Renal Failure Research Articles

Engineering of phosphatidylserine-targeting ROS-responsive polymeric prodrug for the repair of ischemia-reperfusion-induced acute kidney injury.

Ischemia-reperfusion-induced acute kidney injury (IR-AKI) commonly occurs in situations such as hemorrhagic shock, kidney transplantation, and cardiovascular surgery. As one of the significant causes of AKI, IR-AKI is characterized by its high incidence and mortality rates. Currently, effective inflammation control is the key for the treatment of IR-AKI. In this study, we developed an ROS-responsive polymeric prodrugs (Zn-D/DTH) which could target the externalized PS of apoptotic cells, and then responsively released HDM (anti-inflammatory peptides) in the presence of intracellular ROS. Zn-D/DTH effectively ameliorated renal function and mitigated pathological alterations such as the loss of the brush border, tubular dilation, and accumulation of cellular debris within the tubular lumens. Furthermore, Zn-D/DTH greatly reduced the generation of pro-inflammatory factors like IL-6, COX-2, and iNOS in renal tissues, suggesting its protective role largely stems from suppression of the inflammatory response. Additional mechanism exploration revealed that Zn-D/DTH markedly decreased the expression levels of TLR4 and MyD88, as well as the phosphorylation of NF-κB in the damaged kidneys. This, in turn, reduced the number of apoptotic tubular cells and the activity of Caspase 9 and Caspase 3 caused by ischemia-reperfusion. Additionally, Zn-D/DTH treatment showed improvement in the long-term renal damage and fibrosis induced by ischemia-reperfusion. The experimental outcomes indicated that Zn-D/DTH attenuated renal ischemia-reperfusion injury and delayed the transition from acute kidney injury to chronic kidney disease by downregulating the TLR4/MyD88/NF-κB signaling pathway and reducing the expression of apoptotic caspases, thereby inhibiting inflammation and reducing cell apoptosis.

Comparative study of the protective effects of coenzyme Q10 and cinnamon extract on possible kidney damage and dysfunction of amiodarone in rats.

An increase in free oxygen radicals and proinflammatory cytokines and decrease in intracellular adenosine triphosphate account for the nephrotoxic effect of amiodarone. This study investigated the protective effects of Coenzyme Q10 (CoQ10), cinnamon extract (CE) and the combination of the two (CoCE) on possible amiodarone-induced renal injury in rats. Thirty male albino Wistar rats were cetegorized into healthy (HG), amiodarone (ADG), CoQ10 + amiodarone (CoQA), CE + amiodarone (CEA), and CoCE + amiodarone (CoCEA) groups. First, CoQ10 (10mg/kg) and CE (100mg/kg) were orally given. After 1h, 50mg/kg amiodarone was orally given to all groups except for HG. Amiodarone, CoQ10, and CE administration was continued orally at the indicated doses once daily for 10days.Then, blood samples were collected from all groups to determine creatinine, blood urea nitrogen (BUN), and kidney injury molecule (KIM-1) levels, followed by euthanasia and removal of kidney tissues. Oxidative stress and inflammatory parameters were analysed in the tissue samples. Histopathological examination was also performed on the tissues. Amiodarone increased malondialdehyde levels and decreased total glutathione, superoxide dismutase, and catalase levels (p < 0.001). Amiodarone increased the expression and tissue levels of tissue nuclear factor kappa B, tumor necrosis factor-alpha, interleukin-1β and interleukin-6, and led to increases in serum creatinine and BUN and KIM-1 levels (p < 0.001). Amiodarone also caused histopathological damage (p < 0.001).CoQ10, CE and especially CoCE inhibited biochemical changes and tissue damage (p < 0.001). Although CoQ10, CE, and CoCE effectively prevent amiodarone-induced oxidative and inflammatory nephrotoxicity, CoCE appears to be superior.

