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Search Results (3,764)

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15 pages, 1988 KB  
Review
Bone Evaluation with Micro Finite Element Analysis in Animal Models
by Behnam Namiranian, Kenichiro Doi, Salem Alenezi, Sameer B. Shah, Saeed Jerban and Eric Y. Chang
Tomography 2025, 11(9), 101; https://doi.org/10.3390/tomography11090101 (registering DOI) - 1 Sep 2025
Abstract
Micro-computed tomography (micro-CT) is a commonly used tool for bone evaluation in animal model research. Micro-scale finite element analysis (µFEA) has been proposed to account for different loading scenarios, detailed three-dimensional (3D) bone structure, material properties, and distribution obtained from micro-CT to estimate [...] Read more.
Micro-computed tomography (micro-CT) is a commonly used tool for bone evaluation in animal model research. Micro-scale finite element analysis (µFEA) has been proposed to account for different loading scenarios, detailed three-dimensional (3D) bone structure, material properties, and distribution obtained from micro-CT to estimate bone mechanical properties and to predict its potential fracture. The in vivo application of µFEA has been limited to animal models due to the smaller bore size of micro-CT and the long scan time. This narrative review article describes studies that used micro-CT-based µFEA to predict bone mechanical competence, understand bone fracture and remodeling mechanisms, and to evaluate the impacts of the therapeutics, implants, and surgical interventions. Moreover, the concept, limitations, and future potentials of micro-CT-based FEA are discussed. Full article
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18 pages, 990 KB  
Article
Leukocyte-Based Inflammatory Profiles Across Dyslipidemia Phenotypes: Patterns of Eosinophil-Related Indices
by Yazeed Alshuweishi, Muath Alsaidan, Ahmed M. Basudan, Hussam A. Aljohani, Hamad S. Almutairi and Nizar Algarni
Medicina 2025, 61(9), 1579; https://doi.org/10.3390/medicina61091579 (registering DOI) - 31 Aug 2025
Abstract
Background and Objectives: Dyslipidemia, a modifiable cardiovascular risk factor, is associated with chronic low-grade inflammation. While leukocyte-derived indices have been investigated in this context, eosinophil-related inflammatory markers remain underexplored. This study examined patterns of eosinophil-to-lymphocyte ratio (ELR) and eosinophil-adjusted systemic inflammation response index [...] Read more.
Background and Objectives: Dyslipidemia, a modifiable cardiovascular risk factor, is associated with chronic low-grade inflammation. While leukocyte-derived indices have been investigated in this context, eosinophil-related inflammatory markers remain underexplored. This study examined patterns of eosinophil-to-lymphocyte ratio (ELR) and eosinophil-adjusted systemic inflammation response index (EA-SIRI) across dyslipidemia phenotypes. Materials and Methods: In this retrospective study, adult subjects were classified into six dyslipidemia phenotypes. Leukocyte-derived indices were evaluated across groups, and analyses included comparisons of medians, prevalence rates, tertile distributions, odds ratios, and risk estimates. Results: Both ELR and EA-SIRI were significantly higher in individuals with atherogenic dyslipidemia (ELR: 0.18; EA-SIRI: 1.53) and combined dyslipidemia (ELR: 0.17; EA-SIRI: 1.49) compared to the normolipidemic group (ELR: 0.11; EA-SIRI: 0.92). Notably, these patterns were more pronounced in males aged <40 years and younger females (<40), suggesting sex- and age-related variations in eosinophil-related inflammatory responses to dyslipidemia. Moreover, the highest tertiles of both ELR and EA-SIRI exhibited higher triglycerides and lower HDL-C compared to the lowest tertiles (p < 0.001). The odds of atherogenic dyslipidemia were more than doubled in individuals with elevated ELR (OR = 2.02; p < 0.001) and EA-SIRI (OR = 2.19; p < 0.001). ROC curve analysis indicated modest discriminative power for identifying atherogenic dyslipidemia, with ELR and EA-SIRI yielding AUC of 0.60 (p < 0.001) and 0.62 (p < 0.001), respectively. Conclusions: Our findings suggest eosinophil-related inflammation contributes to immunometabolic dysregulation underlying dyslipidemia. ELR and EA-SIRI may offer insights into inflammation-driven lipid disturbances and help detect subclinical inflammatory activity associated with atherogenic lipid profiles. Full article
(This article belongs to the Section Epidemiology & Public Health)
17 pages, 8807 KB  
Article
Establishing Human and Canine Xenograft Murine Osteosarcoma Models for Application of Focused Ultrasound Ablation
by Alayna N. Hay, Alex Simon, Lauren N. Ruger, Jessica Gannon, Sheryl Coutermarsh-Ott, Elliana R. Vickers, William Eward, Nathan J. Neufeld, Eli Vlaisavljevich and Joanne Tuohy
Biomedicines 2025, 13(9), 2122; https://doi.org/10.3390/biomedicines13092122 (registering DOI) - 30 Aug 2025
Abstract
Background: Osteosarcoma (OS) is the most commonly occurring type of bone cancer in both humans and canines. The survival outcomes for OS patients have not improved significantly in decades. A novel and innovative treatment option that is currently under investigation for OS in [...] Read more.
