Local Pain Research Articles

Pain in Children and Adolescents with Cerebral Palsy: A Cross-sectional Survey Study.

This study aims to investigate the prevalence, intensity, and location of pain in children and adolescents with cerebral palsy (CP) and analyze pain-related symptoms and participation restrictions. Children and adolescents aged 2 to 16 years diagnosed with CP were invited to participate in a pain survey. The questionnaire was based on the German Pain Questionnaire for Children, Adolescents and Parents (DSF-KJ). It was administered to children (2-11 years) by their caregivers, while adolescents (12-16 years) were asked to complete the questionnaire themselves or with the help of their caregivers. Fifty-seven of 133 children and adolescents with CP (43%) reported having pain in the past 12 months, of whom 17 (30%) reported chronic pain. Patients with Gross Motor Function Classification System (GMFCS) IV-V reported more frequent pain (p = 0.003) and higher pain intensity (p = 0.011). Lower extremity pain was the most common. Twenty-three percent of participants with pain did not receive any treatment. Pain often restricted participation, specifically by reducing sports activity in patients with GMFCS I-III, focusing attention on patients with GMFCS IV-V, and activities with the family in both GMFCS level categories. Pain is common in children and adolescents with CP and frequently restricts their participation. Therefore, it must be consistently recorded and addressed during the consultation. The goal of treatment should be not only to reduce pain but above all to increase participation.

Dry needling in people with fibromyalgia: A randomized controlled trial of its effects on pain sensitivity and pain catastrophizing influence.

Dry needling (DN) has been demonstrated as an effective treatment for patients with fibromyalgia (FM). It is crucial to take into consideration catastrophizing, a psychological construct that could potentially undermine the short-term efficacy of DN. To analyze the effects of DN in the infraspinatus muscle on both local and remote pressure pain thresholds (PPTs) and its relationship with baseline levels of pain catastrophizing in patients with FM. Randomized controlled trial. All participants were randomly assigned to one of three interventions: DN, sham DN, and no intervention. Hong's fast-in and fast-out technique was implemented during the DN intervention. The primary study outcome pain sensitivity (local and remote PPTs) was assessed at baseline, immediately post, and 24 h post intervention to evaluate short-term effect. Pain catastrophizing was measured at baseline in all participants using the Pain Catastrophizing Scale. To analyze the effect of DN on local and remote PPTs, an analysis of covariance was performed using catastrophism as covariate. Additionally, to examine the possible influence of catastrophism on local PPTs ratings in the subsequent assessment we performed a moderation analysis. A total of 120 women diagnosed with FM. However, during the follow-up period, 24 participants discontinued their involvement, leaving a final cohort of 96 patients who successfully concluded the study. DN showed significant differences in both local PPTs immediately post intervention and 24 h post intervention (MD [95% confidence interval] = 3.21 [0.40-6.02] kg/cm2, p = .019; and 2.84 [0.10-5.58] kg/cm2, p = .039, respectively) compared to sham and no-intervention groups. In addition, DN group results suggest that moderate values of catastrophizing (<35) diminish the effect of DN immediately postintervention. The infraspinatus DN led to a notable reduction in local PPTs among individuals with FM. Additionally, the effectiveness of the DN treatment was influenced by pain catastrophizing.

Art therapy and brain injury: making the invisible visible

The multiple cognitive, somatic, and behavioral changes following head injuries can result in expressive language difficulties that may not be resolved quickly. This paper explores the traumatic brain injury and post-concussive syndrome artwork created by an art therapist and the child of an art therapist, making the invisible neurological consequences of head injuries visible. Our first-person and caregiver perspectives offer examples of visual arts-based communication between patients, health professionals, and family members. Utilizing client imagery as a form of communication may improve patient outcomes through the identification and resultant treatment of overlooked and underdiagnosed symptoms. Experiences such as confusion, fear, localized pain, and mood lability stem not only from the injury itself, but from the experience of damaged microstructures that are often undetectable in standard diagnostic testing. Additionally, symptoms such as temperature and appetite dysregulation, vestibular and proprioceptive disruptions, and circadian rhythm sleep disorders evade standard diagnostic inventories. This may prompt the patient to question the reality of their somatic and cognitive experiences. Research supports the position of the authors: these experiences can be communicated through client imagery, expediting healing and improving overall health. In the spontaneously created art traversing child and adult stages of development, we discovered multiple prevalent themes within the imagery too numerous to ignore. Practice recommendations will be discussed for both art therapists and interprofessional healthcare collaborators concerning the use of imagery and visual expression when working with those who have sustained traumatic brain injuries.

