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Search Results (1,072)

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Keywords = prophylaxis and treatment

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15 pages, 419 KB  
Article
Isavuconazole Therapy for Patients with Hematologic Diseases and Hematopoietic Cell Transplantation with and Without Breakthrough Invasive Fungal Infections
by Fabián Herrera, Diego Torres, Gustavo Mendez, Noelia Mañez, Rosana Jordán, Adriana Manzur, Myrna Cabral, Manuel Alderete, Natalia García Allende, José Benso, Claudia Salgueira, María Laura Pereyra, Hugo Peretti, Carla Niveyro, Maximiliano Castro, Federico Pollastrelli, Silvina García Rojas, Juan Dapás, Agustina Risso Patrón, Verónica Fernández, Rocío Gago and Javier Afeltraadd Show full author list remove Hide full author list
J. Fungi 2025, 11(9), 648; https://doi.org/10.3390/jof11090648 (registering DOI) - 1 Sep 2025
Abstract
There are no data available on the effectiveness and safety of isavuconazole (ISA) for treating breakthrough invasive fungal infections (bIFIs). A retrospective and prospective cohort study was conducted between January 2020 and March 2025 in 13 centers in Argentina. Hematologic diseases (HD) and [...] Read more.
There are no data available on the effectiveness and safety of isavuconazole (ISA) for treating breakthrough invasive fungal infections (bIFIs). A retrospective and prospective cohort study was conducted between January 2020 and March 2025 in 13 centers in Argentina. Hematologic diseases (HD) and hematopoietic cell transplantation (HCT) patients who received ISA for IFI were included and followed for 12 weeks. Patients with proven and probable bIFIs and non-bIFIs were compared. One hundred and sixty-three patients were included. IFIs were classified as proven (13.5%), probable (26.9%) and possible (59.5%). Among 66 proven and probable IFIs, 53% were bIFIs, with aspergillosis and mucormycosis being the most common. Twenty-three (34.8%) patients had acute myelogenous leukemia, and 40.9% had received HCT. Forty-eight (72.7%) patients experienced neutropenia, with a median duration of 26 days (interquartile range [IQR] 16–44). Fluconazole and posaconazole were the most frequently received antifungal prophylaxis. ISA was prescribed as first-line therapy in 31 (46.9%) patients. The other 35 received ISA as a continuation therapy, mainly as a step-down therapy after liposomal amphotericin B. Four (6.1%) patients developed adverse effects, and one discontinued ISA. The 90-day overall clinical response between patients with bIFI vs. non-bIFI was 91.4% vs. 70.9% (p = 0.052). The 90-day overall and IFI-related mortality rates were, respectively, 11.4% vs. 32.3% (p = 0.068) and 5.7% vs. 9.7% (p = 0.659). The study data evidence ISA effectiveness and safety for the treatment of HD and HCT patients with and without bIFIs. Full article
(This article belongs to the Special Issue Personalized Mycology)
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16 pages, 835 KB  
Article
Risk Factors for Perioperative Urinary Tract Infection After Living Donor Kidney Transplantation Characterized by High Prevalence of Desensitization Therapy: A Single-Center Analysis
by Shingo Nishimura, Shota Inoue, Takanori Sekito, Ichiro Tsuboi, Moto Tokunaga, Kasumi Yoshinaga, Yuki Maruyama, Yosuke Mitsui, Tomoaki Yamanoi, Tatsushi Kawada, Risa Kubota, Takuya Sadahira, Yusuke Tominaga, Takehiro Iwata, Satoshi Katayama, Kensuke Bekku, Kohei Edamura, Koichiro Wada, Yasuyuki Kobayashi and Motoo Araki
J. Clin. Med. 2025, 14(17), 6102; https://doi.org/10.3390/jcm14176102 - 28 Aug 2025
Viewed by 186
Abstract
Background/Objectives: Limited research exists on risk factors for urinary tract infections (UTIs) in kidney transplant recipients, particularly in high-risk groups such as ABO-incompatible or donor-specific antibody (DSA)-positive cases. Early UTIs, especially within the first month post-transplant, impact on acute rejection and long-term [...] Read more.
