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Search Results (5,564)

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Keywords = infection and treatment method

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35 pages, 5195 KiB  
Article
A Multimodal AI Framework for Automated Multiclass Lung Disease Diagnosis from Respiratory Sounds with Simulated Biomarker Fusion and Personalized Medication Recommendation
by Abdullah, Zulaikha Fatima, Jawad Abdullah, José Luis Oropeza Rodríguez and Grigori Sidorov
Int. J. Mol. Sci. 2025, 26(15), 7135; https://doi.org/10.3390/ijms26157135 (registering DOI) - 24 Jul 2025
Abstract
Respiratory diseases represent a persistent global health challenge, underscoring the need for intelligent, accurate, and personalized diagnostic and therapeutic systems. Existing methods frequently suffer from limitations in diagnostic precision, lack of individualized treatment, and constrained adaptability to complex clinical scenarios. To address these [...] Read more.
Respiratory diseases represent a persistent global health challenge, underscoring the need for intelligent, accurate, and personalized diagnostic and therapeutic systems. Existing methods frequently suffer from limitations in diagnostic precision, lack of individualized treatment, and constrained adaptability to complex clinical scenarios. To address these challenges, our study introduces a modular AI-powered framework that integrates an audio-based disease classification model with simulated molecular biomarker profiles to evaluate the feasibility of future multimodal diagnostic extensions, alongside a synthetic-data-driven prescription recommendation engine. The disease classification model analyzes respiratory sound recordings and accurately distinguishes among eight clinical classes: bronchiectasis, pneumonia, upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), asthma, chronic obstructive pulmonary disease (COPD), bronchiolitis, and healthy respiratory state. The proposed model achieved a classification accuracy of 99.99% on a holdout test set, including 94.2% accuracy on pediatric samples. In parallel, the prescription module provides individualized treatment recommendations comprising drug, dosage, and frequency trained on a carefully constructed synthetic dataset designed to emulate real-world prescribing logic.The model achieved over 99% accuracy in medication prediction tasks, outperforming baseline models such as those discussed in research. Minimal misclassification in the confusion matrix and strong clinician agreement on 200 prescriptions (Cohen’s κ = 0.91 [0.87–0.94] for drug selection, 0.78 [0.74–0.81] for dosage, 0.96 [0.93–0.98] for frequency) further affirm the system’s reliability. Adjusted clinician disagreement rates were 2.7% (drug), 6.4% (dosage), and 1.5% (frequency). SHAP analysis identified age and smoking as key predictors, enhancing model explainability. Dosage accuracy was 91.3%, and most disagreements occurred in renal-impaired and pediatric cases. However, our study is presented strictly as a proof-of-concept. The use of synthetic data and the absence of access to real patient records constitute key limitations. A trialed clinical deployment was conducted under a controlled environment with a positive rate of satisfaction from experts and users, but the proposed system must undergo extensive validation with de-identified electronic medical records (EMRs) and regulatory scrutiny before it can be considered for practical application. Nonetheless, the findings offer a promising foundation for the future development of clinically viable AI-assisted respiratory care tools. Full article
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13 pages, 1092 KiB  
Article
In Vivo Antibiotic Elution and Inflammatory Response During Two-Stage Total Knee Arthroplasty Revision: A Microdialysis Pilot Study
by Julika Johanna Behrens, Alexander Franz, Frank Alexander Schildberg, Markus Rudowitz, Stefan Grote and Frank Sebastian Fröschen
Antibiotics 2025, 14(8), 742; https://doi.org/10.3390/antibiotics14080742 - 24 Jul 2025
Abstract
Introduction: Two-stage revision with an antibiotic-loaded, temporary static cement spacer is a common treatment for periprosthetic joint infection (PJI) of the knee. However, limited data exists on in vivo antibiotic elution kinetics after spacer implantation. This pilot study uses the technique of [...] Read more.
