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Background Low back pain (LBP) is one of the greatest contributors to disability in the world and there is growing interest on the role of biomarkers in LBP. To purpose of this review was to analyze available evidence on the relationship between inflammatory biomarkers, clinical presentation, and outcomes in patients with acute, subacute and chronic non-specific low back pain (NSLBP). Methods A search was performed in Medline, Embase, Cinahl and Amed databases. Studies which measured levels of inflammatory biomarkers in participants with NSLBP were included. Two reviewers independently screened titles and abstracts, full-texts, and extracted data from included studies. Methodological quality was assessed using the Newcastle Ottawa Quality Assessment Scale. Level of evidence was assessed using the modified GRADE approach for prognostic studies. Results Seven primary studies were included in this review. All results assessed using the modified GRADE demonstrated low to very low quality evidence given the small number of studies and small sample. Three studies examined C-reactive protein (CRP), one of which found significantly higher CRP levels in an acute NSLBP group than in controls and an association between high pain intensity and elevated CRP. Three studies examined tumor necrosis factor alpha (TNF-α), two of which found elevated TNF-α in chronic NSLBP participants compared to controls. Two studies examined interleukin 6 (IL-6), none of which found a significant difference in IL-6 levels between NSLBP groups and controls. Two studies examined interleukin 1 beta (IL-β), none of which found a significant difference in IL-β levels between NSLBP groups and controls. Conclusions This review found evidence of elevated CRP in individuals with acute NSLBP and elevated TNF-Α in individuals with chronic NSLBP. There are a limited number of high-quality studies evaluating similar patient groups and similar biomarkers, which limits the conclusion of this review.

Chronic low back pain (CLBP) affects over 20% of adults worldwide. Despite the socioeconomic burden caused by this condition, there is no gold standard treatment for CLBP, and its etiology remains nonspecific in 85% of cases. Available evidence indicates that CLBP patients have higher postprandial glycemic responses to beverages that rank high on the glycemic index and that this finding correlates with pain severity. Therefore, understanding modifiable factors that predict blood glucose regulation in CLBP patients could reveal important information for the management of the condition. This study aimed to (1) examine the relationship between predictor variables and the overall glycemic response, measured by the incremental area under the curve (IAUC), and (2) assess the temporal changes in patients' blood glucose levels immediately after sucrose intake. This dual approach enables a nuanced understanding of both the cumulative and immediate impacts of sucrose intake on glycemic control, facilitating insights into personalized management strategies for mitigating glycemic variability. A secondary analysis of a case-control randomized controlled crossover trial to identify predictive factors for impaired blood glucose regulation. Vrije Universiteit Brussel, Belgium. Individuals with chronic low back pain (CLBP) were randomized to consume either a sucrose or isomaltulose beverage. Body composition, dietary intake, physical activity levels, psychological factors, and blood glucose levels were measured. Multiple linear regression was used to examine the relationship between baseline variables and postprandial glucose response following intake of the high-glycemic index beverages, and a linear mixed model (LMM) was applied to assess the relationship between sucrose intake and identified potential predictors. Our findings revealed that higher weight (P < 0.001; t = -4.06), higher age (P = 0.003; t = 3.06), higher inflammatory dietary properties (P = 0.025; t = 2.28), worse mental health (P = 0.021; t = 2.34), and lower diet quality (P = 0.002; t = 3.22) were associated with a significant predictive value for altered postprandial sucrose responses. This study is a secondary analysis of a crossover case-control trial, so causal interpretations should be made cautiously. Additionally, postprandial glucose was measured using a self-monitoring finger-prick device, which lacked real-time data, and the findings were specific to women and may not apply to men. These results confirm the potential relevance of targeting lifestyle factors in people with CLBP.

