Search

Objectives: We aimed to analyze the episodes of esophageal food bolus impaction (EFI) occurred over a time of 15 years in children admitted to a large pediatric emergency department (PED), documenting their clinical presentation, underlying pathology, management, biopsy rate, and follow-up visits. Additionally, to combine our institutional experience with the existing literature, a comprehensive review was conducted., Methods: We reviewed the medical records of all children presenting to our PED with EFI from 2010 to 2024. The comprehensive review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement for systematic reviews. Electronic databases including PubMed/Medline and EMBASE were screened. The data obtained was synthesized to map out the actual status and current literature on pediatric EFI., Results: We identified 54 cases of EFI. Overall, 22 patients (41%) had underlying pathology. Previous episodes were reported in 14 cases (26%). Urgent endoscopy was performed in 31 cases (57%). The presence of underlying pathology was associated with the need for endoscopic removal (p = 0.013), as well as the history of previous episodes (p = 0.016). Biopsies were performed in 14 cases (26%). Pediatric gastroenterologists showed a higher rate of performed biopsies compared to surgeons, as well as higher rate of follow-up visits. An underlying disease was found during later clinical follow-up in 5 out of 54 cases of EFI (9%). A comprehensive review of 16 studies revealed high rates of underlying pathology and low rates of biopsies and follow-up visits among children with EFI., Conclusion: Increased vigilance in identifying underlying pathologies in children with EFI is crucial. The importance of performing biopsies, regardless of prior anatomical conditions, and the need for ongoing follow-up to ensure timely and accurate diagnoses should be addressed through shared protocols., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background/objectives: Despite the introduction of innovative therapeutics, lung cancer is still the leading cause of cancer-related death. For this reason, lung cancer still requires deep characterization to identify cellular and molecular targets that can be used to develop novel therapeutic strategies. Three-dimensional cellular models, including patient-derived organoids (PDOs), represent useful tools to study lung cancer biology and may be employed in the future as predictive tools in therapeutic decisions. However, the successful establishment of lung cancer organoids cultures that faithfully represent the respective patient tissues is still challenging due to low success rate and/or overgrowth of normal airway epithelial cells., Methods: We set up a two-step protocol that allows for establishing both short-term and long-term 3D cultures, with different characteristics and success rates., Results: Cancer tissue-originated spheroids (CTOSs) show a 100% success rate and allow for the concomitant isolation of autologous tumor infiltrating leukocytes (TILs). On the contrary, PDOs can be expanded for a medium-long term and bio-banked but retain a lower success rate and the possibility of contamination with normal airway epithelial cells. To overcome these problems, we set up an optimal medium formulation and we implemented rigorous quality controls, leading to a substantial improvement in the success rate of tumoral PDO establishment., Conclusions: Overall, this protocol guarantees flexibility and reliability, also providing useful guidelines for quality control checks to support different experimental settings. The setting up of a robust protocol for lung cancer PDO culture establishment and expansion is a key requirement for their employment both in cancer research and as predictive tools in clinical practice.

Background: To translate and cross-culturally adapt the Parkinson's Disease Caregiver Burden questionnaire (PDBC) into Italian language and to evaluate the psychometric properties of the Italian version in terms of test-retest reliability, internal consistency, and construct validity., Methods: The PDBC-I was developed by forward-backward translation to establish correspondence with the original English latest version. Psychometric properties were estimated in a sample of primary caregivers of individuals with Parkinson's disease. Reliability testing included internal consistency (Cronbach's alpha), test-retest reliability (ICC), the standard error of measurement (SEM) and the minimal detectable change (MDC), also expressed as percentage (MDC%). Validity was estimated by comparing the PDBC -I to the Caregiver Burden Inventory (CBI) and the Short Form 36 (SF-36) (Pearson correlation coefficient)., Results: The questionnaire was administered to 65 caregivers, showing internal consistency of 0.934. ICC value was 0.811 (95% CI 0.708-0.880) for test-retest reliability, and the SEM and the MDC (MDC%) were 5.04 and 13.97 (38.21%), respectively. Low to moderate correlation with all other investigated scales (CBI: r=0.693; SF-36 physical score: r=-0.309; SF-36 mental score: r=-0.588; SF36 total score: -0.470) were found., Conclusions: Despite the PDCB-I holds acceptable psychometric properties to be used in clinical settings of Italian-speaking Countries as a measure of caregiver burden in caregivers of individuals with Parkinson Disease, the caregiver might require the support of a clinician to finalize the compilation of the questionnaire.

Introduction: The Community Physiotherapist model is an on-call service within the primary care setting, consisting of four consultations for people with chronic functional limitations. It was designed, developed and introduced as a project for the first time in Italy in 2021 and it has been shown to be effective and safe., Purpose: Given the novelty of the model, this focus group study aims to explore the perspectives of involved physiotherapists, general practitioners and medical specialists on the perceived efficiency and quality of the service. A qualitative design was used with two balanced multidisciplinary focus groups of 12 participants. The Focus groups were audio recorded and transcribed verbatim. Data were analyzed using thematic analysis., Results: Five themes emerged from the analysis, related to the speed of both referral and intervention, tailored interventions and perceived quality: Efficiency, Perceived quality, Project implementation, Training, and Project dissemination., Conclusion: The study findings showed that the model was appreciated by the professionals involved, although some aspect about communication between professionals and with patients/caregivers, as well as some organizational aspects, needed improvement. Further research should address the perspectives of the patients/caregivers involved.

Purpose: To analyze the referral patterns and the clinical and therapeutic features of patients diagnosed with uveitis in an Italian tertiary referral center to provide a comparison with previously published series from the same center., Methods: Retrospective retrieval of data on all new referrals to the Ocular Immunology Unit in Reggio Emilia (Italy) between November 2015 and April 2022 and comparison with previously published series from the same center., Results: Among the 1557 patients, the male-to-female ratio was 1:1.27. Anterior uveitis was the most common diagnosis (53.7%), followed by posterior (21.6%), pan- (18.5%), and intermediate (6.2%) uveitis. The most identifiable specific diagnoses were anterior herpetic uveitis (18.4%), Fuchs uveitis (12.8%), and tuberculosis (6.1%). Infectious etiologies were the most frequent (34.1%) and were more diffuse among non-Caucasian patients ( p  < 0.001), followed by systemic disease-associated uveitis (26.5%), and ocular-specific conditions (20%). Idiopathic uveitis accounted for 19.4% of cases. Fuchs uveitis presented the longest median diagnostic delay (21 months). Immunosuppressants were administered to 25.2% of patients. Antimetabolites, calcineurin inhibitors, and biologicals were prescribed to 18.4%, 3%, and 11.4% of cases, respectively. Compared to our previous reports, we observed a significant increase in foreign-born patients and in infectious uveitis, a decrease in idiopathic conditions, and an increasing use of non-biological and biological steroid-sparing drugs., Conclusions: The patterns of uveitis in Italy have been changing over the last 20 years, very likely due to migration flows. Diagnostic improvements and a more widespread interdisciplinary approach could reduce the incidence of idiopathic uveitis as well as diagnostic delay.

