Major Etiology Research Articles

Autoimmune thyroid status in subclinical thyroid disorders in patients attending a tertiary care center in Nepal: a hospital-based cross-sectional study

BackgroundThyroid dysfunction is the leading endocrine disorder worldwide. Iodine deficiency disorders, which were once the major etiology of thyroid dysfunctions, now have been succeeded by autoimmune thyroid diseases with the rise in aberrant salt ionization protocols. This study endeavors to access the level of thyroid autoantibodies viz. anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (TGA), and anti-thyroid stimulating hormone receptor (TRAb) in individuals with subnormal thyroid profiles.MethodsThis hospital-based cross-sectional study was conducted at the Department of Clinical Biochemistry, Tribhuvan University for a period of six months. Using non-probability (purposive) sampling method, a total of 60 patients were enrolled with subnormal thyroid profiles to include the population who have not yet started medication. Thyroid hormones (free T3, free T4, TSH) and thyroid antibodies (anti-TPO, TGA, and TRAb) were measured. For non-parametric data, Chi-square test and Kruskal-Wallis test were used. Spearman’s correlation was done to determine the association between variables.ResultsOut of 60 participants, the majority of the population between 25 and 44 years were diagnosed with thyroid dysfunction with female preponderance. Among all, 40% (n = 24) had subclinical hyperthyroid states while, 60% (n = 36) had subclinical hypothyroid states, and 75% (n = 45) of the total exhibited positive thyroid antibodies. In subclinical hypothyroid patients with TSH above 10 µIU/ml, anti TPO (58.5%) and TGA (66.7%) positivity were highly prevalent. On the other hand, TRAb was exclusively positive in hyperthyroid condition (50% among the group) which is by far the first of its kind reported in Nepal.ConclusionThe rise in autoimmune thyroid disease among the Nepalese population infers that addressing iodine deficiency simply through salt iodinization may not be adequate to deal with the rising burden of thyroid disorders, especially in iodine-depleted areas. Also, the increasing prevalence of thyroid autoantibodies positivity in subclinical hypothyroidism in the Nepalese population accounts for the arduous screening and monitoring of autoimmune thyroid disorders in Nepal.

Systematic analysis and characterization of long non-coding RNA genes in inflammatory bowel disease.

The cases of inflammatory bowel disease (IBD) are increasing rapidly around the world. Due to the multifactorial causes of IBD, there is an urgent need to understand the pathogenesis of IBD. As such, the usage of high-throughput techniques to profile genetic mutations, microbiome environments, transcriptome and proteome (e.g. lipidome) is increasing to understand the molecular changes associated with IBD, including two major etiologies of IBD: Crohn disease (CD) and ulcerative colitis (UC). In the case of transcriptome data, RNA sequencing (RNA-seq) technique is used frequently. However, only protein-coding genes are analyzed, leaving behind all other RNAs, including non-coding RNAs (ncRNAs) to be unexplored. Among these ncRNAs, long non-coding RNAs (lncRNAs) may hold keys to understand the pathogenesis of IBD as lncRNAs are expressed in a cell/tissue-specific manner and dysregulated in a disease, such as IBD. However, it is rare that RNA-seq data are analyzed for lncRNAs. To fill this gap in knowledge, we re-analyzed RNA-seq data of CD and UC patients compared with the healthy donors to dissect the expression profiles of lncRNA genes. As inflammation plays key roles in the pathogenesis of IBD, we conducted loss-of-function experiments to provide functional data of IBD-specific lncRNA, lung cancer associated transcript 1 (LUCAT1), in an in vitro model of macrophage polarization. To further facilitate the lncRNA research in IBD, we built a web database, IBDB (https://ibd-db.shinyapps.io/IBDB/), to provide a one-stop-shop for expression profiling of protein-coding and lncRNA genes in IBD patients compared with healthy donors.

Effect of nonsurgical periodontal therapy on interleukin-35 level in gingival crevicular fluid

