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Backgroud: A huge amount of data about psychosocial issues of people with haemophilia (PwH) are available; however, these materials are fragmentary and largely outdated, failing to reflect the impact of current treatment strategies. Aim: Describing the influence of illness on psychosocial aspects of adult PwH (≥18 years) and caregivers of children with haemophilia (CPwH) without inhibitors, in Italy. Methods: Surveys (for adult PwH, CPwH and haemophilia specialists) were developed by a multidisciplinary working group and conducted from November 2019 to June 2020. Results: A total of 120 PwH without inhibitors and 79 CPwH completed the survey. Adult patients reported a significant impairment in many psychosocial aspects, including working activities, relations with family members and social relations. Caregivers generally reported better scores in all aspects of the survey. Mobility, Pain and Mental health domains of EQ-5D were the most frequently impaired in both patients and caregivers, reducing the perceived quality of life. Genetic counselling was an important issue, 53% of CPwH declaring unawareness of their carrier status, as well as the psychological support offered by the reference center, 67.0% of respondents reporting that no psychological support was provided at the time of diagnosis communication. Conclusion: This study provides information about PwH's and CPwH's point of view in the current scenario of continuous innovations in haemophilia treatment and management furthermore, updated insights on psychosocial problems faced by patients and caregivers are reported.

Introduction: Pulmonary involvement is one of the most common extra-articular manifestations of rheumatoid arthritis (RA), a systemic inflammatory disease characterized by joint swelling and tenderness. All lung compartments can be interested in the course of RA, including parenchyma, airways, and, more rarely, pleura and vasculature. Areas covered: The aim of this paper is to review the main RA lung manifestations, focusing on pathogenesis, clinical and therapeutic issues of RA-related interstitial lung disease (ILD). Despite an increasing number of studies in the last years, pathogenesis of RA-ILD remains largely debated and the treatment of RA patients with lung involvement is still challenging in these patients. Expert opinion: Management of RA-ILD is largely based on expert-opinion. Due to the broad clinical manifestations, including both joints and pulmonary involvement, multidisciplinary discussion, including rheumatologist and pulmonologist, is essential, not only for diagnosis, but also to evaluate the best therapeutic approach and follow-up. In fact, the coexistence of different lung manifestations may influence the treatment response and safety. The identification of biomarkers and risk-factors for an early identification of RA patients at risk of developing ILD remains a need that still needs to be fulfilled, and that will require further investigation in the next years.

Objectifs: La pneumopathie interstitielle (PI) représente la principale atteinte pulmonaire dans le syndrome de Gougerot-Sjögren primitif (SGSp). Un certain nombre de patients atteints de SGSp développent une forme fibrosante progressive de PI, mais il n'existe aucune donnée sur la prévalence de telles présentations.L'objectif de cette étude transversale monocentrique était d'explorer la prévalence des formes fibrosantes chez les patients atteints de SGSp présentant une PI. Méthodes: Tous les patients consécutifs remplissant les critères de classification du SGSp et présentant une PI existante ou nouvellement diagnostiquée ont été inclus dans l’étude. Le diagnostic de PI était toujours établi par TDM-HR et les différentes formes ont été déterminées sur la base des critères de classification en vigueur et réparties dans deux groupes selon qu'une forme fibrosante était détectée ou non. Résultats: Trente-quatre patients présentant un SGSp avec PI ont été inclus dans l’étude (3 hommes et 31 femmes, âge médian 69,5 ans, durée moyenne du SGSp 47,5 mois). Une forme fibrosante a été identifiée chez 52,9 % des patients (groupe 1) : pneumopathie interstitielle commune (PIC) chez 13 patients (38,2 %), pneumopathie interstitielle non spécifique (PINS) fibrosante chez 4 patients (11,8 %) et pneumopathie organisée (PO) fibrosante chez 1 patient (2,9 %). Le groupe 2 (16 patients, 47,1 %) comprenait la PINS chez 6 patients (17,6 %), la PO chez 4 patients (11,8 %), la PIL chez 2 patients (5,9 %) et la pneumopathie interstitielle inclassable chez 4 patients (11,8 %). Dans le groupe 1, les patients étaient plus jeunes et la durée du SGSp au moment du diagnostic de PI plus courte. Notamment, la PI a été diagnostiquée avant ou en même temps que le SGSp dans 83,3 % des cas, contre 62,5 % dans le groupe 2 de forme non fibrosante (p < 0,05). Conclusion: Nos données suggèrent une forte prévalence de ce phénotype clinique pulmonaire che

