Search Results (7,301)

Artificial Intelligence (AI) is transforming the healthcare field, offering innovative tools for improving the prediction, detection, and management of diseases. In nephrology, AI holds the potential to improve the diagnosis and treatment of kidney diseases, as well as the optimization of renal replacement therapies. In this review, a comprehensive analysis of recent literature works on artificial intelligence applied to nephrology is presented. Two key research areas structure this review. The first section examines AI models used to support early prediction of acute and chronic kidney disease. The second section explores artificial intelligence applications for hemodialytic therapies in renal insufficiency. Most studies reported high accuracy (e.g., accuracy ≥ 90%) in early prediction of kidney diseases, while fewer addressed therapy optimization and complication prevention, typically reporting moderate-to-high performance (e.g., accuracy ≃ 85%). Filling this gap and developing more accessible AI solutions that address all stages of kidney disease would therefore be crucial to support physicians’ decision-making and improve patient care. Full article

Background: Noninfectious complications of peritoneal dialysis (PD) are common in infants. Mechanical dysfunctions with abdominal compartment syndrome, hydrothorax with respiratory failure, and medication-induced chyloperitoneum are rare during PD. In this case report, we aim to present several life-threatening events and the timely management of a PD infant. Case Presentation: This male infant is a case of infantile nephronophthisis, NPHP3/renal-hepatic–pancreatic dysplasia type 1, with end-stage kidney disease, and he received PD therapy at 4 months of age. Because of the young age with low body weight and hepatosplenomegaly with a limited abdominal cavity, intra-abdominal pressure-associated noninfectious complications frequently occurred. Acute respiratory failure with abdominal dullness was detected at 5 months of age. Abdominal compartment syndrome caused by PD catheter outflow obstruction from omental wrapping was diagnosed via laparoscopic revision surgery. Hyperkalemia, decreased PD drainage volume, and sudden respiratory distress occurred at 10 months old. Hydrothorax due to pleuroperitoneal communication was confirmed by scintigraphy. After thoracoscopic diaphragmatic bleb repair and plication surgery were performed, no recurrence of hydrothorax was observed. Calcium channel blocker-induced chyloperitoneum was observed at 13 months of age. Chylous ascites disappeared after tapering off the calcium channel blocker in 3 days. After the patient grew up with a larger peritoneal cavity, no more pressure-associated complications of PD occurred. Conclusions: The key to successful treatment of rare and life-threatening noninfectious complications of PD in young infants lies in early detection and timely intervention. A limited abdominal cavity is not a contraindication for PD therapy, especially in very young infants with low body weight, because hemodialysis is not a choice of long-term dialysis modality. Full article

Traumatic brain injury (TBI) remains a major global health problem, contributing significantly to morbidity and mortality worldwide. Despite advances in understanding its complex pathophysiology, current therapeutic strategies are insufficient in addressing the long-term cognitive, emotional, and neurological impairments. While the primary mechanical injury is immediate and unavoidable, the secondary phase involves a cascade of biological processes leading to neuroinflammation, blood–brain barrier (BBB) disruption, and systemic immune activation. The heterogeneity of patient responses underscores the urgent need for reliable biomarkers and targeted interventions. Emerging evidence highlights the gut–brain axis as a critical modulator of the secondary phase, with microbiota-derived extracellular vesicles (MEVs) representing a promising avenue for both diagnosis and therapy. MEVs can cross the intestinal barrier and BBB, carrying biomolecules that influence neuronal survival, synaptic plasticity, and inflammatory signaling. These properties make MEVs promising biomarkers for early detection, severity classification, and prognosis in TBI, while also offering therapeutic potential through modulation of neuroinflammation and promotion of neural repair. MEV-based strategies could enable tailored interventions based on the individual’s microbiome profile, immune status, and injury characteristics. The integration of multi-omics with artificial intelligence is expected to fully unlock the diagnostic and therapeutic potential of MEVs. These approaches can identify molecular subtypes, predict outcomes, and facilitate real-time clinical decision-making. By bridging microbiology, neuroscience, and precision medicine, MEVs hold transformative potential to advance TBI diagnosis, monitoring, and treatment. This review also identifies key research gaps and proposes future directions for MEVs in precision diagnostics and gut microbiota-based therapeutics in neurotrauma care. Full article

