Hyperbaric oxygen therapy vs. pharmacological intervention in adults with fibromyalgia related to childhood sexual abuse: prospective, randomized clinical trial.

Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by disruptions in pain processing within the central nervous system. It exhibits a high prevalence among patients with a history of traumatic experiences, notably childhood sexual abuse (CSA). This study compared the efficacy of hyperbaric oxygen therapy (HBOT) to the current pharmacological standard of care for individuals suffering from CSA-related FMS. Forty-eight participants diagnosed with FMS and a history of CSA were randomly assigned to either the HBOT group (60 sessions of 100% oxygen at 2 ATA for 90 min, with air breaks every 5 min) or the medication (MED) group (FDA-approved medications, Pregabalin and Duloxetine). The primary endpoint was the Fibromyalgia impact questionnaire (FIQ) score, while secondary endpoints encompassed emotional status and daily functioning questionnaires, as well as pain thresholds and conditioned pain modulation tests. Brain activity was evaluated through single photon emission computed tomography (SPECT). Results revealed a significant group-by-time interaction for the FIQ score favoring HBOT over MED (p < 0.001), with a large effect size (Cohen's d = - 1.27). Similar findings were observed in emotional symptoms and functional measures. SPECT imaging demonstrated an increase in activity in pre-frontal and temporal brain areas, which correlated with symptoms improvement. In conclusion, HBOT exhibited superior benefits over medications in terms of physical, functional, and emotional improvements among FMS patients with a history of CSA. This associated with increased activity in pre-frontal and temporal brain areas, highlighting the neuroplasticity effect of HBOT.

Corin and Left Atrial Cardiomyopathy, Hypertension, Arrhythmia, and Fibrosis.

Two siblings presented with cardiomyopathy, hypertension, arrhythmia, and fibrosis of the left atrium. Each had a homozygous null variant in CORIN, the gene encoding atrial natriuretic peptide (ANP)-converting enzyme. A plasma sample obtained from one of the siblings had no detectable levels of corin or N-terminal pro-ANP but had elevated levels of B-type natriuretic peptide (BNP) and one of the two protein markers of fibrosis that we tested. These and other findings support the hypothesis that BNP cannot fully compensate for a lack of activation of the ANP pathway and that corin is critical to normal ANP activity, left atrial function, and cardiovascular homeostasis.

Neurophysiological and psychosocial mechanisms of fibromyalgia: A comprehensive review and call for an integrative model.

Research into the neurobiological and psychosocial mechanisms involved in fibromyalgia has progressed remarkably in recent years. Despite this, current accounts of fibromyalgia fail to capture the complex, dynamic, and mutual crosstalk between neurophysiological and psychosocial domains. We conducted a comprehensive review of the existing literature in order to: a) synthesize current knowledge on fibromyalgia; b) explore and highlight multi-level links and pathways between different systems; and c) build bridges connecting disparate perspectives. An extensive panel of international experts in neurophysiological and psychosocial aspects of fibromyalgia discussed the collected evidence and progressively refined and conceptualized its interpretation. This work constitutes an essential step towards the development of a model capable of integrating the main factors implicated in fibromyalgia into a single, unified construct which appears indispensable to foster the understanding, assessment, and intervention for fibromyalgia.

Risk factors, clinical characteristics and prognostic value of acute kidney injury in COVID-19 compared with influenza virus and respiratory syncytial virus.

