Major Etiology Research Articles

Etiology, clinical characteristics, genetic profile, and outcomes of children with refractory rickets at a referral center in India: a cohort study.

Limited research exists regarding the genetic profile, clinical characteristics, and outcomes of refractory rickets in children from India. Patients with refractory rickets aged ≤ 18years were enrolled. Data regarding clinical features, etiology, genotype-phenotype correlation, and estimated glomerular filtration rate (eGFR) were recorded. Seventy-two patients with refractory rickets (non-nutritional, with normal kidney function at presentation) from 65 families attending the pediatric nephrology clinic from 2005-2024 were included. Median (IQR) age at first presentation was 2 (1, 4) years. Clinical features included failure-to-thrive (49 [68.1%]), polyuria (37 [51.4%]), nephrocalcinosis (33 [45.8%]), fractures (10 [13.9%]), and hypokalemic paralysis (4 [5.6%]). Major etiologies included distal renal tubular acidosis (dRTA) [34(47.2%)], hereditary hypophosphatemic rickets (11 [15.3%]), cystinosis (9 [12.5%]), Lowe syndrome (3 [4.2%]), vitamin D-dependent rickets (4 [5.5%]), and Fanconi-Bickel syndrome (3 [4.2%]). Next-generation sequencing identified 61 variants among 71 children tested (85.9%), of which 56 variants (among 55 children) were pathogenic (P)/likely-pathogenic (LP) (77.5% diagnostic-yield). P/LP variants included SLC4A1 (n = 14), CTNS (n = 9), PHEX (n = 8), WDR72 (n = 5), OCRL (n = 2), SLC2A2 (n = 3), ATP6V0A4 (n = 4), VDR (n = 3), CLDN16 (n = 2), ATP6V1B1 (n = 1), SLC12A1 (n = 1), CLCN5 (n = 1), SLC34A3 (n = 1), ATP7B (n = 1), and KCNJ1 (n = 1). Fifteen novel P/LP variants and five novel variants-of-uncertain-significance (VUS) were identified. c.2573C > A in exon 19 among SLC4A1-dRTA (n = 14) was a recurrent mutation. Five patients with cystinosis, two patients with SLC4A1-dRTA, two with WDR72-dRTA, and two with Bartter syndrome showed progression to CKD stage 2 or greater during follow-up. dRTA, X-linked hypophosphatemic rickets, and cystinosis were common causes of refractory rickets. The c.2573C > A variant in exon 19 was a recurrent mutation in SLC4A1-dRTA.

Dissatisfaction after implantation of extended depth-of-focus intraocular lenses.

To evaluate the symptoms, etiology and treatment of patient dissatisfaction after extended depth-of-focus (EDOF) intraocular lens (IOL) implantation. University Eye Clinic, Maastricht University Medical Center, the Netherlands. Retrospective case series. For this study, all medical records of patients who received an EDOF IOL from July 2020 to July 2022 were reviewed. Patients were included if they had reported any dissatisfaction after surgery. The main outcome parameters were reasons for dissatisfaction (subjective complaints) and the presumed etiology of the complaints. Out of 202 patients (354 eyes) who underwent EDOF IOL implantation, 83 eyes (22.8%) of 52 dissatisfied patients were included. Blurred vision was the predominant complaint, reported in 78 eyes (94%). Photic phenomena were reported in 21 eyes (25.3%), with 16 eyes (76.2%) experiencing coexisting blurred vision. The major etiologies for dissatisfaction in this cohort were residual ametropia (51.8%), dry eye disease (26.5%), and posterior capsular opacification (12.0%). Treatments were administered to 85.5% of the eyes, including interventions such as artificial tears, spectacles, or refractive surgery enhancement. A small number of patients (n=12; 5.9%) remained dissatisfied despite intervention. Based on this real-world data study, dissatisfaction following EDOF IOL implantation can be effectively identified and treated in most cases.

Diabetic Nephropathy-Associated Impaired Aortic Function Is Not Mediated by Mean Arterial Pressure and Its Determinants.