Pain Following Obstetric Anal Sphincter Injuries: A Prospective Cohort Study.

Studies characterizing pain and pain management following obstetric anal sphincter injury (OASI) are limited. Our primary objective was to analyze time to pain resolution following OASI. Secondary objectives included analyzing pain severity, location, triggers, and patterns of pain medication use. This was a prospective cohort study of patients with OASIs seen in a postpartum care clinic at a tertiary referral center between 2017 and 2022. We analyzed data on pain resolution, visual analog scale pain scores, pain triggers, pain location, and pain medications. A total of 362 patients were included in this study. In the Kaplan-Meier estimator, 58.5% of patients showed resolution of pain by 3 months following their initial postpartum care clinic visit, and 73.3% showed resolution of pain by 6 months. The median months to pain resolution was 2.2 (95% confidence interval: 1.6-3.0) for patients with third-degree lacerations and 2.3 (95% confidence interval: 1.6-6.8) for patients with fourth-degree lacerations. Visual analog scale scores showed the most improvement in the first 2 months. Common pain triggers included sitting and bowel movements in the first few months, as well as intercourse during later recovery. Pain location varied over time; bilateral pain in the levator ani muscles and obturator internus were most prevalent at each time point. Pain appeared to be predominantly managed by acetaminophen and ibuprofen. Half of patients who experience OASI will have pain resolution by 2-3 months postpartum. Most patients will have resolution of their pain by 6 months postpartum.

Centellicum® improves scarring of traumatic wounds with irregular edges (lacerations).

Centellicum®, a standardized Centella Asiatica extract, has been used orally for fibrosis and scar prevention. The main aim of this 2-month registry pilot study was the reduction of visible, significant scars and keloids after suturing traumatic wounds with irregular edges (lacerations), using Centellicum®. The effects of oral Centellicum® (450 mg/day; 2 capsules) and a standard management (SM) on wound healing were compared with the effects of a control group that used only the standard management. Forty-eight otherwise healthy male subjects with lacerations requiring suturing were included in the study. 25 took Centellicum® in addition to the standard management and 24 followed the standard management only. No side effects were observed with the supplement. Centellicum® supplementation showed very good tolerability and compliance with 98% of the capsules correctly used. The two groups of otherwise healthy male subjects with lacerations were considered comparable at inclusion and there were no dropouts. No infections were observed. At 60 days, the scar dimensions were significantly smaller in the supplemented group (P<0.05). The elevation of the scar above the surrounding, non-affected skin, was also significantly reduced in the Centellicum® group compared to controls (P<0.05). Local pain levels were significantly lower (P<0.05) in the supplement group at 60 days. Additionally, the scar redness score was significantly lower in the supplement group compared to controls (P<0.05) by the end of the study. The incidence of initial keloid formation was significantly lower in the supplemented subjects at 60 days, as determined by finger-point pressure palpation and high-resolution ultrasound (P<0.05). Skin flux, as measured by laser Doppler flowmetry (indicating hypervascularization due to local inflammation) was lower (P<0.05) with Centellicum® at the end of the study. Inflammation, assessed via thermography (hot spots on the healing skin) was less visible and reduced in most areas in the supplement group (P<0.05) in comparison with the control group. Plasma oxidative stress was significantly lower in the Centellicum® group at the end of the study (P<0.05). Oral Centellicum® intake over 2 months improved healing of lacerations and reduced scarring, fibrosis and keloids at the level of the lesions. A larger study setup with more patients and with a prolonged study duration is needed to confirm these initial results.

The emerging role of photodynamic therapy in the treatment of cutaneous infections.

