Search Results (2,062)

Background and aim: Advanced Therapy Medicinal Products (ATMPs) are innovative drugs based on genes, tissues, or cells that target rare and severe diseases. ATMPs have shown promising clinical outcomes but are associated with high costs, raising questions about cost-effectiveness. Hence, this systematic review aims to analyze the cost-effectiveness and cost-utility profiles of the European Medicines Agency-authorized ATMPs for treating rare diseases. Methods: A systematic review was conducted following PRISMA guidelines. Studies were identified by searching PubMed, Embase, Web of Science, and ProQuest scientific databases. Economic evaluations reporting incremental cost-effectiveness/utility ratios (ICERs/ICURs) for ATMPs were included. Costs were standardized to 2023 Euros, and a cost-effectiveness plane was constructed to evaluate the results against willingness-to-pay (WTP) thresholds of EUR 50,000, EUR 100,000, and EUR 150,000 per QALY, as part of a sensitivity analysis. Results: A total of 61 studies met the inclusion criteria. ATMPs for rare blood diseases, such as tisagenlecleucel and axicabtagene ciloleucel, were found to be cost-effective in a majority of studies, with incremental QALYs ranging from 1.5 to 10 per patient over lifetime horizon. Tisagenlecleucel demonstrated a positive cost-effectiveness profile in the treatment of acute lymphoblastic leukemia (58%), while axicabtagene ciloleucel showed a positive profile in the treatment of diffuse large B-cell lymphoma (85%). Onasemnogene abeparvovec for spinal muscular atrophy (SMA) showed uncertain cost-effectiveness results, and voretigene neparvovec for retinal diseases was not cost-effective in 40% of studies, with incremental QALYs around 1.3 and high costs exceeding the WTP threshold set. Conclusions: ATMPs in treating rare diseases show promising economic potential, but cost-effectiveness varies across indications. Policymakers must balance innovation with system sustainability, using refined models and the long-term impact on patient outcomes. Full article

Since its discovery in the late 19th century, spinal muscular atrophy (SMA) has had a significant medical and societal impact, primarily affecting newborns, toddlers, and young adults. While new pharmaceutical strategies are effective in treating SMA in a particular subset of patients, continued research is necessary to improve the well-being of patients. Treatments are needed for those who do not respond to newly approved drugs and older patients with significantly compromised neuron systems. After summarizing SMA genotypes, phenotypes, and approved pharmacological treatments, this review presents ongoing trials for approved and new molecules, new formulations, and administration methods. Based on the work of our lab, we also discuss nutritional interventions that aim to counteract the oxidative stress present in SMA cells. Finally, we assess rehabilitative interventions, focusing on psychological approaches. Full article

Background/Objectives: Sarcopenia is defined by the progressive loss of muscle mass, strength, and/or physical performance associated with aging. Radiofrequency ablation (RFA) of the medial branch nerves is a well-established and effective treatment for lumbar facetogenic pain. While sarcopenia is associated with poor outcomes following epidural steroid injections and lumbar spine surgeries, its impact on clinical outcomes in patients undergoing RFA for facetogenic pain remains unexplored. This study aims to evaluate the influence of sarcopenia on treatment outcomes in this patient cohort. Methods: Patients were classified into sarcopenia (n = 35) and non-sarcopenia groups (n = 67) based on predefined psoas muscle index (PMI) thresholds. The primary outcomes included changes in back pain intensity and the proportion of responders at 1, 3, and 6 months following RFA. The secondary outcome was to identify demographic, clinical, and sarcopenia-related factors predictive of treatment response at each follow-up interval. Results: Both groups demonstrated statistically significant improvements in pain scores compared to baseline at all follow-up points. However, the median pain scores at 3 months post-RFA remained significantly higher in the sarcopenia group. Despite this, the proportion of responders did not differ significantly between the two groups at any time point. At 3 months, the absence of prior spinal surgery was identified as a significant predictor of treatment response. At 6 months, favorable outcomes were significantly associated with the absence of diabetes, no history of spinal surgery, and a higher PMI. Conclusions: Sarcopenia may influence the extent of pain improvement following medial branch nerve RFA. Additionally, patient-specific factors, such as diabetes, prior spinal surgery, and PMI, should be considered when predicting treatment outcomes. Full article