Objectives: We aimed to appraise the real-life efficacy of Crohn's disease exclusion diet (CDED) coupled with partial enteral nutrition (PEN) in inducing clinical and biochemical remission at disease onset and in patients with loss of response to biologics and immunomodulators., Methods: We retrospectively gathered data of patients aged less than 18 years of age with a diagnosis of Crohn's disease (CD), who received CDED coupled with PEN at a tertiary level pediatric inflammatory bowel disease center., Results: Sixty-six patients were identified. Forty (60.6%) started CDED plus PEN at disease onset and 26 (39.4%) received CDED with PEN as add-on therapy. Forty-six (69.7%) patients achieved clinical remission (weighted Pediatric Crohn's Disease Activity Index < 12.5) at the end of phase 1, 44 (66.7%) normalized c-reactive protein levels (<0.5 mg/dL) and 18 (27.2%) patients normalized calprotectin levels (<150 µg/g). Nine of 19 (47.3%) of patients with clinically severe disease (defined by Physician Global Assessment) achieved clinical remission at the end of phase I. Patients with extraintestinal manifestations had statistically lower clinical response rates to the dietary regimen (p = 0.018). Among patients who received CDED + PEN as add-on treatment, a previous successful course of Exclusive Enteral Nutrition was associated with statistically higher clinical remission rates at Week 8 (p = 0.026). Clinical response at Week 4 was an independent predictor of clinical remission and fecal calprotectin normalization at Week 8 (p = 0.002)., Conclusion: CDED with PEN confirmed its efficacy in a real-life setting, proving to be effective also in refractory patients and those with severe disease. Early clinical response predicts clinical remission at the end of phase 1., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Mechano-electric regulations (MER) play an important role in the maintenance of cardiac performance. Mechano-calcium and mechano-electric feedback (MCF and MEF) pathways adjust the cardiomyocyte contractile force according to mechanical perturbations and affects electro-mechanical coupling. MER integrates all these regulations in one unit resulting in a complex phenomenon. Computational modelling is a useful tool to accelerate the mechanistic understanding of complex experimental phenomena. We have developed a novel model that integrates the MER loop for human atrial cardiomyocytes with proper consideration of feedforward and feedback pathways. The model couples a modified version of the action potential (AP) Koivumäki model with the contraction model by Quarteroni group. The model simulates iso-sarcometric and isometric twitches and the feedback effects on AP and Ca 2+ -handling. The model showed a biphasic response of Ca 2+ transient (CaT) peak to increasing pacing rates and highlights the possible mechanisms involved. The model has shown a shift of the threshold for AP and CaT alternans from 4.6 to 4 Hz under post-operative atrial fibrillation, induced by depressed SERCA activity. The alternans incidence was dependent on a chain of mechanisms including RyRs availability time, MCF coupling, CaMKII phosphorylation, and the stretch levels. As a result, the model predicted a 10% slowdown of conduction velocity for a 20% stretch, suggesting a role of stretch in creation of substrate formation for atrial fibrillation. Overall, we conclude that the developed model provides a physiological CaT followed by a physiological twitch. This model can open pathways for the future studies of human atrial electromechanics. KEY POINTS: With the availability of human atrial cellular data, interest in atrial-specific model integration has been enhanced. We have developed a detailed mathematical model of human atrial cardiomyocytes including the mechano-electric regulatory loop. The model has gone through calibration and evaluation phases against a wide collection of available human in-vitro data. The usefulness of the model for analysing clinical problems has been preliminaryly tested by simulating the increased incidence of Ca 2+ transient and action potential alternans at high rates in post-operative atrial fibrillation condition. The model determines the possible role of mechano-electric feedback in alternans incidence, which can increase vulnerability to atrial arrhythmias by varying stretch levels. We found that our physiologically accurate description of Ca 2+ handling can reproduce many experimental phenomena and can help to gain insights into the underlying pathophysiological mechanisms., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

This work introduces the first atrial-specific in-silico human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) model, based on a set of phenotype-specific I Kur ,I KCa and I K1 membrane currents. This model is built on novel in-vitro experimental data recently published by some of the co-authors to simulate the paced action potential of matured atrial-like hiPSC-CMs. The model consists of a system of stiff ordinary differential equations depending on several parameters, which have been tuned by automatic optimization techniques to closely match selected experimental biomarkers. The new model effectively simulates the electronic in-vitro hiPSC-CMs maturation process, transitioning from an unstable depolarized membrane diastolic potential to a stable hyperpolarized resting potential, and exhibits spontaneous firing activity in unpaced conditions. Moreover, our model accurately reflects the experimental rate dependence data at different cycle length and demonstrates the expected response to a specific current blocker. This atrial-specific in-silico model provides a novel computational tool for electrophysiological studies of cardiac stem cells and their applications to drug evaluation and atrial fibrillation treatment., Competing Interests: Declaration of competing interest There are no conflicts of interest: None Declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Work-related burnout is a significant concern amongst healthcare professionals, including physiotherapists. It can negatively impact on both staff well-being and the quality of care delivered to patients., Objectives: To estimate the prevalence of burnout among physiotherapists., Data Sources: PubMed, CINAHL, Web of Science, Embase, Scopus and PsycINFO, from inception to February 1st, 2022., Study Selection or Eligibility Criteria: Studies reporting burnout prevalence among physiotherapists., Data Extraction and Data Synthesis: Prevalence of burnout. Sub-analyses were performed grouping studies based on countries where surveys were conducted, classified as developed or developing countries. The risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale., Results: 32 studies were included in the systematic review and 31 in the meta-analysis, enrolling a total of 5984 physiotherapists from 17 countries. Pooled prevalence (95% confidence interval) of burnout was 8% (4-15). Prevalence figures for Maslach Burnout Inventory dimensions were: (i) emotional exhaustion, 27% (21-34) (ii) depersonalization, 23% (15-32) (iii) low personal accomplishment, 25% (15-40). Both overall and single components prevalence was higher, although not significantly, in studies from developing than in developed countries., Limitations: Tools used to assess burnout and cut-off scores chosen to identify the burnout prevalence differed across studies., Conclusion and Implications of Key Findings: Prevalence of burnout reported by physiotherapists appears high worldwide, in particular in developing countries, and compares with that reported by nurses and physicians. Substantial heterogeneity in the prevalence of burnout, in its definition and assessment methods across studies, and limited quality of most studies precludes drawing definitive conclusions., Systematic Review Registration Number: PROSPERO CRD42022307876 CONTRIBUTION OF THE PAPER., (Copyright © 2024 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.)

