A Pilot Comparative Study between Creatinine- and Cystatin-C-Based Equations to Estimate GFR and Kidney Ultrasound Percentiles in Children with Congenital Anomalies of the Kidney and Urinary Tract.

Congenital anomalies affecting the kidneys present significant challenges in pediatric nephrology, needing precise methods for assessing renal function and guiding therapeutic intervention. Bedside Schwartz formula with the cystatin-C-based Full Age Spectrum formula and Chronic Kidney Disease in Children (CKiD) U 25 formula used in estimating glomerular filtration rate (eGFR) and also to assess if the eGFR in association with kidney length percentiles can be a monitoring parameter for the progression of chronic kidney disease in children with congenital anomalies of the kidney and urinary tract (CAKUT). A total of 64 pediatric patients (median age at diagnostic was 12 months with an interquartile range of 2 to 60) were diagnosed with congenital anomalies in the kidney and urinary tract between June 2018 and May 2023 at "Louis Turcanu" Emergency Hospital for Children in Timisoara, Romania. Baseline characteristics, CAKUT types, associated pathologies, CKD staging, and eGFR using creatinine and cystatin C were analyzed. The mean age at the moment of examination was 116.50 months; (65, 180). Chronic kidney disease staging revealed a predominance of patients in CKD stages G1 and A1. Analysis of eGFR methods revealed a small mean difference between eGFR estimated by creatinine and cystatin C, with a moderate-strong positive correlation observed between the eGFR and ultrasound parameters. Using cystatin-C-based formulas for eGFR, in conjunction with ultrasound measurements, may offer reliable insights into renal function in pediatric patients with congenital anomalies affecting the kidney and urinary tract. However, the economic aspect must be taken into consideration because cystatin C determination is approximately eight times more expensive than that of creatinine. An interdisciplinary approach is crucial for managing patients with CAKUT.

Impact of Cancer Type and Treatment Protocol on Cardiac Function in Pediatric Oncology Patients: An Analysis Utilizing Speckle Tracking, Global Longitudinal Strain, and Myocardial Performance Index.

Pediatric hemato-oncology patients undergoing anthracycline therapy are at risk of cardiotoxicity, with disease type and treatment intensity potentially affecting cardiac function. Novel echocardiographic measures like speckle tracking echocardiography (STE), global longitudinal strain (GLS), and the myocardial performance index (MPI) may predict early changes in cardiac function not detected by traditional methods. This study aimed to assess the impact of cancer type and treatment protocol on these parameters and their potential in predicting long-term cardiac complications. We conducted a single-center, retrospective cohort study of 99 pediatric oncology patients and 46 controls that were assessed at 3, 6, and 12 months. The median age was 10.7 ± 4.4 years for cases and 10.2 ± 3.6 years for controls. STE, GLS, and MPI were measured, and statistical analyses were performed to determine any significant correlations with cardiotoxicity. Significant variations were observed in traditional cardiac function measurements between the patient and control groups, with a lower average ejection fraction (EF) of 62.8 ± 5.7% in patients vs. 66.4 ± 6.1% in controls (p < 0.001), poorer GLS of -16.3 ± 5.1 in patients compared to -19.0 ± 5.4 in controls (p = 0.004), and higher MPI values of 0.37 ± 0.06 in patients compared to 0.55 ± 0.10 in controls, indicating worse overall cardiac function (p < 0.001). However, differences in cardiac function measurements by cancer histology or treatment protocol were not statistically significant. Regression analyses showed that the combination of GLS, SMOD, and MPI increased the odds of cardiac toxicity with an odds ratio of 7.30 (95% CI: 2.65-12.81, p < 0.001). The study underscores the predictive value of the combined GLS, SMOD, and MPI measurements in pediatric oncology patients undergoing anthracycline treatment for cardiotoxicity. Although variations across cancer types and treatment protocols were not significant, the study emphasizes the potential utility of these novel echocardiographic measures in early detection and long-term prediction of anthracycline-induced cardiotoxicity. Further studies in larger, multi-center cohorts are required for validation.

