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9 pages, 235 KiB  
Article
Ceftazidime-Avibactam Plus Aztreonam for the Treatment of Blood Stream Infection Caused by Klebsiella pneumoniae Resistant to All Beta-Lactame/Beta-Lactamase Inhibitor Combinations
by Konstantinos Mantzarlis, Efstratios Manoulakas, Dimitrios Papadopoulos, Konstantina Katseli, Athanasia Makrygianni, Vassiliki Leontopoulou, Periklis Katsiafylloudis, Stelios Xitsas, Panagiotis Papamichalis, Achilleas Chovas, Demosthenes Makris and George Dimopoulos
Antibiotics 2025, 14(8), 806; https://doi.org/10.3390/antibiotics14080806 (registering DOI) - 7 Aug 2025
Abstract
Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and [...] Read more.
Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO2/FiO2 ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO2/FiO2 ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings. Full article
11 pages, 521 KiB  
Article
Comparative Study of Two Classification Criteria Sets in Real Clinical Practice for Behçet’s Disease
by Rafael Gálvez-Sánchez, José Luis Martín-Varillas, Lara Sánchez-Bilbao, Iván Ferraz-Amaro, Elena Aurrecoechea, Diana Prieto-Peña and Ricardo Blanco
J. Clin. Med. 2025, 14(15), 5559; https://doi.org/10.3390/jcm14155559 (registering DOI) - 7 Aug 2025
Abstract
Background: Behçet’s Disease (BD) was traditionally classified according to the International Study Group (ISG), where oral ulcers were mandatory. The International Team for the Revision of the International Criteria for BD (ICBD) introduced a scoring system instead. Our aim was to assess (a) [...] Read more.
Background: Behçet’s Disease (BD) was traditionally classified according to the International Study Group (ISG), where oral ulcers were mandatory. The International Team for the Revision of the International Criteria for BD (ICBD) introduced a scoring system instead. Our aim was to assess (a) sensitivity, (b) concordance between ISG and ICDB criteria in global and severe BD cases (ocular, vascular, and neurological), and (c) evaluate their clinical implications. Methods: Retrospective cohort study including 142 BD patients diagnosed in a well-defined population in Northern Spain, between January 1980 and November 2023. Both ISG and ICBD criteria were compared, sensitivity and concordance were assessed using Prevalence-Adjusted and Bias-Adjusted Kappa (PABAK) and the unadjusted Kappa. Results: A total of 142 BD patients diagnosed by expert rheumatologists (73 men; mean age of 36.4) were studied. Among them, 84 met ISG criteria, while 116 fulfilled ICBD criteria. Sensitivity of ISG and ICBD criteria in the overall cohort was (59.1% and 81.6%), respectively. Among patients with severe manifestations (ocular, vascular, or neurological), sensitivity increased to 71.2% for ISG and 92.5% for ICBD. Overall concordance was moderate (Kappa = 0.490), with 70.4% of patients classified identically. When adjusting prevalence and bias, concordance improved slightly (PABAK = 0.549). Of the 32 patients classified as BD exclusively by ICBD, 7 were receiving anti-TNF therapy, and 2 were receiving apremilast. Conclusions: The ICBD criteria demonstrated higher sensitivity than the traditional ISG criteria in classifying BD, particularly in severe cases. Classifying these additional patients under ICBD facilitated the initiation of on-label biologic treatments, potentially enhancing BD management, especially for severe cases. Full article
(This article belongs to the Section Immunology)
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14 pages, 759 KiB  
Article
Vitamin D Deficiency and Exocrine Pancreatic Insufficiency: An Analysis Carried Out in Orthogeriatric Patients (VIDEP.org)
by Pavol Mikula, Matthias Unseld and Hans Jürgen Heppner
J. Clin. Med. 2025, 14(15), 5558; https://doi.org/10.3390/jcm14155558 (registering DOI) - 7 Aug 2025
Abstract
Introduction: Vitamin D deficiency, a reversible cause of osteoporosis, is increasingly prevalent, showing varying degrees of severity that are notably pronounced among the growing population of multimorbid elderly patients. Given that the aging pancreas undergoes senescent processes leading to impaired function—which negatively impacts [...] Read more.
