Deterioration Of Disease Research Articles

P0946 Switching from intravenous to subcutaneous Infliximab in patients with immune mediated diseases in clinical remission

Abstract Background We aimed to report on the efficacy and safety of elective switching from intravenously (IV) to subcutaneously (SC) administered Infliximab (IFX) in patients with immune mediated diseases. Methods This was a multicenter retrospective study in which we analyzed data collected from consecutive patients with immune mediated diseases treated in a hospital setting. Each hospital department was considered a study center and overall, 8 gastroenterology departments, 6 rheumatology departments and 1 dermatology department from 13 Greek hospitals, that are all referral centers, recruited patients for the study. Patients with Crohn’s disease (CD), Ulcerative Colitis (UC), Spondyloarthritis (SpA), Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and chronic plaque Psoriasis (PsO) who were receiving IFX-IV for maintenance of remission and were switched to IFX-SC based on their physician’s choice were included. All patients with gastrointestinal and skin diseases were in clinical remission, while those with musculoskeletal disease had inactive disease or low disease activity. The primary endpoint was disease deterioration during the follow up period, according to disease specific composite measures. Results Between April 2023 and April 2024, a total of 344 patients (CD=136, UC=62, SpA=52, PsA=38, RA=7, PsO=44, co-existence of more than one disease=5) were switched from IFX-IV to IFX-SC. The mean duration of treatment with IFX before switching was a mean (SD) 53.7 (36.2) months. Eleven patients (3.2%) were receiving combination treatment with an immunomodulator and 2 patients (0.6%) were using oral or iv steroids at the time of switch. After a mean (SD) follow up period of 8 (4) months, 12 patients (3.5%) discontinued treatment with IFX-SC. Five of them (1.5%) because of disease worsening and the remaining 7 (2.0%) because of the occurrence of side effects. All other 332 patients (96.5%) showed favorable response, none of them requested an unscheduled visit, or developed an adverse event (clinical or laboratory) or needed escalation of treatment. Conclusion Elective switching from IFX-IV to IFX-SC seems to be an effective and safe approach in real-world every day clinical practice to maintain long-term clinical remission, inactive disease or low disease activity in patients with immune-mediated diseases.

Cardiac complications of arteriovenous access: a narrative review from a multidisciplinary team perspective

Although cardiovascular disease is common among hemodialysis patients, arteriovenous access creation has been invariably implicated in the evolution of adverse cardiac outcomes or deterioration of pre-existing cardiovascular disease. In most cases, these effects are subclinical but with potential underlying echocardiographic findings. Compared with grafts, arteriovenous fistulas are implicated more often, due to the progressively increased flow from the continuous dilatation of the venous outflow tract in the long term. The increasing flow is in the majority of patients well tolerated by cardiac adaptive alterations. However, the clinical impact is based on the balance between the amount of flow volume and the patient’s cardiac reserves. Having extensively reviewed the existing English literature, we present the pathophysiology and the different types of cardiovascular complications, the indications, types, and efficacy of flow-restrictive procedures in the context of a high-flow AVF, as well as some precautions and considerations for AVF creation in high-risk patients.

Accumulated BCAAs and BCKAs contribute to the HFD-induced deterioration of Alzheimer's disease via a dysfunctional TREM2-related reduction in microglial β-amyloid clearance

Accumulated BCAAs and BCKAs contribute to the HFD-induced deterioration of Alzheimer's disease via a dysfunctional TREM2-related reduction in microglial β-amyloid clearance

Severe Disease Activation after Fingolimod Discontinuation in a Pediatric Multiple Sclerosis Patient: A Case Report and Literature Review.

Adult reports of unexpected severe disease worsening, often termed "rebound," shortly after discontinuing fingolimod in a subset of patients with multiple sclerosis (MS), have grown over the last decade. This phenomenon, however, remains poorly described in pediatric MS patients. We present findings of a 15-year-old who experienced a debilitating relapse 4 weeks after stopping fingolimod to switch to ocrelizumab. Imaging revealed multiple large new lesions far exceeding any previously observed activity level in the patient. Despite prompt high-dose corticosteroids, plasma exchange, and prolonged rehabilitation therapy, significant residual deficits involving cognition, balance, and vision remain from the attack. This case underscores that pediatric MS patients are also at risk of severe disease deterioration after fingolimod withdrawal and require close monitoring when switching therapies.