The Effect Combined Of Intradialytic Exercise: Static Stretching And Dynamic Streching Lower Limb, Increase Physical Funtion In Chronic Kidney Diseases On Haemodialysis Patients Quasi Experiment

Background: Individuals with end-stage kidney disease (ESKD) usually engage in minimal physical activity, as renal failure progresses in chronic kidney disease (CKD), muscle mass and physical function decrease. Physical activity (PA) is important in maintaining/improving health in all population. Aim of this study to evaluate effect exercise of combine static stretching and dynamic stretching increasing Physical Function in CKD on HD patients. Methods: design of this study was quasi experiment in one group 39 respondents CKD on HD patients meet inclusion criteria. Implementation 12 weeks intradialytic exercise combine static and dynamic stretching lower limbs include leg, ankles, knee, femoral and hip. During exercise evaluate using Borg Skill to know level of fatigue. Comparing with before-after test Time Up and Go 3 meters return measurement. Result: The results of this study demonstrate that the mean values of functional balance, which are much lower in this population than in their healthy counterparts, can be improved by a video-based intradialytic exercise program that includes stretching and endurance activities. In particular, notable advancements were noted in the average TUG test 3 meter return result, which is a reliable indicator of hospitalization, cardiovascular events, and mortality in dialysis patients. Conclusion all participants reported after 12 weeks static and dynamic stretching felt more flexible range of motion knee and leg, walking stronger than before and felt more conformable in walking reported, significant different before and after given static and dynamic stretching, both Static and dynamic stretching effective for improving functional balance and physical performance, Recommended static and dynamic stretching to be rutine activity in Hemodialysis unit.

Carbon Monoxide Intoxication Leading to Crush Syndrome and Acute Renal Failure: A Case Report

Carbon Monoxide Intoxication Leading to Crush Syndrome and Acute Renal Failure: A Case Report

MiR-126 accelerates renal injury induced by UUO via inhibition PI3K/ IRS-1/ FAK signaling induced M2 polarization and endocytosis in macrophages

To investigate the role and molecular mechanism of miR-126 in unilateral ureteral occlusion (UUO). We used bioinformatics to analyse miRNAs specifically expressed in UUO. The mouse model of UUO was established using RAW264.7 cells cultured in vitro and in vivo. The mice were divided into control group, miR-126-NC (negative control) group and miR-126-KD (knockdown) group. Then the relative expression of miR-126 was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), the renal fibrosis was detected by Masson staining, and the protein expression of CD68, collagen I and collagen III in the kidney was detected by immunofluorescence assay. Immunohistochemistry detects α-SMA expression. Moreover, Western blotting was performed to measure the expressions of p-PI3K, CD163, CD206, CD86, iNOS, IL-1β, p-FAK, p-Rac-1, p-IRS-1 and MMP9. The relative fluorescence intensity of F-actin and p-FAK was detected by immunofluorescence assay, and the phagocytosis ability of macrophages was determined by phagocytosis assay with fluorescent microspheres. Bioinformatics analysis reveals miR-126-specific overexpression in UUO. Successful transfection of miR-126-NC and miR-126-KD was confirmed by RT-PCR. The selective reduction of miR-126 was validated by Masson, immunohistochemistry and immunofluorescence staining to decrease the area of UUO-induced renal fibrosis and to lower the expression of CD68, α-SMA, collagen I, and collagen III. The reduction of iNOS expression may also be achieved with selective knockdown of miR-126, as verified by cell tests. enhances the phagocytic ability of macrophages and the expression of p-PI3K, CD206, p-FAK, F-actin, p-Rac-1, p-IRS-1 and MMP9. MiR-126 can inhibit the PI3K signaling pathway, promote M1 macrophage polarization, and suppress the activation of FAK and Rac-1, thus accelerating the progression of UUO.

Prenatal metal exposures and kidney function in adolescence in Project Viva.

