Urea Nitrogen Research Articles

Simulated microgravity predisposes kidney to injury through promoting intrarenal artery remodeling.

Spaceflight-induced multi-organ dysfunction affects the health of astronauts and the safety of in-orbit flight. However, the effect of microgravity on the kidney and the underlying mechanisms are unknown. In the current study, we used a hindlimb unweighting (HU) animal model to simulate microgravity and employed histological analysis, ischemia-reperfusion experiments, renal ultrasonography, bioinformatics analysis, isometric force measurement, and other molecular experimental settings to evaluate the effects of microgravity on the kidneys and the underlying mechanisms involved in this transition. Relative to controls, 31-day hindlimb unweighting had no obvious effect on serum creatinine and urea nitrogen levels as well as on renal injury scores; however, animals in the HU group showed an impaired renal recovery to ischemia-reperfusion injury. Ultrasonography showed that renal resistive index was increased, which indicated an altered renal hemodynamics induced by simulated microgravity. The enhanced vasoconstriction mediated by the Rho-kinase pathway and impaired vasodilation mediated by NO-eNOS of the intrarenal artery contributed to the altered renal hemodynamics. Simulated microgravity predisposes the kidney to ischemia-reperfusion injury. The altered renal hemodynamics induced by renal arterial remodeling may account for the increased renal injury susceptibility, providing a target for early intervention in kidney dysfunction under microgravity.

A nomogram based on trauma-induced coagulopathy for predicting hospital mortality in multi-trauma patients: a retrospective study.

Multi-trauma presents significant challenges due to the complexity of injuries and high mortality rates. Early identification and intervention are crucial for improving outcomes in these critically injured patients. This retrospective study analyzed clinical data from multi-trauma patients admitted to the emergency department of Huiyang Sanhe Hospital between January 10, 2020, and September 30, 2022. Univariate and multivariate logistic regression analyses were conducted to identify independent predictors of hospital mortality. A prediction model was developed based on these prognostic markers, visualized using a nomogram, and its discriminative ability and clinical benefit were evaluated. A total of 124 multi-trauma patients were included in the study, with a hospital mortality rate of 26.7%. Univariate and multivariate logistic regression analyses identified trauma-induced coagulopathy (TIC) (OR 4.238, 95% CI 1.46-12.28), blood urea nitrogen (BUN) (OR 1.397, 95% CI 1.09-1.78), and Glasgow Coma Scale (GCS) score (OR 0.720, 95% CI 0.61-0.85) as independent factors of hospital mortality. Therefore, a nomogram incorporating TIC, BUN, and GCS score was constructed and demonstrated excellent predictive performance and clinical impact (AUC 0.898, 95% CI 0.834-0.962). The nomogram developed in this study provided a practical tool for early prediction of hospital mortality in multi-trauma patients. By focusing on TIC, BUN, and GCS score, this model may facilitate rapid bedside assessment and timely intervention. However, further multicenter, prospective studies are required to validate its performance and applicability.

P-20 EARLY ZOLEDRONIC ACID TREATMENT IN A PEDIATRIC CASE OF OSTEOGENESIS IMPERFECTA TYPE V: CLINICAL OUTCOMES AND THE ROLE OF IFITM5 (BRIL) MUTATION

Abstract Introduction Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility, low bone mass, and frequent fractures. OI is typically associated with mutations in the COL1A1 and COL1A2 genes, but a subset of cases, such as OI type V, is linked to mutations in the IFITM5 gene, also known as BRIL (bone-restricted IFITM-like). Clinical Case This report presents a case of a 2-year-old boy diagnosed with OI type V, a rare form of the disease caused by a mutation in BRIL. The patient exhibited multiple recurrent bone fractures beginning in infancy, though there was no family history of bone disease or consanguineous marriage. Physical examination revealed that the patient was of normal weight and height for his age, with neurodevelopmental milestones met. Laboratory tests showed elevated alkaline phosphatase (ALP) levels, indicative of increased bone turnover, while other values were within normal ranges. Radiological evaluations confirmed an active fracture in the left tibia but showed no additional pathological involvement. Genetic testing identified a de novo C>T variant in the IFITM5 gene, confirming the diagnosis of OI type V. The patient was treated with intravenous zoledronic acid (ZA), a bisphosphonate therapy, which is currently being tested in infants and toddlers for OI treatment. The treatment led to a significant reduction in fracture recurrence and a decrease in ALP levels, demonstrating its efficacy in managing the disease. Despite these positive outcomes, certain hallmark features of OI type V, such as hyperplastic callus formation and new periosteal bone growth, were not observed during follow-up, possibly due to the early initiation of ZA therapy. OI type V is distinguished from other forms of OI by hyperplastic callus formation and increased osteoblast activity, often accompanied by elevated ALP levels. Radiographic and histological findings specific to this type include periosteal bone growth and a reticular lamellation pattern in the bone matrix. Although ZA has shown promise in reducing fracture risk and improving clinical outcomes, its long-term efficacy in preventing other disease manifestations, such as intramembranous ossification, remains uncertain. The underlying pathological mechanisms of OI type V, particularly the role of BRIL, are not yet fully understood. Further research into the activation of BRIL in osteoblasts could lead to the development of targeted therapies that address the root cause of the disease. While ZA therapy has been effective in managing the immediate symptoms of OI type V, a deeper understanding of the disease's genetic and molecular basis is crucial for improving long-term treatment outcomes. In conclusion, the IFITM5 (BRIL) mutation is recognized as the genetic cause of OI type V. Early intervention with ZA has shown positive effects in managing the disease, but further research is needed to fully understand the pathological mechanisms and to develop treatments that can address all aspects of the disease.Table 1:Lab workout (age 2)ALP = alkaline phosphatase; AST = aspartate transaminase; BUN = blood urea nitrogen; GGT = gamma-glutamyl transferase; CBC: complete blood count

