Search Results (128)

Background/Objectives: Lumbar disc herniation (LDH) is the most common condition associated with low back pain, and it adversely impacts individuals’ health. The interplay between energy metabolism and apoptosis is critical, as the loss of viable cells in the intervertebral disc (IVD) can lead to a cascade of degenerative changes. Efferocytosis is a key biological process that maintains homeostasis by removing apoptotic cells, resolving inflammation, and promoting tissue repair. Therefore, enhancing mitochondrial energy metabolism and efferocytosis function in IVD cells holds great promise as a potential therapeutic approach for LDH. Methods: In this study, energy metabolism and efferocytosis-related differentially expressed genes (EMERDEGs) were identified from the transcriptomic datasets of LDH. Machine learning approaches were used to identify key genes. Functional enrichment analyses were performed to elucidate the biological roles of these genes. The functions of the hub genes were validated by RT-qPCR. The CIBERSORT algorithm was used to compare immune infiltration between LDH and Control groups. Additionally, we used single-cell RNA sequencing dataset to analyze cell-specific expression of the hub genes. Results: By using bioinformatics methods, we identified six EMERDEGs hub genes (IL6R, TNF, MAPK13, ELANE, PLAUR, ABCA1) and verified them using RT-qPCR. Functional enrichment analysis revealed that these genes were primarily associated with inflammatory response, chemokine production, and cellular energy metabolism. Further, we identified candidate drugs as potential treatments for LDH. Additionally, in immune infiltration analysis, the abundance of activated dendritic cells, neutrophils, and gamma delta T cells varied significantly between the LDH group and Control group. The scRNA-seq analysis showed that these hub genes were mainly expressed in chondrocyte-like cells. Conclusions: The identified EMERDEG hub genes and pathways offer novel insights into the molecular mechanisms underlying LDH and suggest potential therapeutic targets. Full article

Apoptosis plays a crucial role in the progression of intervertebral disc degeneration (IVDD), a significant cause of chronic low back pain. This review explores disc cell apoptosis’s cellular and molecular mechanisms, focusing on nucleus pulposus, annulus fibrosus, and cartilage endplates cells. Apoptotic pathways—intrinsic (mitochondrial), extrinsic (death receptor-mediated), ER stress-mediated, and autophagy-related—are activated by oxidative stress, inflammation, mechanical load, and metabolic disturbances like hyperglycemia. Diabetes exacerbates disc cell apoptosis through AGE-RAGE signaling and mitochondrial dysfunction. Inflammation further amplifies apoptotic cascades via cytokine signaling and ROS generation. The review also examines emerging therapeutic strategies, including antioxidants (e.g., MitoQ, resveratrol), anti-inflammatory agents (e.g., cytokine inhibitors), autophagy modulators (e.g., rapamycin, metformin), and stem cell and gene therapies. While promising preclinical results exist, challenges such as poor bioavailability and clinical translation remain. Enhanced understanding of apoptosis pathways informs future cellular preservation and matrix integrity treatments. Based on a comprehensive literature search from 2000 to 2025, this narrative review synthesizes current knowledge, identifies knowledge gaps, and discusses translational potential. Our findings support a paradigm shift toward mechanism-based therapies that address the root cause of IVDD rather than symptomatic relief alone. Full article

