Dimitrios Kavvadas

Background/Objectives: Aminoglycoside antibiotics such as amikacin are indispensable for treating severe Gram-negative infections, but their clinical use is limited by a well-documented toxicity profile that has focused overwhelmingly on ototoxicity and nephrotoxicity, leaving their action on the peripheral nervous system comparatively unexplored. Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist used in Alzheimer’s disease, has shown protective effects in peripheral-nerve animal models, raising the question of whether it could limit potential amikacin-induced peripheral neurotoxicity. Methods: Adult male Wistar rats were allocated to three groups: Group A: control, no drug administration; Group B: amikacin 20 mg/kg/day intraperitoneally for 14 days; and Group C: concurrent administration of amikacin 20 mg/kg/day plus memantine 10 mg/kg/day intraperitoneally for 14 days. Branches of the brachial plexus and the sciatic nerve were harvested and processed for transmission electron microscopy (TEM), and axonal, myelin and Schwann-cell ultrastructure were assessed in a blinded manner. Results: Group A showed intact axons, compact myelin sheaths and normal Schwann cells. Group B showed pronounced neurotoxic lesions: degeneration of the myelin sheath (splitting, dilation and folding), axoplasmic collapse with swollen organelles, and Schwann cells of abnormal shape. In Group C, memantine markedly attenuated the nerve fiber damage: most axons were preserved, myelin-sheath abnormalities were mild and focal, and numerous normal Schwann cells and unmyelinated nerve fibers were retained. Conclusions: Amikacin exerts a distinct, previously under-recognized ultrastructural neurotoxicity on peripheral nerves, and concurrent memantine confers substantial neuroprotection, supporting a potential adjunctive role for NMDA-receptor antagonism during aminoglycoside therapy.

This systematic review addresses the critical public health concern regarding the pervasive contamination of drinking water by microplastics (MPs). With global plastic production escalating, the degradation of waste into MPs has led to their ubiquity in freshwater sources. This review synthesizes recent findings on the occurrence of MPs in tap and bottled water and evaluates the associated toxicological risks to human health. Results indicate that humans ingest tens of thousands of particles annually, with drinking water being a significant vector. The review highlights that particles, particularly those in the nanoplastic range, can breach biological barriers, leading to bioaccumulation in secondary organs such as the liver and placenta. Toxicological impacts include oxidative stress, inflammation, and metabolic disruption.

Background/Objectives: To evaluate the diagnostic performance of ultrasound-guided attenuation parameter (UGAP) for the assessment of hepatic steatosis in a population at risk for metabolic dysfunction-associated steatotic liver disease (MASLD), using MRI proton density fat fraction (PDFF) as the reference standard, and to also derive optimal population-specific diagnostic thresholds. Methods: In this single-center prospective study, 64 adults at risk for MASLD underwent UGAP measurement and MRI-PDFF. UGAP was performed according to standardized manufacturer-recommended protocols and standardized on the right hepatic lobe. Hepatic steatosis was staged using established MRI-PDFF thresholds. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Cohort-UGAP cut-offs were derived using the Youden index. Associations between UGAP and clinical parameters were assessed using correlation and regression analyses. Results: UGAP correlated strongly with MRI-PDFF (ρ = 0.82, p < 0.001). The areas under the ROC curve (AUCs) for detecting mild, moderate, and severe steatosis were 0.86, 0.96, and 0.96, respectively. Right-lobe acquisitions outperformed left-lobe measurements, while four-region averaging yielded the highest diagnostic performance. UGAP values were associated with BMI, waist circumference, and liver enzymes. Conclusions: UGAP provides an accurate noninvasive assessment of hepatic steatosis, demonstrating high overall diagnostic agreement with MRI-PDFF. Right-lobe acquisition and multi-regional averaging further improve its performance. While cohort-specific threshold optimization may enhance clinical applicability, larger studies are needed to fully confirm its accuracy in advanced stages.