Hearing loss in chronic kidney disease in north Indian population: a prospective study

Background: Chronic kidney disease (CKD) is a global public health challenge. Patients with CKD show various otorhinolaryngological manifestations among which sensorineural hearing loss (SNHL) is the commonest. To determine the incidence of hearing loss and to describe the impact of chronic kidney disease on hearing in a tertiary care hospital of north India. Methods: This was a prospective cross-sectional study on 60 cases of CKD and 60 controls attending the ENT OPD at SMGSH, Jammu after getting (Institutional Ethical Committee) IEC clearance. Results: In the present study, 28 out of 60 patients of CKD had hearing loss. All the patients had SNHL in the high frequency range, sparing low and middle frequencies. There was a positive correlation between the stage and duration of CKD with hearing loss. Also, a significant correlation was found between the hearing loss and serum urea and creatinine levels. Conclusion: It was concluded that patients with chronic kidney disease must be evaluated audiometrically at regular intervals, for early identification, management and rehabilitation of hearing loss in order to reduce the co-morbidity of hearing impairment and improve the quality of life of these individuals.

Effects of Dietary Fiber Supplementation on Modulating Uremic Toxins and Inflammation in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Emerging evidence supports the beneficial effects of dietary fiber supplementation in alleviating gut dysbiosis, which leads to a reduction in uremic toxins and inflammatory markers in chronic kidney disease (CKD) patients. However, current evidence-based renal nutrition guidelines do not provide recommendations regarding dietary fiber intake. We performed a systematic review and meta-analysis to investigate and highlight the effects of dietary fiber supplementation on modulating uremic toxins and inflammatory markers in individuals with CKD, with or without dialysis. The eligible randomized controlled trials (RCTs) were identified from PubMed, Scopus, and Cochrane Central Register of Controlled trials until 27 November 2024. The results were synthesized using a random-effects model and presented as standardized mean differences (SMDs) with a 95% confidence interval (CI). A total of 21 studies with 700 patients were included. When compared with the control group, dietary fiber supplementation ranging from 6 to 50 g/day, for typically more than 4 weeks, could significantly reduce the levels of serum uremic toxins, including p-cresyl sulfate, indoxyl sulfate, and blood urea nitrogen (SMD −0.22, −0.34, −0.25, respectively, with p-values < 0.05), as well as biomarkers of inflammation, including interleukin-6 and tumor necrosis factor alpha (SMD −0.44, −0.34, respectively, with p-values < 0.05). These beneficial effects were consistent across different types of fibers and CKD status (with or without dialysis). However, no significant reduction in serum trimethylamine N-oxide, uric acid, and high-sensitivity C-reactive protein levels was observed with dietary fiber intervention. This study would pave the way for prioritizing dietary quality, particularly a fiber-rich diet, beyond the traditional focus on the quantities of protein, energy, and electrolyte restrictions among individuals with CKD.

Sex differences in aristolochic acid I-induced nephrotoxicity in mice and the effect of estradiol.