ABSTRACT Background: Clinical attachment level (CAL), alveolar bone loss, and periodontal pockets constitute the major signs of periodontitis. The interaction between the host and the bacteria that forms a biofilm on the tooth surface is one of the major etiologies of periodontal disorders. Aim: The aim of this study was to assess interleukin-35 (IL-35) levels pre and post nonsurgical periodontal therapy (NSPT) in healthy individuals and gingivitis and periodontitis patients. Materials and Methods: IL-35 level in gingival crevicular fluid (GCF) and clinical parameters were assessed in 60 individuals. Biochemical analysis was done by enzyme-linked immunosorbent assay. Individuals in Group I were in good health; those in Groups II and III had gingivitis and periodontitis, respectively. Study individuals were evaluated at baseline and 3 months after NSPT. Results: Group III differed from Group II in that it had higher CAL (7.60), plaque index (2.8929), and periodontal probing depth (5.8500 mm) values, as well as lower papillary bleeding index (2.1170) and gingival index (2.1085) values. The concentrations of IL-35 in GCF varied among the groups, with Group III having the lowest concentrations and rising gradually to Groups II and I. In addition, from baseline to 3 months, the IL-35 levels in GCF significantly decreased in both Groups II and III. The results show that Groups II and III have lower GCF levels of IL-35 than Group I, suggesting that IL-35 is a major factor in the development of periodontal diseases. Conclusion: Group I had considerably greater GCF IL-35 values than Group II and III both before and after NSPT.

Single-Cell and Spatial Transcriptomics Revealing the Role of IDO1 in HPV+ Cervical Cancer Tumor Immune Microenvironment and Its Implications in Radiotherapy and Immunotherapy

Persistent infection of human papillomavirus (HPV) is one major etiology of cervical cancer (CC). By now, anti-PD-1 immunotherapy is approved for advanced CC patients, but the response rate was just about 10-20%, tumor immune microenvironment (TIME) might be one factor that affect the efficacy. The indoleamine 2,3-dioxygenase (IDO), a metabolic immune checkpoint, is recently shown to have a correlation-ship with HPV carcinogenesis in CC, with unknown mechanism. This study, using the single cell transcriptomic single-cell sequencing and spatial transcription sequencing analysis/immunologic technology, aimed to exam the role of IDO1 expression in HPV+ CC TIME and explore the changes after radiotherapy. Newly diagnosed advanced HPV- CC and HPV+ CC patients were tested for the tumor and tumor immune microenvironment (TIME) heterogeneity and their changes after fractionated radiation therapy. Tumor tissues were collected, single cell suspension was made for Single-cell RNA sequencing (SCRNAseq) using the 10 × Genomics, while frozen tissue was embedded for spatial transcriptome sequencing (STRNAseq). Seurat 4.0 was used to cluster and annotate cell clusters and map SCRNAseq data to the STRNAseq data. The specific characters of cell clusters were computed by Gene Set Enrichment Analysis (GSEA). SPOTLight and CellChat were used to analyze cell location and interaction respectively. A total of 28631 cells were clustered into 31 cell subsets in HPV- CC and HPV+ CC tissues, including baseline (Pre HPV- CC and Pre HPV+ CC) and 3-week after radiotherapy (Post 3w HPV- CC and Post 3w HPV+CC). There were 10431 epithelial cells (Epi) in all these 4 tumor tissues, with heterogenous IDO1 expression, including IDO1-high Epi, IDO1-low Epi, and IDO1-neg Epi. Interestingly, more than 99% of Epi in Pre HPV- CC tissues were IDO1-neg cells, while more than 99% in Pre HPV+ CC tissue were IDO1-high. Furthermore, the proportion of IDO1-high Epi in Pre HPV+ CC patient dropped to 16.7% after radiotherapy, while the proportion of IDO1-low Epi rase to 63.3%. Using GSEA, the characters of IDO1-high Epi group was shown to have positive regulation of leukocyte chemotaxis and negative regulation of cell adhesion and differentiation. IDO1-high Epi cells also had the hallmark of interferon gamma response. These cells could mainly receive regulative information of interferon gamma pathway from exhausted CD8 T cells, which could affect the apoptosis of tumor cells. This study comprehensively analyzed the immune suppressive role of IDO1-high Epi cells in HPV+ CC TIME at the single-cell transcriptional scale and explored their functional characters in CC radiotherapy. This would be able to provide more evidence to combine with radiotherapy and immunotherapy to improve patients' prognosis.

