Group Of Diseases Research Articles

An Update on Parkinson's Disease and its Neurodegenerative Counterparts.

Neurodegenerative disorders are a group of diseases that cause nerve cell degeneration in the brain, resulting in a variety of symptoms and are not treatable with drugs. Parkinson's disease (PD), prion disease, motor neuron disease (MND), Huntington's disease (HD), spinal cerebral dyskinesia (SCA), spinal muscle atrophy (SMA), multiple system atrophy, Alzheimer's disease (AD), spinocerebellar ataxia (SCA) (ALS), pantothenate kinase-related neurodegeneration, and TDP-43 protein disorder are examples of neurodegenerative diseases. Dementia is caused by the loss of brain and spinal cord nerve cells in neurodegenerative diseases. Even though environmental and genetic predispositions have also been involved in the process, redox metal abuse plays a crucial role in neurodegeneration since the preponderance of symptoms originates from abnormal metal metabolism. Hence, this review investigates several neurodegenerative diseases that may occur symptoms similar to Parkinson's disease to understand the differences and similarities between Parkinson's disease and other neurodegenerative disorders based on reviewing previously published papers. Based on the findings, the aggregation of alpha-synuclein occurs in Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies. Other neurodegenerative diseases occur with different protein aggregation or mutations. We can conclude that Parkinson's disease, Multiple system atrophy, and Dementia with Lewy bodies are closely related. Therefore, researchers must distinguish among the three diseases to avoid misdiagnosis of Multiple System Atrophy and Dementia with Lewy bodies with Parkinson's disease symptoms.

CK1δ/ε kinases regulate TDP-43 phosphorylation and are therapeutic targets for ALS-related TDP-43 hyperphosphorylation

Hyperphosphorylated TAR DNA-binding protein 43 (TDP-43) aggregates in the cytoplasm of neurons is the neuropathological hallmark of amyotrophic lateral sclerosis (ALS) and a group of neurodegenerative diseases collectively referred to as TDP-43 proteinopathies that includes frontotemporal dementia, Alzheimer's disease, and limbic onset age-related TDP-43 encephalopathy. The mechanism of TDP-43 phosphorylation is poorly understood. Previously we reported casein kinase 1 epsilon gene (CSNK1E gene encoding CK1ε protein) as being tightly correlated with phosphorylated TDP-43 (pTDP-43) pathology. Here we pursued studies to investigate in cellular models and in vitro how CK1ε and CK1δ (a closely related family sub-member) mediate TDP-43 phosphorylation in disease. We first validated the binding interaction between TDP-43 and either CK1δ and CK1ε using kinase activity assays and predictive bioinformatic database. We utilized novel inducible cellular models that generated translocated phosphorylated TDP-43 (pTDP-43) and cytoplasmic aggregation. Reducing CK1 kinase activity with siRNA or small molecule chemical inhibitors resulted in significant reduction of pTDP-43, in both soluble and insoluble protein fractions. We also established CK1δ and CK1ε are the primary kinases that phosphorylate TDP-43 compared to CK2α, CDC7, ERK1/2, p38α/MAPK14, and TTBK1, other identified kinases that have been implicated in TDP-43 phosphorylation. Throughout our studies, we were careful to examine both the soluble and insoluble TDP-43 protein fractions, the critical protein fractions related to protein aggregation diseases. These results identify CK1s as critical kinases involved in TDP-43 hyperphosphorylation and aggregation in cellular models and in vitro, and in turn are potential therapeutic targets by way of CK1δ/ε inhibitors.

Frequency of Hematologic and Nonhematologic Conditions in Pediatric Patients with Vascular Anomalies: A Pediatric Health Information System Database Study

Background: Vascular anomalies (VA) are a heterogeneous group of diseases which include vascular malformations and vascular tumors. In the pediatric population, there is a sparsity of data on the frequency of associated hematologic and nonhematologic conditions as well as overall outcomes for patients. Objectives: The objective of this study was to determine the rate of certain concurrent hematologic and nonhematologic conditions in patients with VA who underwent procedures and compare those to patients who did not undergo procedures. To examine the rates of intensive care unit admissions and discharge mortality in patients who had a vascular anomaly. Methods: This is a multicenter retrospective cohort study using data from the Pediatric Health Information System. The database was queried for children 0–18 years old with a diagnosis of a VA who had inpatient encounters between January 2016 and September 2021. Results: The most common hematologic conditions were thrombocytopenia, iron deficiency anemia, and venous thrombosis. The most common nonhematologic condition was electrolyte imbalances. Intensive care unit admissions were highest among patients with other congenital malformations of the peripheral vascular system, cerebral cavernous malformations, and sporadic arteriovenous malformations. Discharge mortality was highest in patients with lymphatic malformations and primary lymphedema. Conclusions: This is the largest database study of pediatric patients with VA and their concurrent medical conditions and outcomes to date. While our study could not prove associations, we hope that our results will serve as a foundation for more extensive research regarding the impact of these identified conditions and outcomes and contribute to improved management of patients with VA.