Circulating Levels of Low-Density Granulocytes and Cell-Free DNA as Predictors of Cardiovascular Disease and Bone Deterioration in SLE Patients.

The present work evaluates the predictive value of low-density granulocytes (LDGs) for the development of cardiovascular disease (CVD) and/or bone deterioration (BD) in a 6-year prospective study in systemic lupus erythematosus (SLE). Considering the high SLE-LDG capacity to form neutrophil extracellular traps (NETs), circulating levels of total cell-free DNA (cirDNA) and relative amounts of mitochondrial and nuclear DNA (mtDNA and nDNA, respectively) were tested as LDG-associated biomarkers to identify SLE patients at risk of CVD and BD. The frequency of total blood LDGs, as well as the CD16negCD14neg (nLDG) and CD16posCD14low (pLDG) subsets, was quantified by flow cytometry in 33 controls and 144 SLE patients. Total cirDNA and relative amounts of mitochondrial (mtDNA) and nuclear (nDNA) cell-free DNA were measured by fluorometry or qPCR in plasma from a subgroup of 117 patients and 23 controls at enrolment. Our findings showed increased blood levels of SLE-nLDGs at enrolment associated with prospective CVD development (pCVD) and the presence of BD, thus revealing LDG expansion as a predictor of both comorbidities in SLE progression. The amounts of the different types of circulating DNA analyzed were increased in patients, especially those presenting with traditional CV risk factors or subclinical atheromatosis. Similar to nLDGs, the nDNA concentration could predict the development of pCVD in SLE, supporting the quantification of cirDNA levels as a surrogate marker of LDGs in clinical practice.

Relation between Serum Uric Acid and Anthropometric Measures in Diabetic Nephropathy Patients

Background: Diabetic nephropathy is a major challenge of diabetes mellitus, leading to significant morbidityand mortality. Raised serum uric acid (SUA) tier is a potential cause of deterioration of kidney disease, such asdiabetic nephropathy.Anthropometric measuresfor instance Body MassIndex (BMI) and waist circumference(WC) are crucial markers of adiposity, which is intimately linked to both progression of diabetic nephropathyand hyperuricemia. Objective: To evaluate the relation between SUAand anthropometric measures in diabetic nephropathy.Methods: Across-sectional study was executed involving 150 patients by convenience sampling diagnosedwith diabetic nephropathy at the Diabetic Clinic of Tertiary care Hospital in Lahore. SUAlevels were measuredusing enzymatic methods, while anthropometric measures, including BMI and waist circumference, wererecorded. The relation between SUA and these anthropometric measures was analyzed using Spearman correlation coefficient. Results: The median (IQR) SUA in diabetic nephropathy patients was 6.9 (5.4-8.6) mg/dl and in healthygroup was 5.2 (4.6-6.2) mg/dl. In diabetic nephropathy group, a significant direct relation of SUAwas foundwith BMI (rho = 0.296, p < 0.001) and also with waist circumference (rho = 0.435, p < 0.001). In healthy group,significant directrelationwasfoundwithwaist circumference only (rho=0.212, p=0.001).SUA,Waist circumference and BMI were higher considerably in diabetic nephropathy when measured against the control. Conclusion: The study demonstrates a significant relationship between elevated SUA levels and adverseanthropometric measures in diabetic nephropathy patients. These findings suggest that managing obesitythrough lifestyle modifications and pharmacotherapy could play a critical role in controlling SUA andpotentially slowing the progression of diabetic nephropathy.

