Search Results (523)

Background: Teicoplanin is widely used for the empirical and targeted treatment of febrile neutropenia in patients with hematological malignancies. However, the pathophysiological alterations typical of this population may substantially affect drug exposure. The aim of this study was to develop and validate a population pharmacokinetic (PopPK) model of teicoplanin in adult hematological patients and to propose individualized dosing strategies. Methods: A retrospective, single-center study including 151 patients and 263 serum concentrations was conducted, with participants assigned to development (n = 100) and validation (n = 51) cohorts. Concentrations were quantified using a turbidimetric immunoassay, and the PopPK model was developed in NONMEM using FOCE-I. Results: Teicoplanin pharmacokinetics were described by a one-compartment model with first-order elimination. Ideal body weight, estimated glomerular filtration rate, and age were identified as significant predictors of clearance. Internal and external validation confirmed the robustness and predictive performance of the model. Monte Carlo simulations showed that conventional regimens (6 mg/kg every 12 h for three loading doses, followed by 6 mg/kg once-daily, or 600 mg every 12 h for three loading doses, followed by 600 mg once-daily) are insufficient to achieve therapeutic trough concentrations (≥15–20 mg/L) within the first 72 h, particularly in patients with preserved renal function or higher body weight. An intensified regimen consisting of five loading doses of 12 mg/kg every 12 h, followed by 12 mg/kg once-daily, enabled rapid attainment and maintenance of trough concentrations ≥ 20 mg/L in patients with lower to intermediate ideal body weight. Conclusions: These findings underscore the importance of intensified dosing strategies and covariate-guided individualization supported by therapeutic drug monitoring to achieve optimal teicoplanin exposure in this vulnerable patient group. Full article

Background and Rationale: Tinospora crispa (L.) Hook.f. & Thomson (T. crispa) is a climbing medicinal plant with long-standing ethnopharmacological use, particularly in inflammatory and hepatic disorders and cancer-related conditions. There is a knowledge gap regarding how wild versus cultivated ecotypes differ in chemotype, bioactivity, and safety, and how this might support or refine traditional use. Study Objectives: This study aimed to compare wild and cultivated ecotypes of T. crispa from the Nile Delta (Egypt) in terms of quantitative and qualitative phytochemical profiles; selected in vitro biological activities (especially antioxidant and cytotoxic actions); genetic markers potentially associated with metabolic variation; and short-term oral safety in an animal model. Core Methodology: Standardized extraction of plant material from wild and cultivated ecotypes. Determination of total phenolics, total flavonoids, and major phytochemical classes (alkaloids, tannins, terpenoids). Metabolomic characterization using UHPLC-ESI-QTOF-MS, supported by NMR, to confirm key compounds such as berberine, palmatine, chlorogenic acid, rutin, and borapetoside C. In vitro bioassays including: Antioxidant activity (e.g., radical-scavenging assay with EC₅₀ determination). Cytotoxicity against human cancer cell lines, with emphasis on HepG2 hepatoma cells and calculation of IC₅₀ values. Targeted genetic analysis to detect single-nucleotide polymorphisms (SNPs) in the gen1 locus that differentiate ecotypes. A 14-day oral toxicity study in rats, assessing liver and kidney function markers and performing histopathology of liver and kidney tissues. Principal Results: The wild ecotype showed a 43–65% increase in total flavonoid and polyphenol content compared with the cultivated ecotype, as well as substantially higher levels of key alkaloids, particularly berberine (around 12.5 ± 0.8 mg/g), along with elevated chlorogenic acid and borapetoside C. UHPLC-MS and NMR analyses confirmed the identity of the main bioactive constituents and defined a distinct chemical fingerprint for the wild chemotype. Bioassays demonstrated stronger antioxidant activity of the wild extract than the cultivated one and selective cytotoxicity of the wild extract against HepG2 cells (IC₅₀ ≈ 85 µg/mL), being clearly more potent than extracts from cultivated plants. Genetic profiling detected a C → T SNP within the gen1 region that differentiates the wild ecotype and may be linked to altered biosynthetic regulation. The 14-day oral toxicity study (up to 600 mg/kg) revealed no evidence of hepatic or renal toxicity, with biochemical markers remaining within physiological limits and normal liver and kidney histology. Conclusions and Future Perspectives: The wild Nile-Delta ecotype of T. crispa appears to be a stress-adapted chemotype characterized by enriched levels of multiple bioactive metabolites, superior in vitro bioactivity, and an encouraging preliminary safety margin. These findings support further evaluation of wild T. crispa as a candidate source for standardized botanical preparations targeting oxidative stress-related and hepatic pathologies, while emphasizing the need for: More comprehensive in vivo efficacy studies. Cultivation strategies that deliberately maintain or mimic beneficial stress conditions to preserve phytochemical richness. Broader geographical and genetic sampling to assess how generalizable the present chemotypic and bioactivity patterns are across the species. Full article