The developing kidney is vulnerable to prenatal environmental factors such as metal exposure, potentially altering the risk of later-life kidney dysfunction. This study examines the relationship between prenatal metal exposures, individually and as mixtures, and adolescent kidney function in Project Viva, a prospective longitudinal birth cohort in Massachusetts, USA. We used data on metals measured in blood during pregnancy including 15 in the first trimester and four in the second trimester. We calculated estimated glomerular filtration rate (eGFR) in adolescents (mean: 17.7 years) using cystatin C- (eGFRcys) and creatinine-based (eGFRcreat) equations for children. We used linear regression for single metal analyses, and Bayesian kernel machine regression and quantile-based g-computation for mixture analyses, adjusting for relevant covariates. To account for multiple comparisons in the single metal analyses, we applied the Holm-Bonferroni procedure to control the false discovery rate. This study included 371 participants with first trimester metals and adolescent eGFR, and 256 with second trimester metals. Each doubling in first trimester cadmium concentration was associated with lower adolescent eGFRcys (β:-1.51; 95% CI:-2.83, -0.18). Each doubling in first trimester chromium (β:-1.45; 95% CI:-2.71, -0.19), nickel (β:-1.91; 95% CI:-3.65, -0.16), and vanadium (β:-1.69; 95% CI:-3.21, -0.17) was associated with lower adolescent eGFRcreat. After adjusting for multiple comparisons, p-values for associations between adolescent eGFR and chromium, nickel, vanadium and cadmium did not meet the criteria for significance. Metal mixture analyses did not identify statistically significant associations with adolescent eGFR. These findings have important implications for future studies investigating the potential mechanisms through which prenatal metal exposures affect long-term kidney health in children.

The effect of TSH on kidney function

Background: The thyroid gland plays a vital role in the regulation of many physiological processes, including kidney function. Aim: The purpose of this study was to investigate the relationship between thyroid-stimulating hormone (TSH) and kidney function in male and female patients with hyperthyroidism, as well as in healthy control subjects. Method: A total of 60 participants from Najaf city, Iraq, were included in the study. This included 10 male and 10 female control subjects, as well as 20 male and 20 female patients with hyperthyroidism. Blood samples were collected from all participants and analyzed for TSH, urea, and creatinine levels. Result: The results showed a significant increase in TSH levels in both male and female patients with hyperthyroidism compared to control subjects. Urea levels were also significantly higher in hyperthyroidism patients compared to controls, while creatinine levels were not significantly different. In addition, there was a significant difference in the effects of TSH on kidney function between male and female patients with hyperthyroidism. Female patients with hyperthyroidism had significantly higher levels of urea and lower levels of creatinine compared to male patients with hyperthyroidism. These findings suggest a direct effect of TSH on kidney function and highlight the need for regular monitoring of kidney function in individuals with hyperthyroidism, particularly women. Further research is needed to fully understand the mechanisms behind the gender differences observed in this study and to develop targeted interventions for both men and women with thyroid disorders. Conclusion: our study provides valuable insights into the relationship between TSH and kidney function and highlights the need for multidisciplinary care and targeted interventions for individuals with thyroid disorders to prevent or minimize the risk of kidney dysfunction.

Identification of Genes Associated with Familial Focal Segmental Glomerulosclerosis Through Transcriptomics and In Silico Analysis, Including RPL27, TUBB6, and PFDN5

Focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome and often leads to progressive kidney failure. Its varying clinical presentation suggests potential genetic diversity, requiring further molecular investigation. This study aims to elucidate some of the genetic and molecular mechanisms underlying FSGS. The study focuses on the use of bioinformatic analysis of gene expression data to identify genes associated with familial FSGS. A comprehensive in silico analysis was performed using the GSE99340 data set from Gene Expression Omnibus (GEO) comparing gene expression in glomerular and tubulointerstitial tissues from FSGS patients (n = 10) and Minimal Change Disease (MCD) patients (n = 8). These findings were validated using transcriptomics data obtained using RNA sequencing from FSGS (n = 3) and control samples (n = 3) from the UAE. Further validation was conducted using qRT-PCR on an independent FFPE cohort (FSGS, n = 6; MCD, n = 7) and saliva samples (FSGS, n = 3; Control, n = 7) from the UAE. Three genes (TUBB6, RPL27, and PFDN5) showed significant differential expression (p &lt; 0.01) when comparing FSGS and MCD with healthy controls. These genes are associated with cell junction organization and synaptic pathways of the neuron, supporting the link between FSGS and the neural system. These genes can potentially be useful as diagnostic biomarkers for FSGS and to develop new treatment options.

