or dienogest before surgery. These medicines may influence the number of CD138-positive cells. Second, ≥5 CD138-positive cells per 10 HPF were defined as the diagnosis of CE; however, different diagnostic criteria may generate different results. Wider implications of the findings CE is primarily caused by intrauterine infection due to a wide variety of microorganisms; however, most CE cases with intrauterine abnormalities were cured by hysteroscopic surgery without antibiotic use. Most CE cases associated with intrauterine abnormalities may be noninfectious CE. Trial registration number not applicable

P-520 Analyses of mosaic embryos reveal critical regions on human chromosome 11 that involve embryo implantation

Abstract Study question Why some mosaic embryos can be implanted, whereas others cannot? What are the secrets hidden in the human genome that control embryo implantation? Summary answer By data-mining genomic information from PGT-A results of 109 mosaic embryos, we have defined the critical regions in chr11 that play essential roles in implantation. What is known already Embryo implantation is usually a bottleneck step for a successful IVF treatment. What factors control the embryo implantation process has been pursued for many years, and the answers remain largely unknown. PGT-A is a widely applied procedure to identify embryos with normal diploid chromosomes to increase the clinical pregnancy rate per embryo transfer. However, some poor responder patients may only have mosaic embryos that can be used for transfer. We thus investigate the critical regions of the human chromosomes that are important for controlling embryo implantation. Study design, size, duration One hundred and nine mosaic blastocysts were analyzed based on PGT-A assay from 94 patients (ages ranging from 30 to 49 years old, mean age = 38.9 years) undergoing IVF between November 2020 and March 2022. The impact of chromosomal regions on implantation was explored by analyzing the sequencing results together with the pregnancy outcome of mosaic embryos. Additional published outcome data of 1000 mosaic embryo transfers was used to confirm our findings. Participants/materials, setting, methods Pregnant outcomes were followed, including hCG examination, sac formation, and live birth. Whole genome data analysis was performed using individual PGT-A results. Different types of chromosome abnormalities were calculated, and heatmap and clustering analysis were used to define the critical chromosome regions for embryo implantation. In addition, gene set enrichment and pathway analyses were conducted to reveal the functions of genes within the critical regions. Main results and the role of chance Among the transferred 109 mosaic embryos, the clinical outcomes of hCG positive, sac formation, and live birth rates were 45.8%, 42.2%, and 32.1%, respectively. There were 74 (67.8%) and 35 (32.1%) embryos carrying single and multiple mosaic chromosomes, respectively, resulting in 182 chromosomal mosaicism events. The trisomy mosaicism (133/182, 73.0%) occurred with higher frequency than monosomy mosaicism (49/182, 26.9%). Using the heatmap and clustering analysis, our data showed clustered monosomy mosaicism in non-pregnant embryos, especially for chr2, chr4, chr11, chr19, and chr22. Further refinement using segmental mosaic embryos has identified the critical regions, ranging from 10M to 40M in size on different chromosomes that are involved in hundreds of protein-coding genes and known dosage-sensitive genes. Importantly, functional analyses of the genes within the critical regions of chromosome 11 revealed enrichments in embryo invasion and angiogenesis, and suggest that loss of the chromosomal copy of these regions may result in implantation failure. Limitations, reasons for caution It’s still preliminary. More data is required to further confirm the conclusion. Wider implications of the findings Our study provides insights into the chromosomal regions involved in human embryo implantation and will improve the embryo prioritizing strategy in future IVF clinics. Importantly it is the first time the genomics information and gene-mapping strategy have been applied in mosaic embryos to uncover mechanisms underlying human embryo implantation. Trial registration number not applicable

Ovarian hyperplasia linked to a mutation in MAN1A2 in a cow with excessive follicular growth and functional oocytes.

Here we report the case of a cow with two ovaries that each exhibited hyperplasia but that otherwise had normal gross morphology. Both ovaries had a large number of tertiary follicles on the ovarian surface. Oocytes from one ovary were studied in more detail. The transcriptome was largely similar to other oocytes. Oocytes could undergo cleavage at a rate consistent with other oocytes and result in blastocyst-stage embryo formation after in vitro maturation and fertilization. Review of the literature from cattle and other species did not reveal reports of a similar type of spontaneous ovarian abnormality. Whole genome sequencing revealed many single nucleotide polymorphisms with predicted large effects on protein structure that could potentially be causative for the phenotype. The variant considered most likely to cause the observed alteration in ovarian function was a mutation in the glycoprotein-modifying enzyme MAN1A2.