Research progress on pathogenesis of skin pigmentation in chronic liver disease

Chronic liver disease (CLD) is a significant global health concern that leads to increased morbidity and mortality, and is associated with skin pigmentation changes. Excessive facial pigmentation is a common characteristic of patients with CLD, although the exact mechanism underlying this phenomenon remains unclear. Melanin, which consists of eumelanin and pheomelanin, is synthesized in melanocytes. Its production is influenced by cysteine levels and is regulated by key enzymes such as tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and tyrosinase-related protein 2 (TYRP2). The transport of melanosomes within melanocytes relies primarily on the coordinated action of F-actin and microtubules. However, the mechanism of melanin transfer from melanocytes to surrounding dendritic cells requires further investigation. Several factors contribute to liver fibrosis including oxidative stress and inflammatory cytokines. This article discusses the factors that are elevated in the serum of patients with chronic liver disease, which may increase melanin deposition. It also introduces the signaling pathways related to melanin synthesis, providing indirect evidence for the pathological mechanisms underlying increased melanin synthesis in CLD. Additionally, the article points out that pigmentation may serve as an important indicator of liver disease deterioration and suggests the formation of a scoring system that combines related factors to enhance the predictive accuracy. In terms of treatment, antioxidants and anti-inflammatory drugs, such as silymarin and vitamin E, may improve CLD and reduce skin pigmentation, but their specific effects still require further investigation. Future research should focus on validating the mechanisms linking pigmentation changes with CLD progression, and exploring therapeutic methods that can simultaneously improve liver function and skin pigmentation, ultimately aiming for better patient outcomes.

Monocyte to high-density lipoprotein ratio as biomarker for cardiovascular health and cognitive function in the elderly diabetic and nondiabetic population: a case–control study

BackgroundAtherosclerosis plays a crucial role in the progression of cardiovascular disease, which is still a major global health concern. Its onset and advancement are significantly influenced by inflammation, especially when it comes to the immune system’s relationship with hypercholesterolemia. Effective serum biomarkers for atherosclerosis are still elusive, despite continuous research into anti-inflammatory therapies. Both monocytes and high-density lipoprotein play important roles in inflammatory and antioxidant processes, while high-density lipoprotein cholesterol (HDL-C) provides protective benefits, and monocytes are involved in the development of atherosclerotic plaque. The monocyte to high-density lipoprotein ratio (MHR) has emerged as a promising predictor of cardiovascular events, potentially more sensitive than each one’s individual levels. Studies have investigated the relationship between MHR and cardiovascular events in a number of diseases, such as acute coronary syndrome and chronic kidney disease. This study investigates the associations between MHR, atherosclerosis, arteriosclerosis, and cognitive impairment in elderly Egyptian populations, exploring its potential as a diagnostic marker and its role in predicting cognitive decline in diabetic individuals.Comprehending this intricate correlation is essential for developing preventive measures and targeted interventions for preventing cardiovascular disease and cognitive deterioration in the geriatrics.ResultsThe study included 100 participants, 50 with type 2 diabetes and 50 nondiabetic, with a mean age of 67 years. Significant negative correlations were found between MHR and the 3MS test (r: − 0.353, p = 0.012) and (r: − 0.170, p = 0.238) and between carotid femoral PWV and the 3MS test in diabetics and in nondiabetics (r: − 0.453, p = 0.001) in both groups, suggesting a potential link between MHR and cognitive impairment.ConclusionThis study highlights the complex relationship between monocyte to HDL-C ratio (MHR), atherosclerosis, and cognitive function in the elderly. Positive correlations were found between MHR and carotid intima-media thickness and carotid femoral PWV, suggesting a role for MHR in atherosclerosis. Notably, a negative correlation between MHR and cognitive function in diabetic individuals suggests a potential link between MHR and cognitive decline.

A framework to conceptualize social prescribing services from a prevention perspective

ObjectiveSocial prescribing models are expanding worldwide to serve multiple goals, such as attending to social conditions that affect people's health, supporting patients with mental health issues or other long-term conditions, facilitating community building and reducing demands on the health care system. Implicitly, many social prescribing services seek to promote health, prevent morbidity or deterioration of disease. Given that the scientific literature currently does not systematically frame these services as preventive service models, we propose a framework to explicitly conceptualize social prescribing from a prevention perspective. MethodsBased on concepts from prevention science (e.g., classifications of prevention approaches), and a comparison of social prescribing models in different countries, we compiled a framework allowing to conceptualize, plan and evaluate social prescribing from a prevention perspective. Examples of social prescribing models were identified using systematic reviews and focused key-word-searches. ResultsOur framework outlines a systematic process for explicitly designing social prescribing models for prevention purposes. It consists of the following steps: defining target populations (e.g., young people with mild mental health issues), formulating intended outcomes (e.g., improved social participation), determining a prevention approach (e.g., universal or indicated prevention), deciding on the implementation setting (e.g., primary or specialized care) and selecting services for prescription (e.g., physical activity outdoors). ConclusionThe framework advances the field by guiding the conceptualization, development and evaluation of social prescribing services. It contributes to widening possible settings for social prescribing and considers potential adverse consequences. Thereby the framework opens up new avenues for social prescribing as preventive service model.