Obstructive uropathy (OU) during fetal development induces a fetal cystic dysplastic kidney. The mechanisms of cyst formation and the onset of renal dysfunction remain unclear. Determining whether nephrogenic potential persists during fetal life may suggest whether early intervention could preserve renal development. We aimed to evaluate residual nephrogenic activity in fetal cystic dysplastic kidneys using β-catenin and CD10 immunostaining, and to assess whether the site of obstruction influences cystogenesis. After appropriate approval, 20 timed-gestation fetal lambs had OU created at 60 days. Males underwent urethral and urachal ligation (n = 8, 3 lost), and females underwent unilateral ureteric ligation (n = 8, 1 lost). Fetuses were sacrificed at 80 days (n = 6) and 140 days (term, n = 10), comparing kidneys with normal controls of the same gestational age using immunohistochemical staining for β-catenin and CD10. Developing fetal cystic dysplastic kidneys were identified at 80 days. β-catenin staining showed the absence of granular cytoplasmic expression in cystic regions, indicating arrested nephrogenesis. In male models, cysts originated exclusively from proximal tubules. Female models exhibited mixed proximal and distal tubular involvement. CD10 staining confirmed the loss of proximal tubular markers. Renal development remained arrested at term. Cyst formation disrupts renal development early in gestation, which persists until term. Differences in cystogenesis between the models suggest that the site of obstruction influences pathogenic mechanisms. Full article

Background/Objectives: The aim of this study was to develop a modified version of the T.O.HO. score for predicting percutaneous nephrolithotomy (PCNL) success. Materials and Methods: Patient demographics, stone-related parameters, perioperative findings, and postoperative outcomes were recorded. We reviewed the data of 155 patients who underwent percutaneous nephrolithotomy (PCNL) between October 2020 and December 2024. Patients were divided into two groups: success and failure. While preserving the validated components of the existing T.O.HO. score, the stone location parameter was restructured to more accurately reflect the anatomic challenges inherent to PCNL and was scored to include locations in the renal pelvis, upper, middle, lower and multiple calyces. The performance of the T.O.HO.-PCNL score in predicting surgical success was evaluated using ROC curve analysis. Results: The overall success rate was 65.8%. Patients in the successful group had smaller stone sizes and shorter operative times and hospital stays (p < 0.01). Preoperative hydronephrosis was more commonly observed among unsuccessful group (p < 0.05). The T.O.HO.-PCNL score was significantly lower in the successful group compared with the unsuccessful group. (p < 0.05). In the multivariate logistic regression analysis, stone size emerged as an independent predictor of PCNL success (OR: 1.076; 95% CI: 1.032–1.122; p < 0.001). ROC curve analysis demonstrated that the T.O.HO.-PCNL score had predictive value for PCNL success, with an optimal cut-off of 8.5 (AUC: 0.598; 95% CI: 0.506–0.690; p = 0.046). Conclusions: The T.O.HO.-PCNL scoring system is a promising nomogram for predicting stone-free status after PCNL in preoperative evaluation. Full article

