Non-pharmacological interventions targeting mobility among people with advanced cancer: a systematic review.

PURPOSE: To synthesise evidence evaluating non-pharmacological interventions targeting mobility among people with advanced cancer, considering the type, efficacy and contextual factors that may influence outcome. METHODS: Systematic review of studies of non-pharmacological interventions in adults (≥ 18 years) with advanced (stage III-IV) cancer, and assessing mobility using clinical or patient-reported outcome measures. Searches were conducted across three electronic databases (MEDLINE, EMBASE and CINAHL) up to June 2024. Methodological quality was assessed using Joanna Briggs Institute tools and contextual factors were evaluated through the Context and Implementation of Complex Interventions framework. A narrative synthesis was conducted due to clinical heterogeneity of included studies. RESULTS: 38 studies encompassing 2,464 participants were included. The most frequent mobility outcome measure was the 6-min walk test (26/38 studies). Exercise was the most common intervention, (33 studies: 27 aerobic and resistance, 5 aerobic, 1 resistance versus aerobic training) and improvements in mobility were found in 21/33 outcomes. Electrotherapy interventions led to significant improvements in mobility in 3/5 studies. Geographical factors (e.g. distance, transport, parking requirements) potentially limited participation in 18/38 studies. A lack of ethnic diversity among populations was evident and language proficiency was an inclusion criterion in 12 studies. CONCLUSION: Exercise and neuromuscular electrical stimulation appear to improve mobility outcomes in advanced cancer. The evaluation of other non-pharmacological interventions targeting mobility should consider access and inclusivity, and be adaptable to the needs of this population.

Facing the COVID-19 pandemic: An Italian feasibility study of a mixed in-person/telerehabilitation intervention for cancer patients.

INTRODUCTION: The COVID-19 pandemic impacted healthcare organizations, necessitating a rapid transition from in-person to virtual care. Our study explored the feasibility of a mixed in-person/telerehabilitation intervention for cancer patients and its effects on cancer-related fatigue (CRF), quality of life (QoL), physical function, patient satisfaction, and perceived usefulness. METHODS: TRACE 2020 is an observational prospective study that enrolled adult cancer patients, between January 2021 and March 2023, who were eligible for a rehabilitation program to be provided also in telerehabilitation. Patients were assessed at baseline and after the rehabilitation program. Adherence to sessions, reasons for non-adherence and adverse events were collected. RESULTS: Of the 23 patients enrolled, 87% received a mixed intervention, with an average of 60% in-person sessions and 40% telerehabilitation sessions. Adherence was very high (91%). Evaluation scales showed an improvement in CRF, QoL, and lower limb strength and a relevant increase in patients' level of physical activity (PA). Most patients reported good satisfaction; the few criticisms mainly concerned difficulties in connectivity, lack of physical contact and difficulties in understanding how to perform exercises during telerehabilitation sessions. The physiotherapist underlined the usefulness of the innovative approach and suggested ways to facilitate future implementation. CONCLUSION: A mixed intervention including telerehabilitation is feasible and accepted by cancer patients. It may have a positive effect on their CRF, QoL, and level of PA and render patient care more flexible. The findings suggest what characteristics the target population for telerehabilitation should have, in order to integrate telerehabilitation in standard care for cancer patients.

A novel STING variant triggers endothelial toxicity and SAVI disease.

Gain-of-function mutations in STING cause STING-associated vasculopathy with onset in infancy (SAVI) characterized by early-onset systemic inflammation, skin vasculopathy, and interstitial lung disease. Here, we report and characterize a novel STING variant (F269S) identified in a SAVI patient. Single-cell transcriptomics of patient bone marrow revealed spontaneous activation of interferon (IFN) and inflammatory pathways across cell types and a striking prevalence of circulating naïve T cells was observed. Inducible STING F269S expression conferred enhanced signaling through ligand-independent translocation of the protein to the Golgi, protecting cells from viral infections but preventing their efficient immune priming. Additionally, endothelial cell activation was promoted and further exacerbated by cytokine secretion by SAVI immune cells, resulting in inflammation and endothelial damage. Our findings identify STING F269S mutation as a novel pathogenic variant causing SAVI, highlight the importance of the crosstalk between endothelial and immune cells in the context of lung disease, and contribute to a better understanding of how aberrant STING activation can cause pathology.