The Association of Periodontitis and different BMI categories with Serum Chemerin Levels -: An Observational Case-Control Study

Background: Chemerin is a adipocytes, epithelial cells, endothelium, fibroblasts, and keratinocytes - derived chemotactic protein. This research was focused on possible connections between glycerin in serum, different body mass indexes (BMI), and appearance of the periodic disease. It is speculated that the findings of our work will help to deepen our comprehension of the interplay of adipokines, obesity, and periodontitis.The purpose of this endeavor is to establish the connections between serum chemerin, the value of BMI, and periodontitis to investigate the association between the indexes associated with the increase in obesity and the onset or aggravation of this disease. Methods: A total of 118 individuals volunteered to be a part of this research. serum obtained before the clinical investigations was the serum sample taken. participants were distributed into six groups: First group (C): 30 subjects with a normal BMI (18.5-24.9 kg/m^2) and a healthy periodontium; second group (Ov): 30 subjects with an overweight BMI (25–29.9 kg/m^2) and a healthy periodontium; third group (Ob): 30 subjects with an obesity BMI (≥ 30) and a healthy periodontium; fourth group (P): 30 periodontitis patients with a normal BMI (18.5-24.9 kg/m^2); fifth group (P+Ov): 30 periodontitis patients with an overweight BMI (25–29.9 kg/m^2) and sixth group (P+Ob): 30 periodontitis patients with obesity BMI (≥ 30). Evaluation of probe debut (PPD), clinical attachment loss (CAL), and bleeding upon probing (BOP) were the methods used in the periodontal test. Results: The findings of the study point out periodontal patients, and in particular, higher body mass index-filled serum levels of chemerin. Among all the study groups, patients with combined very severe obesity and periodontitis (P+Ob) were found to have the highest chemerin levels in their serum. Chemerin (C) of the control group with a weight within the normal range and a healthy area of periodontium was lower in reach. Conclusions: The results suggested that chemerin might be a good indicator biomolecule, which would provide information about the disease progress and deterioration, not only in the cases of overweight subjects but most probably in every person affected. may have a healing effect as its inflammatory effect could be counteracted.

The role of antibody-dependent enhancement in dengue vaccination

Dengue is the most rapidly spreading vector-borne disease worldwide, with over half the global population at risk for an infection. Antibody-dependent enhancement (ADE) is associated with increased disease severity and may also be attributable to the deterioration of disease in vaccinated people. Two dengue vaccines are approved momentarily, with more in development. The increasing use of vaccines against dengue, combined with the development of more, makes a thorough understanding of the processes behind ADE more important than ever. Above that, due to the lack of treatment options, this method of prevention is of great importance. This review aims to explore the impact of ADE in dengue vaccinations, with the goal of enhancing potential vaccination strategies in the fight against dengue.

Role of Emerging Urinary Biomarkers in Predicting Progressive Deterioration of Kidney Function in Congenital Anomalies of Kidney and Urinary Tract: Trefoil Family Factor 3, Alpha Soluble Klotho and Urinary Microalbuminuria