Background: Osteosarcoma (OS) is the most commonly occurring type of bone cancer in both humans and canines. The survival outcomes for OS patients have not improved significantly in decades. A novel and innovative treatment option that is currently under investigation for OS in the veterinary field is the focused ultrasound ablation modality, histotripsy. Histotripsy is a non-thermal, non-invasive, non-ionizing ablation modality that destroys tissue through generation of acoustic cavitation. Objective: In the current study, we sought to investigate the utility of an orthotropic OS xenograft murine model for characterization of chronic ablative and clinical outcomes post-histotripsy ablation. Method: Given the high comparative relevance of canine to human OS, histotripsy was delivered to orthotopic OS tumors in both human and canine xenograft murine models. Results: Histotripsy improved limb function in tumor-bearing mice compared to untreated tumor bearing mice. The results of this study demonstrated the utility of the orthotopic OS xenograft murine model for histotripsy-based preclinical studies. Conclusions: The current study is the first published investigation for the use of an orthotopic xenograft murine model for the development of histotripsy ablation for OS. The developmental process of the model, technical limitations, and future directions are discussed. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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14 pages, 1014 KB  
Article
Microbiological Profiles of Patients with Acute Periprosthetic Joint Infection Undergoing Debridement, Antibiotics, Irrigation and Implant Retention (DAIR)
by Alberto Alfieri Zellner, Niclas Watzlawik, Jonas Roos, Gunnar Thorben Rembert Hischebeth, Ernst Molitor, Alexander Franz and Frank Sebastian Fröschen
Antibiotics 2025, 14(9), 873; https://doi.org/10.3390/antibiotics14090873 (registering DOI) - 30 Aug 2025
Abstract
Background: Periprosthetic joint infection (PJI) is one of the most serious complications following total joint arthroplasty. The debridement, antibiotics, irrigation, and implant retention (DAIR) procedure is commonly employed to treat acute, early-stage infections, but its success is highly variable, influenced by factors [...] Read more.
Background: Periprosthetic joint infection (PJI) is one of the most serious complications following total joint arthroplasty. The debridement, antibiotics, irrigation, and implant retention (DAIR) procedure is commonly employed to treat acute, early-stage infections, but its success is highly variable, influenced by factors such as pathogen virulence and antibiotic susceptibility profiles. This study aimed to evaluate the impact of pathogens responsible for these infections on the outcome of DAIR. Methods: This retrospective, single-center study analyzed the microbiological profiles of 116 patients (66 hips and 50 knees) treated for acute periprosthetic joint infections (PJIs) with DAIR between 2018 and 2022. Acute PJI was defined as a duration of symptom less than three weeks, according to the criteria established by the Tsukayama and Izakovicova classification. Preoperative joint aspirations, intraoperatively collected tissue samples, and sonication of the exchanged mobile parts were analyzed for each case. We differentiated between monomicrobial PJI, polymicrobial PJI (defined as the identification of more than one microorganism from preoperative joint fluid aspiration or intraoperative samples), and difficult-to-treat (DTT) pathogens. Results: In this cohort, the following pathogen profiles were identified: culture-negative cases accounted for 11.1% of infections, while 64.2% were attributed to Gram-positive bacteria, 19.8% to Gram-negative bacteria, and 4.9% to fungal pathogens. Among the identified microorganisms, coagulase-negative staphylococci (CNS) were the most frequently detected, exhibiting a notable oxacillin resistance rate of 52.9% and rifampicin resistance rate of 28.7%. Additionally, no significant difference in revision-free implant survival was found between patients with DTT pathogens and/or polymicrobial PJI and those without such infections. Conclusions: This study highlights that pathogens in prosthetic joint infections (PJIs) do not solely determine outcomes, as patient-specific factors (comorbidities, implant type) may also play a key role. Regional variations in pathogens and antibiotic resistance patterns should guide empirical therapy. For instance, this study found a high reliance on vancomycin due to high oxacillin resistance in CNS, the most frequent causative pathogen. Full article
(This article belongs to the Special Issue Orthopedic Infections: Epidemiology and Antimicrobial Treatment)
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15 pages, 408 KB  
Study Protocol
HIITing Anxiety and Depression in Parkinson’s Disease and Multiple Sclerosis—A Study Protocol of a Transdiagnostic Randomized Controlled Trial (HersenFIT)
by Arianne S. Gravesteijn, Marc B. Rietberg, Vincent de Groot, Mark A. Hirsch, Tim Vanbellingen, Richard T. Jaspers, Chris Vriend, Wilma D. J. van de Berg, Odile A. van den Heuvel, Erwin E. H. van Wegen and on behalf of the HersenFIT Consortium
Brain Sci. 2025, 15(9), 945; https://doi.org/10.3390/brainsci15090945 - 29 Aug 2025
Abstract
Background/Objectives: Parkinson’s disease (PD) and multiple sclerosis (MS) are neurological conditions that result in debilitating non-motor symptoms, such as anxiety and depression, which significantly reduce quality of life and often persist despite pharmacological treatment. As a result, effective alternative treatment strategies are needed. [...] Read more.