Introduction: Vitamin D deficiency, a reversible cause of osteoporosis, is increasingly prevalent, showing varying degrees of severity that are notably pronounced among the growing population of multimorbid elderly patients. Given that the aging pancreas undergoes senescent processes leading to impaired function—which negatively impacts enteral vitamin D absorption and, consequently, elderly bone metabolism—a specific diagnostic and treatment approach is crucial. Our study aimed to determine the prevalence of vitamin D deficiency and exocrine pancreatic insufficiency (EPI) in orthogeriatric patients. We also evaluated differences in vitamin D deficiency severity between patients with normal and impaired pancreatic function. Furthermore, a short-term monitoring of vitamin D level increases after 12 days of substitution therapy in both groups aimed to inform osteoanabolic therapy for specific high-fracture-risk patients, assessing the influence of pancreatic function on substitution efficacy. Methods: We conducted a retrospective, monocentric cohort study, evaluating data from all patients hospitalized with manifest osteoporosis in an orthogeriatric department during a six-month spring/summer period. Demographic data, relevant comorbidities, the type of fracture, the amount of faecal elastase 1 (CALEX® Cap Bühlmann), and the serum levels of 25-hydroxyvitamin D (25(OH)D) were assessed. Results: We found a high prevalence (70.6%) of vitamin D deficiency (25(OH)D < 30 µg/L) among all orthogeriatric patients. Of these, 16% met the criteria for mild to severe EPI. The group with normal exocrine pancreatic function showed a higher average vitamin D value, and their increase in vitamin D levels following short-term substitution was up to 100% greater compared to the group with impaired pancreatic function. Notably, 69% of women and 20% of men met the therapeutic threshold for specific osteoanabolic osteoporosis therapy, even without a T-score. Conclusions: Our findings reveal a very high prevalence of vitamin D deficiency and a high prevalence of EPI in orthogeriatric patients. Those with impaired exocrine pancreatic function exhibit lower baseline vitamin D levels and a diminished capacity for vitamin D absorption during short-term monitoring. These results have significant clinical implications for osteoporotic therapy, given that a substantial proportion of patients, particularly women, meet the criteria for specific osteoanabolic treatment. Full article
(This article belongs to the Special Issue The “Orthogeriatric Fracture Syndrome”—Issues and Perspectives)
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15 pages, 954 KiB  
Article
Anterior Redisplacement After Intramedullary Nail Fixation for Trochanteric Femoral Fractures: Incidence and Risk Factors in 598 Older Patients
by Hironori Kuroda, Suguru Yokoo, Yukimasa Okada, Junya Kondo, Koji Sakagami, Takahiko Ichikawa, Keiya Yamana and Chuji Terada
J. Clin. Med. 2025, 14(15), 5557; https://doi.org/10.3390/jcm14155557 (registering DOI) - 6 Aug 2025
Abstract
Background/Objectives: Anterior redisplacement, defined as a postoperative anterior shift of the distal fragment despite intraoperative reduction, is occasionally observed after cephalomedullary nailing for trochanteric femoral fractures. However, its incidence and associated risk factors remain unclear. This study aimed to determine the incidence of [...] Read more.
Background/Objectives: Anterior redisplacement, defined as a postoperative anterior shift of the distal fragment despite intraoperative reduction, is occasionally observed after cephalomedullary nailing for trochanteric femoral fractures. However, its incidence and associated risk factors remain unclear. This study aimed to determine the incidence of anterior redisplacement following intramedullary nail fixation in geriatric trochanteric fractures, and to identify independent risk factors. Methods: This study retrospectively reviewed data from 598 consecutive hips in 577 patients (aged ≥65 years) who underwent intramedullary nail fixation for trochanteric fractures at a single center (2012–2023). Sagittal reduction on the lateral radiographic view was classified as posterior, anatomical, or anterior according to the position of the distal fragment, and was recorded preoperatively and postoperatively. Anterior redisplacement, the primary outcome, was defined as a change in alignment from a posterior or anatomical position postoperatively to an anterior position on any subsequent follow-up radiograph. Independent risk factors were identified by logistic regression. Results: Among the 543 hips reduced posteriorly (n = 204) or anatomically (n = 