Belimumab-induced periungual pyogenic granulomas: A case report.

Pyogenic granuloma (PG) is a benign vascular neoformation, presenting as a painful red nodule on the skin, mucosa or nail apparatus. It is usually related to local complications such as bleedings and superinfections. The etiology of PG remains still unclear, and several triggers can lead to its formation. In case of multiple lesions, systemic conditions and drugs remain the main causes. Antineoplastic treatments, retinoids, antiretrovirals, hormones and anticonvulsants are frequently implicated in PG formation. In literature, PG has been rarely described in the course of biological treatment due to rheumatological disease. The present case report describes the development of polydactolous PGs in a 21-year-old woman with juvenile systemic lupus erythematosus (jSLE) during treatment with belimumab, a monoclonal antibody directed against BlyS. The clinical presentation, in particular the timing and the multiplicity of the lesions, and the improvement after belimumab discontinuation allowed us to consider PG as drug-induced. This case highlights the importance of considering PG as a potential complication of rheumatologic treatments.

Effectiveness of action observation treatment based on pathological model in hemiplegic children: a randomized-controlled trial.

BACKGROUND: Action observation treatment (AOT) is an innovative therapeutic approach consisting in the observation of actions followed by their subsequent repetition. The standard version of AOT consists in the observation/imitation of a typically developed individual, which is proposed as model (TDM-AOT). AIM: This study aims to compare the effectiveness of AOT based on a pathological ameliorative model (PAM-AOT) versus TDM-AOT in improving upper limb ability in children with unilateral cerebral palsy (UCP). DESIGN: The study consists in a prospective randomized controlled, evaluator-blinded trial (RCT), with two active arms, designed to evaluate the effectiveness of AOT based on pathological model (PAM-AOT) as compared to a standard AOT based on TDM (TDM-AOT). SETTING: The 3-week AOT program was administered in a clinical setting. For some patients, the treatment was delivered at participant's home with the remote support of the physiotherapist (tele-rehabilitation). POPULATION: Twenty-six children with UCP (mean age 10.5±3.09 years; 14 females) participated in the study, with the experimental group observing a pathological model and the control group observing a typically developed model. METHODS: Motor assessments included unimanual and bimanual ability measures conducted at T0 (baseline, before the treatment), T1 (3 weeks after T0), T2 (8-12 weeks after treatment) and T3 (24-28 weeks after treatment); a subset of 16 patients also underwent fMRI motor assessment. Generalized Estimating Equations models were used for statistical analysis. RESULTS: Both groups showed significant improvement in bimanual function (GEE, Wald 106.16; P<0.001) at T1 (P<0.001), T2 (P<0.001), and T3 (P<0.001). Noteworthy, the experimental group showed greater improvement than the control group immediately after treatment (P<0.013). Both groups exhibited similar improvement in unimanual ability (GEE, Wald 25.49; P<0.001). The fMRI assessments revealed increased activation of ventral premotor cortex after treatment in the experimental compared with control group (GEE, Wald 6.26; P<0.012). CONCLUSIONS: Overall, this study highlights the effectiveness of PAM-AOT in achieving short-term improvement of upper limb ability in children with UCP. CLINICAL REHABILITATION IMPACT: These findings have significant implications for rehabilitative interventions based on AOT in hemiplegic children, by proposing a non-traditional approach focused on the most functional improvement achievable by imitating a pathological model.

Pre-Rheumatology Referral Consultation and Investigation Pattern in Children with Joint Complaints: Focus on Juvenile Idiopathic Arthritis.

The diagnosis of juvenile idiopathic arthritis (JIA) is often entrusted to the pediatric rheumatologist specialist. Timely referral to a specialized center is crucial. This study aims to assess the consultation and investigation patterns of patients with joint complaints before rheumatology referral. This longitudinal cohort study included patients with joint complaints who were referred to the Pediatric Rheumatology Unit. The cohort included 301 patients (58% female), 50 of them (17%) diagnosed with JIA. Compared to patients with orthopedic conditions or functional diseases, JIA patients had seen more specialists (p < 0.01) and received a quicker diagnosis (p < 0.01). Patients with early JIA diagnosis (within 3 months from symptoms onset) were younger (8.46 vs. 11.5 years old; p = 0.04), more frequently female (78% vs. 47%, p = 0.03), and with higher erythrocyte sedimentation rate (ESR) values (37 vs. 9 mm/h; p = 0.02) than those diagnosed later. Patients with a late diagnosis of JIA had a significantly longer median time between the first healthcare visit and the PR referral (25 vs. 101 days; p < 0.01). The main contributor to diagnostic delay in JIA was the time required for PR referral after the first healthcare consult. Younger age, female sex, and higher ESR values were associated with earlier diagnosis of JIA.