This scoping review examines how contaminants in drinking water influence children’s neurological development. Evidence across epidemiological, experimental, and mechanistic studies demonstrates that early-life exposure to lead, arsenic, fluoride, manganese, and PFAS is consistently associated with adverse cognitive, behavioral, and neurodevelopmental outcomes. These effects occur even at low exposure levels and involve pathways such as oxidative stress, endocrine disruption, and impaired neuronal signaling. In contrast, data on nitrates and microplastics remain limited, highlighting substantial research gaps. Overall, the findings underscore drinking water quality as a critical determinant of child neurodevelopment and emphasize the need for strengthened monitoring and public health protections.

Background/Objectives: Cisplatin is a potent chemotherapeutic agent whose clinical utility is limited by severe side effects, including neurotoxicity affecting the ocular system. The pathophysiology involves oxidative stress and mitochondrial dysfunction, to which the retina is particularly vulnerable. Selenium (Se), an essential trace element and component of antioxidant enzymes, has shown potential in mitigating cisplatin toxicity, although its efficacy with respect to retinal structure and the influence of administration routes remain underexplored. This study aimed to evaluate the protective efficacy of selenium against cisplatin-induced retinal toxicity and compare the effects of intraperitoneal and oral selenium administration. Methods: Forty adult male Wistar rats were randomized into four groups (n = 10 each): Group A (Cisplatin Monotherapy, 3.5 mg/kg IP for 5 days; cumulative dose 17.5 mg/kg); Group B (Cisplatin + Intraperitoneal Selenium, 2.73 mg/kg; cumulative dose 60 mg/kg); Group C (Control); and Group D (Cisplatin + Oral Selenium). Selenium prophylaxis, administered as sodium selenite (Na₂SeO₃), began two days prior to cisplatin administration and continued for 15 days post-treatment. Retinal evaluation two weeks after cisplatin cessation included light microscopy, semi-quantitative immunohistochemical (IHC) analysis for inflammatory (IL-6) and fibrotic (TGF-β2) markers, and Transmission Electron Microscopy (TEM) for ultrastructural analysis, which were the primary endpoints. Statistical differences in the IHC scores were analyzed via the Kruskal-Wallis H test with Dunn’s post hoc comparisons. Results: Cisplatin monotherapy (Group A) caused severe disruption of the retinal architecture, including edema, reactive gliosis, and significant upregulation of IL-6 and TGF-β2. Ultrastructural analysis revealed mitochondrial swelling (cristolysis) and photoreceptor disk fragmentation. Intraperitoneal selenium (Group B) was associated with significant structural preservation and intact mitochondria, with TGF-β2 levels comparable to those of the controls, although the IL-6 level remained moderately elevated. Conversely, oral selenium (Group D) suppressed both IL-6 and TGF-β2 expression to near-negative levels but provided less ultrastructural protection, resulting in persistent mitochondrial swelling and focal photoreceptor disruption. Conclusions: Systemic cisplatin induces severe subcellular retinal toxicity characterized by mitochondrial damage and photoreceptor degeneration. Selenium supplementation attenuates these effects; however, outcome patterns differ by administration route. Intraperitoneal selenium was associated with greater morphological and ultrastructural preservation despite persistent IL-6 elevation, whereas oral selenium normalized immunohistochemical marker expression to near-control levels but was associated with more pronounced residual subcellular damage on qualitative TEM assessment. These preliminary morphological and immunohistochemical findings suggest that the route of selenium delivery may influence its neuroprotective profile; however, pharmacokinetic measurements and functional retinal assessments, such as electroretinography, are warranted before its clinical translation.