339), anterior redisplacement occurred in 73 (13.4%). The incidence of anterior redisplacement was significantly higher following anatomical compared to posterior reduction (19.5% vs. 3.4%; p < 0.001), and also higher in fractures that were anteriorly aligned preoperatively (18.0%) compared to anatomical (8.5%; p < 0.01) and posterior (6.2%; p < 0.01) alignment. Multivariate analysis revealed two independent predictors: preoperative anterior alignment (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.24–2.81; p = 0.003) and postoperative anatomical (vs. posterior) reduction (OR 6.49, 95% CI 2.92–14.44; p < 0.001). Age, sex, Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association classification, Evans–Jensen classification, nail length, and canal-filling ratio were not associated with redisplacement. No lag-screw cutout occurred during the follow-up. Conclusions: Anterior redisplacement occurred in one of seven geriatric trochanteric fractures despite apparently satisfactory fixation. An anatomical sagittal reduction—traditionally considered “ideal”—increases the risk more than sixfold, whereas a deliberate posterior-buttress is protective. Unlike patient-related risk factors, sagittal reduction is under the surgeon’s control. The study findings provide evidence that choosing a slight posterior bias can significantly improve stability. Full article
(This article belongs to the Special Issue Geriatric Fracture: Current Treatment and Future Options)
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6 pages, 406 KiB  
Brief Report
One-Shot, One Opportunity: Retrospective Observational Study on Long-Acting Antibiotics for SSTIs in the Emergency Room—A Real-Life Experience
by Giacomo Ciusa, Giuseppe Pipitone, Alessandro Mancuso, Stefano Agrenzano, Claudia Imburgia, Agostino Massimo Geraci, Alberto D’Alcamo, Luisa Moscarelli, Antonio Cascio and Chiara Iaria
Pathogens 2025, 14(8), 781; https://doi.org/10.3390/pathogens14080781 - 6 Aug 2025
Abstract
Background: Skin and soft tissue infections (SSTIs) are a major cause of emergency room (ER) visits and hospitalizations. Long-acting lipoglycopeptides (LALs), such as dalbavancin and oritavancin, offer potential for early discharge and outpatient management, especially in patients at risk for methicillin-resistant Staphylococcus aureus [...] Read more.
Background: Skin and soft tissue infections (SSTIs) are a major cause of emergency room (ER) visits and hospitalizations. Long-acting lipoglycopeptides (LALs), such as dalbavancin and oritavancin, offer potential for early discharge and outpatient management, especially in patients at risk for methicillin-resistant Staphylococcus aureus (MRSA) or with comorbidities. Methods: We conducted a retrospective observational cohort study from March to December 2024 in an Italian tertiary-care hospital. Adult patients treated in the ER with a single dose of dalbavancin (1500 mg) or oritavancin (1200 mg) for SSTIs were included. Demographic, clinical, and laboratory data were collected. Follow-up evaluations were performed at 14 and 30 days post-treatment to assess outcomes. Results: Nineteen patients were enrolled (median age 59 years; 53% female). Most had lower limb involvement and elevated inflammatory markers. Three patients (16%) were septic. Fourteen patients (74%) were discharged without hospital admission; hospitalization in the remaining cases was due to comorbidities rather than SSTI severity. No adverse drug reactions were observed. At 14 days, 84% of patients had clinical resolution; only 10% had recurrence by day 30, with no mortality nor readmission reported. Conclusions: LALs appear effective and well-tolerated in the ER setting, supporting early discharge and reducing healthcare burden. Broader use may require structured care pathways and multidisciplinary coordination. Full article
19 pages, 1548 KiB  
Article
Phytochemical Analysis, Antioxidant Activity, and Anticancer Potential of Afzelia quanzensis Welw—Bark Extract: A Traditional Remedy Utilized by Indigenous Communities in KwaZulu-Natal and Eastern Cape Provinces of South Africa
by Siphamandla Qhubekani Njabuliso Lamula, Thando Bhanisa, Martha Wium, Juliano Domiraci Paccez, Luiz Fernando Zerbini and Lisa V. Buwa-Komoreng
Int. J. Mol. Sci. 2025, 26(15), 7623; https://doi.org/10.3390/ijms26157623 - 6 Aug 2025
Abstract
Despite the significant advancements in treatment and prevention, the fight against cancer is ongoing worldwide. This study evaluated the pharmacological properties and anticancer activity of Afzelia quanzensis bark, traditionally used by the indigenous communities of KwaZulu Natal and Eastern Cape Provinces of South [...] Read more.