Study designProspective longitudinal study.ObjectiveTo determine whether systemic cytokines and C-reactive protein (CRP) during an acute episode of low back pain (LBP) differ between individuals who did and did not recover by 6 months and to identify sub-groups based on patterns of inflammatory, psychological, and sleep features associated with recovery/non-recovery.Summary of background dataSystemic inflammation is observed in chronic LBP and may contribute to the transition from acute to persistent LBP. Longitudinal studies are required to determine whether changes present early or develop over time. Psychological and/or sleep-related factors may be related.MethodsIndividuals within 2 weeks of onset of acute LBP (N = 109) and pain-free controls (N = 55) provided blood for assessment of CRP, tumor necrosis factor (TNF), interleukin-6 (IL-6) and interleukin-1β, and completed questionnaires related to pain, disability, sleep, and psychological status. LBP participants repeated measurements at 6 months. Biomarkers were compared between LBP and control participants at baseline, and in longitudinal (baseline/6 months) analysis, between unrecovered (≥pain and disability), partially recovered (reduced pain and/or disability) and recovered (no pain and disability) participants at 6 months. We assessed baseline patterns of inflammatory, psychological, sleep, and pain data using hierarchical clustering and related the clusters to recovery (% change in pain) at 6 months.ResultsCRP was higher in acute LBP than controls at baseline. In LBP, baseline CRP was higher in the recovered than non-recovered groups. Conversely, TNF was higher at both time-points in the non-recovered than recovered groups. Two sub-groups were identified that associated with more (“inflammatory/poor sleep”) or less (“high TNF/depression”) recovery.ConclusionsThis is the first evidence of a relationship between an “acute-phase” systemic inflammatory response and recovery at 6 months. High inflammation (CRP/IL-6) was associated with good recovery, but specific elevation of TNF, along with depressive symptoms, was associated with bad recovery. Depression and TNF may have a two-way relationship.Graphical abstractThese slides can be retrieved under Electronic Supplementary Material.

The early and accurate diagnosis of acute myocardial infarction (AMI) is an important medical and economic challenge. We aimed to prospectively evaluate the performance of the new European Society of Cardiology rapid 0-hour/3-hour (0 h/3 h) rule out protocol for AMI. We enrolled 2,727 consecutive patients presenting with suspected AMI without persistent ST-segment elevation to the emergency department in a prospective international multicenter study. The final diagnosis was adjudicated by 2 independent cardiologists. The performance of the 0 h/3 h rule out protocol was evaluated using 4 high-sensitivity (primary analysis) and 3 sensitive cardiac troponin (cTn) assays. Acute myocardial infarction was the final diagnosis in 473 patients (17.3%). Using the 4 high-sensitivity cTn assays, the 0-hour rule out protocol correctly ruled out 99.8% (95% [confidence interval] CI, 98.7%-100%), 99.6% (95% CI, 98.5%-99.9%), 100% (95% CI, 97.9%-100%), and 100% (95% CI, 98.0%-100%) of late presenters (>6 h from chest pain onset). The 3-hour rule out protocol correctly ruled out 99.9% (95% CI, 99.1%-100%), 99.5% (95% CI, 98.3%-99.9%), 100% (95% CI, 98.1%-100%), and 100% (95% CI, 98.2%-100%) of early presenters (<6 h from chest pain onset). Using the 3 sensitive cTn assays, the 0-hour rule out protocol correctly ruled out 99.6% (95% CI, 98.6%-99.9%), 99.0% (95% CI, 96.9%-99.7%), and 99.1% (95% CI, 97.2%-99.8%) of late presenters; and the 3-hour rule out protocol correctly ruled out 99.4% (95% CI, 98.3%-99.8%), 99.2% (95% CI, 97.3%-99.8%), and 99.0% (95% CI, 97.2%-99.7%) of early presenters. Overall, the 0 h/3 h rule out protocol assigned 40% to 60% of patients to rule out. None of the patients assigned rule out died during 3-months follow-up. The 0 h/3 h rule out protocol seems to allow the accurate rule out of AMI using both high-sensitivity and sensitive cTn measurements in conjunction with clinical assessment. Additional studies are warranted for external validation.