Background: Urinary tract infections (UTIs) are among the most common hospital- and community-acquired infections, creating a substantial healthcare burden due to recurrence, complications, and rising antimicrobial resistance. Accurate diagnosis and timely antimicrobial therapy are essential. This study aimed to identify trends in the etiology, treatment, and resistance patterns of UTIs through a retrospective analysis of urine isolates processed at the Laboratory of Microbiology at University Hospital St. George in Plovdiv, the largest tertiary care and reference microbiology center in Bulgaria, between 2017 and 2022. Materials and Methods: A retrospective single-center study was performed at the hospital’s Microbiology Laboratory. During the study period, 74,417 urine samples from 25,087 hospitalized patients were screened with the HB&L UROQUATTRO system. Positive specimens were cultured on blood agar, Eosin-Methylene Blue, and chromogenic media. Identification was performed using biochemical assays, MALDI-TOF MS, and the Vitek 2 Compact system. Antimicrobial susceptibility testing included disk diffusion, MIC determination, broth microdilution (for colistin), and Vitek 2 Compact, interpreted according to EUCAST standards. Descriptive analysis and temporal resistance trends were evaluated with regression models, and interrupted time-series analysis was applied to assess COVID-19-related effects. Results: Out of 10,177 isolates, Gram-negative bacteria predominated (73%), with Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis as the leading pathogens. Among Gram-positives, Enterococcus faecalis was the most frequent. In the post-COVID-19 period, ESBL production increased in E. coli (34–38%), K. pneumoniae (66–77%), and P. mirabilis (13.5–24%). Carbapenem resistance rose in K. pneumoniae (to 40.6%) and P. aeruginosa (to 24%), while none was detected in E. coli. Colistin resistance increased in K. pneumoniae but remained absent in E. coli and P. aeruginosa. High-level aminoglycoside resistance in E. faecalis was stable (~70%), and vancomycin resistance in E. faecium rose from 4.6% to 8.9%. Conclusions: Both community- and hospital-acquired UTIs in Southeastern Bulgaria are increasingly linked to multidrug-resistant pathogens, particularly ESBL-producing and carbapenem-resistant Enterobacterales. Findings from the region’s largest referral center highlight the urgent need for continuous surveillance, rational antibiotic use, and novel therapeutic approaches. Full article

Background: B7-H3, an immunoregulatory protein of the B7 family, has been associated with both anti-cancer immunity and tumor promotion, with its expression commonly correlated with poor prognosis. Although it is frequently expressed across cancers, its heterogeneity may limit the effectiveness of B7-H3-targeted therapies. Consequently, a sensitive and non-invasive method is needed to assess B7-H3 expression for patient selection and stratification. Single-domain antibody fragments (sdAbs) offer a promising platform for developing such a diagnostic tool. Methods: To generate B7-H3 sdAbs, two Ilamas were immunized with the recombinant human B7-H3 protein. Positive clones were selected through Phage biopanning and characterized for thermal stability, binding specificity, and affinity to human and murine B7-H3 proteins. Selected sdAbs were radiolabeled with Technetium-99m (^99mTc) and evaluated for B7-H3 detection in two xenograft tumor models using micro-SPECT/CT imaging and dissection studies. Results: Sixteen purified sdAbs bound specifically to recombinant B7-H3 proteins and cells expressing native B7-H3 antigens, with nanomolar affinities. The four best-performing sdAbs bound promiscuously to tested mouse and human B7-H3 isoforms. Lead sdAb C51 labeled with ^99mTc displayed specific accumulation across two human B7-H3⁺ tumor models, achieving high contrast with a tumor-to-blood ratio of up to 10 ± 3.16, and a tumor uptake of up to 4.96 ± 1.4%IA/g at 1.5 h post injection. Conclusions: The lead sdAb enabled rapid, specific, and non-invasive imaging of human B7-H3⁺ tumors. Its isoform promiscuity supports broad applicability across cancers expressing different human B7-H3 isoforms. These results support further development for clinical translation to enable patient selection and improved B7-H3-targeted therapies. Full article