Objective: The study aimed to assess the potential impacts of mean arterial pressure (MAP) and its determinants (cardiac output and systemic vascular resistance) on diabetic nephropathy (DNP)-associated impaired aortic function. Methods: This multi-ethnic study included 115 chronic kidney disease (CKD) patients (67 non-dialysis and 48 dialysis). Six aortic function measures were evaluated by SpygmoCor. The stroke volume was determined by echocardiography. Results: Hypertensive nephropathy (HNP) (53.9%), DNP (32.2%), glomerulonephritis (19.1%), and HIV-associated nephropathy (7.8%) composed the major CKD etiologies. Concurrent HNP and DNP were present in 31.1% of the patients. Participants with compared with those without concurrent HNP and DNP experienced more frequent established cardiovascular disease (43.2% versus 14.9%, p = 0.01), a faster pulse wave velocity (p = 0.001), and smaller total arterial compliance as an indicator of proximal aortic stiffness (p = 0.03). DNP was associated with each aortic function measure (p < 0.001-0.02) independent of potential confounders and MAP, as well as its determinants. HNP was not related to aortic function (p > 0.05 for all relationships). MAP and its determinants did not mediate the potential impact of DNP on aortic function (-4.1-6.4% contribution). Covariates that were associated with impaired aortic function measures included MAP and its determinants (p < 0.001-0.01). Conclusions: Mean or distending arterial pressure and its determinants were associated with impaired aortic function in the overall CKD population. However, these hemodynamic factors did not mediate DNP-associated impaired aortic function. Our results suggest that blood pressure lowering can be anticipated to improve impaired aortic function in the overall CKD population but not when it is solely induced by DNP.

Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies.

As the final stage of disease-related tissue injury and repair, fibrosis is characterized by excessive accumulation of the extracellular matrix. Unrestricted accumulation of stromal cells and matrixduring fibrosis impairs the structure andfunction of organs, ultimately leading to organ failure. The major etiology of fibrosis is an injury caused by genetic heterogeneity, trauma, virus infection, alcohol, mechanical stimuli, and drug. Persistent abnormal activation of "quiescent" fibroblasts that interact with or do not interact with the immune system via complicated signaling cascades, in which parenchymal cells are also triggered, is identified as the main mechanism involved in the initiation and progression of fibrosis. Although the mechanisms of fibrosis are still largely unknown, multiple therapeutic strategies targeting identified molecular mechanisms have greatly attenuated fibrotic lesions in clinical trials. In this review, the organ-specific molecular mechanisms of fibrosis is systematically summarized, including cardiac fibrosis, hepatic fibrosis, renal fibrosis, and pulmonary fibrosis. Some important signaling pathways associated with fibrosis are also introduced. Finally, the current antifibrotic strategies based on therapeutic targets and clinical trials are discussed. A comprehensive interpretation of the current mechanisms and therapeutic strategies targeting fibrosis will provide the fundamental theoretical basis not only forfibrosis but also for the development of antifibrotic therapies.

Bacteriological Etiology of Empyema Thoracis Patients Admitted in a Tertiary Care Hospital

Empyema thoracis is the most common complication of pneumonia and is associated with severe morbidity and mortality. Management of empyema thoracis is complex and needs a multimodal approach. Antibiotic therapy is very crucial in management of empyema thoracis and epidemiological data is essential to ensure appropriate antibiotic therapy. This study aimed to explore the bacteriological profile of empyema thoracis in a tertiary care hospital. This cross-sectional study was carried on 30 patients admitted in the Department of Medicine and Department of Respiratory Medicine, Sir Salimullah Medical College and Mitford Hospital (SSMC &amp; MH), Dhaka over a period of six months (March to September 2021). Mean age of the patients was 38±10.94 (SD) years and male–female ratio was 2:1 (66.7% male). The most common symptoms were found cough (86.7%) and fever (83.3%) including major presenting symptoms expectoration (76.7%) and chest pain (70.0%); other symptoms were loss of appetite (50.0%), malaise (46.7%) and hemoptysis (10.0%). The major etiology was the thoracic empyema (56.7%) followed by pneumonia (16.67%), lung abscess (10.0%), liver abscess (6.7%), lung cancer (3.3%), secondary infection (3.3%) and undetermined cases responding to antibiotics (3.3%). Bacteriological profile showed that majority of the cases (56.7%) were Mycobacterium Tuberculosis; others cases were S. aureus (6.7%), S. pyogen (6.7%), E. coli (3.3%), Klebsiella (3.3%) and Pseudomonas (6.7%). It was concluded from the study, more than half of empyema thoracis was etiologically tubercular. Bangladesh Med J. 2023 Sept; 52(3): 27-34

Long-Term Carotid Plaque Progression and the Role of Intraplaque Hemorrhage: Analysis from Deep Learning-based Longitudinal Vessel Wall Imaging.