Introduction: Two-stage revision with an antibiotic-loaded, temporary static cement spacer is a common treatment for periprosthetic joint infection (PJI) of the knee. However, limited data exists on in vivo antibiotic elution kinetics after spacer implantation. This pilot study uses the technique of microdialysis (MD) to collect intra-articular knee samples. The aim was to evaluate MD as an intra-articular sampling method to detect spacer-eluted antibiotics within 72 h after surgery and to determine whether they show specific elution kinetics. Methods: Ten patients (six male, four female; age median 71.5 years) undergoing two-stage revision for knee PJI were included. A MD catheter was inserted into the joint during explantation of the infected inlying implant and implantation of a custom-made static spacer coated with COPAL cement (0.5 g gentamicin (G) and 2 g vancomycin (V)). Over 72 h postoperatively, samples were collected and analyzed for spacer-eluted antibiotics, intravenously administered antibiotics (e.g., cefazolin and cefuroxime), metabolic markers (glucose and lactate), and Interleukin-6 (IL-6). Local and systemic levels were compared. Results: All catheters were positioned successfully and well tolerated for 72 h. Antibiotic concentrations in MD samples peaked within the first 24 h (G: median 9.55 µg/mL [95% CI: 0.4–17.36]; V: 37.57 µg/mL [95% CI: 3.26–81.6]) and decreased significantly over 72 h (for both p < 0.05, G: 4.27 µg/mL [95% CI: 2.26–7.2]; V: 9.69 µg/mL [95% CI: 3.86–24]). MD concentrations consistently exceeded blood levels (p < 0.05), while intravenously administered antibiotics showed higher blood concentrations. Glucose in MD samples decreased from 17.71 mg/dL to 0.89 mg/dL (p < 0.05). IL-6 and lactate concentrations showed no difference between MD and blood samples. Conclusions: Monitoring antibiotics eluted by a static spacer with intra-articular MD for 72 h is feasible. Gentamicin and vancomycin levels remained above the minimal inhibitory concentration. Differentiating infection from surgical response using metabolic and immunological markers remains challenging. Prolonged in vivo studies with MD are required to evaluate extended antibiotic release in two-stage exchanges. Full article
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13 pages, 1200 KiB  
Article
Intra-Host Evolution During Relapsing Parvovirus B19 Infection in Immunocompromised Patients
by Anne Russcher, Yassene Mohammed, Margriet E. M. Kraakman, Xavier Chow, Stijn T. Kok, Eric C. J. Claas, Manfred Wuhrer, Ann C. T. M. Vossen, Aloys C. M. Kroes and Jutte J. C. de Vries
Viruses 2025, 17(8), 1034; https://doi.org/10.3390/v17081034 - 23 Jul 2025
Abstract
Background: Parvovirus B19 (B19V) can cause severe relapsing episodes of pure red cell aplasia in immunocompromised individuals, which are commonly treated with intravenous immunoglobulins (IVIGs). Few data are available on B19V intra-host evolution and the role of humoral immune selection. Here, we report [...] Read more.
Background: Parvovirus B19 (B19V) can cause severe relapsing episodes of pure red cell aplasia in immunocompromised individuals, which are commonly treated with intravenous immunoglobulins (IVIGs). Few data are available on B19V intra-host evolution and the role of humoral immune selection. Here, we report the dynamics of genomic mutations and subsequent protein changes during relapsing infection. Methods: Longitudinal plasma samples from immunocompromised patients with relapsing B19V infection in the period 2011–2019 were analyzed using whole-genome sequencing to evaluate intra-host evolution. The impact of mutations on the 3D viral protein structure was predicted by deep neural network modeling. Results: Of the three immunocompromised patients with relapsing infections for 3 to 9 months, one patient developed two consecutive nonsynonymous mutations in the VP1/2 region: T372S/T145S and Q422L/Q195L. The first mutation was detected in multiple B19V IgG-seropositive follow-up samples and resolved after IgG seroreversion. Computational prediction of the VP1 3D structure of this mutant showed a conformational change in the proximity of the antibody binding domain. No conformational changes were predicted for the other mutations detected. Discussion: Analysis of relapsing B19V infections showed mutational changes occurring over time. Resulting amino acid changes were predicted to lead to a conformational capsid protein change in an IgG-seropositive patient. The impact of humoral response and IVIG treatment on B19V infections should be further investigated to understand viral evolution and potential immune escape. Full article
(This article belongs to the Collection Parvoviridae)
27 pages, 1201 KiB  
Review
Non-Viral Therapy in COVID-19: Where Are We Standing? How Our Experience with COVID May Help Us Develop Cell Therapies for Long COVID Patients
by Aitor Gonzaga, Gema Martinez-Navarrete, Loreto Macia, Marga Anton-Bonete, Gladys Cahuana, Juan R. Tejedo, Vanessa Zorrilla-Muñoz, Eduardo Fernandez-Jover, Etelvina Andreu, Cristina Eguizabal, Antonio Pérez-Martínez, Carlos Solano, Luis Manuel Hernández-Blasco and Bernat Soria
Biomedicines 2025, 13(8), 1801; https://doi.org/10.3390/biomedicines13081801 - 23 Jul 2025
Abstract
Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). [...] Read more.
Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC). Full article
(This article belongs to the Section Gene and Cell Therapy)
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24 pages, 743 KiB  
Review
Surgical Treatment, Rehabilitative Approaches and Functioning Assessment for Patients Affected by Breast Cancer-Related Lymphedema: A Comprehensive Review
by Paola Ciamarra, Alessandro de Sire, Dicle Aksoyler, Giovanni Paolino, Carmen Cantisani, Francesco Sabbatino, Luigi Schiavo, Renato Cuocolo, Carlo Pietro Campobasso and Luigi Losco
Medicina 2025, 61(8), 1327; https://doi.org/10.3390/medicina61081327 - 23 Jul 2025
Abstract
Introduction: Breast cancer therapy is a common cause of lymphedema. The accumulation of protein-rich fluid in the affected extremity leads to a progressive path—swelling, inflammation, and fibrosis—namely, irreversible changes. Methods: A scientific literature analysis was performed on PubMed/Medline, Scopus, Web of Science (WoS), [...] Read more.