Correlation of Speckle-Tracking Echocardiography with Traditional Biomarkers in Predicting Cardiotoxicity among Pediatric Hemato-Oncology Patients: A Comprehensive Evaluation of Anthracycline Dosages and Treatment Protocols.

Speckle tracking-echocardiography (STE) is a novel non-invasive imaging tool capable of quantifying myocardial deformation, and thus holds promise in detecting early subclinical myocardial injury. This study aimed to evaluate the correlation of STE with traditional biomarkers in predicting anthracycline-induced cardiotoxicity in the context of varying dosages and treatment protocols in pediatric hemato-oncology patients. We conducted a retrospective study involving pediatric hemato-oncology patients undergoing anthracycline-based chemotherapy. A total of 99 patients were included in the final analysis, with 82 receiving Doxorubicin, of which 58.5% were males, and 17 receiving Epirubicin, of which 70.6% were males, with a median of 10 years old. Traditional biomarkers, such as Troponin I (cTnI) and B-type natriuretic peptide (BNP), were compared with STE parameters, including the global longitudinal strain (GLS), Simpson method of discs (SMOD), and myocardial performance index (MPI). A comprehensive evaluation was conducted based on different dosages of anthracyclines and different treatment protocols, with a follow-up period of one year post-chemotherapy. It was observed that the cTnI levels in the Doxorubicin group were significantly higher (3.2 ng/mL, p = 0.002) than in the Epirubicin group (2.7 ng/mL). However, BNP and NT-proBNP levels were not significantly different between the two groups (p = 0.096 and p = 0.172, respectively). Regarding STE parameters, a significant negative correlation was observed between the anthracycline dose and GLS (Rho = -0.411, p = 0.001), indicating increased cardiotoxicity with dose elevation. The SMOD and MPI gave significantly better values in the Epirubicin group (59.2 and 0.41 vs. 54.4 and 0.36, respectively). However, the ROC analysis did not find GLS, SMOD, or MPI to be significant independent predictors of cardiotoxicity (p > 0.05). There was also considerable variation in cardiotoxicity between the Doxorubicin and Epirubicin study groups, suggesting that the risk of cardiotoxicity is not solely determined by dose. Our study underlines the potential of STE as a sensitive tool for the early detection and prediction of anthracycline-induced cardiotoxicity in pediatric hemato-oncology patients, but only in association with the clinical findings and cardiac biomarkers. While traditional biomarkers still play a role, STE can offer a more accurate prediction of cardiac risk, potentially leading to better management and outcomes for these patients.

Cutaneous Polymeric-Micelles-Based Hydrogel Containing Origanum vulgare L. Essential Oil: In Vitro Release and Permeation, Angiogenesis, and Safety Profile In Ovo.

Origanum vulgare var. vulgare essential oil (OEO) is known as a natural product with multiple beneficial effects with application in dermatology. Oregano essential oil represents a potential natural therapeutic alternative for fibroepithelial polyps (FPs), commonly known as skin tags. Innovative formulations have been developed to improve the bioavailability and stability of essential oils. In this study, we aimed to evaluate the morphology of a polymeric-micelles-based hydrogel (OEO-PbH), the release and permeation profile of oregano essential oil, as well as to assess in vivo the potential effects on the degree of biocompatibility and the impact on angiogenesis in ovo, using a chick chorioallantoic membrane (CAM). Scanning electron microscopy (SEM) analysis indicated a regular aspect after the encapsulation process, while in vitro release studies showed a sustained release of the essential oil. None of the tested samples induced any irritation on the CAM and the limitation of the angiogenic process was noted. OEO-PbH, with a sustained release of OEO, potentially enhances the anti-angiogenic effect while being well tolerated and non-irritative by the vascularized CAM, especially on the blood vessels (BVs) in the presence of leptin treatment. This is the first evidence of in vivo antiangiogenic effects of a polymeric-micelle-loaded oregano essential oil, with further mechanistic insights for OEO-PbH formulation, involving leptin as a possible target. The findings suggest that the OEO-containing polymeric micelle hydrogel represents a potential future approach in the pathology of cutaneous FP and other angiogenesis-related conditions.