Introduction: Haemophilia management and patients’ quality of life significantly improved. However, data on current patients’, caregivers’ and clinicians’ satisfaction and limitations of treatments and haemophilia management are limited. Aim: Assessing the management satisfaction and unmet needs from the perspective of Italian patients with haemophilia (PWH) without inhibitors (or caregivers if children) and of specialist physicians. Methods: Surveys (for patients≥18 years, caregivers of children and haemophilia specialists) were developed by a multidisciplinary working group and conducted from November 2019 to June 2020. Results: Among 275 participants, 120 (43.6%) were PWH without inhibitors, 79 (28.7%) caregivers and 37 (13.4%) clinicians. Patients and caregivers perceived a higher control of the disease compared to clinicians. However, more than 40% of patients and caregivers reported to feel significantly conditioned by the risk of bleeding during their daily life. PWH reported a 6-month mean/median (range) of bleeds 2.3/.0 (0-24) and caregivers 1.3/.0 (0-16) in children. The treatment burden (frequency of administration) was not satisfactory for more than half adults and caregivers of children treated with prophylaxis. A good access to treatment, haemophilia centres and medical service was reported, with issues associated to the multidisciplinary approach and treatment at emergency department. Conclusions: This large national study provides an updated overview of haemophilia care in Italy from different points of views, highlighting positive aspects and unmet needs. This information can guide future interventions to improve haemophilia management and the assessment of impact of new treatment options.

Recombination is the main contributor to RNA virus evolution, and SARS-CoV-2 during the pandemic produced several recombinants. The most recent SARS-CoV-2 recombinant is the lineage labeled XBB, also known as Gryphon, which arose from BJ.1 and BM.1.1.1. Here we performed a genome-based survey aimed to compare the new recombinant with its parental lineages that never became dominant. Genetic analyses indicated that the recombinant XBB and its first descendant XBB.1 show an evolutionary condition typical of an evolutionary blind background with no further epidemiologically relevant descendant. Genetic variability and expansion capabilities are slightly higher than parental lineages. Bayesian Skyline Plot indicates that XBB reached its plateau around October 6, 2022 and after an initial rapid growth the viral population size did not further expand, and around November 10, 2022 its levels of genetic variability decreased. Simultaneously with the reduction of the XBB population size, an increase of the genetic variability of its first sub-lineage XBB.1 occurred, that in turn reached the plateau around November 9, 2022 showing a kind of vicariance with its direct progenitors. Structure analysis indicates that the affinity for ACE2 surface in XBB/XBB.1 RBDs is weaker than for BA.2 RBD. In conclusion, at present XBB and XBB.1 do not show evidence about a particular danger or high expansion capability. Genome-based monitoring must continue uninterrupted in order to individuate if further mutations can make XBB more dangerous or generate new subvariants with different expansion capability. This article is protected by copyright. All rights reserved.

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Recombination is the main contributor to RNA virus evolution, and SARS-CoV-2 during the pandemic produced several recombinants. The most recent SARS-CoV-2 recombinant is the lineage labeled XBB, also known as Gryphon, which arose from BJ.1 and BM.1.1.1. Here we performed a genome-based survey aimed to compare the new recombinant with its parental lineages that never became dominant. Genetic analyses indicated that the recombinant XBB and its first descendant XBB.1 show an evolutionary condition typical of an evolutionary blind background with no further epidemiologically relevant descendant. Genetic variability and expansion capabilities are slightly higher than parental lineages. Bayesian Skyline Plot indicates that XBB reached its plateau around October 6, 2022 and after an initial rapid growth the viral population size did not further expand, and around November 10, 2022 its levels of genetic variability decreased. Simultaneously with the reduction of the XBB population size, an increase of the genetic variability of its first sub-lineage XBB.1 occurred, that in turn reached the plateau around November 9, 2022 showing a kind of vicariance with its direct progenitors. Structure analysis indicates that the affinity for ACE2 surface in XBB/XBB.1 RBDs is weaker than for BA.2 RBD. In conclusion, at present XBB and XBB.1 do not show evidence about a particular danger or high expansion capability. Genome-based monitoring must continue uninterrupted in order to individuate if further mutations can make XBB more dangerous or generate new subvariants with different expansion capability. This article is protected by copyright. All rights reserved.

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In 2015 the European Respiratory Society (ERS) and the American Thoracic Society (ATS) “Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease” proposed classification criteria for a new research category defined as “Interstitial Pneumonia with Autoimmune Features” (IPAF), to uniformly define patients with interstitial lung disease (ILD) and features of autoimmunity, without a definite connective tissue disease. These classification criteria were based on a variable combination of features obtained from three domains: a clinical domain consisting of extra-thoracic features, a serologic domain with specific autoantibodies, and a morphologic domain with imaging patterns, histopathological findings, or multicompartment involvement. Features suggesting a systemic vasculitis were excluded. Since publication of ERS/ATS IPAF research criteria, various retrospective studies have been published focusing on prevalence; clinical, morphological, and serological features; and prognosis of these patients showing a broad heterogeneity in the results. Recently, two prospective, cohort studies were performed, confirming the existence of some peculiarities for this clinical entity and the possible progression of IPAF to a defined connective tissue disease (CTD) in about 15% of cases. Moreover, a non-specific interstitial pneumonia pattern, an anti-nuclear antibody positivity, and a Raynaud phenomenon were the most common findings. In comparison with idiopathic pulmonary fibrosis (IPF), IPAF patients showed a better performance in pulmonary function tests and less necessity of oxygen delivery. However, at this stage of our knowledge, we believe that further prospective studies, possibly derived from multicenter cohorts and through randomized control trials, to further validate the proposed classification criteria are needed.

