Search Results (317)

Background: Primary spinal gliomas are rare in the pediatric population. Separately, FGFR1 genomic aberrations are also uncommon in spinal cord tumors. We report a case of a previously well adolescent who presented with progressive symptoms secondary to an intramedullary tumor with unique radiological and molecular characteristics. Case Presentation: A previously well 17-year-old male presented with worsening mid-back pain associated with lower limb long-tract signs. Magnetic resonance imaging (MRI) of his neuro-axis reported a long-segment intramedullary lesion with enhancing foci and a multi-septate syrinx containing hemorrhagic components from C4 to T12. The largest enhancement focus was centered at T7. Additional MRI sequences observed no intracranial involvement or vascular anomaly. He underwent an emergent laminoplasty and excision of the thoracic lesion. Intraoperative findings demonstrated a soft, grayish intramedullary tumor associated with extensive hematomyelia that had multiple septations. Active fenestration of the latter revealed blood products in various stages of resolution. Postoperatively, the patient recovered well, with neurological improvement. Final histology reported a circumscribed low-grade glial neoplasm. Further molecular interrogation via next-generation sequencing panels showed FGFR1 p.K656E and V561M alterations. The unique features of this case are presented and discussed in corroboration with a focused literature review. Conclusions: We highlight an interesting case of an intramedullary tumor with unusual radiological and pathological findings. Emphasis is on the importance of tissue sampling in corroboration with genomic investigations to guide clinical management. Full article

Background: Instrument separation is a frequent issue in root canals, often complicated by intriguing anatomical variations that make treatment more challenging. These variations in canal structure can lead to various iatrogenic complications, such as missed canals, instrument separation, gouging, perforation, and overextension of obturation materials. One such complication is instrument breakage, which can disrupt the cleaning and shaping processes and potentially cause pain or discomfort. Materials and Methods: The present systematic review was conducted following PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The present systematic review aimed to identify all clinical trials focused on the removal of separated instruments from endodontic canals using an endodontic surgical approach. Results: A total of 21 studies were included, reporting 22 cases involving surgical approaches for separated instrument removal. Conclusions: The analysis of available evidence, although prim Information added.arily based on clinical cases and case series, emphasizes that surgical approaches for removing separated endodontic instruments are a viable therapeutic option when non-surgical treatments are ineffective or not feasible. Techniques such as apicoectomy, intentional replantation, surgical removal, and the technique provide innovative, customized solutions for addressing complications related to separated instruments, showing favorable clinical and radiographic success rates in follow-up assessments. Full article

Unaccustomed eccentric exercise is well established to induce exercise-induced muscle damage (EIMD), characterized by transient strength loss, delayed onset muscle soreness (DOMS), reduced range of motion, and proprioceptive disturbances. While limb dominance has been proposed as a potential modulator of susceptibility to EIMD, evidence remains inconclusive. This exploratory study aimed to compare alterations in muscle damage indices between dominant and non-dominant knee extensors 48 h after eccentric isokinetic exercise. Eighteen physically active young women (23 ± 2 years) completed two eccentric exercise sessions (5 × 15 maximal contractions at 60°/s), one per limb, with sessions separated by 24–30 days. For all participants, testing was conducted during the early follicular phase. Muscle strength (isometric and eccentric peak torque), DOMS (palpation and pain pressure threshold), range of motion, fatigue index, and position sense were assessed pre- and 48 h post-exercise. Significant reductions in isometric and eccentric peak torque, increased DOMS, impaired position sense, and altered fatigue index were observed 48 h post-exercise in the exercised limb (p < 0.001), with no differences between dominant and non-dominant limbs across all indices. These findings demonstrate that limb dominance does not influence the magnitude of EIMD in knee extensors of young women. Practical implications include equal consideration of both limbs in eccentric training, rehabilitation, and injury prevention programs. Full article