BACKGROUND: Acute Kidney Injury (AKI) complicates a substantial part of patients with COVID-19. Direct viral penetration of renal cells through the Angiotensin Converting Enzyme 2 receptor, and indirect damage by the aberrant inflammatory response characteristic of COVID-19 are likely mechanisms. Nevertheless, other common respiratory viruses such as Influenza and Respiratory Syncytial Virus (RSV) are also associated with AKI. METHODS: We retrospectively compared the incidence, risk factors and outcomes of AKI among patients who were admitted to a tertiary hospital because of infection with COVID-19, influenza (A + B) or RSV. RESULTS: We collected data of 2593 patients hospitalized with COVID-19, 2041 patients with influenza and 429 with RSV. Patients affected by RSV were older, had more comorbidities and presented with higher rates of AKI at admission and within 7 days (11.7% vs. 13.3% vs. 18% for COVID-19, influenza and RSV, respectively p = 0.001). Nevertheless, patients hospitalized with COVID-19 had higher mortality (18% with COVID-19 vs. 8.6% and 13.5% for influenza and RSV, respectively P < 0.001) and higher need of mechanical ventilation (12.4% vs. 6.5% vs.8.2% for COVID-19, influenza and RSV, respectively, P = 0.002). High ferritin levels and low oxygen saturation were independent risk factors for severe AKI only in the COVID-19 group. AKI in the first 48 h of admission and in the first 7 days of hospitalization were strong independent risk factors for adverse outcome in all groups. CONCLUSION: Despite many reports of direct kidney injury by SARS-COV-2, AKI was less in patients with COVID-19 compared to influenza and RSV patients. AKI was a prognostic marker for adverse outcome across all viruses.

Hyperbaric oxygen therapy compared to pharmacological intervention in fibromyalgia patients following traumatic brain injury: A randomized, controlled trial.

Fibromyalgia is a chronic pain syndrome with unsatisfactory response to current treatments. Physical trauma, including traumatic brain Injury (TBI) is among the etiological triggers. Hyperbaric Oxygen therapy (HBOT) is an intervention that combines 100% oxygen with elevated atmospheric pressure. HBOT has been applied as a neuro-modulatory treatment in central nervous system-related conditions. The current study investigated the utility of HBOT for TBI-related fibromyalgia. Fibromyalgia patients with a history of TBI were randomized to either HBOT or pharmacological intervention. HBOT protocol comprised 60 daily sessions, breathing 100% oxygen by mask at 2 absolute atmospheres (ATA) for 90 minutes. Pharmacological treatment included Pregabalin or Duloxetine. The primary outcome was subjective pain intensity on visual analogue scale (VAS); Secondary endpoints included questionnaires assessing fibromyalgia symptoms as well as Tc-99m-ECD SPECT brain imaging. Pain threshold and conditioned pain modulation (CPM) were also assessed. Results demonstrated a significant group-by-time interaction in pain intensity post-HBOT compared to the medication group (p = 0.001), with a large net effect size (d = -0.95) in pain intensity reduction following HBOT compared to medications. Fibromyalgia related symptoms and pain questionnaires demonstrated significant improvements induced by HBOT as well as improvements in quality of life and increase in pain thresholds and CPM. SPECT demonstrated significant group-by-time interactions between HBOT and medication groups in the left frontal and the right temporal cortex. In conclusion, HBOT can improve pain symptoms, quality of life, emotional and social function of patients suffering from FMS triggered by TBI. The beneficial clinical effect is correlated with increased brain activity in frontal and parietal regions, associated with executive function and emotional processing.

Effect of patient COVID-19 vaccine hesitancy on hospital care team perceptions.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic posed new challenges in patient care worldwide. Vaccinations, which have proven efficacious in lowering the COVID-19 hospital burden, are still avoided by large populations. We, therefore, hypothesized that hospital care teams would have worse perceptions regarding the characteristics and care of patients with vaccine hesitancy. AIM: To evaluate whether patient vaccine hesitancy affected the hospital care team (HCT) perceptions. METHODS: We performed a prospective clinical study using structured questionnaires. We approached physicians and nurses with previous experience caring for COVID-19 patients from 11 medical centers across Israel during the fourth COVID-19 surge (September and October 2021). The participants completed a questionnaire with the following parts: (1) Sociodemographic characteristics; (2) Assessment of anger (STAXI instrument) and chronic workplace stress (Shirom-Melamed burnout measure); and (3) Three tools to assess the effect of patient vaccine hesitancy on the HCT perceptions (the difficult doctor-patient relation questionnaire, the medical staff perception of patient's responsibility questionnaire and the characterological derogation questionnaire). Results were evaluated according to each part of the questionnaire and the questionnaire as a whole. Associations between HCT perceptions and their baseline characteristics, anger or chronic workplace stress were assessed. RESULTS: The HCT experienced their relationship with unvaccinated patients as more difficult (P < 0.001, Cohen's d = 0.85), perceived unvaccinated patients as responsible for their medical condition (P < 0.001, d = 1.39) and perceived vaccinated patients as having a higher character value (P < 0.001, d = 1.03). Unvaccinated patients were considered selfish (P < 0.001), less mature (P < 0.001) and less satisfying to care for (P < 0.001). The relationship with unvaccinated patients was more difficult among HCT with higher burnout (r = 0.37, n = 66, P = 0.002). No correlations with baseline characteristics were found. All three study tools showed high internal consistency (α between 0.72 and 0.845). CONCLUSION: Our results should raise awareness of the possible effects of vaccine hesitancy on HCT perceptions regarding unvaccinated patients. In order to minimize the potential negative impact on patient care, designated departments should promote specific patient-centered preparations. Further investigations should assess whether vaccine hesitancy directly affects patient quality of care.