Background: Sodium glucose co-transporter-2 (SGLT-2) inhibitors are antihyperglycemic drugs used in type 2 diabetes mellitus management, and they have associated cardiovascular and renal advantages beyond their glucose-lowering effects, with maintained proof linking gut microbiota modulation to their multiple therapeutic benefits. Aim: This review aims to deliver an overview of the current knowledge regarding the relationship between SGLT-2 inhibitors and the gut microbiota and how this interplay impacts the gut–organ axes such as the lung, heart, brain, liver, and hematological system. Methodology: A literature review was performed in Web of Science, PubMed, and Google Scholar to discover studies that assessed the effects of SGLT-2 inhibitors on gut microbiota composition, microbial metabolites, and associated systemic consequences. Results: SGLT-2 inhibitors modulate gut microbiota and its driven metabolites, strengthening the barrier integrity and alleviating endotoxemia, inflammation, and oxidative stress, resulting in beneficial outcomes across the different gut–organ axes. Conclusion: Gut microbiota modulation is an emerging approach in mediating the multifaceted beneficial impacts of SGLT-2 inhibitors, revealing that their effectiveness goes beyond glycemic control. Future research should concentrate on the microbial taxa and metabolites that mediate these impacts and testing combination approaches that target SGLT-2 pathways and gut microbiota to enhance preservation of different organs. Full article

Background/Objectives: Contrast-induced nephropathy (CIN) is a common iatrogenic or medically induced condition among patients who receive intravenous infusion of iodinated contrast media that can cause renal insufficiency, raise the cost of care, and increase mortality risk. This study evaluated the incidence of CIN and predictors of renal function among cancer patients receiving contrast-enhanced computed tomography (CECT). Methods: A prospective, single-center longitudinal study was conducted at King Abdul-Aziz Medical City’s (Jeddah) medical imaging department from December 2021 to December 2023. Convenience sampling was used to select patients who were exposed to CECT based on data filled in the electronic medical record during the study period. Results: The final sample constituted 80 patients (47.71% attrition, mean age = 55.5 years, 58.75% male). The high attrition rate was associated with participants with incomplete records, those who were lost to follow-up, and those whose follow-up Scr was collected after 72 h from CECT administration. There was no statistically significant change in Scr following contrast exposure (mean increase 0.9 µmol/L; paired t = 1.41, p = 0.162; Wilcoxon p = 0.326). The incidence of CIN was 3.75% (3 of 80 patients; 95% confidence intervals (CI), 1.28–10.39%). Regression analysis showed no statistically significant associations between the percentage change in Scr and age, sex, baseline creatinine, or eGFR category (model R² = 0.07). No clinically meaningful predictors of CIN were identified. Conclusions: The incidence of CIN in this study’s cohort of low-risk cancer patients undergoing CECT was low, and contrast exposure did not produce significant short-term changes in renal function. These findings support the safety of modern contrast agents in oncology imaging, but multi-center studies with larger samples and more robust methods are warranted to refine CIN risk assessment in cancer patients undergoing CECT. Full article

Vitamin C is a small water-soluble molecule primarily cleared by the kidneys. Therefore, its plasma concentration would be expected to increase as kidney function declines. However, studies in patients with chronic kidney disease (CKD) and kidney transplant recipients have shown the opposite: a positive correlation between kidney function and plasma vitamin C levels. In this review, we discuss potential explanations for this counterintuitive finding and suggest alternative mechanisms influencing vitamin C bioavailability in this population. We also explore the hypothesis that this phenomenon may be linked to benzoic acid (benzoate) exposure. Benzoic acid is a widely used food preservative that, like vitamin C, is water-soluble and renally excreted. In individuals with impaired kidney function, reduced clearance may lead to elevated circulating benzoic acid levels, which could increase the likelihood of an in vivo chemical reaction between benzoic acid and vitamin C, resulting in the formation of benzene, which is a known toxic and carcinogenic compound. We summarize experimental evidence demonstrating the vitamin C–benzoic acid reaction in vitro, along with preliminary animal studies suggesting it may also occur in vivo. We also discuss the potential clinical consequences of benzene exposure in the context of patients with kidney function impairment. Given the widespread use of benzoic acid as a food preservative and the ongoing discussion around vitamin C supplementation in patients with kidney disease, this review invites further investigation to evaluate whether this reaction represents a health hazard for this population. Full article