Despite the significant advancements in treatment and prevention, the fight against cancer is ongoing worldwide. This study evaluated the pharmacological properties and anticancer activity of Afzelia quanzensis bark, traditionally used by the indigenous communities of KwaZulu Natal and Eastern Cape Provinces of South Africa to treat cancer and related illnesses. Phytochemical screening, high-performance liquid chromatography–diode array detection (HPLC-DAD), and Fourier-transform infrared spectroscopy (FTIR) analyses were carried out using established protocols. The antioxidant activity was assessed via the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity and nitric oxide radicals. The anticancer activity was evaluated using the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Phytochemical analysis revealed the presence of saponins, flavonoids, terpenoids, alkaloids, steroids, cardiac glycosides, and phlobatannins. The HPLC-DAD analysis detected seven distinctive peaks in the aqueous extract and three distinctive peaks in the methanolic extract. The FTIR spectra of the aqueous extract displayed characteristic peaks corresponding to O-H, C=O, C=C, and =C–H functional groups. Among the tested extracts, the methanol extract exhibited the strongest antioxidant activity, followed by the ethanolic extract, in both DPPH and nitric oxide. The methanol extract showed a higher cell proliferation inhibition against the DU-145 cancer cell line with the percentage of inhibition of 37.8%, followed by the aqueous extract with 36.3%. In contrast, limited activity was observed against PC-3, SK-UT-1, and AGS cell lines. The results demonstrated notable dose-dependent antioxidant and antiproliferative activities supporting the ethnomedicinal use of Afzelia quanzensis bark in cancer management. These findings warrant further investigation into its bioactive constituents and mechanisms of action. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
14 pages, 719 KiB  
Article
Recursive Interplay of Family and Biological Dynamics: Adults with Type 1 Diabetes Mellitus Under the Spotlight
by Helena Jorge, Bárbara Regadas Correia, Miguel Castelo-Branco and Ana Paula Relvas
Diabetology 2025, 6(8), 81; https://doi.org/10.3390/diabetology6080081 - 6 Aug 2025
Abstract
Objectives: Diabetes Mellitus involves demanding challenges that interfere with family functioning and routines. In turn, family and social context impacts individual glycemic control. This study aims to identify this recursive interplay, the mutual influences of family systems and diabetes management. Design: Data was [...] Read more.
Objectives: Diabetes Mellitus involves demanding challenges that interfere with family functioning and routines. In turn, family and social context impacts individual glycemic control. This study aims to identify this recursive interplay, the mutual influences of family systems and diabetes management. Design: Data was collected through a cross-sectional design comparing patients, aged 22–55, with and without metabolic control. Methods: Participants filled out a set of self-report measures of sociodemographic, clinical and family systems assessment. Patients (91) were also invited to describe their perception about disease management interference regarding family functioning. We first examined the extent to which family variables grouped dataset to determine if there were similarities and dissimilarities that fit with our initial diabetic groups’ classification. Results: Cluster analysis results identify a two-cluster solution validating initial classification of two groups of patients: 49 with metabolic control (MC) and 42 without metabolic control (NoMC). Independent sample tests suggested statistically significant differences between groups in family subscales- family difficulties and family communication (p < 0.05). Binary logistic regression shed light on predictors of explained variance to no metabolic control, in four models: Sociodemographic, Clinical data, SCORE-15/Congruence Scale and Eating Behavior. Furthermore, groups differ on family support, level and sources of family conflict caused by diabetes management issues. Considering only patients who co-habit with a partner for more than one year (N = 44), NoMC patients score lower on marital functioning in all categories (p < 0.05). Discussion: Family-Chronic illness interaction plays a significant role in a patient’s adherence to treatment. This study highlights the Standards of Medical Care for Diabetes, considering caregivers and family members on diabetes care. Full article
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11 pages, 215 KiB  
Article
Personalised Prevention of Falls in Persons with Dementia—A Registry-Based Study
by Per G. Farup, Knut Hestad and Knut Engedal
Geriatrics 2025, 10(4), 106; https://doi.org/10.3390/geriatrics10040106 - 6 Aug 2025
Abstract
Background/Objectives: Multifactorial prevention of falls in persons with dementia has minimal or non-significant effects. Personalised prevention is recommended. We have previously shown that gait speed, basic activities of daily living (ADL), and depression (high Cornell scores) were independent predictors of falls in persons [...] Read more.