Objectives: Interstitial lung disease (ILD) represents the main pulmonary involvement in primary Sjogren syndrome (pSS). A proportion of patients with pSS develop a progressive fibrosing form of ILD, but no data are available about the prevalence of these patterns in pSS patients. Aim of this monocentric, cross-sectional study was to investigate the prevalence of fibrosing patterns in pSS patients with ILD. Methods: All consecutive patients fulfilling classification criteria for pSS with a new or previous diagnosis of ILD were enrolled in the study. Diagnosis of ILD was always performed by mean of HRCT and specific patterns were identified according to current classification criteria and divided in two groups according to the detection of a fibrotic pattern. Results: Thirty-four pSS-ILD patients were enrolled in the study (males/females 3/31, median age 69.5 years, median pSS duration 47.5 months). Fibrotic pattern was detected in 52.9% of patients, namely: UIP (13 patients, 38.2%), fibrotic NSIP (4, 11.8%), fibrotic OP (1 2.9%) and group 2 (16 pts, 47.1%) including NSIP (6, 17.6%), OP (4, 11.8%), LIP (2, 5.9%) and unclassifiable (4, 11.8%). These patients were younger and with a shorter pSS duration at ILD diagnosis, in particular ILD diagnosis was prior or concurrent to pSS in 83.3% of cases compared to 62.5% in the group of nonfibrotic pattern (P < 0.05). Conclusion: Our data suggest a high prevalence of this pulmonary clinical phenotype in pSS-ILD patients. Since the course of progressive fibrosing pneumonia generally results in respiratory failure, this result could be worthy of further studies.

Anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (MPO) antibodies, have been frequently identified in patients with idiopathic pulmonary fibrosis (IPF). However, their role remains unclear, and only 7-23% of these patients develops clinically overt vasculitis. We aimed to investigate the clinical, serological, and radiological features and prognosis of anti-MPO-positive interstitial lung disease (ILD) patients. Fifty-eight consecutive patients firstly referred for idiopathic interstitial pneumonia and showing serological positivity of anti-MPO antibodies were retrospectively enrolled. For each patient, clinical data, lung function testing, chest high-resolution computed tomography (HRCT) pattern, and survival were recorded. Thirteen patients developed a rheumatic disease during a median follow-up of 39 months. Usual interstitial pneumonia (UIP) was the most frequent ILD pattern, significantly influencing the patients' survival. In fact, while the 52-week survival of the overall population was 71.4 ± 7.5%, significantly higher than IPF, survivals of anti-MPO patients with UIP pattern and IPF were similar. Forced vital capacity and diffusion lung capacity for CO significantly declined in 37.7 and 41.5% of cases, respectively, while disease progression at chest HRCT was observed in 45.2%. A careful clinical history and evaluation should always be performed in ILD patients with anti-MPO antibodies to quickly identify patients who are developing a systemic rheumatic disease.

Objectives: This study aims to evaluate the diagnostic accuracy of the VECTOR software in patients with connective tissue diseases (CTDs), compared with the reference standard of high-resolution computed tomography (HRCT). Patients and methods: The study included 98 consecutive patients of CTD (24 males, 74 females; median age: 66 years; range, 24 to 85 years) with a recent HRCT. Patients were evaluated in a blindly manner by VECTOR and the results obtained by the algorithm were compared with the presence of interstitial lung disease (ILD) according to HRCT. Results: Interstitial lung disease was detected in 42.8% of subjects. VECTOR correctly classified 81/98 patients, with a diagnostic accuracy of 82.6%; sensitivity and specificity were 88.1% and 78.6%, respectively. Only 5/42 patients with ILD were not correctly classified by VECTOR, while false positive cases were 21.4%. No significant differences were observed according to the radiologic pattern of ILD. Conclusion: VECTOR showed high sensitivity, specificity and diagnostic accuracy, allowing selecting patients to be investigated with HRCT. The relatively high frequency rate of false positive results is acceptable if compared with the lack of effective screening methods for this complication of CTDs.

INTRODUCTION: Interstitial lung disease (ILD) represents one of the most frequent extra-articular manifestations of rheumatoid arthritis (RA) with a deep impact on both quality of life and overall prognosis. A literature search was performed trough some electronic databases, including PubMed, Embase, Scopus, and Web of Science. Areas covered: Many retrospective studies investigated the possible risk factors for RA-ILD, aiming to early identify patients at risk. Among them, male sex, smoking habit, positivity of anti-citrullinated peptide antibodies have been associated to RA-ILD, such as some genetic haplotypes. Histologic and radiologic patterns detected in idiopathic interstitial pneumonias (IIP) have also been observed in RA; among them, usual interstitial pneumonia is the most frequently observed, followed by nonspecific interstitial pneumonia. Since lung involvement can represent the RA onset, an early differential diagnosis with IIP can be difficult or sometimes impossible. High resolution computed tomography represents the gold standard for ILD diagnosis, while multidisciplinary discussion should be required to assess disease staging, severity and progression. Expert opinion: Management of RA-ILD patients are challenging due to the lacking of evidence-based data regarding both assessment and treatment. Moreover, the high variability of clinical presentation and evolution makes difficult to establish the correct therapeutic strategy. Currently, multidisciplinary approach, including at least rheumatologists, pulmonologists, and radiologists, is desirable to define therapy and follow-up strategies.