Carotid atherosclerosis is a major etiology of stroke. Although intraplaque hemorrhage (IPH) is known to increase stroke risk and plaque burden, its long-term effects on plaque dynamics remain unclear. This study aimed to evaluate the long-term impact of IPH on carotid plaque burden progression using deep learning-based segmentation on multi-contrast vessel wall imaging (VWI). Twenty-eight asymptomatic subjects with carotid atherosclerosis underwent an average of 4.7 ± 0.6 VWI scans over 5.8 ± 1.1 years. Deep learning pipelines segmented the carotid vessel walls and IPH. Bilateral plaque progression was analyzed using generalized estimating equations, and linear mixed-effects models evaluated long-term associations between IPH occurrence, IPH volume (%HV), and plaque burden (%WV) progression. Two subjects with ipsilateral IPH developed new ischemic infarcts during follow- up. IPH was detected in 23/50 of arteries. Of arteries without IPH at baseline, 11/39 developed new IPH that persisted, while 5/11 arteries with baseline IPH exhibited it throughout the study. Bilateral plaque growth was significantly correlated (r = 0.54, p < 0.001), but this symmetry was weakened with IPH presence. The progression rate for arteries without IPH was -0.001 %/year (p = 0.895). However, IPH presence or development at any point was associated with a 2.34% absolute increase in %WV (p < 0.001), and %HV was associated with 0.73% per 2-fold increase over the mean of %HV (p = 0.005). IPH may persist asymptomatically for extended periods. While arteries without IPH demonstrated minimal progression under contemporary treatment, IPH significantly accelerated long-term plaque growth.

Development and Validation of a Prediction Model Using Sella Magnetic Resonance Imaging-Based Radiomics and Clinical Parameters for the Diagnosis of Growth Hormone Deficiency and Idiopathic Short Stature: Cross-Sectional, Multicenter Study.

Growth hormone deficiency (GHD) and idiopathic short stature (ISS) are the major etiologies of short stature in children. For the diagnosis of GHD and ISS, meticulous evaluations are required, including growth hormone provocation tests, which are invasive and burdensome for children. Additionally, sella magnetic resonance imaging (MRI) is necessary for assessing etiologies of GHD, which cannot evaluate hormonal secretion. Recently, radiomics has emerged as a revolutionary technique that uses mathematical algorithms to extract various features for the quantitative analysis of medical images. This study aimed to develop a machine learning-based model using sella MRI-based radiomics and clinical parameters to diagnose GHD and ISS. A total of 293 children with short stature who underwent sella MRI and growth hormone provocation tests were included in the training set, and 47 children who met the same inclusion criteria were enrolled in the test set from different hospitals for this study. A total of 186 radiomic features were extracted from the pituitary glands using a semiautomatic segmentation process for both the T2-weighted and contrast-enhanced T1-weighted image. The clinical parameters included auxological data, insulin-like growth factor-I, and bone age. The extreme gradient boosting algorithm was used to train the prediction models. Internal validation was conducted using 5-fold cross-validation on the training set, and external validation was conducted on the test set. Model performance was assessed by plotting the area under the receiver operating characteristic curve. The mean absolute Shapley values were computed to quantify the impact of each parameter. The area under the receiver operating characteristic curves (95% CIs) of the clinical, radiomics, and combined models were 0.684 (0.590-0.778), 0.691 (0.620-0.762), and 0.830 (0.741-0.919), respectively, in the external validation. Among the clinical parameters, the major contributing factors to prediction were BMI SD score (SDS), chronological age-bone age, weight SDS, growth velocity, and insulin-like growth factor-I SDS in the clinical model. In the combined model, radiomic features including maximum probability from a T2-weighted image and run length nonuniformity normalized from a T2-weighted image added incremental value to the prediction (combined model vs clinical model, P=.03; combined model vs radiomics model, P=.02). The code for our model is available in a public repository on GitHub. Our model combining both radiomics and clinical parameters can accurately predict GHD from ISS, which was also proven in the external validation. These findings highlight the potential of machine learning-based models using radiomics and clinical parameters for diagnosing GHD and ISS.

