-
Journal of Cancer 2024Current radiotherapy regimens for glioblastoma (GBM) have limited efficacy and fails to eradicate tumors. Regenerative medicine brings hope for repairing damaged...
Current radiotherapy regimens for glioblastoma (GBM) have limited efficacy and fails to eradicate tumors. Regenerative medicine brings hope for repairing damaged tissue, opening opportunities for elevating the maximum acceptable radiation dose. In this study, we explored the effect of ultra-high dose fractionated radiation on tumor responses and brain injury in immunocompetent mice which can better mimic the tumor-host interactions observed in patients. We also evaluated the role of the hypoxia-inducible factor-1 alpha under radiation as potential target for combating radiation-induced brain injury. : Naïve and Hif-1α heterozygous mice received a fractionated daily dose of 20 Gy for three or five consecutive days. Magnetic resonance imaging (MRI) and histology were performed to assess brain injury post-radiation. The 2×10 human GBM1 luciferase-expressing cells were transplanted with tolerance induction protocol. Fractionated radiotherapy was performed during the exponential phase of tumor growth. Bioluminescence imaging, MRI, and immunohistochemistry staining were performed to evaluate tumor growth dynamics and radiotherapy responses. Additionally, animal lifespan was recorded. : Fractionated radiation of 5×20 Gy induced severe brain damage, starting 3 weeks after radiation. All animals from this group died within 12 weeks. In contrast, later onset and less severe brain injury were observed starting 12 weeks after radiation of 3×20 Gy. It resulted in complete GBM eradication and survival of all treated animals. Furthermore, Hif-1α mice exhibited more severe vascular damage after fractionated radiation of 3×20 Gy. : Ultra-high dose fractionated 3×20 Gy radiation has the potential to fully eradicate GBM cells at the cost of only mild brain injury. The Hif-1α gene is a promising target for ameliorating vascular impairment post-radiation, encouraging the implementation of neurorestorative strategies.
PubMed: 38947383
DOI: 10.7150/jca.95148 -
Neuropsychiatric Disease and Treatment 2024Absence seizures are classically associated with behavioral arrest and transient deficits in consciousness, yet substantial variability exists in the severity of the... (Review)
Review
Absence seizures are classically associated with behavioral arrest and transient deficits in consciousness, yet substantial variability exists in the severity of the impairment. Despite several decades of research on the topic, the pathophysiology of absence seizures and the mechanisms underlying behavioral impairment remain unclear. Several rationales have been proposed including widespread cortical deactivation, reduced perception of external stimuli, and transient suspension of the default mode network, among others. This review aims to summarize the current knowledge on the neural correlates of impaired consciousness in absence seizures. We review evidence from studies using animal models of absence epilepsy, electroencephalography, functional magnetic resonance imaging, magnetoencephalography, positron emission tomography, and single photon emission computed tomography.
PubMed: 38947367
DOI: 10.2147/NDT.S391052 -
Frontiers in Immunology 2024Neuromyelitis optica spectrum disorder (NMOSD) is a clinical syndrome characterized by attacks of acute optic neuritis and transverse myelitis. We report a case with...
Neuromyelitis optica spectrum disorder (NMOSD) is a clinical syndrome characterized by attacks of acute optic neuritis and transverse myelitis. We report a case with paraneoplastic NMOSD that improved after immunosuppressive therapy, surgical resection, and chemotherapy. A 48-year-old woman initially presented with gradual binocular visual loss over the course of one week. The patient was evaluated using magnetic resonance imaging (MRI), computed tomography (CT), visual evoked potential (VEP), pathological biopsy, immunohistochemistry, and autoimmune antibody testing. The brain MRI findings were normal. The VEP revealed prolonged P100 latencies in the right eye and an absence of significant waves in the left eye. Positive serum AQP4-IgG antibodies were found. The patient was diagnosed as NMOSD. Then the patient responded well to treatment with methylprednisolone. An ovarian tumor was found in the patient using abdominal MRI and CT. The tumor was surgically resected, and a pathological biopsy revealed that it was ovarian dysgerminoma. The patient received four rounds of chemotherapy after surgery. One month after the final chemotherapy treatment, a positron emission tomography (PET) scan revealed no tumor. The vision of the patient gradually recovered and serum AQP4 was negative. Furthermore, we summarized the characteristics of patients diagnosed with paraneoplastic NMOSD associated with ovarian neoplasms in previous studies. This is a characteristic case of overlapping NMOSD and ovarian dysgerminoma, demonstrating the importance of tumor therapy in cases of paraneoplastic NMOSD.