Background/Objectives: Cytomegalovirus (CMV) infection is a frequent complication after lung transplantation, especially in high-risk donor-positive/recipient-negative (D+/R−) patients. CMV-specific hyperimmunoglobulin (CMV-HIG), administered either with antivirals or as monotherapy, may be beneficial for preventing or treating CMV infection in selected clinical scenarios. This study evaluated CMV-HIG indications and their impact on clinical outcomes in our lung transplant unit. Methods: We retrospectively analyzed adult lung transplant recipients (2010–2023) who received ≥2 doses of CMV-HIG for universal prophylaxis, monotherapy prophylaxis, preemptive therapy, or treatment of invasive disease. Results: CMV-HIG was administered to 204 out of 336 recipients (61%). CMV-HIG was well tolerated, with no treatment-related adverse events. Indications were preemptive therapy (63%), universal prophylaxis (24%), monotherapy prophylaxis (7%), and treatment of invasive disease (6%). CMV-HIG was well tolerated, with no treatment-related adverse events. No patients developed invasive disease during combination prophylaxis or preemptive treatment. The combination treatment of patients with invasive disease was also effective, and no cases of VGC resistance were detected. CMV-HIG monoprophylaxis has allowed us to delay or prevent viral replication in recipients who developed VGC side effects. Rates of acute rejection, Chronic Lung Allograft Dysfunction (CLAD), and overall survival were similar across CMV risk groups. Conclusions: Our results showed that the combined use of CMV-HIG and antiviral agents is effective in preventing CMV infection and disease in high-risk lung transplant recipients. This combination is also useful in treating invasive disease and preventing VGC resistance. Additionally, CMV-HIG monoprohylaxis can delay or prevent viral replication in recipients experiencing VGC-related side effects. These findings support the use of CMV-HIG in selected clinical settings, although prospective studies are needed to define its potential benefits within the current therapeutic armamentarium. Full article

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. Full article

Background: Androgenetic alopecia (AGA) is the most prevalent form of hair loss in humans. Oral minoxidil and dutasteride are widely used treatments, while intradermal dutasteride mesotherapy has recently gained interest as a complementary approach. However, comparative studies in real-world settings are lacking. Objective: The aim was to compare the effectiveness and safety of four AGA therapies: oral minoxidil alone (OM), OM plus oral dutasteride (OM + OD), OM plus mesotherapy (OM + MD), and a combination of all three (CT). Methods: A retrospective study was conducted, including 280 adult patients (mean age 35 ± 9.4 years) with AGA, excluding those with recent treatment (last 3 months) or other hair loss disorders. The therapeutic response was assessed by comparing treatment outcomes from standardized clinical images at 6 and 12 months using a four-point improvement scale. Patient satisfaction was also assessed using a four-point subjective scale. Results: Participants were divided into four treatment groups. In total, 74 patients (26.4%) were treated with OM, 65 patients (23.2%) with OM + OD, 61 patients (21.8%) with OM + MD, and 80 patients (28.6%) with CT. At 12 months, group 4 treated with CT showed significantly better results in both frontal and vertex areas (p < 0.001), while group 3 (OM + MD) performed best at 6 months in the vertex. Side effects were mild and infrequent, with hypertrichosis being the most common. Erectile dysfunction was reported with a lower incidence than reported in the literature: two patients (3.1%) in group 2 (OM + OD) and three (3.8%) patients in CT. Overall, no serious adverse events were detected. Conclusions: Combining oral minoxidil, oral dutasteride, and mesotherapy with dutasteride yields the most effective results for AGA with a favorable safety profile. Full article

Breast cancer (BC) is the most frequently diagnosed malignancy in women. Currently, BC is treated with a holistic and multidisciplinary approach from diagnostic, surgical, radio-oncological, and medical perspectives, and advances including in early detection and treatment methods have led to improved outcomes for patients in recent years. Yet, BC remains the second most common cause of cancer-related deaths among women and there is an array of gaps to achieve optimal care. To close gaps in cancer care, here we describe a collaborative Request For Proposals (RFP) framework supporting independent initiatives for metastatic breast cancer (MBC) patients and aiming at improving their quality of care. We set up a collaborative framework between Pfizer and Sharing Progress in Cancer Care (SPCC). Our model is based on an RFP system in which Pfizer and SPCC worked together ensuring the independence of the funded projects. We developed a three-step life cycle RFP. The collaborating framework of the project was based on an RFP with a USD 1.5 million available budget for funding independent grants made available from Pfizer and managed in terms of awareness, selection, and monitoring by SPCC. Our three-step model could be applicable and scalable to quality improvement (QI) initiatives that are devoted to tackling obstacles to reaching optimal care. Through this model, seven projects from five different European countries were supported. These projects covered a range of issues related to the experience of patients with MBC: investigator communication, information, and shared decision-making (SDM) practices across Europe; development, delivery, and evaluation of a scalable online educational program for nurses; assessment of disparities among different minority patient groups; development of solutions to improve compliance or adherence to therapy; an information technology (IT) solution to improve quality of life (QoL) of patients with MBC and an initiative to increase awareness and visibility of MBC patients. Overall, an average of 171 healthcare professionals (HCPs) per project and approximately 228,675 patients per project were impacted. We set up and describe a partnership model among different stakeholders within the healthcare ecosystem―academia, non-profit organizations, oncologists, and pharmaceutical companies―aiming at supporting independent projects to close gaps in the care of patients with MBC. By removing barriers at different layers, these projects contributed to the achievement of optimal care for patients with MBC. Full article