Intestinal FXR deficiency induces dysregulation of xanthine oxidase and accounts for sex difference in hyperuricemia

Overproduction of uric acid caused by increased expression and/or enhanced activity of xanthine oxidase (XO) is one of the major etiologies of hyperuricemia, which had a significant sex differences. As an important enzyme involved in production of reactive oxygen species and uric acid, activity of XO is highly correlated with hyperuricemia and its complications. However, the mechanisms underlying XO dysregulation remain unclear, and sex difference in the prevalence of hyperuricemia has been well known. To explore the potential role of intestinal farnesoid X receptor (FXR) on XO regulation and production, and the mechanisms of sex differences in this pathological process. Two hundred and sixty-one dyslipidemia participants and intestine-specific FXR-knockout mice were used to study the relationship between the intestinal FXR and the serum uric acid level. Western blotting, quantitative real-time PCR, and dual-luciferase reporter assay, were applied to clarify the regulatory role of FXR deficiency on XO. Special inhibitors, agonists, siRNA, sex hormones were used to investigate the mechanism of sex difference in FXR deficiency induced hyperuricemia in cell and animal model. Serum fibroblast growth factor 19 (FGF19) levels were lower in hyperuricemia patients in a sex difference manner. Increased local TNFα level driven by intestinal FXR deficiency/inhibition induced overexpression and hyperactivity of intestinal XO, leading to elevated intestinal uric acid synthesis, and subsequently resulting in hyperuricemia. We found that estrogens inhibited XO expression and activity, whereas androgens enhanced XO activity, leading to the sex difference in FXR deficiency induced hyperuricemia. Infliximab treatment eliminated the sex difference in uric acid levels in intestinal FXR-knockout mice. This study demonstrated the role of intestinal FXR in the pathogenesis of hyperuricemia, and partially elucidated the mechanisms underlying the sex differences of hyperuricemia.

Trypsin in pancreatitis: The culprit, a mediator, or epiphenomenon?

Pancreatitis is a common, life-threatening inflammatory disease of the exocrine pancreas. Its pathogenesis remains obscure, and no specific or effective treatment is available. Gallstones and alcohol excess are major etiologies of pancreatitis; in a small portion of patients the disease is hereditary. Pancreatitis is believed to be initiated by injured acinar cells (the main exocrine pancreas cell type), leading to parenchymal necrosis and local and systemic inflammation. The primary function of these cells is to produce, store, and secrete a variety of enzymes that break down all categories of nutrients. Most digestive enzymes, including all proteases, are secreted by acinar cells as inactive proforms (zymogens) and in physiological conditions are only activated when reaching the intestine. The generation of trypsin from inactive trypsinogen in the intestine plays a critical role in physiological activation of other zymogens. It was proposed that pancreatitis results from proteolytic autodigestion of the gland, mediated by premature/inappropriate trypsinogen activation within acinar cells. The intra-acinar trypsinogen activation is observed in experimental models of acute and chronic pancreatitis, and in human disease. On the basis of these observations, it has been considered the central pathogenic mechanism of pancreatitis - a concept with a century-old history. This review summarizes the data on trypsinogen activation in experimental and genetic rodent models of pancreatitis, particularly the more recent genetically engineered mouse models that mimic mutations associated with hereditary pancreatitis; analyzes the mechanisms mediating trypsinogen activation and protecting the pancreas against its' damaging effects; discusses the gaps in our knowledge, potential therapeutic approaches, and directions for future research. We conclude that trypsin is not the culprit in the disease pathogenesis but, at most, a mediator of some pancreatitis responses. Therefore, the search for effective therapies should focus on approaches to prevent or normalize other intra-acinar pathologic processes, such as defective autophagy leading to parenchymal cell death and unrelenting inflammation.

Inpatient Burden of Respiratory Syncytial Virus Infection and Influenza in Children Younger Than 5 Years in Japan, 2011-2022: A Database Study.

Respiratory syncytial virus (RSV) and influenza virus are major viral etiologies of pediatric lower respiratory tract infection, but comparative data on inpatient burden are lacking. Using a large-scale health claims database in Japan, we identified patients under 5 years of age with a confirmed RSV or influenza diagnosis as an outpatient or inpatient between 2011 and 2022. Hospitalization rate, inpatient characteristics, various in-hospital outcomes/complications, and healthcare resource utilization were described. A total of 176,911 RSV-confirmed outpatients, 153,383 influenza-confirmed outpatients, 90,413 RSV-confirmed hospitalizations, and 11,186 influenza-confirmed hospitalizations were identified. Among outpatients, 24.7% of RSV infection and 2.8% of influenza cases required hospitalization within 1 week. There was no co-morbidities/prematurity for 95.0% of RSV hospitalizations and 96.5% of influenza hospitalizations. Proportions of in-hospital outcomes/complications were (RSV infection vs. influenza): oxygen use 47.6% vs. 14.8%, mechanical ventilation 2.1% vs. 0.7%, pneumonia 33.6% vs. 12.8%, otitis media 7.7% vs. 2.3%, febrile seizure 1.5% vs. 34.4%, encephalitis/encephalopathy 0.1% vs. 0.5%, myocarditis < 0.1% vs. 0.6%, antibiotics prescription 48.0% vs. 24.4%. The mean inpatient stay was 6.1 vs. 4.3 days at direct medical costs of 435,744 vs. 315,809 JPY/patient. These trends held true in age-stratified data. In-hospital death occurred in 31 RSV infection and 6 influenza cases. Although both infections resulted in substantial burden, RSV infection led to more frequent hospitalizations, worse in-hospital outcomes, longer inpatient stays, higher medical costs, and more frequent antibiotics prescription compared to influenza. Most RSV hospitalizations occurred among healthy term children, emphasizing the need for prevention measures in all children.