Establishment of nucleic acid sensing pathways-based model in predicting response to immunotherapy and targeted drug in hepatitis virus-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) accounts for 80% of liver cancers, while 70%-80% of HCC developed from chronic liver disease with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection as the major etiology. Immunotherapy is assuming a role as a pillar of HCC treatment, but the remarkable immune-mediated responses are restricted in a minority of patients. Nucleic acid sensing (NAS) pathways are the central pathway of the innate immune system and antiviral immune response to viral infection, but their role in hepatitis virus-related HCC remains undetermined. In our study, we performed a comprehensive bioinformatics analysis based on transcriptomic data of hepatitis virus related-HCCtissues collected from multiple public data sets. Two subgroups were validated based on NAS-relatedgenes in virus-related HCC patients, which were defined as NAS-activatedsubgroups and NAS-suppressed subgroups based on the expression of NAS-related genes. On this basis, a NAS-related risk score (NASRS) predictive model was established for risk stratification and prognosis prediction in the hepatitis virus-related HCC (TCGA-LIHCand ICGC cohorts). The predictive values of the NASRS in prognosis and immunotherapy were also verified in multiple data sets. A nomogram was also established to facilitate the clinical use of NASRS and demonstrate its effectiveness through different approaches. Additionally, six potential drugs binding to the core target of the NAS signature were predicted via molecular docking strategy. We subsequently evaluated the cytotoxic capabilities of potential drug in vitro and in vivo. Based on these results, we conclude that the NASRS model could serve as a power prognostic biomarker and predict responses to immunotherapy, which is meaningful in clinical decision-making of hepatitis virus-related HCC patients.

A Study on Vitamin B12 Levels in Hypothyroid Patients Presenting to a Tertiary Care Teaching Hospital.

Background and aims The prevalence of vitamin B12 deficiency is found to coexist in hypothyroid patients, causing the persistence of symptoms concomitant to both diseases even on adequate thyroxine supplementation. Primary objective To study vitamin B12 levels in patients with hypothyroidism. Secondary objective To study the clinical profile of patients with hypothyroidism with special reference to anemia, and to study the association between vitamin B12 deficiency with anti-thyroid peroxidase (anti-TPO) antibodies and anti-thyroglobulin (anti-Tg) antibodies in patients with hypothyroidism. Methods and results A single-centriccross-sectional study was carried out over a period of one year. Among 100 hypothyroid patients, 68% were found to be vitamin B12 deficient, among whom 73.5% were females. Of patients with raised anti-TPO antibodies,78.6% had vitamin B12 deficiency (p = 0.01), while 78% of patients with raised anti-Tg antibodies were vitamin B12 deficient (p = 0.07). The Pearson correlation coefficient (r) of vitamin B12 with anti-TPO and anti-Tg antibodies was -0.302 (p = 0.002) and -0.253 (p = 0.011), respectively. Conclusion There is a predilection of hypothyroid patients towarddeveloping anemia, with vitamin B12 deficiency as a major etiology. This finding can be correlated with the hematopoietic action of thyroid-stimulating hormones as well as autoimmune thyroid disease predisposing to pernicious anemia.

Superficial Venous Aneurysm (SVA): A Review of Literature and Report of 17 Cases

Background: Superficial Venous Aneurysm (SVA) are rare venous diseases that may be asymptomatic or symptomatic. The major etiology of SVA is still unknown. The study presents 17 cases with no underlying disease or risk factors that presented SVA in uncommon and different veins of the body.
 Methods: 17 patients with SVA were evaluated and treated in our hospital for 11 years. Clinical presentation, treatment, and complications were evaluated.
 Results: 6 of the aneurysms were located in the great saphenous vein, 2 in the small saphenous vein, 6 in the external jugular vein, 1 in the dorsal foot vein, and also 2 in the forearm veins. Ten patients suffered from acute tenderness, pain, and edema of the limb and others presented with soft tissue mass. All 17 patients underwent surgical excisional therapy. No pulmonary emboli were reported in the patients.
 Conclusion: The etiology of SVA is unknown. It may cause occlusion in rare superficial veins in patients with no history of the hyper-coagulopathy state or any major risk factor.