Methylphenidate (MPH) and its active enantiomer, dexmethylphenidate, are widely prescribed as first-line therapies for attention deficit hyperactivity disorder (ADHD), yet their increasing non-medical use highlights significant clinical and toxicological challenges. MPH blocks dopamine (DAT) and norepinephrine (NET) transporters, thereby elevating synaptic catecholamine levels. While this underpins therapeutic efficacy, prolonged or abusive exposure has been associated with mitochondrial impairment, disrupted bioenergetics, and excessive reactive oxygen species (ROS) production, which collectively contribute to neuronal stress and long-term neurotoxicity. Growing evidence suggests that the gut–brain axis may critically influence MPH outcomes: diet-induced shifts in microbiome composition appear to regulate oxidative stress, neuroinflammation, and drug metabolism, opening potential avenues for dietary or probiotic interventions. From a forensic perspective, the detection and monitoring of MPH misuse require advanced methodologies, including enantioselective LC–MS/MS and analysis of alternative matrices such as hair or oral fluids, which enable retrospective exposure assessment and improves abuse surveillance. Despite its established therapeutic profile, MPH remains a compound with a narrow balance between clinical benefit and toxicological risk. Future directions should prioritize longitudinal human studies, biomarker identification for abuse monitoring, and the development of mitochondria-targeted therapies to minimize adverse outcomes and enhance safety in long-term treatment. Full article

Background: Gorlin syndrome (GS) is a rare autosomal dominant disorder, associated with pathogenic PTCH1 or SUFU variants, predisposing to tumors such as basal cell carcinoma, medulloblastoma (MB), odontogenic keratocyst, and, rarely, cardiac fibroma (CF). MB occurs in ~5% of GS cases, typically in early childhood, while CF appears in 1–3%. Their coexistence in childhood is extremely rare. This report describes a pediatric GS case with synchronous MB and CF, focusing on the management priorities between oncologic and cardiac interventions. Methods: A 15-year follow-up is reported for a girl diagnosed at 22 months with desmoplastic/nodular MB and left ventricular CF. GS diagnosis was based on clinical features, imaging, and confirmation of a pathogenic PTCH1 variant (c.3306+1G>T). A literature narrative review on CF in GS was also conducted. Results: MB gross total resection was followed by chemotherapy, during which ventricular tachycardia episodes occurred, managed with cardioversion and antiarrhythmics. Given the favorable prognosis of early-treated MB in GS, oncologic therapy was prioritized. Cardiac status was monitored with ECG, Holter, echocardiography, and cardiac MRI. An adapted AIEOP protocol minimized cardiotoxicity. CF was managed conservatively, with no further arrhythmias and preserved ventricular function throughout 15 years. MB has not recurred. Conclusions: In GS patients with concurrent MB and CF, prioritizing MB treatment and adopting a conservative, closely monitored approach to CF can yield excellent long-term outcomes. In children with MB, especially syndromic forms, routine echocardiography is recommended to detect CF. This case underscores the value of multidisciplinary care in managing complex GS presentations. Full article

Trichophyton indotineae is an emerging dermatophyte species responsible for recalcitrant and terbinafine-resistant dermatophytosis, raising concerns over diagnostic accuracy and treatment efficacy. This study aimed to improve the identification and resistance profiling of T. indotineae by integrating molecular methods with machine learning-assisted analysis of MALDI-TOF mass spectra. A total of 56 clinical isolates within the Trichophyton mentagrophytes complex were analyzed using ITS and ERG1 gene sequencing, antifungal susceptibility testing, and MALDI-TOF MS profiling. Terbinafine resistance was detected in 23 isolates and correlated with specific ERG1 mutations, including F397L, L393S, F415C, and A448T. While conventional MALDI-TOF MS failed to reliably distinguish T. indotineae from closely related species, unsupervised statistical methods (PCA and hierarchical clustering) revealed distinct spectral groupings. Supervised machine learning algorithms, particularly PLS-DA and SVM, achieved 100% balanced accuracy in species classification using 10-fold cross-validation. Biomarker analysis identified discriminatory spectral peaks for both T. indotineae and T. mentagrophytes (3417.29 m/z and 3423.53 m/z). These results demonstrate that combining MALDI-TOF MS with multivariate analysis and machine learning improves diagnostic resolution and may offer a practical alternative to sequencing in resource-limited settings. This approach could enhance the routine detection of terbinafine-resistant T. indotineae and support more targeted antifungal therapy. Full article