Introduction: Breast cancer therapy is a common cause of lymphedema. The accumulation of protein-rich fluid in the affected extremity leads to a progressive path—swelling, inflammation, and fibrosis—namely, irreversible changes. Methods: A scientific literature analysis was performed on PubMed/Medline, Scopus, Web of Science (WoS), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Physiotherapy Evidence Database (PEDro) from inception until 30 June 2024. Results: Breast cancer-related lymphedema (BCRL) is indeed an important healthcare burden both due to the significant patient-related outcomes and the overall social impact of this condition. Even though lymphedema is not life-threatening, the literature underlined harmful consequences in terms of pain, infections, distress, and functional impairment with a subsequent and relevant decrease in quality of life. Currently, since there is no cure, the therapeutic approach to BCRL aims to slow disease progression and prevent related complications. A comprehensive overview of postmastectomy lymphedema is offered. First, the pathophysiology and risk factors associated with BCRL were detailed; then, diagnosis modalities were depicted highlighting the importance of early detection. According to non-negligible changes in patients’ everyday lives, novel criteria for patients’ functioning assessment are reported. Regarding the treatment modalities, a wide array of conservative and surgical methods both physiologic and ablative were analyzed with their own outcomes and downsides. Conclusions: Combined strategies and multidisciplinary protocols for BCRL, including specialized management by reconstructive surgeons and physiatrists, along with healthy lifestyle programs and personalized nutritional counseling, should be compulsory to address patients’ demands and optimize the treatment of this harmful and non-curable condition. The Lymphedema-specific ICF Core Sets should be included more often in the overall outcome evaluation with the aim of obtaining a comprehensive appraisal of the treatment strategies that take into account the patient’s subjective score. Full article
(This article belongs to the Section Surgery)
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13 pages, 482 KiB  
Article
In Vitro Antimicrobial Activity of the Novel Antimicrobial Peptide OMN51 Against Multi-Drug-Resistant Pseudomonas aeruginosa Isolated from People with Cystic Fibrosis
by Moshe Heching, Moshe Cohen-Kutner, Haim Ben-Zvi, Liora Slomianksy, Elital Chass Maurice, Noa Nur Maymon, Shira Mandel, Michal Oholy, Rony Moses, Michal Lavon, Katherine Kaufman, Orel Mayost Lev-Ari, Tamar Shachar, Joel Weinberg, Mordechai R. Kramer and Niv Bachnoff
J. Clin. Med. 2025, 14(15), 5208; https://doi.org/10.3390/jcm14155208 - 23 Jul 2025
Abstract
Background: People with cystic fibrosis (pwCF) frequently suffer from chronic lung infections, with Pseudomonas aeruginosa being the predominant pathogen contributing to disease progression and morbidity. The increasing prevalence of multi-drug-resistant (MDR) P. aeruginosa has diminished treatment options. Antimicrobial peptides (AMPs) have emerged as [...] Read more.
Background: People with cystic fibrosis (pwCF) frequently suffer from chronic lung infections, with Pseudomonas aeruginosa being the predominant pathogen contributing to disease progression and morbidity. The increasing prevalence of multi-drug-resistant (MDR) P. aeruginosa has diminished treatment options. Antimicrobial peptides (AMPs) have emerged as promising alternatives to conventional antibiotics due to their unique membrane-targeting mechanisms. OMN51, a novel bioengineered AMP derived from capitellacin, was evaluated for antimicrobial activity against P. aeruginosa in sputum samples from pwCF. This study aimed to compare the bactericidal effects of OMN51 with those of a range of conventional antibiotics known to have activity against P. aeruginosa clinical isolates derived from pwCF. Methods:P. aeruginosa clinical isolates were obtained from fifty-six unique sputum cultures of pwCF at a tertiary-university-affiliated hospital. Minimum inhibitory concentrations (MICs) of OMN51 and comparator antibiotics were determined using broth microdilution. Antimicrobial susceptibility was evaluated using the Kirby–Bauer disc diffusion method. Results: OMN51 demonstrated in vitro bactericidal activity across all P. aeruginosa isolates, including MDR strains. MIC values for OMN51 ranged from 4 to 16 µg/mL, with no observed resistance or cross-resistance. Comparative analysis revealed the superior efficacy of OMN51 compared with conventional antibiotics. Conclusions: OMN51 exhibits robust in vitro activity against MDR P. aeruginosa, supporting its candidacy as a therapeutic agent for MDR P. aeruginosa- associated infections. Further studies are warranted to assess pharmacokinetics and in vivo safety and efficacy. OMN51 represents a first-in-class, membrane-targeting therapeutic showing promise against MDR P. aeruginosa. Full article
(This article belongs to the Special Issue Cystic Fibrosis: Novel Strategies of Diagnosis and Treatments)
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13 pages, 934 KiB  
Article
Inhaled Corticosteroids and Risk of Staphylococcus aureus Isolation in Bronchiectasis: A Register-Based Cohort Study
by Andrea Arlund Filipsen, Karen Hougaard Frost, Josefin Eklöf, Louise Lindhardt Tønnesen, Anna Kubel Vognsen, Jonas Bredtoft Boel, Mette Pinholt, Christian Østergaard Andersen, Ram Benny Christian Dessau, Tor Biering-Sørensen, Sofie Lock Johansson, Jens-Ulrik Jensen and Pradeesh Sivapalan
J. Clin. Med. 2025, 14(15), 5207; https://doi.org/10.3390/jcm14155207 - 23 Jul 2025
Abstract
Objectives: Non-cystic fibrosis bronchiectasis (BE) is a chronic airway disease with increasing prevalence, reduced quality of life, and increased mortality. Inhaled corticosteroids (ICS) are used in BE despite limited evidence of effect on lung function parameters. ICS may increase the risk of Staphylococcus [...] Read more.