E55 Macrophagic activation syndrome in pediatric rheumatology: about 12 cases

Abstract Introduction Macrophage activation syndrome (MAS) is a serious clinical condition due to inappropriate stimulation of macrophages. It can be primary or secondary to underlying neoplastic, infectious or autoimmune diseases. Some pediatric inflammatory diseases are highly complicated by MAS with a higher incidence in systemic juvenile idiopathic arthritis (SJIA) or systemic lupus erythematosus (SLE). Objective We aim to highlight the features of MAS occurring in the context of pediatric inflammatory diseases according to our epidemiology and local conditions. Materials and methods This is a retrospective, descriptive and analytical study seen over a period of 4 years (from January 2019 to December 2022). The diagnosis of MAS was confirmed according to Ravelli criteria published in 2016 in the presence of mandatory persistent fever and at least four of the following abnormalities: hyperferritinemia> 684 ng/ml, platelet count < 181x103/mm3, liver cytolysis aspartate amino transferase (AST) > 48UI/l, triglyceridemia > 1.56 g/l, fibrinogenemia < 3.6 g/l, after having ruling out infections. The presence of hemophagocytes in the bone marrow aspiration was considered sufficient for the diagnosis in presence of long lasting fever. Results Among 70 patients followed for inflammatory disease, 12 presented with MAS. The age of the patients ranged from 8 months to 17 years during the MAS episode, with a mean age of 8 years 9 months and male: female ratio was 1.4 (7 boys/5 girls). All patients had fever and altered general condition, two had associated hemorrhagic syndrome. On clinical examination, 3 patients had splenomegaly, 3 had hepatomegaly, 2 of which combined splenomegaly and hepatomegaly. Adenopathies were reported in 3 patients. No patient had jaundice or neurological signs. Biological parameters revealed a platelet count< 181 000/mm3 in 58.3% (7 cases), an AST level > 48IU/l in 91,6% (11 cases), hypertriglyceridemia > 156mg/l in 69.2% (9 cases), hypofibrinogenemia < 360 mg/dl in 66.6% (8 cases), and hyperferritinemia >684 ng/ml in 91,6% (11 cases). Eight had bone marrow aspiration, which was inflammatory in 37.5%, normal in 37.5% and hemophagocytosis in 25%. In our series, MAS preceeded the diagnosis of paediatric inflammatory disease in 9 patients, and complicating the evolution of an inflammatory disease in 3 patients. The main aetiology was SLE in 58.3% (7 cases). Other causes were reported such as SJIA in 1, NLRC 4 deficiency without genetic confirmation in 1, PIMS in 1, primary immune deficiency with hypogammaglobulinemia and sarcoidosis like picture in 1 and one case of primary MAS. Recurrence was noted in 3 patients, including 1 SLE, 1 primary MAS and the NLRC 4 deficiency. All patients received bolus intravenous corticosteroids, followed by oral corticosteroids which was weaned off over a period of four months if no disease progression. Ciclosporin A was added to corticosteroids in 4 (33,3%). Biotherapy was administered to 2 patients, the first with NLRC4 deficiency, who received Tocilizumab and infliximab before responding favorably to anakinra 10 mg/kg/d. The second for a PIMS complicated by severe MAS, who received Tocilizumab once without any improvement before switching to anakinra 2 mg/kg/day for 4 months with complete remission. Conclusion and Discussion MAS is a severe syndrome, characterized by non-specific clinical and biological signs, making the diagnosis very difficult. Recently, clinical and biological criteria have been proposed according to the disease, however, the most discriminating biological parameter is hyperferritinemia. This condition must be detected and treated without delay to avoid death. Our series is characterized by the predominance of SLE as the major aetiology of MAS, by its inaugural presentation worsening the prognosis of the underlying inflammatory disease probably related to a delay in consultation, by the low percentage of hemophagocytes in bone marrow aspiration, which could be explained by a lack of knowledge on the part of our cytologists and by a low use of biotherapies.

Pediatric Spine Tumors and Dysontogenetic Masses.

The pediatric spine undergoes complex stages of development and growth, resulting in highly age-dependent physiology and variable susceptibility to certain pathologies. Optimal radiologic evaluation requires image acquisition tailored to the clinical history and an interpretive approach that accounts for demographic variations. In this article, the author discusses the diagnostic approach to pediatric spine masses, beginning with a discussion of normal anatomy and variants, clinical evaluation, and imaging techniques and protocols. The author then covers the major etiologies, imaging appearances, and mimics of pediatric spine masses in the following categories: congenital malformations, genetic syndromes, intramedullary, intradural, epidural, bone, and paraspinal lesions.

Diversity of Streptococcus spp. and genomic characteristics of Streptococcus uberis isolated from clinical mastitis of cattle in Bangladesh.