Community-Associated MRSA—Not So Innocent Sibling per Se: A Case Report

Background: Methicillin-resistant S. aureus (MRSA) is a major healthcare burden and is classified as healthcare-associated (HA-MRSA) and community-associated (CA-MRSA). While HA-MRSA is clinically feared, CA-MRSA is often considered less pathogenic. This case report highlights the serious course of illness due to CA-MRSA infection and provides a treatment strategy for the management of such cases. Case description: A 41-year-old male presented with fever and breathlessness for five days. Upon admission, he was provided empirical treatment for atypical infections and vasopressor support for hypotension. His condition deteriorated, necessitating ventilator support. Although the initial tracheal Bio Fire test indicated MRSA, his clinical manifestations did not match MRSA pneumonia symptoms; however, CA-MRSA was confirmed within 12 h. Skin legions developed within 16 h and progressed gradually from ecchymosis, petechial, and palpable purpura to bullous lesions over 72 h. The antibiotic regimen was modified and optimized with the addition of Clindamycin, Vancomycin, and Meropenem–Colistin. Owing to high IL-6 levels, dual vasopressor support, and acute kidney failure, he was started on early (within 12 h) continuous renal replacement therapy (CRRT) with CytoSorb filter (for 3 days) for cytokine removal. IL-6 levels decreased after two days of CytoSorb use. Subsequently, the patient stabilized with reduced dependence on vasopressor and ventilator assistance. Discussion: Early diagnosis of CA-MRSA and management with CRRT using CytoSorb may help improve patient outcomes. To our knowledge, this is the first report of clinical management of CA-MRSA with CytoSorb therapy in India that resulted in positive outcomes.

Investigation of Lead, Nickel, and Cadmium Levels in Urine Samples of Healthy and Patients with Kidney Failure in Al-muthanna Governorate, Iraq

Background: The Iraqi ecosystem, particularly in the southern area, has been polluted due to human activity. Analyzing biological materials is the most common method for detecting the presence of toxic substances in the human body. Method: Heavy metal levels of Pb, Ni, and Cd in urine specimens collected from individuals with renal failure and healthy individuals residing in Al-Muthanna province were measured by using atomic absorption spectroscopy. Urine Specimens were collected from two cohorts of male and female participants: the group of individuals with renal failure and the group of individuals who are in good condition. The specimens of urine from both the group of patients with renal failure and the group of healthy individuals were taken from the Al-Muthanna governorate in southern Iraq. This governorate served as a focal point for extensive military operations throughout the Gulf War. Results: The concentrations of toxic substances (Pb, Ni, and Cd) in the urine specimens of the cohort of patients suffering from renal failure are 0.411, 0.197, and 0.113 mg/l, respectively. Concentrations of (Pb, Ni, and Cd) in the healthy group are 0.249, 0.101, and 0.0294 mg/l, respectively. The toxic metals found in urine samples can be organized in the following order: Pb &gt; Ni &gt; Cd. Conclusion: The findings indicated that the concentrations of toxic substances in specimens of urine from individuals with renal failure are considerably greater than those in the control group of healthy individuals. According to the findings, patients' incidence of renal failure may be related to the prevalence of harmful compounds in southern Iraq.

Characterization of renal injury in non-squamous non-small cell lung cancer patients treated with pemetrexed: A single-center retrospective study.

Pemetrexed is a key therapeutic agent for advanced non-squamous non-small cell lung cancer (Nsq-NSCLC), yet it is associated with renal toxicity. This study aims to elucidate the incidence, risk factors, and survival impact of renal injury in patients with Nsq-NSCLC treated with pemetrexed. We conducted a retrospective study including 136 patients with Nsq-NSCLC treated with pemetrexed. Data on demographics, renal function, progression-free survival (PFS), and overall survival (OS) were collected. Renal injury was defined as a reduction above 25% in estimated glomerular filtration rate (eGFR) from baseline. Its associated risk factors were analyzed using logistic regression, and impact on survival was analyzed using log-rank test. The creatinine clearance rate (CCr) was calculated, and a CCr < 45 mL/min served as a contraindication for continuing pemetrexed. The study found a 31.6% (43/136) incidence of renal injury, with 9.6% (13/136) having CCr < 45 mL/min and discontinuing pemetrexed. Univariate and multivariate analyses identified factors significantly associated with increased renal injury risk including older age, use of cisplatin, and higher number of pemetrexed cycles. The patients with renal injury had a median PFS (mPFS) of 13.5 months and a median OS (mOS) of 36.0 months, while the patients without had an mPFS of 9.0 months and an mOS of 35.0 months, and these differences were not statistically significant. Renal injury is a considerable complication in patients with Nsq-NSCLC undergoing pemetrexed treatment, with age, platinum type, and pemetrexed treatment cycles as key risk factors. These findings highlight the necessity for careful renal monitoring in this patient population.