Biological Insights and Radiation–Immuno–Oncology Developments in Primary and Secondary Brain Tumors

Malignant central nervous system (CNS) cancers include a group of heterogeneous dis-eases characterized by a relative resistance to treatments and distinguished as either primary tumors arising in the CNS or secondary tumors that spread from other organs into the brain. Despite therapeutic efforts, they often cause significant mortality and morbidity across all ages. Radiotherapy (RT) remains the main treatment for brain cancers, improving associated symptoms, improving tumor control, and inducing a cure in some. However, the ultimate goal of cancer treatment, to improve a patient’s survival, remains elusive for many CNS cancers, especially primary tumors. Over the years, there have thus been many preclinical studies and clinical trials designed to identify and overcome mechanisms of resistance to improve outcomes after RT and other therapies. For example, immunotherapy delivered concurrent with RT, especially hypo-fractionated stereotactic RT, is synergistic and has revolutionized the clinical management and outcome of some brain tumors, in particular brain metastases (secondary brain tumors). However, its impact on gliomas, the most common primary malignant CNS tumors, remains limited. In this review, we provide an overview of radioresistance mechanisms, the emerging strategies to overcome radioresistance, the role of the tumor microenviroment (TME), and the selection of the most significant results of radiation–immuno–oncological investigations. We also identify novel therapeutic opportunities in primary and secondary brain tumors with the purpose of elucidating current knowledge and stimulating further research to improve tumor control and patients’ survival.

HdWGCNA and Cellular Communication Identify Active NK Cell Subtypes in Alzheimer's Disease and Screen for Diagnostic Markers through Machine Learning.

Alzheimer's disease (AD) is a recognized complex and severe neurodegenerative disorder, presenting a significant challenge to global health. Its hallmark pathological features include the deposition of β-amyloid plaques and the formation of neurofibrillary tangles. Given this context, it becomes imperative to develop an early and accurate biomarker model for AD diagnosis, employing machine learning and bioinformatics analysis. In this study, single-cell data analysis was employed to identify cellular subtypes that exhibited significant differences between the diseased and control groups. Following the identification of NK cells, hdWGCNA analysis and cellular communication analysis were conducted to pinpoint NK cell subset with the most robust communication effects. Subsequently, three machine learning algorithms-LASSO, Random Forest, and SVM-RFE-were employed to jointly screen for NK cell subset modular genes highly associated with AD. A logistic regression diagnostic model was then designed based on these characterized genes. Additionally, a protein-protein interaction (PPI) networks of model genes was established. Furthermore, unsupervised cluster analysis was conducted to classify AD subtypes based on the model genes, followed by the analysis of immune infiltration in the different subtypes. Finally, Spearman correlation coefficient analysis was utilized to explore the correlation between model genes and immune cells, as well as inflammatory factors. We have successfully identified three genes (RPLP2, RPSA, and RPL18A) that exhibit a high association with AD. The nomogram based on these genes provides practical assistance in diagnosing and predicting patients' outcomes. The interconnected genes screened through PPI are intricately linked to ribosome metabolism and the COVID-19 pathway. Utilizing the expression of modular genes, unsupervised cluster analysis unveiled three distinct AD subtypes. Particularly noteworthy is subtype C3, characterized by high expression, which correlates with immune cell infiltration and elevated levels of inflammatory factors. Hence, it can be inferred that the establishment of an immune environment in AD patients is closely intertwined with the heightened expression of model genes. This study has not only established a valuable diagnostic model for AD patients but has also delved deeply into the pivotal role of model genes in shaping the immune environment of individuals with AD. These findings offer crucial insights into early AD diagnosis and patient management strategies.

Safety and Efficacy of CT041 in Patients With Refractory Metastatic Pancreatic Cancer: A Pooled Analysis of Two Early-Phase Trials.