Sodium–glucose cotransporter 2 (SGLT2) inhibitors have substantially reshaped the management of type 2 diabetes mellitus (T2DM), owing not only to their glucose-lowering properties but also to their consistent cardiovascular and renal protective effects. Beyond their initial metabolic indication, these agents have emerged as disease-modifying therapies across a broad spectrum of cardiometabolic and renal conditions. Building on the clinical success of first-generation SGLT2 inhibitors, such as empagliflozin and dapagliflozin, next-generation SGLT2-based therapies have been developed with the aim of refining pharmacological selectivity, optimizing pharmacokinetic profiles, and expanding therapeutic applicability beyond diabetes. These innovations include dual SGLT1/SGLT2 inhibition, alternative dosing strategies, and molecular designs tailored to specific clinical phenotypes, such as heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD). This narrative review critically evaluates the evolving landscape of next-generation SGLT2 inhibitors, with a focus on structural and pharmacokinetic innovations, transporter selectivity, glucose-independent mechanisms, and emerging clinical implications. A comprehensive literature search was conducted using PubMed/MEDLINE, Scopus, and Web of Science, encompassing publications from inception to March 2025. Eligible sources included randomized clinical trials, observational studies, meta-analyses, and authoritative reviews published in English. Available evidence indicates that, while conventional SGLT2 inhibitors confer robust and reproducible cardiorenal benefits, newer agents may further extend therapeutic potential through incretin-related effects, modulation of extra-renal pathways, and disease-specific cardiac and renal mechanisms. Nevertheless, evidence supporting incremental clinical benefit beyond established SGLT2 inhibitors remains limited and heterogeneous, particularly for recently developed compounds. Overall safety profiles appear broadly consistent within the class, although long-term data for next-generation agents are still evolving. Key limitations of the current evidence base include reliance on emerging or indirect mechanistic data, heterogeneity in study populations and clinical endpoints, and the relative scarcity of large, outcome-driven trials for newer SGLT2-based therapies. Future research should prioritize mechanism-driven clinical trials, precision-oriented patient stratification, and head-to-head comparative studies to more clearly define the role of next-generation SGLT2 inhibitors in cardiovascular, renal, and metabolic disease management. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and destruction of cartilage, as well as by extra-articular manifestations. Rheumatoid nephropathy is a common complication of RA and its principal target is the renal corpuscle. Vitamin D and its analogs exert immunomodulatory actions throughout the body due to the widespread of their receptors. Our study aimed to compare the effects of cholecalciferol (vitamin D3) and alfacalcidol on renal corpuscle changes in pristane-induced RA model following a 28-day treatment, using geometric morphometrics. Forty female Wistar rats (190–210 g; 12–13 weeks old) were randomly assigned to four groups: the control (Cont) group (n = 10) received saline i.c., the PIA group (n = 10) was administered pristane i.c., PIA-ALF group (n = 10) was administered pristane i.c. and alfacalcidol orally, and the PIA-CH group (n = 10) was injected i.c. with pristane and received cholecalciferol orally. Pristane administration was used for RA induction. At the end of the experiment, the left kidneys were removed and processed by standard histological procedures for geometric morphometric analysis. Geometric morphometric analysis demonstrated that, compared with the control group, the architecture of the renal corpuscles was altered in the PIA (p < 0.0001) and PIA-CH (p = 0.0065) groups. In contrast, no statistically significant differences were observed in the PIA-ALF group (p = 0.3011). Geometric morphometric analysis demonstrated that alfacalcidol, but not cholecalciferol, exertedaprotective effect on the renal corpuscle architecture in pristane-induced rheumatoid arthritis in rats. Full article

Background and Clinical Significance: Kidney transplant recipients have a 2–4-fold higher cancer risk than the general population. The sequential occurrence of multiple myeloma (MM) and native-kidney renal cell carcinoma (RCC) is rare and creates competing priorities between anti-myeloma efficacy and allograft preservation. Case Presentation: A 54-year-old woman with a 2020 living-donor kidney transplant presented in 2024 with bone pain and shoulder swelling. Low-dose whole-body CT showed multiple punched-out osteolytic lesions. Work-up revealed IgG-κ M-protein 38.5 g/L and 25% clonal plasma cells; cytogenetics showed a complex karyotype (R-ISS III). First-line bortezomib/cyclophosphamide/dexamethasone (VCd) was given while maintaining tacrolimus plus low-dose steroid. After four cycles, she achieved very good partial response (M-protein 42.3 to 5.6 g/L) with stable graft function. Follow-up imaging detected a large exophytic mass in the native right kidney; nephrectomy confirmed papillary RCC, type II. Later, the myeloma progressed with epidural extension causing cord compression. Second-line daratumumab/carfilzomib/dexamethasone (DKd) and palliative spine radiotherapy were initiated. The course was complicated by opportunistic infection and pancytopenia, and the patient died in January 2025. Conclusions: Vigilant post-transplant cancer surveillance—including native-kidney RCC—tailored immunosuppression, and multidisciplinary coordination are critical. VCd with tacrolimus may be feasible when graft preservation is prioritized; however, relapsed high-risk MM on DKd carries substantial infectious risk and a guarded prognosis. Full article