Streptococci are the major etiology in mastitis in dairy cattle, a cause of huge economic losses in the dairy industries. This study was aimed to determine the diversity of Streptococcus spp. isolated from clinical mastitis of cattle reared in Bangladesh. A total of 843 lactating cattle reared in four prominent dairy farms and one dairy community were purposively included in this study where 80 cattle were positive to clinical mastitis (CM) based on gross changes in the udder (redness, swelling, and sensitive udder) and/or milk (flakes and/or clots). Milk samples were collected from all the eighty cattle with clinical mastitis (CCM) and twenty five apparently healthy cattle (AHC). Samples were enriched in Luria Bertani broth (LB) and one hundred microliter of the enrichment culture was spread onto selective media for the isolation of Staphylococcus spp., Streptococcus spp., Enterococcus spp., Escherichia coli and Corynebacterium spp., the major pathogen associated with mastitis. Isolates recovered from culture were further confirmed by species specific PCR. Out of 105 samples examined 56.2% (59/105), 17.14% (18/105), 9.52% (10/105) and 22.9% (24/105) samples were positive for Staphylococcus, Streptococcus, Enterococcus faecalis and E. coli, respectively. This study was then directed to the determination of diversity of Streptococcus spp. through the sequencing of 16S rRNA. A total of eighteen of the samples from CCM (22.5%) but none from the AHC were positive for Streptococcus spp. by cultural and molecular examination. Sequencing and phylogenetic analysis of 16S rRNA identified 55.6, 33.3, 5.6 and 5.6% of the Streptococcus isolates as Streptococcus uberis, Streptococcus agalactiae, Streptococcus hyovaginalis and Streptococcus urinalis, respectively. Considering the high prevalence and worldwide increasing trend of S. uberis in mastitis, in-depth molecular characterization of S. uberis was performed through whole genome sequencing. Five of the S. uberis strain isolated in this study were subjected to WGS and on analysis two novel ST types of S. uberis were identified, indicating the presence of at least two different genotypes of S. uberis in the study areas. On virulence profiling, all the isolates harbored at least 35 virulence and putative virulence genes probably associated with intramammary infection (IMI) indicating all the S. uberis isolated in this study are potential mastitis pathogen. Overall findings suggest that Streptococcus encountered in bovine mastitis is diverse and S. uberis might be predominantly associated with CM in the study areas. The S. uberis genome carries an array of putative virulence factors that need to be investigated genotypically and phenotypically to identify a specific trait governing the virulence and fitness of this bacterium. Moreover, the genomic information could be used for the development of new genomic tools for virulence gene profiling of S. uberis.

Cytopathologie du liquide céphalorachidien (LCR) ou liquide cérébrospinal (LCS)

AbstractCytology of cerebrospinal fluid (CSF) is an important tool in the diagnosis of Central Nervous System pathologies. In this review, the major etiologies will be discussed, such as neurodegeneratives diseases, infectious and inflam- maroty diseases and tumoral diseases. Cytology remains the reference in the diagnosis of meningeal dissemination of tumor cells. Less invasive and allowing a fast diagnosis with rapid introduction of drugs, it has proven its relevance in routine practice. Its interpretation often requires comparison with clinical and other biological data.

A systematic study on the treatment of hepatitis B-related hepatocellular carcinoma with drugs based on bioinformatics and key target reverse network pharmacology and experimental verification

BackgroundChronic hepatitis B virus (HBV) infection is the major etiology of hepatocellular carcinoma (HCC). However, the mechanism of hepatitis B-related hepatocellular carcinoma (HBV-related HCC) is still unclear. Therefore, understanding the pathogenesis and searching for drugs to treat HBV-related HCC was an effective strategy to treat this disease.PurposeBioinformatics was used to predict the potential targets of HBV-related HCC. The reverse network pharmacology of key targets was used to analyze the clinical drugs, traditional Chinese medicine (TCM) and small molecules of TCM in the treatment of HBV-related HCC.MethodsIn this study, three microarray datasets totally containing 330 tumoral samples and 297 normal samples were selected from the GEO database. These microarray datasets were used to screen DEGs. And the expression profile and survival of 6 key genes were analyzed. In addition, Comparative Toxicogenomics Database and Coremine Medical database were used to enrich clinical drugs and TCM of HBV-related HCC by the 6 key targets. Then the obtained TCM were classified based on the Chinese Pharmacopoeia. Among these top 6 key genes, CDK1 and CCNB1 had the most connection nodes and the highest degree and were the most significantly expressed. In general, CDK1 and CCNB1 tend to form a complex, which is conducive to cell mitosis. Hence, this study mainly studied CDK1 and CCNB1. HERB database was used to predict small molecules TCM. The inhibition effect of quercetin, celastrol and cantharidin on HepG2.2.15 cells and Hep3B cells was verified by CCK8 experiment. The effects of quercetin, celastrol and cantharidin on CDK1 and CCNB1 of HepG2.2.15 cells and Hep3B cells were determined by Western Blot.ResultsIn short, 272 DEGs (53 upregulated and 219 downregulated) were identified. Among these DEGs, 6 key genes with high degree were identified, which were AURKA, BIRC5, CCNB1, CDK1, CDKN3 and TYMS. Kaplan–Meier plotter analysis showed that higher expression levels of AURKA, BIRC5, CCNB1, CDK1, CDKN3 and TYMS were associated with poor OS. According to the first 6 key targets, a variety of drugs and TCM were identified. These results showed that clinical drugs included targeted drugs, such as sorafenib, palbociclib and Dasatinib. and chemotherapy drugs, such as cisplatin and doxorubicin. TCM, such as the TCM flavor was mainly warm and bitter, and the main meridians were liver and lung. Small molecules of TCM included flavonoids, terpenoids, alkaloids and glycosides, such as quercetin, celastrol, cantharidin, hesperidin, silymarin, casticin, berberine and ursolic acid, which have great potential in anti-HBV-related HCC. For molecular docking of chemical components, the molecules with higher scores were flavonoids, alkaloids, etc. Three representative types of TCM small molecules were verified respectively, and it was found that quercetin, celastrol and cantharidin inhibited the proliferation of HepG2.2.15 cells and Hep3B cells along concentration gradient. Quercetin, celastrol and cantharidin decreased CDK1 expression in HepG2.2.15 and Hep3B cells, but for CCNB1, only cantharidin decreased CCNB1 expression in the two strains of cells.ConclusionIn conclusion, AURKA, BIRC5, CCNB1, CDK1, CDKN3 and TYMS could be potential targets for the diagnosis and prognosis of HBV-related HCC. Clinical drugs include chemotherapeutic and targeted drug, traditional Chinese medicine is mainly bitter and warm TCM. Small molecular of TCM including flavonoids, terpenoids and glycosides and alkaloids, which have great potential in anti-HBV-related HCC. This study provides potential therapeutic targets and novel strategies for the treatment of HBV-related HCC.