Tandem Autologous Stem Cell Transplantation Does Not Benefit High-Risk Myeloma Patients in the Maintenance Era: Real-World Results from The Canadian Myeloma Research Group Database

In patients with multiple myeloma (MM), the presence of high-risk cytogenetic abnormalities is associated with worse disease control and survival. Autologous stem cell transplant (ASCT) does benefit these patients. Tandem transplantation has been explored as a means to deepen responses and further improve survival however, its role remains controversial. This is particularly true in the era of novel agent induction and post-transplant maintenance therapy. The aim of this study was to use the Canadian Myeloma Research Group database and examine a large cohort of real-world patients comparing the outcomes of tandem versus single ASCT specifically in high-risk patients receiving novel agent-based induction and post-transplant maintenance. The data for this study was derived retrospectively from a comprehensive national-level database of Canadian patients with MM. High-risk cytogenetics was defined as presence of del17p, t(4;14), or t(14;16). Those receiving allogeneic transplant were excluded. Tandem transplantation was defined as a second ASCT performed consecutively without interim relapse or progression after first ASCT. Those with relapse or progressive disease within 3 months of completing a first transplant were excluded. We compared response depth, progression-free, and overall survival (OS) based on single or tandem transplantation procedures. The impact of covariates of interest was also assessed. A total of 381 patients with high-risk cytogenetics were identified. A total of 242 received single and 139 patients received tandem transplants. All received post-transplant maintenance. The most common induction regimen for these patients was cyclophosphamide, bortezomib, and steroids (CyBorD, 87%). Forty-one patients (10.8%) required reinduction prior to first ASCT. The best overall responses at any time were 98.3% (90.5% ≥ very good partial response [VGPR]) and 98.6% (89.9% ≥ VGPR) in the single and tandem ASCT groups, respectively. Survival outcomes were similar with the median progression-free survival for single or tandem ASCT of 35.2 and 35.3 months (P = .88) and the median OS were 92.6 and 88.9 months, respectively (P = .72). No statistically significant differences were seen based on type of cytogenetic abnormality or type of maintenance. This was confirmed on multivariate analysis. In the real-world setting, tandem ASCT does not improve outcomes for MM patients with high-risk cytogenetics. This may be driven by the use of effective pre- and post-ASCT therapies. The development of more potent induction and consolidation along with current nearly ubiquitous continuous maintenance therapies until disease progression does not support the use of a second high-dose procedure.

Structural Lung Disease and Clinical Phenotype in Bronchiectasis Patients: The EMBARC CT Study.

Rationale: Chest computed tomography (CT) scans are essential to diagnose and monitor bronchiectasis (BE). To date, few quantitative data are available about the nature and extent of structural lung abnormalities (SLAs) on CT scans of patients with BE. Objectives: To investigate SLAs on CT scans of patients with BE and the relationship of SLAs to clinical features using the EMBARC (European Multicenter Bronchiectasis Audit and Research Collaboration) registry. Methods: CT scans from patients with BE included in the EMBARC registry were analyzed using the validated Bronchiectasis Scoring Technique for CT (BEST-CT). The subscores of this instrument are expressed as percentages of total lung volume. The items scored are atelectasis/consolidation, BE with and without mucus plugging (MP), airway wall thickening, MP, ground-glass opacities, bullae, airways, and parenchyma. Four composite scores were calculated: total BE (i.e., BE with and without MP), total MP (i.e., BE with MP plus MP alone), total inflammatory changes (i.e., atelectasis/consolidation plus total MP plus ground-glass opacities), and total disease (i.e., all items but airways and parenchyma). Measurements and Main Results: CT scans of 524 patients with BE were analyzed. Mean subscores were 4.6 (range, 2.3-7.7) for total BE, 4.2 (1.2-8.1) for total MP, 8.3 (3.5-16.7) for total inflammatory changes, and 14.9 (9.1-25.9) for total disease. BE associated with primary ciliary dyskinesia was associated with more SLAs, whereas chronic obstructive pulmonary disease was associated with fewer SLAs. Lower FEV1, longer disease duration, Pseudomonas aeruginosa and nontuberculous mycobacterial infections, and severe exacerbations were all independently associated with worse SLAs. Conclusions: The type and extent of SLAs in patients with BE are highly heterogeneous. Strong relationships between radiological disease and clinical features suggest that CT analysis may be a useful tool for clinical phenotyping.