OBJECTIVES: Only a third of patients with eosinophilic granulomatosis with polyangiitis (EGPA) are ANCA-positive, mainly directed against MPO. ANCA directed against PR3 are rarely found in EGPA. We aimed to examine the significance of PR3-ANCA in EGPA. METHODS: We set up a retrospective European multicentre cohort including 845 patients. Baseline characteristics and outcomes were analysed and compared according to ANCA status. RESULTS: ANCA status was available for 734 patients: 508 (69.2%) ANCA-negative, 210 (28.6%) MPO-ANCA and 16 (2.2%) PR3-ANCA. At baseline, PR3-ANCA patients, compared with those with MPO-ANCA and ANCA-negative, less frequently had active asthma (69% vs 91% and 93%, P = 0.003, respectively) and peripheral neuropathy (31% vs 71% and 47%, P < 0.0001), more frequently had cutaneous manifestations (63% vs 38% and 34%, P = 0.03) and pulmonary nodules (25% vs 10% and 8%, P = 0.046), and lower median eosinophil count (1450 vs 5400 and 3224/mm3, P < 0.0001). Vasculitis relapse-free survival was shorter for PR3-ANCA (hazard ratio 6.05, P = 0.005) and MPO-ANCA patients (hazard ratio 1.88, P = 0.0002) compared with ANCA-negative patients. CONCLUSION: PR3-ANCA EGPA patients differ from those with MPO-ANCA and negative ANCA, and share clinical features with granulomatosis with polyangiitis. This suggests that PR3-ANCA EGPA could be a particular form of PR3-ANCA-associated vasculitis.

Introduction: Emergency providers should recognize that pneumothorax is a rare but serious complication of shoulder arthroscopy that may require a unique approach to decompression.Case Report: We present a case of a 60-year-old female who presented to the emergency department with right-sided facial swelling, voice change, and shortness of breath three hours after an elective arthroscopic right rotator-cuff repair and was noted to have a right-sided pneumothorax. We also describe a potential novel approach to chest tube decompression that maintains shoulder adduction in patients with recently repaired rotator cuffs.Conclusion: Although most cases of post-arthroscopy pneumothoraces are reported in patients who received regional anesthesia or have underlying lung pathology, it can occur in lower-risk patients as was demonstrated in our case. We also suggest considering an alternative anterior approach between the midclavicular and anterior axillary lines for chest decompression in select patients when a traditional approach is less ideal due to the need to maintain shoulder immobilization postoperatively.

Introduction: Emergency providers should recognize that pneumothorax is a rare but serious complication of shoulder arthroscopy that may require a unique approach to decompression.Case Report: We present a case of a 60-year-old female who presented to the emergency department with right-sided facial swelling, voice change, and shortness of breath three hours after an elective arthroscopic right rotator-cuff repair and was noted to have a right-sided pneumothorax. We also describe a potential novel approach to chest tube decompression that maintains shoulder adduction in patients with recently repaired rotator cuffs.Conclusion: Although most cases of post-arthroscopy pneumothoraces are reported in patients who received regional anesthesia or have underlying lung pathology, it can occur in lower-risk patients as was demonstrated in our case. We also suggest considering an alternative anterior approach between the midclavicular and anterior axillary lines for chest decompression in select patients when a traditional approach is less ideal due to the need to maintain shoulder immobilization postoperatively.

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a group of systemic vasculitides that predominantly affect small vessels, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Pulmonary involvement is frequently observed in AAV patients, with various possible phenotypes in the different diseases. In the last years, among the possible types of lung involvement, a growing interest has been addressed to the interstitial lung disease (ILD). Prevalence of ILD is higher in MPA than in GPA; in fact, ILD has been reported in up to 45% of MPA patients and in 23% of GPA. Anti-MPO antibodies are the main ANCA subtype associated to ILD, in about 46-71% of cases, while anti-PR3 antibodies are reported in 0-29% of patients. High resolution computed tomography (HRCT) frequently detects interstitial lung abnormalities in AAV, up to 66% of patients with MPA, even if with an unclear clinical relevance, specifically in asymptomatic patients. Ground glass opacities, mainly consistent with diffuse alveolar hemorrhage (DAH), are the most frequent finding in MPA patients, but reticulations, interlobular septal thickening and honeycombing are also reported. ILD significantly affects quality of life and survival, with mortality increased 2 to 4 times, particularly higher in MPA patients with pulmonary fibrosis. Currently, immunosuppressive therapy is considered also as a possible treatment of ILD. However, a careful evaluation of progression and severity of lung involvement, should guide the treatment decision in the single patient. In this review, we discuss the available evidence on clinical features, diagnostic work-up, prognosis and management of AAV-ILD.

Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease affecting 0.5-1% of the population worldwide. Interstitial lung disease (ILD) is a serious pulmonary complication of RA and it is responsible for 10-20% of mortality, with a mean survival of 5-8 years. However, nowadays there are no therapeutic recommendations for the treatment of RA-ILD. Therapeutic options for RA-ILD are complicated by the possible pulmonary toxicity of many disease modifying anti-rheumatic drugs (DMARDs) and by their unclear efficacy on pulmonary disease. Therefore, joint and lung involvement should be evaluated independently of each other for treatment purposes. On the other hand, some similarities between RA-ILD and idiopathic pulmonary fibrosis and the results of the recent INBIULD trial suggest a possible future role for antifibrotic agents. From this perspective, we review the current literature describing the pulmonary effects of drugs (immunosuppressants, conventional, biological and target synthetic DMARDs and antifibrotic agents) in patients with RA and ILD. In addition, we suggest a framework for the management of RA-ILD patients and outline a research agenda to fill the gaps in knowledge about this challenging patient cohort.

Background and objective: Recently the term “interstitial pneumonia with autoimmune features” (IPAF) has been proposed to identify patients with interstitial lung disease and autoimmune characteristics, not fulfilling the criteria for specific connective tissue diseases (CTD). Only few data are available about the clinical and serological features of IPAF patients, their survival and the possible evolution in a CTD. The aims of the study were to investigate the demographic and clinico-serologic features of patients with IPAF, their relationship to survival, and the possible evolution in a definite CTD. Patients and methods: Fifty-two patients were consecutively enrolled and prospectively followed for 45 ± 31.6 months. Data about disease onset, serological, clinical and therapeutic features, pulmonary function tests and high-resolution computed tomography were periodically repeated. The survival of patients with IPAF was compared with that of 104 patients with idiopathic pulmonary fibrosis (IPF). Results: The clinical domain for IPAF was satisfied in 44 patients, serological domain in 49 and the morphological domain in 29 patients. During the follow-up, a definite CTD was diagnosed in 7 patients, in particular Sjogren's syndrome in 4 patients, rheumatoid arthritis in 2, and polymyositis in the last. The estimated 5-year survival of IPAF patients 69.5 ± 7.8%, significantly higher than survival observed in IPF patients, and the baseline value of FVC and DLCO were the only factors associated to death. Conclusions: IPAF seems to a distinct entity, with a low tendency to evolve in a definite CTD. Nevertheless, further studies are needed to better define the clinical evolution and the outcome of IPAF.

In the article that appeared on Page 1621-1628, Vol 11, No 4 (April 2019) Issue of the Journal of Thoracic Disease (1), the given and family names of author “Fabrizio Pancaldi” was incorrectly published in the original. The author's name should be corrected as Fabrizio Pancaldi, instead of Pancaldi Fabrizio. The authors regret the error.

About 5000 people in Italy suffer from hemophilia, the most common coagulation disorder. As for other chronic diseases, even in the case of hemophilia, the engagement of the patient is essential: the patients, in fact, must be empowered and helped to become strong partners of the care team and sensitized with respect to their rights and duties for the successful achievement of the goals set by their healthcare path. Hence the initiative to start a new research-intervention project in the field of hemophilia. The study had different phases of research: a first moment inspired by the principles of narrative medicine, aimed at collecting stories and narratives of patients with hemophilia related to the experience of the disease and therapy and expectations of active involvement in the relationship with the clinician. At the same time, among hematologists and patients has been surveyed the experience of therapeutical relationship and communication, to capture the aspects in which they feel effective and the areas of improvement and unmet needs. Subsequently, a workshop dedicated to patients and hematologists was organized to foster mutual awareness between these two targets and the formation of a better communication and relational skills of clinicians. The results of the project formed the basis for a policy brief document, aimed at disseminating recommendations to support better relationship and empathic communication between clinicians and patients.

About 5000 people in Italy suffer from hemophilia, the most common coagulation disorder. As for other chronic diseases, even in the case of hemophilia, the engagement of the patient is essential: the patients, in fact, must be empowered and helped to become strong partners of the care team and sensitized with respect to their rights and duties for the successful achievement of the goals set by their healthcare path. Hence the initiative to start a new research-intervention project in the field of hemophilia. The study had different phases of research: a first moment inspired by the principles of narrative medicine, aimed at collecting stories and narratives of patients with hemophilia related to the experience of the disease and therapy and expectations of active involvement in the relationship with the clinician. At the same time, among hematologists and patients has been surveyed the experience of therapeutical relationship and communication, to capture the aspects in which they feel effective and the areas of improvement and unmet needs. Subsequently, a workshop dedicated to patients and hematologists was organized to foster mutual awareness between these two targets and the formation of a better communication and relational skills of clinicians. The results of the project formed the basis for a policy brief document, aimed at disseminating recommendations to support better relationship and empathic communication between clinicians and patients.