Background/Objectives: Chronic low back pain (LBP) remains a leading cause of disability and healthcare utilization globally, with complex, multifactorial pathophysiology. Despite advances in imaging, diagnosis often remains challenging due to poor correlation between structural findings and clinical symptoms. Recent evidence suggests inflammatory mechanisms may underlie persistent pain. This study investigated whether systemic inflammatory cytokines are altered in military personnel with chronic LBP and examined their relationships with clinical manifestations, psychological factors, and radiological findings. Methods: In this cross-sectional study, we enrolled 50 patients with chronic non-specific LBP (duration ≥ 3 months) and 50 age-, sex-, and BMI-matched healthy controls. All patients underwent a comprehensive clinical assessment, which included evaluation of pain intensity (VAS), neuropathic pain screening (DN4), psychological assessment (HADS), fibromyalgia screening (FIRST), and assessment of functional disability (Oswestry Disability Index and Roland-Morris Disability Questionnaire, EIFEL). Serum levels of IL-6, IL-8, IL-1β, TNF-α, and IL-10 were measured using chemiluminescence and enzyme-linked immunosorbent assay (ELISA) techniques. Radiological findings were documented through MRI and CT imaging of the lumbar spine. Results: Serum IL-8 levels were significantly elevated in patients with chronic LBP compared to healthy controls (8.52 ± 6.7 vs. 4.8 ± 0.56 pg/mL, p < 0.001). Weak positive correlations were observed between IL-8 levels and anxiety scores (r = 0.3, p = 0.02) and functional disability, as measured by the EIFEL questionnaire (r = 0.3, p = 0.04); however, these associations did not remain significant after Bonferroni correction for multiple testing. Similarly, IL-6 showed a weak positive correlation with BMI (r = 0.21, p = 0.03) and a weak negative correlation with lumbar mobility, as assessed by Schober’s test (r = −0.38, p = 0.03), which also did not survive correction for multiple comparisons. Conclusions: This study identified serum IL-8 as a potential biomarker for chronic LBP. While we observed associations between specific inflammatory markers and psychological distress and functional disability, these correlations were weak and did not remain significant after correction for multiple testing. These preliminary findings suggest possible connections between inflammation and the psychophysiological aspects of chronic LBP that warrant further investigation in larger cohorts. Full article

Background: Chronic low back pain (CLBP) is a leading cause of disability, impacting quality of life (QoL), function, and work productivity. Traditional rehabilitation faces challenges in accessibility and adherence. Remote rehabilitation and virtual reality (VR) interventions using motion sensors offer real-time movement tracking, biofeedback, and personalized exercises. This systematic review evaluates their effectiveness in pain reduction, functional improvement, adherence, and QoL. Methods: A systematic search was performed across PubMed, Scopus, Web of Science, and PEDro (2015–2025), including randomized controlled trials, observational, and feasibility studies on adults with CLBP undergoing sensor-based digital rehabilitation. The primary outcomes included pain, functional mobility, and movement biomechanics; secondary outcomes included adherence, QoL, and cost-effectiveness. Eight studies involving 7166 participants were included. Overall, sensor-based remote rehabilitation and VR interventions demonstrated positive effects on pain, function, and adherence. Pain reductions ranged from modest short-term decreases to over 60% in long-term programs (e.g., −68.5% in VAS). Functional improvements included lumbar ROM gains up to +9.9° and better movement control. Adherence was consistently high, with some programs reporting completion rates between 73% and 90%, particularly those incorporating gamification or real-time feedback. Selected studies also showed QoL improvements (e.g., +9.10 points on SF-36) and reductions in work impairment by over 60%. A few trials reported significant decreases in inflammatory markers (e.g., CRP −1.16 mg/L, TNF-α −8.9 pg/mL). Conclusions: Motion sensor-based remote rehabilitation and VR interventions show promising results in pain management, mobility, and adherence for individuals with CLBP. Gamification and biofeedback features enhance engagement, addressing a key challenge of conventional rehabilitation. However, more long-term RCTs and economic evaluations are needed to confirm their effectiveness and cost-efficiency. Full article

Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for a significant proportion of all cancer cases in Korea. This case report presents a unique instance of spontaneous dramatic tumor regression in a 42-year-old Korean male diagnosed with clear cell RCC. The patient initially presented with right lower back pain, weight loss, and a loss of appetite. Following systemic immunotherapy with nivolumab and ipilimumab, and right radical nephrectomy, the patient was diagnosed with metastatic clear cell RCC, with new metastatic lesions detected in the liver, and on the chest wall on follow-up imaging. Second-line systemic treatment with pazopanib was initiated. Shortly thereafter, the patient developed severe systemic inflammatory syndrome, resulting in a mental stupor and acute kidney failure. Intensive care, including continuous renal replacement therapy and high-dose immunosuppressants, was administered. The patient’s condition improved significantly with the intensive care regimen, leading to unintended tumor regression. These potentially fatal side effects occurred without infection, as confirmed by negative blood and urine cultures, and were attributed to the recent introduction of pazopanib. Follow-up imaging showed a significant reduction in hepatic metastatic lesions and the disappearance of chest wall nodules. This is the first reported case of RCC tumor regression following the side effects of pazopanib, underscoring the need for further studies into the immune mechanisms involved in RCC treatment and highlighting potential therapeutic strategies that leverage innate immune responses. Full article

