Coexistencia de dos manifestaciones osteoarticulares paraneoplásicas en un paciente afecto de adenocarcinoma pulmonar

Sr. Director: Existen descritos en la literatura una amplia variedad de trastornos musculosqueléticos paraneoplásicos. De ellos, la osteoartropatía hipertrófica (OH), la dermatomiositis y la poliartritis paraneoplásica son los que se citan con mayor frecuencia. El síndrome hombromano (SHM), variante clínica de la distrofia simpática refleja, es otra entidad reumatológica ocasionalmente asociada a neoplasia. El motivo de esta carta es comunicar el caso de un paciente afecto de adenocarcinoma pulmonar que presentó concomitantemente una OH y un SHM. Se trata de un varón de 61 años de edad, fumador de 60 paquetes/año y con criterios clínicos de bronquitis crónica, que ingresó en enero de 1988 en nuestro hospital por hemoptisis. En 1985, a raíz de ser ingresado en otro centro por un episodio de neumonía, se constató la existencia de un nódulo en LSD. Ocho meses antes de ingresar en nuestro centro el paciente inició de forma insidiosa algias en ambas regiones tibiales junto con dolor y tumefacción en rodillas. Tres meses antes del ingreso se añadió al cuadro dolor en hombro derecho junto con tumefacción difusa de la mano del mismo lado. En la semana previa al internamiento el paciente sufrió varios episodios de hemoptisis por lo que fue ingresado para estudio

Espondilitis piógenas del adulto. Análisis de 15 casos

La espondilitis piógena es una entidad clínica poco frecuente que últimamente ha experimentado un considerable aumento, relacionado con la adicción a drogas por vía parenteral. Se presentan 15 casos tratados en el período entre 1981-1988. La etiología más frecuente fue el estafilococo dorado (53%), seguida de gérmenes gramnegativos (47%). Es de destacar la presencia de factores predisponentes en un 47% de pacientes. El cuadro clínico consistió en una raquialgia acompañada de fiebre en el 73% de los casos. La radiología era normal en las etapas iniciales, pero no la gammagrafía con Ga y Te. El tratamiento fue inicialmente conservador, estando indicada la cirugía cuando se presentaron alteraciones neurológicas, abscesos paravertabrales o imposibilidad diagnóstica. En la serie presentada, 4 de los J5 pacientes fueron sometidos a tratamiento quirúrgic

Cost-utility and biological underpinnings of Mindfulness-Based Stress Reduction (MBSR) versus a psychoeducational programme (FibroQoL) for fibromyalgia: a 12-month randomised controlled trial (EUDAIMON study)

Background: The EUDAIMON study focuses on fibromyalgia syndrome (FMS), a prevalent chronic condition characterized by pain, fatigue, cognitive problems and distress. According to recent reviews and meta-analyses, Mindfulness-Based Stress Reduction (MBSR) is a promising therapeutic approach for patients with FMS. The measurement of biomarkers as part of the analysis of MBSR effects would help to identify the neurobiological underpinnings of MBSR and increase our knowledge of FMS pathophysiology. The main objectives of this 12-month RCT are: firstly, to examine the effectiveness and cost-utility for FMS patients of MBSR as an add-on to treatment as usual (TAU) versus TAU + the psychoeducational programme FibroQoL, and versus TAU only; secondly, to examine pre-post differences in brain structure and function, as well as levels of specific inflammatory markers in the three study arms and; thirdly, to analyse the role of some psychological variables as mediators of 12-month clinical outcomes. Methods: Effectiveness, cost-utility, and neurobiological analyses performed alongside a 12-month RCT. The participants will be 180 adult patients with FMS recruited at the Sant Joan de Deu hospital (St. Boi de Llobregat, Spain), randomly allocated to one of the three study arms: TAU + MBSR vs. TAU + FibroQol vs. TAU. A comprehensive assessment to collect functional, quality of life, distress, costs, and psychological variables will be conducted pre-, post-intervention, and at 12-month post-intervention. Fifty per cent of study participants will be evaluated at pre- and post-treatment using Voxel-Based Morphometry, Diffusion Tensor Imaging, pseudo-continuous Arterial Spin Labeling, and resting state fMRI. A cytokine multiplex kit of high-sensitivity will be applied (cytokines IL-6, IL-8, IL-10 + high-sensitivity CRP test). Discussion: The findings obtained from this RCT will indicate whether MBSR is potentially cost-effective for FMS and contribute to knowledge of any brain and inflammatory changes associated with MBSR in FMS patients. Specifically, we will determine whether there are morphometric and functional changes associated with participation in MBSR in brain regions related to meta-awareness, body awareness, memory consolidation-reconsolidation, emotion regulation and in networks postulated to underpin the sensory-discriminative, cognitive-evaluative and affective-motivational aspects of the pain experience