Phenotypic drug discovery (PDD) involves screening compounds for their effects on cells, tissues, or whole organisms without necessarily understanding the underlying molecular targets. PDD differs from target-based strategies as it does not require knowledge of a specific drug target or its role in the disease. This approach can lead to the discovery of drugs with unexpected therapeutic effects or applications and allows for the identification of drugs based on their functional effects, rather than through a predefined target-based approach. Ultimately, disease definitions are mostly symptom-based rather than mechanism-based, and the therapeutics should be likewise. In recent years, there has been a renewed interest in PDD due to its potential to address the complexity of human diseases, including the holistic picture of multiple metabolites engaging with multiple targets constituting the central hub of the metabolic host-microbe interactions. Although PDD presents challenges such as hit validation and target deconvolution, significant achievements have been reached in the era of big data. This article explores the experiences of researchers testing the effect of a thymic peptide hormone, thymosin alpha-1, in preclinical and clinical settings and discuss how its therapeutic utility in the precision medicine era can be accommodated within the PDD framework., Competing Interests: The authors declare that EG, CC, and LR are involved in the “A phase II trial to assess the activity and tolerability of Thymosin alpha 1 in Cystic Fibrosis Patients” EudraCT Number: 2019-001441-40, sponsored by SciClone. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Garaci, Paci, Matteucci, Costantini, Puccetti and Romani.)

Interconnected mechanisms of ischemia and reperfusion (IR) has increased the interest in IR in vitro experiments using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). We developed a whole-cell computational model of hiPSC-CMs including the electromechanics, a metabolite-sensitive sarcoplasmic reticulum Ca2+-ATPase (SERCA) and an oxygen dynamics formulation to investigate IR mechanisms. Moreover, we simulated the effect and action mechanism of levosimendan, which recently showed promising anti-arrhythmic effects in hiPSC-CMs in hypoxia. The model was validated using hiPSC-CM and in vitro animal data. The role of SERCA in causing relaxation dysfunction in IR was anticipated to be comparable to its function in sepsis-induced heart failure. Drug simulations showed that levosimendan counteracts the relaxation dysfunction by utilizing a particular Ca2+-sensitizing mechanism involving Ca2+-bound troponin C and Ca2+ flux to the myofilament, rather than inhibiting SERCA phosphorylation. The model demonstrates extensive characterization and promise for drug development, making it suitable for evaluating IR therapy strategies based on the changing levels of cardiac metabolites, oxygen and molecular pathways., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Non-small-cell lung carcinoma (NSCLC) is the most common lung cancer and one of the pioneer tumors in which immunotherapy has radically changed patients' outcomes. However, several issues are emerging and their implementation is required to optimize immunotherapy-based protocols. In this work, we investigate the ability of the Bromodomain and Extra-Terminal protein inhibitors (BETi) to stimulate a proficient anti-tumor immune response toward NSCLC. By using in vitro, ex-vivo, and in vivo models, we demonstrate that these epigenetic drugs specifically enhance Natural Killer (NK) cell cytotoxicity. BETi down-regulate a large set of NK inhibitory receptors, including several immune checkpoints (ICs), that are direct targets of the transcriptional cooperation between the BET protein BRD4 and the transcription factor SMAD3. Overall, BETi orchestrate an epigenetic reprogramming that leads to increased recognition of tumor cells and the killing ability of NK cells. Our results unveil the opportunity to exploit and repurpose these drugs in combination with immunotherapy., (© 2024. The Author(s).)

The phasic cardiovascular activity influences the central nervous system through the systolic baroreceptor inputs, inducing widespread inhibitory effects on behavior. Through transcranial magnetic stimulation (TMS) delivered during resting-state over the left primary motor cortex and across the different cardiac phases, we measured corticospinal excitability (CSE) and distinct indices of intracortical motor inhibition: short (SICI) and long (LICI) interval, corresponding to GABA A and GABA B neurotransmission, respectively. We found a significant effect of the cardiac phase on short-intracortical inhibition, without any influence on LICI. Specifically, SICI was stronger at systole compared to diastole. These results show a tight relationship between the cardiac cycle and the inhibitory neurotransmission within M1, and in particular with GABA A -ergic-mediated motor inhibition. We hypothesize that this process requires greater motor control via the gating mechanism and that this, in turn, needs to be recalibrated through the modulation of intracortical inhibition., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: The study aimed to assess the longitudinal impact of endoscopic healing (EH) and histological healing (HH) in a cohort of paediatric patients affected by ulcerative colitis (UC)., Methods: This was a retrospective single-centre longitudinal study. 86 children with UC who underwent endoscopic re-assessment while in clinical and biochemical remission were included. Partial EH was defined as a Mayo Endoscopic Subscore (MES) of 1 and complete EH was defined as a MES of 0. HH was defined as the absence of active inflammation in all biopsies. The cumulative incidence of clinical relapse was evaluated during follow-up., Results: At the second endoscopic re-evaluation, 59 (68.6%) patients achieved EH (MES ≤1). Of these patients, 39 (66%) achieved complete EH. 20 of the 39 patients who achieved complete EH attained complete HH. Patients who achieved partial and complete EH showed higher recurrence-free survival rates compared to those who did not (p < 0.01 and p < 0.01, respectively). Amongst patients with complete EH, those who achieved complete HH had lower recurrence rates when compared to patients who still showed microscopic inflammation (p = 0.049)., Conclusion: Achievement of EH and HH is associated with fewer disease relapses, with patients achieving HH showing longer relapse-free survival rates., Competing Interests: Conflict of interest Paolo Lionetti has served as a speaker and as an advisory board member for AbbVie, Janssen, and Sandoz. All the other authors have no conflict of interest to declare., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Physical performance is poorly addressed in dialysis patients, due to several clinical and organizational barriers. In this study we investigated the physical functional status of a cohort of dialysis patients, using a multidimensional assessment., Methods: Four hundred and forty-six individuals from 8 hemodialysis centers (176 females), mean age 67.5 ± 14.1 years, and dialysis vintage 62 ± 72.1 months, were assessed by a multidimensional battery including Short Form Health Survey (SF12), Elderly Falls Screening Test (EFST), Short Physical Performance Battery (SPPB), and Handgrip Strength Test (HST). Individuals were stratified into 3 groups (poor, moderate, and good performers) according to the SPPB score. Functional assessments were performed by staff nurses, with the support of physiotherapists and nephrologists., Results: According to SPPB, 53.4% of dialysis patients showed a severe physical impairment. A significant difference emerged among the 3 SPPB groups for age, HST, EFST, and SF12. The main predictors of the SPPB score group were age (p = 0.0001), EFST (p = 0.028 moderate performers and p = 0.0001 poor performers), dominant HST (p = 0.04 moderate performers), and SF12 physical (p = 0.003 moderate performers and p = 0.0001 poor performers). Each age group showed physical performance comparable to a healthy general population of 10 years older., Conclusions: Our results confirmed the severe impairment of physical function in the end stage kidney disease population. The multidimensional assessment showed that SPPB test is an effective tool to stratify the dialysis population. Moreover, EFST, HST, and SF12 may contribute to the definition of a tailored physical activity program based on patient characteristics., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Primary health care systems have a key role in meeting health needs of community, including function. The aim of this paper is to describe the population involved in the Community Physiotherapist project and their health outcomes over a one-year period., Methods: The Community Physiotherapist is an on-call service which requires a request by general practitioners or medical specialists. Reason for prescription, waiting time for service delivery, diagnostic categories, provided intervention, number of interventions and outcomes were recorded for everyone included in the project. Possible differences in characteristics between individuals referred by medical specialists and general practitioners were also investigated., Results: From January to December 2022, 409 individuals were referred to the Community Physiotherapist pathway. Functional goals were achieved in 79.5% of interventions, without reported adverse events. In most cases physiotherapists provided counselling or caregiver training and 3.3% of individuals needed a full rehabilitation program. The groups of individuals referred by the two types of prescribers showed no significant differences, apart, as expected, from their median age., Conclusions: The introduction of the Community Physiotherapist model within the primary care setting allows to provide appropriate, effective and safe interventions. Sharing the project among all the health professionals helped to support its appropriateness and effectiveness. Results also indicate that a new organizational model, such as the Community Physiotherapist, will take a long time to be implemented., (© 2023. The Author(s).)