Objectives: Non-cystic fibrosis bronchiectasis (BE) is a chronic airway disease with increasing prevalence, reduced quality of life, and increased mortality. Inhaled corticosteroids (ICS) are used in BE despite limited evidence of effect on lung function parameters. ICS may increase the risk of Staphylococcus aureus (S. aureus) infections in patients with BE, but this is unexplored. We examined the association between ICS use prior to BE diagnosis at different doses and the risk of S. aureus isolation in patients with BE. Methods: We conducted a national register-based cohort study including Danish patients with a BE diagnosis code between 2001 and 2018 with a 1-year follow-up time from the date of diagnosis. ICS exposure was categorized based on accumulated prescriptions redeemed 365 days before BE diagnosis and divided into none, low, moderate, or high use based on clinically relevant doses. A cause-specific Cox proportional hazards regression model was used to estimate the risk of S. aureus isolation. A sensitivity analysis, an inverse probability of treatment weighted model (IPTW), was performed. Results: A total of 5093 patients were included in this study. S. aureus was isolated in 156 patients (3.1%). High-dose ICS was associated with an increased risk of S. aureus isolation, HR 3.81 (95% CI 2.51; 5.79). No association for low or moderate use was found, low-dose HR 1.22 (95% CI 0.77; 1.93), and moderate-dose HR 1.24 (95% CI 0.72; 2.16). IPTW analysis yielded similar results. Conclusions: High-dose ICS use in patients with BE was associated with an increased risk of S. aureus isolation. ICS should be used cautiously in patients with BE. Full article
(This article belongs to the Section Respiratory Medicine)
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11 pages, 1067 KiB  
Article
Assessment of the Anti-Biofilm Effect of Cefiderocol Against 28 Clinical Strains of Multidrug-Resistant Gram-Negative Bacilli
by Marta Díaz-Navarro, Emilia Cercenado, Andrés Visedo, Mercedes Marín, Marina Machado, Álvaro Irigoyen-von-Sierakowski, Belén Loeches, Juana Cacho-Calvo, Julio García-Rodríguez, Enea G. Di Domenico, Patricia Muñoz and María Guembe
Antibiotics 2025, 14(8), 738; https://doi.org/10.3390/antibiotics14080738 - 23 Jul 2025
Abstract
Objectives: Cefideroccol (FDC) is a siderophore cephalosporin with potent antibacterial activity against a wide range of Gram-negative multidrug-resistant (MDR) microorganisms. We investigated the anti-biofilm capacity of FDC against clinical strains. Methods: This multicenter study was conducted on 28 selected strains of [...] Read more.
Objectives: Cefideroccol (FDC) is a siderophore cephalosporin with potent antibacterial activity against a wide range of Gram-negative multidrug-resistant (MDR) microorganisms. We investigated the anti-biofilm capacity of FDC against clinical strains. Methods: This multicenter study was conducted on 28 selected strains of MDR Gram-negative bacilli isolated from clinical samples of Pseudomonas aeruginosa (n = 5), Acinetobacter baumannii (n = 11), and Klebsiella pneumoniae (n = 12). We first determined the minimum inhibitory concentration (MIC) of each strain using the microdilution method. We also defined the minimum biofilm inhibitory concentration (MBIC) as a ≥50% reduction in tetrazolium salt (XTT) (as recommended in the 2017 Spanish Microbiology Protocols [SEIMC] for the microbiological diagnosis of infections related to the formation of biofilms). We also analyzed the reduction in the following biofilm variables after an 8 mg/mL FDC treatment: the CFU count, the cell viability, the biomass, the metabolic activity, and extracellular α or β polysaccharides. Results: The MIC50 and MBIC50 of FDC were 0.5 mg/L and 64 mg/L, respectively. We observed a mean (SD) fold increase in the susceptibility to FDC between planktonic and sessile cells for P. aeruginosa, A. baumannii, and K. pneumoniae of 9.60 (0.55), 6.27 (2.28), and 6.25 (2.80), respectively. When 8 mg/mL of FDC was tested, we observed that the best median (IQR) percentage reductions were obtained for cell viability and the extracellular matrix (73.1 [12.4–86.5] and 79.5 [37.3–95.5], respectively), particularly for P. aeruginosa. The lowest percentage reduction rates were those obtained for biomass. Conclusions: We demonstrated that the susceptibility to FDC was significantly reduced when strains were in a biofilm state. The best percentage reduction rates for all biofilm-defining variables were observed for P. aeruginosa. Our results need to be validated using a larger collection of clinical samples. Full article
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14 pages, 690 KiB  
Article
Ibrutinib in Combination with Lenalidomide Revlimid/Dexamethasone in Relapsed/Refractory Multiple Myeloma (AFT-15)
by Yvonne Efebera, Vera Suman, Shira Dinner, Taylor O’Donnell, Ashley Rosko, John Mckay, Peter Barth, Patrick Hagen, Saad Usmani, Paul Richardson and Jacob Laubach
Cancers 2025, 17(15), 2433; https://doi.org/10.3390/cancers17152433 - 23 Jul 2025
Abstract
Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival. Method: A 3 + 3 phase I trial was conducted to determine the [...] Read more.
Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival. Method: A 3 + 3 phase I trial was conducted to determine the maximum tolerated dose (MTD) of IBR in combination with LEN + dexamethasone (DEX) in patients with relapsed/refractory (RR) MM who had at least one prior line of therapy. Three dose levels (DLs) were planned. The cycle length was 28 days. IBR was administered orally daily in doses of 560 mg on DL1-2 and 840 mg on DL3, LEN was administered orally on days 1–21 in doses of 15 mg on DL1 and 25 mg on DL2-3, and DEX was administered orally on days 1, 8, 15, and 22 in a dose of 40 mg if age < 75 years or in a dose of 20 mg if it was ≥75 years for DL1-3. Patients with a glomerular filtration rate (GFR) <60 but ≥30 mL/min were treated in accordance with the manufacturer’s instructions with LEN 10 mg. Dose-limiting toxicities (DLTs) included the following: grade 4 neutropenia lasting more than 5 days, thrombocytopenia, febrile neutropenia, nausea, vomiting or diarrhea; grade 3 thrombocytopenia with bleeding or platelet transfusion; and grade 3–4 hyperglycemia or a thrombotic/embolic event, and other nonhematologic toxicities. The overall response rate (ORR) was defined as the percentage of patients with a partial response (PR), very good partial response (VGPR), or complete response (CR) according to IMWG criteria on two consecutive evaluations at least 4 weeks apart. The clinical benefit rate (CBR) was defined as the percentage of patients with stable disease (SD) or a better outcome on two consecutive evaluations at weeks apart. Results: Fourteen patients (DL1: six patients; DL2: three patients; DL3: five patients) were registered for the study from March 2019 to May 2023, prior to its closure due to limited accrual. Thirteen patients are included in the summary of toxicities and response as one patient on DL3 halted participation prior to the start of the treatment. Two patients on DL3 were excluded from the determination of MTD: one having discontinued cycle 1 treatment due to COVID-19 infection and the another having mistakenly taken 280 mg/day of IBR instead of the assigned 840 mg/day dose during cycle 1. Only one patient developed a DLT, on DL1 with grade 3 non-viral hepatitis. The median number of cycles administered was 4 (range: 1–56). Severe toxicities reported included grade 4 lymphocytopenia (1), grade 4 thrombocytopenia (1), and grade 5 sepsis in the setting of PD (1). Disease responses included a VGPR on DL1 and CR on DL3. Thus, the ORR was 15.4% (90% CI: 2.8–41.0%). One patient on DL1 maintained SD for 4.6 years before discontinuing the treatment to undergo an alternative therapy. Another five patients maintained SD for ≥ 2 consecutive cycles. Thus, the CBR was 61.5% (90% CI: 35.5–83.4%). Conclusions: The combination of LEN with IBR in RR MM proved feasible, with manageable toxicities and the majority of discontinuations being due to disease progression. Full article
(This article belongs to the Special Issue Multiple Myeloma: Diagnosis and Therapy)
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7 pages, 540 KiB  
Case Report
Simultaneous Central Nervous System and Cutaneous Relapse in Acute Myeloid Leukemia
by Eros Cerantola, Laura Forlani, Marco Pizzi, Renzo Manara, Mauro Alaibac, Federica Lessi, Angelo Paolo Dei Tos, Chiara Briani and Carmela Gurrieri
Hemato 2025, 6(3), 25; https://doi.org/10.3390/hemato6030025 - 23 Jul 2025
Abstract
Introduction: Acute Myeloid Leukemia (AML) is a hematologic malignancy characterized by the clonal expansion of myeloid progenitors. While it primarily affects the bone marrow, extramedullary relapse occurs in 3–5% of cases, and it is linked to poor prognosis. Central nervous system (CNS) involvement [...] Read more.
Introduction: Acute Myeloid Leukemia (AML) is a hematologic malignancy characterized by the clonal expansion of myeloid progenitors. While it primarily affects the bone marrow, extramedullary relapse occurs in 3–5% of cases, and it is linked to poor prognosis. Central nervous system (CNS) involvement presents diagnostic challenges due to nonspecific symptoms. CNS manifestations include leptomeningeal dissemination, nerve infiltration, parenchymal lesions, and myeloid sarcoma, occurring at any disease stage and frequently asymptomatic. Methods: A 62-year-old man with a recent history of AML in remission presented with diplopia and aching paresthesias in the left periorbital region spreading to the left frontal area. The diagnostic workup included neurological and hematological evaluation, lumbar puncture, brain CT, brain magnetic resonance imaging (MRI) with contrast, and dermatological evaluation with skin biopsy due to the appearance of nodular skin lesions on the abdomen and thorax. Results: Neurological evaluation showed hypoesthesia in the left mandibular region, consistent with left trigeminal nerve involvement, extending to the periorbital and frontal areas, and impaired adduction of the left eye with divergent strabismus in the primary position due to left oculomotor nerve palsy. Brain MRI showed an equivocal thickening of the left oculomotor nerve without enhancement. Cerebrospinal fluid (CSF) analysis initially showed elevated protein (47 mg/dL) with negative cytology; a repeat lumbar puncture one week later detected leukemic cells. Skin biopsy revealed cutaneous AML localization. A diagnosis of AML relapse with CNS and cutaneous localization was made. Salvage therapy with FLAG-IDA-VEN (fludarabine, cytarabine, idarubicin, venetoclax) and intrathecal methotrexate, cytarabine, and dexamethasone was started. Subsequent lumbar punctures were negative for leukemic cells. Due to high-risk status and extramedullary disease, the patient underwent allogeneic hematopoietic stem cell transplantation. Post-transplant aplasia was complicated by septic shock; the patient succumbed to an invasive fungal infection. Conclusions: This case illustrates the diagnostic complexity and poor prognosis of extramedullary AML relapse involving the CNS. Early recognition of neurological signs, including cranial nerve dysfunction, is crucial for timely diagnosis and management. Although initial investigations were negative, further analyses—including repeated CSF examinations and skin biopsy—led to the identification of leukemic involvement. Although neuroleukemiosis cannot be confirmed without nerve biopsy, the combination of clinical presentation, neuroimaging, and CSF data strongly supports the diagnosis of extramedullary relapse of AML. Multidisciplinary evaluation remains essential for detecting extramedullary relapse. Despite treatment achieving CSF clearance, the prognosis remains unfavorable, underscoring the need for vigilant clinical suspicion in hematologic patients presenting with neurological symptoms. Full article