The rs4354668 polymorphism in the SLC1A2 gene for the EAAT2 glutamate transporter is associated with an increased risk of harmful drug use - an exploratory study on a university student population.

Evidence suggests that decreased dopamine secretion in mesocorticolimbic pathways could predispose to increased susceptibility to substance addiction. It has been proposed to define such a phenomenon as the reward deficit syndrome (RDS). Dopaminergic projections of the reward system receive glutaminergic projections from cortex. Research indicates that a reduction in the stimulating glutamatergic transmission on the dopaminergic system could represent an alternative phenotype of RDS. Potential source of this type of abnormality is glutamate reuptake which depends on excitatory amino acid transport proteins (EAAT) function. The most important of them is EAAT2, polymorphisms of which have been linked to several mental disorders. We analyzed the genetic and psychometric data of 125 young adults (n = 125) for the effect of the rs4354668 polymorphism of the SLC1A2 gene for EAAT2 on the risky or harmful drug use (RHDU). After exploratory analysis we used logistic regression models to assess the probability of RHDU in individual groups. In the final model T/T variant of rs4354668 was significantly associated with a lower probability of RHDU occurrence compared to G/G variant (OR: 0.021; 95% CI: 0.001 - 0.275; p = 0.009). Other significant predictors of RHDU were smoking status and risky or harmful drinking of alcohol. The results obtained may indicate a possible relationship of the risk of harmful drug use with variants of the rs4354668 polymorphism of the SLC1A2 gene for EAAT2. Subjects with the T/T variant of this polymorphism appear to be less at risk of developing drug use disorders.

Association of Maternal Serum Vitamin D Level with Hydatidiform Mole-A Systemic Review

Hydatidiform mole is an abnormal type of pregnancy, in which a potentially anomalous ovum is abnormally fertilized resulting in a subsequently non-viable conceptus becoming an enlarged growth in the uterus with dangerous complications. These moles can occur as either complete or partial, each with its own unique features. Like other risk factor, nutritional risk factors are associated with increased likelihood of development of HM. Low dietary intake of carotene, inadequate protein and animal fats are thought to be associated with increased risk of HM. Vitamin D is a steroid hormone with receptors found throughout the body including ovary, uterus, and placenta and has natural immunomodulator with anti-inflammatory properties. At the ovarian level, vitamin D has been shown to enhance ovulation. In the human syncytiotrophoblast, vitamin D and its components act together to enhance the expressions of human chorionic gonadotropin (hCG), human placental lactogen, estrogen and progesterone. Furthermore, vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues and 1,25(OH)2D3 also inhibits angiogenesis and metastasis. Deficiency of vitamin D may lead to increased ROS and decreased antioxidative defense systems that could lead to oxidative injury in patients with HM. In the human syncytiotrophoblast, vitamin D and its components act together to enhance the expressions of human chorionic gonadotropin (hCG), human placental lactogen, estrogen and progesterone. Furthermore, vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues and 1,25(OH)2D3 also inhibits angiogenesis and metastasis. Deficiency of vitamin D may lead to increased ROS and decreased antioxidative defense systems that could lead to oxidative injury in patients with HM. Studies showed there is significant association of low vitamin D level and obstetric complications like early pregnancy loss, premature rupture of membrane, fetal growth restriction and also many extra-skeletal diseases like ovary and colon cancer. In developing countries like-Bangladesh, vitamin D deficiency is much more common and starting in early life and persisting across the life span due to limited exposure to sunlight and low consumption of animal sources food. Therefore, this study was intended to determine the association of vitamin D and hydatidiform mole in a Bangladeshi woman, which may help in deciding about vitamin D supplementation as a preventive measure of hydatidiform mole.

Prevalence of karyotype alterations in couples with recurrent pregnancy loss in a tertiary center in Brazil.