Long non-coding RNAs (lncRNAs) are transcripts without coding potential that are pervasively expressed from the genome and have been increasingly reported to play crucial roles in all aspects of cell biology. They have been also heavily implicated in cancer development and progression, with both oncogenic and tumor suppressor functions. In this work, we identified and characterized a novel lncRNA, TAZ-AS202, expressed from the TAZ genomic locus and exerting pro-oncogenic functions in non-small cell lung cancer. TAZ-AS202 expression is under the control of YAP/TAZ-containing transcriptional complexes. We demonstrated that TAZ-AS202 is overexpressed in lung cancer tissue, compared with surrounding lung epithelium. In lung cancer cell lines TAZ-AS202 promotes cell migration and cell invasion. TAZ-AS202 regulates the expression of a set of genes belonging to cancer-associated pathways, including WNT and EPH-Ephrin signaling. The molecular mechanism underlying TAZ-AS202 function does not involve change of TAZ expression or activity, but increases the protein level of the transcription factor E2F1, which in turn regulates the expression of a large set of target genes, including the EPHB2 receptor. Notably, the silencing of both E2F1 and EPHB2 recapitulates TAZ-AS202 silencing cellular phenotype, indicating that they are essential mediators of its activity. Overall, this work unveiled a new regulatory mechanism that, by increasing E2F1 protein, modifies the non-small cell lung cancer cells transcriptional program, leading to enhanced aggressiveness features. The TAZ-AS202/E2F1/EPHB2 axis may be the target for new therapeutic strategies., (© 2023. The Author(s).)

Background: Balance disorders in children are complex and disabling. The pediatric balance scale assesses functional balance in the contest of everyday tasks. It is recommended for balance assessment in children. The cross-cultural validation of an assessment instrument allows to assess individuals in the appropriate cultural context. We designed our study with the aim of translating and cross-cultural adapting the Pediatric Balance Scale into Italian, and investigating the reliability of the translated version., Methods: Two forward translation of the Pediatric Balance Scale were conducted. Two blind backward translations were subsequently performed. A multidisciplinary group compared the content of the translations with those of the original Pediatric Balance Scale. Ambiguities and discrepancies were amended. To assess conceptual equivalence of the translation, we conducted cognitive debriefing involving physiotherapists, parents, and children. Suggestions for rewording were sought and considered for eventual modification. The Italian Pediatric Balance Scale was administered to 18 children with typical development (age 4.7-7.9 years, female 61.1%, scores 51-56), and to 18 children with atypical development (age 4.9-15.0 years, female 44.4%, scores 38-56). Test-retest reliability (i.e., intrarater and interrater reliability, and agreement between raters) of the scale was assessed by mean of single-rating, absolute-agreement, two-way mixed effects model intra-class correlation coefficients (ICC3,1) and the Bland-Altman method. The standard error of measurement and the minimal detectable change were subsequently computed., Results: The forward and backward translations showed no substantial differences in content; wording discrepancies were resolved by consensus. The multidisciplinary group proposed some minor changes. Twenty-three physiotherapists, 36 parents, and 36 children participated in cognitive interviewing and further changes were made. Perfect agreement was observed in test-retest reliability assessment of the Italian pediatric balance scale in children with typical development. High reliability (intrarater: ICC3,1 0.998, 95% CI 0.994 to 0.999; interrater: ICC3,1 0.994, 95% CI 0.984 to 0.998) and agreement among raters (Bland-Altman plots: 89%, 95% CI 67% to 97%, of the data within the 95% CI limits of the bias estimate) were found assessing children with atypical development. Very small standard error of measurement and the minimal detectable change values were observed (intrarater: 0.212 and 0.588; interrater: 0.368 and 1.019)., Conclusions: The present study provides a translated and cross-culturally adapted Italian version of the Pediatric Balance Scale. The full cross-cultural validity of the tool requires further steps to complete the psychometric testing.

Thalidomide has emerged as an effective immunomodulator in the treatment of pediatric patients with inflammatory bowel disease (IBD) refractory to standard therapies. Cereblon (CRBN), a component of E3 protein ligase complex that mediates ubiquitination and proteasomal degradation of target proteins, has been identified as the primary target of thalidomide. CRBN plays a crucial role in thalidomide teratogenicity, however it is unclear whether it is also involved in the therapeutic effects in IBD patients. This study aimed at identifying the molecular mechanisms underpinning thalidomide action in pediatric IBD. In this study, ten IBD pediatric patients responsive to thalidomide were prospectively enrolled. RNA-sequencing (RNA-seq) analysis and functional enrichment analysis were carried out on peripheral blood mononuclear cells (PBMC) obtained before and after twelve weeks of treatment with thalidomide. RNA-seq analysis revealed 378 differentially expressed genes before and after treatment with thalidomide. The most deregulated pathways were cytosolic calcium ion concentration, cAMP-mediated signaling, eicosanoid signaling and inhibition of matrix metalloproteinases. Neuronal signaling mechanisms such as CREB signaling in neurons and axonal guidance signaling also emerged. Connectivity Map analysis revealed that thalidomide gene expression changes were similar to those exposed to MLN4924, an inhibitor of NEDD8 activating enzyme, suggesting that thalidomide exerts its immunomodulatory effects by acting on the ubiquitin-proteasome pathway. In vitro experiments on cell lines confirmed the effect of thalidomide on candidate altered pathways observed in patients. These results represent a unique resource for enhanced understanding of thalidomide mechanism in pediatric patients with IBD, providing novel potential targets associated with drug response., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The study of mechanism of action of Thymosin alpha 1 (Tα1) and the basis of the pleiotropic effect in health and disease, is one of the main focus of our ongoing research. Tα1 is a thymic peptide that demonstrates a peculiar ability to restore homeostasis in different physiological and pathological conditions (i.e., infections, cancer, immunodeficiency, vaccination, and aging) acting as multitasking protein depending on the host state of inflammation or immune dysfunction. However, few are the information about mechanisms of action mediated by specific Tα1-target protein interaction that could explain its pleiotropic effect. We investigated the interaction of Tα1 with Galectin-1 (Gal-1), a protein belonging to an oligosaccharide binding protein family involved in a variety of biological and pathological processes, including immunoregulation, infections, cancer progression and aggressiveness. Using molecular and cellular methodological approaches, we demonstrated the interaction between these two proteins. Tα1 specifically inhibited the hemagglutination activity of Gal-1, the Gal-1 dependent in vitro formation of endothelial cell tubular structures, and the migration of cancer cells in wound healing assay. Physico-chemical methods revealed the details of the molecular interaction of Tα1 with Gal-1. Hence, the study allowed the identification of the not known until now specific interaction between Tα1 and Gal-1, and unraveled a novel mechanism of action of Tα1 that could support understanding of its pleiotropic activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: The Nottingham Clavicle Score (NCS) is a patient-reported outcome measure developed to evaluate treatment results of clavicle, acromioclavicular and sternoclavicular joint pathologies. Valid, reliable and user-friendly translations of outcome measure instruments are needed to allow comparisons of international results. The aim of this cross-sectional study was to translate and adapt the NCS into German and evaluate the psychometric properties of the German version., Methods: The translation and cross-cultural adaptation of the NCS were completed using a 'translation-back translation" method and the final version was administered to 105 German-speaking patients. The psychometric properties of this version (NCS-G) were evaluated in terms of feasibility, reliability, validity and sensitivity to change., Results: No major differences occurred between the NCS translations into German and back into English, and no content- or linguistic-related difficulties were reported. The Cronbach's alpha for the NCS-G was 0.885, showing optimal internal consistency. The Intraclass Correlation Coefficient for test-retest reliability was 0.907 (95% CI 0.844-0.945), with a standard error of measurement of 5.59 points and a minimal detectable change of 15.50 points. The NCS-G showed moderate to strong correlation with all other investigated scales (Spearman correlation coefficient: qDASH: ρ =  - 0.751; OSS: ρ = 0.728; Imatani Score: ρ = 0.646; CMS: ρ = 0.621; VAS: ρ =  - 0.709). Good sensitivity to change was confirmed by an effect size of 1.17 (95% CI 0.89-1.47) and a standardized response mean of 1.23 (95% CI 0.98-1.45)., Conclusions: This study demonstrated that NCS-G is reliable, valid, reproducible and well accepted by patients, showing analogous psychometric properties to the original English version., Level of Evidence: Level III., (© 2022. The Author(s).)