CT041 is a chimeric antigen receptor (CAR)-modified T-cell therapy that specifically targets claudin18.2 in solid tumors. Here, we report the pooled analysis results of two exploratory clinical trials to evaluate CT041 in patients with previously treated pancreatic cancer (PC). These two multicenter, open-label phase I/Ib trials (CT041-CG4006, CT041-ST-01) have a similar target population and evaluation schedule. The primary objective was to assess the safety and tolerability of CT041, whereas secondary objectives included efficacy, pharmacokinetics, and immunogenicity. The combined cohort comprised 24 patients with advanced PC. Among them, five patients (20.8%) had previously received one line of therapy, whereas 19 (79.2%) received ≥2 lines of therapy. The most common treatment-emergent adverse events of grade 3 or more were preconditioning-related hematologic toxicities. Cytokine release syndrome (CRS) and GI disorders were most reported grade 1 or 2 adverse events. The overall response rate and disease control rate were 16.7% and 70.8%. The median progression-free survival (mPFS) after infusion was 3.3 months (95% CI, 1.8 to 6.2), and the median overall survival (mOS) was 10.0 months (95% CI, 5.5 to 17.6). The median duration of response (mDoR)was 9.5 months (95% CI, 2.6 to Not reached), with a DoR rate at 12 months of 50% (95% CI, 5.8 to 84.5). The mPFS (6.0 v 1.0 months, P < .001) and mOS (17.6 v 4.0 months, P < .001) were prolonged in patients achieving partial response/stable disease than the progressive disease group. CA19-9 levels had reduced by at least 30% in 17 (70.8%) patients. In patients with metastatic PC after progression on previous therapy, CT041 demonstrated a tolerable safety profile and encouraging anticancer efficacy signals. Response benefit observed here needs to be ascertained in the future.

#1507 Genetics in suspected cases of hereditary kidney diseases

Abstract Background and Aims Hereditary kidney diseases are the fifth cause of chronic kidney disease (CKD). They are responsible for around 10% of adults with kidney replacement therapy. Genetic testing in suspected cases allows us to make a definitive diagnosis, prognosis, therapeutic options and family counselling. Method We present a descriptive study from Hospital Clínic Barcelona (Spain) of all genetic tests performed in suspected cases of hereditary kidney diseases between 2019 and 2023 by using whole exome sequencing. Diseases are classified into these groups: cyst kidney diseases, Alport syndrome spectrum (ASS), complement-related kidney diseases, tubulointerstitial kidney disease (TID), CKD of unknow etiology (CKDUE), podocytopathies, and miscellaneous. All analyses were made with blood samples. Results As of December 31st, genetic test has been made in 198 patients, of which 172 have definitive results (82/172 women). Genetic tests increase over time with 10 (2019), 15 (2020), 36 (2021), 56 (2022) and 81 (2023). The most frequent suspected genetic kidney diseases were cyst-related (n = 57) followed by CKDUE (n = 43), complement-related kidney disease (n = 27), ASS (n = 20), podocytopathies (n = 16) and TID (n = 6). Globally, 104 genetic alterations were detected; 40,7% (70/172) were pathogenic or likely pathogenic (P/LP) variants; and 19,8% (34/172) were variants of uncertain significance (VUS). The highest test performance was observed in the cyst-related group with 70,2% (40/57) followed by ASS with 45% (9/20) and TID with 33,1% (2/6) while the lowest performance groups were CKDUE and complement-related diseases with 25,6% (11/43) and 11,1% (3/27) respectively. The most frequent P/LP variants identified per group were PKD1 (28/40) and PKD2 (12/40) in cyst-related; COL4A4 (5/9) in ASS; CFH, COQ8B and C3 (1/3 each one) in complement-related; UMOD and MUC (1/2 each one) in TID; COL4A4 (2/11) in CKDUE; and TRPC6:1, LMXB1, COL4A3, COL4A5 and COQB8 (1/5 each one) in podocytopathies. The highest genetic heterogeneity was found in CKDUE with 28 genetic variants detected (11 P/LP and 17 VUS). Conclusion Although the comparison between the different groups of diseases is complex, because of the different genetic study indication in each one, as well as their prevalence and the performance of the test, in our cohort the most suspected hereditary kidney diseases in which a genetic test was performed was cyst-related diseases, with the highest P/LP variants found and the highest test performance. However, it is worth noting that more than half of the patients had non-related cystic disease, thus increasing the knowledge and detection of less common genetic kidney diseases. CKDUE is the second group with more P/LP variants and with the highest heterogeneity. It is essential that national health systems provide access to genetic tests to complete the study of CKD of unknow etiology.

#1964 Diagnosis performance of urine oxalate/creatinine ratio for hyperoxaluria screening