Background: Heat therapy (HT) and electroacupuncture (EA) are widely utilized pain relief methods, but the analgesic mechanisms of their combined application remain unclear. Methods: In acetic acid (AA)-induced writhing test and complete Freund’s adjuvant (CFA)-induced inflammatory pain tests, mice received one of three treatments: EA at bilateral ST36, HT via a 45 °C heating pad, or the combination (EA + HT). To probe underlying pathways, separate groups were pretreated with caffeine, DPCPX (a selective adenosine A₁ receptor antagonist), or naloxone (an opioid receptor antagonist). Spinal expression of glial fibrillary acidic protein (GFAP) and phosphorylated p38 (p-p38) was examined by Western blot and immunofluorescence. Results: Both EA and HT individually reduced AA-induced writhing, with the combination (EA + HT) exhibiting the greatest analgesic effect. EA’s analgesic effect was reversed by caffeine and DPCPX and partially by naloxone, while HT’s effect was reversed by caffeine and DPCPX but was unaffected by naloxone. AA injection elevated spinal p-p38 and GFAP expression, which were attenuated by either EA or HT, with the most substantial suppression observed in the EA + HT group. In the CFA model, both treatments alleviated mechanical allodynia, while the combined treatment resulted in significantly greater analgesia compared to either treatment alone. Conclusions: EA combined with HT synergistically enhances analgesia in both AA and CFA pain models, accompanied by reduced spinal inflammation and astrocyte activation. EA’s analgesic effects appear to involve adenosine A₁ receptor pathways and, to a lesser extent, opioid receptor mechanisms, whereas HT’s effects involve adenosine A₁ receptor pathways. Full article

Spinal cord injury (SCI) is a major disability that, to this day, does not have a permanent cure. The spinal cord extends caudally through the body structure of the vertebral column and is part of the central nervous system (CNS). The spinal cord enables neural communication and motor coordination, so injuries can disrupt sensation, movement, and autonomic functions. Mechanical and traumatic damage to the spinal cord causes lesions to the nerves, resulting in the disruption of relayed messages to the extremities. Various forms of treatment for the spinal cord include functional electrical stimulation (FES), epidural electrical stimulation (EES), ‘SMART’ devices, exoskeleton and robotic systems, transcranial magnetic stimulation, and neuroprostheses using AI for the brain–computer interface. This research is going to analyse and review these current treatment methods for spinal cord injury and identify the current gaps and limitations in these, such as long-term biocompatibility, wireless adaptability, cost, regulatory barriers, and risk of surgery. Future advancements should work on implementing wireless data logging with AI algorithms to increase SCI device adaptability, as well as maintaining regulatory and health system integration. Full article

Cryotherapy could stimulate immune responses and induce abscopal effects. A novel technique was developed for treating spinal bone tumors involving the use of frozen tumor-containing autologous bone grafts for anterior spinal reconstruction following total en-bloc spondylectomy, with the aim of activating cryoimmunity. This study focused on analyzing changes in the T-cell receptor (TCR) repertoire after surgery to evaluate T-cell diversity. Blood samples were collected pre- and post-operatively, with subsequent RNA extraction and immunosequencing. Compared to pre-surgery samples, the diversity and abundance of the Complementarity-Determining Region 3, regions of the TCR α and β chains decreased, suggesting that more selective clones may have emerged and influenced immune responses. Through TCR repertoire analysis, this study demonstrated that transplantation of frozen tumor-containing autologous bone impacted the immune system. This study is expected to provide a foundation for developing treatments that may enhance immune activation. Full article

Background and Objectives: Acute metastatic cord compression (AMSCC) and femoral impending/pathological fracture negatively impact a patient’s quality of life, morbidity and survival, and are considered significant life events. This study aims to compare AMSCC and FMD as distinct yet overlapping metastatic orthopedic emergencies, addressing whether they represent sequential disease stages or distinct patient subpopulations—an analysis critical for prognosis and treatment planning. Materials and Methods: Records of all patients who underwent surgery for a femoral metastatic disease (FMD) over a decade (2004–2015) and patients who were treated for acute metastatic spinal compression (AMSCC) (2007–2017) were retrieved. There were no patients lost to follow-up. Results: The treatment cohorts were similar in terms of age, gender, tumour origin, and the number of spinal metastases. Fifty-four patients were diagnosed with AMSCC. Following treatment, the Frankel muscle grading improved by 0.5 ± 0.8 grades. Two hundred and eighteen patients underwent surgical intervention for FMD. Seventy percent of femoral metastases were located in the femoral neck and trochanteric area. Impending fractures accounted for 52% of the cohort. The FMD cohort, including impending and pathological fractures, was similar to the AMSCC cohort in terms of age and the time interval between cancer diagnosis and surgery (56.7 ± 74.2 vs. 51.6 ± 69.6, respectively, p = 0.646). The Karnofsky functional score was higher for the FMD cohort (63.3 ± 16.2) than for the AMSCC cohort (48.5 ± 19.5; p < 0.001). The mean survival time for the FMD cohort was double that of the AMSCC, at 18.4 ± 23.5 months versus 9.1 ± 13.6 months, respectively (p = 0.006). Conclusions: In conclusion, this study is novel in proposing that FMD and AMSCC are distinct clinical entities, differing in their impact on patient function and, most importantly, on patient survival. Full article