Impact of HLA-B51 on Uveitis and Retinal Vasculitis: Data from the AIDA International Network Registries on Ocular Inflammatory Disorders.

PURPOSE: The clinical relevance of human leukocyte antigen (HLA) subtypes such as HLA-B51 on Behçet's disease (BD)-related uveitis and non-infectious uveitis (NIU) unrelated to BD remains largely unknown. METHODS: Data were prospectively collected from the International AIDA Network Registry for BD and for NIU. We assessed differences between groups (NIU unrelated to BD and positive for HLA-B51, BD-related uveitis positive for HLA-B51 and BD-related uveitis negative for HLA-B51) in terms of long-term ocular complications, visual acuity (VA) measured by best corrected visual acuity (BCVA), anatomical pattern, occurrence of retinal vasculitis (RV) and macular edema over time. RESULTS: Records of 213 patients (341 eyes) were analyzed. No differences in complications were observed (p = 0.465). With regard to VA, a significant difference was detected in median BCVA (p = 0.046), which was not maintained after Bonferroni correction (p = 0.060). RV was significantly more prevalent in NIU-affected patients who tested positive for HLA-B51, irrespective of the systemic diagnosis of BD (p = 0.025). No differences emerged in the occurrence of macular edema (p = 0.99). CONCLUSIONS: Patients with NIU testing positive for HLA-B51 exhibit an increased likelihood of RV throughout disease course, irrespective of a systemic diagnosis of BD. The rate of complications as well as VA are comparable between NIU cases unrelated to BD testing positive for HLA-B51 and uveitis associated with BD. Therefore, it is advisable to perform the HLA-B typing in patients with NIU or retinal vasculitis, even in the absence of typical BD features.

Brain 18 F-FDG PET reveals cortico-subcortical hypermetabolic dysfunction in juvenile neuropsychiatric systemic lupus erythematosus.

BACKGROUND: In juvenile systemic lupus erythematosus (j-SLE) with neuropsychiatric (NP) symptoms, there is a lack of diagnostic biomarkers. Thus, we study whether PET-FDG may identify any metabolic dysfunction in j-NPSLE. METHODS: A total of 19 18FDG-PET exams were consecutively performed using PET-MRI system in 11 non-sedated patients presenting with j-NPSLE (11-18y) for less than 18 months (m) and without any significant lesion at MRI. Psychiatric symptoms were scored from 0 (none) to 3 (severe) at PET time. PET images were visually analyzed and voxel-based analyses of cerebral glucose metabolism were performed using statistical parametric mapping (spm) with an age-matched control group, at threshold set > 50 voxels using both p < 0.001 uncorrected (unc.) and p < 0.05 corrected family wise error (FWE). RESULTS: Patients exhibited mainly psychiatric symptoms, with diffuse inflammatory j-NPSLE. First PET (n = 11) was performed at a mean of 15y of age, second/third PET (n = 7/n = 1) 6 to 19 m later. PET individual analysis detected focal bilateral anomalies in 13/19 exams visually but 19/19 using spm (unc.), mostly hypermetabolic areas (18/19). A total of 15% of hypermetabolic areas identified by spm had been missed visually. PET group analysis (n = 19) did not identify any hypometabolic area, but a large bilateral cortico-subcortical hypermetabolic pattern including, by statistical decreasing order (unc.), thalamus, subthalamic brainstem, cerebellum (vermis and cortex), basal ganglia, visual, temporal and frontal cortices. Mostly the subcortical hypermetabolism survived to FWE analysis, being most intense and extensive (51% of total volume) in thalamus and subthalamus brainstem. Hypermetabolism was strictly subcortical in the most severe NP subgroup (n = 8, scores 2-3) whereas it also extended to cerebral cortex, mostly visual, in the less severe subgroup (n = 11, scores 0-1), but difference was not significant. Longitudinal visual analysis was inconclusive due to clinical heterogeneity. CONCLUSIONS: j-NPSLE patients showed a robust bilateral cortico-subcortical hypermetabolic network, focused subcortically, particularly in thalamus, proportionally to psychiatric features severity. Further studies with larger, but homogeneous, cohorts are needed to determine the sensitivity and specificity of this dysfunctional pattern as a potential biomarker in diffuse inflammatory j-NPSLE with normal brain MRI.