Abstract Background and Aims Primary and secondary hyperoxaluria is characterized by significantly elevated urinary oxalate levels, increased risk of kidney stones, nephrocalcinosis, and chronic kidney disease. Patients with enteric hyperoxaluria are especially at high-risk populations. However, identifying hyperoxaluric individuals within these populations remains challenging due to difficulties in obtaining complete urine collections. This study aims to evaluate the diagnostic performance of the urine oxalate/creatinine ratio to improve the screening of hyperoxaluria. Method We pooled data from an adult tertiary renal exploration center, including living donors, short bowel syndrome patients, bariatric surgery patients, and individuals with nephrolithiasis or other nephrological issues undergoing 24-hour urine analysis. We assessed the relationship between the urine oxalate/creatinine ratio and 24-hour oxalate excretion. The diagnostic performance of the ratio was analyzed using ROC curves, and an optimal diagnostic threshold was established. Results Of the 1485 initially included adult patients reported in Table 1, 37% lacked complete urine collections, resulting in a study population of 974 individuals (453 females, 521 males, median age 48 years, median renal function 97 ml/min/1.73 m²). Nineteen percent had hyperoxaluria, with a higher prevalence in females (25% vs. 13% in males). Median 24-hour oxaluria was 548 (432,740) µmol/d in the diseased group and 244 (188,309) µmol/d in the healthy group. A strong correlation (Spearman's rank correlation rho= 0.8, p &amp;lt; 0.001) was found between the urine oxalate/creatinine ratio and 24-hour oxalate excretion. ROC curves for both genders exhibited similar performance, with an optimal threshold for the entire population yielding an AUC of 0.97 (0.962-0.981). The diagnostic threshold for maximum sensitivity was an oxalate/creatinine ratio of 0.025 mmol/mmol (Sensitivity = 1, Specificity = 0.65, PPV = 0.4, NPV = 1), while for maximum specificity, it was an oxalate/creatinine 0.074 mmol/mmol (Sensitivity= 0.31, Specificity = 1, PPV = 1, NPV = 0.862). The optimal diagnostic threshold chosen by the minimum distance from the left-upper corner was an oxalate/creatinine 0.034 mmol/mmol (Sensitivity= 0.92, Specificity = 0.91, PPV = 0.69, NPV = 0.98) (Fig. 1). Conclusion The urine oxalate/creatinine ratio demonstrates excellent diagnostic performance and is efficient in screening hyperoxaluric patients within high-risk populations. However, the positive predictive value is insufficient to be a standalone reliable diagnostic test. Therefore, 24-hour urine oxalate measurement remains necessary for diagnosis.

Myoclonus improvement after seizures in progressive myoclonic epilepsy type 7: a case report

BackgroundProgressive Myoclonic Epilepsy (PME) is a group of rare diseases that are difficult to differentiate from one another based on phenotypical characteristics.Case reportWe report a case of PME type 7 due to a pathogenic variant in KCNC1 with myoclonus improvement after epileptic seizures.DiscussionMyoclonus improvement after seizures may be a clue to the diagnosis of Progressive Myoclonic Epilepsy type 7.

#1999 Retrospective observational study of uremic pruritus prevalence on dialysis

Abstract Background and Aims In Spain, the prevalence of moderate-severe Uremic Pruritus (UP) was 46% and 40% in the DOPPS I and DOPPS. This symptom is usually underdiagnosed and could worsen the quality of life, as some recent studies have revealed. The last reports regarding UP prevalence date back to 2004, hence we decided to assess its current frequency of this while exploring the degree of recognition along with other UP-associated factors. Method This study includes 192 patients in renal replacement therapy (RRT), retrospectively recruited from our centre. Data were collected from revisit medical records in 2021. UP was evaluated using a visual analogic scale (VAS). In addition, age, time on dialysis, UP treatment, haemoglobin, eosinophils, plasma levels of calcium, phosphorus, urea, parathyroid hormone, c-reactive protein (CRP), and clearance (measured by KT/V) were also recorded. Results Average patient age was 61.3 years old, with an average time in dialysis of 37.4 months. The most common group of chronic kidney disease was glomerular diseases (25.5%). The patient distribution by RRT was: 51.9% in haemodialysis (HD), 36.5% in peritoneal dialysis (PD), and 11.6% in home haemodialysis (HHD). UP average prevalence was 56.7% (50% in HHD, 55.2% in HD and 60.9% in PD), of which 69.8% had a VAS ≥ 5. UP was statistically associated with older age (p = 0.017) and higher plasmatic phosphorus (p = 0.015). Notably, only 51.9% UP patients had been prescribed specific drugs for itching. Among UP treated patients, 70.9% improved 3 or more VAS points (with no differences among drugs). Interestingly, this improvement was associated with lower calcium levels (p &amp;lt; 0.0001), the absence of peripheral artery disease (PAD) (p = 0.035), and the shortest time on dialysis (p = 0.001). Conclusion Despite the advances made in HD techniques and the recent incorporation of biocompatible solutions in PD, UP remains a frequent symptom among dialysis patients, without relevant prevalence improvements over the last 20 years. UP was misdiagnosed and mistreated in our unit, since just 51.9% of patients with UP were under treatment. In addition, clinical response to treatment was appropriate in 70.9% of patients, and our results suggest that calcium, PAD, and time on dialysis could predict the response to the treatment. Therefore, our study supports previous data, highlighting UP as a frequent underdiagnosed symptom among dialysis patients; and opens the path for new research in the identification of novel prognosis markers.