Background and Objectives: Spondylarthritis is a complex group of inflammatory diseases closely associated with the HLA-B27 antigen. However, the role of non-HLA-B27 alleles in the disease’s pathogenesis has gained significant scholarly attention in recent years. Case presentation: This case study presents a 49-year-old male with a history of progressive inflammatory back pain, characterized by morning stiffness and restricted spinal mobility developed over several years. Initially presenting with non-specific symptoms, the patient eventually experienced persistent axial pain and deteriorating functional limitations, which required further evaluation. Radiographic imaging supported the diagnosis of ankylosing spondylitis (AS) by identifying bilateral sacroiliitis. HLA genotyping revealed a negative result for HLA-B27 but positive results for HLA-B13 and HLA-B37. This finding serves as a foundation for exploring alternative genetic factors contributing to spondylarthritis (SpA). HLA-B13 and HLA-B37 exhibit structural and functional similarities to HLA-B27, particularly in their peptide-binding grooves. This resemblance may lead to overlapping peptide repertoires and increased T cell cross-reactivity. Moreover, these alleles belong to overlapping cross-reactive groups (CREGs) and share the Bw4 epitope. This suggests that they may contribute to disease pathogenesis via similar mechanisms, such as molecular mimicry and the dysregulation of natural killer (NK) cell interactions, as observed in HLA-B27. Conclusions: This case emphasizes the necessity of expanding diagnostic criteria to incorporate non-HLA-B27 markers, particularly for patients who are HLA-B27-negative. Enhancing our understanding of the roles of alternative genetic markers can improve diagnostic accuracy, enable personalized treatment approaches, and enhance outcomes for the diverse SpA patient population. Full article

Background: Ozone therapy is used for its immunomodulatory, antioxidant, and analgesic properties in several fields. It can be useful in the rehabilitation of musculoskeletal disorders. Studies showed that O₂-O₃ therapy can reduce pain and improve functioning in patients affected by low back pain and knee osteoarthritis. Only a few studies have been published about the efficacy of this treatment in upper limb disease. Objective: The aim of this study is to investigate the use of ozone therapy in upper limb pathologies, evaluating its quantity, quality, and reported results in upper limb musculoskeletal disease, supraspinatus tendinopathy, shoulder impingement, adhesive capsulitis, chronic epicondylitis, and carpal tunnel syndrome. O₂-O₃ reduces inflammation by stimulating anti-inflammatory cytokines and inactivating pro-inflammatory molecules, relieves pain by interacting with pain receptors and improving blood circulation, promotes the regeneration of damaged tissues by stimulating growth factors and improving vascularization, and, finally, activates endogenous antioxidant defense systems by protecting cells from oxidative damage. Methods: A comprehensive search was conducted on PubMed and Scopus using the following MeSH terms: ozone therapy, infiltration joint, musculoskeletal disease, rehabilitation, upper limb, shoulder, wrist, hand, elbow, including English papers published in the last five years. Results: Five papers have been selected: four randomized controlled trials and one retrospective cohort study. The RCTs compared the effectiveness of intra-articular ozone injection with steroid injection alone or with other conservative treatments in shoulder diseases; one paper studied the effectiveness of ozone injection and orthoses in carpal tunnel syndrome compared to orthoses alone; one paper used ozone injections compared with steroid injection in patients with chronic lateral epicondylitis. A total of 218 patients were studied in these trials. Conclusions: Ozone treatment seemed to improve pain and function as well as other therapies in upper limb musculoskeletal disease. However, the trials’ protocols and the upper limb areas treated are different. Further studies are needed to define the effectiveness of ozone therapy in upper limb diseases in rehabilitation fields. Full article