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16 pages, 720 KiB  
Article
Demographic and Clinical Profile of Patients with Osteogenesis Imperfecta Hospitalized Due to Coronavirus Disease (COVID)-19: A Case Series of 13 Patients from Brazil
by Luana Lury Morikawa, Luiz Felipe Azevedo Marques, Adriele Evelyn Ferreira Silva, Patrícia Teixeira Costa, Lucas Silva Mello, Andrea de Melo Alexandre Fraga and Fernando Augusto Lima Marson
Healthcare 2025, 13(15), 1779; https://doi.org/10.3390/healthcare13151779 - 23 Jul 2025
Abstract
Background: Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder characterized by bone fragility, most often caused by pathogenic variants in type I collagen genes. In this context, we aimed to describe the clinical and epidemiological characteristics of patients with OI who [...] Read more.
Background: Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder characterized by bone fragility, most often caused by pathogenic variants in type I collagen genes. In this context, we aimed to describe the clinical and epidemiological characteristics of patients with OI who were hospitalized for coronavirus disease (COVID)-19 in Brazil between 2020 and 2024. Methods: We conducted a retrospective descriptive analysis using data from the Brazilian Unified Health System (SUS, which stands for the Portuguese Sistema Único de Saúde) through the Open-Data-SUS platform. Patients with a confirmed diagnosis of OI and hospitalization due to COVID-19 were included. Descriptive statistical analysis was performed to evaluate demographic, clinical, and outcome-related variables. We included all hospitalized COVID-19 cases with a confirmed diagnosis of OI between 2020 and 2024. Results: Thirteen hospitalized patients with OI and COVID-19 were identified. Most were adults (9; 69.2%), male (7; 53.8%), self-identified as White (9; 69.2%), and all were residents of urban areas (13; 100.0%). The most frequent symptoms were fever (10; 76.9%), cough (9; 69.2%), oxygen desaturation (9; 69.2%), dyspnea (8; 61.5%), and respiratory distress (7; 53.8%). Two patients had heart disease, one had chronic lung disease, and one was obese. As for vaccination status, five patients (38.5%) had been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Four patients (30.8%) required admission to an intensive care unit (ICU), and six (46.2%) required noninvasive ventilatory support. Among those admitted to the ICU, only two required invasive mechanical ventilation. The clinical outcome was death in two cases (15.4%). Both patients were male, White, and had not been vaccinated against SARS-CoV-2. One was 47 years old, was not admitted to the ICU, but required noninvasive ventilation. Despite the underlying condition most patients had favorable outcomes, consistent with an international report. Conclusions: This is the first report to describe the clinical and epidemiological profile of patients with OI hospitalized for COVID-19 in Brazil, providing initial insights into how a rare bone disorder intersects with an acute respiratory infection. The generally favorable outcomes observed—despite the underlying skeletal fragility—suggest that individuals with OI are not necessarily at disproportionate risk of severe COVID-19, particularly when appropriately monitored. The occurrence of deaths only among unvaccinated patients underscores the critical role of SARS-CoV-2 vaccination in this population. Although pharmacological treatment data were unavailable, the potential protective effects of bisphosphonates and vitamin D merit further exploration. These findings support the need for early preventive strategies, systematic vaccination efforts, and dedicated clinical protocols for rare disease populations during infectious disease outbreaks. Full article
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26 pages, 1616 KiB  
Article
Infections with Staphylococcus spp. in Children Undergoing Anticancer Therapy or Haematopoietic Cell Transplantation: A Nationwide Multicentre Study
by Anna Jabłońska, Monika Richert-Przygońska, Kamila Jaremek, Krzysztof Czyżewski, Wanda Badowska, Walentyna Balwierz, Ewa Bień, Tomasz Brzeski, Radosław Chaber, Wojciech Czogała, Bożenna Dembowska-Bagińska, Katarzyna Derwich, Katarzyna Drabko, Katarzyna Dzierżanowska-Fangrat, Jowita Frączkiewicz, Agnieszka Gietka, Jolanta Goździk, Olga Gryniewicz-Kwiatkowska, Łukasz Hutnik, Ninela Irga-Jaworska, Krzysztof Kałwak, Grażyna Karolczyk, Aleksandra Królak, Pawel Łaguna, Katarzyna Machnik, Hanna Mańko-Glińska, Agnieszka Mizia-Malarz, Wojciech Młynarski, Jakub Musiał, Katarzyna Mycko, Tomasz Ociepa, Sonia Pająk, Jarosław Peregud-Pogorzelski, Filip Pierlejewski, Marcin Płonowski, Małgorzata Salamonowicz-Bodzioch, Małgorzata Sawicka-Żukowska, Katarzyna Semczuk, Katarzyna Skowron-Kandzia, Weronika Stolpa, Tomasz Szczepański, Anna Szmydki-Baran, Renata Tomaszewska, Tomasz Urasiński, Agnieszka Urbanek-Dądela, Justyna Urbańska-Rakus, Paweł Wawryków, Olga Zając-Spychała, Patrycja Zalas-Więcek, Agnieszka Zaucha-Prażmo, Joanna Zawitkowska, Iwona Żak and Jan Styczyńskiadd Show full author list remove Hide full author list
J. Clin. Med. 2025, 14(15), 5200; https://doi.org/10.3390/jcm14155200 - 22 Jul 2025
Abstract
Background: Staphylococcus spp. represent the most prevalent Gram-positive organisms in children with malignancies or undergoing haematopoietic cell transplantation (HCT), contributing to significant morbidity and mortality. This study aimed to assess the epidemiology, risk factors, treatment strategies, and outcomes of staphylococcal infections (SIs) [...] Read more.