To assess the prevalence and type of chromosomal abnormalities in Brazilian couples with recurrent pregnancy loss (RPL) and compare the clinical characteristics of couples with and without chromosome abnormalities. We assessed the medical records of 127 couples with a history of two or more miscarriages, referred to a tertiary academic hospital in Belo Horizonte, Brazil, from January 2014 to May 2023. Karyotype was generated from peripheral blood lymphocyte cultures, and cytogenetic analysis was performed according to standard protocols by heat-denatured Giemsa (RHG) banding. Abnormal karyotypes were detected in 10 couples (7.8%). The prevalence of chromosomal abnormalities was higher among females (6.3%) compared to males (2.0%), but this difference was not statistically significant (p=0.192). The mean number of miscarriages was. 3.3 ± 1.1 in couples with chromosome abnormalities and 3.1 ± 1.5 in couples without chromosome abnormalities (p=0.681). Numerical chromosomal anomalies (6 cases) were more frequent than structural anomalies. Four women presented low-grade Turner mosaicism. No differences were found between couples with and without karyotype alterations, except for maternal age, which was higher in the group with chromosome alterations. The prevalence of parental chromosomal alterations in our study was higher than in most series described in the literature and was associated with increased maternal age. These findings suggest that karyotyping should be part of the investigation for Brazilian couples with RPL, as identifying the genetic etiology may have implications for subsequent pregnancies.

Correlation between types of ventricular septal defect and chromosomal abnormalities in low-risk non-invasive prenatal testing.

The aim of this study was to examine whether there is a correlation between different types of ventricular septal defects (VSD) and chromosomal abnormalities in the low-risk setting of non-invasive prenatal testing (NIPT) and to evaluate the prognosis of fetuses with varying types of VSD. Cases of pregnant women who underwent amniocentesis due to fetal VSD were collected by Tianjin Central Hospital of Obstetrics and Gynecology from May 2017 to May 2022. Exclusions were made for those without NIPT, with high-risk NIPT results, genetic disorders, and those lost to follow-up. Data collected included ultrasound classification of VSD, prenatal NIPT results, copy-number variations (CNVs) results, and neonatal outcomes. The prevalence of pathogenic CNVs was investigated in 74 cases of VSDs. Of these cases, 45 were isolated VSDs (9 muscular and 36 non-muscular) and 29 were non-isolated VSDs (10 with intracardiac and 19 with extra-cardiac structural anomalies). The results revealed that the incidence of pathogenic CNVs was lower in isolated VSDs compared to non-isolated VSDs in a low-risk NIPT condition (χ2 = 9.344, P = 0.002). There was no significant difference in the prevalence of pathogenic CNVs between VSDs with intracardiac and extra-cardiac structural anomalies (P = 0.541). Moreover, VSDs associated with intracardiac structural anomalies had the highest rate of surgical intervention. When NIPT is low-risk and VSD is isolated, the likelihood of fetal chromosomal defects is not increased. However, if there are intra- or extra-cardiac structural abnormalities present alongside VSD, the possibility of pathogenic CNV is considerably greater, necessitating invasive prenatal diagnosis. Isolated muscular VSDs usually do not require surgery, which can be used as a basis for prenatal counseling regarding fetal VSD.

Mutational and Carcinogenic Potential of Amaltas Fruit Via Oxidation

Long term intake of plant-based medicines without knowing their toxicities and mutagenic potentials is common globally. Therefore, current work is an extension of cancer patient survey at Nuclear Institute of Medicine and Radiotherapy (NIMRA), for long term utilization of medicinal plant. Genotoxic potential Amaltas fruit (AF) was tested by Cicer arietinum L. and Allium cepa L plant assay. Abnormality index (A.I.), types of abnormalities and oxidative damages were the major parameters of genotoxicity. Analysis of variance (ANOVA) revealed statistically significant differences (LSD) at p≤ 0.05 for A.I. and oxidative damage in both assay plants, except negative control. Both A.I. and oxidative damages revealed incubation dependent increase. In both assay plant the major chromosomal aberration induced was fragmentation. AF induced polyploid cells, apoptotic cells and elongated cells only in Cicer arietinum L. assay. Oxidative damages in the form of nuclear membrane and cell membrane damage were observed in aberrant cells along with ghost cells. It is concluded that AF is capable to cause genotoxic effect incubation dependent manner. High rate of fragmented cells reflects its mutagenicity and carcinogenicity mediated oxidation of DNA and membranes in both assay plants. Induction of more ghost cells and less frequent apoptosis reflects activation of oncogene. Development of Pilus like projections in ghost cells depicts proliferation potential of defected cells. Prolonged utilization of AF was the cause of cancer in surveyed patients. Allium cepa L. was more sensitive as assay plant to the genotoxin. It is recommended that AF must be used occasionally.