Emotion regulation and the salience network: a hypothetical integrative model of fibromyalgia.

Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbances and other symptoms, and has a substantial socioeconomic impact. Current biomedical and psychosocial treatments are unsatisfactory for many patients, and treatment progress has been hindered by the lack of a clear understanding of the pathogenesis of fibromyalgia. We present here a model of fibromyalgia that integrates current psychosocial and neurophysiological observations. We propose that an imbalance in emotion regulation, reflected by an overactive 'threat' system and underactive 'soothing' system, might keep the 'salience network' (also known as the midcingulo-insular network) in continuous alert mode, and this hyperactivation, in conjunction with other mechanisms, contributes to fibromyalgia. This proposed integrative model, which we term the Fibromyalgia: Imbalance of Threat and Soothing Systems (FITSS) model, should be viewed as a working hypothesis with limited supporting evidence available. We hope, however, that this model will shed new light on existing psychosocial and biological observations, and inspire future research to address the many gaps in our knowledge about fibromyalgia, ultimately stimulating the development of novel therapeutic interventions.

CD55-deficiency in Jews of Bukharan descent is caused by the Cromer blood type Dr(a-) variant.

The complement system regulator CD55 was initially found to carry the Cromer blood group system antigens, and its complete loss of function was subsequently revealed to cause a severe monogenic gastrointestinal syndrome characterized by protein-losing enteropathy and susceptibility to venous thrombosis. Here we present homozygosity to the CD55 c.596C>T; p.Ser199Leu variant, which was previously described as the Cromer Dr(a-) genotype, in two Bukharan Jewish CD55-deficiency patients with variable disease severity. We confirm that this missense variant causes aberrant splicing and deletion of 44 bp in exon 5, leading to premature termination and low expression of the CD55 protein. Furthermore, Patient 1 exhibited a mildly abnormal B cell immunophenotyping profile. By population screening we established that this variant is highly prevalent in the Bukharan Jewish population, with a carrier frequency of 1:17, suggesting that many similar patients are un- or mis-diagnosed. The phenotypic variability, ranging from abdominal pain when eating a high-fat diet to the full CD55-deficiency phenotype, is likely related to modifiers affecting the proportion of the variant that is able to escape aberrant splicing. Establishing the diagnosis of CD55-deficiency in a timely manner, even in patients with milder symptoms, may have a critical effect on their management and quality-of-life since treatment with the complement inhibitor eculizumab is highly effective in ameliorating disease manifestations. Awareness of founder mutations within certain populations can further guide genetic testing and prevent a diagnostic odyssey, by placing this CD55 variant high on the differential diagnosis.

Elevated Serum Amyloid A Levels Contribute to Increased Platelet Adhesion in COVID-19 Patients.