Background: Staphylococcus spp. represent the most prevalent Gram-positive organisms in children with malignancies or undergoing haematopoietic cell transplantation (HCT), contributing to significant morbidity and mortality. This study aimed to assess the epidemiology, risk factors, treatment strategies, and outcomes of staphylococcal infections (SIs) in paediatric haemato-oncology (PHO) and HCT patients in Poland over a 12-year period. Methods: A retrospective, multicentre study was conducted across 17 paediatric oncology centres in Poland. The clinical and microbiological data of patients under the age of 18, diagnosed with malignancies or post-HCT, were analysed for confirmed SI between 2012 and 2023. The variables assessed included demographics, underlying conditions, infection type and source, antimicrobial susceptibility, treatment, and 30-day infection-free survival. Results: Among 1725 patients with SI, 1433 were PHO and 292 were HCT patients. The cumulative incidence of SI was 12.7% in PHO and 14.3% in HCT patients (p = 0.008). The 30-day survival rate was significantly higher in PHO compared to HCT patients (98.4% vs. 93.2%, p < 0.001). Most deaths were caused by S. epidermidis, S. haemolyticus, and S. hominis, predominantly involving methicillin-resistant coagulase-negative Staphylococci (MRCNS). Multivariate Cox regression identified undergoing HCT (HR = 3.0, 95% CI: 1.6–5.6, p < 0.001) and treatment of infection > 10 days (HR = 2.0, 95% CI: 1.1–3.6, p = 0.019) as independent risk factors for mortality. Conclusions: Staphylococcal infections pose a significant challenge in paediatric oncology and transplant populations. Optimising prevention, diagnostics, and antimicrobial therapy is crucial for improving outcomes in these high-risk groups. Full article
(This article belongs to the Section Clinical Pediatrics)
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52 pages, 3227 KiB  
Review
Advances in Photodynamic Treatment of Precancerous and Cancerous Gynecological Diseases
by Polina Alekseeva, Vladimir Makarov, Kanamat Efendiev, Aida Gilyadova and Victor Loschenov
Cancers 2025, 17(15), 2421; https://doi.org/10.3390/cancers17152421 - 22 Jul 2025
Abstract
High mortality rates and poor quality of life result from the late-stage detection and frequent recurrence of gynecological neoplasms. Background/Objectives: The aim of this study was to conduct a systematic analysis of the energy parameters of photodynamic therapy (PDT) in the treatment [...] Read more.
High mortality rates and poor quality of life result from the late-stage detection and frequent recurrence of gynecological neoplasms. Background/Objectives: The aim of this study was to conduct a systematic analysis of the energy parameters of photodynamic therapy (PDT) in the treatment of cervical and vulvar lesions, with a focus on stimulating immune responses leading to human papillomavirus (HPV) eradication and lesion regression without adverse effects, such as thermal damage. Methods: A total of 46 peer-reviewed studies published between January 2010 and April 2024 were analyzed. These studies focused on PDT applications for cervical and vulvar lesions, sourced from Google Scholar, Scopus, and Web of Science. Results: Although PDT shows promise, significant limitations exist, such as insufficient consideration of individual tumor characteristics, restricted treatment depths, and the heterogeneous distribution and low selectivity of photosensitizer (PS) accumulation in tumors. Tumor hypoxia further reduces PDT’s effectiveness, and most studies overlook immune system activation, which is crucial for targeting HPV infections and improving antitumor responses. Conclusions: Advancing the research into PDT’s molecular and cellular mechanisms, optimizing the immune response stimulation, and improving the PS and delivery methods could enhance the safety and effectiveness of cervical and vulvar neoplasm treatments. The use of personalized PDT parameters may reduce the side effects and enhance the outcomes for patients suffering from gynecological diseases. Full article
(This article belongs to the Special Issue New Advances in the Diagnosis of Gynecological Cancer)
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11 pages, 402 KiB  
Article
Antibiotic Effect on Clinical Response and Remission in Pediatric Inflammatory Bowel Disease
by Caeley Dye, Caroline M. Sierra, Khaled Bahjri, Mallory Cohen and Gautam Nagendra
Pediatr. Rep. 2025, 17(4), 77; https://doi.org/10.3390/pediatric17040077 - 21 Jul 2025
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Abstract
Objective: Gut dysbiosis has been implicated in the pathology of inflammatory bowel disease (IBD). There is some evidence to suggest that the use of antibiotic treatment can incite an early clinical response or remission when used in conjunction with standard-of-care (SOC) therapy [...] Read more.
