A Fixed Combination of Palmitoylethanolamide and Melatonin (PEATONIDE) for the Management of Pain, Sleep, and Disability in Patients with Fibromyalgia: a Pilot Study

Fibromyalgia is characterized by chronic widespread pain, fatigue, and sleep disturbances. Recent theories attribute fibromyalgia to central sensitization syndromes, suggesting altered nociceptive processing leads to hyperalgesia and allodynia. Standardized effective treatments are currently lacking. Palmitoylethanolamide and melatonin have shown pain-relieving effects in chronic pain conditions, including fibromyalgia, with excellent safety. Our open-label study assessed the impact of a daily combination of 1200 mg of palmitoylethanolamide and 0.2 mg of melatonin on pain, sleep, and quality of life in fibromyalgia patients. Between June 2023 and March 2024, 50 patients (2016 ACR criteria) were treated and evaluated at baseline, 1 month, 3 months, and 4 months (1 month discontinuation). The assessments included VAS for pain, ISI for insomnia, HAQ for health assessments, and a tender points evaluation. The patients, averaging 54.12 years old with a 3:1 female-to-male ratio, showed significant improvements in VAS, ISI, and HAQ scores relative to their own baselines and a reduction in tender points at 1 and 3 months, which was maintained at 4 months. No adverse events were reported. This study is the first to demonstrate the efficacy of a palmitoylethanolamide and melatonin combination as an adjunct therapy in fibromyalgia, highlighting its potential to reduce pain and improve sleep and quality of life

Role of adalimumab biosimilar in the treatment of non-anterior uveitis associated with Behçet’s syndrome

Introduction: To evaluate the efficacy of SB5, an adalimumab biosimilar, in the management of Behçet’s syndrome (BS)-related uveitis. Methods: Data from eight BS patients (16 eyes) with active non-anterior uveitis and/or systemic uncontrolled disease or performing non-medical switch to SB5 were retrospectively collected and analyzed. Results: Complete control of uveitis was observed in all 16 eyes without relapses during follow-up. The number of relapses 12 months prior to SB5 initiation and at last follow-up was 100 and 0 per 100 patients/year, respectively (p = 0.010). At baseline, four eyes had active retinal vasculitis, whereas at 3 months and at last follow-up, retinal vasculitis had resolved in all of them (p = 0.018). Median visual acuity did not vary significantly between baseline and last follow-up visit (p = 0.109). No ocular complications emerged during treatment. Conclusions: SB5 is effective in the treatment of BS-related non-anterior uveitis. It reduces uveitis relapses and controls retinal vasculitis while allowing preservation of visual acuity

Neridronate for transient osteoporosis of the hip in a child

Transient osteoporosis of the hip (TOH) is usually reported in middle-aged men or during pregnancy as a benign self-limiting condition. Nevertheless, its impact on quality of life in terms of pain and disability is considerable. Also, it can lead to insufficiency fractures or, more rarely, evolve into osteonecrosis. This condition is anecdotally described in the pediatric age and very little is known about how it may affect the growing bone. We herein describe a case of TOH in a 10-year-old child treated at our pediatric rheumatology service and summarize the pediatric cases of TOH previously reported in literature. There are two points of interest in our case report, the first one being the unusual complication of TOH with a femoral physis fracture and the second the complete recovery after the off-label therapy with bisphosphonates. We suggest that interventional medical treatment could be considered in selected cases of juvenile TOH, to prevent any possible irreversible damage on the femoral physis. As far as we know, this is the first report of neridronate employment in children affected by TOH

Neurocognitive and Psychopathological Predictors of Weight Loss After Bariatric Surgery: A 4-Year Follow-Up Study

Twenty to thirty percent of patients experience weight regain at mid and long-term follow- up. Impaired cognitive functions are prevalent in people suffering from obesity and in those with binge eating disorder, thereby, affecting the weight-loss outcomes. The aim of our study was to investigate neurocognitive and psychopathological predictors of surgical efficacy in terms of percentage of excess weight loss (%EWL) at follow-up intervals of one year and 4-year. Psychosocial evaluation was completed in a sample of 78 bariatric surgery candidates and included psychometric instruments and a cognitive battery of neuropsychological tests. A schedule of 1-year and 4-year follow-ups was implemented. Wisconsin Sorting Card Test total correct responses, scores on the Raven’s Progressive Matrices Test, and age predicted %EWL at, both, early and long-term periods after surgery while the severity of pre-operative binge eating (BED) symptoms were associated with lower %EWL only four years after the operation. Due to the role of pre-operative BED in weight loss maintenance, the affected patients are at risk of suboptimal response requiring ongoing clinical monitoring, and psychological and pharmacological interventions when needed. As a result of our findings and in keeping with the latest guidelines we encourage neuropsychological assessment of bariatric surgery candidates. This data substantiated the rationale of providing rehabilitative interventions tailored to cognitive domains and time specific to the goal of supporting patients in their post-surgical course