Background/Objectives: Parkinson’s disease (PD) and multiple sclerosis (MS) are neurological conditions that result in debilitating non-motor symptoms, such as anxiety and depression, which significantly reduce quality of life and often persist despite pharmacological treatment. As a result, effective alternative treatment strategies are needed. Exercise therapy—particularly aerobic training—has shown promise in alleviating non-motor symptoms, potentially through neuroplastic adaptations. However, traditional aerobic exercise is often time-consuming and monotonous, limiting long-term adherence. High-intensity interval training (HIIT) offers a time-efficient and potentially more engaging alternative, though its effects on non-motor symptoms in PD and MS remain understudied. Methods: This transdiagnostic randomized controlled trial will enroll 48 participants (24 PD, 24 MS) with clinically significant affective symptoms (hospital anxiety and depression scale [HADS] ≥ 8). The participants will be randomly assigned to one of three 8-week interventions: (1) HIIT, 5–6 intervals of 45 s of high-intensity cycling; (2) continuous aerobic training (CAT), 50 min of low-intensity cycling; (3) movement advice (MA), step goals, and physical education. The primary (affective symptoms) and secondary outcomes (cognition, fatigue, sleep, motor function) will be assessed at four time points: 4 and 1 weeks pre intervention, and 1 and 4 weeks post intervention. Weekly blood samples and pre/post brain imaging will be collected to study biofluid and MRI measures for potential neuroplasticity. Linear mixed models will analyze the time and group effects. Discussion: This trial will assess whether HIIT can more effectively improve non-motor and motor symptoms in PD and MS than CAT or MA. A multimodal approach will explore both the clinical outcomes and underlying mechanisms, informing scalable and engaging rehabilitation strategies. Full article
(This article belongs to the Section Neuropsychiatry)
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15 pages, 295 KB  
Review
Diagnosing Plantar Plate Injuries: A Narrative Review of Clinical and Imaging Approaches
by Jeong-Jin Park, Hyun-Gyu Seok and Chul Hyun Park
Diagnostics 2025, 15(17), 2188; https://doi.org/10.3390/diagnostics15172188 - 29 Aug 2025
Viewed by 62
Abstract
Background: Plantar plate injuries represent a common yet frequently underdiagnosed etiology of forefoot pain and metatarsophalangeal joint instability. Diagnostic accuracy is often compromised by nonspecific clinical presentations and significant symptom overlap with other forefoot pathologies, including Morton’s neuroma and synovitis. Early and accurate [...] Read more.
Background: Plantar plate injuries represent a common yet frequently underdiagnosed etiology of forefoot pain and metatarsophalangeal joint instability. Diagnostic accuracy is often compromised by nonspecific clinical presentations and significant symptom overlap with other forefoot pathologies, including Morton’s neuroma and synovitis. Early and accurate identification is essential to prevent progression to irreversible deformity. Methods: This narrative review synthesizes recent literature on the clinical evaluation, imaging modalities, and differential diagnosis of plantar plate injuries. A comprehensive literature search in a narrative review format of key databases and relevant journals was performed to critically appraise the diagnostic accuracy, advantages, limitations, and clinical implications of various diagnostic techniques. Results: Physical examination maneuvers—including the drawer test, toe purchase test, and Kelikian push-up test—provide important diagnostic insights but are constrained by operator dependency and lack of standardization. Among imaging modalities, MRI and dynamic ultrasound offer high diagnostic utility, with MRI providing superior specificity and ultrasound enabling functional, real-time assessment. Emerging techniques such as dorsiflexion-stress MRI and dual-energy CT show promising diagnostic potential, though broader clinical validation is lacking. Differential diagnosis remains a major challenge, given the clinical and radiological similarities shared with other forefoot conditions. Conclusions: Accurate diagnosis of plantar plate injuries necessitates a multimodal strategy that combines clinical suspicion, structured physical examination, and advanced imaging. Acknowledging the limitations of each diagnostic modality and integrating findings within the broader clinical context are essential for timely and accurate diagnosis. Future research should prioritize validation of diagnostic criteria, enhanced access to dynamic imaging, and the development of consensus-based grading systems to improve diagnostic precision and patient outcomes. Full article
(This article belongs to the Special Issue Advances in Foot and Ankle Surgery: Diagnosis and Management)
17 pages, 2501 KB  
Article
Nontraumatic Fat Embolism and Fat Embolism Syndrome in Patients with Purulent Bacterial Bronchopneumonia
by Beáta Ágnes Borsay, Barbara Dóra Halasi, Róbert Kristóf Pórszász, Katalin Károlyi, Teodóra Tóth and Péter Attila Gergely
J. Clin. Med. 2025, 14(17), 6097; https://doi.org/10.3390/jcm14176097 - 28 Aug 2025
Viewed by 210
Abstract
Background: Fat embolism frequently occurs as a result of trauma, such as long bone fractures and orthopedic surgeries, as well as in certain non-traumatic conditions. The formation can be attributed to mechanical or biochemical processes. According to Hullman’s biochemical hypothesis, elevated C-reactive [...] Read more.