Suppression of ferroptosis through the SLC7A11/glutathione/glutathione peroxidase 4 axis contributes to the therapeutic action of the Tangshenning formula on diabetic renal tubular injury

BackgroundTangshenning (TSN) is a safe and effective formula to treat diabetic nephropathy (DN), and clinical studies have demonstrated that its therapeutic effects are related to oxidative stress improvements in patients. Herein, this study aims to explore the potential mechanism of how TSN alleviates diabetic renal tubular injury.MethodsThe ultrahigh pressure liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-QTOF/MS) was used to identify the chemical composition and serum components of TSN. KK-Ay mice served to investigate the protective effects and regulatory mechanisms of TSN on tubular damage in DN. Furthermore, inhibitors and inducers of ferroptosis were employed in high glucose-cultured tubular epithelial cells (TECs) to verify the potential mechanisms of TSN. The expressions of proteins related to renal tubular injury, ferroptosis and solute carrier family 7, member 11 (SLC7A11)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis were analyzed by western blot and immunofluorescence. Mitochondrial ultrastructure was observed in kidney tissues and TECs by a transmission electron microscope. Pathological changes in the renal tissues were observed by HE, PAS, and Prussian blue staining. Ferroptosis-related reactive oxygen species (ROS), malondialdehyde (MDA), ferrous ion, the intake of cystine, GSH, and oxidized glutathione (GSSG) were evaluated and contrasted in vivo or in vitro.Results51 compounds of TSN powder and 11 components in TSN-containing serum were identified by UPLC-QTOF/MS method. Administration of TSN ameliorated the elevated levels of proteinuria, serum creatinine, blood urea nitrogen, abnormal expression of renal tubular injury markers, and pathological damage to the renal tubules in DN mice model. Intriguingly, a strong inhibition of ferroptosis after TSN treatment occurred in both DN mice model and high glucose-cultured TECs. Notably, induction of ferroptosis by erastin attenuated the protective effect of TSN in high glucose-cultured TECs, while the ferroptosis inhibition by ferrostatin-1 treatment protected renal tubular, which was similar to TSN, suggesting the contribution of TSN-mediated by the inhibition of ferroptosis in DN progression. Mechanistically, TSN upregulated the SLC7A11/GSH/GPX4 axis to inhibit ferroptosis.ConclusionTSN may delay the DN progression and attenuate the renal tubular injury by inhibiting the ferroptosis regulated by the SLC7A11/GSH/GPX4 axis.

Evaluation of TNF-α and TNF-R1 immunomarkers in Renal Failure Patients in Karbala province

Renal failure is characterized by height level of pro-inflammatory cytokines, mainly Tumor necrosis factor-alpha (TNF-α) and its receptor TNF-R1. The aim was to investigate the association of TNF-α and TNF-R1 levels in Renal Failure.This study was carried out from February 2022 to March 2023 in the labs of Thi-Qar University's Col1ege of Education for Pure Sciences. In partnership with Al-Hussein Teaching Hospital, Nasiriyah General Hospital, and Thi-Qar Center for Nephrology and Dialysis in Thi-Qar Province .The study comprised (100) patients for both sex : (40 patients with diabetes mellitus), (40 patients without diabetes mellitus) whose serum urea level and serum creatinine level were examined, and (40 healthy).The level of biochemical indicators were measured, which included urea, creatinine, albumin and total protein where the study discovered a considerable rise in urea and creatinine levels compared to healthy subjects and standard rates, and this increase is related 'with a decrease GFR', while there is decrease in rate of albumin and total protein. The statistical analysis' findings revealed a considerable difference (p &lt;0.05) in patients with RF in concentration of the TNF-α and TNF-R1, where they were examined for 80 samples of RF patients, and 40 healthy samples in the control group. The number of RF patients in Thi-Qar province showed a marked increase in the yearly rate of hemodialysis. A third of all patients had a considerable prevalence of RF linked to hypertension. The study concluded that a significant effect of TNF-α is associated with markers of kidney disease severity and distant organ dysfunction among patients with RF. In addition, this study found a correlation between the effects of TNF- α on end-stage renal disease. Extensive studies are needed to confirm these relationships.