Background: Ischemia–reperfusion injury is a major contributor to early graft dysfunction after kidney transplantation and is associated with endothelial damage, reflected by circulating soluble thrombomodulin (sTM). This exploratory study aimed to assess very early graft-level changes in renal vein sTM during reperfusion using a paired-kidney design, in which kidneys from the same donor were preserved using different strategies: static cold storage (SCS) and hypothermic machine perfusion (HMP). Methods: Renal vein blood samples were collected intraoperatively at 1 and 30 min after reperfusion. Plasma sTM concentrations were determined using ELISA. Early graft function was monitored during the first 7 days post-transplantation. Results: Cold ischemia time was longer in the HMP group than in the SCS group (20 ± 8 h vs. 13 ± 6 h, p < 0.05). At 1 min post-reperfusion, sTM levels were comparable between groups. In the HMP group, sTM decreased significantly between 1 and 30 min after reperfusion, whereas no change was observed in the SCS group. Between-group differences at either time point did not reach statistical significance. Early renal function parameters improved in both groups, with no significant inter-group differences. No cases of delayed graft function or graft thrombosis occurred. Conclusions: Kidney preservation strategy may modulate very early graft-level endothelial responses during reperfusion, reflected by renal vein sTM dynamics. Although a limited sample size may have reduced the ability to detect between-group differences, very early renal vein sTM measurements may provide insight into ischemia–reperfusion injury. Clinical relevance requires validation in larger studies. Full article

Microinflammation serves as a central mechanism linking metabolic diseases and cancer. This study integrates gene expression profiles from irritable bowel syndrome (IBS), obesity, type 2 diabetes (T2D), colorectal cancer (CRC), renal cell carcinoma (RCC), and pancreatic cancer (PC) to identify shared molecular drivers of inflammation-mediated pathology. Weighted gene co-expression network analysis (WGCNA) revealed three highly preserved modules (blue, brown, turquoise) enriched in RNA processing, spliceosome assembly, ribosome biogenesis, and proteostasis regulation. Key hub genes, along with regulatory miRNAs have interconnected networks that modulate transcription, mRNA maturation, protein synthesis, and inflammatory signaling. Although classical inflammatory pathways were not directly enriched, their activity appears to be indirectly shaped by disruptions in RNA-processing and proteostasis machinery. Additionally, gut microbiota-derived products and altered metabolic states may further reinforce these transcriptional and post-transcriptional imbalances. Collectively, these findings reveal conserved molecular signatures that bridge microinflammation, metabolic disease, and oncogenesis, and highlight potential diagnostic and therapeutic targets centered on RNA regulation, proteostasis, and miRNA-mediated control Full article

Aims: Chronic kidney disease (CKD) is associated with adverse cardiovascular outcomes, yet few contemporary studies stratify outcomes by specific CKD stages in the era of modern percutaneous coronary intervention (PCI) techniques and new-generation drug-eluting stents (DESs). We aim to assess the relationship between CKD and post-PCI outcomes in an updated, stage-specific, and long-term cohort. Methods: We retrospectively analyzed 11,489 patients who underwent PCI between 2010 and 2020. Kidney function was classified as preserved (eGFR ≥ 60 mL/min/1.73 m²), stage III CKD (eGFR 30–59), or stage IV/V CKD (eGFR < 30) using the CKD-EPI equation. The primary endpoint was a composite of all-cause mortality, non-fatal myocardial infarction (MI), and target vessel revascularization (TVR) at 1 year; secondary endpoints included individual components and outcomes through 5 years. Associations were evaluated using multivariable Cox regression. Results: Stage III and stage IV/V CKD were present in 18% and 5.6% of patients, respectively. At 1 year, both stage III (HR 2.13, p < 0.01) and stage IV/V CKD (HR 4.91, p < 0.01) were associated with higher risk of the composite endpoint. Mortality rose sharply with CKD severity (33% in stage IV/V vs. 4% in preserved renal function), and MI risk was significantly higher in stage IV/V CKD. These associations persisted after 5 years. Unadjusted TVR risk was higher in stage IV/V CKD but lost significance after adjustment. Conclusions: CKD, particularly in advanced stages, is independently associated with increased mortality and MI after PCI, with effects persisting in the long term. While advanced CKD showed higher unadjusted TVR risk, this was not independent after adjustment. These findings support individualized treatment strategies and extended follow-up in PCI patients with CKD. Full article