Background: Fat embolism frequently occurs as a result of trauma, such as long bone fractures and orthopedic surgeries, as well as in certain non-traumatic conditions. The formation can be attributed to mechanical or biochemical processes. According to Hullman’s biochemical hypothesis, elevated C-reactive protein levels facilitate the precipitation of very-low-density lipoproteins and chylomicrons, forming fat globules that may result in fat embolism. Based on the abovementioned hypothesis, this study aims to detect fat embolism in autopsy patients (postmortem) suffering from bronchopneumonia and determine its possible role as a cause of death. Methods: A group of autopsies of deceased individuals with bacterial purulent bronchopneumonia with confirmed or presumed elevated C-reactive protein levels was rigorously selected, excluding those with other potential causes of fat embolism such as cardiopulmonary resuscitation, hypothermia, and diabetes mellitus. Multiple organs were sampled for frozen section analysis using Oil Red O fat staining and assessed for the presence and extent of fat embolism. The Falzi score, as modified by Janssen, was employed for the lung tissue. Results: In 73% of the cases, predominantly sporadic, Grade 0 or Grade I fat embolism was observed; however, in none of the cases was fat embolism identified as the cause of death or as a significant contributing factor. Furthermore, neither fat embolism syndrome nor multiorgan fat embolism were detected. Conclusions: Although an elevated C-reactive protein level facilitates the formation of fat globules and fat embolism, its role as a direct cause of mortality remains uncertain. It may predispose individuals to such conditions and potentially interact with other factors, such as minor soft tissue trauma, to exacerbate the severity of fat embolism or its clinical manifestations. These findings underscore the necessity for further comprehensive investigations within the contexts of infection/inflammation, fat embolism, and dyslipidemia. Full article
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12 pages, 232 KB  
Article
Surgical Site Infection Rate in Sutured Versus Stapled Wound Closure After Orthopedic Limb Surgeries: A Prospective Cohort Study
by Nada Naaman, Danya Aljafari, Tala Allam, Omar Batouk, Muhammad Anwar Khan, Syed Faisal Zaidi and Mona Aldabbagh
Surgeries 2025, 6(3), 72; https://doi.org/10.3390/surgeries6030072 - 28 Aug 2025
Viewed by 139
Abstract
Objectives: Surgical site infection (SSI) is a demanding post-surgical complication. SSI has been linked to significant morbidity, mortality, and rising healthcare expenditure. Staples and sutures are the most utilized methods in orthopedic skin closure. The aim of this study was to compare the [...] Read more.
Objectives: Surgical site infection (SSI) is a demanding post-surgical complication. SSI has been linked to significant morbidity, mortality, and rising healthcare expenditure. Staples and sutures are the most utilized methods in orthopedic skin closure. The aim of this study was to compare the rate of SSI in sutured versus stapled wound closure after orthopedic limb surgeries. Methods: A prospective cohort study was conducted between September 2019 and March 2021. Patient demographics, method of wound closure, and potential risk factors associated with SSI were recorded. A multivariate logistic regression analysis was performed to identify independent risk factors associated with SSI. Results: A total of 775 patients were included. Eighteen patients (2.3%) acquired an SSI. 3.5% of the staples group and 1.1% of the suture group contracted an SSI (p = 0.028, univariate analysis). Length of hospital stay (LOS) was significantly higher in the staples group (p < 0.001). Use of antibiotics (AOR 5.938; 95%CI 1.693–20.820), LOS (AOR: 1.047, 95% CI:1.013–1.083), and duration of antibiotic prophylaxis (AOR:1.076, 95% CI: 1.010–1.147) were independent risk factors of SSI. Conclusions: The use of staples was associated with longer hospital stays. Use of antibiotics, prolonged hospital stays, and extended antibiotic prophylaxis were independent risk factors for SSI. These findings suggest that the choice of closure method may impact hospital stay, which could influence SSI risk. Full article
16 pages, 481 KB  
Review
Resident Training in Minimally Invasive Spine Surgery: A Scoping Review
by Michael C. Oblich, James G. Lyman, Rishi Jain, Dillan Prasad, Sharbel Romanos, Nader Dahdaleh, Najib E. El Tecle and Christopher S. Ahuja
Brain Sci. 2025, 15(9), 936; https://doi.org/10.3390/brainsci15090936 - 28 Aug 2025
Viewed by 135
Abstract
Background/Objectives: Minimally invasive spine surgery (MISS) is complex and requires proficiency with a variety of technological and robotic modalities. Acquiring these skills is a long and involved process, often with a steep learning curve. This paper seeks to characterize the state of [...] Read more.