Study for Evaluation of Hydrogels after the Incorporation of Liposomes Embedded with Caffeic Acid.

Caffeic acid (CA), a phenolic acid, is a powerful antioxidant with proven effectiveness. CA instability gives it limited use, so encapsulation in polymeric nanomaterials has been used to solve the problem but also to obtain topical hydrogel formulas. Two different formulas of caffeic acid liposomes were incorporated into three different formulas of carbopol-based hydrogels. A Franz diffusion cell system was used to evaluate the release of CA from hydrogels. For the viscoelastic measurements of the hydrogels, the equilibrium flow test was used. The dynamic tests were examined at rest by three oscillating tests: the amplitude test, the frequency test and the flow and recovery test. These carbopol gels have a high elasticity at flow stress even at very low polymer concentrations. In the analysis of the texture, the increase of the polymer concentration from 0.5% to 1% determined a linear increase of the values of the textural parameters for hydrogels. The textural properties of 1% carbopol-based hydrogels were slightly affected by the addition of liposomal vesicle dispersion and the firmness and shear work increased with increasing carbomer concentration.

Antibiotic Resistance Patterns of Uropathogens Causing Urinary Tract Infections in Children with Congenital Anomalies of Kidney and Urinary Tract.

Background: Urinary tract infections (UTI) are common in children worldwide. Congenital anomalies of kidney and urinary tract (CAKUT) increase the risk of UTI and consequently antibiotic resistance. Antibiotic resistance represents an important public health issue worldwide. We aimed to evaluate the local trend in terms of bacterial uropathogen resistance in the western part of Romania in children with CAKUT and UTI. Methods: 252 children with CAKUT were admitted to our hospital over a five-year period. Of them, 91 developed at least one UTI episode, with a total number of 260 positive urine cultures. We collected data about age at diagnosis of CAKUT, sex, origin environment, type and side of CAKUT, number of UTIs, type of uropathogen, and uropathogens antibiotic resistance. Results: Distribution of uropathogens was Escherichia coli (38.84%), Klebsiella spp. (21.15%), Enterococcus spp. (15.76%), Proteus spp. (8.07%), Pseudomonas spp. (8.07%), Enterobacter spp. (2.3%), other Gram-negative bacteria (2.3%), and other Gram-positive bacteria (3.45%). High antibiotic resistance was detected for ampicillin, amoxicillin, and second-generation cephalosporins. Escherichia coli presented high resistance for cefepime and ceftriaxone. Pseudomonas spp. remained susceptible to amikacin, quinolones, and colistin. Vancomycin, teicoplanin, linezolid, and piperacillin/tazobactam remained effective in treating Gram-positive UTI. Conclusions: High antibiotic resistance was identified for frequently used antibiotics. Lower antibiotic resistance was observed for some broad-spectrum antibiotics. Understanding uropathogens' antibiotic resistance is important in creating treatment recommendations, based on international guidelines, local resistance patterns, and patient particularities.

Challenges in the Surgical Treatment of Atrioventricular Septal Defect in Children With and Without Down Syndrome in Romania-A Developing Country.

Background: Atrioventricular septal defect (AVSD) is a cardiac malformation that accounts for up to 5% of total congenital heart disease, occurring with high frequency in people with Down Syndrome (DS). We aimed to establish the surgical challenges and outcome of medical care in different types of AVSD in children with DS compared to those without DS (WDS). Methods: The study included 62 children (31 with DS) with AVSD, evaluated over a 5 year period. Results: Complete AVSD was observed in 49 (79%) children (27 with DS). Six children had partial AVSD (all WDS) and seven had intermediate types of AVSD (4 with DS). Eight children had unbalanced complete AVSD (1 DS). Median age at diagnosis and age at surgical intervention in complete AVSD was not significantly different in children with DS compared to those WDS (7.5 months vs. 8.6). Median age at surgical intervention for partial and transitional AVSDs was 10.5 months for DS and 17.8 months in those without DS. A large number of patients were not operated: 13/31 with DS and 8/31 WDS. Conclusion: The complete form of AVSD was more frequent in DS group, having worse prognosis, while unbalanced AVSD was observed predominantly in the group without DS. Children with DS required special attention due to increased risk of pulmonary hypertension. Late diagnosis was an important risk factor for poor prognosis, in the setting of suboptimal access to cardiac surgery for patients in Romania. Although post-surgery mortality was low, infant mortality before surgery remains high. Increased awareness is needed in order to provide early diagnosis of AVSD and enable optimal surgical treatment.