Background/Objectives: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide, requiring accurate and accessible diagnostic tools. Methods: A systematic review evaluated the diagnostic performance of Ultrasound-Derived Fat Fraction (UDFF), with a primary focus on prospective studies comparing UDFF to MRI Proton Density Fat Fraction (MRI-PDFF) as the reference standard and a secondary appraisal of its performance against other modalities. Additional parameters, such as technical feasibility, inter-observer agreement, and proposed thresholds, were summarized to support clinical applicability. Results: Seven prospective MRI-based studies (n = 862) demonstrated excellent correlation (average r = 0.848) and reproducibility (inter-observer intraclass correlation coefficient ICC = 0.978, intra-observer ICC = 0.980) of UDFF, with high diagnostic accuracy across steatosis grades (AUCs ≥ 0.89). Additional studies comparing UDFF with Controlled Attenuation Parameter (CAP), histology, and other quantitative ultrasound techniques (attenuation- or backscatter-based methods) confirmed high sensitivity and specificity, particularly for advanced steatosis, and emphasized the potential of UDFF as a comprehensive quantitative biomarker. Proposed UDFF cut-offs for mild, moderate, and severe steatosis ranged from 5% to 23%, demonstrating high sensitivity and specificity. Factors like body position, probe pressure, and visceral fat influenced measurements, underscoring the need for standardized protocols. Conclusions: UDFF seems to offer a reliable and cost-effective quantitative ultrasound modality. So far, it correlates strongly with MRI-PDFF and accurately grades steatosis, especially for S2–S3. Given cut-off variability and protocol sensitivity, broad routine adoption may be premature. Therefore, we recommend further studies focusing on standardized acquisition and cut-off calibration to MRI-PDFF.

The aim of the present study is to examine the possibility of nephrotoxicity following the intravitreal injection of the antifungal agents voriconazole and micafungin. Μale and female New Zealand white rabbits were divided into the control group C that received no medication and the study groups that underwent either one or two intravitreal injections of voriconazole or micafungin solution, respectively, or one co-administration of the two agents. Euthanasia was performed ten days after the last intravitreal administration, and kidney tissue samples were obtained and prepared for electron microscopy study, as well as immunohistochemical study for EGFR and IL-6 markers. Ultrastructural alterations of the renal tissue were found in places of limited extent, more evident at the level of the proximal tubules. The expression of the two markers was positive, especially in the double and the combined administration of the two drugs, both in the renal corpuscle and the tubules. The finding of the aforementioned histological lesions triggers the need for an additional study of the effect of the specific drugs on the kidney to establish whether these alterations are reversible or not. Redesigning the dosage regimen during intravitreal administration of these agents could be a future therapeutic goal to prevent potential nephrotoxicity. The intravitreal concentrations used in rabbits, particularly for voriconazole, closely approximate those used in humans, supporting the clinical relevance of the findings.

INPLASY202590124 Quantitative ultrasound for hepatic steatosis: A systematic review highlighting the diagnostic performance of Ultrasound-Derived Fat Fraction Keywords: Ultrasound; UDFF; MRI-PDFF; …

Background/Objectives: Sarcopenia, defined as the progressive loss of muscle mass and function, is increasingly recognized in pediatric cancer patients as a significant clinical and prognostic factor. Sarcopenia in children arises from malignancy-related inflammation, malnutrition, and treatment toxicity, negatively affecting treatment response, recovery, and quality of life. Methods: We searched MEDLINE and Scopus for English-written articles published over the last five years using synonyms for the terms “sarcopenia” and “pediatric cancer”. Screening and data extraction were performed in a duplicate-blinded method. We qualitatively synthesized eligible articles. Results: Recent studies identify pre-treatment sarcopenia as a marker of poor prognosis, especially in hepatoblastoma and neuroblastoma. Total psoas muscle area (tax) and skeletal muscle index (SMI) are emerging diagnostic tools, though standardized methods remain lacking. Sarcopenia’s etiology is multifactorial, involving impaired mitochondrial metabolism, chemotherapy-induced appetite loss, and systemic inflammation. Sarcopenic obesity is common, particularly among leukemia survivors, often masked by normal BMI. Survivors also face reduced bone density, impaired immunity, and persistent muscle loss, linked to prior therapies such as radiotherapy and hematopoietic stem cell transplantation. Increase in muscle mass post-treatment correlates with better survival outcomes. Conclusions: Early detection of sarcopenia can support timely interventions such as nutritional support and physical activity. Yet, significant diagnostic heterogeneity across existing studies hampers definitive conclusions regarding its true prevalence and the optimal assessment method. Standardized diagnostic criteria are urgently needed to enable more reliable prevalence estimates and evidence-based clinical strategies.