Associations of Lipid Profiles With the Onset of HEV-Related Acute Liver Failure: A Multicenter Cohort Study.

Hepatitis E virus (HEV) is one of the major etiologies for acute liver failure. This multicenter retrospective cohort study aimed to investigate the associations of lipid profiles with the risk of HEV-related acute liver failure (HEV-ALF) among hospitalized patients with acute hepatitis E. A total of 1061 participants were obtained from three tertiary medical centers in Jiangsu, China, between February 2018 and May 2024. Univariate and multivariate Cox regression models were constructed to assess the associations between lipid profiles and the risk of HEV-ALF onset. The time-dependent area under the receiver-operating-characteristic curve (AUROC) and decision curve analysis were used to further evaluate the predictive value of blood lipids. After adjusting for potential confounders, total cholesterol (HR = 0.535, 95% CI: 0.437-0.656, p < 0.001), high-density lipoprotein-cholesterol (HR = 0.065, 95% CI: 0.027-0.154, p < 0.001), low-density lipoprotein-cholesterol (HR = 0.653, 95% CI: 0.512-0.833, p = 0.001), and apolipoprotein A (ApoA) (HR = 0.006, 95% CI: 0.002-0.020, p < 0.001) were significantly associated with a reduced risk of HEV-ALF. Moreover, blood ApoA exhibited excellent discrimination ability and net benefit for predicting 7-day (AUROC = 82.47%, 95% CI: 77.92-87.02) and 14-day (AUROC = 78.81%, 95% CI: 74.13-83.49) HEV-ALF onset. The findings may provide further evidence on the progression of HEV infection and future risk prediction.

FNDC5/Irisin mitigates high glucose-induced neurotoxicity in HT22 cell via ferroptosis.

Diabetes-induced neuropathy represents a major etiology of dementia, highlighting an urgent need for the development of effective therapeutic interventions. In this study, we explored the role of fibronectin type III domain containing 5 (FNDC5)/Irisin in mitigating hyperglycemia-induced neurotoxicity in HT22 cells and investigated the underlying mechanisms. Our findings reveal that high glucose conditions are neurotoxic, leading to reduced viability of HT22 cells and increased apoptosis. Furthermore, the elevated expression of the intracellular ferroptosis marker Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4), along with increased levels of ferrous ions and malondialdehyde (MDA), suggests that high glucose conditions may induce ferroptosis in HT22 cells. FNDC5/Irisin treatment effectively mitigates high glucose-induced neurotoxicity and ferroptosis in HT22 cells. Mechanistically, FNDC5/Irisin enhances cellular antioxidant capacity, regulates ACSL4 expression, and improves intracellular redox status, thereby inhibiting ferroptosis and increasing HT22 cell survival under high-glucose conditions. These results highlight the neuroprotective potential of FNDC5/Irisin in high glucose environments, offering a promising avenue for developing treatments for diabetes-related neurodegenerative diseases.

Significant stenosis without thrombus may be the third most common etiology of acute coronary syndrome