Oleogel Formulations for the Topical Delivery of Betulin and Lupeol in Skin Injuries-Preparation, Physicochemical Characterization, and Pharmaco-Toxicological Evaluation.

The skin integrity is essential due to its pivotal role as a biological barrier against external noxious factors. Pentacyclic triterpenes stand as valuable plant-derived natural compounds in the treatment of skin injuries due to their anti-inflammatory, antioxidant, antimicrobial, and healing properties. Consequently, the primary aim of the current investigation was the development as well as the physicochemical and pharmaco-toxicological characterization of betulin- and lupeol-based oleogels (Bet OG and Lup OG) for topical application in skin injuries. The results revealed suitable pH as well as organoleptic, rheological, and textural properties. The penetration and permeation of Bet and Lup oleogels through porcine ear skin as well as the retention of both oleogels in the skin were demonstrated through ex vivo studies. In vitro, Bet OG and Lup OG showed good biocompatibility on HaCaT human immortalized cells. Moreover, Bet OG exerted a potent wound-healing property by stimulating the migration of the HaCaT cells. The in ovo results demonstrated the non-irritative potential of the developed formulations. Additionally, the undertaken in vivo investigation indicated a positive effect of oleogels treatment on skin parameters by increasing skin hydration and decreasing erythema. In conclusion, oleogel formulations are ideal for the local delivery of betulin and lupeol in skin disorders.

New, Biocompatible, Chitosan-Gelled Microemulsions Based on Essential Oils and Sucrose Esters as Nanocarriers for Topical Delivery of Fluconazole.

Biocompatible gel microemulsions containing natural origin excipients are promising nanocarrier systems for the safe and effective topical application of hydrophobic drugs, including antifungals. Recently, to improve fluconazole skin permeation, tolerability and therapeutic efficacy, we developed topical biocompatible microemulsions based on cinnamon, oregano or clove essential oil (CIN, ORG or CLV) as the oil phase and sucrose laurate (D1216) or sucrose palmitate (D1616) as surfactants, excipients also possessing intrinsic antifungal activity. To follow up this research, this study aimed to improve the adhesiveness of respective fluconazole microemulsions using chitosan (a biopolymer with intrinsic antifungal activity) as gellator and to evaluate the formulation variables' effect (composition and concentration of essential oil, sucrose ester structure) on the gel microemulsions' (MEGELs) properties. All MEGELs were evaluated for drug content, pH, rheological behavior, viscosity, spreadability, in vitro drug release and skin permeation and antifungal activity. The results showed that formulation variables determined distinctive changes in the MEGELs' properties, which were nevertheless in accordance with official requirements for semisolid preparations. The highest flux and release rate values and large diameters of the fungal growth inhibition zone were produced by formulations MEGEL-FZ-D1616-CIN 10%, MEGEL-FZ-D1216-CIN 10% and MEGEL-FZ-D1616-ORG 10%. In conclusion, these MEGELs were demonstrated to be effective platforms for fluconazole topical delivery.

What if body fat percentage association with FINDRISC score leads to a better prediction of type 2 diabetes mellitus?