The purpose of our study was to monitor the long-term changes in physical functioning and health-related quality of life in individuals who received outpatient rehabilitation after COVID-19. Individuals referred to outpatient rehabilitation for post-COVID-19 physical therapy were assessed before the treatment, at the end of the treatment, and 2 and 6 months after the end of the treatment. The physical functioning was assessed by Barthel Index, Timed Up and Go test, Short Physical Performance Battery test (SPPB), Patient-Specific Functioning Scale (PSFS), and EuroQOL 5D-3L. Friedman's test was utilized to assess changes in the assessments. The proportions of individuals showing variation in performance equal to or greater than the absolute minimal detectable change (MDC) value of the SPPB and PSFS were calculated. Forty-four cases were monitored for 7.3-15.6 months. At baseline, they showed substantial independence in activities of daily living, moderate mobility limitations, and below-average health-related quality of life. Their status significantly improved over time (Friedman's test P = 0.002 to <0.001); post hoc analysis confirmed the improvement of mobility and health-related quality of life at 6-month follow-up relative to the baseline. After accounting for MDC values, 55% meaningfully improved on SPPB and 45% on PSFS, although some worsened (11 and 5%, respectively) and the remaining showed no meaningful change. Despite good independence in activities of daily living and perceived health, individuals surviving the COVID-19 may not have fully recovered their premorbid functioning status seven to 15 months after the infection., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Some individuals with hemiplegia show a postural disorder called pusher behavior. Various underlying theoretical mechanisms have been proposed, thus leading to various treatment approaches., Objectives: The aim of this scoping review is to identify and analyze the available evidence on the treatment approaches for pusher behavior., Methods: Two independent reviewers conducted a literature search for original studies reporting on treatments for pusher behavior. Studies were searched in PubMed, Scopus, Web of Science, CINAHL and PEDro from their inception to December 2020. Treatment approaches were grouped in homogeneous areas based on the supposed underlying mechanism. To assess the reporting of the interventions, the Template for Intervention Description and Replication (TIDieR) was used., Results: Thirty-one papers describing 45 interventions were included in the review. Most of the studies were case reports (i.e. including 1 person) (n = 16), followed by randomized controlled trials (n = 5), single subject design trials (n = 5), non-randomized controlled trials (n = 3), and case series (i.e. including more than 1 person) (n = 2). Treatment approaches were grouped into five categories: visual feedback, somatosensory cues, visual-somatosensory integration, brain stimulation, and other nonspecific treatments. The median number of TIDIeR items reported was 7 (range 4 to 10)., Conclusion: Pusher behavior is still little-known. Five main categories of treatment approaches based on the alleged etiological underlying mechanisms have been identified. Most of studies are case reports; controlled trials should be further conducted. Intervention reporting should be improved to allow treatment replication in larger trials.

The COVID-19 pandemic has had a significant impact on new cancer diagnoses. This study aims to evaluate the implications of the lockdown period on new lung cancer diagnoses in northern Italy. We compared 2020 with 2019 cancer registry data, reporting the variations by age, stage, and treatments. In 2020, 303 lung cancer cases were registered, 21 fewer than in 2019. Cases fell in men (-31 patients, 9.6%) but not in women (+10 patients, +3.1%). A significant drop in stage I from 19.8% to 12.9% ( p < 0.05) and an increase in stage III (12.7% vs. 19.1%; p < 0.05) was observed. Histological confirmation dropped (70.1% vs. 60.1%; p < 0.05) while cytology increased (12% vs. 20.8%; p < 0.01). Surgery declined (28.7% vs. 21.5%; p < 0.05) but increased in stage III (19.5% vs. 25.9%; p = 0.46), while chemotherapy increased (17.6% vs. 34.3%; p < 0.01) for all stages. During the pandemic, new lung cancer diagnoses dropped only in men. The reorganization of health services has ensured a decrease in surgical interventions (due to the unavailability of operating rooms) counterbalanced by an increase in chemotherapy.

Objective: To describe the Family and Community Physiotherapist model, which aims to incorporate rehabilitation services within primary health care in Tuscany, Italy., Methods: The Department of Health Professions of the Central Tuscany local health authority designed the model during 2020-2021. We describe the four phases of the organizational case study implementation of the model, namely: (i) analysis of the political and organizational framework, as well as determination of changing health-care needs; (ii) model co-design and training of multiprofessional health-care workers (local general practitioners, physiatrists and geriatricians); (iii) delivery and surveillance of rehabilitation services; and (iv) evaluation., Findings: During the initial roll-out of the project in April-December 2021, general practitioners referred 165 patients with a mean age of 83.7 years (standard deviation: 11.1) to the Family and Community Physiotherapist. Interventions were mainly activated for patients with comorbidities (64/165; 38.8%), followed by those with long-term immobilization issues (36/165; 21.8%). The most commonly provided intervention was counselling, contributing to the achievement of objectives for 127 patients (77.0%). A full rehabilitation path was proposed for only 10 patients (6.1%). No additional costs were incurred by the health authority during the implementation of the model., Conclusion: Our model facilitated the provision of rehabilitative care in the community, preventing the exacerbation of chronic conditions and meeting the population health needs in non-hospital environments. The model overcame the typical lack of integration within health-care services with flexibility, promoting care proximity solutions to cope with health challenges such as an ageing population and the coronavirus disease., ((c) 2022 The authors; licensee World Health Organization.)