Abstract Background Plaque rupture (PR), plaque erosion (PE) and calcified nodule (CN) are known as major etiologies of acute coronary syndrome (ACS). On the other hand, significant stenosis without thrombus (SSWT) can be sometimes observed in culprit plaque of ACS. However, incidence and clinical feature of SSWT in ACS patients are not well known in Japanese. Method This is a sub study of TACTICS registry which include ACS patients (n=702) undergoing primary percutaneous coronary intervention (PCI) under optical coherence tomography (OCT) in Japan. Using this registry data, we compared the clinical features and OCT findings of SSWT in ACS patients in comparison with PR, PE and CN. Major adverse cardiac event (MACE) was defined as death, non-fatal myocardial infarction, heart failure, or ischemia-driven revascularization at 1-year. Results Plaque rupture (PR: n=411, 61%) and plaque erosion (PE: n=178, 26%) were 2 major etiologies, which was followed by SSWT (n=59, 9%) and calcified nodule (CN: n=28, 4%). Clinical characteristics are shown in table 1. Patients with SSWT was slightly older than PR and PE but younger than CN. Proportion of male was fewer than PR and PE but greater than CN. In terms of traditional coronary risk factors, there were significant differences in prevalences of diabetes, active smoking, and hemodialysis among different etiologies. In SSWT, non-ST elevation myocardial infarction was the main type of ACS followed by unstable angina and ST elevation myocardial infarction (51%, 39% and 10%, respectively), which may be associated with the least CK level and greater TIMI flow. Lesion was less complex with lower proportion of type B2 or C, shorter procedure time, lower proportion of multivessel disease and lower syntax score. OCT findings are shown in table 2. Regarding lipid component and calcification, SSWT showed similar finding as PE. Cholesterol crystal was relatively less as compared to PR and PE. Kaplan-Meier survival curve showing MACE and ischemia driven-TLR are shown in figure 1 and 2. MACE and TLR was the least in SSWT. Conclusion SSWT was the third most common etiology of ACS with different feature from PR, PE and CN.

Impact of sex and age on culprit plaque type of acute coronary syndrome in Japanese patients from TACTICS registry

Abstract Background In acute coronary syndrome (ACS), plaque rupture (PR) is the most frequent etiology followed by plaque erosion (PE) while calcified nodule (CN) is the least etiology. These three are known as major etiologies of ACS. Traditionally, it has been believed that sex and age have impact on etiology of ACS. For example, plaque erosion was thought to often occur in young female while calcified nodule often occur in elderly patients. However, impact of sex and age have not been well described. Methods This is a sub-study from TACTICS registry which consist of 702 Japanese ACS patients who underwent primary percutaneous coronary intervention under optical coherence tomography (OCT) from multicenter. Based on the OCT findings, patients were divided into PR, PE, CN and others. These data were stratified by sex and ages (&amp;lt;50, 50s, 60s, 70s, 80 or over). In this sub-study, we mainly focused on 3 major etiologies of ACS (PR, PE, CN) and compared incidence and clinical characteristics based on sex and ages. Results Distribution of culprit plaque type in ACS patients are shown in figure 1A (male) and 1B (female). PR remained top etiology of ACS in any sex and any age category. However, trend of PE was different between male and female. In male, as patients get younger, incidence of PE increased. In male patients under 50, incidence of PE was almost similar as PR. On the other hand, in female, incidence of PE was greatest in 70s followed by 80 or over. Surprisingly, young female showed the least incidence of PE. CN was the least etiology of three but increased especially from 80. Clinical characteristics are shown in table 1A (male) and 1B (female). In male, most of the baseline characteristics differ between different ages while in female, most of the baseline characteristic did not differ between different ages. Conclusion In our data, PE was more distinct in younger male ACS patients while PE was not that distinct in younger female ACS patients. The impact of sex and age on culprit plaque type of ACS might be variable depending on population.

Characteristics and Outcome of Primary Budd Chiari Syndrome due to Myeloproliferative Disorder in Egyptian Patients, A Single Center Study

Abstract Background Budd–Chiari syndrome (BCS) is a rare life-threatening disorder caused by obstruction of the hepatic venous outflow tract at any level between the small hepatic veins and the right atrium, hence also known as hepatic venous outflow tract obstruction (HVOTO). Primary BCS is often related to multiple thrombophilic conditions, including primary myeloproliferative disorders. Aim of the Work The present study aimed to assess characteristics of Primary Budd Chiari syndrome due to Myeloproliferative disorder in Egyptian patients and the outcome of the radiologic endovascular intervention (TIPS or angioplasty) Patients and Methods This was a retrospective cohort study that was carried out in The Tropical Medicine department, at Ain Shams University Hospitals. A total of 37 patients were enrolled, including 12 males and 25 females, with an age of 15-49 years (mean: 32 years) with primary BCS and MPDs during the interval between January 2006 and March 2023. Results JAK2 was positive in 64.9% of BCS patients, more in ET patients. ET was more frequent in BCS due to MPDs. Furthermore, these results validate routine inclusion of JAK2V617F in the diagnostic workup of BCS. Rate of stent occlusion was high 33.3% due MPDs thrombophilic burden nature. Conclusion MPDs are major aetiology of BCS. TIPS placement is an effective treatment for portal hypertension, but in any case, long-term high intensity anticoagulation treatment is essential in order to prevent recurrent thrombosis.