Coronavirus disease-19 (COVID-19) patients are prone to thrombotic complications that may increase morbidity and mortality. These complications are thought to be driven by endothelial activation and tissue damage promoted by the systemic hyperinflammation associated with COVID-19. However, the exact mechanisms contributing to these complications are still unknown. To identify additional mechanisms contributing to the aberrant clotting observed in COVID-19 patients, we analyzed platelets from COVID-19 patients compared to those from controls using mass spectrometry. We identified increased serum amyloid A (SAA) levels, an acute-phase protein, on COVID-19 patients' platelets. In addition, using an in vitro adhesion assay, we showed that healthy platelets adhered more strongly to wells coated with COVID-19 patient serum than to wells coated with control serum. Furthermore, inhibitors of integrin aIIbß3 receptors, a mediator of platelet-SAA binding, reduced platelet adhesion to recombinant SAA and to wells coated with COVID-19 patient serum. Our results suggest that SAA may contribute to the increased platelet adhesion observed in serum from COVID-19 patients. Thus, reducing SAA levels by decreasing inflammation or inhibiting SAA platelet-binding activity might be a valid approach to abrogate COVID-19-associated thrombotic complications.

The economic burden of fibromyalgia: A systematic literature review.

INTRODUCTION: Fibromyalgia (FM) is a common disorder characterised by heterogeneous symptoms often leading to decreased functioning, work productivity and quality of life. Although a multimodal approach is used to treat FM, a significant proportion of patients show low satisfaction with perceived care, potentially resulting in an inefficient use of health care resources. The aim of the present review is to summarize the available evidence about the economic impact of FM and the specific cost drivers of health care expenditure for the syndrome. METHODS: MedLine and Web of Science databases were searched to identify eligible articles. Studies reporting direct medical and non-medical costs and/or indirect costs of FM were included. Annual costs per person were extrapolated from each study and converted to United States Dollars ($) after adjusting the local currency for inflation in year 2019. RESULTS: The 36 studies included in the final synthesis differed considerably in their design and in the cost categories analysed. Overall risk of bias was high. Estimates for the total annual direct costs per patient ranged from $ 1750 to $ 35,920 in the USA and from $ 1250 to $ 8504 in Europe. In most included studies, medications were the major contributor to overall expenditures. CONCLUSION: Fibromyalgia represents a substantial economic burden to health care systems and society. A better understanding of this complex disorder may not only improve quality of life of FM patients, but also have a significant impact on direct and indirect costs associated with the syndrome.

Fibromyalgia: one year in review 2022.

Fibromyalgia syndrome (FM) is a chronic widespread pain syndrome characterised by fatigue, sleep disturbances and many idiopathic pain symptoms. The aim of this review is to describe and summarise the most recent findings concerning the diagnosis, aetiopathogenesis and treatment of fibromyalgia syndrome published between January 2021 and January 2022 and appearing on PubMed database. In particular, last year's literature focused on the impact of COVID-19 pandemic on FM patients, on new aetiopathogenetic horizons and the last conclusions about pharmacological and non-pharmacological interventions.

The Montreal Cognitive Assessment Test (MoCA) as a screening tool for cognitive dysfunction in fibromyalgia.

OBJECTIVES: Cognitive dysfunction is one of the criteria for the diagnosis of fibromyalgia (FM) and is typically based on self-report questionnaires such as the Symptom Severity Scale. However, recent studies have shown that there is no correlation between these subjective measures of cognitive dysfunction and more lengthy objective measures of cognitive functioning. This points to the need for a briefer valid evaluation tool for cognitive dysfunction in FM. The aim of this study is to examine whether the Montreal Cognitive Assessment (MoCA) test is a valid measure of cognitive assessment in FM patients, by comparing it to a comprehensive computerised cognitive assessment battery. METHODS: Sixty-two FM patients (55 women, 7 men, mean age = 46.17 years, sd=12.56) were administered the MoCA and a computerised cognitive assessment battery. FM symptoms were assessed on the Fibromyalgia Impact Questionnaire (FIQ), the Widespread Pain Index (WPI), the Symptom Severity Scale (SSS), and the Beck Depression Inventory (BDI-2). Patient effort was controlled on the TOMM (Test of Memory Malingering). RESULTS: Moderate positive correlations were found between the MoCA and the computerised cognitive scores as follows: Global Cognitive Score (r=0.493**, p=0.00), Memory Index Score (r= 0.384**, p=0.002), Executive Function Index Score (r=0.461**, p=0.00), Attention Index Score (r=0.310*, p=0.016), Information Processing Speed Index Score (r=0.435**, p=0.001), and Motor Skills (r=0.406**, p=0.002). CONCLUSIONS: The MoCA is an acceptable cognitive screening test for the cognitive evaluation of FM patients.