Background and Clinical Significance: Nephrotic syndrome predisposes patients to venous thromboembolism. This case highlights the challenges of diagnosing pulmonary embolism in nephrotic syndrome patients with renal dysfunction, and emphasizes the utility of ventilation–perfusion lung scintigraphy when the contrast is contraindicated. Case Presentation: A 52-year-old male presented with fatigue, left back pain, dyspnea, and lower limb edema. The laboratory findings indicated nephrotic syndrome with significant proteinuria, hypoalbuminemia, and impaired renal function. Elevated inflammatory markers and lung infiltrates on chest CT suggested pneumonia. Despite antibiotic therapy, lung shadows, and elevated D-dimer persisted. Lower extremity ultrasound was negative for deep vein thrombosis. Due to concerns about contrast-associated nephropathy, ventilation–perfusion lung scintigraphy was performed, revealing a right lung base mismatch, leading to a diagnosis of pulmonary embolism and infarction. A kidney biopsy confirmed minimal change in disease. The patient achieved complete remission of nephrotic syndrome and was discharged on oral anticoagulation. His oral anticoagulation was discontinued after 3 months due to sustained remission and the absence of deep vein thrombosis. Conclusions: Pulmonary embolism and infarction can occur even in the absence of deep vein thrombosis. ventilation–perfusion lung scintigraphy is useful for detecting pulmonary embolism in patients with impaired renal function. Full article

Background/Objectives: Low back pain (LBP) is a leading cause of disability worldwide. Diclofenac, a non-steroidal anti-inflammatory drug (NSAID), and thiocolchicoside, a muscle relaxant, are commonly combined to target inflammation and muscle spasm. However, the efficacy and safety of their combination remain under discussion. This systematic review evaluates the efficacy and safety of diclofenac-thiocolchicoside therapy for LBP and other musculoskeletal conditions. Methods: A systematic review was conducted following PRISMA guidelines. Eligible studies included randomized controlled trials (RCTs) and observational studies comparing diclofenac-thiocolchicoside combination with placebo, monotherapy, or alternative treatments. A search was performed in PubMed, Scopus, and relevant websites, identifying articles published up to 30 September 2024. Studies from trial registries were excluded. Risk of bias was assessed using Revised Cochrane Risk of Bias for randomized trials (RoB 2) for RCTs and the Newcastle-Ottawa Scale (NOS) for observational studies. Evidence certainty was evaluated with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. Results were visualized using Robvis, tables, and graphs. Results: Of 393 identified records, 9 studies (1097 patients) met the inclusion criteria. Seven RCTs reported significant pain reduction and functional improvement with combination therapy compared to placebo or active controls. However, study heterogeneity, dosage variations, and risk of bias limited comparability. Adverse events (AEs) included gastrointestinal (GI) discomfort and drowsiness, though no severe complications were consistently reported. Conclusions: Despite methodological limitations, the diclofenac-thiocolchicoside combination demonstrates promising efficacy for acute LBP and musculoskeletal pain management. However, there is no clear evidence of its clinical superiority over other available treatments, due to study heterogeneity and potential biases. Rigorous, standardized research with larger sample sizes and consistent methodologies is essential to definitively establish the efficacy and safety of diclofenac-thiocolchicoside, providing clearer guidance for clinical decision-making. Full article

Background: Pyoderma gangrenosum (PG) is a rare inflammatory cutaneous disorder that frequently occurs in association with systemic diseases such as inflammatory bowel disease (IBD). This case report describes a 23-year-old female with Crohn’s disease (CD) who developed PG and was successfully treated with adalimumab. The objective of this study is to present the clinical course, treatment approach, and outcomes while reviewing the existing literature on the efficacy of adalimumab in PG management. Methods: A case report is presented, detailing clinical presentation, diagnostic evaluation, and treatment strategy. Additionally, a systematic review was conducted using PubMed to assess studies on adalimumab in PG, focusing on treatment response, remission rates, and adverse effects. Results: The patient presented with ulcerative lesions on her lower extremities and sacroiliitis. After corticosteroid therapy, adalimumab was initiated, leading to significant ulcer healing, reduced back pain, and CD remission. The systematic review identified seven studies on adalimumab in PG. Findings suggest that adalimumab is effective in steroid-refractory cases, with remission achieved in a significant proportion of patients. The most common adverse effects were infections, but overall, adalimumab showed a favorable safety profile. Conclusions: This case highlights the importance of early diagnosis and multidisciplinary management of PG in CD patients. Adalimumab appears to be a promising therapeutic option, particularly for steroid-resistant PG, though further research is needed to establish standardized treatment protocols. Full article

