Search Results (4,567)

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

Ischemic stroke is a primary cause of cerebrovascular diseases and continues to be one of the leading causes of death and disability among patients worldwide. Pathological processes caused by vascular damage due to stroke occur in a time-dependent manner and are classified into three categories: acute, subacute, and chronic. Current treatments for ischemic stroke are limited to effectiveness in the early stages. In this study, we investigated the therapeutic effect of an oriental medicine, Gosha-jinki-gan (TJ107), on improving chronic ischemic stroke using the mouse model with middle cerebral artery occlusion (MCAO). The changes in the intracerebral inflammatory response (macrophages (F4/80), TLR2•4, IL-23, IL-17, TNF-α, and IL-1β) were examined using real-time RT-PCR. The MCAO mice showed the increased expression of glial fibrillary acidic protein (GFAP) and of F4/80, TLR2, TLR4, IL-1β, TNF-α, and IL-17 in the brain tissue from the MCAO region. This suggests that they contribute to the expansion of the ischemic stroke infarct area and to the worsening of the neurological symptoms of the MCAO mice in the chronic phase. On the other hand, the administration of TJ107 was proven to reduce the infarct area, with decreased GFAP expression, suppressed macrophage infiltration in the brain, and reduced TNF-α, IL-1β, and IL-17 production compared with the MCAO mice. This study first demonstrated Gosha-jinki-gan’s therapeutic effects on the chronic ischemic stroke. Full article

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a worldwide challenge. There are an estimated 17–24 million patients worldwide, with an estimated 60 percent or more who have not been diagnosed. Without a known cure, no specific curative medication, disability lasting years to being life-long, and disagreement among healthcare providers as to how to most appropriately treat these patients, ME/CFS patients are in need of assistance. Appropriate healthcare provider education would increase the percentage of patients diagnosed and treated; however, in-school healthcare provider education is limited. To address the latter issue, the New Jersey Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Association (NJME/CFSA) has developed an independent, incentive-driven, learning program for students of the health professions. NJME/CFSA offers a yearly scholarship program in which applicants write a scholarly paper on an ME/CFS-related topic. The efficacy of the program is demonstrated by the 2024–2025 first place scholarship winner’s essay, which addresses the biological basis of ME/CFS and how the healthcare provider can improve the quality of life of ME/CFS patients. For the reader, the essay provides an update on what is known regarding the biological underpinnings of ME/CFS, as well as a medical student’s perspective as to how the clinician can provide care and support for ME/CFS patients. The original essay has been slightly modified to demonstrate that ME/CFS is a worldwide problem and for publication. Full article

Study Design: Prospective observational study. Background: Lumbar spinal stenosis (LSS) impairs balance and gait function, increasing fall risk and limiting quality of life. Although postoperative recovery of balance is clinically important, longitudinal data using multidimensional balance assessments are limited. Methods: A prospective cohort study was conducted in 101 patients (mean age 74.9 ± 6.9 years) undergoing surgery for LSS. The Brief Balance Evaluation Systems Test (Brief BESTest), Oswestry Disability Index (ODI), Modified Falls Efficacy Scale (MFES), Zurich Claudication Questionnaire (ZCQ), and Visual Analog Scales (VAS) for pain/numbness were evaluated preoperatively and at 6 and 12 months postoperatively. Changes over time and correlations between Brief BESTest and PROMs were analyzed. Results: The total Brief BESTest score significantly improved from 13.3 ± 5.3 preoperatively to 16.1 ± 5.1 at 6 months and 16.0 ± 5.1 at 12 months (p < 0.01). Subdomains including Anticipatory Adjustments, Postural Responses, Sensory Orientation, and Stability in Gait improved significantly, while Stability Limits did not. At 12 months postoperatively, ODI decreased by 19.1%, ZCQ symptom and function scores improved by 0.8 and 0.9 points, respectively, and VAS scores improved by 17.1 mm for low back pain, 26.5 mm for lower limb pain, and 19.5 mm for numbness, all showing marked improvements from baseline. MFES also increased significantly postoperatively. The Brief BESTest score correlated significantly with MFES and ZCQ-PFS at baseline, and with ODI, ZCQ, and VAS scores at 12 months. Conclusions: Balance ability in LSS patients improved after surgery, as measured by the Brief BESTest, with clinically meaningful changes maintained for 12 months. Improvements in balance were significantly associated with reductions in pain, disability, and fear of falling, suggesting the Brief BESTest is a comprehensive indicator of postoperative recovery. Full article