Oligodendrocyte precursor cells (OPCs) are a distinct and dynamic glial population that retain proliferative and migratory capacities throughout life. While traditionally recognized for differentiating into oligodendrocytes (OLs) and generating myelin to support rapid nerve conduction, OPCs are now increasingly appreciated for their diverse and non-canonical roles in the central nervous system (CNS), including direct interactions with neurons. A notable feature of OPCs is their expression of diverse ion channels that orchestrate essential cellular functions, including proliferation, migration, and differentiation. Given their widespread distribution across the CNS, OPCs are increasingly recognized as active contributors to the development and progression of various neurological disorders. This review aims to present a detailed summary of the physiological and pathological functions of ion channels in OPCs, emphasizing their contribution to CNS dysfunction. We further highlight recent advances suggesting that ion channels in OPCs may serve as promising therapeutic targets across a broad range of disorders, including, but not limited to, multiple sclerosis (MS), spinal cord injury, amyotrophic lateral sclerosis (ALS), psychiatric disorders, Alzheimer’s disease (AD), and neuropathic pain (NP). Finally, we discuss emerging therapeutic strategies targeting OPC ion channel function, offering insights into potential future directions in the treatment of CNS diseases. Full article

Background/Objectives: Limited robust data support the use of antibiotic combinations in the treatment of orthopedic infections. However, in certain situations, the combination of antibiotics seems to be beneficial. This review aims to outline the circumstances under which a combination of antibiotics may be utilized in the treatment of orthopedic infections. Methods: We reviewed the existing guidelines on orthopedic infections and focused on situations where antibiotic combinations are recommended or proposed optionally. We chose vitro and animal studies that provide evidence for the effectiveness of several widely recommended combinations. Results: The combinations serve multiple purposes: they provide empirical coverage while awaiting microbiological results, offer targeted treatment for difficult-to-treat infections, and facilitate oral treatment primarily for staphylococcal infections. The objectives include enhancing bacterial coverage against Gram-positive and Gram-negative bacteria, achieving synergistic effects with bactericidal agents, and reducing the risk of antibiotic resistance. The review outlines specific combinations for fracture-related infections, periprosthetic joint infections, spinal infections, and anterior cruciate ligament reconstruction infections, emphasizing the importance of tailoring antibiotic choices based on local epidemiology and patient history. The review also addresses potential drawbacks of combination therapy, such as toxicity, higher costs, and drug interactions, underscoring the complexity of managing orthopedic infections effectively. Conclusions: According to the guidelines, several different proposals are made, depending in part on the countries’ epidemiology. In a well-defined situation, various authors propose either monotherapy or a combination of antibiotics. When a combination is suggested, the choice of antibiotics is based on the expected effect: broadening the spectrum, enhancing bactericidal activity, achieving a synergistic effect, or reinforcing biofilm activity to optimize the treatment. Full article