Frequency of Abnormal Findings on Chest Radiographs: Analysis of Chest X-Ray Reports in the Metropolis

Introduction: To achieve the highest diagnostic accuracy of AI services in radiology, it is necessary to test and validate them on data sets that consider the balance of classes of various abnormalities. Information about the frequency of abnormal findings in practical healthcare is essential for creation of such datasets. Objective: To establish the frequency of chest X-ray abnormalities using big data from the healthcare system of a Russian metropolis. Materials and methods: We conducted an observational multicenter retrospective sample study by retrieving 562,077 chest X-ray reports dated February 18, 2021 to June 11, 2021 from the Unified Radiological Information Service of the Unified Medical Information Analysis System of the city of Moscow, which were then analyzed and automatically labeled using the Medlabel tool. The results were processed in Microsoft Excel and using the Python 3.9 programming language. Group differences were determined using the chi-square test. Results: Among all analyzed reports, cardiomegaly was the most frequent abnormal finding (12.23 %), while the proportion of other abnormalities did not exceed 3.0 %. Among all abnormal chest X-rays, 79.60 % showed only one abnormality with cardiomegaly found in 80.78 % of cases. Among the reports with two or more abnormal findings, cardiomegaly was detected in only 43.36 % of cases, whereas opacities (64.98 %) and infiltration/consolidation (64.50 %) prevailed. Conclusions: The proportion of abnormal chest X-rays was 16.7 %. In terms of the frequency of occurrence, cardiomegaly ranked first followed by focal pulmonary opacity and infiltration/consolidation. It is worth noting that the frequency of certain types of abnormalities varied significantly between the tests with one and several (two or more) abnormal findings, which should be taken into account when training and testing AI services.

Clinical Features and Risk Factors for Drug-Induced Liver Injury: A Retrospective Study From China

PurposeWith the prolongation of human life expectancy and the outbreak of COVID-19, antineoplastic agents, anti-infective drugs, and cardiovascular system drugs have been widely applied, resulting in a growing incidence of drug-induced liver injury (DILI) year by year. This study aimed to investigate signals, clinical characteristics, and risk factors in patients with liver injury. MethodsA retrospective analysis was conducted on inpatients clinically diagnosed with DILI from 2019 to 2021 in one tertiary hospital in mainland China. The hepatic biochemical indices, clinical manifestations and suspected drugs of the patients were counted. We determined causality assessed by the Roussel Uclaf Causality Assessment Method in patients that the biochemistry met the diagnostic criteria recommended by the International Serious Adverse Events Consortium and compared them with contemporaneous patients diagnosed as DILI but with hepatic biochemical abnormalities only to identify the injure types and risk factors for DILI. FindingsA total of 1167 patients from 2639 initial participants with DILI were included. According to the injured target cells, it can be divided into hepatocellular injury type 351 cases (30.08%), cholestatic injury type 97 cases (8.31%), mixed injury type 27 cases (2.31%), and biochemical abnormal only type 692 cases (59.30%). It involved 1738 cases of suspected drugs, 349 drugs, and the top 3 drug categories were antineoplastic agents, anti-infectives, and traditional Chinese medicines, with Cyclophosphamide, Atorvastatin, and Liuzasulfapyridine as the top 3 in order of ranking. The main symptoms of patients were darker urine, decreased appetite, and yellow sclera. The overall prognosis of patients with DILI was favorable, with 280 recovered cases (23.99%), 691 improved cases (59.21%), 189 not improved cases (16.20%), and 7 deaths (0.60%). There were significant differences in gender, age, malignancy, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, gamma-glutamyltransferase, albumin, international normalized ratio, and prognosis among patients with different injury types (P < 0.05). Multiple logistic regression analysis showed that female (odds ratio [OR] = 1.897, P < 0.001), alcohol use (OR = 1.905, P = 0.001), malignancy (OR = 0.417, P < 0.001), and pregnancy (OR = 0.201, P = 0.011) were independent factors influencing DILI. ImplicationsFor most patients with liver injury, the manifestations are mild elevation of liver biochemistry without other symptoms (biochemical abnormal only type). The rest of the patients are predominantly of the hepatocellular injury type. Female and alcohol abuse patients are the risk factors of DILI, reminding clinicians to strengthen education on safe drug use, give individualized treatment, and regularly monitor liver function indexes in the patients.