About 5000 people in Italy suffer from hemophilia, the most common coagulation disorder. As for other chronic diseases, even in the case of hemophilia, the engagement of the patient is essential: the patients, in fact, must be empowered and helped to become strong partners of the care team and sensitized with respect to their rights and duties for the successful achievement of the goals set by their healthcare path. Hence the initiative to start a new research-intervention project in the field of hemophilia. The study had different phases of research: a first moment inspired by the principles of narrative medicine, aimed at collecting stories and narratives of patients with hemophilia related to the experience of the disease and therapy and expectations of active involvement in the relationship with the clinician. At the same time, among hematologists and patients has been surveyed the experience of therapeutical relationship and communication, to capture the aspects in which they feel effective and the areas of improvement and unmet needs. Subsequently, a workshop dedicated to patients and hematologists was organized to foster mutual awareness between these two targets and the formation of a better communication and relational skills of clinicians. The results of the project formed the basis for a policy brief document, aimed at disseminating recommendations to support better relationship and empathic communication between clinicians and patients.

Influx of matter from impacting meteoroids and hydrothermal crater weathering are important factors modifying the rock and mineral inventory of young planets undergoing heavy bombardment. These processes may have influenced not only the geochemical environment of, e.g., early Mars and other planets, but also the peculiar prebiotic chemistry on early Earth. Here, we present a synergistic experimental and computational investigation of the intermediates of chemical reactions of the formamide-based synthesis of canonical and non-canonical nucleobases by thermochemistry in hot hydrothermal crater environments. We put our findings into context with previously investigated plasma-initiated synthesis occuring directly during impact. Both processes result into the formation of all canonical nucleobases, hypoxanthine, purine, and into the onset of the simplest amino acid glycine. Furthermore, it turns out that radical species such as CN and H play a key role in the plasma-assisted impact chemistry. However, post-impact thermochemistry is essential for the origin of formamidine and 2-aminoacetonitrile, intermediate species detected in this study by means of FTIR spectroscopy.

Influx of matter from impacting meteoroids and hydrothermal crater weathering are important factors modifying the rock and mineral inventory of young planets undergoing heavy bombardment. These processes may have influenced not only the geochemical environment of, e.g., early Mars and other planets, but also the peculiar prebiotic chemistry on early Earth. Here, we present a synergistic experimental and computational investigation of the intermediates of chemical reactions of the formamide-based synthesis of canonical and non-canonical nucleobases by thermochemistry in hot hydrothermal crater environments. We put our findings into context with previously investigated plasma-initiated synthesis occuring directly during impact. Both processes result into the formation of all canonical nucleobases, hypoxanthine, purine, and into the onset of the simplest amino acid glycine. Furthermore, it turns out that radical species such as CN and H play a key role in the plasma-assisted impact chemistry. However, post-impact thermochemistry is essential for the origin of formamidine and 2-aminoacetonitrile, intermediate species detected in this study by means of FTIR spectroscopy.

The BQ.1 SARS-CoV-2 variant, also known as Cerberus, is one of the most recent Omicron descendant lineages. Compared to its direct progenitor BA.5, BQ.1 has some additional spike mutations in some key antigenic sites, which confer further immune escape ability over other circulating lineages. In such a context, here, we perform a genome-based survey aimed at obtaining a complete-as-possible nuance of this rapidly evolving Omicron subvariant. Genetic data suggest that BQ.1 represents an evolutionary blind background, lacking the rapid diversification that is typical of a dangerous lineage. Indeed, the evolutionary rate of BQ.1 is very similar to that of BA.5 (7.6 x 10(-4) and 7 x 10(-4) subs/site/year, respectively), which has been circulating for several months. The Bayesian Skyline Plot reconstruction indicates a low level of genetic variability, suggesting that the peak was reached around 3 September 2022. Concerning the affinity for ACE2, structure analyses (also performed by comparing the properties of BQ.1 and BA.5 RBD) indicate that the impact of the BQ.1 mutations may be modest. Likewise, immunoinformatic analyses showed moderate differences between the BQ.1 and BA5 potential B-cell epitopes. In conclusion, genetic and structural analyses on SARS-CoV-2 BQ.1 suggest no evidence of a particularly dangerous or high expansion capability. Genome-based monitoring must continue uninterrupted for a better understanding of its descendants and all other lineages.

An analysis of the structural effect of the mutations of the B.1.640.2 (IHU) Spike Receptor Binding Domain (RBD) and N-terminal Domain (NTD) is reported along with a comparison with the sister lineage B.1.640.1. and a selection of variants of concern. The effect of the mutations on the RBD–ACE2 interaction was also assessed. The structural analysis applied computational methods that are able to carry out in silico mutagenesis to calculate energy minimization and the folding energy variation consequent to residue mutations. Tools for electrostatic calculation were applied to quantify and display the protein surface electrostatic potential. Interactions at the RBD–ACE2 interface were scrutinized using computational tools that identify the interactions and predict the contribution of each interface residue to the stability of the complex. The comparison among the RBDs shows that the most evident differences between the variants is in the distribution of the surface electrostatic potential: that of B.1.640.1 is as that of the Alpha RBD, while B.1.640.2 appears to have an intermediate surface potential pattern with characteristics between those of the Alpha and Delta variants. Moreover, the B.1.640.2 Spike includes the mutation E484K that in other variants has been suggested to be involved in immune evasion. These properties may hint at the possibility that B.1.640.2 emerged with a potentially increased infectivity with respect to the sister B.1.640.1 variant, but significantly lower than that of the Delta and Omicron variants. However, the analysis of their NTD domains highlights deletions, destabilizing mutations and charge alterations that can limit the ability of the B.1.640.1 and B.1.640.2 variants to interact with cellular components, such as cell surface receptors.