Background: Identifying the etiological factors of syringomyelia, which can cause progressive neurological deficits in the spinal cord, is critically important for both diagnosis and treatment. This study aimed to assess the cranial morphometric features of patients with idiopathic syringomyelia by conducting comparative analyses with individuals diagnosed with Chiari Type I, Chiari Type I accompanied by syringomyelia, and healthy controls, in order to elucidate the potential structural contributors to the pathogenesis of idiopathic syringomyelia. Methods: In this retrospective and comparative study, a total of 172 patients diagnosed with Chiari Type I and/or syringomyelia between 2016 and 2024, along with 156 radiologically normal individuals, were included. The participants were categorized into four groups: healthy controls, Chiari Type I, Chiari Type I with syringomyelia, and idiopathic syringomyelia (defined as syringomyelia without an identifiable cause). Midline sagittal T1-weighted MR images were used to obtain quantitative measurements of the posterior fossa, cerebellum, intracranial area, and foramen magnum. All measurements were stratified and statistically analyzed by sex. Results: In cases with idiopathic syringomyelia, both the posterior fossa area and the cerebellum/posterior fossa ratio differed significantly from those of healthy controls. In male patients, the foramen magnum diameter was significantly larger in the Chiari + syringomyelia group compared with the idiopathic group. A significant correlation was found between the degree of tonsillar descent and selected morphometric parameters in female subjects, whereas no such correlation was observed in males. Both Chiari groups exhibited significantly smaller posterior fossa dimensions compared with the healthy and idiopathic groups, indicating greater neural crowding. Additionally, in Chiari Type I patients, increasing degrees of tonsillar descent were associated with a decreased incidence of syringomyelia. Conclusions: Anatomical variations such as a reduced posterior fossa area or altered foramen magnum diameter may contribute to the pathogenesis of idiopathic syringomyelia. Cranial morphometric analysis appears to offer diagnostic value in these cases. Further prospective, multicenter studies incorporating advanced neuroimaging modalities, particularly those assessing cerebrospinal fluid dynamics, are warranted to better understand the mechanisms underlying syringomyelia of unknown etiology. Full article

Background: A precise radiographic evaluation of adolescent idiopathic scoliosis (AIS) is essential for effective treatment planning and follow-up. The pelvic axial rotation (PAR) and horizontal balance of the pelvis are critical factors to consider throughout the treatment and monitoring of AIS. While some previous studies have examined spinal curvature in relation to PAR direction and the direction of the major curve (DMC) in AIS patients, this study aims to explore the relationship between scoliosis morphology, pelvic axial rotation (PAR), and the direction of the major curve in patients with adolescent idiopathic scoliosis. Methods: Radiographic images of 397 patients diagnosed with AIS between 2023 and 2024 at a Tertiary Referral Hospital were retrospectively evaluated. Morphological and morphometric measurements, including sex, Lenke and Risser classifications, lower leg discrepancy, Cobb angle, PAR direction, and major curvature direction, were performed. Results: The mean age of the 397 patients (246 female, 151 male) was 14.47 ± 2.29. There is no significant correlation between PAR and DMC (p = 0.919). No significant differences were found in terms of sex (p = 0.603). Regardless of the PAR direction, major curvature was more common on the left side (57.7%). Furthermore, a positive correlation was noted between the Cobb angle and LLD. Conclusions: Our study contributes to a growing body of literature questioning the deterministic role of PAR in AIS. While previous reports have emphasized the directional correlation between the pelvis and spinal curvature, our findings suggest that pelvic rotation may not be a reliable indicator of curve direction in all patients. This highlights the complexity of AIS biomechanics and underscores the need for individualized radiographic and clinical evaluation rather than a reliance on generalized compensatory models. Full article

Background: The treatment landscape for spinal muscular atrophy (SMA) has changed significantly with the approval of gene-based therapies such as nusinersen for adults with SMA (pwSMA). Despite their efficacy, high costs and treatment burden highlight the need for biomarkers to objectify or predict treatment response. This study aimed to identify such biomarkers. Methods: A proteomic analysis of cerebrospinal fluid (CSF) from pwSMA (n = 7), who either significantly improved (SMA Improvers) or did not improve in motor function (SMA Non-Improvers) under nusinersen therapy, was performed. Data are available via ProteomeXchange with identifier PXD065345. Candidate biomarkers—Neuronal Pentraxin 2 (NPTX2), Contactin 5 (CNTN5), and Anthrax Toxin Receptor 1 (ANTXR1)—were investigated by ELISA in serum and CSF from an independent pwSMA cohort (n = 14) at baseline, 2 and 14 months after therapy initiation. Biomarker concentrations were correlated with clinical outcomes. Additionally, NPTX2 was stained in spinal cord sections from a mild SMA mouse model (FVB.Cg-Smn1tm1Hung Tg(SMN2)2Hung/J). Results: CSF NPTX2 levels decreased in pwSMA after 14 months of nusinersen therapy, independent of clinical response. The change in NPTX2 serum levels over 14 months of nusinersen treatment correlated with the change in HFMSE during this period. CNTN5 and ANTXR1 showed no significant changes. In the SMA mouse model, NPTX2 immunoreactivity increased at motoneuron loss onset. Conclusions: NPTX2 emerges as a potential biomarker of treatment response to nusinersen in pwSMA suggesting its significant pathophysiological role in late-onset SMA, warranting further investigation. Full article