IntroductionChronic kidney disease is an irreversible fate of many CAKUT (Congenital Abnormalities of the Kidneys and Urinary Tract) patients. Biomarkers involved in the disease progression are raised early in the disease process and aid in identifying the individuals at risk of progressive renal function decline. AimsTo determine and compare the initial levels of urinary biomarkers in patients of CAKUT with asymptomatic controls and to correlate the same with progression of renal disease. ResultsThis study includes 66 children with CAKUT and 22 healthy controls. Initial levels of three urinary Biomarkers: Trefoil family factor 3 (TFF3), Alpha soluble Klotho and Albumin-to-creatinine ratio (ACR) was recorded. Kidney function was assessed initially and at the end of 1 y follow up. Progressive deterioration of renal disease was noted in 26 (fall in GFR by >10 ml/min/m2). Median levels of urinary TFF3, alpha soluble Klotho and ACR was higher in patients with CAKUT (263, 18, 56 mcg/gCr) as compared to controls (15, 5, 6 mcg/gCr) and was further higher in patients having a progressive kidney disease (586, 40, 182 mcg/gCr). The cut-off value of the TEF3 to diagnose progressive renal disease was 178 mcg/g Cr with sensitivity and specificity of 95 % and 96 %, respectively. Using a cut-off of 29 mg/g Cr for ACR, sensitivity and specificity were 97 and 96 %, respectively.Urinary soluble Klotho was a relatively poor urinary biomarker with sensitivity and specificity of only 70 and 78 %, respectively, at a cut-off value of 18 mcg/g Cr. ConclusionTFF3 and ACR are useful biomarkers which can be included in the biomarker panel to identify patients having a progressive renal disease and are at a risk of developing CKD.

Machine Learning as a Tool for Auxiliary Diagnosis of Osteoporosis

By making predictions from the model created with machine learning, specifically supervised learning, this essay focuses on the auxiliary diagnosis of osteoporosis. The chosen dataset includes highly relevant indexes that determine the diagnosis of osteoporosis. After doing the feature selection and one-hot encoding to preprocess the dataset, we then split the dataset into validation and training sets to avoid overfitting. Then, to train the model for prediction, we used the neuron network, chose ReLU and Sigmoid functions as activation functions, and changed the number of neurons and epochs to find the best-fit model. Through further measurement, evaluation, and application, including plotting the binary cross entropy error diagram and analyzing the classification report, the model is examined as highly accurate and desirable. With an appreciable degree of accuracy, this model for auxiliary diagnosis is able to prevent disease development or deterioration by detecting early symptoms and vulnerable populations, reduce the probability for doctors to misdiagnose, and improve the efficiency and quality of the osteoporosis diagnosis, therefore enhancing patient experiences.

Research progress of traditional Chinese medicine on the treatment of diarrhea by regulating intestinal microbiota and its metabolites based on renal-intestinal axis.

Intestinal microbiota and its metabolites are involved in many physiological processes of the human body and play a vital role in maintaining human health. The occurrence of kidney disease can cause intestinal microbiota imbalance, resulting in diarrhea. The change of intestinal microbiota and its metabolites content can aggravate renal function injury, which has a bidirectional regulating effect. The theory of renal-intestinal axis further clarified that the impaired renal function is related to the imbalance of intestinal microorganisms, and the impaired intestinal barrier is related to the accumulation of toxin products. Because of its unique therapeutic advantages, Traditional Chinese Medicine can treat diarrhea by enhancing the growth of beneficial bacteria, inhibiting pathogenic bacteria and immune regulation, and slow down the continuous deterioration of kidney disease. This paper focuses on the relationship between intestinal microbiota and its metabolites and diarrhea, the influence of Traditional Chinese Medicine on intestinal microbiota in the treatment of diarrhea, and the role of intestinal microbiota and its metabolites in the renal-intestinal axis. It provides a theoretical basis for Traditional Chinese Medicine to regulate intestinal microbiota and its metabolites based on the renal-intestinal axis theory to treat nephrology-induced diarrhea, and also provides a new idea and method for Traitional Chinese Medicine to treat nephrology-induced diarrhea.

Digital markers of asthma exacerbations: a systematic review.