USE OF MISOPROSTOL IN ABORTION ON MEDICAL GROUNDS – OUR CLINICAL EXPERIENCE

Purpose. In clinical practice in hospital conditions, the preferred choice of behavior regarding fetal anomalies is to perform a medical abortion after the opinion of a specialized committee in the hospital. There are no observations conducted by other authors on abortions related to termination of pregnancy for medical reasons at a different time. The team conducts its observation in hospital conditions. Material/Methods: Conducted own retrospective study for the period January 2021 – February 2024 with the participation of 45 patients who went through a pregnancy termination committee on medical grounds. All women who passed through the committee for medically indicated abortion, in which fetal anomalies incompatible with life or severely debilitating were found, were examined. Women are at different stages of pregnancy, age, education, number of pregnancies and births, concomitant diseases, a type of test to diagnose abnormalities in the fetus (invasive and non-invasive). The type of abnormality that is the cause of an abortion on medical grounds has also been investigated. The dosage applied is- 1st tablet of 400 mg Misoprostol per vagine, second and third tablets in 3 hours sub buccal, the maximum dose is 5 tablets in 24 hours or 2000 microgram Misoprostol. Results. For 88,9% of the cases, they have a positive opinion of the commission in the hospital structure, and 11,1% have a refusal. Group matching of patients was performed by education and whether they had good outpatient follow-up, regardless of the duration of pregnancy. Patients with higher education had better outpatient follow-up (χ2=15.497, p=0.000) than those with secondary and primary education. There was a significant association between the dosing regimen and pregnancy severity; the relationship between the two-dose regimen was significant (χ2=53.862, p=0.000), and the three-dose regimen was highly successful in 73.3% of cases. Conclusion. The correct choice of method of application of the therapeutic regimen requires preliminary and detailed medical preparation of the patient and good clinical experience of the treating doctor. The applied therapeutic approach reduces the risk to the patient and has a rapid recovery period. Early and timely diagnosis has an important informative value.

Role of Mri in Characterization of Congenital Malformations of Brain in A Tertiary Care Centre-A Retrospective Study

Background: Congenital brain anomalies are rare among the congenital anomalies of various organ systems. It is crucial to recognise these disorders as soon as possible because of the extensive neurological deficiency and negative consequences they can cause. Neuroimaging is a reliable way to accurately diagnose the majority of congenital brain abnormalities. There aren't enough statistics available in developing countries like India about the frequency and types of brain abnormalities. The purpose of this study is to examine the prevalence and range of frequently occurring congenital brain abnormalities. Objective: To study the whole spectrum of all substantial and frequently occurring congenital abnormalities as well as the proportional distribution of the various brain malformations in a tertiary care centre. Methods and materials: The study was conducted at Department of Radio-Diagnosis, Medical College Kolkata from 1st September 2022 to 31st August 2023. All MRI brain examinations at our hospital over a period of one year were retrospectively reviewed and analysed by sex, age at presentation, type of congenital cerebral malformation, and other associated congenital cerebral malformations. Results: This study included 24 patients. The total number of brain malformations identified in these patients was 33. The age of patients at first MRI imaging ranged from 5 days to 16 years. There were 14 males and 10 females. The most common malformations were corpus callosum dysgenesis (24%), Heterotropia (15%) and Lissencephaly (12%). Seven patients (29.1%) had more than one congenital brain malformation. Conclusion: The variety and complexity of congenital brain abnormalities is remarkable. The correct diagnosis is essential for the best care of these unfortunate conditions, and MRI plays a significant role in this process. Identification of distinctive neuroimaging findings of various congenital brain anomalies are immensely helpful in diagnosing the anomalies and further management.

Objective and automatic assessment approach for diagnosing attention-deficit/hyperactivity disorder based on skeleton detection and classification analysis in outpatient videos

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is diagnosed in accordance with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria by using subjective observations and information provided by parents and teachers. However, subjective analysis often leads to overdiagnosis or underdiagnosis. There are two types of motor abnormalities in patients with ADHD. First, hyperactivity with fidgeting and restlessness is the major diagnostic criterium for ADHD. Second, developmental coordination disorder characterized by deficits in the acquisition and execution of coordinated motor skills is not the major criterium for ADHD. In this study, a machine learning-based approach was proposed to evaluate and classify 96 patients into ADHD (48 patients, 26 males and 22 females, with mean age: 7y6m) and non-ADHD (48 patients, 26 males and 22 females, with mean age: 7y8m) objectively and automatically by quantifying their movements and evaluating the restlessness scales.MethodsThis approach is mainly based on movement quantization through analysis of variance in patients’ skeletons detected in outpatient videos. The patients’ skeleton sequence in the video was detected using OpenPose and then characterized using 11 values of feature descriptors. A classification analysis based on six machine learning classifiers was performed to evaluate and compare the discriminating power of different feature combinations.ResultsThe results revealed that compared with the non-ADHD group, the ADHD group had significantly larger means in all cases of single feature descriptors. The single feature descriptor “thigh angle”, with the values of 157.89 ± 32.81 and 15.37 ± 6.62 in ADHD and non-ADHD groups (p < 0.0001), achieved the best result (optimal cutoff, 42.39; accuracy, 91.03%; sensitivity, 90.25%; specificity, 91.86%; and AUC, 94.00%).ConclusionsThe proposed approach can be used to evaluate and classify patients into ADHD and non-ADHD objectively and automatically and can assist physicians in diagnosing ADHD.