Cutaneous infections pose ongoing challenges to standard treatments due to resistance and limited efficacy. Photodynamic therapy (PDT) emerges as a promising supplement or an alternative to address complicated cases. In this review, we comprehensively review PDT's safety and efficacy in treating cutaneous infections. A PubMed systematic review with search terms for PDT treatment, hair, skin, and nail infections. There were a total of 43 studies on the use of PDT in cutaneous infections which discussed the treatment of viral (N.=20), bacterial (N.=11), fungal (N.=9), and protozoal (N.=3) infections. There is evidence for using PDT, mostly 5-aminolevulinic acid (5-ALA) and methyl aminolevulinate (MAL), in the treatment of cutaneous infections. Most evidence for viral infections involved treatment with 5-ALA PDT in condyloma acuminatum (CoAc), verruca vulgaris, and molluscum contagiosum. In bacterial infections, 5-ALA and MB PDT have been used to achieve complete remission in refractory Pseudomonas and atypical mycobacteria infections without recurrence. In onychomycosis, MAL PDT achieved a 40.9% cure rate and MB PDT showed a 77.8-100% cure rate with no reports of recurrence. Parasitic infections, such as leishmaniasis have also been successfully treated with both 5-ALA and MAL PDT. PDT is a promising treatment option for cutaneous infections, with growing evidence for its utility in treating cutaneous bacterial, viral, fungal, and parasitic infections, particularly those that fail standard treatments. Side effects were mostly limited to localized pain with good outcomes and low recurrence rates.

Swimmer arm-to-shoulder test for early differentiation between shoulder and cervical spine pathology in patients with shoulder pain

BackgroundSeveral tests have been suggested for screening and diagnosis of cervical spine and shoulder girdle conditions underlying shoulder pain with variable degrees of clinical accuracy. The present study aimed to test the reliability, clinical benefit and screening value of the Swimmer Arm-to-Shoulder (SAS) test; a new clinical test developed to differentiate shoulder impingement from cervical radiculopathy in patients with shoulder pain of ≤ 12 weeks.MethodsThe study included 718 patients aged 40–65 years, with unilateral and localized shoulder girdle pain lasting for ≤ 12 weeks. Diagnosis based on clinical, electromyography and radiological findings was considered as the reference gold standard for test assessment.ResultsClinical diagnosis identified shoulder pathology in 288 patients (40.1%) and cervical spine pathology in 430 patients (59.9%). SAS test was positive in 274 patients (38.2%). The SAS test proved to be effective in distinguishing shoulder from cervical spine pathology with a sensitivity of 89.2% (95% CI: 85.0-92.6%), specificity of 96.1% (95% CI: 93.8–97.7%), PPV of 93.8% (95% CI: 90.5–96.0%), NPV of 93.0% (95% CI: 90.5–94.9%), LR + of 22.6% (95% CI: 14.1–36.0%), LR- of 0.11 (95% CI: 0.08–0.16) and accuracy of 93.3% (95% CI: 91.2–95.0%).ConclusionsSAS test is an easy to perform, patient dependent and reliable as a screening test and diagnosis confirmatory test.

Neural therapy in notalgia paresthetica.

Notalgia Paresthetica (NP) is a type of chronic sensory neuropathy characterized by localized itching, pain and dysesthesias including numbness, tingling, burning, coldness, hypo- and hyperesthesia. It is frequently underdiagnosed and thus, there is no established standard of care for treatment. The objective of our study was to evaluate the efficacy of neural therapy in patients with NP. Patients aged 30-60 years with a diagnosis of NP for at least 6 months were included in our study. Intralesional and segmental neural therapy was administered to the patients in five sessions, with one-week intervals between each session. Patients were evaluated with numeric rating scale (NRS) for pain, the PainDETECT Questionnaire for neuropathic pain, the Short Form-12 (SF-12) for quality of life and the 5-D Itch Scale for pruritus. A total of 12 patients diagnosed with NP were included in the study. The median age of the patients included in the study was 45 years (33-59). 58.3% (n = 7) of the patients were female and 41.7% (n = 5) were male. The median duration of pain was 24 (6-60) months. Itching was observed in 75% (n = 9) and hypoesthesia was present in 58.3% (n = 7) of the patients. Comparisons were made with assessment scales before and 3 months after treatment. There was a significant difference in the pre-treatment NRS, PainDETECT Questionnaire, physical component of SF-12 and 5-D itch scale scores compared to post-treatment. Neural therapy represents a promising complementary treatment method for the reduction of pain, neuropathic pain, and pruritus in patients with NP. Furthermore, it has been demonstrated to enhance quality of life.