Objective: Gut dysbiosis has been implicated in the pathology of inflammatory bowel disease (IBD). There is some evidence to suggest that the use of antibiotic treatment can incite an early clinical response or remission when used in conjunction with standard-of-care (SOC) therapy to treat IBD-related flares. Furthermore, antibiotics have been historically investigated for use as a bridge when initiating biologic therapy while waiting for peak biologic treatment effect to occur. This study investigated and compared the time to clinical response when treated with combination antibiotics, metronidazole monotherapy, or SOC therapy in pediatric patients with an active IBD flare. Methods: This study was a retrospective, Institution Review Board-approved, single-centered cohort study which included patients who were less than 18 years of age with a confirmed diagnosis of IBD who received conventional treatment alone or with either combination antibiotic therapy or metronidazole monotherapy to treat an active IBD flare between March 2013 and January 2024. Patients were excluded if they received antibiotic therapy to treat an active infection, had positive stool cultures or enteric pathogen polymerase chain reaction panel, or had colonic disease limited to the rectum. Results: Fifty-nine patients were included and divided into metronidazole monotherapy (n = 18), SOC therapy (n = 20), and combination antibiotics (n = 21). The primary outcome of days to clinical response was not significantly different across all groups; however, patients who received combination antibiotics achieved the fastest time to clinical response (median (IRQ))—4 days (1, 65), compared to 7.5 days (1, 119) for the SOC group and 9 days (2, 217) for the metronidazole group. Secondary outcomes of achievement of clinical response, remission, or failure were determined to be non-significant between all groups. Conclusions: There is no significant difference in time to clinical response, attaining clinical response or remission, or treatment failure rate for patients treated with combination antibiotics, metronidazole monotherapy, or SOC. However, results of this study suggest that the use of combination antibiotics plus SOC may lead to a faster time to clinical response and remission compared to SOC therapy alone. Further studies are warranted to elucidate the role of antimicrobial therapy in management of pediatric IBD. Full article
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46 pages, 9773 KiB  
Review
Visceral Arterial Pseudoaneurysms—A Clinical Review
by Ashita Ashish Sule, Shreya Sah, Justin Kwan, Sundeep Punamiya and Vishal G. Shelat
Medicina 2025, 61(7), 1312; https://doi.org/10.3390/medicina61071312 - 21 Jul 2025
Viewed by 239
Abstract
Background and Objectives: Visceral arterial pseudoaneurysms (VAPAs) are rare vascular lesions characterized by the disruption of partial disruption of the arterial wall, most commonly involving the intima and media. They have an estimated incidence of 0.1–0.2%, with the splenic artery most commonly [...] Read more.
Background and Objectives: Visceral arterial pseudoaneurysms (VAPAs) are rare vascular lesions characterized by the disruption of partial disruption of the arterial wall, most commonly involving the intima and media. They have an estimated incidence of 0.1–0.2%, with the splenic artery most commonly affected. Their management poses unique challenges due to the high risk of rupture. Timely recognition is crucial, as unmanaged pseudoaneurysms have a mortality rate of 90%. This narrative review aims to synthesize current knowledge regarding the epidemiology, etiology, clinical presentation, diagnostic methods, and management strategies for VAPAs. Materials and Methods: A literature search was performed across Pubmed for articles reporting on VAPAs, including case reports, review articles, and cohort studies, with inclusion of manuscripts that were up to (date). VAPAs are grouped by embryological origin—foregut, midgut, and hindgut. Results: Chronic pancreatitis is a primary cause of VAPAs, with the splenic artery being involved in 60–65% of cases. Other causes include acute pancreatitis, as well as iatrogenic trauma from surgeries, trauma, infections, drug use, and vascular diseases. VAPAs often present as abdominal pain upon rupture, with symptoms like nausea, vomiting, and gastrointestinal hemorrhage. Unruptured pseudoaneurysms may manifest as pulsatile masses or bruits but are frequently asymptomatic and discovered incidentally. Diagnosis relies on both non-invasive imaging techniques, such as CT angiography and Doppler ultrasound, and invasive methods like digital subtraction angiography, which remains the gold standard for detailed evaluation and treatment. A range of management options exists that are tailored to individual cases based on the aneurysm’s characteristics and patient-specific factors. This encompasses both surgical and endovascular approaches, with a growing preference for minimally invasive techniques due to lower associated morbidity. Conclusions: VAPAs are a critical condition requiring prompt early recognition and intervention. This review highlights the need for ongoing research to improve diagnostic accuracy and refine treatment protocols, enhancing patient outcomes in this challenging domain of vascular surgery. Full article
(This article belongs to the Section Surgery)
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