Background/Objectives: Multifactorial prevention of falls in persons with dementia has minimal or non-significant effects. Personalised prevention is recommended. We have previously shown that gait speed, basic activities of daily living (ADL), and depression (high Cornell scores) were independent predictors of falls in persons with mild and moderate cognitive impairment. This study explored person-specific risks of falls related to physical, mental, and cognitive functions and types of dementia: Alzheimer’s disease (AD), vascular dementia (VD), mixed Alzheimer’s disease/vascular dementia (MixADVD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Methods: The study used data from “The Norwegian Registry of Persons Assessed for Cognitive Symptoms” (NorCog). Differences between the dementia groups and predictors of falls, gait speed, ADL, and Cornell scores were analysed. Results: Among study participants, 537/1321 (40.7%) reported a fall in the past year, with significant variations between dementia diagnoses. Fall incidence increased with age, comorbidity/polypharmacy, depression, and MAYO fluctuation score and with reduced physical activity, gait speed, and ADL. Persons with VD and MixADVD had high fall incidences and impaired gait speed and ADL. Training of physical fitness, endurance, muscular strength, coordination, and balance and optimising treatment of comorbidities and medication enhance gait speed. Improving ADL necessitates, in addition, relief of cognitive impairment and fluctuations. Relief of depression and fluctuations by psychological and pharmacological interventions is necessary to reduce the high fall risk in persons with DLB. Conclusions: The fall incidence and fall predictors varied significantly. Personalised interventions presuppose knowledge of each individual’s fall risk factors. Full article
20 pages, 1388 KiB  
Article
Beyond Bone Mineral Density: Real-World Fracture Risk Profiles and Therapeutic Gaps in Postmenopausal Osteoporosis
by Anamaria Ardelean, Delia Mirela Tit, Roxana Furau, Oana Todut, Gabriela S. Bungau, Roxana Maria Sânziana Pavel, Bogdan Uivaraseanu, Diana Alina Bei and Cristian Furau
Diagnostics 2025, 15(15), 1972; https://doi.org/10.3390/diagnostics15151972 - 6 Aug 2025
Abstract
Background/Objectives: Osteoporosis remains a leading cause of morbidity in postmenopausal women, yet many high-risk individuals remain undiagnosed or untreated. This study aimed to assess the prevalence of osteoporosis and osteopenia, treatment patterns, and skeletal fragility indicators in a large cohort of postmenopausal [...] Read more.
Background/Objectives: Osteoporosis remains a leading cause of morbidity in postmenopausal women, yet many high-risk individuals remain undiagnosed or untreated. This study aimed to assess the prevalence of osteoporosis and osteopenia, treatment patterns, and skeletal fragility indicators in a large cohort of postmenopausal women undergoing DXA screening. Methods: We analyzed data from 1669 postmenopausal women aged 40–89 years who underwent DXA evaluation. BMD status was categorized as normal, osteopenia, or osteoporosis. Treatment status was classified based on active antiosteoporotic therapy, calcium/vitamin D supplementation, hormonal therapy (historical use), or no treatment. Logistic regression models were used to explore independent predictors of osteoporosis and treatment uptake. Results: A total of 45.0% of women had osteoporosis and 43.5% had osteopenia. Despite this, 58.5% of the population, over half of women with osteoporosis, were not receiving any active pharmacologic treatment. Bisphosphonates were the most prescribed therapy (17.9%), followed by calcium/vitamin D supplements (20.6%). A prior history of fragility fractures and radiological bone lesions were significantly associated with lower BMD (p < 0.05). Historical hormone replacement therapy (HRT) use was not associated with current BMD (p = 0.699), but women with HRT use reported significantly fewer fractures (p < 0.001). In multivariate analysis, later menopause age and low BMD status predicted higher odds of receiving active treatment. Conclusions: Our findings highlight a substantial care gap in osteoporosis management, with treatment primarily initiated reactively in more severe cases. Improved screening and earlier intervention strategies are urgently needed to prevent fractures and reduce the long-term burden of osteoporosis. Full article
(This article belongs to the Special Issue Diagnosis and Management of Osteoporosis)
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12 pages, 693 KiB  
Article
Efficacy and Safety of the Combination of Durvalumab Plus Gemcitabine and Cisplatin in Patients with Advanced Biliary Tract Cancer: A Real-World Retrospective Cohort Study
by Eishin Kurihara, Satoru Kakizaki, Masashi Ijima, Takeshi Hatanaka, Norio Kubo, Yuhei Suzuki, Hidetoshi Yasuoka, Takashi Hoshino, Atsushi Naganuma, Noriyuki Tani, Yuichi Yamazaki and Toshio Uraoka
Biomedicines 2025, 13(8), 1915; https://doi.org/10.3390/biomedicines13081915 - 6 Aug 2025
Abstract
Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and [...] Read more.
Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and safety of GCD treatment for advanced biliary tract cancer in real-world conditions. Methods: The study subjects were 52 patients with biliary tract cancer who received GCD therapy between January 2023 and May 2024. The observation parameters included the modified Glasgow Prognostic Score (mGPS), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), tumor markers (CEA, CA19-9), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: The cohort included 36 men and 16 women, with a median age of 73.0 years. There were 36 cases of cholangiocarcinoma (distal: 10, perihilar: 19, intrahepatic: 7), 13 cases of gallbladder cancer, and 3 cases of ampullary carcinoma. The stages were locally advanced in 30 cases and metastatic in 22 cases. Biliary drainage was performed in 30 cases. There were 38 cases receiving first-line therapy and 14 cases receiving second-line or later treatments. The median values at the start of GCD therapy were ALB 3.7 g/dL, CRP 0.39 mg/dL, NLR 2.4, PLR 162.5, CEA 4.8 ng/mL, and CA19-9 255.9 U/mL. The mGPS distribution was 0:23 cases, 1:18 cases, and 2:11 cases. The treatment outcomes were ORR 25.0% (CR 2 cases, PR 11 cases), DCR 78.8% (SD 28 cases, PD 10 cases, NE 1 case), median PFS 8.6 months, and median OS 13.9 months. The PLR was suggested to be useful for predicting PFS. A decrease in CEA at six weeks after the start of treatment was a significant predictor of PFS and OS. Gallbladder cancer had a significantly poorer prognosis compared to other cancers. The immune-related adverse events included hypothyroidism in two cases, cholangitis in one case, and colitis in one case. Conclusions: The ORR, DCR, and PFS were comparable to those in the TOPAZ-1 trial. Although limited by its retrospective design and small sample size, this study suggests that GCD therapy is an effective treatment regimen for unresectable biliary tract cancer in real-world clinical practice. Full article
(This article belongs to the Special Issue Advanced Research in Anticancer Inhibitors and Targeted Therapy)
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22 pages, 885 KiB  
Article
MRI-Based Radiomics for Outcome Stratification in Pediatric Osteosarcoma
by Esther Ngan, Dolores Mullikin, Ashok J. Theruvath, Ananth V. Annapragada, Ketan B. Ghaghada, Andras A. Heczey and Zbigniew A. Starosolski
Cancers 2025, 17(15), 2586; https://doi.org/10.3390/cancers17152586 - 6 Aug 2025
Abstract
Background/Objectives: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents; the survival rate is as low as 24%. Accurate prediction of clinical outcomes remains a challenge due to tumor heterogeneity and the complexity of pediatric cases. This study [...] Read more.
Background/Objectives: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents; the survival rate is as low as 24%. Accurate prediction of clinical outcomes remains a challenge due to tumor heterogeneity and the complexity of pediatric cases. This study aims to improve predictions of progressive disease, therapy response, relapse, and survival in pediatric OS using MRI-based radiomics and machine learning methods. Methods: Pre-treatment contrast-enhanced coronal T1-weighted MR scans were collected from 63 pediatric OS patients, with an additional nine external cases used for validation. Three strategies were considered for target region segmentation (whole-tumor, tumor sampling, and bone/soft tissue) and used for MRI-based radiomics. These were then combined with clinical features to predict OS clinical outcomes. Results: The mean age of OS patients was 11.8 ± 3.5 years. Most tumors were located in the femur (65%). Osteoblastic subtype was the most common histological classification (79%). The majority of OS patients (79%) did not have evidence of metastasis at diagnosis. Progressive disease occurred in 27% of patients, 59% of patients showed adequate therapy response, 25% experienced relapse after therapy, and 30% died from OS. Classification models based on bone/soft tissue segmentation generally performed the best, with certain clinical features improving performance, especially for therapy response and mortality. The top performing classifier in each outcome achieved 0.94–1.0 validation ROC AUC and 0.63–1.0 testing ROC AUC, while those without radiomic features (RFs) generally performed suboptimally. Conclusions: This study demonstrates the strong predictive capabilities of MRI-based radiomics and multi-region segmentations for predicting clinical outcomes in pediatric OS. Full article
(This article belongs to the Special Issue The Roles of Deep Learning in Cancer Radiotherapy)
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16 pages, 858 KiB  
Review
Unraveling the Core of Endometriosis: The Impact of Endocrine Disruptors
by Efthalia Moustakli, Anastasios Potiris, Themos Grigoriadis, Athanasios Zikopoulos, Eirini Drakaki, Ioanna Zouganeli, Charalampos Theofanakis, Angeliki Gerede, Athanasios Zachariou, Ekaterini Domali, Peter Drakakis and Sofoklis Stavros
Int. J. Mol. Sci. 2025, 26(15), 7600; https://doi.org/10.3390/ijms26157600 - 6 Aug 2025
Abstract
Globally, endometriosis affects almost 10% of reproductive-aged women, leading to chronic pain and discomfort. Endocrine-disrupting compounds (EDCs) seem to play a pivotal role as a causal factor. The current manuscript aims to explain potential molecular pathways, synthesize current evidence regarding EDCs as causative [...] Read more.