Background Pelvic congestion syndrome(PCS) is a complex condition, with ongoing controversies regarding its diagnosis, treatment, and long-term effects, especially concerning reproductive health. Endovenous embolization performed for PCS may alter pelvic hemodynamics and ovarian perfusion, which may change ovarian reserve and menstrual cycle characteristics. This study aimed to investigate the efficacy and impact of endovenous embolization on ovarian reserve and menstrual cycle parameters in patients with PCS. Methods This retrospective, single-centre study analysed data from 81 patients diagnosed with PCS who underwent endovenous embolization. Symptom-specific Visual Analogue Scale(VAS) scores, serum anti-Müllerian hormone(AMH), follicle-stimulating hormone(FSH), luteinizing hormone(LH), estradiol(E2), prolactin levels, and menstrual cycle characteristics were evaluated before and 6 and 12 months after the procedure. The primary outcome of this study was improvement in symptoms. Secondary outcomes included changes in serum hormone levels and menstrual cycle characteristics. We categorized our study population into four age groups(< 30, 30–34, 35–39, and 40–44 years) to minimize the impact of age as a confounding variable. These groups were designated as G1, G2, G3, and G4, respectively. Results A statistically significant decrease was observed in VAS scores related to chronic pelvic pain(CPP), dyspareunia, and dysmenorrhea. A statistically significant decrease in serum AMH levels was observed 6 and 12 months after endovenous embolization. We observed a decline in AMH levels in G1, G2, G3, and G4(9.75±6.67%, 9.48±4.38%, 12.49±12.11%, and 13.79±11.46%, respectively). No significant changes were found in serum FSH, LH, E2, and prolactin levels. Additionally, a statistically significant decrease in menstrual cycle duration was detected after the procedure. Conclusions Our study demonstrated that endovenous embolization appears to be an effective treatment modality for symptom relief. The effect of endovenous embolization on ovarian reserve was generally consistent with physiological changes associated with age, but changes in patients under the age of 30 should not be overlooked. Larger, prospective, multi-centre studies are warranted to validate these findings and explore the long-term effects of endovenous embolization regarding reproductive health. Trial registration Not applicable.

Clinical work-up for suspected cardiac chest pain is resource intensive. Despite expectations, high-sensitivity cardiac troponin assays have not made decision making easier. The impact of recently validated rapid triage protocols including the 0-hour/1-hour hs-cTn protocols on care and outcomes may be limited by the heterogeneity in interpretation of troponin profiles by clinicians. We have developed machine learning (ML) models which digitally phenotype myocardial injury and infarction with a high predictive performance and provide accurate risk assessment among patients presenting to EDs with suspected cardiac symptoms. The use of these models may support clinical decision-making and allow the synthesis of an evidence base particularly in non-T1MI patients however prospective validation is required. We propose that integrating validated real-time artificial intelligence (AI) methods into clinical care may better support clinical decision-making and establish the foundation for a self-learning health system. This prospective, multicenter, open-label, cluster-randomized clinical trial within blinded endpoint adjudication across 12 hospitals (n = 20,000) will randomize sites to the clinical decision-support tool or continue current standard of care. The clinical decision support tool will utilize ML models to provide objective patient-specific diagnostic probabilities (ie, likelihood for Type 1 myocardial infarction [MI] versus Type 2 MI/Acute Myocardial Injury versus Chronic Myocardial Injury etc.) and prognostic assessments. The primary outcome is the composite of cardiovascular mortality, new or recurrent MI and unplanned hospital re-admission at 12 months post index presentation. Supporting clinicians with a decision support tool that utilizes AI has the potential to provide better diagnostic and prognostic assessment thereby improving clinical efficiency and establish a self-learning health system continually improving risk assessment, quality and safety. ANZCTR, Registration Number: ACTRN12620001319965, https://www.anzctr.org.au/.