Aristolochic acid I (AAI), the most prominent component of aristolochic acids and found in nearly all aristolochic herbs, has been demonstrated significant nephrotoxicity. In this study, an acute nephrotoxicity model of AAI mice was established by a single dose injection of AAI. It was observed that there are differences of the sensitivity to AAI nephrotoxicity in female and male mice, with male mice exhibiting nephrotoxic effects even at lower doses. After the administration of estradiol (E2), serum levels of creatinine and urea nitrogen in male mice were observed to decrease. We used UPLC-MS/MS to determine the pharmacokinetics and renal tissue distribution of AAI and its metabolite aristololactam I (ALI). It was found that AAI had a longer plasma half-life in female mice, while the content of ALI in renal tissue of male mice was much higher than that in female. The administration of E2 was found to extend the half-life of AAI and reduce the levels of ALI in the kidneys of male mice. The proposed mechanism may involve the reduction of renal OATs transporter activity by E2, leading to decreased concentrations of ALI in the renal tubules. This reduction may mitigate its toxic effects on epithelial cells and diminish the production of its harmful metabolites, thereby alleviating AAI-induced nephrotoxicity.

In vitro and in vivo evidence of the effectiveness of gallic acid on glycerol-induced acute kidney injuries.

Because acute kidney injuries (AKI) are one of the critical health problems worldwide, studies on the risk factors, mechanisms, and treatment strategies seem necessary. Glycerol (GLY), known to induce cell necrosis via myoglobin accumulation in renal tubules, is widely used as an AKI model. This study aimed to evaluate the protective effects of gallic acid (GA) against GLY-induced AKI. The study utilized both in vivo and in vitro models. In vivo, healthy rats were divided into six groups: control (normal saline), GLY (10mg/kg, intramuscularly), GLY + GA10 (10mg/kg), GLY + GA50 (50mg/kg), GLY + GA100 (100mg/kg), and GA (100mg/kg). GA was administered by gavage for seven consecutive days, followed by a single intramuscular injection of GLY. Kidney biomarkers, lactate dehydrogenase (LDH), oxidative stress markers, inflammatory indices, and histological parameters were assessed 72h post-injection. In vitro, human embryonic kidney 2 (HK-2) cells were incubated with GLY and GA at different concentrations (30, 60, and 125μg/ml) to evaluate cell viability, reactive oxygen species (ROS) production, oxidative stress, and inflammatory cytokines. GLY administration significantly elevated renal dysfunction markers, including blood urea nitrogen and creatinine, alongside oxidative stress and reduced cell viability. GA treatment improved kidney biomarkers, enhanced antioxidant enzyme activity, and reduced inflammatory cytokines. Histological analyses also showed improved kidney structural integrity in GA-treated rats compared to the GLY group. This study confirmed that GLY induces AKI through oxidative stress, inflammation, and structural damage. GA exhibited significant renal protective effects by enhancing antioxidant defenses and reducing inflammation. These findings support GA as a potential natural supplement for preventing or treating renal diseases.

Crosstalk: Biochemical Signatures and Clinical Implications in Rare Hereditary Hemolytic Anemias (Hereditary Spherocytosis).

Clinical Hereditary Hemolytic Anemia (HAA) particularly Hereditary Spherocytosis (HS) encompasses diverse genetic disorders causing premature red blood cell destruction and intrinsic RBC defects. There's a pressing need for standardized diagnostic protocols tailored to the Asian population, particularly in Saudi Arabia, underscoring the significance of thorough blood biochemistry analysis. A case-control prospective study was conducted at King Abdulaziz University, samples were obtained from King Fahad, hospital Jeddah, Saudi Arabia, serving a significant population, and blood samples from 27 patients meeting ethical criteria for HHA and HS. Inclusion criteria included diagnosed patients of any age and sex, while exclusion criteria encompass chronic infections, metabolic diseases, pregnancy, and lactation. Blood profiling was conducted following strict protocols, aiming to glean insights into patients' management and therapeutic strategies. Despite an intended larger sample size, limitations in availability led to the inclusion of 27 patient analyses. Among 27 participants, males comprised 59.3%, females 40.7%. Anemia types indicated 22.2% Type 1 (HHA) and 77.8% Type 3 (HS). Age groups (<30, 31-59, ≥60 years) highlighted HS prevalence, notably in older individuals. Blood pressure analysis revealed age-related increases, especially in those over 60 with systolic BP (147.33 ± 9.86 mm/Hg) (p≤0.02) and diastolic BP (85.67 ± 9.01 mm/Hg) (p≤0.03) emphasizing agespecific monitoring. Temperature variations were noted across ages, significant in patients over 60 (35.93 ± 1.100C) (p≤0.09), indicating potential clinical relevance. Iron levels showed no age-related differences, while Blood Urea Nitrogen (BUN) levels rose with age, particularly in those over 60 (35.83 ± 16.67 mm/dL) (p≤0.04), suggesting age-related influence. Alkaline Phosphatase levels increased with age, especially in patients aged 31 to 59 (205.80±123.17IU/L)(p≤0.001), warranting further investigation. Similarly, Aspartate Transferase levels rose with age, especially in patients aged 31 to 59 (134.69 ± 284.58 U/L) (p≤0.01),), underlining age-specific considerations. Notable differences in BUN (15.03 mm/dL and 29.06 mm/dL)and Aspartate Transferase (33.01 U/L and 115.66 U/L) levels were observed among different anemia types with no major significant alteration in LDH. The results suggest unique biochemical signatures with potential renal and hepatic implications, underscoring the importance of biochemical assessment in managing hereditary hemolytic anemias, particularly HS.