Temporomandibular Disorders Management—What’s New? A Scoping Review

Temporomandibular disorders include various conditions that impact the masticatory system, affecting its structure, function, or physiology. Clinicians face a complex array of therapeutic options when treating this group of diseases, emphasizing the importance of evaluating the current evidence to guide decisions in patient care. The main objective of this article is to conduct a scoping review on the available treatment approaches to manage temporomandibular disorders (TMDs). An extensive search of the literature was performed on Scopus, Pubmed, Embase, and Web of Science. Systematic reviews published in the last 5 years were considered. Out of the 2183 publications identified, 109 studies were included in this review. Among them, 39 articles focused on the non-invasive approach, while 120 delved into the minimally invasive approach, and 15 explored the surgical approach. Non-invasive or conservative approaches like cognitive-behavioral therapy, physical therapy, and acupuncture offer effective pain management and functional improvements in TMDs. Emerging treatments offer promising alternatives for treating these disorders. Surgery should be reserved for severe cases, with conservative therapies used in conjunction with invasive procedures for optimal patient outcomes.

Visfatin Related to the Severity of Non-ST-Segment Elevation Acute Coronary Syndrome: A Retrospective Study of 164 Patients at a Tertiary Chest Pain Center

Acute coronary syndrome (ACS) poses a pervasive threat to individuals grappling with cardiovascular afflictions, manifesting as unstable angina, non-ST-segment elevation myocardial infarction (NSTEMI), ST-segment elevation myocardial infarction (STEMI), or sudden cardiac death, depending on vascular obstruction’s extent and location. NSTEMI, closely linked to substantial morbidity and mortality, has become the primary cause of hospitalization in ischemic heart disease patients. Swift prognostication of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is crucial, necessitating the identification of precise markers. This study, conducted from January 2020 to March 2021, explored the correlation between serum visfatin levels and NSTE-ACS severity. A total of 164 patients undergoing coronary angiography were enrolled, with a control group (n = 55) exhibiting less than 50% coronary stenosis. NSTE-ACS patients were categorized based on angiography outcomes into single-vessel (n = 41), double-vessel (n = 28), and multivessel (n = 40) groups. Serum visfatin levels, meticulously quantified, showed significant elevation in NSTE-ACS patients (n = 109) compared to the control group (n = 55) (P&lt;0.01). Visfatin correlated positively with the GRACE score (r = 0.397, P&lt;0.01). In the multivessel disease group, visfatin levels were notably higher (P&lt;0.01). After adjusting for cardiovascular risk factors, visfatin emerged as an independent predictor of affected coronary arteries (OR 0.205; 95% CI 0.032–0.378; P=0.02). Receiver-operating characteristic (ROC) curves demonstrated enhanced prognostic ability when combining visfatin with age, hypertension, and diabetes for multivessel disease (AUC: 0.839, sensitivity: 65.0%, specificity: 89.7%, P&lt;0.001). Elevated serum visfatin in NSTE-ACS patients suggests its role as an independent harbinger for the number of affected coronary arteries, potentially indicating severity in NSTE-ACS patients.

#787 Kidney genetics—a reproducible and curated database of kidney-disease associated genes

Abstract Background and Aims Genetic insights are becoming increasingly influential in the understanding and treatment of various kidney diseases (KD). Hundreds of genes associated with monogenic kidney disease have been identified, providing valuable insights into their diagnosis, management, and monitoring. However, the lack of a unified and standardized database of genes assigned to kidney diseases has led to diagnostic blind spots and comparability issues among current studies of kidney genetics. To address this gap, we created “Kidney-Genetics”, a regularly updated, automated and publicly accessible database, which aims to provide a comprehensive list of all relevant genes associated with kidney disease. Methods Kidney disease-associated gene information was compiled from various sources, including: (1) Genomics England and Australia PanelApp [1], (2) a comprehensive literature review of published gene lists, (3) clinical diagnostic panels for kidney disease, (4) a Human Phenotype Ontology (HPO)-based [2] search in rare disease databases (OMIM, Orphanet), and (5) a PubTator [3] API-based automated literature extraction from PubMed. An evidence-scoring system was developed to distinguish high- evidence genes from low evidence genes and candidate genes. High-evidence genes were defined as those present in two or more of the five resources and were manually curated based on predetermined criteria or, in the case of existing ClinGen [4] curation, their data and scores were used. Genes with a score of one or less were accordingly classified as candidate genes. Additionally, genes were grouped into different categories for later genotype-phenotype correlation matching (see Fig. 1). Results The Kidney-Genetics database currently contains detailed information on 3025 kidney-associated genes with detailed annotations on gene expression, kidney phenotype, inheritance mode, disease onset, possible syndromic disease mode and genetic variation. The number of genes extracted from the five analyzed sources of information are as follows: (1) 534, (2) 822, (3) 956, (4) 789, and (5) 2158 (see Fig. 2). Notably, 598 genes (19.8%) of the total 3025 genes are present in two or more of the analyzed information sources, thus meeting our evidence criteria, indicating high confidence and their potential for diagnostic use. Of these high-evidence genes, 526 (88.0%) are present in at least one, and 56 (9.4%) are present in all 10 comprehensive diagnostic laboratory panels. To ensure currency, Kidney-Genetics will be updated regularly and automatically on a monthly basis. We will also provide phenotypic and functional clustering results to facilitate gene grouping. Conclusion By utilizing Kidney-Genetics, clinicians, geneticists, and researchers can examine genomic data and improve their understanding of the genetic components of diverse KDs. The code and results are freely available on GitHub (kidney-genetics.org) [5]. A standardized pipeline and automated system keep our database on the cutting edge of kidney research and diagnostics. Screening efforts toward manual curation (such as through the ClinGen initiative) and assignment of diagnostic genes to kidney disease groups (e.g., syndromic vs. isolated; adult vs. pediatric; cystic, nephrotic, etc.) are currently under development.