INTRODUCTION: Nowadays, the efforts regarding the prevention of type 2 diabetes mellitus (T2DM) are focused on decreasing overweight, obesity and visceral fat accumulation or percent body fat (PBF) risk factors. AIM: The aim of this study was to investigate whether use of bioelectrical impedance analysis (BIA) for measuring PBF could be a reliable method to improve risk assessment of T2DM. Participants, Materials and Methods: This cross-sectional study performed in 2016 enrolled 341 healthy medical students from western Romania, aged 18 to 44 years old, 143 females and 198 males. Anthropometric measurements, PBF (BIA machine InBody720®) determination, along with the Finnish Diabetes Risk (FINDRISC) assessment form, were performed for each participant. RESULTS: 27.6% of the entire cohort was determined as being overweighed and 12% obese. FINDRISC score showed that 5% from the entire group have a moderate to very high risk to develop T2DM in the following 10 years. FINDRISC score was correlated with waist-to-hip ratio (WHR) and PBF showing strong and positive correlations to both parameters (WHR: 0.477, p<0.001; PBF: 0.561, p<0.001). DISCUSSIONS: Our results indicate a stronger correlation between FINDRISC score with PBF compared to FINDRISC and WHR for the entire cohort, and for both males and females. CONCLUSIONS: We recommend PBF measured by BIA (respecting quality control procedures) as a potential parameter to be considered into the risk model predictions for T2DM, as it is an accessible and affordable tool to use in the primary level of healthcare.

Development and evaluation of new microemulsion-based hydrogel formulations for topical delivery of fluconazole.

The aim of the present investigation was to develop and evaluate microemulsion-loaded hydrogels (MEHs) for the topical delivery of fluconazole (FZ). The solubility of FZ in oils, surfactants and cosurfactants was evaluated to identify the components of the microemulsion. The pseudo-ternary phase diagrams were constructed using the novel phase diagram by micro-plate dilution method. Carbopol EDT 2020 was used to convert FZ-loaded microemulsions into gel form without affecting their structure. The selected microemulsions were assessed for globule size, zeta potential and polidispersity index. Besides this, the microemulsion-loaded hydrogel (MEH) formulations were evaluated for drug content, pH, rheological properties and in vitro drug release through synthetic membrane and excised pig ear skin in comparison with a conventional hydrogel. The optimised MEH FZ formulations consisting of FZ 2%, Transcutol P 11.5% and 11%, respectively, as oil phase, Lansurf SML 20-propyleneglycol 52% and 50%, respectively, as surfactant-cosurfactant (2:1), Carbopol EDT 2020 1.5% as gelling agent and water 34.5% and 37%, respectively, showed highest flux values and high release rate values, and furthermore, they had low surfactant content. The in vitro FZ permeation through synthetic membrane and excised pig ear skin from the studied MEHs was best described by the zero-order and first-order models. Finally, the optimised MEH FZ formulations showed similar or slightly higher antifungal activity as compared to that of conventional hydrogel and Nizoral® cream, respectively. The results suggest the potential use of developed MEHs as vehicles for topical delivery of FZ, encouraging further in vitro and in vivo evaluation.

[Thermal stability evaluation of some W/O/W double emulsions containing 1% piroxicam by rheological measurements]. / Evaluarea stabilitatii termice a unor emulsii duble H/L/H cu piroxicam prin determinari reologice.

UNLABELLED: The aim of this work was to evaluate thermal stability of some W/O/W concentrated double emulsions (with 80% dispersed phase) containing 1% piroxicam following their theological behaviour at various temperatures. W/O/W double emulsions containing 1% piroxicam were prepared using the two-step procedure. RESULTS: The variable parameter of formulations was the hydrophilic macromolecule compound dispersed in the internal and external aqueous phases (hydroxyethylcellulose and Carbopol 940). Rheological behaviour and viscosity of the obtained W/O/W double emulsions was measured at 15 degrees C, 20 degrees C, 25 degrees C, 30 degrees C and 35 degrees C respectively, after preparation. The obtained results demonstrated that the studied W1/O/W2 double emulsions containing 1% piroxicam were stable under applied thermal stress, although they exhibited some differences in rheological properties caused by formulation variable.