Background/Objectives: Correction surgery for adult spinal deformity (ASD) reduces disability but may lead to spinal stiffness. Cultural diversity may also influence how this stiffness affects daily life. We aimed to evaluate the impact of correction surgery on Japanese patients with ASD using a newly developed questionnaire and to clarify how these patients adapt to their living environment postoperatively in response to spinal stiffness. Methods: This retrospective study included 74 Japanese patients with operative ASD (mean age: 68.2 ± 7.5 years; fusion involving >5 levels) with a minimum follow-up of 1 year. Difficulties in performing various activities of daily living (ADLs) were assessed using a novel 20-item questionnaire tailored to the Oriental lifestyle. The questionnaire also evaluated lifestyle and environmental changes after surgery. Sagittal and coronal spinal parameters were measured using whole-spine radiographs, and clinical outcomes were assessed using the ODI and SRS-22 scores. Results: Coronal and sagittal alignment significantly improved postoperatively. Although the total ADL score remained unchanged, four trunk-bending activities showed significant deterioration. The lower instrumented vertebrae level and pelvic fusion were associated with lower scores in 11 items closely related to trunk bending or the Oriental lifestyle. After surgery, 61% of patients switched from a Japanese-style mattress to a bed, and 72% swapped their low dining table for one with chairs. Both the ODI and SRS-22 scores showed significant postoperative improvements. Conclusions: Trunk-bending activities worsened postoperatively in Japanese patients with ASD, especially those who underwent pelvic fusion. Additionally, patients often modified their living environment after surgery to accommodate spinal stiffness. Full article

Diabetes mellitus (DM) is one of the leading causes of death and disability worldwide and its prevalence continues to rise. Chronic hyperglycemia exposes patients to severe complications. Among these, diabetic vascular lesions are the most destructive. Their primary driver is the synergistic interaction between hyperglycemia-induced oxidative stress and chronic inflammation. This review systematically elucidates how multiple pathological pathways—namely, metabolic dysregulation, mitochondrial dysfunction, endoplasmic reticulum stress, and epigenetic reprogramming—cooperate to drive oxidative stress and inflammatory cascades. Confronting this complex pathological network, natural products, unlike conventional single-target synthetic drugs, exert multi-target synergistic effects, simultaneously modulating several key pathogenic networks. This enables the restoration of redox homeostasis and the suppression of inflammatory responses, thereby improving vascular function and delaying both microvascular and macrovascular disease progression. However, the clinical translation of natural products still faces multiple challenges and requires comprehensive mechanistic studies and rigorous validation to fully realize their therapeutic potential. Full article

Background: More than 1500 genes are associated with developmental delay and intellectual disability, with variants in many of these genes contributing to a shared phenotype. The discovery of variants of uncertain significance (VUS) found in these genes during genetic testing can lead to ambiguity and further delay in diagnosis and medical management. Phenotyping, additional genetic testing, and functional studies can all add valuable information to help reclassify these variants. Here we demonstrate the clinical utility of epigenetic signatures in prioritizing variants of uncertain significance in genes associated with developmental delay (DD) and intellectual disability (ID). Methods: Genome sequencing was performed in a male with developmental delay. He was found to have VUSs in both PHF6 and DDB1 genes, linked with Börjeson–Forssman–Lehmann syndrome (BFLS) and White–Kernohan syndrome (WHIKERS), respectively. These two disorders share a similar phenotype but have distinct inheritance patterns and molecular pathogenic mechanisms. DNA methylation profiling (DNAm) of whole blood was performed using the clinically validated EpiSign assay. Results: The proband’s methylation profile demonstrated a strong correlation with the BFLS methylation signature, supporting the PHF6 variant as a likely cause of his neurodevelopmental disorder. Conclusions: Epigenetic testing for disorders with distinct methylation patterns can provide diagnostic utility when a patient presents with variants of uncertain significance in genes associated with developmental delay. Epigenetic signatures can also guide genetic counselling and family planning. Full article