Chronic nonspecific low back pain (CNSLBP) might be associated with increased pain sensitivity and inflammation. High-intensity interval training (HIIT) has been suggested to reduce pain outcomes and inflammatory markers, but its effects compared to moderate-intensity continuous training (MICT) remain unclear. This study aimed to evaluate the acute effects of HIIT on pain sensitivity and inflammatory markers in persons with CNSLBP compared to healthy controls (HCs) and to determine how these effects differ from MICT. Twenty persons with CNSLBP and twenty HCs were assessed before (PRE) and after (POST) a single HIIT and MICT protocol for pain sensitivity (cuff pressure pain threshold (cPPT), temporal summation of pain (TS), conditioned pain modulation (CPM)), and inflammatory markers (IL-6, TNF-α). Data were analyzed using one-way ANOVAs, paired t-tests, and correlation analyses. At PRE, persons with CNSLBP exhibited lower cPPT (28.2 ± 7.1, Δ = −5.5, p = 0.040), higher TS (1.11 ± 0.89, Δ = 0.79, p = 0.042), and lower CPM (36.2 ± 11.6, Δ = −10.0, p = 0.023) compared to HCs. HIIT resulted in PRE–POST improvements in cPPT (38.9 ± 12.6, Δ = 5.2, p = 0.019) in HCs. No PRE–POST differences were observed in pain processing in those with CLBP. No PRE or PRE–POST differences were observed in the inflammatory markers in either group. The current exploratory study suggests that a single HIIT session might have a beneficial effect on pain sensitivity in HCs but does not alter acute pain sensitivity or inflammatory markers in persons with CNSLBP. Further research is needed to clarify the involved mechanisms and explore the (relation with the) long-term effects of HIIT. Full article

Background/Objectives: The aim of the study is to investigate the role of microRNA-17 (miRNA-17), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in the pathogenesis of lumbar degenerative disc disease (LDDD). The goal is to explore how miRNA-17 regulates inflammation and apoptosis within the intervertebral discs, with a particular focus on its involvement in inflammatory pathways via NF-κB signaling. This research seeks to uncover the molecular mechanisms that contribute to LDDD and its associated chronic lower back pain and disability. Methods: A case–control study was conducted, involving 110 patients diagnosed with LDDD and 17 healthy control individuals. Serum levels of miRNA-17, TNF-α, and IL-6 were measured using quantitative real-time PCR and enzyme-linked immunosorbent assays (ELISAs). The patients were further categorized based on the severity of their condition using the Oswestry Disability Index (ODI), which classified them into five subgroups. The correlation between miRNA-17 expression, pro-inflammatory cytokines, and disease severity was analyzed statistically. Results: The results demonstrated a significant downregulation of microRNA-17 in patients with LDDD compared to healthy controls. Inflammatory markers TNF-α and IL-6 were found to be significantly elevated in the patient group. A peak in inflammation and miRNA-17 expression was observed in patients with moderate to severe disability (ODI Grade 3), while inflammation levels decreased in more advanced stages of the disease (ODI Grades 4 and 5), suggesting a possible shift in disease dynamics. Conclusions: This study demonstrates that miRNA-17 plays a regulatory role in inflammation during the progression of LDDD, particularly through the modulation of TNF-α and IL-6 levels. The findings indicate that inflammation is most pronounced in the mid-stages of LDDD, while the later stages are characterized by structural damage rather than ongoing inflammation. These insights could help guide future therapeutic strategies aimed at targeting the molecular mechanisms underlying LDDD, potentially improving patient outcomes. Full article

Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, frequently present with extra-intestinal manifestations. Virtually all patients with IBD could be at risk for developing inflammatory arthropathies within the spectrum of spondyloarthritis (SpA). In this context, prompt recognition of musculoskeletal “red flags” (lower back pain, dactylitis, enthesitis, swelling of peripheral joints, musculoskeletal chest pain, family history of SpA, psoriasis, and anterior uveitis) is crucial for early referral and multidisciplinary management by gastroenterologists and rheumatologists. Recent advances have refined diagnostic tools including questionnaires, alongside imaging modalities and laboratory markers, enhancing the detection of SpA in IBD patients. Effective treatment strategies targeting both gastrointestinal and musculoskeletal symptoms may significantly reduce long-term morbidity in these patients. In this narrative review, we aimed to underscore the importance of integrating clinical, diagnostic, and therapeutic approaches for optimal patient management and outcome over time. Full article

Objective: The purpose of this systematic review is to identify and appraise the evidence on the effectiveness of using wearable devices to promote physical activity and reduce pain in people with chronic musculoskeletal pain. Methods: Systematic searches of electronic databases PubMed, CINAHL, and Medline (Ovid) were undertaken for randomised control trials and observational studies of wearable-based interventions in patients with chronic musculoskeletal conditions. Result: Thirteen studies were included in this review. The methodological quality of the included articles was found to vary between moderate and high quality. Studies included patients with osteoarthritis hip/knee (number; n = 5), low back pain (n = 3), rheumatoid arthritis (n = 1), juvenile idiopathic arthritis (n = 1), inflammatory arthritis (n = 1), spondylarthritis (n = 1), and ankylosing spondylitis (n = 1). The intervention group of some of the studies included additional components associated with the use of wearable devices such as step or diet diary, motivational interviewing or counselling, goal setting, and multidimensional and tailored exercise programme interventions delivered in person, remotely, or in a hybrid format. Intervention duration ranged from 1 week to 28 weeks. There were no serious adverse events related to the use of wearables. Overall, evidence from this systematic review shows that wearable technology intervention was effective in increasing physical activity significantly, especially where extra components (counselling, coaching, prescribed physical activity, goal setting, physiotherapist) were used among clinical and non-clinical populations. However, no significant effect was found in pain reduction with the use of wearable devices. Conclusions: It is concluded that the use of wearable technology should be encouraged in patients with chronic musculoskeletal conditions. Additional research is needed, such as increasing the duration of the intervention, which may have an impact on pain. Full article

Acute pancreatitis is an inflammatory condition of the exocrine pancreas that is a common indication for hospital admission and has had an increasing incidence in the last few decades. The diagnosis of acute pancreatitis requires the satisfaction of two out of three criteria: (1) abdominal pain radiating to the back, (2) serum lipase or amylase levels three or more times the upper limit of the normal level, and (3) findings indicating pancreatitis obtained via a computed tomography (CT) scan or magnetic resonance imaging (MRI). The different etiologies include gallstones, autoimmune disorders, alcohol abuse, smoking, hypertriglyceridemia, obesity, drugs, and post-endoscope retrograde cholangiopancreatography (ERCP). The initial investigation includes serum amylase and lipase analysis, a lipid panel including triglycerides, analysis of immunoglobulins, a full blood count, electrolyte analysis, a hemoglobin A1c test, a complete metabolic panel, and transabdominal ultrasound. The initial therapy includes oxygen supplementation, the provision of intravenous fluids, pain control, and a nutrition regime. Early oral feeding is encouraged if tolerated; if not, liquid supplement provision or enteral tube feeding within 48 h of admission has shown better outcomes. Some complications of acute pancreatitis are necrosis, infection, insulin resistance leading to diabetes mellitus, and pancreatic exocrine insufficiency requiring enzyme supplementation. Patients need to attend regular follow-ups and abstain from alcohol and smoking (if warranted) to prevent the recurrence of acute pancreatitis. The mortality rate of acute pancreatitis has decreased in the past few decades because of better management skills, but the recent rise in acute pancreatitis episodes is concerning. Sustained endeavors through clinical trials are required to establish a broad variety of drugs that can be used for acute pancreatitis episodes. Full article