Background/Objectives: Limited research exists on risk factors for urinary tract infections (UTIs) in kidney transplant recipients, particularly in high-risk groups such as ABO-incompatible or donor-specific antibody (DSA)-positive cases. Early UTIs, especially within the first month post-transplant, impact on acute rejection and long-term graft outcomes, highlighting the need for risk factor identification and management. Methods: Among 157 living donor kidney transplant cases performed at our institution between 2009 and 2024, 128 patients were included after excluding cases with >72 h of perioperative prophylactic antibiotics or urological complications. UTI was defined as the presence of pyuria and a positive urine culture, accompanied by clinical symptoms requiring antibiotic treatment, occurring within one month post-transplantation. Results: The median onset of UTI was postoperative day 8 (interquartile range, IQR: 6.8–9.3). No subsequent acute rejection episodes were observed. The median serum creatinine at 1 month postoperatively was 1.3 mg/dL (IQR: 1.1–1.7), and this was not significantly different from those who did not develop UTI. In univariate analysis, low or high BMI (<20 or >25), longer dialysis duration (>2.5 years), desensitization therapy (plasmapheresis + rituximab), elevated preoperative neutrophil-to-lymphocyte ratio (NLR) (≥3), and longer warm ischemic time (WIT) (≥7.8 min) were significantly associated with an increased infection risk of UTI (p = 0.010, 0.036, 0.028, 0.015, and 0.038, respectively). Multivariate analyses revealed that abnormal BMI, longer dialysis duration, desensitization therapy, and longer WIT were independent risk factors for UTI (p = 0.012, 0.031, 0.008, and 0.033, respectively). The incidence of UTI increased with the number of risk factors: 0% (0/16) for zero, 10% (5/48) for one, 31% (16/51) for two, 45% (5/11) for three, and 100% (2/2) for four risk factors. Conclusions: Desensitization therapy, BMI, dialysis duration, and WIT were identified as independent risk factors for perioperative UTI. In patients with risk factors, additional preventive strategies should be considered, with extended antibiotic prophylaxis being one potential option. Full article
(This article belongs to the Section Nephrology & Urology)
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17 pages, 1969 KB  
Article
Shifting Paradigms in Antifungal Prophylaxis and Their Effects on Candidemia Outcomes in Hematological Malignancies: A 14-Year Experience from a Single Tertiary Center
by Fazıl Çağrı Hunutlu, Fahir Özkalemkaş, Beyza Ener, Dilay Demirayak, Büşra Çalışır, Hikmet Öztop, İbrahim Ethem Pınar, Vildan Gürsoy, Tuba Ersal, Tuba Güllü Koca, Emin Halis Akalın and Vildan Özkocaman
J. Fungi 2025, 11(9), 630; https://doi.org/10.3390/jof11090630 - 28 Aug 2025
Viewed by 174
Abstract
Evolving antifungal prophylaxis approaches have reshaped candidemia patterns and outcomes in hematological malignancy (HM) patients. This study aimed to evaluate temporal changes in candidemia incidence, species distribution, and factors associated with mortality in relation to prophylaxis practices. Adult HM patients with candidemia between [...] Read more.
Evolving antifungal prophylaxis approaches have reshaped candidemia patterns and outcomes in hematological malignancy (HM) patients. This study aimed to evaluate temporal changes in candidemia incidence, species distribution, and factors associated with mortality in relation to prophylaxis practices. Adult HM patients with candidemia between 2009 and 2023 were included. Clinical and microbiological data were analyzed, and candidemia rates were compared across different prophylaxis periods. Sixty-six patients were identified, with acute myeloid leukemia (AML) being the most common underlying malignancy (40.9%). Non-albicans Candida species predominated, especially C. krusei and C. tropicalis. In AML patients, candidemia incidence significantly decreased over time (β = −0.694, p = 0.004), with the lowest rates observed during the extended-release posaconazole tablet era (2016–2023). However, 30-day mortality remained high (53%) and unchanged across periods. Multivariate analysis identified C. tropicalis and total parenteral nutrition as independent risk factors for 30-day mortality (OR: 4.3 and 4.6, p < 0.05), while antifungal prophylaxis was protective (OR: 0.07, p = 0.017). In patients with AML, posaconazole prophylaxis, particularly in the extended-release tablet formulation, significantly reduced the incidence of candidemia. However, overall 30-day mortality rates remained high, with C. tropicalis being a major contributor. Thus, individualized prophylaxis and treatment strategies are crucial for improving outcomes. Full article
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21 pages, 11899 KB  
Article
The Long-Term Efficacy of Cephalosporin in Elderly Hip Fracture Patients: A Comprehensive Analysis
by Huiqing Pan, Xiao Wang, Qingjian Ou, Juan Wang and Zisheng Ai
J. Clin. Med. 2025, 14(17), 6086; https://doi.org/10.3390/jcm14176086 - 28 Aug 2025
Viewed by 261
Abstract
Objectives: This study aims to evaluate the association between antibiotic prophylaxis (particularly cephalosporins) and clinical outcomes in elderly hip fracture patients. Methods: We analyzed 4044 elderly hip fracture patients (2008–2022) from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database using [...] Read more.