Long-Term Outcomes of Minimally Invasive Endoscopic Versus Sternotomy Surgical Resection of Primary Cardiac Tumors.

Primary cardiac tumors are uncommon, often benign, but can be potentially life threatening. Minimally invasive endoscopic (ENDO) techniques have been shown to be a feasible alternative for tumor resection compared with conventional sternotomy (CS). This study compared the clinical and surgical outcomes of a small series of patients undergoing cardiac tumor resection operations. Between November 2009 and December 2022, 34 consecutive patients underwent cardiac tumor resection using either ENDO (n = 21) or CS (n = 13) techniques. We compared early perioperative outcomes, echocardiographic outcomes, and long-term clinical and tumor recurrence outcomes. Baseline characteristics were similar between groups; however, the ENDO group included younger patients (56 ± 16 vs 62 ± 17 years) and more female patients (83% vs 53%). The tumor was located in the left atrium (n = 19, 56%), right atrium (n = 5, 15%), or either ventricle (n = 4, 12%). In-hospital mortality and stroke frequency were similar for both groups (n = 0). There was no significant difference in cardiopulmonary bypass or cross-clamp times, respiratory or renal failure, or intensive care unit or hospital lengths of stay. At follow-up (ENDO, 42 [2 to 131] months vs CS, 54 [1 to 156] months), there were no deaths in the ENDO group and 2 patients died in the CS group (P = 0.21). No patients in either group experienced tumor recurrence. In selected patients, both ENDO and CS approaches to primary cardiac tumor resection were safe, effective, durable, and associated with similarly good early and late results.

Epigenetic DNA Methylation and Protein Homocysteinylation: Key Players in Hypertensive Renovascular Damage

Hypertension has been a threat to the health of people, the mechanism of which, however, remains poorly understood. It is clinically related to loss of nephron function, glomerular sclerosis, or necrosis, resulting in renal functional declines. The mechanisms underlying hypertension’s development and progression to organ damage, including hypertensive renal damage, remain to be fully elucidated. As a developing approach, epigenetics has been postulated to elucidate the phenomena that otherwise cannot be explained by genetic studies. The main epigenetic hallmarks, such as DNA methylation, histone acetylation, deacetylation, noncoding RNAs, and protein N-homocysteinylation have been linked with hypertension. In addition to contributing to endothelial dysfunction and oxidative stress, biologically active gases, including NO, CO, and H2S, are crucial regulators contributing to vascular remodeling since their complex interplay conducts homeostatic functions in the renovascular system. Importantly, epigenetic modifications also directly contribute to the pathogenesis of kidney damage via protein N-homocysteinylation. Hence, epigenetic modulation to intervene in renovascular damage is a potential therapeutic approach to treat renal disease and dysfunction. This review illustrates some of the epigenetic hallmarks and their mediators, which have the ability to diminish the injury triggered by hypertension and renal disease. In the end, we provide potential therapeutic possibilities to treat renovascular diseases in hypertension.

Clinical Pharmacology of Asciminib: A Review.