Ocular Manifestations in Juvenile Behçet's Disease: A Registry-Based Analysis from the AIDA Network.

INTRODUCTION: This study aims to characterize ocular manifestations of juvenile Behçet's disease (jBD). METHODS: This was a registry-based observational prospective study. All subjects with jBD from the Autoinflammatory Diseases Alliance (AIDA) Network BD Registry showing ocular manifestations before 18 years were enrolled. RESULTS: We included 27 of 1000 subjects enrolled in the registry (66.7% male patients, 45 affected eyes). The median (interquartile range [IQR]) age at ocular involvement was 14.2 (4.7) years. Uveitis affected 91.1% of eyes (anterior 11.1%, posterior 40.0%, panuveitis 40.0%), retinal vasculitis 37.8% and other manifestations 19.8%. Later onset (p = 0.01) and male predominance (p = 0.04) characterized posterior involvement. Ocular complications occurred in 51.1% of eyes. Patients with complications had earlier onset (p < 0.01), more relapses (p = 0.02) and more prolonged steroidal treatment (p = 0.02). The mean (standard deviation [SD]) central macular thickness (CMT) at the enrolment and last visit was 302.2 (58.4) and 293.3 (78.2) µm, respectively. Fluorescein angiography was pathological in 63.2% of procedures, with a mean (SD) Angiography Scoring for Uveitis Working Group (ASUWOG) of 17.9 (15.5). At the last visit, ocular damage according to the BD Overall Damage Index (BODI) was documented in 73.3% of eyes. The final mean (SD) best corrected visual acuity (BCVA) logMAR was 0.17 (0.47) and blindness (BCVA logMAR < 1.00 or central visual field ≤ 10°) occurred in 15.6% of eyes. At multivariate regression analysis, human leukocyte antigen (HLA)-B51 + independently predicted a + 0.35 change in the final BCVA logMAR (p = 0.01), while a higher BCVA logMAR at the first assessment (odds ratio [OR] 5.80; p = 0.02) independently predicted blindness. CONCLUSIONS: The results of this study may be leveraged to guide clinical practice and future research on this rare sight-threatening condition.

JAK inhibitors in the treatment of adult patients with juvenile idiopathic arthritis: a retrospective monocentric experience.

OBJECTIVES: This study aims to evaluate the efficacy and safety of JAK inhibitors (JAKi) in a monocentric cohort of adult patients with juvenile idiopathic arthritis (JIA). METHODS: Patients attending a rheumatology transition clinic were retrospectively included in case of: i) JIA diagnosis according to current classification criteria (1); ii) age ≥18 years and iii) treatment with JAKi for at least 3 months. RESULTS: Seventeen adult patients with JIA were treated with JAKi (as first JAKi, 9 patients (52.9%) received tofacitinib and 8 (47.1%) baricitinib). At 3 months after JAKi initiation, 8 patients (47%) achieved a response and 4 patients (23.5%) achieved disease remission (3 patients with baricitinib and 1 with tofacitinib, 37.5% vs. 16.7%, p=0.294). None of those with systemic JIA and enthesitis-related arthritis obtained remission; the remission rate at 3 months was higher, although not significantly, in the oligoarticular subset compared to the polyarticular subset (37.5% vs. 20%). Patients with ≤1 active joint involvement at JAKi start had a higher remission rate (50% vs. 22.2%). Subjects who achieved remission on JAKi had a significantly lower pre-treatment DAS28-CRP compared to those with still active disease (p=0.010, Mann-Whitney U=4). A pre-treatment DAS28-CRP <3.76 predicted response to JAKi with 100% sensitivity and 84.6% specificity (p=0.023). The remission rate was lower among patients who had been treated with ≥2 biological drugs before JAKi start (9% vs. 66.7%; p=0.05). One patient in concomitant treatment with leflunomide developed severe arterial hypertension. CONCLUSIONS: JAKi may represent an effective and safe treatment option for adult JIA patients with low/moderate disease activity, particularly in case of oligoarticular involvement.

