Complex regional pain syndromes (CRPS) are characterized by persistent and severe pain after trauma or surgery. Neuro-immune alterations are assumed to play a pathophysiological role. Here we set out ...to investigate whether patients with CRPS have altered systemic pro- and anti-inflammatory cytokine profiles compared to controls on mRNA and protein level. We studied blood cytokine mRNA and protein levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF), interleukin-2 (IL-2) and IL-8 and the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor-β1 (TGFβ1) in 40 prospectively recruited patients with CRPS I, two patients with CRPS II, and 34 controls. Quantitative real-time PCR and enzyme linked immunosorbent assay were used. Additionally, the patients underwent quantitative sensory testing and were assessed with the McGill pain questionnaire and the Hospital anxiety and depression scale. Patients with CRPS had higher blood TNF and IL-2 mRNA levels (
p
=
0.005;
p
=
0.04) and lower IL-8 mRNA levels (
p
<
0.001) than controls. The mRNA for the anti-inflammatory cytokines IL-4 and IL-10 was reduced in the patient group (
p
=
0.004;
p
=
0.006), whereas TGFβ1 mRNA levels did not differ between groups. These results were paralleled by serum protein levels, except for TGFβ1, which was reduced in patients with CRPS, and for IL-8, which gave similar protein values in both groups. Sensory testing showed a predominant loss of small fiber-related modalities in the patient group. The shift towards a pro-inflammatory cytokine profile in patients with CRPS suggests a potential pathogenic role in the generation of pain.
Posttraumatic TNF-alpha signaling may be one of the factors responsible for pain and hyperalgesia in complex regional pain syndromes (CRPS). In order to further specify the role of TNF-alpha we ...investigated tissue (skin) and serum concentrations in three different patient groups: patients with osteoarthritis and planned surgery, with acute traumatic upper limb bone fracture waiting for surgery, and with CRPS I. Thirty patients (10 in each group) were recruited. Mean CRPS duration was 36.1±8.1weeks (range 8–90weeks). Skin punch biopsies were taken at the beginning of the surgery in osteoarthritis and fracture patients and from the affected side in CRPS patients. Blood samples were taken before the respective procedures. Skin and serum TNF-alpha levels were quantified by ELISA. Compared to patients with osteoarthritis, skin TNF-alpha was significantly elevated in CRPS (p<0.001) and fracture patients (p<0.04). Skin TNF-alpha in CRPS patients was higher than in patients with acute bone fracture (p<0.02). In contrast, serum TNF-alpha values were the same in osteoarthritis and CRPS, and lower in fracture patients (p<0.03). Our results indicate a local but not systemic increase of TNF-alpha in CRPS patients. This increase persists for months after limb trauma and may offer the opportunity for targeted treatment.
We provide evidence that elevated serum osteoprotegerin reflects pathophysiological processes of complex regional pain syndrome.
Osteoprotegerin (OPG) is important for bone remodeling and may ...contribute to complex regional pain syndrome (CRPS) pathophysiology. We aimed to assess the value of OPG as a biomarker for CRPS and a possible correlation with radiotracer uptake in 3-phase bone scintigraphy (TPBS). OPG levels were analyzed in 23 CRPS patients (17 women; mean age 50±9.0years; disease duration: 12weeks IQR 8–24), 10 controls (6 women; mean age 58±9.6years) and 21 patients after uncomplicated fractures (12 women; mean age: 43±15years; time after fracture: 15weeks IQR: 6–22). The CRPS and control patients also underwent TPBS. OPG in CRPS patients was significantly increased by comparison with both control groups (P=0.001; Kruskal-Wallis test; CRPS patients: 74.1pg/mL IQR: 47.1–100.7; controls: 46.7pg/mL IQR: 35.5–55.0; P=0.004; fracture patients: 45.9pg/mL IQR: 37.5–56.7; P=0.001). As a diagnostic test for CRPS, OPG had a sensitivity of 0.74, specificity of 0.80, positive predictive value of 68% and negative predictive value of 84%. Receiver operating characteristic curve analysis showed an area under the curve of 0.80 (CI: 0.68–0.91). For the CRPS-affected hand, a significant correlation between OPG and TPBS region of interest analysis in phase III was detected (carpal bones; r=0.391; P=0.03). The persistent OPG increase in CRPS indicates enhanced osteoblastic activity shown by increased radiotracer uptake in TPBS phase III. A contribution of bone turnover to CRPS pathophysiology is likely. OPG might be useful as a biomarker for CRPS.
Traditional Chinese Medicine acupuncture compared to sham acupuncture with Streitberger placebo needles shows a minimal relief of capsaicin-induced pain in healthy subjects.