Adolescent female reproductive system dysplasia: a clinical study of 356 cases

Objective: To explore the age of onset and consultation, the main clinical manifestations, common types of combined malformations, the relationship of endometriosis, surgical prognosis and different types of proportion of adolescent female reproductive system dysplasia. Methods: The medical records of 356 patients (aged 10-19) with female reproductive system dysplasia in Women's Hospital, School of Medicine, Zhejiang University from January 2003 to August 2018 were collected and retrospectively analyzed. Results: (1) Among the 356 adolescent dysplasia patients, uterine dysplasia (23.6%, 84/356), oblique vaginal septum syndrome (OVSS; 22.5%, 80/356) and vaginal dysplasia (21.6%, 77/356) were the most frequent ones, followed by multi-sectional dysplasia (16.0%, 57/356), other types of developmental abnormalities like external genitaliaand urogenital fistula (13.5%, 48/356) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome; 2.8%, 10/356). (2) There were significant differences between the median age of onset and the age of consultation of patients with OVSS and other types of abnormalities except hymen atresia (both P<0.05). In contrast, there were no significant differences between the age of onset and the age of consultation of the patients of uterine dysplasia, vaginal dysplasia, hymen atresia, MRKH syndrome and multi-sectional dysplasia (all P>0.05). (3) The clinical manifestations were lack of specificity, and mainly abnormal finding was lower abdominal pain. (4) After admission, the majority of patients underwent comprehensive cardiopulmonary examination (71.3%, 254/356) and urinary system examination (63.5%, 226/356). Only 18.3% (65/356) of patients had completed abdominal organ examination, and 5.9% (21/356) skeletal system examination. About other systemic malformations, urological malformations were the most common (27.5%, 98/356), followed by anorectal malformation (0.6%, 2/356), heart malformations (0.3%, 1/356), and spinal malformations (0.3%, 1/356). 46.4% (84/181) of the surgical patients were diagnosed with combined endometriosis. Patients with obstructive genital tract malformations were more likely to combine with endometriosis than non-obstructive ones [50.3% (74/147) vs 29.4% (10/34); P<0.05]. However, there was no significant difference between the severity of endometriosis of those two kinds (P>0.05). (5) Totally 308 patients were followed up successfully with a median of 25.0 years old, and 20 cases were treated again; 12.0% (37/308) of them were suffering from menstrual disorder and 33.1% (102/308) of them with dysmenorrhea. Totally 130 patients had sexually active reported no sexual problems. Conclusions: Uterine dysplasia, OVSS and vaginal dysplasia are the most common syndromes in adolescent female reproductive system dysplasia along with frequent cases of coexisting urinary malformations and increasing risks of endometriosis. Meanwhile, the lack of specificity of clinical manifestations might delay the timely diagnosis and treatment after the onset of symptoms. Nonetheless, most patients could achieve good surgical outcomes.

Computer-aided colorectal cancer diagnosis: AI-driven image segmentation and classification

Colorectal cancer is an enormous health concern since it is among the most lethal types of malignancy. The manual examination has its limitations, including subjectivity and data overload. To overcome these challenges, computer-aided diagnostic systems focusing on image segmentation and abnormality classification have been developed. This study presents a two-stage approach for the automatic detection of five types of colorectal abnormalities in addition to a control group: polyp, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, serrated adenoma, adenocarcinoma. In the first stage, UNet3+ was used for image segmentation to locate the anomalies, while in the second stage, the Cross-Attention Multi-Scale Vision Transformer deep learning model was used to predict the type of anomaly after highlighting the anomaly on the raw images. In anomaly segmentation, UNet3+ achieved values of 0.9872, 0.9422, 0.9832, and 0.9560 for Dice Coefficient, Jaccard Index, Sensitivity, Specificity respectively. In anomaly detection, the Cross-Attention Multi-Scale Vision Transformer model attained a classification performance of 0.9340, 0.9037, 0.9446, 0.8723, 0.9102, 0.9849 for accuracy, F1 score, precision, recall, Matthews correlation coefficient, and specificity, respectively. The proposed approach proves its capacity to alleviate the overwhelm of pathologists and enhance the accuracy of colorectal cancer diagnosis by achieving high performance in both the identification of anomalies and the segmentation of regions.