In vivo toxic and lethal cardiorespiratory effects of a synthetic quaternary ammonium salt derivative of haloperidol in mice.

To investigate the toxicity of N-n-butyl haloperidol iodide (F2), a quaternary ammonium salt derivative of haloperidol, in mice for potential therapeutic purposes. The acute median lethal dose (LD50) of F2 was determined using the Bliss method following intravenous administration in mice. Routine surface electrocardiograms (ECGs) and arterial blood pressures (aBPs) were recorded under general anesthesia in untreated and pharmacologically vagotomized mice injected with F2. Sublethal doses of F2 were tested for their effects on aBP, heart rate, and biochemical parameters such as lactate dehydrogenase (LDH), blood urea nitrogen (BUN), and serum lactate levels. Histopathological changes in the heart, lungs, liver, and kidneys were evaluated after F2 administration. The acute LD50 of F2 was determined to be 5.11 mg/kg. A 10 mg/kg dose of F2 caused severe hypotension, second-degree atrioventricular block, progressive prolongation of Pmurr intervals, and death due to cardiac asystole. Similar ECG and aBP changes were observed in atropine-pretreated mice, indicating that cholinergic effects do not play a major role in F2-induced toxicity. Sublethal doses of F2 (1.2 and 2.4 mg/kg) caused dose-dependent decreases in aBP and increases in heart rate. F2 induced significant, dose-dependent increases in LDH, BUN, and serum lactate levels. Histopathological analysis revealed acute lung lesions at 10 mg/kg, with no significant changes observed in the heart, liver, or kidneys. Acute intravenous injection of F2 exhibits dose-dependent cardiopulmonary toxicity, characterized by severe hypotension, arrhythmias, and biochemical changes. These findings highlight the potential risks of F2 and the need for further evaluation of its safety profile for therapeutic use.

Eleutherococcus senticosus Alleviates Aristolochic-Acid-Induced Acute Kidney Damage by Inhibiting the NLRP3/IL-1β Signaling Pathway in Mice.

Eleutherococcus senticosus (ES) exerts various pharmacological effects, including renoprotection in a rat model of renal ischemia-reperfusion injury. However, the mechanisms of these effects remain unclear. Therefore, we investigated the effects and mechanisms of ES on aristolochic acid (AA)-induced acute kidney injury in mice. The experimental mice were divided into the control group, the model group (AA-induced acute kidney injury model), the model + ES group (Eleutherococcus senticosus boiled-free granules treated by gavage for two weeks), the model + fasudil group (fasudil administered intraperitoneally for three days), and the model + ES + fasudil group. After AA intervention in normal mice, the expression of ASC and NLRP3 and the levels of IL-1β, IL-18, and TNF-α were significantly elevated in mouse renal tissues (P < 0.05). However, AA-induced renal dysfunction was ameliorated by both ES and fasudil, which was confirmed by the decrease in serum creatinine and blood urea nitrogen levels, as well as by renal histopathological abnormalities such as renal tubule dilation and tubular formation. In addition, the inflammatory response of AA-induced renal inflammation was inhibited by both ES and fasudil, and the expression of ASC and NLRP3 and the levels of IL-1β, IL-18, and TNF-α were significantly higher in mouse renal tissues after the treatment of either ES or fasudil (P < 0.05). ES may be a potential treatment agent for aristolochic-acid-triggered nephropathy, with inhibition of the NLRP3/IL-1β as one plausible underlying mechanism.

Milk Performance and Grazing Behaviour of Cinisara Cows Supplemented with Low- and High-Polyphenols Faba Bean Varieties

