Search Results (2,396)

Background: Older adults are at elevated risk of falls, especially when prescribed AEDs (AEDs) for neuropathic pain. The sedative and neuropsychiatric effects of these agents contribute significantly to fall-related morbidity. However, existing studies often lack stratification by age and dose. Objective: To systematically evaluate the incidence and drug-specific risk of falls and fall-related adverse events (AEs) in older adults prescribed AEDs for neuropathic pain. Methods: A systematic search was performed across PubMed, Scopus, CINAHL, ScienceDirect, and Cochrane Library databases up to May 2025. Studies were selected using PICOS criteria and included RCTs and controlled cohort studies reporting on AED-related AEs among participants aged ≥60 years. The methodological quality was assessed using RoB 2, ROBINS-I, and GRADE frameworks. Meta-analyses were performed using logit event rates and fixed-effects modeling via Comprehensive Meta-Analysis v3.7. Publication bias was evaluated using Begg’s and Egger’s tests. Results: Twenty-three studies met the inclusion criteria. The pooled logit event rate for falls was −1.693 (95% CI: −1.993 to −1.393), corresponding to a 15.5% incidence. Gabapentin showed the lowest fall risk (~10%), while pregabalin and carbamazepine were associated with higher rates of dizziness (up to 21.6%), sedation (~15.5%), and ataxia (~17.8%). Heterogeneity was low (I² = 0–22.3%) across outcomes. Conclusions: AEDs carry a clinically significant fall risk in older adults, with dose-dependent patterns. Gabapentin may present a safer profile, while pregabalin and carbamazepine warrant cautious use and monitoring. These findings inform individualized prescribing and fall prevention strategies in geriatric neuropathic pain management. Full article

Background/Objectives:Hydrogels are highly hydrated, biocompatible polymer networks increasingly investigated as drug-delivery systems (DDS) for analgesics. Their ability to modulate local release, prolong drug residence time, and reduce systemic toxicity positions them as promising platforms in perioperative, chronic, and localized pain settings. This scoping review aimed to systematically map clinical applications, efficacy, and safety of hydrogel-based DDS for analgesics, while also documenting non-DDS uses where the matrix itself contributes to pain modulation through physical mechanisms. Methods: Following PRISMA-ScR guidance, PubMed, Embase, and Cochrane databases were searched without publication date restrictions. Only peer-reviewed clinical studies were included; preclinical studies and non-journal literature were excluded. Screening and selection were performed in duplicate. Data extracted included drug class, hydrogel technology, clinical setting, outcomes, and safety. Protocol was registered with Open Science Framework. Results: A total of 26 clinical studies evaluating hydrogel formulations as DDS for analgesics were included. Most were randomized controlled trials, spanning 1996–2024. Local anesthetics were the most frequent drug class, followed by opioids, corticosteroids, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and neuromodulators. Application sites were predominantly topical/transdermal and perioperative/incisional. Across the DDS cohort, most of the studies reported improved analgesic outcomes, including reduced pain scores and lower rescue medication use; neutral or unclear results were rare. Safety reporting was limited, but tolerability was generally favorable. Additionally, 38 non-DDS studies demonstrated pain reduction through hydrogel-mediated cooling, lubrication, or barrier effects, particularly in burns, ocular surface disorders, and discogenic pain. Conclusions: Hydrogel-based DDS for analgesics show consistent clinical signals of benefit across diverse contexts, aligning with their mechanistic rationale. While current evidence supports their role as effective, well-tolerated platforms, translational gaps remain, particularly for hybrid nanotechnology systems and standardized safety reporting. Non-DDS applications confirm the intrinsic analgesic potential of hydrogel matrices, underscoring their relevance in multimodal pain management strategies. Full article