Introduction: Mavacamten (MAVA), Blebbistatin (BLEB), and Omecamtiv mecarbil (OM) are promising drugs directly targeting sarcomere dynamics, with demonstrated efficacy against hypertrophic cardiomyopathy (HCM) in (pre)clinical trials. However, the molecular mechanism affecting cardiac contractility regulation, and the diseased cell mechano-energetics are not fully understood yet. Methods: We present a new metabolite-sensitive computational model of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) electromechanics to investigate the pathology of R403Q HCM mutation and the effect of MAVA, BLEB, and OM on the cell mechano-energetics. Results: We offer a mechano-energetic HCM calibration of the model, capturing the prolonged contractile relaxation due to R403Q mutation (∼33%), without assuming any further modifications such as an additional Ca 2+ flux to the thin filaments. The HCM model variant correctly predicts the negligible alteration in ATPase activity in R403Q HCM condition compared to normal hiPSC-CMs. The simulated inotropic effects of MAVA, OM, and BLEB, along with the ATPase activities in the control and HCM model variant agree with in vitro results from different labs. The proposed model recapitulates the tension-Ca 2+ relationship and action potential duration change due to 1 µM OM and 5 µM BLEB, consistently with in vitro data. Finally, our model replicates the experimental dose-dependent effect of OM and BLEB on the normalized isometric tension. Conclusion: This work is a step toward deep-phenotyping the mutation-specific HCM pathophysiology, manifesting as altered interfilament kinetics. Accordingly, the modeling efforts lend original insights into the MAVA, BLEB, and OM contributions to a new interfilament balance resulting in a cardioprotective effect., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Forouzandehmehr, Paci, Koivumäki and Hyttinen.)

Objective: To evaluate the influence of lung adenocarcinoma second predominant pattern on the maximal standard uptake value (SUVmax) and its prognostic effect in different histologic groups., Methods: We retrospectively collected surgically resected pathologic stage I and II lung adenocarcinoma from nine European institutions. Only patients who underwent preoperative PET-CT and with available information regarding SUVmax of T (SUVmaxT) and N1 (SUVmaxN1) component were included., Results: We enrolled 344 patients with lung adenocarcinoma. SUVmaxT did not show any significant relation according to the second predominant pattern ( p = 0.139); this relationship remained nonsignificant in patients with similar predominant pattern. SUVmaxT influenced the disease-free survival in the whole cohort ( p = 0.002) and in low- and intermediate-grade predominant pattern groups ( p = 0.040 and p = 0.008, respectively). In the high-grade predominant pattern cohort and in the pathologic N1 cases, SUVmaxT lost its prognostic power. SUVmaxN1 did not show any significant correlation with predominant and second predominant patterns and did not have any prognostic impact on DFS., Conclusions: SUVmaxT is influenced only by the adenocarcinoma predominant pattern, but not by second predominant pattern. Concurrently, in high-grade predominant pattern and pN1 group the prognostic power of SUVmaxT becomes nonsignificant.

Background: Persistent air leak and the management of intraoperative blood loss are common threats in thoracic surgical practice. The availability of new procedures, technology and materials is constantly evolving topical hemostats and surgical sealants must be added to this toolkit. Topical hemostats and surgical sealants differ according to their chemical nature and physical characteristics, to their origin and mechanism of action, regulatory/registration and vigilance paths. A Delphi consensus was set to highlight the different points of view on the use of topical haemostatic products and sealants among the members of Italian Society of thoracic surgery., Methods: The board was formed by a group of five Italian experts; in the first phase after a careful review of the scientific literature and two rounds, the board finally generated 16 consensus statements for testing across a wider audience. During the second phase, the statements were collated into a questionnaire, which was electronically sent to a panel of 46 Italian surgeons, experts in the field., Results: Out of 46 Italian surgeons, 33 (72%) panel members responded to the Delphi questionnaire. All the items reached a positive consensus, with elevated levels of agreement, as demonstrated by the presence of a 100% consensus for nine items. For the remaining 7 statements the minimum level of consent was 88% (29 participants approved the statement and 4 disagreed) and the maximum was 97% (32 participants approved the statement and 1 was in disagreement)., Conclusions: The present Delphi analysis shows that air leak and intraoperative bleeding are clinical problems well known among thoracic surgeons. Nevertheless, the aim of the scientific societies and of the group of experts is to execute the education activities in the surgery community. This Delphi survey suggest the need of wider and updated scientific information about technical and registration characteristics of most recent technologic solutions, such as the of topical hemostats and surgical sealants to provide healthcare and administrative staff with the opportunity to work and interact through a common and shared language and eventually to guarantee minimal requirements of assistance., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-619/coif). PC serves as an unpaid editorial board member of Journal of Thoracic Disease from November 2020 to October 2022. GM serves as an unpaid editorial board member of Journal of Thoracic Disease from February 2021 to January 2023. LV serves as an unpaid editorial board member of Journal of Thoracic Disease from October 2022 to September 2024. GC participated on an Advisory Board supported by BD in the past 36 months. MN participated on an Advisory Board supported by Bard Limited in the past 36 months. MS received honoraria by J&J, Medtronic and Medela for speakers fee, and participated on an Advisory Board supported by BD, and he was a member of ESTS board of directors in the past 36 months. MT participated on an Advisory Board supported by BD in the past 36 months. GC is an unpaid member of the Oncologic network of Sicilian Region in the past 36 months. AI is an unpaid member of Editorial Board of the “Monaldi Archives for Chest Disease” and unpaid member of Editorial Board of the Video-Assisted Thoracic Surgery in the past 36 months. GLP is an unpaid Councillor of the Italian Thoracic Surgery Society from 2021 to 2023 and an unpaid Scientific Coordinator Pulmonary Nodule Recommendations Group PNR of Italian Thoracic Surgery Society from 2021 to 2023. RC participated on an Advisory Board supported by BD in the past 36 months. The other authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Objective: The presence of micropapillary and solid adenocarcinoma patterns leads to a worse survival and a significantly higher tendency to recur. This study aims to assess the impact of pT descriptor combined with the presence of high-grade components on long-term outcomes in early-stage lung adenocarcinomas., Methods: We retrospectively collected data of consecutive resected pT1-T3N0 lung adenocarcinoma from nine European Thoracic Centers. All patients who underwent a radical resection with lymph-node dissection between 2014 and 2017 were included. Differences in Overall Survival (OS) and Disease-Free Survival (DFS) and possible prognostic factors associated with outcomes were evaluated also after performing a propensity score matching to compare tumors containing non-high-grade and high-grade patterns., Results: Among 607 patients, the majority were male and received a lobectomy. At least one high-grade histological pattern was seen in 230 cases (37.9%), of which 169 solid and 75 micropapillary. T1a-b-c without high-grade pattern had a significant better prognosis compared to T1a-b-c with high-grade pattern (p = 0.020), but the latter had similar OS compared to T2a (p = 0.277). Concurrently, T1a-b-c without micropapillary or solid patterns had a significantly better DFS compared to those with high-grade patterns (p = 0.034), and it was similar to T2a (p = 0.839). Multivariable analysis confirms the role of T descriptor according to high-grade pattern both for OS (p = 0.024; HR 1.285 95% CI 1.033-1.599) and DFS (p = 0.003; HR 1.196, 95% CI 1.054-1.344, respectively). These results were confirmed after the propensity score matching analysis., Conclusions: pT1 lung adenocarcinomas with a high-grade component have similar prognosis of pT2a tumors., (© 2022. The Author(s).)