Amyotrophic lateral sclerosis (ALS) remains a progressive neurodegenerative disease, lacking effective causal therapies. The Wobbler mouse model harboring a spontaneous autosomal recessive mutation in the vacuolar protein sorting associated protein (Vps54), has emerged as a valuable model for investigating ALS pathophysiology and potential treatments. This model exhibits cellular and phenotypic parallels to human ALS, including protein aggregation, microglia and astrocyte activation, as well as characteristic disease progression at distinct stages. Exploring the underlying pathomechanisms and identifying therapeutic targets requires a comprehensive analysis of gene and protein expression. In this study, we examined the expression of three well-established housekeeping genes and proteins—calnexin, ß-actin, and ßIII-tubulin—in the cervical spinal cord of the Wobbler model. These candidates were selected based on their demonstrated stability across various systems like animal models or cell culture. Calnexin, an integral protein of the endoplasmic reticulum, ß-actin, a structural component of the cytoskeleton, and ß-tubulin III, a component of microtubules, were quantitatively assessed using quantitative reverse transcription-polymerase chain reaction (RT-PCR) for gene expression and Western blotting for protein expression. Our results revealed no significant differences in the expression of CANX, ACTB, and TUBB3 between spinal cords of wild-type and Wobbler mice at the symptomatic stage (p40) at both the gene and protein levels. These findings suggest that the pathophysiological alterations induced by the Wobbler mutation do not significantly affect the expression of these crucial housekeeping genes and proteins at p40. Overall, this study provides a basis for further investigations using the Wobbler mouse model, while highlighting the potential use of calnexin, ß-actin, and ßIII-tubulin as reliable reference genes and proteins in future research to aid in the discovery for effective therapeutic interventions. Full article

Background: Spinal metastases (SMs) are associated with poor prognosis and significant morbidity. We hypothesize that artificial intelligence (AI) models can enhance the identification and clinical utility of genetic and molecular signatures associated with SMs, improving diagnostic accuracy and enabling personalized treatment strategies. Methods: A systematic review of five databases was conducted to identify studies that used AI to predict genetic alterations and SMs outcomes. Accuracy, area under the receiver operating curve (AUC), and sensitivity were used for comparison. Data analysis was performed in R. Results: Eleven studies met the inclusion criteria, covering three different primary tumor origins, comprising a total of 2211 patients with an average of 201 ± 90 patients (range: 76–359 patients) per study. EGFR, Ki-67, and HER-2 were studied in ten (90.9%), two (18.1%), and one (9.1%) study, respectively. The weighted average AUC is 0.849 (95% CI: 0.835–0.863) and 0.791 (95% CI: 0.738–0.844) for internal and external validation of the established models, respectively. Conclusions: AI, through radiomics and machine learning, shows strong potential in predicting molecular markers in SMs. Our study demonstrates that AI can predict molecular markers in SMs with high accuracy. Full article

Background/Objectives: Spinal cord injuries (SCIs) are among the most debilitating conditions and are a leading cause of disability in young people. This study aimed to analyze the causes of SCIs, assess injury severity using the AIS scale, and evaluate complications during rehabilitation in a hospital setting. Methods: The study involved 176 individuals with SCI, including 142 with a traumatic SCI (TSCI) and 34 with a non-traumatic SCI (NTSCI), rehabilitated at various times post-injury. The data on injury causes, paresis type, complications, wheelchair use, gender, age, and treatment methods were collected. The injury severity was assessed using the AIS. Results: A significant gender difference was found between the TSCI and NTSCI groups (85.2% male vs. 61.8% male). TSCI individuals were also younger. The causes of TSCI were traffic accidents, falls from height, and diving, while the causes for NTSCI included spinal ischemia, tumors, degenerative disc disease, and inflammation. TSCI individuals had more AIS A lesions (52.8% vs. 26.5%) and more cervical injuries (53.5% vs. 14.7%), whereas NTSCI individuals had more AIS C lesions (38.2% vs. 18.3%) and thoracic damage (58.8% vs. 35.2%). TSCI patients were more often treated surgically (95.7% vs. 61.8%) and used wheelchairs (88% vs. 55.9%). No significant differences were found in terms of complications between the groups, though TSCI individuals underwent more chronic rehabilitation. Conclusions: Our research shows that there are significant differences between TSCI and NTSCI both in terms of the level of damage and the severity of damage to neural structures (AIS scales), and thus significant differences in the patients’ functioning in later life for both groups of individuals. Full article