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Galvanic current has been emerging as a novel therapy to regenerate chronic tissue lesions, including musculoskeletal and dermatological lesions. Recently, the NLRP3 inflammasome and IL-1β release have been identified as a signaling pathway triggered upon galvanic current application. However, the parameters for the clinical application of galvanic current remain subjective to the experience of the facultative in charge. In this study we used an in vitro model of macrophage culture and application of different combinations of the parameters of galvanic current to study IL-1β production and cell death. Increasing electric charge of galvanic current induces the release of IL-1β, but electric charges equal or higher to 144 mC also increase cell death. The release of IL-1β have a substantial variation within different electric charge of galvanic currents, being increased by decreasing the current and increasing the time of current application. Within the range of current intensities studied, the most optimal protocol for maximizing IL-1β release without inducing cell death was identified at electric charges equal to or near 144 mC, applied over a total duration of approximately 25 s. Our findings lay the groundwork for future in vivo studies assessing different electric charge of galvanic current, with the aim of yielding clinically relevant outcomes., Competing Interests: Declarations. Competing interests: A.P-F’s contract was supported by MVClinic Institute and Prim. P.P. declares that he is an inventor in a patent filed on March 2020 by the Fundación para la Formación e Investigación Sanitaria de la Región de Murcia (PCT/EP2020/056729) for a method to identify NLRP3-immunocompromised sepsis patients. P.P. is consultant and co-founder of Viva in vitro diagnostics SL. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Inflammasomes are multiprotein complexes that regulate the bioactive production of IL-1β and IL-18, being implicated in the inflammatory response of different diseases. The inflammasome formed by the cytosolic sensor NLRP3 is highly promiscuous, as it could be activated by different pathogen- and sterile-signals. However, few models have studied the implication of NLRP3 in tissue damage-induced inflammation, particularly the implication of NLRP3 in tendinopathies. Here, we aimed to investigate the implication of NLRP3 in a mouse model of tendinopathy by collagenase degradation of the extracellular matrix in the Achilles' mice tendon. We found that NLRP3 was involved in the production of IL-1β, but another ASC-dependent inflammasome was required to produce IL-18 during sterile tissue damage. Our study suggests that in the immune response to extracellular matrix degradation different inflammasomes, probably expressed in different cell compartments, were able to differentially control IL-1β and IL-18 production in vivo. These results suggest the potential use of therapies targeting ASC as beneficial in the treatment of tendinopathies., (© 2024 The Author(s).)

Introduction: The recurrent nature of hidradenitis suppurativa (HS), even under maintained systemic treatment, makes it necessary to have effective local treatments; however, the response to these therapies is variable (44-81%). The application of galvanic current (GC) has demonstrated its utility in humans in treating lesions structurally similar to those of HS. With this background, the main objective of this study was to evaluate the efficacy and safety of ultrasound-guided percutaneous GC in inflamed and/or draining tunnels of HS., Methods: This was an open study (one-way repeated measures design over time). Patients were evaluated at 4 and 12 weeks after receiving GC. A combined clinical response at week 12 (absence of suppuration/inflammation on examination and clinical interview) was considered the principal variable of efficacy. Adverse effects potentially associated with GC were reported by telephone and at each visit., Results: Twenty-six patients were included, with a male/female ratio of 5:8. The mean age was 35.84 (13.14) years. At 12 weeks after the administration of GC, a complete response was achieved in 77% (20/26) of the treated lesions. No serious adverse effects were observed, and the mean procedural pain assessed by the numeric rating scale was 0.03 (0.2)., Conclusion: GC has proven to be effective and well tolerated in inflamed and draining tunnels of patients with HS., (© 2024. The Author(s).)