Spinal Adhesive Arachnoidopathy, the Disorder More Than Simply Adhesive Arachnoiditis: A Comprehensive Systematic Review of 510 Cases.

Spinal adhesive arachnoidopathy (SAA) is a chronic pathology associated with persistent inflammatory responses in the arachnoid. Adhesive arachnoiditis (AA) is one of the major forms of SAA, with accompanying secondary complications. Therefore, we aimed to systematically review both clinical and animal model studies related to SAA to gain a deeper understanding of this unique pathology. A literature search was conducted in PubMed, EMBASE, and Cochrane Library databases to retrieve relevant publications up to October 2022. Clinical manifestations, etiologies, imaging modalities, treatments, and prognosis in patients with SAA were collected. Data from animal experiments related to SAA were also extracted. A total of 176 studies, including 147 clinical and 29 animal model studies, with a total of 510 patients were enrolled in this study. Pain (37.5%), abnormal nerve sensations (39.58%), and abnormal motor function (78.75%) were the top three common symptoms of SAA. Major etiologies included trauma (22.7%), infection (17.73%), surgery (15.37%), and hemorrhage (13.48%). MRI was widely used to confirm the diagnosis. AA could be involved in cervical (96/606, 15.84%), thoracic (297/606, 49.01%), lumbar (174/606, 28.71%), and sacrococcygeal (39/606, 6.44%) vertebral segments. Patients with AA in cervical segments had a higher post-surgery recovery rate (p = 0.016) compared to that of other segments. The common pathological diagnoses of SAA were AA (80.82%), AA combined with arachnoid cyst (12.79%), arachnoid calcification/scars (3.43%), and arachnoid web/fibrosis (2.97%). Patients with AA were more likely to develop syringomyelia, compared with patients with other forms of SAA (p < 0.001). Animal studies mainly focused on new AA therapeutic agents (n = 14), the pathomechanism of AA (n = 14), and the development of new MRI sequences for improved diagnosis (n = 1). The pathological consequences of SAA are more complex than AA and manifest in different forms, such as AA combined with arachnoid cyst, arachnoid calcification/scars, and arachnoid web/fibrosis. In many instances, AA was associated with secondary syringomyelia. Unspecific clinical manifestations of SAA may easily lead to misdiagnosis and missed diagnosis. Although SAA may result from multiple etiologies, including spinal trauma, meningitis, spinal surgery, and hemorrhage, the pathogenesis and treatment of SAA have still not been standardized.

Epidemiology of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD)

Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) together represent the majority of individuals with steatotic liver disease (SLD). MASLD and ALD prevalence continues to rise globally, which is driven by several factors including an aging population, increasing prevalence of cardiometabolic risk factors such as obesity and diabetes mellitus, and the increasing trends in high-risk unhealthy alcohol use which surged during the COVID-19 pandemic. As a result, MASLD, as well as ALD-related cirrhosis and hepatocellular carcinoma, is also on the rise, becoming major etiologies contributing to end-stage liver disease among adults awaiting liver transplantation. Accurately understanding MASLD and ALD epidemiology is critical to guide healthcare resource planning and health policy. Accurate estimates of MASLD and ALD epidemiology are particularly important to understand in the context of recent updates in nomenclature terminology. This review provides an updated assessment of existing literature describing the epidemiology of MASLD and ALD.

Intranasal Application of Diluted Saline Alleviates Ischemic Brain Injury in Association with Suppression of Vasopressin Neurons

Plain Language SummaryNeuroendocrine disorders during cerebral stroke are a major etiology of ischemic brain injury that occurs following the occlusion of the cerebral artery. A hypothalamic neuropeptide, antidiuretic hormone or vasopressin (VP), is a key neuroendocrine factor in ischemic brain injury. To identify the way to reduce the overly produced VP following the stroke, this study used a rat model of cerebral stroke and tested the effects of intranasal application/drops of low concentration saline-0.09% NaCl (IAL) on VP neuronal activity that determines VP secretion. The results revealed for the first time that IAL inhibition of stroke-evoked VP neuronal activation and its associated brain damage is related to IAL inhibition of ischemia-evoked astrocytic process retraction around VP neurons and increase in excitatory inputs on VP neurons from the mitral cells in the activated olfactory bulb in the ischemic side. Similar but weaker effects also occurred at oxytocin neurons that co-exist with VP neurons but exert neural protective effects. These findings highlight that IAL (or commercially available purified water?) inhibition of VP neuronal activity may provide a simply available protective strategy in the early stage of cerebral stroke after further clinical trials.