Background Postoperative visceral pain is common after surgery and previous studies have demonstrated that oxycodone is an effective treatment. In this study, we compared the effects of preemptive oxycodone to equal dose of sufentanil on postoperative pain and serum level of inflammatory factors (TNF-α, IL-6, IL-10) after laparoscopic cholecystectomy. Methods Forty patients undergoing laparoscopic cholecystectomy were randomized into preemptive oxycodone group or preemptive sufentanil group. Patients were given either oxycodone 0.1 mg/kg (oxycodone group, n  = 20) or sufentanil 0.1 μg/kg (sufentanil group, n = 20) for preemptive analgesia. We evaluated pain/sedation scores at 0 h, 0.5 h, 2 h, 4 h, 6 h, 8 h and 24 h after surgery and measured serum concentrations of TNF-α, IL-6 and IL-10 before surgery and at 0 h, 6 h and 24 h after surgery. Results Twenty patients were recruited in each group. Numerical rating scale (NRS) of visceral pain in the oxycodone group at 2 h when resting (0.5(0,2.75) vs 3(2,4), P  = 0.008) and moving (0.5(0,3) vs 3(2.25,4), P  = 0.015) and 4 h when moving (2(0,3) vs 3(0,4.75), P  = 0.043) after surgery were significantly lower than the sufentanil group. Serum concentrations of TNF-α at 6 h (38.68 ± 10.49 vs 73.02 ± 16.27, P <0.001) and 24 h (43.12 ± 8.40 vs 74.00 ± 21.30, P <0.001) in the oxycodone group were lower than the sufentanil group. Conclusions Preemptive oxycodone 0.1 mg/kg administration could effectively suppress visceral pain at 2 h and 4 h after surgery and had lower inflammatory marker, serum TNF-α, level when compared to equal dose of sufentanil. Trial registration Clinical trials registration number: ChiCTR-IOR-17013738 http://www.chictr.org.cn/showproj.aspx?proj=17346 . Date of registration: 6th December 2017.

BACKGROUND: Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to insulin. IR has been associated with multiple conditions, including chronic pain. Fibromyalgia (FM) is one of the common generalized chronic painful conditions with an incidence rate affecting 3% to 6% of the population. Substantial interest and investigation into FM continue to generate many hypotheses. The relationship between IR and FM has not been explored. IR is known to cause abnormalities in the cerebral microvasculature, leading to focal hypoperfusion. IR also has been shown to cause cognitive impairment in FM patients, as in parkinsonism. As demonstrated by advanced imaging methods, similar brain perfusion abnormalities occur in the brain of patients with FM as with IR. OBJECTIVES: To determine the potential association between FM and IR. SETTING: Subspecialty pain medicine clinics. STUDY DESIGN: Observational cross-sectional study. METHODS: Laboratory data was extracted through a retrospective review of medical records from patients who had met the American College of Rheumatology (ACR) criteria for FM. The Hemoglobin A1c (HbA1c) values from 33 patients with FM were compared with the means of the glycated HbA1c levels of 2 control populations. In addition, established indices of IR [Quantitative Insulin Sensitivity Check Index (QUICKI) and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)] were calculated in a subgroup of patients in whom the analytes necessary for these calculations were available. To assess for confounding factors, the associations between HbA1c, QUICKI, HOMA-IR, fasting insulin levels, and glucose, after controlling for age, were explored by multiple analyses of variance with relation to gender and ethnicity. RESULTS: We found an association between IR and FM that was independent of age, gender, and ethnicity. We found that patients with FM belong to a distinct population that can be segregated from the control groups by their HbA1c levels, a surrogate marker of IR. This was demonstrated by analyzing the data after introducing an age correction into a linear regression model. This strategy showed significant differences between patients with FM and control subjects (P < 0.0001 and P = 0.0002, for 2 separate control populations, respectively). A subgroup analysis using the QUICKI and HOMA-IR showed that all patients with FM in this subgroup (100%) exhibited laboratory abnormalities pointing to IR. LIMITATIONS: Small observational cross-sectional study. There are also intrinsic limitations that are attributed to cross-sectional studies. CONCLUSION: The association demonstrated in this study warrant further investigation, including the pursuit of randomized, double-blind clinical trials to determine the effect of improving insulin sensitivity in FM related pain scores. Such studies could unveil a potential pathogenetic relationship between FM, central pain, and IR. Based on these initial findings, we present the hypothesis that IR may underlie pathological mechanisms leading to central pain. If confirmed, this may lead to a paradigm shift in the management of central pain. KEY WORDS: Fibromyalgia, insulin resistance, chronic widespread pain, hemoglobin A1c