Bariatric and metabolic surgery during COVID-19 outbreak phase 2 in Italy: why, when and how to restart

In Italy elective bariatric and metabolic surgery was cancelled on February 21,2020 at the beginning of the so-called phase 1 of the SARS-CoV-2 outbreak. Gradually it was restarted on May 4,2020 at the beginning of the so-called phase 2, when epidemiological data showed containment of the infection. Before the outbreak in eight high-volume bariatric centers 840 patients were surgically treated developing a Covid-19 infection, during phase 1, in only 5 cases (0.6%) without mortality. The post-operative complication rate was similar when compared to the 836 subjects submitted to bariatric surgery the year before. Since the high prevalence of infection in subjects with BMI. 30, it was argued that early intervention on obesity during phase 2 could help to minimize the effects of the disease in the event of a possible reversion to a SARS-CoV-2 outbreak phase 1. At the same time a prospective observational study from July 1 till the WHO declaration of the end of the pandemic has started in the eight high volume centers to monitor the post-operative outcome and its effect on SARS-CoV2 infection. (C) 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved

Free-amino acid metabolic profiling of visceral adipose tissue from obese subjects

Interest in adipose tissue pathophysiology and biochemistry have expanded considerably in the past two decades due to the ever increasing and alarming rates of global obesity and its critical outcome defined as metabolic syndrome (MS). This obesity-linked systemic dysfunction generates high risk factors of developing perilous diseases like type 2 diabetes, cardiovascular disease or cancer. Amino acids could play a crucial role in the pathophysiology of the MS onset. Focus of this study was to fully characterize amino acids metabolome modulations in visceral adipose tissues (VAT) from three adult cohorts: (i) obese patients (BMI 43-48) with metabolic syndrome (PO), (ii) obese subjects metabolically well (O), and (iii) non obese individuals (H). 128 metabolites identified as 20 protein amino acids, 85 related compounds and 13 dipeptides were measured by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) and gas chromatography-/mass spectrometry GC/MS, in visceral fat samples from a total of 53 patients. Our analysis indicates a probable enhanced BCAA (leucine, isoleucine, valine) degradation in both VAT from O and PO subjects, while levels of their oxidation products are increased. Also PO and O VAT samples were characterized by: elevated levels of kynurenine, a catabolic product of tryptophan and precursor of diabetogenic substances, a significant increase of cysteine sulfinic acid levels, a decrease of 1-methylhistidine, and an up regulating trend of 3-methylhistidine levels. We hope this profiling can aid in novel clinical strategies development against the progression from obesity to metabolic syndrome

Free-amino acid metabolic profiling of visceral adipose tissue from obese subjects

Interest in adipose tissue pathophysiology and biochemistry have expanded considerably in the past two decades due to the ever increasing and alarming rates of global obesity and its critical outcome defined as metabolic syndrome (MS). This obesity-linked systemic dysfunction generates high risk factors of developing perilous diseases like type 2 diabetes, cardiovascular disease or cancer. Amino acids could play a crucial role in the pathophysiology of the MS onset. Focus of this study was to fully characterize amino acids metabolome modulations in visceral adipose tissues (VAT) from three adult cohorts: (i) obese patients (BMI 43-48) with metabolic syndrome (PO), (ii) obese subjects metabolically well (O), and (iii) non obese individuals (H). 128 metabolites identified as 20 protein amino acids, 85 related compounds and 13 dipeptides were measured by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) and gas chromatography-/mass spectrometry GC/MS, in visceral fat samples from a total of 53 patients. Our analysis indicates a probable enhanced BCAA (leucine, isoleucine, valine) degradation in both VAT from O and PO subjects, while levels of their oxidation products are increased. Also PO and O VAT samples were characterized by: elevated levels of kynurenine, a catabolic product of tryptophan and precursor of diabetogenic substances, a significant increase of cysteine sulfinic acid levels, a decrease of 1-methylhistidine, and an up regulating trend of 3-methylhistidine levels. We hope this profiling can aid in novel clinical strategies development against the progression from obesity to metabolic syndrome