Objective: To compare the description of interventions defined as "usual care" in control groups with those provided in experimental groups in physiotherapy randomized clinical trials for multiple sclerosis., Methods: Two independent reviewers conducted a literature search and study selection from five databases from their inception to February 2021. Randomized clinical trials aimed to physiotherapy multiple sclerosis treatment and providing "usual care" in the control group were included. Intervention reporting was assessed using the TIDieR checklist. Word and reference counts for each group were extracted. The methodological quality was assessed by the PEDro scale., Results: Twenty-four articles were included. The TIDieR total scores, word, and reference count were statistically higher in the experimental group, when compared to the control group (p < 0.001). The TIDieR total score is not correlated with PEDro score, word, publication year, or reference counts., Conclusion: Control treatments identified as "usual care" are underdescribed when compared to experimental treatments, affecting the validity, generalizability, and interpretability of results., (© 2022. Fondazione Società Italiana di Neurologia.)

CNNs and other deep learners are now state-of-the-art in medical imaging research. However, the small sample size of many medical data sets dampens performance and results in overfitting. In some medical areas, it is simply too labor-intensive and expensive to amass images numbering in the hundreds of thousands. Building Deep CNN ensembles of pre-trained CNNs is one powerful method for overcoming this problem. Ensembles combine the outputs of multiple classifiers to improve performance. This method relies on the introduction of diversity, which can be introduced on many levels in the classification workflow. A recent ensembling method that has shown promise is to vary the activation functions in a set of CNNs or within different layers of a single CNN. This study aims to examine the performance of both methods using a large set of twenty activations functions, six of which are presented here for the first time: 2D Mexican ReLU, TanELU, MeLU + GaLU, Symmetric MeLU, Symmetric GaLU, and Flexible MeLU. The proposed method was tested on fifteen medical data sets representing various classification tasks. The best performing ensemble combined two well-known CNNs (VGG16 and ResNet50) whose standard ReLU activation layers were randomly replaced with another. Results demonstrate the superiority in performance of this approach.

Objectives: Lung cancer is increasingly diagnosed as a second cancer. Our goal was to analyse the characteristics and outcomes of early-stage resected lung adenocarcinomas in patients with previous cancers (PC) and correlations with adenocarcinoma subtypes., Methods: We retrospectively reviewed data of patients radically operated on for stage I-II lung adenocarcinoma in 9 thoracic surgery departments between 2014 and 2017. Overall survival (OS) and time to disease relapse were evaluated between subgroups., Results: We included 700 consecutive patients. PC were present in 260 (37.1%). Breast adenocarcinoma, lung cancer and prostate cancer were the most frequent (21.5%, 11.5% and 11.2%, respectively). No significant differences in OS were observed between the PC and non-PC groups (P = 0.378), with 31 and 75 deaths, respectively. Patients with PC had smaller tumours and were more likely to receive sublobar resection and to be operated on with a minimally invasive approach. Previous gastric cancer (P = 0.042) and synchronous PC (when diagnosed up to 6 months before lung adenocarcinoma; P = 0.044) were related, with a worse OS. Colon and breast adenocarcinomas and melanomas were significantly related to a lower incidence of high grade (solid or micropapillary, P = 0.0039, P = 0.005 and P = 0.028 respectively), whereas patients affected by a previous lymphoma had a higher incidence of a micropapillary pattern (P = 0.008)., Conclusions: In patients with PC, we found smaller tumours more frequently treated with minimally invasive techniques and sublobar resection, probably due to a more careful follow-up. The impact on survival is not uniform and predictable; however, breast and colon cancers and melanoma showed a lower incidence of solid or micropapillary patterns whereas patients with lymphomas had a higher incidence of a micropapillary pattern., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Contractility has become one of the main readouts in computational and experimental studies on cardiomyocytes. Following this trend, we propose a novel mathematical model of human ventricular cardiomyocytes electromechanics, BPSLand, by coupling a recent human contractile element to the BPS2020 model of electrophysiology. BPSLand is the result of a hybrid optimization process and it reproduces all the electrophysiology experimental indices captured by its predecessor BPS2020, simultaneously enabling the simulation of realistic human active tension and its potential abnormalities. The transmural heterogeneity in both electrophysiology and contractility departments was simulated consistent with previous computational and in vitro studies. Furthermore, our model could capture delayed afterdepolarizations (DADs), early afterdepolarizations (EADs), and contraction abnormalities in terms of aftercontractions triggered by either drug action or special pacing modes. Finally, we further validated the mechanical results of the model against previous experimental and in silico studies, e.g., the contractility dependence on pacing rate. Adding a new level of applicability to the normative models of human cardiomyocytes, BPSLand represents a robust, fully-human in silico model with promising capabilities for translational cardiology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bartolucci, Forouzandehmehr, Severi and Paci.)

Background: Only a small number of studies have explored the clinicopathological features of pulmonary adenocarcinoma (PA) associated with 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) false-negative (FN) results. Herein, we investigated the FDG-PET diagnostic performance by stratifying PAs according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification., Methods: From January 2002 to December 2016, all consecutive patients who underwent pulmonary resection for stage I PA at six thoracic surgery institutions were retrospectively reviewed. The diagnostic performance of FDG-PET was analysed according to IASLC/ATS/ERS classification and two validated subclassifications. Univariable and multivariable logistic analysis were used to identify predictors of FDG-PET FN results., Results: Five hundred and fifty (550) patients with stage I PA were included in the analyses. Most of the patients were male (n=354 [64.4%]) and smokers (n=369 [67.1%]). Ninety-seven (n=97 [17.6%]) FN cases were observed at FDG-PET imaging. On multivariable analysis, a lepidic pattern was found to be independently associated with FDG-PET FN results (odds ratio [OR], 3.20; p<0.001), while a solid pattern more commonly presented with a positive finding (OR, 0.40; p=0.066). According to Nakamura's classification, we observed an independent association between lepidic pattern and FDG-PET FN results (OR, 3.17; p<0.001), while solid/micropapillary patterns were independently related with increased FDG uptake (OR, 0.35; p=0.021). According to Yoshizawa's classification, Intermediate-grade tumours were independently correlated with FN FDG-PET results (OR, 2.78; p=0.005)., Conclusions: In our cohort, histopathological features were significantly associated with FDG uptake. In particular, some adenocarcinoma subtypes (mostly Lepidic pattern) have a tendency towards FN FDG-PET findings. The correlation between computed tomography findings, clinical characteristics, and FDG uptake is mandatory, in order to tailor the precise diagnostic and therapeutic pathway for each patient., (Copyright © 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