This study is primarily aimed at assessing serum changes on a large panel of proteins in patients with chronic back pain following spa therapy, as well as evaluating different spa therapy regimens as a preliminary exploratory clinical study. Sixty-six patients with chronic back pain secondary to osteoarthritis were randomly enrolled and treated with daily mud packs and bicarbonate-alkaline mineral water baths, or a thermal hydrotherapy rehabilitation scheme, the combination of the two regimens or usual medication only (control group), for two weeks. Clinical variables were evaluated at baseline, after 2 and 12 weeks. One thousand serum proteins were tested before and after a two-week mud bath therapy. All spa treatment groups showed clinical benefit as determined by improvements in VAS pain, Roland Morris disability questionnaire and neck disability index at both time points. The following serum proteins were found greatly increased (≥2.5 fold) after spa treatment: inhibin beta A subunit (INHBA), activin A receptor type 2B (ACVR2B), angiopoietin-1 (ANGPT1), beta-2-microglobulin (B2M), growth differentiation factor 10 (GDF10), C-X-C motif chemokine ligand 5 (CXCL5), fibroblast growth factor 2 (FGF2), fibroblast growth factor 12 (FGF12), oxidized low density lipoprotein receptor 1 (OLR1), matrix metallopeptidase 13 (MMP13). Three proteins were found greatly decreased (≤0.65 fold): apolipoprotein C-III (Apoc3), interleukin 23 alpha subunit p19 (IL23A) and syndecan-1 (SDC1). Spa therapy was confirmed as beneficial for chronic back pain and proved to induce changes in proteins involved in functions such as gene expression modulation, differentiation, angiogenesis, tissue repair, acute and chronic inflammatory response.

Background: Acupuncture effectively reduces chronic neck pain and plasma Substance P (SP) levels, but upstream molecular mechanisms remain unknown. Objectives: We aimed to identify circulating microRNAs (miRNAs) associated with acupuncture-induced SP reduction and explore potential neuroplasticity mechanisms. Methods: We performed longitudinal plasma miRNA profiling (Affymetrix miRNA 4.0 Array, ~4600 miRNAs) in chronic neck pain patients: Acupuncture group (n = 3; 0, 4, 8 weeks) and Control group (n = 3; 0, 4 weeks). Linear Mixed-Effects Models (LMMs) tested associations between each miRNA and SP dynamics (miRNA × Time × Group interaction). Statistical significance was validated using permutation testing (2000 iterations). Results: Screening identified 53 miRNAs significantly associated with SP, validated by permutation testing (p < 0.001). Fourteen high-confidence miRNAs showed significant three-way interactions, indicating treatment-specific SP relationships. The most significant was miR-1302-6 (p = 7.65 × 10−6), followed by miR-181b-2. These miRNAs displayed diverse temporal patterns: some (miR-196b, miR-6788) increased during treatment, while others (let-7d, miR-1302-6) decreased parallel to SP. Functional enrichment revealed striking convergence on neuroplasticity pathways: axon guidance (p = 2.61 × 10−6), MAPK signaling (p = 4.18 × 10−5), neuron projection development (p = 7.52 × 10−10), and synaptic structures (p = 9.52 × 10−12). Conclusions: This exploratory study provides first molecular evidence for an acupuncture-miRNA-SP axis in chronic pain. The enrichment of neuroplasticity pathways suggests acupuncture may induce structural remodeling of nociceptive circuits rather than simply suppressing inflammation, offering novel mechanistic insights and potential biomarkers for personalized acupuncture therapy. The trial was registered with the Korean Clinical Trial Registry (KCT0005363).