PubMed: 38947316
DOI: 10.3389/fimmu.2024.1424243 -
World Journal of Orthopedics Jun 2024Dual mobility (DM) bearings have gained significant attention in the field of total hip arthroplasty (THA) as a valid treatment option in cases of revision for... (Review)
Review
Dual mobility (DM) bearings have gained significant attention in the field of total hip arthroplasty (THA) as a valid treatment option in cases of revision for instability after THA whereas its use in primary THA is still a matter of debate. This manuscript explores the pathology, incidence, diagnosis, treatment options, prognosis, ongoing studies in the literature, and future perspectives related to the use of DM bearings employed in primary THA. DM bearings are primarily designed to address one of the major concerns in THA: Instability of the prosthetic hip. Instability is both for the surgeon and the patient a devastating postoperative complication, leading to significant pain and subsequent apprehension by the patient and may require revision surgeries. The use of DM implants poses the worry of wear-related complications, such as accelerated polyethylene wear and osteolysis, which also pose challenges to long-term implant survival. This technique has seen a steady rise in recent years, with multiple studies reporting favorable outcomes. The incidence of their utilization varies among institutions and surgeons, reflecting differing preferences and patient populations. The diagnosis of instability and wear-related complications in THA often involves clinical assessment, imaging modalities such as X-rays, computed tomography scans, and sometimes advanced imaging techniques like magnetic resonance imaging. DM bearings can be considered as an option when patients present neurologic pathologies such as Parkinson's disease or recurrent dislocations after THA. DM bearings provide an additional articulation point within the implant, facilitating a greater range of motion and inherent stability. This design allows for reduced risk of dislocation and improved functional outcomes. Various implant manufacturers offer different designs and sizes of DM bearings to suit individual patient needs. Current literature suggests that the use of DM bearings in primary THA has demonstrated promising outcomes in terms of enhanced stability, reduced dislocation rates, and improved patient satisfaction. However, long-term studies with larger patient cohorts are necessary to establish the durability and longevity of these implants. Several ongoing studies are investigating the role of DM bearings in primary THA. These studies focus on evaluating long-term implant survivorship, assessing wear patterns, analyzing patient-reported outcomes, and comparing the effectiveness of DM bearings with traditional THA designs. The future of DM bearings in primary THA holds potential for further advancements. Research efforts are aimed at refining implant materials, optimizing designs, and studying the influence of surgical techniques on implant performance. Additionally, continued investigation into the long-term outcomes and cost-effectiveness of DM bearings will play a crucial role in shaping their future use. While further research is warranted, the current evidence supports their potential as a beneficial solution in improving surgical outcomes and patient satisfaction.
PubMed: 38947268
DOI: 10.5312/wjo.v15.i6.512 -
World Journal of Orthopedics Jun 2024A discoid meniscus is a morphological abnormality wherein the meniscus loses its normal 'C' shape. Although most patients are asymptomatic, patients might still present... (Review)
Review
A discoid meniscus is a morphological abnormality wherein the meniscus loses its normal 'C' shape. Although most patients are asymptomatic, patients might still present with symptoms such as locking, pain, swelling, or giving way. Magnetic resonance imaging is usually needed for confirmation of diagnosis. Based on a constellation of factors, including clinical and radiological, different approaches are chosen for the management of discoid meniscus. The purpose of this review is to outline the treatment of discoid meniscus, starting from conservative approach, to the different surgical options for this condition. The PubMed and Google Scholar databases were used for this review. Studies discussing the treatment of discoid meniscus from 2018 to 2023 were searched. Initially there were 369 studies retrieved, and after removal of studies using the exclusion criteria, 26 studies were included in this review. Factors such as stability, presence of tear, and morphology can help with surgical planning. Many approaches have been used to treat discoid meniscus, where the choice is tailored for each patient individually. Postoperatively, factors that may positively impact patient outcomes include male sex, body mass index < 18.5, age at symptom onset < 25 years, and duration of symptoms < 24 months. The conventional approach is partial meniscectomy with or without repair; however, recently, there has been an increased emphasis on discoid-preserving techniques such as meniscoplasty, meniscopexy, and meniscal allograft transplantation.