Acupuncture is frequently ...used to treat pain, although data supporting the analgesic efficacy from placebo-controlled studies is sparse. In order to get evidence for acupuncture analgesia we performed a study with 2 well-recognized experimental human pain models – the cold-pressor (CP) test and intradermal capsaicin injection. Fifty healthy men were included. Our study compared Traditional Chinese Medicine-based acupuncture to sham acupuncture with Streitberger placebo needles in a randomized, controlled, double-blinded trial. The primary endpoint was the reduction of mean pain intensity during 3minutes of CP test or of mean pain intensity within 10minutes after capsaicin injection. Secondary parameters were defined to substantiate the findings. To ensure comparability, somatosensory (measured by quantitative sensory testing) and psychological parameters were investigated and found to be the same in both groups. Analyses (repeated-measures analyses of variance) showed a significant (P=0.009) but clinically questionable pain reduction in the verum group for capsaicin-induced pain, which was mainly driven by an effect of Traditional Chinese Medicine acupuncture on small pain ratings (max. reduction from 7/100 rating at baseline to 2.5/100 at intervention). Neither pin-prick hyperalgesia, nor allodynia, nor neurogenic flare associated with capsaicin injection, nor pain ratings during the CP test, were significantly different between groups. In addition, there was no placebo response. Attitude towards acupuncture and partial unblinding did not affect the results. We conclude that acupuncture on predefined points has a minor effect on experimental pain in healthy subjects.
Abstract Objectives Liquid biopsy (LBx) provides diagnostic, prognostic and predictive insights for malignant diseases and offers promising applications regarding tumor burden, tumor heterogeneity ...and clonal evolution. Methods The Augsburg Longitudinal Plasma Study (ALPS) is a prospective trial for patients with metastatic cancer that comprises sequential collection of LBx samples, tumor tissue, radiological imaging data, clinical information and patient-reported outcomes. Peripheral blood plasma is collected based on the individual patient’s staging intervals and LBx-derived ctDNA analyses are performed using CAncer Personalized Profiling sequencing (CAPP-seq). Results From April 2021 to October 2023, 419 patients have been enrolled. A total of 1,293 LBx samples were collected, 419 samples (100 %) at the beginning of the study and an average of 3 (range 1–12) during the 30-month follow-up period of the current interim analysis. 380 tissue biopsy (TBx) samples (90.7 %) were available at baseline and 39.6 % had ≥1 TBx samples at follow-up. Lung cancer patients are most prevalent in ALPS (n=147), followed by colorectal (n=38), prostate (n=31) and gastroesophageal cancer (n=28). On average, 12.0 ng/mL plasma cell-free DNA (cfDNA) could be isolated. First CAPP-seq analyses in 60 patients comprised 110 samples and demonstrated a detection sensitivity of 0.1 %. Conclusions The first interim analysis of ALPS confirms feasibility for comprehensive longitudinal evaluation of LBx and demonstrates suitability for ctDNA evaluation.
Abstract The effect of oligofructose and/or curdlan oligosaccharides (CO) addition on the characteristics of probiotic fermented beverages processed with water-soluble rice extract (WSRE) was ...evaluated. The products were assessed for the physicochemical characteristics, rheological parameters, and probiotic survival (L. casei) during storage (28 days, 7 °C). Probiotic counts higher than 108 CFU mL-1 and 106 CFU mL-1 were observed during storage and after simulated gastrointestinal conditions (SGIC). Oligofructose addition increased the red color of the products (increase in a* values) and acted as a prebiotic component during storage and SGIC, increasing probiotic survival. CO addition resulted in higher acidity (lower pH and higher titratable acidity values) and lower consistency (lower k and higher n values). It acted as a prebiotic component during fermentation, storage, and SGIC, promoting the highest increase in probiotic survival. Furthermore, CO improved the storage stability, reducing the post-acidification and the alterations in the rheological parameters.
O uso do product placement em séries de TV tem crescido substancialmente nos últimos anos e, por isso, existe a necessidade de entender melhor como o público percebe o uso desta estratégia de ...marketing. Frente a isso, este trabalho objetiva analisar a percepção que brasileiros e americanos têm em relação ao uso de product placement em séries de TV. Para o desenvolvimento do estudo, realizou-se uma pesquisa quantitativa com brasileiros e americanos, aplicada, principalmente, através de redes sociais. Além de questões de perfil do consumidor, investigaram-se os seguintes construtos: percepção geral do uso de product placement em séries de TV; aceitação do seu uso; atitudes para com o seu uso; interesse e a intenção de compra que o product placement desperta. Verificou-se que brasileiros e americanos têm boa aceitação do uso da estratégia. Americanos apresentam atitudes mais favoráveis ao uso de product placement, enquanto brasileiros têm uma percepção geral mais positiva e também apresentam maior interesse na marca e maior intenção de compra despertada através do uso de placements.
Background: The objective of this study was to determine whether differentiation between demyelinating and axonal neuropathies could be enhanced by comparing conduction time changes in defined ...segments of the total peripheral nerve pathway. Methods: Compound muscle action potentials (CMAPs) were elicited by cathodal stimulation of the tibial nerve at the ankle and popliteal fossa, and by paravertebral neuromagnetic stimulation at proximal and distal cauda equina while recording from muscles of the foot, shin, and thigh. Segmental conduction times were calculated in normal subjects; in patients with lumbosacral radiculopathy, distal symmetric diabetic neuropathy, amyotrophic lateral sclerosis, acute and chronic inflammatory demyelinating polyneuropathy; and in patients with anti–myelin‐associated glycoprotein, myelomatous, and Charcot–Marie–Tooth type 1a polyneuropathies. Results: Distal cauda equina latency and CMAP duration and segmental conduction times in upper leg and cauda equina facilitated differentiation of demyelinating from axonal neuropathies, even in the presence of a range of reduced amplitude CMAPs. Conclusions: Within the demyelinating neuropathy spectrum, it was further possible to distinguish subtypes. Muscle Nerve, 2011
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