Background/Objectives: While intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke (AIS) within 4.5 h of symptom onset, many patients present beyond this time window. Recent trials suggest that IVT may be both effective and safe in selected patients treated after the standard time window. Methods: We searched MEDLINE, Scopus, and ClinicalTrials.gov for randomized-controlled clinical trials (RCTs) and individual patient-data meta-analyses (IPDMs) of RCTs comparing IVT plus best medical treatment (BMT) to BMT alone in AIS patients who were last-known-well more than 4.5 h earlier. The primary efficacy outcome was a 90-day excellent functional outcome [modified Rankin Scale (mRS)-scores of 0–1]. Secondary efficacy outcomes included good functional outcome (mRS-scores 0–2) and reduced disability (≥1-point reduction across all mRS-strata). The primary safety outcome was symptomatic intracranial hemorrhage (sICH); secondary safety outcomes were any ICH and 3-month all-cause mortality. Subgroup analyses were performed stratified by different thrombolytics, time-windows, imaging modalities, and affected circulation. Results: Nine studies were included, comprising 1660 patients in the IVT-group and 1626 patients in the control-group. IVT significantly improved excellent functional outcome (RR = 1.24; 95%CI:1.14–1.34; I² = 0%) and good functional outcome (RR = 1.18; 95%CI:1.05–1.33; I² = 70%). IVT was associated with increased odds of reduced disability (common OR = 1.3; 95%CI:1.15–1.46; I² = 0%) and increased risk of sICH (RR = 2.75; 95%CI:1.49–5.05; I² = 0%). The rates of any ICH and all-cause mortality were similar between the two groups. No significant subgroup differences were documented. Conclusions: IVT in the extended time window improved functional outcomes without increasing mortality, despite a higher rate of sICH. Full article

Background: Multisegmental lumbar degenerative disease (ms-LDD) is a common condition in older adults, often requiring surgical intervention. While rigid stabilization remains the gold standard, it is associated with complications such as adjacent segment disease (ASD), higher blood loss, and longer recovery times. The Dynesys dynamic stabilization system offers an alternative by preserving motion while stabilizing the spine. However, data comparing Dynesys with fusion in multisegmental cases are limited. Objective: This study evaluates the clinical and radiographic outcomes of Dynesys dynamic stabilization versus rigid stabilization in the treatment of ms-LDD. Methods: A retrospective analysis was conducted on 53 patients (mean age: 62.25 ± 15.37 years) who underwent either Dynesys dynamic stabilization (n = 27) or PLIF (n = 26) for ms-LDD involving at least seven motion segments. Clinical outcomes were assessed using the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI), while radiological parameters such as lumbar lordosis (LL), sagittal vertical axis (SVA), and spinopelvic parameters (pelvic incidence, pelvic tilt and, sacral slope) were analyzed. A two-stage surgical approach was employed in the Dynesys group to enhance osseointegration, particularly in elderly osteoporotic patients. Results: Both groups showed significant improvements in VAS and ODI scores postoperatively (p < 0.001), with no significant differences between them. However, the Dynesys group demonstrated superior sagittal alignment correction, with a significant increase in LL (p < 0.002) and a significant decrease in SVA (p < 0.0015), whereas changes in the rigid stabilization group were not statistically significant. Additionally, the Dynesys group had fewer complications, including a lower incidence of ASD (0 vs. 6 cases). The two-stage technique facilitated improved screw osseointegration and reduced surgical risks in osteoporotic patients. Conclusions: Dynesys dynamic stabilization is an effective alternative to rigid stabilization in ms-LDD, offering comparable pain relief and functional improvement while preserving motion and reducing ASD risk. The two-stage approach enhances long-term stability, making it particularly suitable for elderly or osteoporotic patients. Further long-term studies are needed to confirm these findings. Full article