Primary flap closure of perineal defects to avoid empty pelvis syndrome after pelvic exenteration in gynecologic malignancies: An old question to explore a new answer

: Pelvic exenteration (PE) is a radical oncological surgical procedure proposed in patients with recurrent or persistent gynecological cancers. The radical alteration of pelvic anatomy and of pelvic floor integrity can cause major postoperative complications. Fortunately, PE can be combined with reconstructive procedures to decrease complications and functional and support problems of pelvic floor, reducing morbility and mortality and increasing quality of life. Many options for reconstructive surgery have been described, especially a wide spectrum of surgical flaps. Different selection criteria have been proposed to select patients for primary perineal defect flap closure without achieving any strict indication of the best option. The aim of this review is to focus on technical aspects and the advantages and disadvantages of each technique, providing an overview of those most frequently used for the treatment of pelvic floor defects after PE. Flaps based on the deep inferior epigastric artery, especially vertical rectus abdominis musculocutaneous (VRAM) flaps, and gracilis flaps, based on the gracilis muscle, are the most common reconstructive techniques used for pelvic floor and vaginal reconstruction. In our opinion, reconstructive surgery may be considered in case of total PE or type II/III PE and in patients submitted to prior pelvic irradiation. VRAM could be used to close extended defects at the time of PE, while gracilis flaps can be used in case of VRAM complications. Fortunately, numerous choices for reconstructive surgery have been devised. As these techniques continue to evolve, it is advisable to adopt an integrated, multi-disciplinary approach within a tertiary medical center

Inhibition of p85, the non-catalytic subunit of phosphatidylinositol 3-kinase, exerts potent antitumor activity in human breast cancer cells

: The phosphoinositide 3-kinases (PI3Ks) are heterodimers consisting of the catalytic subunit p110 and the regulatory subunit p85. The PI3K/Akt pathway is strongly deregulated in breast cancer (BC) representing one of the mechanisms of resistance to therapies. Therefore, the identification of inhibitors of PI3K components represents one of the main goals to produce therapeutic agents. Here, we evaluated the efficacy of a phosphopeptide 1257 (P-1257) that targeting p85 strongly inhibits PI3K activity. We tested the effects of P-1257 administration in vitro and in vivo using BC cells expressing different levels of ErbB-2 and resistant or responsive to Trastuzumab. We demonstrated that inhibition of p85 activity by P-1257 induces cell death and sensitizes JIMT-1 and KPL-4 ErbB-2-overexpressing BC cells to Trastuzumab treatment. It is noteworthy that P-1257 delivery in vivo by electroporation or liposomes significantly inhibits the proliferation of tumor cells engrafted at subcutaneous and visceral sites. Overall, our data indicate that the p85 subunit is a valid target for therapeutic approaches and suggest that the structure of the peptide used in our study could be utilized for the development of novel drugs to apply in combination with therapies that fail to cure BCs with high PI3K activity

Evolution of Rheumatoid-Arthritis-Associated Interstitial Lung Disease in Patients Treated with JAK Inhibitors: A Retrospective Exploratory Study

Background: The aim of this multicenter retrospective study was to investigate the effectiveness and safety of the available JAK-inhibitors (JAKi) in patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD). Methods: We retrospectively analyzed patients with classified RA and RA-ILD undergoing JAKi in 6 Italian tertiary centers from April 2018 to June 2022. We included patients with at least 6 months of active therapy and one high-resolution chest tomography (HRCT) carried out within 3 months of the start of JAKi treatment. The HRCT was then compared to the most recent one carried out within 3 months before the last available follow-up appointment. We also kept track of the pulmonary function tests. Results: We included 43 patients with RA-ILD and 23 males (53.48%) with a median age (interquartile range, IQR) of 68.87 (61.46–75.78) treated with JAKi. The median follow-up was 19.1 months (11.03–34.43). The forced vital capacity remained stable in 22/28 (78.57%) patients, improved in 3/28 (10.71%) and worsened in 3/28 (10.71%). The diffusing capacity of lung for carbon monoxide showed a similar trend, remaining stable in 18/25 (72%) patients, improving in 2/25 (8%) and worsening in 5/25 (20%). The HRCT remained stable in 37/43 (86.05) cases, worsened in 4/43 (9.30%) and improved in the last 2 (4.65%). Discussion: This study suggests that JAKi therapy might be a safe therapeutic option for patients with RA-ILD in a short-term follow-up