Cardiac screening in pediatric patients with neurofibromatosis type 1: similarities with Noonan syndrome?

Both Neurofibromatosis type 1 (NF1) and Noonan syndrome (NS) are RASopathies. Characteristic cardiac phenotypes of NS, including specific electrocardiographic changes, pulmonary valve stenosis and hypertrophic cardiomyopathy have not been completely studied in NF1. Purpose: The aims of this study were to assess: (1) similarities in the prevalence and types of ECG and conventional echocardiographic findings described in NS in asymptomatic patients with NF1, and (2) the presence of discrete myocardial dysfunction in NF1 patients using myocardial strain imaging. Methods: Fifty-eight patients with NF1 (ages 0–18 years), and thirty-one age-matched healthy controls underwent cardiac assessment including blood pressure measurements, a 12-lead ECG, and detailed echocardiography. Quantification of cardiac chamber size, mass and function were measured using conventional echocardiography. Myocardial strain parameters were assessed using 2-Dimensional (2D) Speckle tracking echocardiography. Results: Asymptomatic patients with NF1 had normal electrocardiograms, none with the typical ECG patterns described in NS. However, patients with NF1 showed significantly decreased calculated Z scores of the left ventricular internal diameter in diastole and systole, reduced left ventricular mass index and a higher incidence of cardiac abnormal findings, mainly of the mitral valve, in contrast to the frequently described types of cardiac abnormalities in NS. Peak and end systolic global circumferential strain were the only significantly reduced speckle tracking derived myocardial strain parameter. Conclusions: Children with NF1 demonstrated more dissimilarities than similarities in the prevalence and types of ECG and conventional echocardiographic findings described in NS. The role of the abnormal myocardial strain parameter needs to be explored.

A mandibular advancement device attenuates the abnormal morphology and function of mitochondria from the genioglossus in obstructive sleep apnea-hypopnea syndrome rabbits.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is a serious and potentially life-threatening disease. Mandibular advancement device (MAD) has the characteristics of non-invasive, comfortable, portable and low-cost, making it the preferred treatment for mild-to-moderate OSAHS. Our previous studies found that abnormal contractility and fibre type distribution of the genioglossus could be caused by OSAHS. However, whether the mitochondria participate in these tissue changes is unclear. The effect of MAD treatment on the mitochondria of the genioglossus in OSAHS is also uncertain. To examine the morphology and function of mitochondria from the genioglossus in a rabbit model of obstructive sleep apnea-hypopnea syndrome (OSAHS), as well as these factors after insertion of a mandibular advancement device (MAD). Thirty male New Zealand white rabbits were randomised into three groups: control, OSAHS and MAD, with 10 rabbits in each group. Animals in Group OSAHS and Group MAD were induced to develop OSAHS by injection of gel into the submucosal muscular layer of the soft palate. The rabbits in Group MAD were fitted with a MAD. The animals in the control group were not treated. Further, polysomnography (PSG) and cone-beam computed tomography (CBCT) scan were used to measure MAD effectiveness. CBCT of the upper airway and PSG suggested that MAD was effective. Rabbits in the three groups were induced to sleep for 4-6 h per day for eight consecutive weeks. The genioglossus was harvested and detected by optical microscopy and transmission electron microscopy. The mitochondrial membrane potential was determined by laser confocal microscopy and flow cytometry. Mitochondrial complex I and IV activities were detected by mitochondrial complex assay kits. OSAHS-like symptoms were induced successfully in Group OSAHS and rescued by MAD treatment. The relative values of the mitochondrial membrane potential, mitochondrial complex I activity and complex IV activity were significantly lower in Group OSAHS than in the control group; however, there was no significant difference between Group MAD and the control group. The OSAHS-induced injury and the dysfunctional mitochondria of the genioglossus muscle were reduced by MAD treatment. Damaged mitochondrial structure and function were induced by OSAHS and could be attenuated by MAD treatment.