The BQ.1 SARS-CoV-2 variant, also known as Cerberus, is one of the most recent Omicron descendant lineages. Compared to its direct progenitor BA.5, BQ.1 has some additional spike mutations in some key antigenic sites, which confer further immune escape ability over other circulating lineages. In such a context, here, we perform a genome-based survey aimed at obtaining a complete-as-possible nuance of this rapidly evolving Omicron subvariant. Genetic data suggest that BQ.1 represents an evolutionary blind background, lacking the rapid diversification that is typical of a dangerous lineage. Indeed, the evolutionary rate of BQ.1 is very similar to that of BA.5 (7.6 × 10−4 and 7 × 10−4 subs/site/year, respectively), which has been circulating for several months. The Bayesian Skyline Plot reconstruction indicates a low level of genetic variability, suggesting that the peak was reached around 3 September 2022. Concerning the affinity for ACE2, structure analyses (also performed by comparing the properties of BQ.1 and BA.5 RBD) indicate that the impact of the BQ.1 mutations may be modest. Likewise, immunoinformatic analyses showed moderate differences between the BQ.1 and BA5 potential B-cell epitopes. In conclusion, genetic and structural analyses on SARS-CoV-2 BQ.1 suggest no evidence of a particularly dangerous or high expansion capability. Genome-based monitoring must continue uninterrupted for a better understanding of its descendants and all other lineages.

Comparison of the surface electrostatic potential of the N-terminal (NTD) and the Receptor Binding Domains (RBD) of the Wuhan and Omicron Spikes. The entire Spikes are represented with transparent ribbon models. Only the NTD and RBD surfaces of the chain A are represented. Domain net charges are reported within parenthesis beside the domain labels. Surface color ranges from -5.0 (red) to + 5.0 (blue) kT/e. Image, graphical abstract

The COVID-19 pandemic continues to have a threatening impact on a global scale, largely due to the emergence of newly SARS-CoV-2 variants. The Mu (PANGO lineage B.1.621), was first identified in Colombia in January 2021 and was classified as a variant of interest (VOI) in August 2021, due to a constellation of mutations that likely-mediate an unexpectedly enhanced immune resistance to inactivated vaccine-elicited antibodies. Despite recent studies suggesting that the Mu variant appears to have less infectivity than the Delta variant, here we examined the structural effect of the Mu spike protein mutations and predicted the potential impact on infectivity of the Mu variant compared with the Delta and Delta plus spike protein.

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OBJECTIVE Little is known about the short-term dynamics of methicillin-resistant Staphylococcus aureus (MRSA) transmission between patients and their immediate environment. We conducted a real-life microbiological evaluation of environmental MRSA contamination in hospital rooms in relation to recent patient activity. DESIGN Observational pilot study. SETTING Two hospitals, hospital 1 in Zurich, Switzerland, and hospital 2 in Ann Arbor, Michigan, United States. PATIENTS Inpatients with MRSA colonization or infection. METHODS At baseline, the groin, axilla, nares, dominant hands of 10 patients and 6 environmental high-touch surfaces in their rooms were sampled. Cultures were then taken of the patient hand and high-touch surfaces 3 more times at 90-minute intervals. After each swabbing, patients' hands and surfaces were disinfected. Patient activity was assessed by interviews at hospital 1 and analysis of video footage at hospital 2. A contamination pressure score was created by multiplying the number of colonized body sites with the activity level of the patient. RESULTS In total, 10 patients colonized and/or infected with MRSA were enrolled; 40 hand samples and 240 environmental samples were collected. At baseline, 30% of hands and 20% of high-touch surfaces yielded MRSA. At follow-up intervals, 8 (27%) of 30 patient hands, and 10 (6%) of 180 of environmental sites were positive. Activity of the patient explained 7 of 10 environmental contaminations. Patients with higher contamination pressure score showed a trend toward higher environmental contamination. CONCLUSION Environmental MRSA contamination in patient rooms was highly dynamic and was likely driven by the patient's MRSA body colonization pattern and the patient activity.

About 5000 people in Italy suffer from hemophilia, the most common coagulation disorder. As for other chronic diseases, even in the case of hemophilia, the engagement of the patient is essential: the patients, in fact, must be empowered and helped to become strong partners of the care team and sensitized with respect to their rights and duties for the successful achievement of the goals set by their healthcare path. Hence the initiative to start a new research-intervention project in the field of hemophilia. The study had different phases of research: a first moment inspired by the principles of narrative medicine, aimed at collecting stories and narratives of patients with hemophilia related to the experience of the disease and therapy and expectations of active involvement in the relationship with the clinician. At the same time, among hematologists and patients has been surveyed the experience of therapeutical relationship and communication, to capture the aspects in which they feel effective and the areas of improvement and unmet needs. Subsequently, a workshop dedicated to patients and hematologists was organized to foster mutual awareness between these two targets and the formation of a better communication and relational skills of clinicians. The results of the project formed the basis for a policy brief document, aimed at disseminating recommendations to support better relationship and empathic communication between clinicians and patients.