Shear wave elastography and dispersion imaging for hepatic veno-occlusive disease prediction after pediatric hematopoietic stem cell transplantation: a feasibility study.

Non-invasive imaging modalities are warranted for diagnosing and monitoring veno-occlusive disease because early diagnosis and treatment improve the prognosis. To evaluate the usefulness of liver shear wave elastography (SWE) and shear wave dispersion (SWD) imaging in diagnosing and monitoring veno-occlusive disease in pediatric patients. We conducted a prospective cohort study at a single tertiary hospital from March 2021 to April 2022. The study protocol included four ultrasound (US) sessions: a baseline US and three follow-up US after hematopoietic stem cell transplantation. Clinical criteria, including the European Society for Blood and Marrow Transplantation criteria, were used to diagnose veno-occlusive disease. We compared clinical factors and US parameters between the veno-occlusive disease and non-veno-occlusive disease groups. The diagnostic performance of US parameters for veno-occlusive disease was assessed by plotting receiver operating characteristic (ROC) curves. We describe temporal changes in US parameters before and after veno-occlusive disease diagnosis. Among the 38 participants (mean age 10.7 years), eight developed veno-occlusive disease occurring 17.0 ± 5.2 days after hematopoietic stem cell transplantation. Liver stiffness, as measured by SWE (15.0 ± 6.2kPa vs. 5.8 ± 1.8 kPa; P<0.001), and viscosity, as assessed with SWD (17.7 ± 3.1m/s/kHz vs. 14.3 ± 2.8m/s/kHz; P=0.015), were significantly higher in the veno-occlusive disease group compared to the non-veno-occlusive disease group at the time of diagnosis. Liver stiffness demonstrated the highest area under the ROC (AUROC) curves at 0.960, with an optimal predictive value of >6.5kPa, resulting in sensitivity and specificity of 100% and 83.3%, respectively. Viscosity demonstrated an AUROC of 0.783, with an optimal cutoff value of 13.9m/s/kHz for predicting veno-occlusive disease, with a sensitivity of 100% and specificity of 53.3%, respectively. Liver stiffness increased with disease severity and decreased during post-treatmentfollow-up. SWE may be a promising technique for early diagnosis and severity prediction of veno-occlusive disease. Furthermore, liver viscosity assessed by SWD may serve as an additional marker of veno-occlusive disease.

Anti-pruritic effect of L-carnitine against chloroquine-induced pruritus mediated via nitric oxide pathway.

Pruritus, or itching, is a distressing symptom associated with various dermatological and systemic diseases. L-carnitine (βeta hydroxy-γ-tri methyl amino-butyric acid), is a naturally occurring substance, it controls numerous physiological processes. The present research aims to identify L-carnitine for its anti-pruritic effect via nitric oxide-dependent mechanism. Chloroquine-induced pruritus serves as an experimental model to investigate possible therapeutic interventions. In this study, we evaluated the efficacy of L-carnitine in combating oxidative stress, nitric oxide, and inflammatory cytokines in a chloroquine-induced pruritus model. L-carnitine treatment significantly reduced scratching behavior compared to the disease group (***P < 0.001 vs. chloroquine group), indicating its antipruritic potential. The markers of oxidative stress, GST, GSH, Catalase, and LPO were dysregulated in the disease model, but administration of L-carnitine restored GST, GSH, and Catalase levels and decreased LPO levels (***P < 0.001 vs. chloroquine group), thereby alleviating oxidative stress. L-carnitine also reduced nitric oxide synthase (NOS) activity, suggesting that it modulates nitric oxide signaling pathways involved in pruritus. In addition, L-carnitine lowered levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), inflammatory marker nuclear factor kappa B (p-NFκB) and also reduces an inflammatory enzyme, cyclooxygenase-2 (COX-2), determined by ELISA (Enzyme-Linked Immunosorbent Assay) (***P < 0.001 vs. chloroquine group). It downregulates nNOS mRNA expression confirmed by real-time polymerase chain reaction (RT-PCR). These findings highlight the therapeutic effects of L-carnitine in alleviating chloroquine-induced pruritus.