Asciminib is a first-in-class allosteric inhibitor of the kinase activity of BCR::ABL1, specifically targeting the ABL myristoyl pocket (STAMP). This review focuses on the pharmacokinetic (PK) and pharmacodynamic data of asciminib, which is approved at a total daily dose of 80 mg for the treatment of adult patients with chronic myeloid leukemia in chronic phase who are either resistant or intolerant to ≥ 2 tyrosine kinase inhibitors or those harboring the T315I mutation (at a dose of 200 mg twice daily). Asciminib is predicted to be almost completely absorbed from the gut, with an absolute bioavailability (F) of approximately 73%. It should be administered in a fasted state, as food (particularly high-fat meals) reduces exposure. Asciminib displays a slightly greater than dose-proportional increase in exposure, with no time-dependent changes in PK observed following repeated dosing. This drug shows low clearance (6.31 L/h), with a moderate volume of distribution (111 L) and high human plasma protein binding (97.3%). The apparent terminal elimination half-life (t1/2) across studies was estimated to be between 7 and 15h. The PK of asciminib is not substantially affected by body weight, age, gender, race, or renal or hepatic impairment. Asciminib is primarily metabolized via CYP3A4-mediated oxidation (36.0%) and UGT2B7- and UGT2B17-mediated glucuronidation (13.3% and 7.8%, respectively); biliary secretion via breast cancer resistance protein contributes to about 31.1% to total systemic clearance, which is mainly through hepatic metabolism and biliary secretion through the fecal pathway, with renal excretion playing a minor role. The potential for PK drug interaction for asciminib both as a victim and a perpetrator has been summarized here based on clinical and predicted drug-drug interaction studies. Robust exposure-response models characterized asciminib exposure-efficacy and exposure-safety relationships. In patients without the T315I mutation, the exposure-efficacy analysis of the time course of BCR::ABL1IS percentages highlighted the existence of a slightly positive, albeit not clinically significant, relationship. Higher exposure was required for efficacy in patients harboring the T315I mutation compared with those who did not. The exposure-safety relationship analysis showed no apparent association between exposure and adverse events of interest over the broad range of exposure or dose levels investigated. Asciminib has also been shown to have no clinically relevant effect on cardiac repolarization. Here, we review the clinical pharmacology data available to date for asciminib that supported its clinical development program and regulatory applications.

Validation of CASPRI, GO-FAR, PIHCA scores in predicting favorable neurological outcomes after in-hospital cardiac arrest; A five-year three center retrospective study in IRAN

BackgroundPredicting neurological outcomes following in-hospital cardiac arrest is crucial for guiding subsequent clinical treatments. This study seeks to validate the effectiveness of the CASPRI, GO-FAR, and PIHCA tools in predicting favorable neurological outcomes after in-hospital cardiac arrest.MethodThis retrospective study utilized a Utstein-style structured form to review the medical records of patients who experienced in-hospital cardiac arrest between March 2018 and March 2023. Predictors were examined using multivariable logistic regression, and the validity of the tools was assessed using ROC curves. Statistical analysis was conducted using SPSS version 25 software.ResultsOut of the 1100 patients included in the study, 42 individuals (3.8%) achieved a favorable neurological outcome. multivariable regression analysis revealed that age, respiratory failure, resuscitation shift, duration of renal failure, and CPC score 24 h before cardiac arrest were significantly associated with favorable neurological outcomes. The predictive abilities of the CASPRI, GO-FAR, and PIHCA scores were calculated as 0.99 (95% CI, 0.98–1.00), 0.98 (95% CI, 0.97–0.99), and 0.96 (95% CI, 0.94–0.99) respectively. A statistically significant difference was observed in the predictive abilities of the CASPRI and PIHCA scores (P = 0.001), while the difference between CASPRI and GO-FAR did not reach significance (P = 0.057). Additionally, there was no significant difference between the predictive abilities of GO-FAR and PIHCA scores (P = 0.159).ConclusionThe study concludes that CASPRI and GO-FAR scores show strong potential as objective measures for predicting favorable neurological outcomes post-cardiac arrest. Integrating these scores into clinical decision-making may enhance treatment and care strategies, in the Iranian healthcare context.

The role of systemic immune-inflammatory index in predicting contrast-induced nephropathy in non-ST-segment elevation myocardial infarction cases.

Aim: Systemic immune-inflammation index (SII) is obtained by multiplying the platelets by the ratio of neutrophils to lymphocytes. We aimed to examine the relationship between contrast induced nephropathy (CIN) development and SII in non-ST-segment elevation myocardial infarction (NSTEMI) patients.Methods: 1124 NSTEMI patients included and divided into two groups according to the development of CIN. The relationship between SII and CIN development was examined.Results: Among two groups, significant differences were observed in terms of age, chronic renal failure, presence of critical stenoses in the LAD, SII and C-reactive protein (CRP). It was calculated that a value of 709 and above for SII had a predictive power with 74% sensitivity and 74% specificity for CIN.Conclusion: SII has the potential to predict the development of CIN in NSTEMI patients.