Background: Previous studies have often reported a link between advanced age and inadequate cancer pain management. Given Italy’s demographic profile as the country with the oldest population in Europe, it offers an ideal setting to explore whether this association remains valid today. Aim: This study aimed primarily to assess the influence of advanced age on the adequacy of pain management among patients receiving treatment in Italian radiotherapy (RT) departments, and secondarily, to identify age-specific determinants of analgesic undertreatment. Methods: In this prospective, multicenter study, we enrolled 2104 consecutive patients attending 13 RT centers between October and November 2019. Pain intensity was evaluated using the numeric rating scale (NRS), and patients reporting scores ≥ 1 (n = 1353) were included in the analysis. Pain management adequacy was assessed using the Pain Management Index (PMI), with negative values indicating undertreatment. A two-step statistical approach was employed: variable selection via Least Absolute Shrinkage and Selection Operator regression, followed by Classification and Regression Tree analysis to identify key predictors. Separate analyses were performed for the overall population, older adults (≥65 years), and younger adults (18–64 years). Results: Overall, 42% of patients were undertreated (PMI < 0), without significant differences between older (41.0%) and younger patients (43.1%). However, factors contributing to undertreatment varied according to age. For the entire cohort, non-cancer pain was associated with substantially higher rates of undertreatment (74.3%) compared to cancer-related pain (34.2%). Among cancer patients, those receiving curative RT had poorer pain control (49.4%) than those receiving palliative RT (28.8%). In older patients, geographic location strongly influenced pain management, with higher rates of undertreatment in central and southern Italy compared to the north (e.g., palliative RT: 64.0% vs. 15.4%, respectively). Conversely, younger patients showed no geographical differences; instead, timing of assessment (beginning vs. end of RT) influenced outcomes, with improved PMI values towards the end of treatment. Conclusions: Unlike previous studies, advanced age itself was not associated with inadequate analgesia. However, the determinants of inadequate pain management differed significantly by age: geographic disparities were predominant among older patients, while assessment timing influenced outcomes for younger patients. Further longitudinal research and targeted interventions are needed to address these age-dependent challenges. Full article

Dry eye disease (DED) is a prevalent condition characterized by ocular surface inflammation and pain. This study evaluated the long-term progression of DED by analyzing clinical and molecular status, considering the impact of chronic ocular pain. Patients with DED were evaluated at two visits (V1 and V2) separated by at least two years. Evaluations included validated symptom questionnaires alongside slit-lamp examination, corneal sensitivity testing, and sub-basal nerve plexus analysis. Basal tear samples were collected for multiplex quantification of 20 cytokines and substance P (SP), and conjunctival cells were obtained to analyze 25 genes and 12 microRNAs (miRNA). Based on the presence or absence of chronic ocular pain, patients were then divided into two groups. Patients improved in DED-related symptoms, with no changes observed in ocular surface signs. Corneal dendritic cell density decreased, along with epidermal growth factor (EGF), fractalkine, and monocyte chemoattractant protein (MCP-1) tear levels, whereas interleukin (IL)-10 and SP tear levels increased. Neurotrophic tyrosine kinase, receptor, type (NTRK)1 gene expression was significantly downregulated, especially in patients without chronic ocular pain. miR-665 expression decreased significantly in DED patients. Monitoring corneal dendritic cells, tear cytokines, and gene/miRNA expression offers promising tools for tracking DED progression. Distinguishing the presence of chronic ocular pain as a separate symptom is crucial to optimizing therapeutic strategies and DED progression. Full article