Measurement of some immunological Indicators in patients with recurrent oral lichen planus and some viral infections

Oral lichen planus(OLP) usually appears in the form of skin lesions with multiple oral symptoms. Research indicates that it may be an autoimmune disease and is believed to be related to some viral infections. aims to determine the level of some immune indicators in patients with OLP and some types of viral infections associated with it. The research also aimed to determine the level of these indicators in patients who suffered from recurrence of the infection. Methods: ELISA technology was used to determine the level of immune indicators, Results the percentage of patients infected with OLP was 48.9%, while those infected with OLP+HCV, OLP+HBsV, and OLP+HSV-1 were 9.4%, 6.2%, and 5.2%, respectively. Some immune indicators are in higher concentrations in females than in males. While there was variation in the levels of some other measured indicators, as they appeared in higher concentrations in patients infected with OLP+HBsV than in other groups, followed by the group of patients infected with OLP+HCV. In the group of patients with OLP, the infection was recurrent at a rate of 93.6%, while the non-recurrence rate was 6.4%. The immune indicators S-IgA, IgG, and C3 each appeared in higher concentrations in non-recurring disease cases, while the rest of the immune indicators appeared in higher concentrations in recurrent cases, and they varied. The levels of these immune indicators in other disease groups under study among those who have recurrence than in the other group. Conclusion: Some immunological indicators are increase in OLP patients and also, in HBsV infections and the disease may be recurrent in same family.

Juvenile dermatomyositis with Anti-SAE antibodies in a Moroccan child associated with pseudo-angioedema: a case report

BackgroundJuvenile Dermatomyositis (JDM) is the leading cause of non-infectious inflammatory myopathy in children. It is a heterogeneous group of autoimmune diseases characterized by a variable combination of muscular, dermatological, and visceral involvement. Myositis-specific autoantibodies help define homogeneous subgroups with common clinical characteristics and prognoses. Anti-SAE (small ubiquitin-like modifier 1 (SUMO-1) activating enzyme) antibodies are among the most recently discovered specific autoantibodies. The presence of these antibodies is very rare, making it challenging to define clinical features and prognosis in the juvenile form. We report the first case of an African patient with juvenile dermatomyositis and positive anti-SAE antibodies.Case ReportA 5-year-3-month-old Moroccan boy presented to the pediatric emergency department with dysphagia that had been evolving for two days, preceded two months earlier by facial erythema associated with fatigue, lower limb pain, difficulty walking, and progressive inflammatory polyarthralgia. On admission, the child had a heliotrope rash with predominant pseudo-angioedema on the lips, periungual telangiectasia, and Gottron’s papules over the bilateral interphalangeal and metatarsophalangeal joints. The patient had a more pronounced proximal muscle weakness in the lower limbs. He had no urticaria, fever, arthritis, calcinosis, cutaneous ulcers, or lipodystrophy. The Joint examination was normal, as was the pleuropulmonary examination. The electroneuromyography showed myogenic changes in all four limbs. Laboratory findings showed elevated levels of creatine phosphokinase and lactate dehydrogenase and a mild inflammatory syndrome. The electrocardiogram was normal. The anti-SAE antibodies were positive. The boy was diagnosed with juvenile dermatomyositis. He received methylprednisolone bolus therapy followed by oral prednisone. The latter was gradually tapered in combination with weekly intramuscular methotrexate. As a result, dysphagia disappeared within 48 h. After two weeks, there was an improvement in the muscular score and a significant regression of facial pseudo-angioedema.ConclusionWe report the first African patient with anti-SAE autoantibody-positive JDM. He had a typical dermatological manifestation of JDM associated with pseudo-angioedema predominant on the lips; a rarely reported sign in DM and JDM patients. The patient responded well to corticosteroid therapy and methotrexate.

Microarray analysis of microrna expression in peripheral blood mononuclear cells of patients with polymyositis and dermatomyositis.

MicroRNAs (miRNAs) represent a new class of biomarkers in the context of connective tissue disorders. The miRNA expression profiles in peripheral blood mononuclear cells (PBMCs) of patients with polymyositis (PM) and dermatomyositis (DM) have not been fully elucidated. The objective is to investigate miRNAs expression profile in PBMCs of patients with PM/DM. Microarray technology was used to identify differentially expressed miRNAs in PBMCs obtained from 6 untreated PM/DM patients and 3 healthy controls (HCs). TaqMan-based stem-loop real-time PCR detection was used for validation in a cohort of 34 PM/DM patients and 20 HCs. Microarray analysis revealed 38 differentially expressed miRNAs (24 up-regulated and 14 down-regulated) in PM/DM patients compared to HCs. Four miRNAs (miR-320a, miR-335-3p, miR-34a-5p and miR-454-3p) were chosen for real-time PCR validation. The expression of miR-34a-5p was significantly upregulated in PM/DM group (P < 0.05). In subgroup analysis, miR-34a-5p was significantly upregulated in interstitial lung disease (ILD) group and DM group (P < 0.001). The level of SIRT1, a validated target of miR-34a, was significantly lower in PBMCs of PM/DM patients compared with HCs. MiR-34a-5p may potentially participate in the pathogenesis of PM/DM through SIRT1, and may serve as a potential new biomarker for PM/DM-ILD.