Breast cancer is the most common malignancy and leading cause of cancer-related mortality among women worldwide. Oestrogen receptor (ER)-positive disease accounts for the majority of cases, where endocrine and targeted therapies have substantially improved survival. Nevertheless, resistance to therapy remains inevitable, emphasising the need for precision strategies informed by molecular profiling. The molecular landscape of ER-positive breast cancer is increasingly complex, characterised by diverse genomic alterations driving resistance and progression. Advances in next-generation sequencing and circulating tumour DNA (ctDNA) technologies enable the dynamic assessment of tumour heterogeneity and clonal evolution, informing prognostication and guiding biomarker-driven therapy. Uniquely, this review integrates molecular phenotyping with clinical treatment algorithms for advanced ER-positive breast cancer, providing a practical framework to translate genomic insights into patient care. Key genomic alterations and targeted strategies with demonstrated clinical benefit, including oral selective ER degraders (SERDs) and PI3K/AKT/mTOR inhibitors in selected biomarker populations, are highlighted. Emerging targets, such as human epidermal growth factor 2 (HER2) mutations, and the potential of ctDNA monitoring to detect resistance and guide therapeutic escalation are also discussed. Incorporating molecular profiling, as recommended by international guidelines, into routine clinical decision making can personalise therapy and optimise patient outcomes. Addressing real-world challenges, including cost and accessibility, will be critical to achieving equitable implementation of precision oncology for patients with ER-positive breast cancer worldwide. Full article

Background/Objectives: The maintenance of peri-implant soft tissue health is critical for the long-term success of implant therapy, particularly in edentulous patients rehabilitated with mandibular overdentures. Leukocyte- and platelet-rich fibrin (L-PRF) has been proposed as an autologous biomaterial to enhance peri-implant tissue quality. This randomized controlled clinical trial evaluated the effect of L-PRF on peri-implant mucosal thickness in edentulous patients treated with mandibular implant-retained overdentures. Methods: Edentulous patients received two interforaminal implants to retain a mandibular overdenture and were randomly assigned to a test group (L-PRF applied during surgery) or a control group (standard protocol without L-PRF). Clinical measurements of keratinized mucosal thickness and width were recorded at baseline, 12 weeks, and 24 weeks. Volumetric analyses of soft and hard tissue changes were performed using digital superimposition of STL models. The trial was conducted in accordance with the Declaration of Helsinki and approved by the Scientific Ethics Committee of the Aconcagua Health Service. All participants provided written informed consent. Results: A significant increase in keratinized mucosal thickness was observed in the L-PRF group at 12 and 24 weeks compared with baseline (p < 0.01). No significant differences were detected between the groups in soft tissue volume (p = 0.12) or bone volume (p = 0.45). Mucosal width remained stable in both groups throughout follow-up. Conclusions: The application of L-PRF at implant placement resulted in a significant gain in peri-implant mucosal thickness, suggesting a soft tissue modulating effect. Enhancing keratinized mucosal thickness during implant surgery may improve peri-implant tissue quality and support long-term stability of mandibular overdentures. Full article

The PML::RARA fusion resulting from t(15;17) is the genetic hallmark of acute promyelocytic leukemia (APL), typically detected by cytogenetics and/or fluorescence in situ hybridization (FISH) studies. Rarely, APL patients present with normal cytogenetics and FISH findings, complicating diagnosis and delaying life-saving therapy. We report a 23-year-old male with clinical, morphologic and immunophenotypic features consistent with APL but negative for FISH studies. Despite prompt initiation of all-trans retinoic acid (ATRA) based on clinical suspicion, the patient succumbed to intracranial hemorrhage. Quantitative reverse transcriptase PCR (qRT-PCR) confirmed a long isoform PML::RARA fusion. A review of 34 published cytogenetics- and FISH-negative cases since 1995 demonstrates that RT-PCR-based methods reliably detect cryptic fusions. While advanced genomic approaches may identify these fusions at higher resolution, their accessibility, complexity, cost, and turnaround time often limit diagnostic utility in the urgent setting of APL. Given the extreme rarity of this subset, cytogenetics and FISH remain the standard frontline tests; however, these cases underscore the critical need to incorporate molecular testing into routine workflows. Early recognition and timely therapy are essential to reducing mortality in cryptic APL, and these cases also provide insight into mechanisms of atypical leukemia biology. Full article