The high degradability of crude protein (CP) from fresh grass can impair its utilization in ruminants. The presence of a moderate level of polyphenolic substances in the diet of grazing animals could help to overcome this problem. The study aimed to evaluate the effects of supplementation with two varieties of faba bean, with different polyphenol contents, on milk yield and quality, as well as on grazing behaviour, in Cinisara grazing cows. A total of 30 cows, homogeneous per days in milk (61 ± 29) and milk yield (12.9 kg ± 3.2), fed on a mixed pasture (CP 17.9% DM) and supplied with grains (an equal mixture of barley, oats, and wheat) and mixed hay (CP 10.2% DM), were assigned to three dietary treatments and supplemented as follows: control group (C, 10 cows), 1 kg of hay, 6 kg of grains mixture, and 0.4 kg soybean meal; low polyphenols group (LP, 10 cows), 1 kg of hay, 4 kg of grains mixture, and 2 kg/d of faba bean var. Torrelama (total polyphenols 4.4 mg GAE/g DM; CP 28.4% DM); high polyphenols group (HP, 10 cows), 2 kg of hay, 4 kg of grains mixture, and 2 kg/d of faba bean var. Fanfare (total polyphenols 16.4 mg GAE/g DM; CP 28.9% DM). All groups were allowed to graze for 20 h/d on natural pasture forage. The HP supplement tended to increase the milk yield compared to that of the LP and C groups (17.1 vs. 15.3 and 14.6 kg/d, respectively; p = 0.057) but reduced the protein (3.20 vs. 3.39 and 3.47%; p = 0.009) and casein proportions (2.45 vs. 2.67 and 2.74%, respectively; p = 0.007) compared to those from the LP and C treatments. HP milk also showed a higher milk urea nitrogen (MUN) value compared to that of C milk, while an intermediate level was measured in LP milk (25.5 vs. 22.9 and 20.9 mg/dl, respectively; p = 0.036). No dietary effect was evident in the milk fatty acid profile. Eating time at pasture and biting rate were not affected by supplementation. The results do not seem to suggest a difference in the efficiency of use of supplements with different polyphenol contents. In any case, they seem to demonstrate that the use of faba beans, regardless of their polyphenol content, represents a valid alternative to soyabeans, also taking into account the tendency for an increased milk yield found by integrating pasture grazing with faba beans possessing a high level of polyphenols, without significant worsening of the qualitative characteristics of the milk or negatively affecting grazing behaviour.

Effect of rapamycin-eluting stents on in-stent restenosis and early inflammatory response in coronary artery narrowing animal models

Objectiveit was to evaluate the efficacy and safety of rapamycin-eluting stents at different doses in the treatment of coronary artery narrowing in miniature pigs.Methodsa total of 20 miniature pigs were randomly assigned into four groups: S1 group (low-dose rapamycin-coated stent, 55 µg/mm2), S2 group (medium-dose rapamycin-coated stent, 120 µg/mm2), S3 group (high-dose rapamycin-coated stent, 415 µg/mm2), and D0 group (bare metal stent). The stent size was 3.0 mm × 18 mm, with an over-expansion ratio of 1.1. Each group consisted of five pigs. Stent implantation was followed by euthanasia and tissue collection after 1 month. Vascular measurements, inflammatory response scores, cardiovascular injury scores, endothelialization scores, liver and kidney function indices, and myocardial injury markers were compared among the groups.Resultsthe neointimal thickness in the S2 and S3 groups was significantly lower than that in the S1 and D0 groups (S1 group: 24.08 ± 3.95, S2 group: 1.86 ± 0.28, S3 group: 2.72 ± 0.74, D0 group: 22.85 ± 3.15, P < 0.05). The residual lumen area in the S2 and S3 groups was significantly larger than that in the S1 and D0 groups (S1 group: 2.73 ± 0.51, S2 group: 4.25 ± 0.78, S3 group: 3.91 ± 0.73, D0 group: 2.91 ± 0.44, P < 0.05). The neointimal area in the S2 and S3 groups was significantly smaller than that in the S1 and D0 groups (S1 group: 3.44 ± 0.84, S2 group: 1.78 ± 0.25, S3 group: 2.07 ± 0.41, D0 group: 3.43 ± 0.72, P < 0.05). The degree of lumen narrowing in the S2 and S3 groups was significantly lower than that in the S1 and D0 groups (S1 group: 44.25 ± 3.66%, S2 group: 14.19 ± 2.01%, S3 group: 15.29 ± 2.45%, D0 group: 21.79 ± 3.51%, P < 0.05). The inflammation scores of coronary artery walls in the S2 and S3 groups of miniature pigs were markedly lower than those in the S1 and D0 groups (P < 0.05). The cardiovascular injury scores (P = 0.072) and endothelialization scores (P = 0.085) differed slightly among the four groups (P > 0.05). Post-operative liver function indicators (alanine transaminase, aspartate transaminase), kidney function indicators (blood urea nitrogen, serum creatinine), and myocardial injury markers (creatine kinase, creatine kinase-MB) also showed neglectable differences among the four groups (P > 0.05).Conclusionmedium and high doses of rapamycin-eluting stents effectively inhibit neointimal hyperplasia and local vascular inflammatory response in miniature pigs without causing damage to liver and kidney functions or myocardial cells. These stents demonstrate high efficacy and safety. Rapamycin-coated coronary stents, as an effective treatment for coronary artery stenosis, may achieve further improvement in therapeutic efficacy through optimization of drug dosage and stent design.