Association between 23 drugs and inflammatory bowel disease: a two-sample Mendelian randomization study

BackgroundInflammatory bowel disease (IBD) is a group of diseases characterized by chronic and recurrent inflammation of the gastrointestinal tract. The etiology of IBD remains multifaceted and poorly understood, resulting in limited treatment options that primarily target disease induction and remission maintenance. Thus, the exploration of novel therapeutic options for IBD among existing medications is advantageous. Mendelian randomization analysis (MR) serves as a valuable tool in investigating the relationship between drugs and diseases. In this study, MR analysis was employed to investigate the potential causal relationship between 23 approved drugs for the treatment of various diseases and IBD.MethodWe performed a two-sample MR analysis using publicly available genome-wide association study (GWAS) statistics. The inverse variance weighting (IVW) method was used as the main analysis method, supplemented by the remaining four methods (weighted median, MR Egger regression, simple and weighted models), and Meta-analysis was performed to expand the sample size to obtain a more reliable composite causal effect. Finally, Cochran’s Q statistic and the MR-Egger test for directed pleiotropy were applied to determine whether significant heterogeneity or directed pleiotropy existed.ResultsIn the main MR analysis (IVW), drugs with a negative causal association with the risk of IBD were immunosuppressant {OR (95% CI) = 0.7389 [0.6311–0.8651], p = 0.0046} and diabetes drugs {OR (95% CI) = 0.9266 [0.8876–0.9674], p = 0.0058}. A positive causal association with the risk of IBD was found for salicylic acid and derivatives {OR (95% CI) = 1.2737 [1.0778–1.5053], p = 0.0345}. Negative causal associations with UC risk were identified for immunosuppressants {OR (95% CI) = 0.6660 [0.5133–0.8640], p = 0.0169} and diabetes medications {OR (95% CI) = 0.9020 [0.8508–0.9551], p = 0.0046}; positive causal associations with UC risk were found for β-receptor blockers {OR (95% CI) = 1.1893 [1.0823–1.3070], p = 0.0046}. A negative causal association with the risk of CD was found for immunosuppressants {OR (95% CI) = 0.6957 [0.5803–0.8341], p = 0.0023}. There was no statistically significant association between the remaining 19 drugs and IBD and subtypes.ConclusionThis MR study provides evidence suggesting that immunosuppressants have a mitigating effect on the risk of IBD and demonstrate consistent efficacy in subtypes of ulcerative colitis (UC) and Crohn’s disease (CD). Additionally, diabetes medications show potential in reducing the risk of IBD, particularly in cases of UC, while β-blockers may elevate the risk of UC. Conversely, salicylic acid and its derivatives may increase the risk of IBD, although this effect is not consistently observed in the subtypes of the disease. These findings offer new insights into the prevention and management of IBD.

Correlation Between Serum microRNA-18a Level and Endothelial Function and Prognosis in Female Coronary Heart Disease Patients.

The aim was to analyze the correlation between serum microRNA (miR)-18a level, endothelial function, and prognosis in female coronary heart disease (CHD) patients. One hundred sixtyfemale patients admitted to our hospital for the first occurrences of chest pain and tightness were divided into CHD and non-CHD groups based on the coronary angiography results. Clinical data, laboratory indexes, serum miR-18a level, and endothelial function [flow-mediated dilation (FMD) function, endothelin 1 (ET-1), and nitric oxide (NO)] were compared. There were no significant differences in clinical data (except CHD family history) between 2 groups. Coronary heart disease group had significantly lower levels of NO and FMD, while significantly higher levels of miR-18a and ET-1 than non-CHD group (P <.05). Pearson correlation showed that serum miR-18a level was positively correlated with ET-1 (r = 0.492, P <.001), and negatively correlated with NO and FMD (r = -0.504, -0.307, P <.001). The receiver operating characteristic) curve showed that the area under the curve of serum miR-18a level in predicting the occurrence of CHD in women was 0.878 (95% CI: 0.828-0.928). Compared with good prognosis group, poor prognosis group had signifi-cantly lower NO, and FMD levels, while higher proportions of acute coronary syndrome, multivessel disease, miR-18a, and ET-1 levels (P <.05). The expression of serum miR-18a in female CHD patients was high, which was related to endothelial function. The increase in serum miR-18a level was a risk factor for the occurrence of MACE in female CHD patients during follow-up, and the serum miR-18a level could effectively predict the occurrence of CHD in female patients.