PubMed: 38947261
DOI: 10.5312/wjo.v15.i6.520 -
World Journal of Orthopedics Jun 2024In this case report featured in , Kelmer describe a rare finding of a 28-year-old female patient who presented with a recurrent fibroreactive nodule 7 months following...
In this case report featured in , Kelmer describe a rare finding of a 28-year-old female patient who presented with a recurrent fibroreactive nodule 7 months following the resection of a primary cyclops lesion, suggesting recurrent cyclops syndrome. The patient had undergone an initial anterior cruciate ligament reconstruction for a non-contact right knee injury and reported successful recovery. Two years later, the patient sustained a repeat right knee injury followed by a positive McMurray test and acute pain with terminal extension. Arthroscopic synovectomy confirmed magnetic resonance imaging (MRI) finding of a cyclops lesion, which was surgically removed. Seven months postoperatively, the patient reported stiffness and difficulty with terminal extension. Repeat MRI indicated a recurrent cyclops lesion, which was surgically resected. Following resection of the second lesion, the patient underwent physical therapy and achieved full range of motion, maintaining complete recovery 19 months postoperatively. Recurrent cyclops lesions have rarely been reported in the literature, and this article is novel in its report of recurrent cyclops syndrome following a bone-patellar tendon-bone allograft. The presentation of this unusual finding exposes a need for further investigation of cyclops lesion pathology, which will aid its prevention and treatment.
PubMed: 38947257
DOI: 10.5312/wjo.v15.i6.495 -
Current Tropical Medicine Reports Dec 2023This review aims to elucidate the etiologies of brain abscesses in the tropics. Despite the similarities in causes of brain abscesses across global regions, tropical...
PURPOSE OF REVIEW
This review aims to elucidate the etiologies of brain abscesses in the tropics. Despite the similarities in causes of brain abscesses across global regions, tropical settings manifest distinguishing characteristics, prominently observed on computed tomography or magnetic resonance imaging.
RECENT FINDINGS
In tropical climates, the leading conditions predisposing individuals to brain abscesses are polymicrobial bacterial infections originating from paranasal sinuses, dental sources, and otitis media. However, the tropics present unique etiologies to be aware of, including (Chagas disease), free-living amoebas like , infections from (melioidosis), fungi such as , and . Given the differential diagnoses, which include neoplastic, inflammatory, and demyelinating diseases, a stereotactic biopsy coupled with a microbiological assessment remains valuable for accurate diagnosis.
SUMMARY
In tropical regions, brain abscesses are a concern when confronted with mass-occupying or other types of brain lesions. Successful clinical management of brain abscesses typically combines surgical intervention and extended anti-microbial treatment. However, specific parasitic invasions like Chagas disease, free-living amoebas, and necessitate targeted anti-parasitic therapies. Furthermore, international policy efforts should focus on prevention measures in resource limited regions with heightened risks and disease burden.
PubMed: 38947183
DOI: 10.1007/s40475-023-00306-8 -
Journal of Pain Research 2024Synovitis, the inflammation of joint synovia, is a prominent feature of osteoarthritis (OA) manifested by enhanced synovial vascularity, endothelial leakage, and...
PURPOSE
Synovitis, the inflammation of joint synovia, is a prominent feature of osteoarthritis (OA) manifested by enhanced synovial vascularity, endothelial leakage, and perivascular oedema. In this pilot study, we assessed the effect of topical diclofenac in hand OA (HOA) using the established semi-quantitative methods Magnetic Resonance Imaging (MRI) and Ultrasonography (US), and compared them with Fluorescent Optical Imaging (FOI), an emerging imaging modality.
PATIENTS AND METHODS
Ten patients with symptomatic and diagnosed HOA used topical diclofenac for 14 days, with FOI, MRI, US, and subjective pain assessed at Baseline and after 7 (Day 8), and 14 (Day 15) days of treatment. Changes in synovitis were assessed for all 10 joints of the hand (via sum scores), and separately for the two joints most affected by synovitis. A new, fully quantitative approach for objective synovitis assessment based on the FOI images was also developed and applied.