With the increase in use of digital technologies, there is growing interest in digital markers, where technology is used to detect early markers of disease deterioration. The aim of this systematic review is to summarise the evidence relating to digital markers of asthma exacerbations. A systematic search of the following databases was conducted, using key search terms relating to asthma, digital and exacerbations: Ovid MEDLINE, EMBASE, Psycinfo, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials. Studies that aimed to explore the relationship between any digitally measured marker and asthma exacerbations using any form of portable digital sensor technology were included. 23 papers were included. The digital markers related to five key categories: environmental, physiological, medication, lung function and breath-related parameters. The most commonly studied marker was lung function, which was reported in over half (13 out of 23) of the papers. However, studies were conflicting in terms of the use of lung function parameters as a predictor of asthma exacerbations. Medication parameters were measured in over a third of the studies (10 out of 23) with a focus on short-acting β-agonist (SABA) use as a marker of exacerbations. Only four and two studies measured heart rate and cough, respectively; however, both parameters were positively associated with exacerbations in all reported studies. Several digital markers are associated with asthma exacerbations. This suggests a potential role for using parameters such as heart rate, SABA use and, potentially, cough as digital markers of asthma exacerbations.

Abstract P231: Self-administration of Remifentanil Induces Endothelial Dysfunction in Thoracic Aorta and Impaired Cavernosal Reactivity of Wistar Rats

Aims: Recent studies have implicated the use of prescription opioids as a risk factor for cardiovascular diseases (CVD), with associations including myocardial infarction, coronary artery disease and vascular deterioration. Further, opioid-dependent patients show increased vascular aging and arterial stiffness when compared to opioid-naïve controls. Our hypothesis was that rats dependent on remifentanil (a fentanyl analog) after a 12-day operant self-administration (SA) study lead to vascular dysfunction in thoracic aorta. Because erectile dysfunction (ED) is associated with arterial stiffness and is positively correlated with its severity, we hypothesized that opioid SA impaired corpus cavernosum (CC) reactivity as well. Methods: Male Wistar rats (12 weeks-old) were implanted with intravenous catheters and learned to lever press (FR1) for remifentanil (1µg/kg/infusion). A separate group of rats received passive yoked infusions of saline administered in synchrony with remifentanil-treated animals to control volumetric vascular effects. Following administration, animals were euthanized, and aorta and CC collected to evaluate function using both pin and strip myographs. Concentration-response curves to phenylephrine (Phe; 10 -11 -10 -4 M), sodium nitroprusside (SNP) and acetylcholine (Ach or SNP; 10 -10 -10 -4 M) were performed to test contractility and endothelium-independent and -dependent relaxation respectively. Results: Remifentanil-treated rats showed rapidly acquired SA behavior, exhibiting robust and selective drug-paired lever pressing when compared to the non-drug paired lever. In contrast, yoked saline-treated controls rarely exhibited lever pressing. Endothelium-dependent relaxation in the aorta was diminished in the remifentanil group (Rmax: Control: 68.7±2.7 vs. Remi: 47.8±3.7%; p<0.05). There were no observed alterations in endothelium-independent relaxation or vascular contraction. However, CC contraction was slightly shifted to the right in remifentanil treated rats (pEC 50 : Control: 6.04±0.09 vs. Remi: 5.66±0.12; p<0.05). No changes were observed in the CC relaxant response. These findings indicate that 12 days of remifentanil administration results in endothelial dysfunction in large arteries and impaired cavernosal reactivity. Long-term exposure may lead to aortic stiffness exacerbating ED severity and increases in pulse-wave velocity in opioid-dependent patients contributing to the onset of hypertension.