Globally, endometriosis affects almost 10% of reproductive-aged women, leading to chronic pain and discomfort. Endocrine-disrupting compounds (EDCs) seem to play a pivotal role as a causal factor. The current manuscript aims to explain potential molecular pathways, synthesize current evidence regarding EDCs as causative agents of endometriosis, and highlight implications in the general population and clinical work. A thorough review of experimental, epidemiologic, and mechanistic research studies was conducted to explain the association between EDCs and endometriosis. Among the primary EDCs under investigation are polychlorinated biphenyls, dioxins, phthalates, and bisphenol A (BPA). Despite methodological heterogeneity and some discrepancies, epidemiologic evidence supports a positive association between some increased levels of BPA, phthalates, and dioxins in urine or in blood, and endometriosis. Experiments support some effect of EDCs on endometrial cells and causing endometriosis. EDCs function as xenoestrogens, alter immune function, induce oxidative stress, and disrupt progesterone signaling. Epigenetic reprogramming may play a role in mediating EDC-induced endometriosis. Endocrine, immunological, and epigenetic pathways link EDCs and endometriosis. Prevention techniques require deeper comprehension of those factors. Causal linkages and possible treatment targets should be based on longitudinal studies and multi-omics techniques. Restriction of EDCs could be beneficial for endometriosis prevalence limitation. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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9 pages, 1050 KiB  
Article
Analysis of Calcaneal Fracture-Related Complications—A Retrospective Chart Review
by Géraldine Désirée Sturz-Jantsch, Melanie Winter, Stefan Hajdu and Thomas Haider
J. Clin. Med. 2025, 14(15), 5535; https://doi.org/10.3390/jcm14155535 - 6 Aug 2025
Abstract
Background/Objectives: The calcaneus is the most commonly injured tarsal bone, potentially resulting in long-term functional deficiencies and disability. The type of treatment mainly depends on fracture type and morphology. Treatment of these fractures can be challenging due to a limited soft tissue [...] Read more.
Background/Objectives: The calcaneus is the most commonly injured tarsal bone, potentially resulting in long-term functional deficiencies and disability. The type of treatment mainly depends on fracture type and morphology. Treatment of these fractures can be challenging due to a limited soft tissue envelope and is frequently associated with complications. The aim of this study was to classify fracture types and identify factors associated with in-hospital complications. Methods: Patients with calcaneal fractures treated at our level I trauma center between 1997 and 2017 were included. Demographic data, comorbidities, fracture characteristics, type of treatment, complications and revisions, compliance and accompanying injuries were evaluated. Results: A total of 238 patients (m = 163, f = 75) at a mean age of 40 years sustaining either uni- or bilateral calcaneal fracture resulting in a total of 288 calcaneal fractures. Concomitant injuries were present in 103 patients (35.9%). Traumatic spine lesions were present in 21.9%. Complications were recorded in 59 fractures (20.5%). Open fractures were more likely to develop complications (76.0% vs. 15.2%, p < 0.001). Significant complication (33% vs. 14%, p < 0.001) and wound complication rates (29% vs. 10%, p < 0.001) were found in multiple-injured patients. All open fractures were surgically treated on the day of admission. In calcaneal fractures with a Böhler angle below 0 degrees, more complications were seen (33% vs. 17%, p < 0.05). Conclusions: High complication rates following calcaneal fractures were detected, with an increased likelihood in open fractures and in patients with multiple injuries. A negative Böhler angle was associated with worse outcomes. Full article
(This article belongs to the Section Orthopedics)
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13 pages, 1625 KiB  
Article
Difficulties of Eating and Masticating Solid Food in Children with Spinal Muscular Atrophy—Preliminary Study
by Ewa Winnicka, Adrianna Łabuz, Zbigniew Kułaga, Tomasz Grochowski and Piotr Socha
Nutrients 2025, 17(15), 2561; https://doi.org/10.3390/nu17152561 - 6 Aug 2025
Abstract
Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder that frequently affects bulbar function, including feeding and swallowing. Although disease-modifying therapies have improved motor outcomes, little is known about the persistence of oromotor difficulties, particularly with regard to solid food intake. Objective: [...] Read more.
Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder that frequently affects bulbar function, including feeding and swallowing. Although disease-modifying therapies have improved motor outcomes, little is known about the persistence of oromotor difficulties, particularly with regard to solid food intake. Objective: This study aimed to evaluate mastication and swallowing performance in children with SMA undergoing treatment, and to investigate the association between tongue strength and feeding efficiency. Methods: Twenty-two children with SMA types 1–3 were assessed using the Test of Masticating and Swallowing Solids in Children (TOMASS-C) and the Iowa Oral Performance Instrument (IOPI). Key TOMASS-C outcomes included the number of bites, chewing cycles, swallows, and total eating time. Tongue strength was measured in kilopascals. Results: Most participants showed deviations from age-specific normative values in at least one TOMASS-C parameter. Tongue strength was significantly lower than reference values in 86% of participants and correlated negatively with all TOMASS-C outcomes (p < 0.001). Children with weaker tongue pressure required more swallows, more chewing cycles, and longer eating times. Conclusions: Despite pharmacological treatment, children with SMA experience persistent difficulties in eating solid foods. Tongue strength may serve as a non-invasive biomarker for bulbar dysfunction and support dietary decision-making and therapeutic planning. Full article
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14 pages, 1614 KiB  
Article
Adverse Pathology After Radical Prostatectomy in Low- and Intermediate-Risk Prostate Cancer: A Propensity Score-Matched Analysis of Long-Term Health-Related Quality of Life
by Michael Chaloupka, Alexander Buchner, Marc Kidess, Benedikt Ebner, Yannic Volz, Nikolaos Pyrgidis, Stephan Timo Ledderose, Dirk-André Clevert, Julian Marcon, Philipp Weinhold, Christian G. Stief and Maria Apfelbeck
Diagnostics 2025, 15(15), 1969; https://doi.org/10.3390/diagnostics15151969 - 6 Aug 2025
Abstract
Background and Objective: Adverse pathology to high-risk prostate cancer (PCa) after radical prostatectomy (upgrading) poses a threat to risk stratification and treatment planning. The impact on sexual function, urinary continence, and health-related quality of life (HRQOL) remains unclear. Methods: From 2004 [...] Read more.
Background and Objective: Adverse pathology to high-risk prostate cancer (PCa) after radical prostatectomy (upgrading) poses a threat to risk stratification and treatment planning. The impact on sexual function, urinary continence, and health-related quality of life (HRQOL) remains unclear. Methods: From 2004 to 2024, 4189 patients with preop low-/intermediate-risk PCa (Gleason score 6 or 7a, PSA ≤ 20 ng/mL) underwent radical prostatectomy at our department and were analyzed. Primary endpoint was HRQOL, erectile function, and urinary continence. Secondary endpoint was rate of salvage therapies and biochemical-free survival. Propensity score matching was performed using “operative time”, “robot-assisted surgery”, “blood loss”, “nerve-sparing surgery”, “age”, and “BMI” to represent comparable surgical approach. Median follow-up was 39 months (Interquartile-range (IQR) 15–60). Key Findings and Limitations: Patients who were upgraded to high-risk PCa showed a higher rate of postoperative radiotherapy and androgen-deprivation therapy compared to patients who were not upgraded (21% vs. 7%, p < 0.001; 9% vs. 3%, p = 0.002). Five-year biochemical recurrence-free survival was 68% in the upgrading group vs. 84% in the no-upgrading group (p < 0.001). We saw no difference in patient-reported HRQOL, urinary continence, or erectile function. Multivariable analysis showed that postoperative upgrading was a significant risk for not achieving good overall HRQOL (OR: 0.77, 95% CI: 0.61–0.97, p = 0.028) during the follow-up. Conclusions and Clinical Implications: Although postoperative upgrading to high-risk PCa leads to worse oncologic outcomes and higher salvage therapy rates, this study indicates that its impact on health-related quality of life is minimal and should not deter a cautious approach to radical prostatectomy. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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