Objectives: This study aims to evaluate the association between antibiotic prophylaxis (particularly cephalosporins) and clinical outcomes in elderly hip fracture patients. Methods: We analyzed 4044 elderly hip fracture patients (2008–2022) from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database using inverse probability treatment weighting (IPTW). Cox proportional hazards models assessed mortality risk, while logistic regression evaluated infection and Intensive Care Unit (ICU) admission risks. Dose–response and subgroup analyses were performed for significant findings. Results: In total, 166 patients received no antibiotics, 2589 received Cephalosporin monotherapy, 403 received non-cephalosporin therapy, and 886 received Cephalosporin combination therapy. After IPTW adjustment, monotherapy showed significantly lower mortality risk versus combination therapy at all timepoints (hazard ratio (HR) for 28-day mortality: 0.46, 95% confidence interval (95% CI): 0.28–0.75; HR for 90-day mortality: 0.60, 95% CI: 0.44–0.82; HR for 180-day mortality: 0.67, 95% CI: 0.51–0.87; HR for 1-year mortality: 0.71, 95% CI: 0.57–0.89). The SII cut-off values were 1310.1 for 28-day mortality, 2077.5 for both 90-day and 180-day mortality, 1742.2 for 1-year mortality, 2199.7 for ICU admission, and 1930.7 for infection. Subgroup analyses showed that males and internal fixation patients derived more benefits after cephalosporin monotherapy treatment at all time nodes. Patients with multiple injuries had a lower risk of 28-day mortality, while high-comorbidity patients (CCI ≥ 5) and those with osteoporosis exhibited particular advantages with cephalosporin monotherapy. Conclusions: Cephalosporin monotherapy appears non-inferior to combination therapy for elderly hip fracture patients, potentially reducing long-term mortality risk, especially in males, internal fixation cases, and patients with CCI ≥ 5 and osteoporosis. Full article
(This article belongs to the Section Orthopedics)
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20 pages, 1296 KB  
Article
Examining the Long-Term Impact of Malaria Chemoprophylaxis in Everyday Life in Rural Gambian Adolescents
by Brittany Miller, Andy Hoang, Griffin Litwin, Matthew C. H. Jukes, Hechmi Kilani and Elena L. Grigorenko
Adolescents 2025, 5(3), 46; https://doi.org/10.3390/adolescents5030046 - 28 Aug 2025
Viewed by 216
Abstract
Children in sub-Saharan Africa remain vulnerable to contracting malaria. While chemoprophylaxis is effective in preventing disease, its impact on social well-being is less understood. In this cross-sectional follow-up study conducted in 2001, we examined the role of chemoprophylaxis on social well-being in rural [...] Read more.
Children in sub-Saharan Africa remain vulnerable to contracting malaria. While chemoprophylaxis is effective in preventing disease, its impact on social well-being is less understood. In this cross-sectional follow-up study conducted in 2001, we examined the role of chemoprophylaxis on social well-being in rural Gambia. Participants were 141 adolescents (age: 14.8–19.5; 40% male) from five villages, drawn from a longitudinal cohort in which one group received chemoprophylaxis in infancy, while the other received a placebo and began prophylaxis 1–2 years post-trial. Using a walking interview methodology, participants guided researchers through five village locations. Their narrations were coded for emotional content and social themes, followed by network analyses examining the relationships between these themes across treatment groups and gender. Emotional response analysis revealed significant gender differences in valence, with females exhibiting higher positive emotional tone than males (X2 = 5.85, p = 0.016). Treatment effects showed gender-specific patterns: among males, the placebo group exhibited higher positive valence compared to the chemoprophylaxis group (X2 = 8.34, p = 0.004), while females showed no treatment differences (X2 = 1.11, p = 0.291). Affect analysis revealed high positive responses across all groups with no significant differences. Network analysis revealed significant gender differences in how adolescents organize social themes within their communities. Females demonstrated higher centrality in eigenvector (global influence; p = 0.039) and degree centrality (number of direct edges; p < 0.001), indicating greater interconnectedness and influence within the networks. No significant treatment group differences were observed in the network structure across any centrality indicators (all p > 0.05). This study provides an example of how the social–ecological framework and ecologically valid assessment methods, such as the walking interview, can be applied to investigate the interplay between early childhood health interventions, social dynamics, and individual development in a rural African context. The findings revealed that gender exerts a stronger influence than early treatment on adolescent social–emotional development. Full article
(This article belongs to the Section Adolescent Health Behaviors)
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10 pages, 576 KB  
Article
Real-World Use of Extended Half-Life Factor IX in Children with Haemophilia B
by Athina Dettoraki, Aikaterini Michalopoulou, Stefanos Saslis, Konstantina Dakou, Ioanna Stamati, Sotiria Thymianou, Zoey Kapsimali, Olympia Papakonstantinou and Helen Pergantou
Life 2025, 15(9), 1352; https://doi.org/10.3390/life15091352 - 26 Aug 2025
Viewed by 281
Abstract
Introduction Limited studies have reported data on the real-world clinical use of extended half-life (EHL) IX products in children and adolescents with haemophilia B, also referred to as people with haemophilia B (PWHB). Aim To examine the real-life experience with EHL factor IX [...] Read more.