Cost-utility and biological underpinnings of Mindfulness-Based Stress Reduction (MBSR) versus a psychoeducational programme (FibroQoL) for fibromyalgia: a 12-month randomised controlled trial (EUDAIMON study)

Background: The EUDAIMON study focuses on fibromyalgia syndrome (FMS), a prevalent chronic condition characterized by pain, fatigue, cognitive problems and distress. According to recent reviews and meta-analyses, Mindfulness-Based Stress Reduction (MBSR) is a promising therapeutic approach for patients with FMS. The measurement of biomarkers as part of the analysis of MBSR effects would help to identify the neurobiological underpinnings of MBSR and increase our knowledge of FMS pathophysiology. The main objectives of this 12-month RCT are: firstly, to examine the effectiveness and cost-utility for FMS patients of MBSR as an add-on to treatment as usual (TAU) versus TAU + the psychoeducational programme FibroQoL, and versus TAU only; secondly, to examine pre-post differences in brain structure and function, as well as levels of specific inflammatory markers in the three study arms and; thirdly, to analyse the role of some psychological variables as mediators of 12-month clinical outcomes. Methods: Effectiveness, cost-utility, and neurobiological analyses performed alongside a 12-month RCT. The participants will be 180 adult patients with FMS recruited at the Sant Joan de Déu hospital (St. Boi de Llobregat, Spain), randomly allocated to one of the three study arms: TAU + MBSR vs. TAU + FibroQol vs. TAU. A comprehensive assessment to collect functional, quality of life, distress, costs, and psychological variables will be conducted pre-, post-intervention, and at 12-month post-intervention. Fifty per cent of study participants will be evaluated at pre- and post-treatment using Voxel-Based Morphometry, Diffusion Tensor Imaging, pseudo-continuous Arterial Spin Labeling, and resting state fMRI. A cytokine multiplex kit of high-sensitivity will be applied (cytokines IL-6, IL-8, IL-10 + high-sensitivity CRP test). Discussion: The findings obtained from this RCT will indicate whether MBSR is potentially cost-effective for FMS and contribute to knowledge of any brain and inflammatory changes associated with MBSR in FMS patients. Specifically, we will determine whether there are morphometric and functional changes associated with participation in MBSR in brain regions related to meta-awareness, body awareness, memory consolidation-reconsolidation, emotion regulation and in networks postulated to underpin the sensory-discriminative, cognitive-evaluative and affective-motivational aspects of the pain experience. Trial registration: NCT02561416. Registered 23 September 201

Study protocol for a randomised, double-blinded, placebo-controlled phase III trial examining the add-on efficacy, cost-utility and neurobiological effects of low-dose naltrexone (LDN) in patients with fibromyalgia (INNOVA study)

Introduction There is evidence that low-dose naltrexone (LDN; <5.0 mg/day) reduces pain and improves the quality of life of people with fibromyalgia syndrome (FMS). However, no randomised controlled trials with long-term follow-ups have been carried out. The INNOVA study will evaluate the add-on efficacy, safety, cost-utility and neurobiological effects of LDN for reducing pain in patients with FMS, with a 1-year follow-up. Methods and analysis A single-site, prospective, randomised, double-blinded, placebo-controlled, parallel design phase III trial will be performed. Eligibility criteria include being adult, having a diagnosis of FMS and experiencing pain of 4 or higher on a 10-point numerical rating scale. Participants will be randomised to a LDN intervention group (4.5 mg/day) or to a placebo control group. Clinical assessments will be performed at baseline (T0), 3 months (T1), 6 months (T2) and 12 months (T3). The primary endpoint will be pain intensity. A sample size of 60 patients per study arm (120 in total), as calculated prior to recruitment for sufficient power, will be monitored between January 2022 and August 2024. Assessment will also include daily ecological momentary evaluations of FMS-related symptoms (eg, pain intensity, fatigue and sleep disturbance), and side effects via ecological momentary assessment through the Pain Monitor app during the first 3 months. Costs and quality-adjusted life years will be also calculated. Half of the participants in each arm will be scanned with MRI at T0 and T1 for changes in brain metabolites related to neuroinflammation and central sensitisation. Inflammatory biomarkers in serum will also be measured. Ethics and dissemination This study has been approved by the Ethics Committee of the Fundació Sant Joan de Déu. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media and community engagement activities. Trial registration number NCT04739995

Study protocol for a three-arm randomized controlled trial investigating the effectiveness, cost-utility, and physiological effects of a fully self-guided digital Acceptance and Commitment Therapy for Spanish patients with fibromyalgia