Osteomyelitis of the Proximal Ulna Positive for Aeromonas sobria Presenting as Olecranon Bursitis: A Case Report

Background Osteomyelitis is a bone infection, often arising secondary to trauma or infection. It most often occurs in the long bones such as the femur and tibia, and is characterized by swelling, pain, erythema, and constitutional symptoms. Olecranon bursitis often shares many of the characteristic findings of osteomyelitis including swelling, redness, edema, and localized pain. Case Presentation We report the case of a 71-year-old female with a history of osteoporosis, hyperlipidemia, and hypothyroidism who presented with symptoms and physical exam findings consistent with olecranon bursitis, but was determined to have posterior ulnar osteomyelitis from Aeromonas sobria. Unlike the common presentations of osteomyelitis, this patient presented without fever, pain, or associated erythema of the posterior ulna. X-rays were nondiagnostic but revealed subtle changes in the proximal ulna. An MRI was obtained which was concerning for a diagnosis of osteomyelitis versus neoplasm. Operative cultures and pathology confirmed osteomyelitis, and the patient was successfully treated with debridement of the affected tissue, followed by antibiotics PO for 42 days. The patient recovered with a full range of motion after two months, with no radiographic evidence of ulno-humeral arthritis. Conclusions While olecranon bursitis is one of the most common musculoskeletal diagnoses of the elbow, osteomyelitis of the proximal ulna is exceedingly rare. While MRI is not part of the standard work-up for olecranon bursitis, in this case, it was critical for obtaining the proper diagnosis. This case illustrates the importance of accurate radiographic interpretation as well as a high index of suspicion for underlying pathology when treating routine conditions such as olecranon bursitis.

The influence of pain on community reintegration after spinal cord injury.

Community reintegration is an important goal for people living with a spinal cord injury (SCI), and pain is suspected to limit reintegration due to its limitations in daily functioning, mood, and sleep. To determine the influence of pain on community reintegration in manual wheelchair users with SCI. The Reintegration to Normal Living Index was used to determine community reintegration, while the DN4 and the Wheelchair User's Shoulder Pain Index were used to determine the presence of neuropathic and shoulder pain respectively. Associations and differences between the pain variables and participants with and without pain were analyzed with Spearman correlations and Mann-Whitney U-tests using SPSS v27 at 0.05 significance level and 95% confidence interval. Of the 122 participants, 85.2% reported current pain, with a 77.7% median for community reintegration. Neuropathic pain (53.3%) was more common and severe than nociceptive shoulder pain (14.8%). There was no significant difference in community reintegration between participants with and without pain, nor any correlation between the overall presence of pain and community reintegration. The severity of pain, particularly shoulder pain, was negatively associated with taking trips out of town (p < 0.01), and overall community reintegration (p < 0.05). It is not the mere presence of pain that influences community reintegration, but rather the severity and the location of pain. Shoulder care and pain management need to be included in the rehabilitation program, as these are important considerations when rehabilitating people with SCI back into their communities.

A pilot study of novel ultrahigh-frequency dorsal root ganglia stimulation for chronic lower limb pain: Focusing on safety and feasibility.

This single-arm, open-label, single-center observational pilot study assessed the safety and efficacy of ultrahigh-frequency dorsal root ganglia (UHF-DRG) stimulation in patients with chronic leg pain with or without low back pain. Such high-frequency electrostimulation had not been conducted in the human central nervous system previously. The primary objective was to evaluate the safety of UHF-DRG stimulation (2 Hz pulses with 50 msec pulse-width and 500 kHz intrapulse sine waves, 5-min duration per stimulation) by identifying incident adverse events (AE) and severe adverse events (SAE) during the trial. The secondary objectives included assessment of pain reduction using a numerical rating score (NRS), presence of paraesthesia, and changes in four pain medications (weak opioids, anticonvulsants, antidepressants, and non-steroid-anti-inflammatory drugs). One DRG lead was implanted for one day then removed, and the patients received maximal three times of UHF stimulation in total. The study focused on ten cases. Two of them did not complete the study due to difficulty of lead implantation. There was no SAE in this trial. Among the ten cases, AEs occurred in eight, three experienced injection-related local pain and one of them had a post-dural-puncture headache, others had symptoms un-related to implantation procedure or UHF stimulation. The average NRS was reduced from 6.4 ± 1.1 at baseline to 2.9 ± 1.1 on the second-day post-implantation, and it was striking that the NRS was maintained at 3.6 ± 2.8 until 2 days after lead removal. The results showed a trend of lower frequency in medication use for all types of analgesics. In this first-in-human pilot study, we discovered that intermittent pulsed UHF-DRG stimulations ameliorated chronic lower limb pain for an extended period in humans. Our finding opens up a new neuromodulatory concept and may initiate a novel paradigm for treating intractable pain.