Background/Objectives: Minimally invasive spine surgery (MISS) is complex and requires proficiency with a variety of technological and robotic modalities. Acquiring these skills is a long and involved process, often with a steep learning curve. This paper seeks to characterize the state of MISS training in neurosurgical and orthopedic residency programs, focusing on their effectiveness at minimizing substantial learning curves in the field, as well as highlighting potential areas for future growth. Methods: We conducted a scoping review of the PubMed, Scopus, and Embase databases utilizing the PRISMA extension for scoping reviews. Results: Of the 100 studies initially identified, 16 were included in our final analysis. MISS training types could be broadly grouped into four categories: virtual simulation (including AR and VR), physical models, hybrid didactic and simulation, and mentored training. Training with these modalities led to improvements in resident performance across multiple different MISS techniques, including percutaneous pedicle screw fixation, MIS dural repair, MIS-TLIF, MIS-LLIF, MIS-ULBD, microscopic discectomy/disk herniation repair, percutaneous needle placement, and surgical navigation. Specific improvements included reduced error rate, operation time, and fluoroscopy exposure, as well as increased procedural knowledge, accuracy, and confidence. Conclusions: The incorporation of MISS training modalities in spine surgery residency leads to increases in simulated performance and could serve as a means of overcoming significant learning curves in the field. Full article
(This article belongs to the Special Issue Neurosurgery: Minimally Invasive Surgery in Brain and Spine)
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20 pages, 2622 KB  
Case Report
WHO Grade II or III Solitary Fibrous Tumors (Hemangiopericytomas) of the Spine: Two Case Reports with a Comprehensive Review of the Literature
by Kazuyuki Segami, Yutaro Okamura, Syu Takahashi, Yasuo Ueda, Koji Kanzaki and Yoshifumi Kudo
J. Clin. Med. 2025, 14(17), 6068; https://doi.org/10.3390/jcm14176068 - 27 Aug 2025
Viewed by 266
Abstract
Solitary fibrous tumors (SFTs) of the spine are rare. SFTs, especially those classified as WHO grade II or III (previously termed hemangiopericytomas), are aggressive neoplasms with a high recurrence rate and metastatic potential. In the literature, descriptions of SFTs are limited to case [...] Read more.
Solitary fibrous tumors (SFTs) of the spine are rare. SFTs, especially those classified as WHO grade II or III (previously termed hemangiopericytomas), are aggressive neoplasms with a high recurrence rate and metastatic potential. In the literature, descriptions of SFTs are limited to case reports and small case series. To our knowledge, 157 cases, including the current case, have been reported since Schirger’s 1958 report on spinal SFTs. This report describes two cases of WHO grade II and III SFTs in the spine and presents a review of the literature. In the first case, an extradural WHO grade II SFT recurred 6 years after the first surgery, and a second surgery was performed, including wide excision of the surrounding tissue. The patient has remained recurrence-free for 16 years since the second surgery. In the second case, an intradural extramedullary WHO grade III SFT was resected, including the dura mater, and the patient has remained recurrence-free for 3 years since the surgery. Few reports have described tumor recurrence and long-term outcomes after reoperation, as in the first case, or extensive resection including the dura, as in the second case. Furthermore, the literature review not only summarizes patients’ general and surgical information, but also indicates, based on multivariate analysis, that gross total resection (GTR) is an important factor in preventing recurrence and metastasis. This is the first study to comprehensively examine previous reports and identify risk factors for recurrence and metastasis. In addition, because recurrences have been reported long after surgery, we believe that even if GTR is performed surgically, it is important to conduct follow-ups to check for long-term recurrence. Full article
(This article belongs to the Section Orthopedics)
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39 pages, 4115 KB  
Review
Navigation Between Alzheimer’s Disease (AD) and Its Various Pathophysiological Trajectories: The Pathogenic Link to Neuroimmunology—Genetics and Neuroinflammation
by Abdalla Bowirrat, Albert Pinhasov, Aia Bowirrat and Rajendra Badgaiyan
Int. J. Mol. Sci. 2025, 26(17), 8253; https://doi.org/10.3390/ijms26178253 - 26 Aug 2025
Viewed by 628
Abstract
One hundred and eighteen years have passed since Alzheimer’s disease (AD) was first diagnosed by Alois Alzheimer as a multifactorial and complex neurodegenerative disorder with psychiatric components. It is inaugurated by a cascade of events initiating from amnesic-type memory impairment leading to the [...] Read more.