(1) Background: Sub-Saharan Africa is experiencing the fastest urbanization worldwide. People in rural areas still have a traditional and rural lifestyle, whereas the Westernization of diet and lifestyle is already evident in urban areas. This study describes dietary habits of families in Burkina Faso living at different levels of urbanization. (2) Methods: Data on lifestyle, socio-economic conditions, health status and anthropometry were collected from 30 families living in rural villages, a small town and the capital city. A food frequency questionnaire and a 24 h recall diary were used to estimate dietary habits and macronutrients intake. (3) Results: The urban cohort showed a more diversified diet, with a higher intake of animal protein and, especially in children, a higher consumption of simple sugars. Fiber intake was significantly higher in the rural and semi-urbanized cohorts. As expected, overweight and obesity gradually increased with the level of urbanization. In semi-urbanized and urban families, we observed coexistence of under- and over-nutrition, whereas in rural families, a portion of children were wasted and stunted, and adults were underweight. (4) Conclusions: These three cohorts represent a model of the effect on diet of rural-to-urban migration. Rural diet and traditional habits are replaced by a Western-oriented diet when families move to urbanized areas. This dietary transition and increased socio-economic status in newly developing urban areas have a major impact on disease epidemiology, resembling the past evolution in Western countries.

Purpose: To evaluate the clinical relevance of subcentimetric lymph node biopsy via mediastinoscopy in patients with presumed ocular sarcoidosis (OS)., Methods: Retrospective study of consecutive patients who underwent biopsy via mediastinoscopy for suspected OS. The biopsy outcomes and clinical features of patients with subcentimetric nodes and of those with lymph nodes >1 cm were compared., Results: A total of 67 patients with presumed OS were included. Forty-two patients (63%) had lymph nodes ≥1 cm in diameter, while 25(37%) showed subcentimetric lymph nodes. Biopsy was consistent with sarcoidosis in 83% of patients with lymph nodes ≥1 cm and in 76% of patients with subcentimetric lymph nodes (p = .60). Patients with OS who had subcentimetric lymph nodes had less lymphopenia (p = .01), lower lysozyme values (p = .03) and a longer diagnostic delay compared to those with larger lymph nodes., Conclusions: The biopsy of subcentimetric lymph nodes via mediastinoscopy may provide a histological diagnosis and reduce diagnostic delay.

Background: Lack of effective peer-review process of predatory journals, resulting in more ambiguity in reporting, language and incomplete descriptions of processes might have an impact on the reliability of PEDro scale. The aim of this investigation was to compare the reliability of the PEDro scale when evaluating the methodological quality of RCTs published in predatory (PJs) and non-predatory (NPJs) journals, to more confidently select interventions appropriate for application to practice., Methods: A selected sample of RCTs was independently rated by two raters randomly selected among 11 physical therapists. Reliability of each item of the PEDro scale and the total PEDro score were assessed by Cohen's kappa statistic and percent of agreement and by Intraclass Correlation Coefficients (ICC) and the Standard Error of Measurement (SEM), respectively. The Chi-square test was used to compare the rate of agreement between PJs and NPJs., Results: A total number of 298 RCTs were assessed (119 published in NPJs). Cronbach's alphas were .704 and .845 for trials published in PJs and NPJs, respectively. Kappa values for individual scale items ranged from .14 to .73 for PJs and from .09 to .70 for NPJs. The ICC was .537 (95% CI .425-.634) and .729 (95% CI .632-.803), and SEM was 1.055 and 0.957 for PJs and NPJs, respectively. Inter-rater reliability in discriminating between studies of moderate to high and low quality was higher for NPJs (k = .57) than for PJs (k = .28)., Conclusions: Interrater reliability of PEDro score of RCTs published in PJs is lower than that of trials published in NPJs, likely also due to ambiguous language and incomplete reporting. This might make the detection of risk of bias more difficult when selecting interventions appropriate for application to practice or producing secondary literature., (© 2022. The Author(s).)

Background: The aim of the present study was to investigate outcomes of anti-TNF-alpha (ATA) withdrawal in selected pediatric patients with inflammatory bowel disease who achieved clinical remission and mucosal and histological healing (MH and HH)., Methods: A retrospective analysis was performed on children and adolescents affected by Crohn disease (CD) and ulcerative colitis (UC) who were followed up at 2 tertiary referral centers from 2008 through 2018. The main outcome measure was clinical relapse rates after ATA withdrawal., Results: One hundred seventy patients received scheduled ATA treatment; 78 patients with CD and 56 patients with UC underwent endoscopic reassessment. We found that MH was achieved by 32 patients with CD (41%) and 30 patients with UC (53.6%); 26 patients with CD (33.3%) and 22 patients with UC (39.3%) achieved HH. The ATA treatment was suspended in 45 patients, 24 affected by CD and 21 by UC, who all achieved concurrently complete MH (Simplified Endoscopic Score for CD, 0; Mayo score, 0, respectively) and HH. All the patients who suspended ATA shifted to an immunomodulatory agent or mesalazine. In contrast, 17 patients, 8 with CD and 9 with UC, continued ATA because of growth needs, the persistence of slight endoscopic lesions, and/or microscopic inflammation. Thirteen out of 24 patients with CD who suspended ATA experienced disease relapse after a median follow-up time of 29 months, whereas no recurrence was observed among the 9 patients with CD who continued treatment (P = 0.05). Among the patients with UC, there were no significant differences in relapse-free survival among those who discontinued ATA and those who did not suspend treatment (P = 0.718)., Conclusions: Despite the application of rigid selection criteria, ATA cessation remains inadvisable in CD. In contrast, in UC, the concurrent achievement of MH and HH may represent promising selection criteria to identify patients in whom treatment withdrawal is feasible., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Purpose: Shoulder pain is one of the most common musculoskeletal problems of the world's population. In particular, in water polo athletes, the frequency of injuries or pain to this joint is very high. The incidence of psychosocial factors in musculoskeletal pain is well recognized, even if they seem to be more present in chronic pain, rather than in acute pain., Case Description: The patient was a semi-professional water polo player with acute shoulder pain which occurred during a game. At first, the pain was very mild, but it progressively got worse after the visit to the casualty department where, even in the absence of any confirmed structural lesions, the patient is ordered to refrain from any active movements. The patient became worried, so his anxiety levels increased which worsened his symptoms. The physiotherapist opted for a "hands-off/hands-on approach"., Outcomes: Significative improvements were observed in all the considered outcome measures, the patient obtained complete recovery in a very short period of time and then he was able to return to his sport., Discussions: Psychosocial factors such as anxiety, fear and catastrophizing can modulate pain responses in a subject without structural problems. Thus, counseling and education in pain science can be an effective therapeutic method, especially with conditions of acute, as well as chronic, pain., Level of Evidence: 4., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)