Nutritional factors play a crucial role in many gynecological disorders, particularly those influenced by estrogen. Uterine fibroids are benign tumors that affect a large proportion of women of reproductive age, especially between 30 and 40 years. These lesions may cause significant symptoms, including pelvic pain, heavy menstrual bleeding, and infertility. In younger women, the onset of fibroids is often associated with familial and genetic predisposition, whereas in adulthood, hormonal influences linked to environmental factors and states of exogenous or endogenous hyperestrogenism are more frequently observed. In both contexts, supportive management through an appropriate diet may provide clinical benefit. Although the precise pathogenesis remains incompletely understood, hormonal, genetic, and environmental components—particularly hyperestrogenism—are considered key contributors to fibroid development. Current evidence suggests that consumption of saturated fats, particularly from red meat and full-fat dairy, may raise circulating estrogen concentrations and contribute to the development of fibroids. In contrast, diets abundant in fiber, fruits, and vegetables appear to exert a protective effect, potentially lowering fibroid risk. Obesity, through increased aromatization and consequent estrogen production, also represents an established risk factor. This narrative review aims to explore the role of nutritional determinants in the onset and progression of uterine fibroids, with a specific focus on the impact of individual nutrients, foods, and dietary patterns on clinical outcomes. Particular emphasis is placed on obesity and macronutrient composition (e.g., high-fat versus high-fiber dietary regimens) as potential modulators of circulating estrogen levels and, consequently, fibroid growth dynamics. Furthermore, the potential of nutritional strategies as complementary therapeutic approaches, capable of integrating established clinical practices, is examined. Full article

Objective: Morphine is a widely used analgesic for severe pain, but tolerance is a major challenge in long-term pain management. This study examined the potential of Daflon^® to enhance morphine’s pain-relieving effects and to reduce tolerance in a rat model with neuropathic pain induced by partial sciatic nerve transection (PSNT). Methods: Male Wistar rats were divided into five groups: (1) Sham + Saline, (2) PSNT + Saline, (3) PSNT + morphine, (4) PSNT + Daflon, and (5) PSNT + morphine + Daflon. Morphine tolerance was induced through continuous intrathecal infusion (15 µg/µL/h, i.t.) for 7 days, starting on day 7 post-PSNT, while Daflon was administered orally (50 mg/kg/day, oral) for 7 days. Pain relief was assessed using tail-flick and paw withdrawal on days 1, 4, and 7 after osmotic pump implantation. Spinal cords were collected for immunohistochemistry to analyze glial expression, and serum biomarkers (TNF-α, IL-1β, IL-6, and IL-10) were measured to evaluate neuroinflammation. Results: The results showed that oral Daflon significantly enhanced morphine’s analgesic effects, evidenced by improved pain thresholds in all behavioral tests. Moreover, Daflon reduced morphine tolerance. Mechanistically, Daflon upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and activated heme oxygenase-1 (HO-1), reducing oxidative stress and modulating neuroinflammation through glial regulation. Combining morphine and Daflon reduces pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and enhances anti-inflammatory IL-10 serum level, showing a synergistic effect in managing neuropathic pain with greater efficacy and lower drug dependence. Histology and immunohistochemistry evaluations further confirmed that morphine and Daflon co-treatment substantially reduced mononuclear cell infiltration, astrocyte activation (as indicated by GFAP expression), and microglial activation (as indicated by Iba-1 expression) compared to single treatment. Conclusions: Our findings suggest that dual therapy synergistically targets both oxidative stress and inflammatory pathways, leading to stronger neuroprotection and pain relief. Importantly, the combination approach may allow for lower opioid dosages, minimizing the risks of opioid-related side effects. Overall, morphine and Daflon co-administration offers a promising and safer strategy for managing neuropathic pain and preserving spinal cord integrity. Full article