Background and Clinical Significance: Non-palpable migrated contraceptive implants pose significant challenges for removal and are associated with neurovascular complications. Traditional open surgery near nerves is associated with postoperative morbidity. Migrated or deeply embedded implants near critical structures can result in severe complications, such as neuropathy, and their removal typically requires open surgical intervention. Case Presentation: We report a novel, minimally invasive, ultrasound (US)-guided technique for removing a migrated etonogestrel Implanon^® implant that caused ulnar neuropathy. A 38-year-old woman presented with severe neuropathic pain and paresthesia (NPRS 10/10; QuickDASH 55) along her left ulnar nerve following multiple failed removal attempts that induced deep migration. US confirmed the proximity of the implant to the ulnar nerve. Initial US-guided removal exacerbated her symptoms. Hydrodissection (HD) with 50 mL of 5% dextrose in water (D5W) without local anesthetic (LA) was performed to reduce inflammation and achieve separation. The implant migrated proximally during extraction. An additional HD with 50 mL of D5W without LA distally repositioned the implant. Percutaneous stabilization using a 25-gauge needle enabled secure removal. The intact 4 cm implant was extracted under real-time US guidance without open surgery. The patient experienced immediate symptom relief (NPRS 2/10; QuickDASH 4.5 at one month) and full resolution (NPRS 0/10; QuickDASH 0) with no motor deficits at one year. Conclusions: This case represents the first documented percutaneous removal of a nerve-adherent implant using combined US-guided D5W HD and needle stabilization, marking a paradigm shift in the management of such cases. This approach confirms the safety of US-guided foreign body removal using HD for nerve-adjacent implants and demonstrates the efficacy of combining D5W HD with needle stabilization. Surgical morbidity was avoided, while excellent long-term outcomes were achieved. Full article

Photodynamic therapy (PDT) has become a widely used modality for treating actinic keratosis (AK) and non-melanoma skin cancers (NMSC), as well as other inflammatory or infectious diseases. Despite its efficacy, limitations such as incomplete responses and pain have motivated the exploration of protocol enhancements. This review examines the clinical and biological rationale for light fractionation—dividing the total light dose into two separate exposures with a dark interval—as a strategy to improve PDT outcomes. We reviewed preclinical and clinical studies evaluating fractionated illumination using 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL). The findings consistently demonstrate superior efficacy of fractionated schemes, particularly with ALA, showing higher complete response rates in AK, superficial basal cell carcinoma (sBCC), and Bowen’s disease (BD), and improved long-term tumor control compared to single illumination. The better outcomes are attributed to increased reactive oxygen species (ROS) generation following tissue reoxygenation during the dark interval and greater susceptibility of partially damaged cells to subsequent illumination. Fractionated PDT also shows a favorable safety and cosmetic profile. These results support considering light fractionation protocols as a standard approach for optimizing PDT efficacy in dermatologic oncology, particularly in lesions with limited depth and high recurrence risk. Full article

Background: Functional massage is a soft tissue intervention that combines tissue compression with specific joint movements to enhance muscle function, improve joint mobility and reduce pain. The physical working capacity at the fatigue threshold (PWC_FT) uses surface electromyography to determine the highest exercise intensity that can be sustained indefinitely. The purpose of this study, therefore, was to examine the influence of FM on a multi-joint exercise such as cycle ergometry. Methods: Twelve healthy college-aged men volunteered for the current study. On two occasions, separated by seven days and in randomized order, subjects either completed a 14 min FM on both legs prior to an incremental cycle ergometer test to determine PWC_FT, or rested for 14 min before performing the same cycling test. Results: The paired samples t-tests revealed a significant (p < 0.05) difference for the absolute and relative PWC_FT values between the no-FM and FM conditions. Conclusions: These results indicate that FM may delay the onset of neuromuscular fatigue for whole-body exercise. Full article

Heart rate variability (HRV) is often modulated by pain; therefore, the objective of this study was to assess whether the induction of delayed-onset muscle soreness (DOMS) is already affected by HRV alterations during exercise, in spite of the fact that pain evolves only post-exercise. An isokinetic dynamometer was used to induce DOMS in this study on 19 young male elite handball players who were subjected to HRV measurements throughout a DOMS-inducing exercise session. The result of this study indicated that the heart rate (HR) dependence of time–frequency domain parameters could be described by an exponential-like function, while entropy showed a V-shaped function, with a minimum “turning point” separated by descending and ascending intervals. The DOMS protocol upshifted the time–frequency domain HRV parameters in the entire HR range, contrary to the sample entropy values that were systematically downshifted, indicative of an upregulated sympathetic tone. The group-averaged HR-dependent sample entropy function showed a nonlinear character under exercise, with lower values for higher DOMS than for the group with lower DOMS below the turning-point HR, and vice versa above it. The differences between the respective HRV(HR) point sets representing the low-DOMS and high-DOMS groups were quantified using a statistical method and found to be significant at the current sample size for all the HRV parameters used. Since oxidative stress is implicated in DOMS, we are the first to report that nonlinear alterations may impact HRV in a HR-dependent manner in DOMS using a Piezo2 interpretation. This finding provides further indirect evidence for an initiating neural microdamage that prevails under DOMS-inducing exercise, and the diagnostic detection of this point may provide control for avoiding further injury risk in sports and exercise activities. Full article