Introduction Limited studies have reported data on the real-world clinical use of extended half-life (EHL) IX products in children and adolescents with haemophilia B, also referred to as people with haemophilia B (PWHB). Aim To examine the real-life experience with EHL factor IX products in PWHB regarding the clinical experience with standard half-life products (SHL). Methods A retrospective review of medical records of PWHB who have been prescribed EHL IX factor concentrates was conducted. Results Fourteen male PWHB were enrolled in the study, all with severe bleeding phenotypes being on prophylaxis (1–6 years old: n = 3, 7–12 years old: n = 5 and 13–18 years old: n = 6). Four of them were previously untreated patients; nine out of fourteen children (64%) had severe, four had moderate, and one child had mild haemophilia B. Median length of follow-up was 45 months (range 16–84 months). Children who transitioned from SHL prophylaxis to EHL prophylaxis experienced changes in their treatment outcomes. The median dosing interval increased from 3.5 days to 7 days, mean trough levels rose from 4.3% to 15.3% among children with severe haemophilia B, and the mean annual bleeding rate (ABR) decreased from 1.8 to 1 (p = 0.3, Wilcoxon test). Significant differences were found in EHL vs. SHL use regarding (a) the factor IX consumption for prophylaxis and bleeds (p = 0.046, t-test), with the EHL consumption (45.6 IU/kg/week) being significantly lower than the SHL consumption (70.3 IU/kg/week), and (b) the factor IX consumption only for prophylaxis (p = 0.022, t-test), with the EHL consumption (37.0 IU/kg/week) being significantly lower than the SHL consumption (66.0 IU/kg/week). There was no inhibitor development. Conclusion This study demonstrates the successful use of EHL prophylaxis in PWHB. Full article
(This article belongs to the Section Medical Research)
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16 pages, 436 KB  
Review
Orphan Cytochromes P450 as Possible Pharmacological Targets or Biomarkers in Breast Cancer
by Barbara Licznerska, Hanna Szaefer and Wanda Baer-Dubowska
Curr. Issues Mol. Biol. 2025, 47(9), 682; https://doi.org/10.3390/cimb47090682 - 25 Aug 2025
Viewed by 269
Abstract
Although significant advances in the treatment of breast cancer have been made over the last few decades, searching for more effective prophylaxis and therapy for this type of cancer is still topical. Orphan cytochromes (CYPs) P450 are enzymes whose functions and substrates are [...] Read more.
Although significant advances in the treatment of breast cancer have been made over the last few decades, searching for more effective prophylaxis and therapy for this type of cancer is still topical. Orphan cytochromes (CYPs) P450 are enzymes whose functions and substrates are not fully known. The overexpression of some orphan CYPs in breast cancer tissue warrants attention as a possible breast cancer prophylaxis/treatment target or biomarker. Of particular interest is CYP4Z1, which seems to be specific for breast cancer, including triple-negative breast cancer (TNBC). The currently available data indicate that inhibition of CYP4Z1 breast-specific expression may reduce the growth, progression, angiogenesis, and invasiveness of breast cancer. Although less specific, the other orphan CYPs, such as CYP2W1, CYP2S1, CYP2U1, and CYP4X1, exhibit significantly higher expression in breast tumors compared to normal tissues. The available data indicate that these CYP isoforms catalyze the hydroxylation of fatty acids. Their products, such as epoxyeicosatrienoic acids (EETs) or hydroxyeicosatetraenoic acids (HETEs), are considered critical modulators of cancer progression. Therefore, inhibition of the expression and activity of these orphan CYPs might be more useful in cancer treatment than in prophylaxis. This review summarizes current knowledge of orphan CYPs in breast tissue and their possible application in drug targeting or prognosis assessment. Full article
(This article belongs to the Special Issue Future Challenges of Targeted Therapy of Cancers: 2nd Edition)
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29 pages, 2209 KB  
Review
Pulmonary Aspergillosis in Immunocompromised Critically Ill Patients: Prevalence, Risk Factors, Clinical Features and Diagnosis—A Narrative Review
by Maria Grazia Bocci, Laura Cascarano, Giulia Capecchi, Antonio Lesci, Valerio Sabatini, Dorotea Rubino, Giulia Valeria Stazi, Gabriele Garotto, Stefania Carrara, Antonella Vulcano, Chiara Gori, Franca Del Nonno, Daniele Colombo, Laura Falasca, Emanuela Caraffa, Stefania Cicalini and Carla Fontana
J. Fungi 2025, 11(9), 617; https://doi.org/10.3390/jof11090617 - 24 Aug 2025
Viewed by 868
Abstract
Aspergillosis in immunocompromised individuals is a serious and potentially life-threatening infection, as the weakened immune system cannot effectively fight the Aspergillus fungus. This review provides an in-depth examination of aspergillosis in patients with various conditions that compromise immunity, including hematological disorders, HIV, SARS-CoV-2 [...] Read more.