CLINICAL PROFILE OF ASCTES BASED ON PRESENTATION AND LABORATORY FINDINGS:AN INSTITUTIONAL EXPERIENCE FROM MAHARASHTRA,INDIA

Introduction: Ascites is the fluid collection in the potential space of the peritoneal cavity. Alcoholic liver disease and intra-abdominal malignancy are two major etiologies behind it. Also, diagnosis of tuberculous ascites should be thought of due to endemicity. Cirrhotic patients at any time during the course of disease, invariably present with ascites which is one of the marker of decompensation. In our context, etiology behind ascites and its correlation with symptoms and clinical findings not yet studied, so present study is conceptualised. Aim: To study clinical profile of ascites based on presentation and laboratory findings Methods: This is a cross-sectional retrospective descriptive hospital based record review of patients presented with ascites in a tertiary center of Maharashtra . One hundred fourteen patients with ascites under regular follow up of SMBT Hospital were reviewed. Data regarding presenting complaints, examination findings, relevant investigations during first visit and final diagnosis were retrieved from our own record keeping and recorded information were then evaluated. Results: Patients having ascites have myriad of symptoms and signs, commonest clinical feature being icterus (74, 64.9%). Most of them were anemic at presentation. Forty-two (36.8%) had high blood urea and 36 (31.5%) with high creatinine suggesting approximately 30-40% cases presented with deranged renal function test. Ninety-three (81.5%) had raised total serum bilirubin. Similarly, PT/INR derangements were in 74 (64.9%) and 57 (50%) suggesting deranged liver function. Serum albumin was less than 3.5 gram/decilitre in 83(72.8%) cases. Among the patients studied, 80 (70.1%) had high Serum-Ascites Albumin Gradient (SAAG) suggesting transudative type of ascites and rest 34 had low SAAG suggesting exudative type of ascites. Overall assessment revealed, majority of patients (71.05%) had Chronic liver disease (CLD) as the cause of ascites. Conclusions: Ascites due to chronic liver disease was the main finding with etiology supported by laboratory findings. Significant numbers of the patients had deranged renal function on top of liver function derangement, so these parameters need to be properly taken care of.

Profil Klinis dan Kesintasan Pasien Karsinoma Sel Hati di Rumah Sakit Rujukan Tersier Indonesia Tahun 2015-2021

Introduction. Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world and Indonesia. This study aimed to describe the clinical presentation and survival rate of HCC patients in Dr. Cipto Mangunkusumo Hospital (RSCM) as the Indonesian tertiary referral hospital in year 2015-2021 Methods. Cohort study was performed in year 2015-2021. Clinical presentations at the time of diagnosis were recorded from electronical health record. All HCC patients were followed up until death. One-year survival based on staging was assessed using log rank test and presented with Kaplan Meier curve. Results. A total of 799 HCC patients were included. Majority of HCC patients were male, 619 patients (77.5%), and aged 55 (SD 11.9) years. Hepatitis B was the major etiology, found in 500 patients (62.6%). Median of alfa feto-protein (AFP) was 1,109 (0.8-3,462,499) ng/ml. At the time of diagnosis, Barcelona Clinic Liver Cancer (BCLC) stage C (37.7%) was the most commonly found. Portal vein thrombosis was found in 205 patients (25.7%). There were 271 (33.9%) HCC patients received curative and palliative treatment, and others had supportive care. One year survival rate of HCC was 61.2%. One year survival rate of HCC based on staging for BCLC A, BCLC B, BCLC C, and BCLC D were 91.1%, 68.6%, 47.6%, and 13.3%, respectively (log-rank test: p<0.001). Conclusion. The majority of patients diagnosed with HCC were at an advanced stage so that the one-year survival is poor.