Sivelestat sodium protects against renal ischemia/reperfusion injury by reduction of NETs formation.

Ischemia-reperfusion injury (IRI) often results in renal impairment. While the presence of neutrophil extracellular traps (NETs) is consistently observed, their specific impact on IRI is not yet defined. Sivelestat sodium, an inhibitor of neutrophil elastase which is crucial for NET formation, may offer a therapeutic approach to renal IRI, warranting further research. A mouse model was established for early-stage renal IRI, confirmed by injury markers and histological assessments. The involvement of NETs in renal I/R was demonstrated using immunofluorescence and Western blot. Renal function and pathology were further evaluated through a comprehensive set of methods, including Periodic Acid-Schiff staining (PAS) and Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) staining, enzyme-linked immunosorbent assay (ELISA), Real time Glomerular Filtration Rate (RT-GFR) monitoring, Polymerase Chain Reaction (PCR), biochemical analysis, and additional Western blot and immunofluorescence assays. We firstly quantified NET expression in renal IRI mice, noting a peak at 24 hours. Subsequently, sivelestat sodium treatment was administered, resulting in decreased MPO, CitH3, and attenuated tubular damage. Moreover, it resulted in a decrease in serum levels of creatinine, blood urea nitrogen (BUN), as well as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Additionally, it lowered the abundance of renal tissue inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and mitigated the levels of oxidative stress indicators malondialdehyde (MDA) and 4 Hydroxynonenal (4HNE), accompanied by a decline in renal cell apoptosis and an enhancement of GFR in renal I/R mice. Sivelestat sodium ameliorates renal IRI by downregulating neutrophil NETs, reducing inflammation, oxidative stress, and apoptosis, thereby enhancing renal function.

Evaluating the impact of ESICM 2023 guidelines and the new global definition of ARDS on clinical outcomes: insights from MIMIC-IV cohort data

BackgroundIn 2023, the European Society of Intensive Care Medicine (ESICM) recommended updated criteria for acute respiratory distress syndrome (ARDS). In 2024, Matthay et al. updated the global ARDS definition in AJRCCM, titled “A New Global Definition of Acute Respiratory Distress Syndrome.” However, the impact of this new definition on ARDS treatments is currently unknown.ObjectiveThis study aims to determine the effect of the new ARDS definition on patients with hypoxemic respiratory failure and study the heterogeneity of patients in the new definition to guide treatment.MethodsClinical consultation data from the Medical Information Mart for Intensive Care IV database were extracted using Structured Query Language based on the PostgreSQL tool (version 10.0). Data were analyzed using Python (version 3.9) and the deep learning framework Pytorch. Kaplan–Meier survival analysis was used to compare survival between the old and new definitions. A hierarchical clustering approach was applied to identify potential ARDS clinical subtypes.ResultsThe new definition diagnosed ARDS earlier and included individuals with lower mortality rates compared with the Berlin definition. Patients meeting the new definition but not the Berlin criteria exhibited a favorable response to non-invasive ventilation strategies (p = 0.009). The XGBoost classifier, trained to predict subphenotypes, achieved an AUC of 0.88 ± 0.02 on the training set. Additionally, mortality was significantly associated with patients with hypoxemia compared with survivors, particularly regarding respiratory parameters. Easily accessible metrics, such as respiratory rate and urea nitrogen (BUN), can help diagnose ARDS in high-risk populations in resource-limited settings.ConclusionsThe new ARDS definition offers advantages in earlier detection, more accurate grading, and more precise diagnosis in resource-limited settings compared with the Berlin definition. This study also established a robust prediction model for early ARDS identification, improving the patient prognosis and reducing the mortality rate.

A Therapeutic Approach of Chitosan-loaded p-Coumaric Acid Nanoparticles to Alleviate Diabetic Nephropathy in Wister Rats.