Aspergillosis in immunocompromised individuals is a serious and potentially life-threatening infection, as the weakened immune system cannot effectively fight the Aspergillus fungus. This review provides an in-depth examination of aspergillosis in patients with various conditions that compromise immunity, including hematological disorders, HIV, SARS-CoV-2 pneumonia, influenza, and those who have undergone solid organ transplants. The clinical manifestations of aspergillosis are influenced by factors such as the host’s underlying comorbidities, immune response, and immune suppression due to medications or treatments. The review delves into the epidemiology of aspergillosis, exploring various risk factors that predispose individuals to infection. It also discusses the wide range of clinical symptoms, highlighting the challenges in diagnosis and the importance of early detection. The review contrasts traditional diagnostic approaches with emerging molecular techniques, emphasizing the role of advanced diagnostics in improving outcomes. A proposed clinical decision-making flowchart is provided to assist healthcare professionals in managing suspected cases of aspergillosis. In addition to diagnostic challenges, the review addresses antifungal prophylaxis, pre-emptive therapy, and the growing concern of pharmacological resistance to antifungal agents. It concludes with a discussion of future research directions, underscoring the need for improved therapeutic strategies and preventative measures in immunocompromised patients to reduce the burden of this severe fungal infection. Full article
(This article belongs to the Special Issue Fungal Infections in Intensive Care Medicine)
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16 pages, 584 KB  
Article
Effectiveness and Safety of Sacituzumab Govitecan in Real-World Clinical Practice in Patients with Metastatic Triple-Negative and HR+/HER2-Negative Breast Cancer
by Fernando Lago-Ballester, Adrián Martínez-Orea, Ana Laorden-Carrasco, María Sacramento Díaz-Carrasco, José Carlos Titos-Arcos, María Carmen Mira-Sirvent, Ginés Luengo-Gil and Mónica Martínez-Penella
Biomedicines 2025, 13(9), 2059; https://doi.org/10.3390/biomedicines13092059 - 23 Aug 2025
Viewed by 477
Abstract
Background/Objectives: Sacituzumab govitecan (SG) is an antibody–drug conjugate targeting Trop-2 that has demonstrated clinical benefits in randomised trials for patients with metastatic triple-negative breast cancer (mTNBC) and metastatic hormone receptor-positive/HER2-negative (HR+/HER2− mBC) disease. However, real-world data on its effectiveness and safety are limited, [...] Read more.
Background/Objectives: Sacituzumab govitecan (SG) is an antibody–drug conjugate targeting Trop-2 that has demonstrated clinical benefits in randomised trials for patients with metastatic triple-negative breast cancer (mTNBC) and metastatic hormone receptor-positive/HER2-negative (HR+/HER2− mBC) disease. However, real-world data on its effectiveness and safety are limited, especially in patients with poor performance status or central nervous system (CNS) involvement. This study aimed to evaluate the real-world outcomes of SG in these two subtypes. Methods: We conducted a retrospective, multicentre, observational study across three tertiary hospitals in Spain. Patients with mTNBC or HR+/HER2− mBC treated with SG between June 2022 and March 2025 were included. Clinical data, treatment history, adverse events (AEs), and survival outcomes were also recorded. The median progression-free survival (mPFS) and median overall survival (mOS) were estimated using Kaplan–Meier analysis. Univariate and multivariate analyses were performed to identify the factors influencing outcomes. The association between granulocyte colony-stimulating factor (G-CSF) prophylaxis and neutropenia was assessed using Fisher’s exact test. Results: A total of 56 patients were included in this study (33 with mTNBC and 23 with HR+/HER2− mBC). In the mTNBC group, mPFS was 4.0 months (95% CI: 1.94–5.98) and mOS was 11.0 months (95% CI: 4.80–17.12). In the HR+/HER2− mBC group, mPFS was 3.7 months (95% CI: 2.02–5.44) and mOS was 20.2 months (95% CI: 3.9–36.5). Fatigue, neutropenia, and gastrointestinal toxicity were the most common AEs. Primary G-CSF prophylaxis was not associated with a reduced incidence of neutropenia (p = 0.434). Conclusions: In routine practice, SG shows effectiveness comparable to that of randomised trials across both subtypes, with a safety profile consistent with pivotal studies. The observed toxicity profile was consistent with that described in pivotal clinical trials and other studies. The prophylactic use of G-CSF was not associated with an impact on the occurrence of neutropenia, but the incidence of neutropenia was lower than that in clinical trials and other studies that did not administer G-CSF prophylactically. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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10 pages, 381 KB  
Communication
Multiwave Locked System Laser Treatment Reduces the Bacterial Load in the Gingival Sulcus of Dogs After Plaque Removal
by Ivana Pallante, Paolo Squarzoni, Elisa Mazzotta, Nicola Pozzato and Monica Monici
Vet. Sci. 2025, 12(8), 767; https://doi.org/10.3390/vetsci12080767 - 16 Aug 2025
Viewed by 383
Abstract
Periodontal disease is a prevalent condition in companion animals. It is crucial to prevent the plaque and bacteria on tooth surfaces to avoid gingivitis and the more harmful periodontitis. The aim of the present study was to assess the impact of MLS laser [...] Read more.