Background: Understanding the mechanisms underlying dental pain caused by pulpitis in humans has led to the development of animal models, such as the rat, which enable the study of the mechanisms underlying inflammation; the use of these models is considered ethically justified when the anticipated scientific benefits outweigh the potential impacts on animals in the harm/benefit balance. Objective: To develop a rat model of mechanically induced pulpitis and to evaluate the potential impact on animal well-being. Methods: Pulpitis was mechanically induced in male Lewis rats (13–16 weeks, 350–400 g) which were anesthetized and endotracheally intubated. Following pulp exposure, the cavity was sealed with either amalgam (n = 10) or zinc phosphate cement (n = 10). Following recovery and return to their housing, behavioral assessments and histological evaluations using Hematoxylin and Eosin (H&E) staining were conducted in separate cohorts at two time points: 3 h and 5 days following the procedure. Results: A standardized model of mechanically induced pulpitis was established and verified clinically and by histopathological analysis, which showed evidence of the inflammatory process and revealed no statistically significant differences in the scoring of pain, discomfort, or distress, nor in the measurements of food and water consumption or body weight. Conclusions: The behavioral assessments conducted in this study supported the implementation of a safe and easily reproducible model for future research aimed at elucidating the mechanisms underlying pulp inflammation. Full article

Inflammatory arthritis (IA) is a chronic condition marked by joint dysfunction and pain, posing significant challenges for effective drug delivery. This study separated Perilla frutescens leaf-derived exosome-like nanovesicles (PFE) to effectively penetrate the stratum corneum barrier. These nanovesicles and indomethacin (IND) were subsequently developed into a nanogel designed for topical drug delivery systems (PFE-IND-GEL). PFE exhibited a typical vesicular structure with a mean diameter of 98.4 ± 1.3 nm. The hydrodynamic size and zeta potential of PFE-IND-GEL were 129.6 ± 5.9 nm and −17.4 ± 1.9 mV, respectively. Mechanistic investigations in HaCaT keratinocytes showed that PFE significantly downregulated tight junction proteins (ZO-1 and Occludin, p < 0.01) via modulation of the IL-17 signaling pathway, as evidenced by transcriptomic analysis. In a sodium urea crystal-induced rat IA model, the topical application of PFE-IND-GEL significantly reduced joint swelling (p < 0.05) and serum levels of inflammatory cytokines (IL-6, IL-1α, TNF-α) compared to control groups. Histopathological analysis confirmed the marked attenuation of synovial inflammation and cartilage preservation in treated animals. These findings underscore the dual role of PFE as both a topical permeation enhancer and an anti-inflammatory agent, presenting a promising strategy for managing IA. 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

Background/Objectives: Iron deficiency without anaemia (IDNA) is common in non-dialysis-dependent chronic kidney disease (CKD) and contributes to fatigue, reduced exercise tolerance, and impaired quality of life (QoL). While intravenous (IV) iron replacement is known to benefit anaemic patients, its role in IDNA remains uncertain. This study aimed to evaluate the impact of ferric derisomaltose (FDI) on patient-reported QoL outcomes in CKD patients with IDNA. Methods: This was a post hoc analysis of the double-blind, multicentre Iron and the Heart randomised controlled trial. Fifty-four participants with IDNA (ferritin < 100 µg/L or transferrin saturation < 20% and haemoglobin 110–150 g/L) and CKD stages G3b–G5 were randomised 1:1 to receive either 1000 mg FDI (n = 26) or placebo (n = 28). An additional 10 iron-replete CKD patients served as controls. SF-36v2 QoL surveys were collected at baseline, 1 month, and 3 months. Results: SF-36v2 scores declined across all domains, but deterioration was consistently milder in the FDI group. Role physical declined by 3% in the FDI group versus 12% with placebo and 4% in controls. Bodily pain improved by 2.8% with FDI but worsened by 1.5% in the placebo group. Mental health improved by 3.4 points with FDI and declined by 2.7 points in the placebo group, creating a 6.1-point separation. While differences did not reach statistical significance, likely due to small sample size, the consistent trends favour FDI. Conclusions: IV iron may attenuate QoL decline in non-dialysis-dependent CKD patients with IDNA. These findings support the need for larger, adequately powered trials to assess patient-centred outcomes in this population. Full article