Fibromyalgia syndrome - a risk factor for poor outcomes following orthopaedic surgery: A systematic review.

BACKGROUND: Fibromyalgia (FM) is a complex syndrome incorporating many features associated with poor outcome in orthopaedic surgery. Aim of the present review was to comprehensively characterize the available evidence on the consequences of pre-existent FM on the outcomes of orthopaedic surgery. METHODS: We performed a systematic search in MedLine and Web of Science (WOS) to identify studies evaluating the effect of FM on patient-centred outcomes, opioids consumption and postoperative complications. RESULTS: The search strategy identified 519 records in PubMed and 507 in WOS. A total of 27 articles were deemed eligible for inclusion in qualitative synthesis. Based on quality assessment, 10 studies were rated as good quality, 10 as fair quality and 7 as poor quality. Studies reporting the prevalence of FM in consecutive patients undergoing orthopaedic surgery (n = 19) were included in quantitative synthesis. The pooled prevalence of FM in patients undergoing orthopaedic surgery was 4.1% (95% CI: 2.4-6.8) in those receiving hip or knee surgery, 10.1% (95% CI: 5.7-17.2) in those receiving shoulder or elbow surgery and 21.0% (95% CI: 18.5-23.7) in those receiving spinal surgery. The results of our systematic review consistently report FM as a significant risk factor for less satisfaction, higher pain, worse functional outcome, increased risk for postoperative opioids prescription and higher rate of medical and surgical complications following orthopaedic surgery. CONCLUSION: Identifying pre-existing FM in patients scheduled for elective orthopaedic surgery may help to better assess the benefit/risk ratio, improve patients' awareness and minimize any discrepancy between expectancy and results.

Diagnostic and therapeutic care pathway for fibromyalgia.

Early diagnosis and timely and appropriate treatments positively influence the history of fibromyalgia syndrome (FM), with favourable repercussions at clinical, psychological, social and economic levels. Notwithstanding, there are still significant problems with timeliness of diagnosis, access to pharmacological therapies - particularly to innovative ones - and appropriate and effective taking in charge of patients. All the aforementioned factors have a great impact on FM patients' quality of life. Indeed, even though the World Health Organisation recognised FM as a chronic condition in the International Classification of Diseases 10th edition (ICD-10), many countries still fail to recognise the syndrome, and this negatively influences the capability to appropriately protect and care for patients. This is the case in several European Countries. In Italy, a few Regions have started to put in place precise indications for people suffering from FM, aiming at the implementation of diagnostic-therapeutic pathways. The Diagnostic-Therapeutic Care Pathway (DTCP) provides an important tool to meet the needs of patients suffering from chronic diseases. They present the organisation of an integrated assistance network. This includes a seamless path for disease prevention, diagnosis and treatment, by means of cooperation among physicians and other healthcare professionals.

Fibromyalgia position paper.

Fibromyalgia syndrome is one of the most common causes of chronic widespread pain, but pain accompanies a wide range of ancillary symptoms. To date, its aetiopathogenesis remains elusive, and diagnosis is exquisitely clinical, due to the lack of biomarkers or specific laboratory alterations in fibromyalgia patients. This position paper has the purpose to summarise the current scientific knowledge and expert opinions about the main controversies regarding fibromyalgia syndrome, namely: (i) fibromyalgia definition and why it is still not recognised in many countries as a distinct clinical entity; (ii) fibromyalgia severity and how to evaluate treatment outcome; (iii) how to treat fibromyalgia and which is a correct approach to fibromyalgia patients.