Background: In chronic obstructive pulmonary disease (COPD), multiple recurrent severe exacerbations that require hospitalization can occur. These events are strongly associated with death and other clinical complications., Objectives: We aimed to develop a prognostic model that could identify patients with COPD that are at risk of multiple recurrent severe exacerbations within 3 years., Design: Prospective cohort., Methods: The derivation cohort comprised patients with stable, moderate-to-severe COPD. Multivariable logistic regression analyses were performed to develop the final model. Based on regression coefficients, a simplified index (ESEx) was established. Both, model and index, were assessed for predictive performance by measuring discrimination and calibration., Results: Over 3 years, 16.4% of patients with COPD experienced at least three severe recurrent exacerbations. The prognostic model showed good discrimination of high-risk patients, based on three characteristics: the number of severe exacerbations in the previous year, performance in the five-repetition sit-to-stand test, and in the 6-minute-walk test. The ESEx index provided good level of discrimination [areas under the receiver operating characteristic curve (AUCs): 0.913]., Conclusions: The ESEx index showed good internal validation for the identification of patients at risk of three recurrent severe COPD exacerbations within 3 years. These tools could be used to identify patients who require early interventions and motivate patients to improve physical performance to prevent recurrent exacerbations., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)

Background: The recovery of community ambulation is a common concern among individuals after stroke., Objectives: (1) To develop a potential readily applicable prognostic model able to correctly discriminate stroke patients who will not become independent community walkers at discharge; (2) To investigate the effects of early reassessment during the first month of treatment on the prediction accuracy of this model., Methods: This was a prospective cohort study. A consecutive sample of 80 patients at ≤60 days poststroke were assessed at baseline of outpatient physical rehabilitation and reassessed one month later. Non-functional community ambulation was measured., Results: Seventy-four patients were followed until discharge. Of these, 47 patients were non-functional community walkers at discharge. A prediction model based on baseline performance in the five repetition sit-to-stand [5-STS] test was able to discriminate those patients of the sample (Area-under-curve = 0.956), and again with data from reassessment (AUC = 0.952). A time of 21 s at baseline was a highly prognostic cut-off point for discrimination (sensitivity = 87.2% and 85.1%). The combined use of baseline and reassessment data improved sensitivity (98.1%)CONCLUSION:Early findings of the 5-STS among stroke patients is an independent prognostic factor associated with independent community walking at discharge. It could discriminate individuals who will not become community walkers at discharge.

Percutaneous needle electrolysis using tri-beveled needles with a specific protocol (5 mA applied for 25 s) has demonstrated to provoke a clinical reduction of recurrent bacterial infections in mammary fistulas. However, the bactericidal effect of needle electrolysis in this pathology remains theoretical. This in vitro study evaluated the bactericidal effect of this protocol and whether it changed when introducing small variations. Staphylococcus aureus were generated in saline solution (9 Log 10  CFU/mL) and treated in three different experiments including the main protocol and introducing variations in needle gauge, intensity, and total dosage, respectively. After 24 h, the viable cell count showed that the protocol had an average reduction of 5 log 10  CFU/ml compared to the control group. While variations in needle gauge did not modify this effect, variations in current intensity or dosage did. This study demonstrated that the bacterial effect was greater by increasing either current intensity or total dosage, and it decreased with substantial reductions of these parameters., (© 2022. The Author(s).)

The NLRP3 inflammasome coordinates inflammation in response to different pathogen- and damage-associated molecular patterns, being implicated in different infectious, chronic inflammatory, metabolic and degenerative diseases. In chronic tendinopathic lesions, different non-resolving mechanisms produce a degenerative condition that impairs tissue healing and which therefore complicates their clinical management. Percutaneous needle electrolysis consists of the application of a galvanic current and is an emerging treatment for tendinopathies. In the present study, we found that galvanic current activates the NLRP3 inflammasome and induces an inflammatory response that promotes a collagen-mediated regeneration of the tendon in mice. This study establishes the molecular mechanism of percutaneous electrolysis that can be used to treat chronic lesions and describes the beneficial effects of an induced inflammasome-related response., Competing Interests: AP PhD contract was supported by MVClinic Institute and Prim, JG, CM, PE, RM, AG, JB, FM No competing interests declared, FM, FV Employe of MVClinic Institute, PP Inventor in a patent filed on March 2020 by the Fundación para la Formación e Investigación Sanitaria de la Región de Murcia (PCT/EP2020/056729) for a method to identify NLRP3-immunocompromised sepsis patients. Is consultant of Glenmark Pharmaceutical and co-founder of Viva in vitro diagnostics SL, (© 2022, Peñin-Franch et al.)