Fibromyalgia is a chronic syndrome characterized by widespread musculoskeletal pain, fatigue, non-restorative sleep, and cognitive impairment. Its pathogenesis reflects a complex interplay between central and peripheral mechanisms, including altered pain modulation, neuroinflammation, mitochondrial dysfunction, autonomic imbalance, and genetic and epigenetic factors. Evidence from neuroimaging, omics studies, and neurophysiology supports this multifactorial model. Epidemiological updates confirm a global prevalence of 2–8%, with a strong female predominance and a significant impact on quality of life and healthcare costs. Diagnostic criteria have evolved from the 1990 American College of Rheumatology tender points to the 2010/2011 revisions and the 2016 update, improving case ascertainment but still lacking objective biomarkers. Recent omics and systems biology approaches have revealed transcriptional, proteomic, and metabolic signatures that may enable molecularly informed stratification. Therapeutic management remains multidisciplinary, combining pharmacological interventions (e.g., duloxetine, pregabalin, milnacipran) with non-pharmacological strategies such as graded aerobic exercise and cognitive behavioral therapy. Emerging approaches include drug repurposing to target neuroinflammation, mitochondrial dysfunction, and nociceptive pathways. Despite promising advances, progress is limited by small sample sizes, heterogeneous cohorts, and lack of standardization across studies. Future priorities include large-scale validation of biomarkers, integration of multi-omics with clinical phenotyping, and the design of precision-guided trials. By synthesizing mechanistic insights with clinical evidence, this review provides an updated framework for the diagnosis and management of fibromyalgia, highlighting pathways toward biomarker-guided, personalized medicine. Full article

Deep Gluteal Syndrome (DGS) has traditionally been defined as a clinical entity caused by sciatic nerve (SN) entrapment. However, recent anatomical and imaging studies suggest that muscle- and tendon-origin pathologies—including enthesopathy—may also serve as primary pain generators. This narrative review aims to broaden the current understanding of DGS by integrating muscle and tendon pathologies into its diagnostic and therapeutic framework. The literature was selectively reviewed from PubMed, Cochrane Library, Google Scholar, PEDro, and Web of Science to identify clinically relevant studies illustrating evolving concepts in DGS pathophysiology, diagnosis, and management. We review clinical features and diagnostic tools including physical examination, MRI, and dynamic ultrasonography, with special attention to deep external rotator enthesopathy. Treatment strategies are summarized, including conservative therapy, ultrasound-guided injections, hydrodissection, and prolotherapy. This narrative synthesis underscores the importance of recognizing muscle-origin enthesopathy and soft-tissue pathologies as significant contributors to DGS. A pathophysiology-based, multimodal approach is essential for accurate diagnosis and effective treatment. Full article

Background: Lower limb malalignment is a hallmark of knee osteoarthritis, with surgical correction techniques evolving from traditional mechanical alignment (MA) to kinematic alignment (KA) approaches. Restrictive kinematic alignment (rKA) represents a hybrid strategy combining principles from both techniques. This study evaluated short-term functional outcomes following robotic-assisted total knee arthroplasty (RoTKA), comparing MA versus rKA alignment strategies. Methods: This prospective, randomized, single-center study enrolled 96 patients with grade 3–4 idiopathic knee osteoarthritis (Kellgren–Lawrence classification). Patients were randomized to MA (n = 49, mean age 67 ± 9 years) or rKA (n = 47, mean age 66 ± 7 years) groups. Preoperative hip–knee–ankle (HKA) angles were 172.6° ± 1.1° and 172.9° ± 0.9° for MA and rKA groups, respectively. Outcomes were assessed using Visual Analog Scale (VAS) pain scores, range of motion (ROM), Knee Society Score (KSS), Oxford Knee Score (OKS) (primary outcome), SF-36, and Forgotten Joint Score (FJS-12). Results: Postoperative HKA angles were 179.5° ± 1.2° (MA) and 176.0° ± 1.5° (rKA). At 14 days postoperatively, knee ROM increased by 20.5% in the MA group and 25.7% in the rKA group, with a statistically significant 5.2% intergroup difference, indicating faster postoperative recovery (p = 0.008). VAS pain scores decreased by 7% in the rKA group while increasing by 13% in the MA group (p < 0.001). At one-year follow-up, FJS-12 scores were significantly higher in the rKA group (94.8 ± 3.2 vs. 91.9 ± 2.2, p < 0.001). No significant differences were observed in KSS, OKS, or SF-36 score between groups. Conclusions: Restrictive kinematic alignment demonstrated superior early postoperative outcomes compared to mechanical alignment in RoTKA, with significantly reduced pain and improved ROM. While one-year functional outcomes were comparable between techniques, rKA may offer advantages in the immediate postoperative period, supporting its consideration as a viable alignment strategy in robotic-assisted knee arthroplasty. Full article