The trends in death of primary liver cancer caused by specific etiologies worldwide: results from the Global Burden of Disease Study 2019 and implications for liver cancer management

BackgroundOver past decades, epidemiological patterns of liver cancer (LC) have changed dramatically. The Global Burden of Disease (GBD) study provides an opportunity for tracking the progress in cancer control with its annual updated reports at national, regional and global level, which can facilitate the health decision-making and the allocation of health resources. Therefore, we aim to estimate the global, regional and national trends of death caused by liver cancer due to specific etiologies and attributable risks from 1990 to 2019.Materials and methodsData was collected from the GBD study 2019. Estimated annual percentage changes (EAPC) were used to quantify the trends of age-standardized death rate (ASDR). We applied a linear regression for the calculation of estimated annual percentage change in ASDR.ResultsFrom 1990 to 2019, the ASDR of liver cancer decreased globally (EAPC = − 2.23, 95% confidence interval [CI]: − 2.61 to − 1.84). Meanwhile, declining trends were observed in both sexes, socio-demographic index (SDI) areas, and geographies, particularly East Asia (EAPC = − 4.98, 95% CI: − 5.73 to − 4.22). The ASDR for each of the four major etiologies fell globally, while liver cancer caused by hepatitis B had the largest drop (EPAC = − 3.46, 95% CI: − 4.01 to − 2.89). China has had dramatic decreases in death rates on a national scale, particularly when it comes to the hepatitis B etiology (EAPC = − 5.17, 95% CI: − 5.96 to − 4.37). However, certain nations, such as Armenia and Uzbekistan, saw a rise in liver cancer mortality. Controlling smoking, alcohol, and drug use contributed to a drop in LC-related mortality in the majority of socio-demographic index areas. Nevertheless, the excessive body mass index (BMI) was portrayed as the underlying cause for LC fatalities.ConclusionFrom 1990 to 2019, there was a worldwide decrease in deaths caused by liver cancer and its underlying causes. However, rising tendencies have been observed in low-resource regions and countries. The trends in drug use- and high BMI-related death from liver cancer and its underlying etiologies were concerning. The findings indicated that efforts should be increased to prevent liver cancer deaths through improved etiology control and risk management.

The etiology and mortality of altered level of consciousness in the emergency room: before and after coronavirus disease

Background: Coronavirus disease 2019 (COVID-19) has resulted in social, economic, medical, and psychological changes. New-onset altered level of consciousness (ALC) is a classical presentation in real-world medicine. This study investigated changes in ALC in the emergency room (ER) in the periods before (BC) and after (AC) COVID-19.Methods: This was a retrospective study of patients with ALCs who visited the ER of a tertiary referral center, and their medical records BC and AC were compared. A consortium allocated and analyzed the etiologies of ALC in a case-by-case discussion. The time point for etiological assessment was the time of discharge from the ER.Results: In total, 1,936 patients with ALCs (731 and 1,205 in BC and AC, respectively) were investigated. The most common etiology was systemic infection (25.9%), followed by metabolic causes (20.8%). Systemic infections (22.9% vs. 30.8%, P<0.001) and stroke (14.6% vs. 18.2%, P=0.037) were lower in AC than in BC, respectively, whereas rates of toxicity (15.4% vs. 6.0%, P<0.001) and traumatic brain injury (TBI; 5.9% vs. 0.8%, P<0.001) were higher in AC than in BC. The overall mortality rate of ALC in the ER was 18.5%.Conclusion: This study demonstrated that the major etiologies of ALC in the ER were extra-cranial (58.5%). The mortality of ALC in the ER and the incidence of toxic cause and TBI increased in AC, suggesting a change in medical circumstances after the Pandemic.

Genetically programmed retinoic acid deficiency during gastrulation phenocopies most known developmental defects due to acute prenatal alcohol exposure in FASD.