This study evaluated the renoprotective effects of p-Coumaric acid nanoparticles (PCNPs) in nephropathic rats. Six groups of male Albino Wistar rats were randomly assigned. Group 1 was the control, while Group 2 received 45 mg/kg of streptozotocin (STZ) to induce diabetic nephropathy. Groups 3, 4, and 5 received STZ (45 mg/kg) along with PCNPs at doses of 20, 40, and 80 mg/kg, respectively. Group 6 received 80 mg/kg of PCNPs without STZ. Body weight, blood glucose, insulin, hemoglobin (Hb), and glycosylated hemoglobin (HbA1c) levels were measured. Blood urea, serum creatinine, kidney antioxidant enzymes, and lipid peroxidation levels were also analyzed. Histological and immunohistochemical studies of kidney tissues were performed. PCNPs (80 mg/kg) significantly reduced serum glucose, creatinine, and urea levels while increasing insulin levels and antioxidant activity in the kidneys. Histological analysis revealed that nephropathic rats exhibited cellular damage, including shrinkage of Bowman's capsule and lesions in the kidneys, along with degeneration in the Islets of Langerhans in the pancreas. PCNPs treatment restored these morphological alterations in the pancreas, liver, and kidneys to near-normal. Furthermore, nephropathic rats had elevated IL-6 and TNF-α expression in the renal tubules and glomeruli, which was reduced following PCNPs treatment. The findings suggest that PCNPs exhibit antihyperglycemic, antioxidant, antiglycation, and renoprotective effects in STZ-induced diabetic nephropathy.

Evaluation of the predictive value of the glucose-to-potassium ratio in predicting in-hospital mortality of patients with sepsis and septic shock.

In this study, we aimed to evaluate the role of the glucose-to-potassium ratio in predicting in-hospital mortality and prognosis of patients diagnosed with sepsis and septic shock in an emergency department and admitted to an emergency critical intensive care unit (ICU). This study was aretrospective and observational evaluation of nontraumatic sepsis and septic shock patients > 18years of age who were admitted to the emergency department of atertiary training and research hospital and had available glucose and potassium values at the time of admission. The patients were evaluated over a24-month period. The primary goal of this study was to examine the relationship between the glucose-to-potassium ratio and in-hospital mortality in sepsis patients. Data derived from 175 patients were included in the statistical analysis. Blood urea nitrogen, creatinine, lactate dehydrogenase, direct bilirubin, C‑reactive protein, and lactate levels were found to be significantly higher in the nonsurvivor group than in the survivor group (p < 0.05). On the other hand, hemoglobin, hematocrit, albumin, pH, HCO3 and base excess levels were found to be statistically significantly higher in the survivor group than in the nonsurvivor group (p < 0.05). The glucose-to-potassium ratio was not significant in terms of predicting mortality in sepsis patients (p = 0.324). In the receiver-operating characteristic (ROC) analysis of various parameters' significance in terms of predicting mortality, APACHE2 scores had the highest area under the curve (AUC) value (0.729). According to the results of this study, the glucose-to-potassium ratio did not have asignificant value in predicting mortality risk in sepsis and septic shock patients admitted from the emergency department to the emergency critical ICU.

Inefficient Dialysis and Hematological Abnormalities in End-Stage Renal Disease Patients: A Cross-Sectional Study

Purpose: End-stage renal disease (ESKD) necessitates hemodialysis, a life-sustaining therapy that mimics kidney function. This study aimed to investigate the association between markers of inadequate dialysis efficacy and the prevalence of hematological abnormalities in patients undergoing hemodialysis. Methods: A cross-sectional study was conducted among 61 patients receiving hemodialysis at Mesallata Central Hospital, Libya, in October 2024. Data were collected on hematological parameters (white blood cell count, hemoglobin, mean corpuscular volume, and platelet count) and laboratory markers of dialysis adequacy, including blood urea nitrogen (BUN), serum creatinine, and Kt/V values. Statistical analyses assessed correlations between dialysis adequacy markers and hematological abnormalities. Results: The findings revealed significant associations between elevated BUN and serum creatinine levels, lower Kt/V values, and the presence of anemia and thrombocytopenia. Suboptimal dialysis adequacy (Kt/V &lt; 1.2) was observed in 67.2% of patients. Anemia was prevalent, with 75.4% of patients exhibiting low hemoglobin levels and 77% and 86.9% showing reduced mean corpuscular volume and hemoglobin levels, respectively. Elevated white blood cell counts were present in 23% of patients. Significant correlations were found between Kt/V values and serum creatinine (r = -0.68, p &lt; 0.01) as well as hemoglobin levels (r = 0.45, p &lt; 0.01). Conclusion: These results suggest a potential link between inadequate dialysis efficacy and hematological abnormalities in hemodialysis patients. Optimizing dialysis protocols and continuous monitoring are essential to improve patient outcomes and address these complications.

Effects of Sedation on Haematological, Biochemical, Coagulation Profile, and Kaolin-Activated Thromboelastography in Rabbits.