Pain remains one of the most burdensome symptoms in rheumatoid arthritis (RA), often persisting despite inflammatory remission and profoundly impairing quality of life. This review aimed to evaluate the clinical efficacy and mechanistic pathways by which Janus kinase (JAK) inhibitors alleviate RA-related pain. Evidence from randomized clinical trials demonstrates that JAK inhibitors have demonstrated rapid and significant pain relief, often exceeding that of methotrexate or biologic DMARDs. Improvements in patient-reported pain scores seem to typically emerge within 1–2 weeks and are sustained over time. Beyond anti-inflammatory effects, JAK inhibitors modulate central sensitization and nociceptive signaling by attenuating IL-6 and GM-CSF activity, reducing astrocyte and microglial activation, and downregulating nociceptor excitability in dorsal root ganglia and spinal pathways. Preclinical models further suggest that JAK inhibition interrupts neuroimmune feedback loops critical to chronic pain maintenance. Comparative and network meta-analyses consistently position JAK inhibitors among the most effective agents for pain control in RA. However, individual variability in response, partly due to differential JAK-STAT activation and cytokine receptor uncoupling, underscores the need for biomarker-guided treatment approaches. JAK inhibitors represent a mechanistically distinct and clinically impactful class of therapies that target both inflammatory and non-inflammatory pain in RA. Their integration into personalized pain management strategies offers a promising path to address one of RA’s most persistent unmet needs. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is associated with impaired functional capacity, persistent fatigue, and poor health-related quality of life despite advances in pharmacological therapy. Exercise training has been proposed as a non-pharmacological intervention, but its efficacy and safety remain incompletely defined. This systematic review aimed to evaluate the effects of exercise training on functional aerobic capacity and quality of life in adults with SLE. Methods: A comprehensive search of PubMed, EMBASE, Cochrane Library, and PEDro was conducted to identify randomized controlled trials published up to October 2022, in accordance with the PRISMA guidelines. Results: Twelve randomized controlled trials involving 619 participants were included. Exercise interventions were heterogeneous and comprised aerobics, resistance, combined programs, vibration training, home-based protocols, and counseling strategies, with durations ranging from 6 weeks to 12 months. Supervised aerobic and combined interventions consistently improved functional aerobic capacity, while quality of life benefits were reported across several domains, particularly physical health, vitality, and fatigue. Additional positive effects were observed on fatigue, depression, pain, sleep, insulin sensitivity, and self-care ability, without evidence of increased disease activity. Conclusions: Structured exercise is safe and can meaningfully enhance functional capacity and quality of life in patients with SLE, supporting its incorporation into multidisciplinary clinical management. Full article

Introduction: In clinical practice, the presence of abnormal physiological root resorption frequently results in the retention of deciduous teeth. Also, unilateral mastication may contribute to the altered physiological process of root resorption. This delayed exfoliation and retention of deciduous teeth may compromise the integrity of adjacent soft tissue. In recent years, ozone therapy can be considered a promising strategy in accelerating healing and reducing pain in both traumatic and autoimmune ulcers. Case Presentation: This case report describes a 12 year-old male patient with localized damaged gingival tissue resulting from chronic trauma due to the retention of a deciduous tooth. Following the application of gaseous ozone therapy, complete mucosal healing was achieved. Conclusions: This case supports the potential of ozone therapy in paediatric soft tissue management. Full article