Background: Traumatic brain injury (TBI) remains a significant contributor to global mortality and long-term neurological disability. Accurate prognostic biomarkers are crucial for enhancing prognostic accuracy and guiding personalized clinical management. Objective: This review assesses the prognostic value of arterial spin labeling (ASL), a non-invasive MRI technique, in adult and pediatric TBI, with a focus on quantitative cerebral blood flow (CBF) and arterial transit time (ATT) measures. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and IEEE databases, including observational studies and clinical trials that applied ASL techniques (pCASL, PASL, VSASL, multi-PLD) in TBI patients with functional or cognitive outcomes, with outcome assessments conducted at least 3 months post-injury. Results: ASL-derived CBF and ATT parameters demonstrate potential as prognostic indicators across both acute and chronic stages of TBI. Hypoperfusion patterns correlate with worse neurocognitive outcomes, while region-specific perfusion alterations are associated with affective symptoms. Multi-delay and velocity-selective ASL sequences enhance diagnostic sensitivity in TBI with heterogeneous perfusion dynamics. Compared to conventional perfusion imaging, ASL provides absolute quantification without contrast agents, making it suitable for repeated monitoring in vulnerable populations. ASL emerges as a promising prognostic biomarker for clinical use in TBI. Conclusion: Integrating ASL into multiparametric models may improve risk stratification and guide individualized therapeutic strategies. Full article

Gene replacement using adeno-associated viral (AAV) vectors has become a major therapeutic avenue for neurodegenerative diseases (NDD). In single-gene diseases with loss-of-function mutations, the objective of gene therapy is to express therapeutic transgenes abundantly in cell populations that are implicated in the pathological phenotype. X-ALD is one of these orphan diseases. It is caused by ABCD1 gene mutations and its main clinical form is adreno-myelo-neuropathy (AMN), a disabling spinal cord axonopathy starting in middle-aged adults. Unfortunately, the main cell types involved are yet poorly identified, complicating the choice of cells to be targeted by AAV vectors. Pioneering gene therapy studies were performed in the Abcd1^-/y mouse model of AMN with AAV9 capsids carrying the ABCD1 gene. These studies tested ubiquitous or cell-specific promoters, various routes of vector injection, and different ages at intervention to either prevent or reverse the disease. The expression of one of these vectors was studied in the spinal cord of a healthy primate. In summary, gene therapy has made promising progress in the Abcd1^-/y mouse model, inaugurating gene replacement strategies in AMN patients. Because X-ALD is screened neonatally in a growing number of countries, gene therapy might be applied in the future to patients before they become overtly symptomatic. Full article

Background: We aimed to analyze radiographic sagittal balance parameters in patients who underwent a TLIF procedure for single-level degenerative spondylolisthesis with a mean follow-up of 8.6 years and to determine whether lumbar lordosis affects long-term clinical outcomes. Methods: This prospective study included 32 patients who underwent single-level TLIF surgery for degenerative spondylolisthesis. Radiographic analysis of sagittal balance parameters and clinical examination including Oswestry Disability Index (ODI) scores were performed preoperatively, postoperatively, and at the last follow-up. A minimal clinically important difference threshold of 30% was accepted as clinically relevant. Results: Mean postoperative lumbar lordosis (LL) and segmental lordosis (SL) failed to improve postoperatively; nevertheless significant improvements in short- and long-term postoperative ODI scores were demonstrated (p < 0.001). Thoracic kyphosis (TK) and global sagittal balance parameters shifted anteriorly after 8.6 years (p < 0.001), but this increase did not affect clinical outcomes. Conclusions: Adequate decompression and solid bone fusion are foremost required to achieve improved long-term clinical outcomes in single-level TLIF procedures. In our studied cohort, failure to improve lordosis did not impair clinical outcomes postoperatively. With aging, thoracic kyphosis and anterior malalignment increase, and after 8.6 years, clinical improvements are starting to become insignificant. Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic immune-mediated neurological disorder that primarily affects young adults and is frequently accompanied by psychiatric comorbidities such as depression and anxiety, both of which significantly diminish patients’ quality of life (QoL). This study investigated the effect of two oral disease-modifying therapies (DMTs), fingolimod and cladribine, on mental health and QoL in patients with relapsing-remitting MS (RRMS). The aim of the study was to compare levels of depression, anxiety, and health-related quality of life (HRQoL) in RRMS patients treated with fingolimod or cladribine, and to evaluate their associations with clinical and radiological parameters. Materials and Methods: Eighty RRMS patients aged 18 to 50 years with Expanded Disability Status Scale (EDSS) scores of 3.0 or less, no recent disease relapse, and no history of antidepressant use were enrolled. Forty patients were treated with fingolimod and forty with cladribine. Depression and anxiety were assessed using the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). QoL was evaluated using the Multiple Sclerosis QoL-54 (MSQOL-54) instrument. Additional clinical data, including MRI-based lesion burden, EDSS scores, age, disease duration, and occupational status, were collected. Results: No statistically significant differences were observed between the two groups regarding HDRS and HARS scores (p > 0.05). However, patients treated with fingolimod had significantly higher scores in the Energy/Fatigue subdomain (7.55 ± 2.02 vs. 6.56 ± 2.57, p = 0.046) and Composite Mental Health (CMH) score (64.73 ± 15.01 vs. 56.00 ± 18.93, p = 0.029) compared to those treated with cladribine. No significant differences were found in the independent items of the MSQOL-54. A negative correlation was identified between total lesion load and QoL scores. Conclusions: Although fingolimod and cladribine exert comparable effects on depression and anxiety levels, fingolimod may be associated with better mental health outcomes and reduced fatigue in RRMS patients. Furthermore, lesion burden and clinical parameters such as age and EDSS score may independently influence QoL, regardless of the DMT used. Full article