Evaluating the safety and efficacy of aminolevulinic acid 20% topical solution activated by blue light in the treatment of facial cutaneous squamous cell carcinoma in situ

Background: Cutaneous squamous cell carcinoma in situ (isSCC) is a common skin cancer occurring from sun exposure and often appears on the face. Treatment is primarily surgical but less invasive treatments are desirable. Currently, aminolevulinic acid for photodynamic therapy (ALA-PDT) is approved in the US and Canada for the treatment of single and multiple non-hyperkeratotic actinic keratoses of the face and scalp. This study evaluated the safety, tolerability, and efficacy of ALA-PDT for treatment of facial isSCC.Methods: Thirty-two patients with biopsy-confirmed isSCC on the face were recruited. Lesions 0.4–1.3 cm in diameter were included. Per the actinic keratosis treatment protocol, the lesion was debrided with a 4 x 4 gauze and ALA 20% topical solution was applied to the lesion and adjacent skin and incubated for 18–24 hours, followed by blue light therapy 16 minutes 40 seconds at 10 J/cm2. Patients underwent two treatments with ALA-PDT spaced 28 +/- 3 days apart. The area of the original lesion was excised eight weeks following the second treatment for histopathological assessment. The primary efficacy endpoint was the complete absence histologically of the isSCC at end of treatment. The secondary efficacy endpoint was the achievement of clinical clearance of the skin lesion. Safety assessment was done through adverse events and local skin reactions (LSRs; erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) and site pain within 15 minutes of each treatment session.Results: Of the 32 patients enrolled, two did not complete the study. No residual SCCis was detected in 30/30 (100%) patients. Clinical clearance was achieved in 30/30 (100%) of the patients by the end of treatment. None of the patients experienced related adverse events and only 2/30 (5%) experienced an AE of hypertension and was considered to be unrelated. The most common LSRs were erythema and scaling and were primarily mild, seen to occur immediately after both treatments and diminished over time. The average median ± SD immediate post-treatment pain score was 2.56 ± 2.15 on the VAS scale.Conclusion: The ALA-PDT protocol outlined in this study appears to be a very effective, safe and well-tolerated treatment option for isSCC on the face.

Safety and Effectiveness of Percutaneous Ethanol Injection as a Treatment for Locally Recurrent Papillary Thyroid Carcinoma

Background: Reoperation for recurrent papillary thyroid cancer (PTC) is associated with a high risk of complications and limited success in achieving sustained remission. Percutaneous ethanol injection (PEI) presents a potential non-surgical alternative for managing locally recurrent PTC. Objectives: This study aimed to evaluate the safety and effectiveness of PEI in treating recurrent PTC. Methods: From October 2017 to September 2021, PEI was administered to 39 recurrent lesions (23 lateral and 16 central) in 17 patients with PTC. The median follow-up duration was 21.4 months (range, 4.1 - 37.9), with ethanol injections delivered every 3 months under ultrasound (US) guidance as needed. Results: Most patients tolerated the treatment well, experiencing only mild local pain, though one patient reported Horner syndrome following the procedure. In terms of treatment frequency, 31 lesions required 3 or fewer injections, while the remaining lesions required more. The mean initial volume of the lesions decreased from 0.12 mm³ (range: 0.06 - 0.34 mm³) to 0.03 mm³ (range: 0.0 - 0.14 mm³), representing an average reduction of 72.6% (range: 20.0 - 100.0%). Of the 39 lymph nodes treated in 17 patients, 21 lymph nodes (54%) were completely resolved. Seven lymph nodes remain under ongoing ethanol treatment, while 11 lymph nodes in 4 patients were addressed with alternative treatments, including surgery. Conclusions: Percutaneous ethanol injection appears to be a safe and effective treatment option for managing locally recurrent thyroid carcinomas in select patients. However, further comparative, prospective, long-term studies are needed to evaluate PEI’s impact on patient survival and recurrence rates.