Background and Clinical Significance: Serratus Anterior Muscle Pain Syndrome (SAMPS) is an underdiagnosed cause of anterior chest wall pain, often attributed to myofascial trigger points of the serratus anterior muscle (SAM) or dysfunction of the Long Thoracic Nerve (LTN), leading to significant disability and affecting ipsilateral upper limb movement and quality of life. Current diagnosis relies on exclusion and physical examination, with limited treatment options beyond conservative approaches. This case report presents a novel approach to chronic SAMPS, successfully diagnosed using Sonoguided Digital Palpation (SDP) and treated with ultrasound-guided hydrodissection of the LTN using 5% dextrose in water (D5W) without local anesthetic (LA), in a patient where conventional treatments had failed. Case Presentation: A 72-year-old male presented with a three-year history of persistent left chest pain radiating to the upper back, exacerbated by activity and mimicking cardiac pain. His medical history included two percutaneous coronary interventions. Physical examination revealed tenderness along the anterior axillary line and a positive hyperirritable spot at the mid axillary line at the 5th rib level. SDP was used to visualize the serratus anterior fascia (SAF) and LTN, and to reproduce the patient’s concordant pain by palpating the LTN. Ultrasound-guided hydrodissection of the LTN was then performed using 20–30cc of D5W without LA to separate the nerve from the surrounding tissues, employing a “fascial unzipping” technique. The patient reported immediate pain relief post-procedure, with the pain reducing from 9/10 to 1/10 on the Numeric Rating Scale (NRS), and sustained relief and functional improvement at the 12-month follow-up. Conclusions: Sonoguided Digital Palpation (SDP) of the LTN can serve as a valuable diagnostic adjunct for visualizing and diagnosing SAMPS. Ultrasound-guided hydrodissection of the LTN with D5W without LA may provide a promising and safe treatment option for patients with chronic SAMPS refractory to conservative management, resulting in rapid and sustained pain relief. Further research, including controlled trials, is warranted to evaluate the long-term efficacy and generalizability of these findings and to compare D5W to other injectates. Full article

Pulsed radiofrequency (PRF) current applied to peripheral nerves is a modality used in interventional pain medicine, but its underlying mechanisms remain unclear. This study aimed to investigate whether ex vivo exposure of human monocytic THP-1 cells to PRF current or to heat induces β-endorphin production. Methods: THP-1 cells were exposed to PRF current for 15 min or incubated at elevated temperatures (42 °C to 50 °C) for 3 or 15 min. Flow cytometry was used to assess cell viability, and β-endorphin concentrations in culture supernatants were quantified by ELISA. In a separate experiment, cells were stimulated with lipopolysaccharide (LPS) to compare its effects on β-endorphin release. Results: A 3 min exposure to temperatures ≥ 46 °C reduced THP-1 cell viability, whereas a 15 min exposure to PRF current or to heat at 42 °C did not impair viability. Both PRF current and mild heat significantly enhanced β-endorphin release. β-Endorphin levels in the supernatant of LPS-stimulated cells were comparable to those of cells exposed to PRF current. Conclusions: Ex vivo application of PRF current or mild heat enhanced β-endorphin production from THP-1 cells without significant cytotoxicity. These preliminary findings warrant further investigation using primary human monocytes and in vivo models to assess therapeutic potential. Full article