Objective Fibromyalgia (FM) is a prevalent pain syndrome with significant healthcare and societal costs. The aim of the SMART-FM-SP study is to determine the effectiveness, cost-utility, and physiological effects in patients with FM of a digital intervention (STANZA®) currently marketed in the United States, which delivers smartphone-based, fully self-guided Acceptance and Commitment Therapy (Digital ACT) for treating FM-related symptoms. Methods A single-site, parallel-group, superiority, randomized controlled trial (RCT) will be conducted, including a total of 360 adults diagnosed with FM. Individuals will be randomly allocated (1:1:1) to treatment as usual (TAU), to TAU plus 12 weeks of treatment with Digital ACT, or to TAU plus 12 weeks of treatment with digital symptom tracking (i.e. FibroST). Participants will be assessed at baseline, post-treatment, and 6-month follow-up. An intention-to-treat analysis using linear mixed models will be computed to analyze the effects of Digital ACT on functional impairment (primary outcome), as measured by the Fibromyalgia Impact Questionnaire Revised at 6 months from the inception of the treatment. Secondary outcomes include impression of change, symptoms of distress, pain catastrophising, quality of life, cost-utility, and selected biomarkers (cortisol and cortisone, immune-inflammatory markers, and FKBP5 gene polymorphisms). The role of ACT-related processes of change will be tested with path analyses. Conclusions This study is the first RCT that tests Digital ACT for Spanish patients with FM. Results will be important not only for patients and clinicians, but also for policy makers by examining the cost-utility of the app in a public healthcare context

Machine learning to understand the immune-inflammatory pathways in fibromyalgia

Fibromyalgia (FM) is a chronic syndrome characterized by widespread musculoskeletal pain, and physical and emotional symptoms. Although its pathophysiology is largely unknown, immune-inflammatory pathways may be involved. We examined serum interleukin (IL)-6, high sensitivity C-reactive protein (hs-CRP), CXCL-8, and IL-10 in 67 female FM patients and 35 healthy women while adjusting for age, body mass index (BMI), and comorbid disorders. We scored the Fibromyalgia Severity Score, Widespread Pain Index (WPI), Symptom Severity Scale (SSS), Hospital Anxiety (HADS-A), and Depression Scale and the Perceived Stress Scale (PSS-10). Clinical rating scales were significantly higher in FM patients than in controls. After adjusting for covariates, IL-6, IL-10, and CXCL-8 were lower in FM than in HC, whereas hs-CRP did not show any difference. Binary regression analyses showed that the diagnosis FM was associated with lowered IL-10, quality of sleep, aerobic activities, and increased HADS-A and comorbidities. Neural networks showed that WPI was best predicted by quality of sleep, PSS-10, HADS-A, and the cytokines, while SSS was best predicted by PSS-10, HADS-A, and IL-10. Lowered levels of cytokines are associated with FM independently from confounders. Lowered IL-6 and IL-10 signaling may play a role in the pathophysiology of F

The time of blood sampling for osteocalcin determinations.

Sir: We have read the interesting article by Pietschmann et al about the serum osteocalcin concentrations in patients with rheumatoid arthritis.' In their work there was no mention of the time at which blood samples were taken for osteocalcin determination. Several studies have shown a circadian rhythm of serum osteocalcin in normal adults, with peak values during the night and a nadir during the morning hours.2 3 Therefore, in our opinion, if osteocalcin is used as a marker in clinical investigations of bone metabolism it is important to mention the time at which blood was collected for its measurement. Otherwise, interpretation of results may be difficult and comparison with values obtained in other studies impossible

Septic arthritis complicating hip osteoarthritis.

Four patients with osteoarthritis of the hip, who developed septic arthritis of the affected joint, are reported. The septic arthritis developed insidiously and was diagnosed with difficulty. One patient died, two required subsequent joint excision, and one arthrodesis despite antibiotics. The presence of a recognised predisposing factor to septic arthritis, such as rheumatoid arthritis or a surgically replaced joint, can provide a diagnostic pointer. These cases suggest that osteoarthritis, similarly, is a predisposing factor. It is concluded that joint sepsis should be considered if a patient with osteoarthritis develops new symptoms from a single joint with associated systemic features

Septic arthritis complicating hip osteoarthritis.

Four patients with osteoarthritis of the hip, who developed septic arthritis of the affected joint, are reported. The septic arthritis developed insidiously and was diagnosed with difficulty. One patient died, two required subsequent joint excision, and one arthrodesis despite antibiotics. The presence of a recognised predisposing factor to septic arthritis, such as rheumatoid arthritis or a surgically replaced joint, can provide a diagnostic pointer. These cases suggest that osteoarthritis, similarly, is a predisposing factor. It is concluded that joint sepsis should be considered if a patient with osteoarthritis develops new symptoms from a single joint with associated systemic features