RESULTS
The semi-quantitative analysis of the sum scores showed a small decrease in synovitis throughout the treatment duration across the different imaging modalities. The effect of the treatment was more prominent on the two most affected joints, with a synovitis reduction vs Baseline of 21.1% and 34.2% on Day 8 and Day 15, respectively, in the FOI. The quantitative FOI pixel analysis further strengthened the evidence for this effect, with observed reduction of 17.8% and 42.4% for Days 8 and 15, respectively. A similar trend was observed for subjective pain perception, with a reduction of 7.2 and 13.3 mm on Days 8 and 15.
CONCLUSION
This pilot study evidenced the effect of topical diclofenac on reducing synovitis in hand OA in semi- and fully quantitative analyses, with the effect being stronger in the most affected joints. Further, supporting studies are needed to probe the accuracy of the quantitative pixel analysis of FOI images.
PubMed: 38947131
DOI: 10.2147/JPR.S463633 -
Research Square Jun 2024Accurate prediction of the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is crucial for disease management. Machine learning techniques...
Accurate prediction of the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is crucial for disease management. Machine learning techniques have demonstrated success in classifying AD and MCI cases, particularly with the use of resting-state functional magnetic resonance imaging (rs-fMRI) data.This study utilized three years of rs-fMRI data from the ADNI, involving 142 patients with stable MCI (sMCI) and 136 with progressive MCI (pMCI). Graph signal processing was applied to filter rs-fMRI data into low, middle, and high frequency bands. Connectivity-based features were derived from both filtered and unfiltered data, resulting in a comprehensive set of 100 features, including global graph metrics, minimum spanning tree (MST) metrics, triadic interaction metrics, hub tendency metrics, and the number of links. Feature selection was enhanced using particle swarm optimization (PSO) and simulated annealing (SA). A support vector machine (SVM) with a radial basis function (RBF) kernel and a 10-fold cross-validation setup were employed for classification. The proposed approach demonstrated superior performance, achieving optimal accuracy with minimal feature utilization. When PSO selected five features, SVM exhibited accuracy, specificity, and sensitivity rates of 77%, 70%, and 83%, respectively. The identified features were as follows: (Mean of clustering coefficient, Mean of strength)/Radius/(Mean Eccentricity, and Modularity) from low/middle/high frequency bands of graph. The study highlights the efficacy of the proposed framework in identifying individuals at risk of AD development using a parsimonious feature set. This approach holds promise for advancing the precision of MCI to AD progression prediction, aiding in early diagnosis and intervention strategies.
PubMed: 38947050
DOI: 10.21203/rs.3.rs-4549428/v1 -
MedRxiv : the Preprint Server For... Jun 2024Weekly Steroids in Muscular Dystrophy (WSiMD) was a pilot study to evaluate once weekly prednisone in patients with Limb Girdle and Becker muscular dystrophy (LGMD and...
BACKGROUND
Weekly Steroids in Muscular Dystrophy (WSiMD) was a pilot study to evaluate once weekly prednisone in patients with Limb Girdle and Becker muscular dystrophy (LGMD and BMD, respectively). At study endpoint, there were trends towards increased lean mass, reduced fat mass, reduced creatine kinase and improved motor function. The investigation was motivated by studies in mouse muscular dystrophy models in which once weekly glucocorticoid exposure enhanced muscle strength and reduced fibrosis.
METHODS
WSiMD participants provided blood samples for aptamer serum profiling at baseline and after 6 months of weekly steroids. A subset completed magnetic resonance (MR) evaluation of muscle at study onset and endpoint.
RESULTS/CONCLUSIONS
At baseline compared to age and sex-matched healthy controls, the aggregate serum protein profile in the WSiMD cohort was dominated by muscle proteins, reflecting leak of muscle proteins into serum. Disease status produced more proteins differentially present in serum compared to steroid-treatment effect. Nonetheless, a response to prednisone was discernable in the WSiMD cohort, even at this low dose. Glucocorticoids downregulated muscle proteins and upregulated certain immune process- and matrix-associated proteins. Muscle MR fat fraction showed trends with functional status. The prednisone-responsive markers could be used in larger trial of prednisone efficacy.
PubMed: 38947030
DOI: 10.1101/2024.06.14.24308858