Periodontal disease is a prevalent condition in companion animals. It is crucial to prevent the plaque and bacteria on tooth surfaces to avoid gingivitis and the more harmful periodontitis. The aim of the present study was to assess the impact of MLS laser treatment on the bacterial load by analyzing the gingival swabs of a total of 16 owned dogs with no history of dental disease that were selected from a cohort of patients admitted for plaque removal and dental hygiene procedures. Following each dental hygiene session, each dog received a single MLS laser therapy treatment (808–905 nm diode laser, frequency 36 Hz, and fluence 0.16 J/cm2). Swabs were collected from the two upper premolars before and after the laser treatment. These were submitted for mesophilic bacteria counts, and microbiological analysis was conducted on 10 positive cultures to evaluate the changes in the oral bacterial microbiota. MLS laser therapy statistically significantly reduced the mesophilic bacteria count by 1 log, with higher pre-laser treatment counts (n = 0.44; 5.77 ± 0.21 95%CI) in comparison to post-laser treatment counts (n = 0.73; 4.80 ± 0.346 95%CI). The MLS laser therapy was found to reduce the bacterial load in 80% of the subjects (p < 0.05). No significant differences pre- and post-laser treatment were observed in the bacteria species isolated from the microbiological cultures. MLS laser therapy appears to be a useful, non-invasive method for reducing the bacterial load in the treatment and prophylaxis of periodontal disease in dogs. Full article
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24 pages, 1548 KB  
Review
Onychomycosis in Diabetics: A Common Infection with Potentially Serious Complications
by Aditya K. Gupta, Amanda Liddy, Lee Magal, Avner Shemer, Elizabeth A. Cooper, Ditte Marie L. Saunte and Tong Wang
Life 2025, 15(8), 1285; https://doi.org/10.3390/life15081285 - 13 Aug 2025
Viewed by 813
Abstract
Onychomycosis is a prevalent and clinically relevant complication among individuals with diabetes. It is associated with an elevated risk of secondary fungal and bacterial infections, foot ulceration, and, in advanced cases, amputation. Factors contributing to the increased prevalence of onychomycosis in this population [...] Read more.
Onychomycosis is a prevalent and clinically relevant complication among individuals with diabetes. It is associated with an elevated risk of secondary fungal and bacterial infections, foot ulceration, and, in advanced cases, amputation. Factors contributing to the increased prevalence of onychomycosis in this population include age, peripheral vascular disease, poor glycemic control, neuropathy, suboptimal foot hygiene, and nail trauma. While dermatophytes are the most common pathogens, diabetic patients are more prone to mixed infections involving Candida species with varying antifungal susceptibility profiles, necessitating accurate identification to guide therapy. Prompt diagnosis and early intervention are important to prevent complications. Systemic antifungals such as terbinafine and itraconazole are considered first-line therapies, particularly for moderate to severe onychomycosis. However, drug interactions, renal, hepatic, and metabolic comorbidities may necessitate individualized treatment plans. For patients with mild to moderate disease, or contraindications to oral therapy, topical agents such as efinaconazole or tavaborole offer viable alternatives. Adjunctive measures, including education on foot hygiene, prompt treatment of tinea pedis, and environmental sanitization, are important in preventing recurrence and reinfection. This review summarizes the epidemiology, diagnosis, and treatment considerations for onychomycosis in diabetic patients, emphasizing the need for individualized care to improve outcomes in this high-risk population. Full article
(This article belongs to the Section Medical Research)
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12 pages, 822 KB  
Article
Evaluation of Different Initial Doses of Envarsus in De Novo Kidney Transplant Recipients
by Patricio Más-Serrano, Antonio Franco, Iván Beltrá-Picó, Marcos Díaz-González, Claudia Colomer, Isabel Gascón, Elena de la Cruz, Javier Pérez-Contreras, Ricardo Nalda-Molina and Amelia Ramón-López
J. Clin. Med. 2025, 14(16), 5687; https://doi.org/10.3390/jcm14165687 - 11 Aug 2025
Viewed by 374
Abstract
Background/Objectives: Envarsus is a novel prolonged-release formulation of tacrolimus with enhanced bioavailability. The summary of product characteristics recommends an initial dose of 0.17 mg/kg/day for the prophylaxis of rejection in kidney transplant recipients, which may be excessive. This study aimed to compare [...] Read more.