Inflammasome Proteins Are Reliable Biomarkers of the Inflammatory Response in Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is caused by abnormal blood vessel dilation and subsequent rupture, resulting in blood pooling in the subarachnoid space. This neurological insult results in the activation of the inflammasome, a multiprotein complex that processes pro-inflammatory interleukin (IL)-1 cytokines leading to morbidity and mortality. Moreover, increases in inflammasome proteins are associated with clinical deterioration in many neurological diseases. Limited studies have investigated inflammasome protein expression following aSAH. Reliable markers of the inflammatory response associated with aSAH may allow for earlier detection of patients at risk for complications and aid in the identification of novel pharmacologic targets. Here, we investigated whether inflammasome signaling proteins may serve as potential biomarkers of the inflammatory response in aSAH. Serum and cerebrospinal fluid (CSF) from fifteen aSAH subjects and healthy age-matched controls and hydrocephalus (CSF) no-aneurysm controls were evaluated for levels of inflammasome signaling proteins and downstream pro-inflammatory cytokines. Protein measurements were carried out using Simple Plex and Single-Molecule Array (Simoa) technology. The area under the curve (AUC) was calculated using receiver operating characteristics (ROCs) to obtain information on biomarker reliability, specificity, sensitivity, cut-off points, and likelihood ratio. In addition, a Spearman r correlation matrix was performed to determine the correlation between inflammasome protein levels and clinical outcome measures. aSAH subjects demonstrated elevated caspase-1, apoptosis-associated speck-like protein with a caspase recruiting domain (ASC), IL-18 and IL-1β levels in serum, and CSF when compared to controls. Each of these proteins was found to be a promising biomarker of inflammation in aSAH in the CSF. In addition, ASC, caspase-1, and IL-1β were found to be promising biomarkers of inflammation in aSAH in serum. Furthermore, we found that elevated levels of inflammasome proteins in serum are useful to predict worse functional outcomes following aSAH. Thus, the determination of inflammasome protein levels in CSF and serum in aSAH may be utilized as reliable biomarkers of inflammation in aSAH and used clinically to monitor patient outcomes.

Epidural block with lidocaine ameliorates kidney function deterioration and fibrosis of chronic kidney disease in rats

BackgroundAccording to evidences from clinical practices and experiments, renal denervation achieved by removing both the afferent and sympathetic nerves has therapeutic impacts on poor renal function and hypertension in chronic kidney disease (CKD). Epidural anesthesia is presumed to function on the target spine segments with a complete sympathetic block. Based on this perspective, we hypothesized that epidural block with lidocaine could ameliorate renal injury in CKD rats. Method and ResultsMale Sprague-Dawley rats weighing 250–300 g were randomized into four groups: control, CKD, CKD + sham, and CKD + epidural block with lidocaine groups. CKD was induced by resection of the lower and upper thirds of the left kidney followed by right nephrectomy one week later. Significant differences in renal function, sympathetic activation as well as renal fibrosis parameters were observed between CKD and control rats. These parameters corresponded with typical phenotypes of CKD rats. Epidural block with lidocaine improved renal function as well as renal fibrosis, and reversed the abnormalities of the renal function and cardiovascular parameters either fully or partially. ConclusionEpidural block with lidocaine confers renal protection, which is presumably mediated by decreasing sympathetic nerve activities in the renal region and other target organs in CKD.

Pro-inflammatory monocytes promote deterioration of coronary heart disease in chip-(clonal hematopoiesis of indeterminate potential)-patients without preferential accumulation in the plaque

Pro-inflammatory monocytes promote deterioration of coronary heart disease in chip-(clonal hematopoiesis of indeterminate potential)-patients without preferential accumulation in the plaque

Rapid deterioration of steatotic liver disease due to portal vein stenosis after pancreaticoduodenectomy

Steatotic liver disease after pancreatoduodenectomy occurs due to various factors, such as exocrine pancreatic insufficiency, impaired intestinal absorption, and malnutrition. The mechanism of steatogenesis differs to that of conventional steatotic liver disease associated with obesity and insulin resistance. We experienced a rare case of rapidly progressive steatotic liver disease accompanied by portal vein stenosis in the early postoperative period after subtotal stomach-preserving pancreaticoduodenectomy for distal cholangiocarcinoma. Although there was a complication due to postoperative drain infection, the patient was discharged from hospital with no nutritional problems. Two months postoperatively, the patient presented to the emergency room with dyspnea. CT showed a markedly steatotic liver, ascites, and portal vein stenosis. A portal vein stent was inserted transhepatically and the steatotic liver disease gradually improved. During the postoperative course, there were no problems indicated by nutritional markers; although the patient had diarrhea associated with postoperative pancreatic exocrine insufficiency, the symptoms were mild and improved after administration of oral pancrelipase. Before the intervention, the patient had intestinal edema, exacerbation of diarrhea, and a low serum zinc concentration, suggesting that impaired absorption caused by intestinal blood stasis and gut barrier dysfunction contributed to the development of steatotic liver disease.