Blood sampling and analysis are essential procedures for assessing the health status of exotic pets. While careful manual restraint is generally recommended, sedation may be necessary in specific cases. However, the use of chemical restraint may introduce analytical variations. The aim of this study is to determine the effects of sedation with butorphanol, midazolam, ketamine and dexmedetomidine on haematological, biochemical and coagulation parameters (prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen), as well as thromboelastography in adult healthy New Zealand rabbits (Oryctolagus cuniculus). Two groups of adult New Zealand rabbits, housed under identical conditions and considered healthy based on normal physical examination and unremarkable clinical histories, were included in the study. The non-sedated group comprised ten rabbits, while the sedated group consisted of fifteen. Blood samples were collected via jugular venipuncture, and haematological, biochemical and coagulation profiles were performed. In conclusion, some variation in haematological and biochemical values were observed depending on sex and/or sedation protocols. Sex can influence haematology in terms of haemoglobin concentration, lymphocyte and platelet count; biochemistry in alanine aminotransferase, chloride, gamma-glutamyl transferase, potassium, sodium, calcium, total cholesterol, urea nitrogen, but not in coagulation parameters. Meanwhile, sedation can affect haematology in terms of leucocyte and lymphocyte count and biochemistry in total bilirubin, calcium, total protein, sodium, albumin, glucose, creatinine, phosphorous. Plasma-based coagulation assays showed increased prolongation of aPTT and PT, although these changes do not seem to be clinically relevant. There were no changes observed in thromboelastographic parameters.

Dose-Dependent Hepatorenal Damage Induced by Erythrosine: A Study of Biochemical, Oxidative Stress, DNA Damage, and Histopathological Effects in Wistar Rats.

This study aimed to provide insights into the hepatorenal toxicity induced by erythrosine, a synthetic red dye commonly used in food and pharmaceuticals, which has raised concerns over its potential health risks. Twenty-four rats were randomly divided into four groups (n = 6). The first group was the control group and the other group received one of three doses of erythrosine based on acceptable daily intake (¼ ADI, ½ ADI, and ADI, 0.1 mg/kg body weight). This study examined biological activity via biochemical enzyme analysis, oxidative stress indices, DNA damage, and histopathology. Compared with the control group, erythrosine administration increased the serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, total protein, urea, creatinine, and uric acid at the highest erythrosine dose. The catalase and the superoxide dismutase activity decreased in both tissues at the highest dose. The glutathione-S-transferase activity increased at the ¼ ADI dose and decreased at higher doses in both tissues. In contrast, acetylcholinesterase activity was greater in erythrosine-treated rats than in control rats. Oxidative stress indices indicated increased lipid peroxidation, hydrogen peroxide content, and lactate dehydrogenase activity. The comet assay was used to assess DNA damage, revealing significant damage in the erythrosine-treated groups. Histopathological examination revealed necrotic and degenerative changes in the liver and kidney tissues. The findings underscore dose-dependent hepatorenal toxicity and highlight the novelty of demonstrating a comprehensive link between erythrosine exposure, oxidative stress, and DNA damage. These results emphasize the need for cautious evaluation of synthetic dye consumption due to potential health risks.

Hydroxyurea mitigates diabetic kidney disease through mTOR-S6K signaling pathway in STZ-induced diabetic mice

BackgroundDiabetic kidney disease (DKD) is the leading risk factor for end-stage renal disease (ESRD). Hydroxyurea (HU), a sickle cell disease (SCD) drug approved by FDA, shows protective effect in nephropathy. This study aims to understand whether the application of HU could be effective to treat DKD.MethodsThe streptozotocin (STZ)-induced diabetic mice, and high glucose (HG)-treated human renal mesangial cells (HRMCs) were used to investigate the effect of HU on DKD. Serum creatinine and blood urea nitrogen levels reflecting renal function were evaluated. Histology was used to evaluate pathological changes. Indicators of inflammation and apoptosis were detected. Lastly, the mTOR-S6K pathway was explored by detecting the protein expression of S6K and phosphorylated S6K.ResultsIn STZ-induced diabetic mice, administration of HU (20 mg/kg) in drinking water for 16 weeks resulted in significant reductions in creatinine and urea nitrogen levels, alongside mitigating histopathological damage. Additionally, HU effectively suppressed the inflammatory response and apoptosis within the kidneys. HRMC cells were cultivated in HG conditions, and HU effectively attenuated the HG-induced inflammation and apoptosis. Moreover, HU treatment significantly inhibited the mTOR signaling pathway in both in both in vivo and in vitro experiments.ConclusionThis study unveils a new role of HU in alleviating diabetic kidney disease by modulating inflammation and apoptosis through the mTOR-S6K pathway. However, since HU did not significantly affect blood glucose levels, its therapeutic potential may be best realized when used in combination with standard antidiabetic therapies. Such a combination approach could simultaneously address hyperglycemia and renal dysfunction, offering a more comprehensive management strategy for DKD.