Background: Intervertebral disc degeneration (IVDD) is closely linked to low back pain (LBP), a leading cause of disability worldwide. IVDD is characterized by the loss of proteoglycans (PGs), extracellular matrix (ECM) degradation, and reduced hydration of the nucleus pulposus (NP). Extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) exhibit tissue repair and immunomodulatory effects and are emerging as promising cell-free therapeutics. Methods: We established a rat IVDD model via fluoroscopy-guided needle puncture of three consecutive coccygeal discs and confirmed degeneration through Alcian Blue and hematoxylin & eosin (H&E) staining. The gene expression of inflammatory and pain markers (ADRβ2, COMP, CXCL1, COX2, PPTA, MMP13, YKL40) was measured by qPCR. Subsequently, we implanted hUC-MSCs or EVs to evaluate their reparative potential. Results: Upregulation of inflammatory and pain genes in IVDD was associated with an immunomodulatory response. Tracking DiI-labelled hUC-MSCs and EVs revealed enhanced survival of hUC-MSCs, retention of EVs, and dispersion within rat tail discs; EVs showed greater retention than hUC-MSCs. Implanted EVs were internalized by NP cells and remained within degenerative IVDs. EVs passively diffused, accumulated at the injury site, interacted with host cells, and enhanced function, as shown by increased expression of human chondrocyte-related markers (SOX9, TGFβ1, TGFβ2, COL2) compared to hUC-MSC treatment. Histological analysis of two weeks post-transplantation showed NP cellular patterns resembling chondromas in treated discs. EVs integrated into and distributed within degenerated NP regions, with greater glycosaminoglycan (GAG) content. Conclusions: Overall, hUC-MSC EVs demonstrated superior regenerative capacity, supporting a safe, cell-free strategy for disc repair. Full article

Background/Objectives: Understanding the relationship between plasma connecting peptide (C-peptide) levels and health-related quality of life (HRQoL) can inform diabetes management strategies. This study aimed to assess plasma C-peptide levels, HRQoL, and their association in patients with prediabetes, type 1 diabetes (T1D), and type 2 diabetes (T2D) attending outpatient departments (OPDs) in tertiary care hospitals. Methods: A cross-sectional survey was conducted between 1 January and 30 June 2023, using the EuroQoL Five Dimensions (EQ-5D-5L) instrument. Participants with prediabetes, T1D, or T2D were recruited from OPDs in diabetology, endocrinology, general practice, and family medicine at Sheikh Zayed Hospital (SZH) and Mayo Hospital (MH) in Pakistan. Plasma C-peptide levels were measured and HRQoL was assessed using EQ-5D-5L and the EQ Visual Analog Scale (VAS). Results: A total of 301 patients were included: 42 with prediabetes (14%), 70 with T1D (23.2%), and 189 with T2D (62.8%). The median C-peptide level was 0.46 nmol/L (IQR 0.13–0.85), the HRQoL score was 78.5% (IQR 63.2–100%), and the EQ VAS score was 85% (IQR 70–90%). C-peptide levels were significantly correlated with HRQoL scores (r = 0.14, p < 0.02) and differed across mobility, daily activity, pain/discomfort, and anxiety/depression domains (all p < 0.02). HRQoL scores significantly varied among the three groups (p < 0.0001), particularly in the aforementioned domains. Conclusions: C-peptide levels and HRQoL differ significantly across diabetes types, with lower C-peptide associated with reduced mobility, increased pain, and mental health issues. These findings underscore the importance of targeting C-peptide regulation to enhance HRQOL in diabetic populations. Full article