Background/Objectives: Envarsus is a novel prolonged-release formulation of tacrolimus with enhanced bioavailability. The summary of product characteristics recommends an initial dose of 0.17 mg/kg/day for the prophylaxis of rejection in kidney transplant recipients, which may be excessive. This study aimed to compare the pharmacokinetics of four different initial doses of Envarsus: 0.15 mg/kg/day (group 1), 0.12 mg/kg/day (group 2), 0.10 mg/kg/day (group 3), and 0.08 mg/kg/day (group 4). Induction therapy included thymoglobulin, sirolimus, and prednisone, with Envarsus initiated once serum creatinine levels fell below 3 mg/dL. Methods: A comprehensive pharmacokinetic sampling strategy was implemented between 48 and 72 h post-transplant, allowing for the calculation of AUC using the trapezoidal method. Additionally, trough levels at 72 h were assessed, with the therapeutic range defined as 5–8 ng/mL. Patients with trough concentrations above 8 ng/mL either had their tacrolimus dose reduced or their treatment temporarily discontinued for 24 h. Kidney function was evaluated three months post-transplant. Results: A total of 167 patients completed the study (39 in group 1, 43 in group 2, 42 in group 3, and 43 in group 4). The groups were balanced in baseline characteristics. Compared with groups 1 and 2, groups 3 and 4 had significantly lower mean trough concentrations (7.9 ng/mL and 6.5 ng/mL vs. 11.3 ng/mL and 10.8 ng/mL, respectively) and lower AUC values (310 ng·h/mL and 271 ng·h/mL vs. 458 ng·h/mL and 390 ng·h/mL, respectively). Additionally, the proportion of patients with supratherapeutic drug levels was lower in groups 3 and 4 (47.6% and 37.2% vs. 76.9% and 67.4%, respectively), as was the proportion of patients requiring a skipped dose (14.3% and 14.0% vs. 30.8% and 27.9%, respectively). Importantly, the percentage of patients within the therapeutic range was higher in the 0.08 mg/kg/day group (41.9%), demonstrating improved drug level stability at this dose. Despite these differences, kidney function remained similar in all groups at three months, and no significant differences in the incidence of adverse events were observed among the four dosing groups. Conclusions: An initial dose of 0.08 mg/kg/day resulted in adequate tacrolimus exposure, improved the proportion of patients within the therapeutic range, and minimized unnecessary drug accumulation. These findings suggest that a lower initial dose of Envarsus may be preferable to optimize drug exposure while improving therapeutic precision. Full article
(This article belongs to the Section Pharmacology)
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14 pages, 286 KB  
Hypothesis
Botulinum Toxin-A, Generating a Hypothesis for Orofacial Pain Therapy
by Yair Sharav, Rafael Benoliel and Yaron Haviv
Toxins 2025, 17(8), 389; https://doi.org/10.3390/toxins17080389 - 4 Aug 2025
Viewed by 735
Abstract
Orofacial pain encompasses a spectrum of disorders ranging from musculoskeletal disorders, such as myofascial pain, and temporomandibular disorders to neuropathic situations, such as trigeminal neuralgia and painful post-traumatic trigeminal neuropathy, and neurovascular pain such as orofacial migraine and cluster orofacial pain. Each require [...] Read more.
Orofacial pain encompasses a spectrum of disorders ranging from musculoskeletal disorders, such as myofascial pain, and temporomandibular disorders to neuropathic situations, such as trigeminal neuralgia and painful post-traumatic trigeminal neuropathy, and neurovascular pain such as orofacial migraine and cluster orofacial pain. Each require tailored prophylactic pharmacotherapy, such as carbamazepine, gabapentin, pregabalin, amitriptyline, metoprolol, and topiramate. Yet a substantial subset of patients remains refractory. Botulinum toxin type A (BoNT-A) has demonstrated growing efficacy in the treatment of multiple forms of orofacial pain, which covers the whole range of these disorders. We describe the analgesic properties of BoNT-A for each of the three following orofacial pain disorders: neuropathic, myofascial, and neurovascular. Then, we conclude with a section on the neuromodulatory mechanisms of BoNT-A. This lays the basis for the generation of a hypothesis for the segmental therapeutic action of BoNT-A on the whole range of orofacial pain disorders. In addition, the advantage of BoNT-A for providing a safe sustained effect after a single application for chronic pain prophylaxis is discussed, as opposed to the daily use of current conventional prophylactic medications. Finally, we summarize the clinical applications of BoNT-A for chronic orofacial pain therapy. Full article
18 pages, 2346 KB  
Article
TDM-Based Approach for Properly Managing Intravenous Isavuconazole Treatment in a Complex Case Mix of Critically Ill Patients
by Milo Gatti, Matteo Rinaldi, Riccardo De Paola, Antonio Siniscalchi, Tommaso Tonetti, Pierluigi Viale and Federico Pea
Antibiotics 2025, 14(8), 777; https://doi.org/10.3390/antibiotics14080777 - 1 Aug 2025
Viewed by 464
Abstract
Objectives: To assess the role of a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program of isavuconazole in preventing under- or overexposure with the intent of improving efficacy and safety outcomes in the critically ill patients. Methods: This retrospective study [...] Read more.