One hundred and eighteen years have passed since Alzheimer’s disease (AD) was first diagnosed by Alois Alzheimer as a multifactorial and complex neurodegenerative disorder with psychiatric components. It is inaugurated by a cascade of events initiating from amnesic-type memory impairment leading to the gradual loss of cognitive and executive capacities. Pathologically, there is overwhelming evidence that clumps of misfolded amyloid-β (Aβ) and hyperphosphorylated tau protein aggregate in the brain. These pathological processes lead to neuronal loss, brain atrophy, and gliosis culminating in neurodegeneration and fueling AD. Thus, at a basic level, abnormality in the brain’s protein function is observed, causing disruption in the brain network and loss of neural connectivity. Nevertheless, AD is an aging disorder caused by a combination of age-related changes and genetic and environmental factors that affect the brain over time. Its mysterious pathology seems not to be limited to senile plaques (Aβ) and neurofibrillary tangles (tau), but to a plethora of substantial and biological processes, which have also emerged in its pathogenesis, such as a breakdown of the blood–brain barrier (BBB), patients carrying the gene variant APOE4, and the immuno-senescence of the immune system. Furthermore, type 2 diabetes (T2DM) and metabolic syndrome (MS) have also been observed to be early markers that may provoke pathogenic pathways that lead to or aggravate AD progression and pathology. There are numerous substantial AD features that require more understanding, such as chronic neuroinflammation, decreased glucose utilization and energy metabolism, as well as brain insulin resistance (IR). Herein, we aim to broaden our understanding and to connect the dots of the multiple comorbidities and their cumulative synergistic effects on BBB dysfunction and AD pathology. We shed light on the path-physiological modifications in the cerebral vasculature that may contribute to AD pathology and cognitive decline prior to clinically detectable changes in amyloid-beta (Aβ) and tau pathology, diagnostic biomarkers of AD, neuroimmune involvement, and the role of APOE4 allele and AD–IR pathogenic link—the shared genetics and metabolomic biomarkers between AD and IR disorders. Investment in future research brings us closer to knowing the pathogenesis of AD and paves the way to building prevention and treatment strategies. Full article
(This article belongs to the Special Issue Pharmacological Treatment of Neuroinflammation)
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15 pages, 2398 KB  
Article
Propensity Score-Matched Comparison of Six-Strand All-Inside and Conventional Four-Strand Hamstring Autografts for ACL Reconstruction
by Young Jin Seo, Si Young Song and Dongju Kim
J. Clin. Med. 2025, 14(17), 6010; https://doi.org/10.3390/jcm14176010 - 25 Aug 2025
Viewed by 301
Abstract
Background/Objectives: All-inside ACL reconstruction has emerged as a minimally invasive alternative to conventional techniques, with potential advantages in graft configuration and reduced surgical trauma. This study aimed to compare the clinical outcomes of all-inside and full tibial tunnel ACL reconstruction, focusing on graft [...] Read more.
Background/Objectives: All-inside ACL reconstruction has emerged as a minimally invasive alternative to conventional techniques, with potential advantages in graft configuration and reduced surgical trauma. This study aimed to compare the clinical outcomes of all-inside and full tibial tunnel ACL reconstruction, focusing on graft diameter, postoperative stability, and functional recovery. We hypothesized that the all-inside technique would allow for thicker grafts and yield superior postoperative knee stability and functional outcomes, with postoperative anterior laxity as a major outcome of interest. Methods: This retrospective comparative study reviewed patients who underwent ACL reconstruction between January 2020 and February 2024. From January 2020 to September 2022, a four-strand hamstring autograft with full tibial tunnel technique (FT-4) was used, while from September 2022, a six-strand hamstring autograft with the all-inside technique (AI-6) was adopted to enable thicker grafts and optimize fixation. Among a total of 103 patients, 1:1 propensity score matching (PSM) was performed based on age, sex, BMI, laterality, ALL reconstruction, meniscal lesion, and preoperative anterior laxity (SSD). Graft diameter and clinical outcomes, including knee stability and functional scores, were compared between the matched groups. Results: After PSM, two comparable groups of 29 patients each were established. Graft diameter was significantly larger in the AI-6 group (9.5 ± 0.7 mm) compared to the FT-4 group (7.8 ± 0.8 mm, p < 0.001), while other baseline characteristics remained well balanced between the groups. At the final follow-up, both groups exhibited significant improvements