Background: Midaortic Syndrome (MAS) is a rare vascular condition characterized by segmental narrowing of the thoracic and abdominal aorta, often involving ostial narrowing of the renal or visceral arteries. While open surgical repair has been the standard treatment, it carries significant morbidity, especially in high-risk patients. Endovascular techniques, including the Chimney approach, provide a minimally invasive alternative to preserve and reestablish both aortic and branch vessel perfusion. This study evaluates the feasibility, safety, and early and midterm outcomes of the Chimney technique used in a cohort of patients with MAS. Methods: Between 2019 and 2025, 9 patients with MAS and branch vessel involvement underwent endovascular repair using the Chimney technique at Brüderklinikum Julia Lanz Hospital in the Mannheim Teaching Hospital of Heidelberg University. Pre-procedural planning was based on computed tomography angiography. Technical success, peri-procedural complications, changes in blood pressure, renal function, and target-vessel stent patency were monitored. Patients were followed over a median of 3 years (range, 0.08–6 years). Results: Nine patients (mean age 77.2 ± 8.7 years; 66.6% female) underwent endovascular repair for midaortic syndrome. All patients were unfit for open surgery. Comorbidities included hypertension (100%), coronary artery disease (100%), and chronic kidney disease (77.7%). Technical success and target-vessel patency were 100%, with no intraoperative deaths, impairment of renal function, or 30-day mortality. One patient (11.1%) developed an access-site hematoma, which was managed conservatively. Median hospital stay was 6 days. During a median 3-year follow-up (range 1 month–6 years), all chimney stents remained patent, patients experienced durable symptom relief, blood pressure improvement, and freedom from reintervention. Conclusions: The Chimney technique offers a safe and effective endovascular option for high-risk patients with Midaortic Syndrome, achieving high technical success, preserved branch-vessel patency, and improvement of symptoms. Larger studies with longer follow-up are warranted to confirm durability and optimize patient selection for this technique. Full article

Background: X-linked hypophosphatemic rickets (XLH) is a rare hereditary disorder characterized by renal phosphate wasting and impaired bone mineralization. Oral manifestations such as spontaneous periapical lesions and dental abscesses in the absence of caries or trauma may precede systemic features in XLH due to underlying dentin hypomineralization and enamel–dentin junction defects, and could serve as early diagnostic indicators. Case Report: We report on the case of a 4-year-old boy referred to our pediatric dental unit with recurrent intraoral fistulas persisting over the past year. Clinical examinations and an orthopantomogram revealed extensive root resorption and periapical pathology affecting multiple primary molars without evident caries or trauma. Laboratory investigations showed hypophosphatemia, elevated renal phosphate loss, and raised inflammatory markers (CRP (C-reactive protein) and granulocytes). Genetic testing of the child and his mother confirmed a diagnosis of X-linked hypophosphatemic rickets. Management: Due to behavioral challenges, treatment proceeded with difficulty over multiple visits. Endodontic treatment was initiated using a formalin–resorcinol technique; however, several primary molars developed progressive necrosis and required extraction. Orthodontic space maintainers were placed to preserve arch integrity and support future eruption. The patient remains under follow-up and is currently awaiting Burosumab therapy. Despite systemic management, spontaneous necroses of the primary molars persist, highlighting the refractory nature of dental involvement in XLH. Conclusions: This case underscores the pivotal role of pediatric dentists in recognizing systemic diseases through oral findings and demonstrates the challenges of managing XLH-related dental pathology, even under targeted systemic therapy. Early interdisciplinary collaboration is essential to optimize both dental and systemic outcomes in affected children. Full article