Lesion mapping and functional characterization of hemiplegic children with different patterns of hand manipulation.

Brain damage in children with unilateral cerebral palsy (UCP) affects motor function, with varying severity, making it difficult the performance of daily actions. Recently, qualitative and semi-quantitative methods have been developed for lesion classification, but studies on mild to moderate hand impairment are lacking. The present study aimed to characterize lesion topography and preserved brain areas in UCP children with specific patterns of hand manipulation. A homogeneous sample of 16 UCP children, aged 9 to 14 years, was enrolled in the study. Motor assessment included the characterization of the specific pattern of hand manipulation, by means of unimanual and bimanual measures (Kinematic Hand Classification, KHC; Manual Ability Classification System, MACS; House Functional Classification System, HFCS; Melbourne Unilateral Upper Limb Assessment, MUUL; Assisting Hand Assessment, AHA). The MRI morphological study included multiple methods: (a) qualitative lesion classification, (b) semi-quantitative classification (sq-MRI), (c) voxel-based morphometry comparing UCP and typically developed children (VBM-DARTEL), and (d) quantitative brain tissue segmentation (q-BTS). In addition, functional MRI was used to assess spared functional activations and cluster lateralization in the ipsilesional and contralesional hemispheres of UCP children during the execution of simple movements and grasping actions with the more affected hand. Lesions most frequently involved the periventricular white matter, corpus callosum, posterior limb of the internal capsule, thalamus, basal ganglia and brainstem. VMB-DARTEL analysis allowed to detect mainly white matter lesions. Both sq-MRI classification and q-BTS identified lesions of thalamus, brainstem, and basal ganglia. In particular, UCP patients with synergic hand pattern showed larger involvement of subcortical structures, as compared to those with semi-functional hand. Furthermore, sparing of gray matter in basal ganglia and thalamus was positively correlated with MUUL and AHA scores. Concerning white matter, q-BTS revealed a larger damage of fronto-striatal connections in patients with synergic hand, as compared to those with semi-functional hand. The volume of these connections was correlated to unimanual function (MUUL score). The fMRI results showed that all patients, but one, including those with cortical lesions, had activation in ipsilesional areas, regardless of lesion timing. Children with synergic hand showed more lateralized activation in the ipsilesional hemisphere both during grasping and simple movements, while children with semi-functional hand exhibited more bilateral activation during grasping. The study demonstrates that lesion localization, rather than lesion type based on the timing of their occurrence, is more associated with the functional level of hand manipulation. Overall, the preservation of subcortical structures and white matter can predict a better functional outcome. Future studies integrating different techniques (structural and functional imaging, TMS) could provide further evidence on the relation between brain reorganization and specific pattern of manipulation in UCP children.

Models of Care in Providing Comprehensive Healthcare on Cancer Survivors: A Scoping Review with a TIDieR Checklist Analysis.

BACKGROUND: The study's aim is to identify the models of care used to provide survivorship care plans (SCPs) to cancer survivors in healthcare services, describing what kind of professionals are involved, in which settings and timings, and their feasibility. METHODS: The Joanna Briggs Institute methodology for scoping reviews is followed. Studies that considered the SCPs applying different models of care, in any healthcare setting on any adult cancer survivors who completed oncological treatments, have been included. Pubmed, Embase, Cochrane Library, Scopus, and Cinahal were searched from 2013 to 2023 with these keywords: "Survivorship Care Plan", "Oncology", and "Program". The study selection process was reported with the PRISMA-ScR. A total of 325 records were identified, 42 were screened, and, ultimately, 23 articles were included. RESULTS: The models of care include: SCP standardization in hospitals; self-support oriented; consultation-based; primary or specialist direct referral; shared care; a multimodal approach. Multidisciplinary teams were involved in the SCP models of care. The settings were private clinics or cancer centers. One-hour SCP interventions were most frequently delivered through in-person visits, by telephone, or online. CONCLUSIONS: Implementing SCPs is feasible in healthcare contexts, but with challenges, like time and resource management. Patient-centered programs promoting coordinated care are promising models of care.