Effect of experimental knee pain location on gait kinematics.

In this study, we investigated whether experimental knee pain alters lower limb kinematics and knee arthrokinematics during gait, and if this motor adaptation depends on the spatial characteristics of the painful stimulus. Twenty-one participants walked on a treadmill for 60-s trials, either without stimulation or while experiencing painful electrical stimulation in the medial, lateral or anterior region of the knee. Perceived pain location was analyzed using pain drawing. Gait spatiotemporal parameters, lower limb kinematics, and dispersion of the knee helical axes on the sagittal plane were quantified for each trial and compared between conditions using ANOVAs with repeated measures or Friedman tests. Pain perception was localized in the area the stimulation was applied to. Compared to walking without pain, participants demonstrated reduced knee extension (1.5 ± 1.5 degrees, p = 0.002) and reduced hip extension (0.8 ± 1.1 degrees, p = 0.037) when pain was induced in the anterior region, but not medially or laterally. Anterior knee pain increased the mean distance of the helical axes during late stance (0.7 [0.3, 1.4], p = 0.010), while medial pain increased both mean distance (0.3 [0.1, 0.5], p = 0.037) and mean angle (1.2 ± 1.4, p = 0.010) during early swing. Acute, experimental knee pain alters gait kinematics and increases the dispersion of the helical axis. These adaptations depend on the spatial characteristics of the painful stimulus. These adaptations may reflect an attempt of the central nervous system to protect the painful tissue while searching for a less painful movement strategy.

Postpartum thromboprophylaxis with enoxaparin: a prospective cohort study on patients' adherence, injection experience, and information retention after counselling by pharmacists.

This research aimed to determine postpartum females' self-reported adherence to and experience with short-term thromboprophylaxis using enoxaparin injection, after counselling by pharmacists. It also sought to assess their knowledge of thromboprophylaxis, injection techniques, and confidence in self-injecting. This prospective cohort study was conducted at a public tertiary hospital in Malaysia from March to June 2023. Self-injection-naïve postpartum females who were initiated on thromboprophylaxis and counselled by a pharmacist were conveniently sampled. Knowledge regarding thromboprophylaxis, injection readiness, and technique were assessed one day after the counselling session. A telephonic interview was conducted at the end of the 10-day therapy to determine adherence and adverse effects experienced. A total of 259 subjects were successfully followed up, with 87.6% (n = 227) adherent to the therapy. Nonadherence was predominantly due to forgetfulness; four had their treatment withheld due to bleeding. One-third of subjects experienced localised pain and bruising. Subjects answered a median of 5/7 knowledge questions and recalled a median of 8/10 injection steps correctly, with those who read the information leaflet provided after counselling scoring significantly higher (P = .02). The majority declared moderate confidence in their ability to self-inject. Subjects who intended to self-inject (P < .01) and were more confident (P = .02) demonstrated better injection technique. Postpartum females counselled by pharmacists largely adhered to short-term enoxaparin for thromboprophylaxis. The impact of the counselling session may be enhanced by addressing their psychological readiness to self-inject, awareness of adverse effects identification, mitigation, and management, as well as setting reminders to prevent forgetfulness to inject.

Safety and immunogenicity of freeze-dried human rabies vaccines: A phase 3 clinical trial of Zagreb and Essen regimes

ABSTRACT Recently optimized freeze-dried rabies vaccines (Vero cell) are promising for rabies prevention; however, comparisons of Essen 5-dose and Zagreb 4-dose regimens are needed for clinical applications. This phase III clinical trial aimed to assess the safety and immunogenicity of candidate freeze-dried rabies vaccines developed for human use by Shandong Yeedo Biotechnology (Registration No.: CTR20182016, http://www.chinadrugtrials.org.cn/index.html). In total, 40 participants in stage I and 1797 subjects in stage II with an age range of 10–60 years were recruited. Both 4-dose and 5-dose experimental vaccines were well-tolerated in stage 1, with similar overall adverse event (AE) rates. In stage 2, systemic fever (35.39%) and local pain (48.91%) were common, and the rate of Grade 3 AEs was approximately 2.5%. Rates of local reactions and unsolicited AEs differed among groups (p = .045 and 0.011). Immunogenicity analyses showed higher antibody levels, seroconversion rates, and pre-immune seroconversion rates in the 4-dose experimental group versus the 5-dose group (p < .001) on day 7 post-first dose, with similar GMCs (geometric mean concentrations) by day 14. Pre-immune negative subjects had comparable antibody levels in the 4-dose and 5-dose experimental groups, outperforming the 5-dose control group (p = .039). The rate difference (95% CI) for first-dose seroconversion at 14 days post-vaccination among pre-immune antibody-negative subjects indicated non-inferiority between the 5-dose experimental and control groups. Overall, the Shandong Yeedo rabies vaccine demonstrated satisfactory safety and efficacy, offering a new option for rabies prevention.