Background: Ischemia with no obstructive coronary artery disease (INOCA) is characterized by myocardial ischemia in the absence of significant coronary artery stenosis. Despite the lack of major obstructive lesions, patients often present with chest pain, making diagnosis and management a significant challenge. Materials and Methods: A comprehensive search strategy of electronic databases (2000 to 2024) was used to identify studies assessing pathophysiology, diagnosis, surgical treatments, interventions, and outcomes in INOCA. Clinical trials, observational studies, case-control studies, and cohort studies were included. Results: Emerging surgical treatments may have a role in certain subgroups of INOCA patients, particularly those with severe and persistent symptoms or underlying pathophysiological factors that do not respond adequately to pharmacological therapies. Transmyocardial revascularization (TMR) and sympathetic denervation procedures reduce coronary vasospasm in refractory angina. Trials have shown promise for coronary sinus occlusion. Autologous stem cell therapy is an innovative surgical approach that has shown promise in early trials but remains investigational. Selective surgical cardiac vein retroperfusion remains largely experimental, with limited clinical data. Conclusions: This review highlights the need for ongoing research and clinical trials to assess the effectiveness of surgical and nonsurgical options in INOCA. Although current data on surgical interventions is limited, these treatments may offer hope for patients with refractory symptoms. A personalized and multidisciplinary approach to management is essential for optimal patient outcomes. Full article

Background: Spontaneous retroperitoneal hematomas constitute a rare clinical entity, yet their incidence has markedly increased during the SARS-CoV-2 pandemic. The pathophysiological substrate is incompletely elucidated, being influenced by anticoagulant therapy, vascular inflammatory alterations induced by SARS-CoV-2 infection, and comorbidities in critically ill patients that exacerbate hemorrhagic risk. Methods: We performed a comprehensive literature review of published case reports and case series on spontaneous retroperitoneal hematomas in COVID-19 patients, complemented by our institutional experience, in order to synthesize current diagnostic and therapeutic approaches. Results: Available evidence indicates that most cases occur in anticoagulated patients, with clinical manifestations often limited to nonspecific abdominal or lumbar pain. Diagnosis relies primarily on contrast-enhanced CT imaging. Reported therapeutic strategies include conservative management, endovascular embolization, and surgical intervention, with outcomes ranging from complete recovery to fatal progression, particularly in elderly and comorbid individuals. Conclusions: Spontaneous retroperitoneal hematomas in the setting of SARS-CoV-2 infection represent a diagnostic and therapeutic challenge associated with considerable morbidity and mortality. Early recognition, prompt imaging, and individualized multidisciplinary management are essential, while further research is needed to clarify incidence, risk factors, and preventive strategies. Full article

Introduction: Twelve-lead electrocardiography (ECG) remains an essential diagnostic tool for patients presenting with chest pain. Timely recognition of specific electrocardiographic patterns is critical for guiding reperfusion strategies and predicting adverse outcomes. Among these, Wellens’ pattern is a high-risk marker of critical left anterior descending (LAD) artery stenosis and an impending anterior myocardial infarction. Although typically described in clinically stable patients without heart failure, its occurrence in the setting of acute decompensation is rare. Case Report: We report the case of a 66-year-old male with hypertension, obesity, and active smoking who presented with exertional chest pain, dyspnea, and signs of acute heart failure. Initial ECG revealed biphasic T waves in V2–V4, consistent with type A Wellens’ pattern. Laboratory evaluation demonstrated elevated troponin I, while point-of-care ultrasound (POCUS) identified systolic and diastolic dysfunction, lateral wall hypokinesia, pericardial effusion, and cardiogenic pulmonary edema. The patient received acute management with antiplatelet therapy, statins, diuretics, and anticoagulation, followed by referral for coronary angiography. This revealed critical stenosis (>90%) of the proximal LAD, successfully treated with percutaneous coronary intervention and drug-eluting stent implantation. The in-hospital course was uneventful, and guideline-directed medical therapy was optimized at discharge, including dual antiplatelet therapy, beta-blocker, renin–angiotensin system inhibitor, and SGLT2 inhibitor. Conclusions: This case highlights the need for early recognition of Wellens’ pattern, even in atypical contexts such as acute heart failure. Integrating ECG interpretation with bedside POCUS facilitated diagnostic accuracy and guided an early invasive strategy, preventing extensive myocardial infarction. In resource-limited settings, strengthening frontline diagnostic capabilities and referral networks is crucial to improving patient outcomes. Full article