Hsa_circ_0088196 Predicts Adverse Pregnancy Outcomes in Preeclampsia Patients and Contributes to Endothelial Cell Injury Via Modulating the miR-145-5p/FLT1 Axis.

Preeclampsia (PE) is a specific hypertension-related disease in pregnancies, causing adverse pregnancy outcomes. Endothelial cell dysfunction is a major etiology of PE, of which the regulation could affect disease progression. This study focused on hsa_circ_0088196, evaluating its clinical significance in PE and its effect on endothelial cell injury, aiming to identify a novel biomarker for PE and complete its regulating mechanism in disease development. The study enrolled 165 normal pregnancies and 165 pregnancies with gestational hypertension. The significance of hsa_circ_0088196 in discriminating gestational hypertension, predicting PE, and predicting adverse pregnancy outcomes was evaluated based on its serum expression. The effect and mechanism of hsa_circ_0088196 in HUVEC injury were assessed by CCK8, Transwell, ELISA, and western blotting. Significant downregulation of hsa_circ_0088196 could distinguish gestational hypertension pregnancies and predict the risk of PE. Gestational hypertension pregnancies developed PE showed a lower serum hsa_circ_0088196 level, which also discriminated PE patients, predicted severe conditions and adverse pregnancy outcomes. Overexpressing hsa_circ_0088196 alleviated the enhanced proliferation, migration, inflammation, and angiogenesis by hypoxia/reoxygenation (H/R), which was reversed by miR-145-5p. Silencing miR-145-5p showed similar effects on H/R-induced endothelial cell injury, which was reversed by FLT1. Moreover, FLT1 was positively regulated by hsa_circ_0088196, indicating its involvement in the regulation of HUVEC injury by hsa_circ_0088196. Reduced serum hsa_circ_0088196 served as a biomarker for the diagnosis of gestational hypertension, risk evaluation of PE, and the prediction of adverse pregnancy outcomes. hsa_circ_0088196 suppressed endothelial cell injury induced by H/R through modulating the miR-145-5p/FLT1 axis.

Natural course and predictors of consciousness recovery in children with prolonged disorder of consciousness

Prolonged disorder of consciousness (DoC) is a rising challenge. Pediatric data on diagnosis and prognosis of prolonged DoC were too limited and heterogeneous, making it difficult to define the natural course and evaluate the prognosis. The present study explored the emergence from the Minimally Conscious State (eMCS) incidence at different months postinjury drawing the natural course, and detected the predictors of the incidence in children with prolonged DoC. A hospital-based prospective cohort study was conducted. Kaplan–Meier curves, as well as univariate and multivariate COX regression analysis, were performed. The study enrolled 383 pediatric DoC individuals, including 220 males (57.4%), with an average age of 3.9 (1.9–7.3) years. The median duration between onset and rehabilitation is 30.0 (21.0–46.0) days. At enrollment, the ratio of vegetative state/unresponsive wakefulness syndrome (VS/WUS) to MCS is 78.9%–21.1%. Traumatic brain injury and infection are the major etiologies (36.8% and 37.1%, respectively), followed by hypoxia cerebral injury (12.3%). For children with prolonged DoC, the cumulative incidence of eMCS at months 3, 6, 12, and 24 was 0.510, 0.652, 0.731, 0.784 VS 0.290, 0.418, 0.539, 0.603 in the traumatic VS non-traumatic subgroup, respectively. For children in a persistent vegetative state (PVS), the cumulative incidence of emergence at months in 3, 6, 12, 24, 36 and 48 was testified as 0.439, 0.591, 0.683, 0.724, 0.743 and 0.743 in the traumatic subgroup, and 0.204, 0.349, 0.469, 0.534, 0.589 and 0.620 in the non-traumatic subgroup. Participants who exhibit any of the following four demographical and/or clinical characteristics—namely, older than 4 years at onset, accepted rehabilitation within 28 days of onset, remained MCS at enrollment, or with etiology of traumatic brain injuries—had a significantly positive outcome of consciousness recovery (eMCS). Moreover, both prolongation of the central somatosensory conductive time (CCT) (level 2) and absence of N20 (level 3) independently predict a negative outcome. In children with prolonged DoC, we found that 12 months postinjury was critical to eMCS, and a preferred timepoint to define chronic vegetative state (VS). The characteristics including age, etiology, time before rehabilitation, consciousness state, and SEP results were useful predictors of conscious recovery.Trial registration Registered 06/11/2018, the registration number is chiCTR1800019330 (chictr.org.cn). Registered prospectively.