Pressure Pain Threshold, Depression and Anxiety in Women with Primary Dysmenorrhea: A Prospective Cohort Study

Background: Primary dysmenorrhea is one of the main chronic pain conditions in women and is often associated with various psychiatric disorders and some painful conditions. Women with dysmenorrhea report the presence of abdominal and lumbar allodynia at the end of the menstrual cycle, suggesting an association between menstrual pain and increased mechanical hypersensitivity in the abdominal and lumbar regions. Therefore, the general objective of this study was to measure pressure pain thresholds and depressive and anxiety symptoms in Mexican women with primary dysmenorrhea. Methods: This prospective cohort study used a cross-sectional design with female students; being older than 17 years of age, being available during menstruation, and having moderate-to-severe primary dysmenorrhea diagnosed by a physician were inclusion criteria. After providing informed consent, the women completed a questionnaire assessing demographic information, variations in menstrual patterns, and menstrual pain and its severity. Similarly, the Beck Depression Inventory and Anxiety Inventory were administered to the participants prior to obtaining pressure pain thresholds at specific abdominal and lumbar points. The data were entered into a computerized database. Exploratory analysis was performed via Student’s t test, Pearson’s chi-square test, or analysis of variance. Statistical significance was considered when p &lt; 0.05. Results: A total of 69 women were included in the study. The mean ± standard deviation age of all participants was 20.9 ± 1.9 years. The main locations of menstrual pain were the lower abdomen (87.0%) and the lumbar region (10.1%). In terms of pain severity, 65.2% of the participants reported moderate pain, and 34.8% reported severe pain. With respect to the pain pressure threshold at the six evaluated points, the threshold in the abdominal region was significantly lower than the threshold in the lumbar region (p &lt; 0.05). No relationship was found between the severity of dysmenorrhea pain and the level of depression or anxiety or with the pain pressure thresholds (p &gt; 0.05). Conclusions: The severity of dysmenorrhea pain in the participating women was not associated with anxiolytic or depressive states. No significant relationship was found between the severity of dysmenorrhea and the sensitivity of the pressure pain threshold in the areas evaluated.

Optimizing Treatment Outcomes in Crohn's Disease: A Comprehensive Systematic Review and Meta-Analysis of Regenerative Therapies with Emphasis on Platelet-Rich Plasma.

Crohn's disease (CD) is a chronic inflammatory disorder that significantly affects patients' quality of life; conventional treatments often provide limited relief. This systematic review and meta-analysis explored the potential of regenerative therapies, particularly platelet-rich plasma (PRP), as an adjunctive treatment for CD. The study protocol was registered with PROSPERO (CRD42024576683), and a comprehensive search was conducted across major databases, such as PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. The search included terms related to CD and PRP. Studies assessing the efficacy of PRP in CD treatment were selected. Statistical analysis was conducted using the PICO framework with R software (version 4.3.2) and meta-package. Of the 29 studies identified, 10 met the inclusion criteria, comprising pilot studies and controlled trials. Nine studies focused on Crohn's disease perianal fistulas (CDPF), and one focused on colonic CD. Among 138 patients with CDPF, 82.44% showed some fistula healing after PRP treatment, with 48.05% achieving complete resolution. In a sub-analysis, combining PRP with a stromal vascular fraction (SVF) resulted in a 58.62% complete healing rate, whereas combining PRP with adipose-derived stem cells (ASCs) showed even higher efficacy at 85.89%. PRP treatment alone resulted in a lower complete healing rate of 38.51%. PRP was well tolerated, with minor side effects such as localized pain. These findings suggest that PRP, especially when combined with stem cells, offers a promising new approach for treating CD. However, larger trials are needed to confirm its long-term benefits and refine its clinical applications.