Effectiveness and Safety of Biosimilars in Pediatric Non-infectious Uveitis: Real-Life Data from the International AIDA Network Uveitis Registry.

INTRODUCTION: Since many biological drug patents have expired, biosimilar agents (BIOs) have been developed; however, there are still some reservations in their use, especially in childhood. The aim of the current study is to evaluate the efficacy and safety of tumor necrosis factor (TNF) inhibitors BIOs as treatment for pediatric non-infectious uveitis (NIU). METHODS: Data from pediatric patients with NIU treated with TNF inhibitors BIOs were drawn from the international AutoInflammatory Disease Alliance (AIDA) registries dedicated to uveitis and Behçet's disease. The effectiveness and safety of BIOs were assessed in terms of frequency of relapses, risk for developing ocular flares, best-corrected visual acuity (BCVA), glucocorticoids (GCs)-sparing effect, drug survival, frequency of ocular complications, and adverse drug event (AE). RESULTS: Forty-seven patients (77 affected eyes) were enrolled. The BIOs employed were adalimumab (ADA) (89.4%), etanercept (ETA) (5.3%), and infliximab (IFX) (5.3%). The number of relapses 12 months prior to BIOs and at last follow-up was 282.14 and 52.43 per 100 patients/year. The relative risk of developing ocular flares before BIOs introduction compared to the period following the start of BIOs was 4.49 (95% confidence interval [CI] 3.38-5.98, p = 0.004). The number needed to treat (NNT) for ocular flares was 3.53. Median BCVA was maintained during the whole BIOs treatment (p = 0.92). A significant GCs-sparing effect was observed throughout the treatment period (p = 0.002). The estimated drug retention rate (DRR) at 12-, 24-, and 36-month follow-up were 92.7, 83.3, and 70.8%, respectively. The risk rate for developing structural ocular complications was 89.9/100 patients/year before starting BIOs and 12.7/100 patients/year during BIOs treatment, with a risk ratio of new ocular complications without BIOs of 7.1 (CI 3.4-14.9, p = 0.0003). Three minor AEs were reported. CONCLUSIONS: TNF inhibitors BIOs are effective in reducing the number of ocular uveitis relapses, preserving visual acuity, allowing a significant GCs-sparing effect, and preventing structural ocular complications. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05200715.

Diagnostic and prognostic role of synovial tissue analysis in juvenile idiopathic arthritis: a monocentric study.

OBJECTIVES: This study investigates the diagnostic role of synovial tissue analysis in children presenting with arthritis and assesses its prognostic significance to predict clinical outcome in juvenile idiopathic arthritis (JIA). METHODS: Synovial samples of paediatric patients undergoing synovial biopsy between 1995 and 2020 were analysed histologically and immunohistochemically. Relationships between histological/immunohistochemical parameters and clinical variables were assessed. RESULTS: Synovial biopsy was performed for diagnosis in 65 cases allowing to correctly classify 79% of patients.At histological analysis on 42 JIA samples, any difference in the number of synovial lining layers, subsynovial elementary lesions, fibrin deposit, Krenn Synovitis Score, inflammatory infiltrate score and pattern emerged between JIA subsets or on treatment exposure. Synovial tissue analysis predicted outcome: higher number of synovial layers predicted worse disease course (>4 flares during follow-up; 4.5 vs 3.0, p=0.035), even after adjusting for age at diagnosis and observation time (OR 2.2, p=0.007); subjects who had switched>2 biological disease-modifying antirheumatic drugs had higher prevalence of subsynovial elementary lesions (55.6% vs 10.3%, p=0.005) and fibrin deposits in synovial lining (60.0% vs 22.6%, p=0.049), even after adjustment for observation time and age at diagnosis (OR 8.1, p=0.047). At immunohistochemistry on 31 JIA samples, higher CD3 expression was described in polyarticular compared with oligoarticular subset (p=0.040). Patients with severe disease course had higher CD20+ rate (OR 7, p=0.023), regardless of JIA subset and treatment exposure. CONCLUSIONS: Synovial tissue analysis might support the clinicians in the diagnostic approach of paediatric patients presenting with arthritis and guide the clinical management in JIA.