in anterior laxity, functional scores, and pivot shift grades (all p < 0.001). The AI-6 group demonstrated superior outcomes with a significantly higher Lysholm score (82.2 ± 6.7 vs. 75.6 ± 8.9, p = 0.002), lower WOMAC score (8.0 ± 4.3 vs. 12.9 ± 10.5, p = 0.023), and reduced anterior laxity (1.6 ± 1.1 mm vs. 2.5 ± 1.4 mm, p = 0.005) compared to the FT-4 group, whereas no significant differences were observed in the IKDC, Tegner, Korean knee score, or pivot shift test results. A simple linear regression revealed a significant negative correlation between graft diameter and postoperative anterior laxity (B = −0.398, p = 0.048). Conclusions: The present study demonstrated that the use of a six-strand hamstring graft configuration in the AI-6 technique resulted in significantly thicker grafts and was associated with reduced postoperative anterior knee laxity compared to the FT-4 technique. While interpretation of these findings requires caution in light of MCID thresholds, the AI-6 group showed favorable outcomes in anterior laxity and selected functional scores, such as the Lysholm and WOMAC. This technique may offer practical clinical value, particularly in populations prone to smaller graft diameters, as it facilitates adequate graft thickness through multifold preparation, with the all-inside approach accommodating the inherent graft shortening. Full article
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14 pages, 692 KB  
Systematic Review
Image-Based Robotic Unicompartmental Knee Arthroplasty Results in Fewer Radiologic Outliers with No Impact on Revision Rates Compared to Imageless Systems: A Systematic Review
by Horia Tomescu, George M. Avram, Giacomo Pacchiarotti, Randa Elsheikh, Octav Russu, Andrej M. Nowakowski, Michael T. Hirschmann and Vlad Predescu
J. Clin. Med. 2025, 14(17), 5996; https://doi.org/10.3390/jcm14175996 - 25 Aug 2025
Viewed by 345
Abstract
Background: Robotic-assisted unicompartmental knee arthroplasty (UKA) enhances the precision of component alignment compared to conventional techniques. Although various robotic systems exist, direct comparisons assessing their relative clinical performance remain limited. The purpose of this study is to provide a comparison between image-based [...] Read more.
Background: Robotic-assisted unicompartmental knee arthroplasty (UKA) enhances the precision of component alignment compared to conventional techniques. Although various robotic systems exist, direct comparisons assessing their relative clinical performance remain limited. The purpose of this study is to provide a comparison between image-based and imageless robotic UKA. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Five databases were searched: PubMed (via MEDLINE), Epistemonikos, Cochrane Library, Web of Science, and Scopus. Inclusion criteria were (1) studies comparing rUKA and cUKA with radiologic parameters and revision rates (prospective or retrospective), (2) human subjects, (3) meta-analyses for cross-referencing, and (4) English language. Data collected included (1) pre- and postoperative radiologic parameters, (2) radiologic outliers, and (3) revisions and their causes. A random-effects meta-analysis was employed to enable a generalizable comparison. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated for continuous variables, and log odds ratios (LORs) with 95% CIs for binary outcomes. Results: Image-based robotic UKA was associated with fewer joint line height outliers (LOR = 3.5, 95% CI: 0.69–6.30, p = 0.015) using a 2° threshold. HKA outliers (thresholds 2–3°) were also reduced (LOR = 0.6, 95% CI: 0.09–1.19, p = 0.024). Posterior tibial and posterior femoral implant fit were significantly lower with image-based systems (LOR = 1.7, 95% CI: 1.37–2.03, respectively, LOR = 1.7, 95% CI: 1.29–1.91; p < 0.001 for both). No significant differences in revision rates were observed. Conclusions: Image-based robotic systems may result in fewer outliers in key radiologic parameters, including hip–knee angle, joint-line height, posterior tibial, and posterior femoral fit, though reporting remains highly heterogeneous. Full article
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13 pages, 667 KB  
Article
Evaluation of the Diagnostic Accuracy of Serum Albumin and Globulin in Pyogenic Spondylitis
by Hideo Mitsui, Hyonmin Choe, Masashi Shimoda, Hironori Yamane, Yuta Hieda, Koki Abe, Yohei Ito, Hiroyuki Ike, Ken Kumagai, Naomi Kobayashi and Yutaka Inaba
J. Clin. Med. 2025, 14(17), 6001; https://doi.org/10.3390/jcm14176001 - 25 Aug 2025
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Abstract
Background: Serum markers are commonly used to diagnose bone and joint infections; however, their accuracy for diagnosing pyogenic spondylitis remains unproven. This study aimed to validate the diagnostic accuracy of inflammatory, nutritional, and immunological serum markers for spinal infections and identify the most [...] Read more.