CTIM-15. LOCOREGIONAL ADMINISTRATION OF B7-H3-CAR T CELLS EXPRESSING 41BB LIGAND FOR PEDIATRIC PATIENTS WITH PRIMARY CNS TUMORS: PRELIMINARY RESULTS FROM A PHASE I STUDY

Abstract Outcomes for pediatric patients with diffuse midline glioma (DMG) and relapsed/refractory CNS malignancies remain poor. Loc3CAR is an ongoing, first-in-human, phase I clinical trial (NCT05835687) evaluating intracranial delivery of B7-H3-CAR T cells expressing 41BB ligand (B7-H3-CAR-T) for patients ≤21 years old with i) relapsed/refractory B7-H3+ CNS tumors (Cohort A), or ii) DMG post-radiation (Cohort B). Treatment included 6 intracerebroventricular B7-H3-CAR-T infusions administered over 7 weeks. Primary and secondary outcomes were safety and disease response, respectively. To date, 84% (21/25) of tumors screened were B7-H3+ (median H-score 200; range 0-300). CAR-T products were successfully manufactured for all patients enrolled on the collection/manufacture phase of the trial (n=11). Eight patients (7 cohort A; 1 cohort B) were treated with a total of 42 infusions on dose level 1 (1x107/3x107 CAR+ T cells/dose). Post-infusion, multiple participants exhibited neurologic findings suggestive of on-tumor CAR-T activation, including seizure, dysphasia, and localized pain. One patient, with a large tumor burden and high B7-H3 expression (H-score = 300), experienced a dose limiting toxicity with unresponsiveness and decorticate posturing approximately 16 hours post-infusion #1. Their clinical status rapidly improved following CSF removal and intravenous dexamethasone. Common adverse events attributable to B7-H3-CAR-T included headache (8/8), fever (7/8), and nausea/vomiting (5/8). Two of 7 (29%) evaluable patients achieved clinical benefit with stable disease at week 8. B7-H3-CAR-T and inflammatory cytokines were detected in the CSF from all patients evaluated. Circulating tumor DNA (ctDNA) was measured using a novel DNA methylation-based sequencing pipeline and detected in the CSF from 6/8 patients. For 2 patients, ctDNA abundance increased post-infusion, followed by clearance, suggesting subclinical antitumor activity. Single cell RNAseq of immune cells in the CSF from 1 patient analyzed to date, demonstrated abundant Tregs post-infusion #4, suggesting B7-H3-CAR-T may induce local anti-inflammatory responses. Overall, intracranially administered B7-H3-CAR-T have an acceptable safety profile and warrant continued exploration for pediatric patients with CNS tumors.

A case series and review of stereotactic body radiation therapy for contiguous multilevel spine metastases.

A majority of published series report on stereotactic body radiation therapy (SBRT) for 1-2 contiguous vertebral levels due to concerns regarding setup accuracy and radiation toxicity. This study evaluates patients with metastases spanning ≥ 3 contiguous levels treated with SBRT and augments its findings with a review of other studies investigating multilevel spine SBRT. Analysis of a prospectively collected database of 49 patients with 55 metastases spanning ≥ 3 contiguous vertebral levels treated with SBRT at a single institution (2002-2023) was performed. Outcomes identified included local failure (LF), pain response, overall survival, and toxicity. The median single-fraction prescription dose was 15Gy (range: 8-18); multifractionated treatment utilized prescription doses of 18-30Gy in 2-5 fractions. Median follow-up was 7 months (range: 1-103). The 6-month, 1-year, and 2-year cumulative incidence rates of LF were 7%, 11%, and 11%, respectively. No prognostic factors were associated with LF. Pain was reported to improve or remain stable for 49 lesions (89%). Ten adverse radiation events (18%) were identified; pain flare (5%), dermatitis (4%), and vertebral compression fracture (VCF, 9%). The 3-month, 6-month, and 1-year cumulative incidence rates of VCF were 4%, 7%, and 7%, respectively. No instances of esophageal toxicity or myelopathy were observed. This study of multilevel SBRT is one of the largest to investigate outcomes in this challenging clinical scenario. Spine SBRT confers low rates of LF and toxicity for patients with multilevel disease, which was previously considered a relative contraindication. Spine SBRT may be considered in this patient population instead of low-dose palliative RT.