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, largely due to its profound intratumoral heterogeneity and immunosuppressive microenvironment. Various classifications of GBM subtypes were created based on transcriptional and methylation profiles. This effort, followed by the development of new technology such as single-nuclei sequencing (snRNAseq) and spatial transcriptomics, led to a better understanding of the glioma cells’ plasticity and their ability to transition between diverse cellular states. GBM cells can mimic neurodevelopmental programs to resemble oligodendrocyte or neural progenitor behavior and hitchhike the local neuronal network to support their growth. The tumor microenvironment, especially under hypoxic conditions, drives the tumor cell clonal selection, which then reshapes the immune cells’ functions. These adaptations contribute to immune evasion by progressively disabling T cell and myeloid cell functions, ultimately establishing a highly immunosuppressive tumor milieu. This complex and metabolically constrained environment poses a major barrier to effective antitumor immunity and limits the success of conventional therapies. Understanding the dynamic interactions between glioma cells and their microenvironment is essential for the development of more effective immunotherapies and rational combination strategies aimed at overcoming resistance and improving patient outcomes. Full article

Osteoarthritis (OA) remains a major contributor to pain and disability; however, the current management is largely reactive, focusing on symptoms rather than preventing irreversible cartilage loss. This review first examines the mechanistic foundations for pharmacological chondroprotection—illustrating how conventional agents, such as glucosamine sulfate and chondroitin sulfate, can potentially restore extracellular matrix (ECM) components, may attenuate catabolic enzyme activity, and might enhance joint lubrication—and explores the delivery challenges posed by avascular cartilage and synovial diffusion barriers. Subsequently, a practical “What–How–When” framework is introduced to guide community pharmacists in risk screening, DMOAD selection, chronotherapeutic dosing, safety monitoring, and lifestyle integration, as exemplified by the CHONDROMOVING infographic brochure designed for diverse health literacy levels. Building on these strategies, the P4–4P Chondroprotection Framework is proposed, integrating predictive risk profiling (physicians), preventive pharmacokinetic and chronotherapy optimization (pharmacists), personalized biomechanical interventions (physiotherapists), and participatory self-management (patients) into a unified, feedback-driven OA care model. To translate this framework into routine practice, I recommend the development of DMOAD-specific clinical guidelines, incorporation of chondroprotective chronotherapy and interprofessional collaboration into health-professional curricula, and establishment of multidisciplinary OA management pathways—supported by appropriate reimbursement structures, to support preventive, team-based management, and prioritization of large-scale randomized trials and real-world evidence studies to validate the long-term structural, functional, and quality of life benefits of synchronized DMOAD and exercise-timed interventions. This comprehensive, precision-driven paradigm aims to shift OA care from reactive palliation to true disease modification, preserving cartilage integrity and improving the quality of life for millions worldwide. Full article