Objectives: To assess the role of a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program of isavuconazole in preventing under- or overexposure with the intent of improving efficacy and safety outcomes in the critically ill patients. Methods: This retrospective study included critical patients receiving intravenous isavuconazole for prophylaxis or treatment of invasive fungal infections (IFI) and undergoing at least one TDM-guided ECPA in the period 1 March 2021–31 March 2025. Desired isavuconazole exposure was defined as trough concentrations (Cmin) of 1.0–5.1 mg/L. Efficacy outcome was assessed by means of bronchoalveolar (BAL) galactomannan (GM) index, breakthrough IFI, and 30-day mortality rate, whereas safety was assessed by means of hepatic test disturbances (HTD). Univariate analysis was carried out for assessing potential variables associated with isavuconazole under- or overexposure and for comparing features of solid organ transplant (SOT) recipients vs. non-SOT patients. Proportions of isavuconazole Cmin underexposure, desired exposure, and overexposure were assessed at different timepoints from starting therapy. Trends over time of HTD in relation to isavuconazole exposure were assessed separately in patients having HTD or not at baseline. Results: Overall, 32 critical patients were included. A total of 166 TDM-guided ECPAs were provided. Median (IQR) average isavuconazole Cmin was 3.5 mg/L (2.1–4.6 mg/L). Proportions of ECPAs with isavuconazole Cmin under- and overexposure were 4.2% (7/166) and 16.3% (27/166), respectively. Patients experiencing underexposure had higher body mass index (30.1 vs. 25.5 kg/m2; p < 0.001). Trends of isavuconazole Cmin under- and overexposure changed over time, significantly decreasing the former (10.5% <7 days vs. 4.3% 7–28 days vs. 0.0% >28 days; p < 0.001) and increasing the latter (5.3% <7 days vs. 12.8% 7–28 days vs. 29.3% >28 days; p < 0.001). HTD occurred in 15/32 patients, most of whom (10/15) were affected just at baseline. Patients with transient or persistent overexposure trended toward a higher risk of HTD compared to those without (33.3% vs. 8.3%; p = 0.11). Conclusions: A real-time TDM-guided approach could be a valuable tool for optimizing isavuconazole exposure, especially whenever dealing with obese patients or with prolonged treatment. Full article
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24 pages, 624 KB  
Review
Integrating Artificial Intelligence into Perinatal Care Pathways: A Scoping Review of Reviews of Applications, Outcomes, and Equity
by Rabie Adel El Arab, Omayma Abdulaziz Al Moosa, Zahraa Albahrani, Israa Alkhalil, Joel Somerville and Fuad Abuadas
Nurs. Rep. 2025, 15(8), 281; https://doi.org/10.3390/nursrep15080281 - 31 Jul 2025
Viewed by 688
Abstract
Background: Artificial intelligence (AI) and machine learning (ML) have been reshaping maternal, fetal, neonatal, and reproductive healthcare by enhancing risk prediction, diagnostic accuracy, and operational efficiency across the perinatal continuum. However, no comprehensive synthesis has yet been published. Objective: To conduct a scoping [...] Read more.
Background: Artificial intelligence (AI) and machine learning (ML) have been reshaping maternal, fetal, neonatal, and reproductive healthcare by enhancing risk prediction, diagnostic accuracy, and operational efficiency across the perinatal continuum. However, no comprehensive synthesis has yet been published. Objective: To conduct a scoping review of reviews of AI/ML applications spanning reproductive, prenatal, postpartum, neonatal, and early child-development care. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus through April 2025. Two reviewers independently screened records, extracted data, and assessed methodological quality using AMSTAR 2 for systematic reviews, ROBIS for bias assessment, SANRA for narrative reviews, and JBI guidance for scoping reviews. Results: Thirty-nine reviews met our inclusion criteria. In preconception and fertility treatment, convolutional neural network-based platforms can identify viable embryos and key sperm parameters with over 90 percent accuracy, and machine-learning models can personalize follicle-stimulating hormone regimens to boost mature oocyte yield while reducing overall medication use. Digital sexual-health chatbots have enhanced patient education, pre-exposure prophylaxis adherence, and safer sexual behaviors, although data-privacy safeguards and bias mitigation remain priorities. During pregnancy, advanced deep-learning models can segment fetal anatomy on ultrasound images with more than 90 percent overlap compared to expert annotations and can detect anomalies with sensitivity exceeding 93 percent. Predictive biometric tools can estimate gestational age within one week with accuracy and fetal weight within approximately 190 g. In the postpartum period, AI-driven decision-support systems and conversational agents can facilitate early screening for depression and can guide follow-up care. Wearable sensors enable remote monitoring of maternal blood pressure and heart rate to support timely clinical intervention. Within neonatal care, the Heart Rate Observation (HeRO) system has reduced mortality among very low-birth-weight infants by roughly 20 percent, and additional AI models can predict neonatal sepsis, retinopathy of prematurity, and necrotizing enterocolitis with area-under-the-curve values above 0.80. From an operational standpoint, automated ultrasound workflows deliver biometric measurements at about 14 milliseconds per frame, and dynamic scheduling in IVF laboratories lowers staff workload and per-cycle costs. Home-monitoring platforms for pregnant women are associated with 7–11 percent reductions in maternal mortality and preeclampsia incidence. Despite these advances, most evidence derives from retrospective, single-center studies with limited external validation. Low-resource settings, especially in Sub-Saharan Africa, remain under-represented, and few AI solutions are fully embedded in electronic health records. Conclusions: AI holds transformative promise for perinatal care but will require prospective multicenter validation, equity-centered design, robust governance, transparent fairness audits, and seamless electronic health record integration to translate these innovations into routine practice and improve maternal and neonatal outcomes. Full article
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