Background: Serum markers are commonly used to diagnose bone and joint infections; however, their accuracy for diagnosing pyogenic spondylitis remains unproven. This study aimed to validate the diagnostic accuracy of inflammatory, nutritional, and immunological serum markers for spinal infections and identify the most effective combinations. Methods: The retrospective cohort study analyzed 656 patients who visited the hospital for spinal diseases between 1 January 2004 and 31 March 2021; a total of 76 were diagnosed with pyogenic spondylitis. Blood samples were analyzed for serum albumin (Alb), total protein (TP), globulin (Glb), C-reactive protein (CRP), platelet count, white blood cell count, neutrophil count, lymphocyte count, and monocyte count. Combination markers, including albumin–globulin ratio (AGR), CRP–albumin ratio (CAR), CRP–AGR (CAGR), neutrophil–lymphocyte ratio (NLR), and platelet–lymphocyte ratio (PLR), were also evaluated. Receiver operating characteristic curves were used to determine each marker’s diagnostic performance. Furthermore, multivariate analysis was performed to examine the odds ratios. Results: Patients with pyogenic spondylitis showed significantly different levels in Alb (p < 0.0001), Glb (p < 0.0001), CRP (p < 0.0001), platelet count (p < 0.0001), WBC count (p < 0.0006), neutrophil count (p = 0.0019), lymphocyte count (p = 0.0085), AGR (p < 0.0001), CAR (p < 0.0001), CAGR (p < 0.0001), NLR (p < 0.0001), and PLR (p < 0.0001). CRP (AUC = 0.80) showed good diagnostic accuracy, while combination markers CAR (AUC = 0.82) and CAGR (AUC = 0.83) had the highest areas under the curve (AUC). Multivariate analysis indicated that decreased age and the presence of comorbidities (including chronic kidney disease, chronic liver disease, malignancy, or diabetes), were independent predictors of early pyogenic spondylitis (OR_age = 0.93, OR_comorbidities = 16.98, p_age = 0.0005, and p_comorbidities = 0.0001). In patients with low-inflammatory pyogenic spondylitis, significant differences were observed in TP (p = 0.0293), Glb (p = 0.0012), CRP (p = 0.0023), platelet count (p = 0.0108), AGR (p = 0.0044), CAR (p = 0.0006), CAGR (p = 0.0004), PLR (p = 0.0192), and NLR (p = 0.0027), with CAGR showing the highest AUC (AUC = 0.70) among them. Conclusions: Serum combination markers (AGR, CAGR, CAR, PLR, and NLR) showed diagnostic value for pyogenic spondylitis, with CAGR achieving the highest accuracy. In low-inflammatory pyogenic spondylitis patients (CRP ≤ 1.0 mg/dL), these markers may aid diagnosis. Full article
(This article belongs to the Special Issue Clinical Advances in Orthopedic Infections)
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17 pages, 5829 KB  
Article
Improving Efficacy and Reducing Systemic Toxicity: An In Vitro Study on the Role of Electrospun Gelatin Nanofiber Membrane for Localized Melanoma Treatment
by Jason Sun, Yi-Chung Lai, Bing-Wu Shee, Chih-Hsiang Fang, Ching-Yun Chen and Jui-Sheng Sun
Bioengineering 2025, 12(9), 910; https://doi.org/10.3390/bioengineering12090910 - 25 Aug 2025
Viewed by 411
Abstract
Malignant melanoma is a highly metastatic skin cancer, representing about 5% of all cancer diagnoses in the United States. Conventional chemotherapy often has limited effectiveness and severe systemic side effects. This study explores a localized, topical delivery system using cisplatin-loaded nanomembranes as a [...] Read more.
Malignant melanoma is a highly metastatic skin cancer, representing about 5% of all cancer diagnoses in the United States. Conventional chemotherapy often has limited effectiveness and severe systemic side effects. This study explores a localized, topical delivery system using cisplatin-loaded nanomembranes as a safer and more targeted alternative. Cell viability assays established the safe cisplatin concentrations for tissue culture. Gelatin-based nanomembranes incorporating cisplatin were fabricated via electrospinning. Biocompatibility and therapeutic efficacy were tested by applying the membranes to cultured melanoma and normal skin cells. Controlled drug release profiles were evaluated by adjusting cross-linking times. Cisplatin concentration between 3.125 and 12.5 µg/mL were found safe. Nanomembranes with these doses effectively eliminated melanoma cells with minimal harm to healthy skin cells. Drug-free membranes showed high biocompatibility. Cross-linking duration allowed tunable and stable drug release. Cisplatin-loaded gelatin nanomembranes offer a promising topical therapy for melanoma, enhancing drug targeting while reducing systemic toxicity. This approach may serve as a cost-effective alternative to systemic treatments like immunotherapy. Future research will focus on in vivo testing and clinical application. Full article
(This article belongs to the Section Nanobiotechnology and Biofabrication)
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