Influence of Right and Left Bundle Branch Block in Patients With Cardiogenic Shock and Cardiac Arrest.

The study investigates the prognostic impact of right bundle branch block (RBBB) and left bundle branch block (LBBB) in patients with cardiogenic shock (CS) compared with no bundle branch block (BBB). In patients with heart failure, existence of RBBB and LBBB has influence on prognosis. Prospective registry-study. ICU of a tertiary academic hospital in Germany. Adult patients with CS. None. Consecutive patients with CS were included. The prognostic impact of RBBB and LBBB on 30-day all-cause mortality was tested within the entire cohort and in the subgroup of CS patients with cardiac arrest at admission. The final study cohort comprised 248 patients. Patients with RBBB showed the highest 30-day all-cause mortality followed by LBBB and no BBB (72.5% vs. 52.9% vs. 50.0%; log-rank p = 0.015). These findings were consistent even after solely including CS patients with cardiac arrest (90.0% vs. 73.3% vs. 62.2%; log-rank p = 0.008). After adjustment for lactate, norepinephrine, troponin I, Acute Physiology Score, Society of Cardiovascular Angiography & Interventions shock stage, and heart rate in a multivariable Cox regression analysis, RBBB still revealed a negative impact on 30-day all-cause mortality (hazard ratio [HR], 1.807; 95% CI, 1.107-2.947; p = 0.018), whereas LBBB was not associated with 30-day all-cause mortality. In this multivariable Cox regression model lactate (HR, 1.065; 95% CI, 1.018-1.115; p = 0.006), troponin I (HR, 1.003; 95% CI, 1.001-1.005; p = 0.001), and Acute Physiology Score (HR, 1.033; 95% CI, 1.001-1.066; p = 0.041) were as well associated with 30-day all-cause mortality. Finally, no association of RBBB was found with the incidence of liver or severe renal failure. Besides the Acute Physiology Score, lactate, and troponin levels, RBBB was associated with an increased 30-day all-cause mortality in consecutive CS patients with and without cardiac arrest, whereas LBBB showed no prognostic impact.

Risk Factor Analysis Including Inflammatory Markers for ICU Admission and Survival After Pneumonectomy

Background and Objectives: To assess the impact of preoperative inflammatory parameters on the necessity for intensive care unit (ICU) admission and survival after pneumonectomy. Materials and Methods: We enrolled 207 adult patients who underwent pneumonectomy between December 2016 and January 2022. We collected data from patients’ electronic medical records. Results: The preoperative albumin level was statistically lower, need for blood transfusion was higher, and length of hospital stay was longer in ICU-admitted patients (p = 0.017, p = 0.020, and p = 0.026, respectively). In multivariate analysis, intra-pericardial pneumonectomy and postoperative complications were predictive factors for ICU admission (OR = 3.46; 95%CI: 1.45–8.23; p = 0.005 and OR = 5.10; 95%CI: 2.21–11.79; p &lt; 0.001, respectively). Sleeve or pericardial pneumonectomy (p = 0.010), intraoperative vascular injury (p = 0.003), the need for mechanical ventilation (p &lt; 0.001), acute renal failure (p = 0.018), sepsis (p = 0.008), respiratory failure (p &lt; 0.001), pneumonia (p = 0.025), the need for blood transfusion (p = 0.047), elevated blood urea nitrogen (BUN) (p = 0.046), and elevated creatinine levels (p = 0.004) were more common in patients who died within 28 days. Patients who died within 90 days exhibited higher preoperative neutrophil-to-lymphocyte ratio (NLR) values (p = 0.019) and serum creatinine levels (p = 0.008), had a greater prevalence of sleeve or intra-pericardial pneumonectomy (p = 0.002), the need for mechanical ventilation (p &lt; 0.001), intraoperative vascular injury (p = 0.049), sepsis (p &lt; 0.001), respiratory failure (p = 0.019), and contralateral pneumonia (p = 0.008) than those who did not. Conclusions: Intra-pericardial pneumonectomy and postoperative complications are independent predictors of ICU admission after pneumonectomy. Tracheal sleeve and intra-pericardial procedures, intraoperative and postoperative complications, the need for blood transfusion, preoperative NLR ratio, BUN and creatinine levels may also be potential risk factors for mortality.