Fetal Alcohol Spectrum Disorder (FASD) arises from maternal consumption of alcohol during pregnancy affecting 2%-5% of the Western population. In Xenopus laevis studies, we showed that alcohol exposure during early gastrulation reduces retinoic acid (RA) levels at this critical embryonic stage inducing craniofacial malformations associated with Fetal Alcohol Syndrome. A genetic mouse model that induces a transient RA deficiency in the node during gastrulation is described. These mice recapitulate the phenotypes characteristic of prenatal alcohol exposure (PAE) suggesting a molecular etiology for the craniofacial malformations seen in children with FASD. Gsc +/Cyp26A1 mouse embryos have a reduced RA domain and expression in the developing frontonasal prominence region and delayed HoxA1 and HoxB1 expression at E8.5. These embryos also show aberrant neurofilament expression during cranial nerve formation at E10.5 and have significant FASD sentinel-like craniofacial phenotypes at E18.5. Gsc +/Cyp26A1 mice develop severe maxillary malocclusions in adulthood. Phenocopying the PAE-induced developmental malformations with a genetic model inducing RA deficiency during early gastrulation strongly supports the alcohol/vitamin A competition model as a major molecular etiology for the neurodevelopmental defects and craniofacial malformations seen in children with FASD.

Neonatal Intraventricular Hemorrhage Presenting as Pyrexia of Newborn: A Case Report

Abstract: 
 Background Temperature instability is a relatively common presenting symptom in a Neonatal Intensive Care Unit (NICU) with sepsis being one of the major etiologies that need to be ruled out. However, an important differential diagnosis is a central fever. Many cases of Intracranial Hemorrhage/Intraventricular Hemorrhage (ICH/IVH) present with temperature dysregulation with no other clear associated symptoms, and cranial imaging for early identification and treatment of ICH/IVH is crucial. 
 Case report A 3-day-old male born at 33 weeks and four days of gestation who was admitted to the neonatal critical care unit due to prematurity and respiratory distress was noted to be febrile during the fourth hospital day. The septic screen was negative, and the patient continued to spike fever while on broad-spectrum antimicrobial treatment. Due to an unexplained drop in his hematocrit, cranial ultrasound was done, and grade III IVH was identified. The patient continued to improve clinically, but the exact etiology of his IVH was not identified. His fever resolved without interventions, and his IVH continued to decrease in size. Serial cranial imaging was done in NICU, and no neurosurgical interventions were warranted. He was referred to neurosurgery and neurology and followed in the infant’s high-risk clinic. 
 Discussion Sepsis is the top of differentials when managing a newborn infant in NICU. However, we must always keep our minds open to other differentials, including central hyperthermia. Extreme prematurity is a major risk factor for ICH/IVH in the neonatal period; nonetheless, other risk factors are identified, and many cases of ICH/IVH had no identified causative factor or even risk factors. 
 Conclusion Identifying clinical presentation and risk factors associated with ICH and IVH in NICU patients is crucial for early diagnosis and offers appropriate management. A high index of suspicion is required to promptly diagnose ICH/IVH resulting in central fever and avoid unnecessary workup and treatment.

Machine learning-based identification of cuproptosis-related markers and immune infiltration in severe community-acquired pneumonia.

Severe community-acquired pneumonia (SCAP) is one of the world's most common diseases and a major etiology of acute respiratory distress syndrome (ARDS). Cuproptosis is a novel form of regulated cell death that can occur in various diseases. Our study explored the degree of immune cell infiltration during the onset of severe CAP and identified potential biomarkers related to cuproptosis. Gene expression matrix was obtained from GEO database indexed GSE196399. Three machine learning algorithms were applied: The least absolute shrinkage and selection operator (LASSO), the random forest, and the support vector machine-recursive feature elimination (SVM-RFE). Immune cell infiltration was quantified by single-sample gene set enrichment analysis (ssGSEA) scoring. Nomogram was constructed to verify the applicability of using cuproptosis-related genes to predict the onset of severe CAP and its deterioration toward ARDS. Nine cuproptosis-related genes were differentially expressed between the severe CAP group and the control group: ATP7B, DBT, DLAT, DLD, FDX1, GCSH, LIAS, LIPT1, and SLC31A1. All 13 cuproptosis-related genes were involved in immune cell infiltration. A three-gene diagnostic model was constructed to predict the onset of severe CAP: GCSH, DLD, and LIPT1. Our study confirmed the involvement of the newly discovered cuproptosis-related genes in the progression of SCAP.

Evaluation and Diagnosis of Acute Chest Pain

Acute chest pain is a frequent cause of visits to emergency departments. As the major etiologies of such pain include life-threatening acute myocardial infarction, aortic dissection, and pulmonary embolism, prompt diagnosis and management are essential. After exclusion of coronary artery disease, other cardiac causes must be considered. In this review, we discuss the diagnosis of acute chest pain with a focus on clinical symptoms and the initial examination.