Background: Interstitial lung disease (ILD) is a severe systemic manifestation of rheumatoid arthritis (RA). High-resolution computed tomography (HRCT) represents the gold standard for the diagnosis of ILD, but its routine use for screening programs is not advisable because of both high cost and X-ray exposure. Velcro crackles at lung auscultation occur very early in the course of interstitial pneumonia, and their detection is an indication for HRCT. Recently, we developed an algorithm (VECTOR) to detect the presence of Velcro crackles in pulmonary sounds and showed good results in a small sample of RA patients. The aim of the present investigation was to validate the diagnostic accuracy of VECTOR in a larger population of RA patients, compared with that of the reference standard of HRCT, from a multicentre study. Methods: To avoid X-ray exposure, we enrolled 137 consecutive RA patients who had recently undergone HRCT. Lung sounds of all patients were recorded in 4 pulmonary fields bilaterally with a commercial electronic stethoscope (ES); subsequently, all HRCT images were blindly evaluated by a radiologist, and audio data were analysed by means of VECTOR. Results: Fifty-nine of 137 patients showed ILD (43.1%). VECTOR correctly classified 115/137 patients, showing a diagnostic accuracy of 83.9% and a sensitivity and specificity of 93.2 and 76.9%, respectively. Conclusions: VECTOR may represent the first validated tool for the screening of RA patients who are suspected for ILD and who should be directed to HRCT for the diagnosis. Moreover, early identification of RA-ILD could contribute to the design of prospective studies aimed at elucidating unclear aspects of the disease.

Objective. To describe nailfold videocapillaroscopy (NVC) features of patients with antisynthetase syndrome (AS) and to investigate possible correlations with clinical and serological features of the disease. Methods. We retrospectively analyzed NVC images of 190 patients with AS [females/males 3.63, mean age 49.7 ± 12.8 yrs, median disease duration 53.7 mos (interquartile range 82), 133 anti-Jo1 and 57 non-anti-Jo1-positive patients]. For each patient, we examined number of capillaries, giant capillaries, microhemorrhages, avascular areas, ramified capillaries, and the presence of systemic sclerosis (SSc)-like pattern. Finally, we correlated NVC features with clinical and serological findings of patients with AS. Concomitantly, a historical cohort of 75 patients with antinuclear antibody-negative primary Raynaud phenomenon (RP) and longterm followup was used as a control group (female/male ratio 4.13/1, mean age 53.9 ± 17.6 yrs) for NVC measures. Results. NVC abnormalities were observed in 62.1% of AS patients compared with 29.3% of primary RP group (p < 0.001). An SSc-like pattern was detected in 67 patients (35.3%) and it was associated with anti-Jo1 antibodies (p = 0.002) and also with a longer disease duration (p = 0.004). Interestingly, there was no significant correlation between the presence of SSc-like pattern and RP, and only 47% of patients with SSc-like pattern had RP. Conclusion. NVC abnormalities are commonly observed in AS, independently from the occurrence of RP. The presence of an SSc-like pattern could allow identification of a more defined AS subtype, and prospective studies could confirm the association with clinical and serological features of AS.

Background: Interstitial lung disease (ILD) is a severe systemic manifestation of rheumatoid arthritis (RA). High-resolution computed tomography (HRCT) represents the gold standard for the diagnosis of ILD, but its routine use for screening programs is not advisable because of both high cost and X-ray exposure. Velcro crackles at lung auscultation occur very early in the course of interstitial pneumonia, and their detection is an indication for HRCT. Recently, we developed an algorithm (VECTOR) to detect the presence of Velcro crackles in pulmonary sounds and showed good results in a small sample of RA patients. The aim of the present investigation was to validate the diagnostic accuracy of VECTOR in a larger population of RA patients, compared with that of the reference standard of HRCT, from a multicentre study. Methods: To avoid X-ray exposure, we enrolled 137 consecutive RA patients who had recently undergone HRCT. Lung sounds of all patients were recorded in 4 pulmonary fields bilaterally with a commercial electronic stethoscope (ES); subsequently, all HRCT images were blindly evaluated by a radiologist, and audio data were analysed by means of VECTOR. Results: Fifty-nine of 137 patients showed ILD (43.1%). VECTOR correctly classified 115/137 patients, showing a diagnostic accuracy of 83.9% and a sensitivity and specificity of 93.2 and 76.9%, respectively. Conclusions: VECTOR may represent the first validated tool for the screening of RA patients who are suspected for ILD and who should be directed to HRCT for the diagnosis. Moreover, early identification of RA-ILD could contribute to the design of prospective studies aimed at elucidating unclear aspects of the disease.

Objective. To describe nailfold videocapillaroscopy (NVC) features of patients with antisynthetase syndrome (AS) and to investigate possible correlations with clinical and serological features of the disease. Methods. We retrospectively analyzed NVC images of 190 patients with AS [females/males 3.63, mean age 49.7 ± 12.8 yrs, median disease duration 53.7 mos (interquartile range 82), 133 anti-Jo1 and 57 non-anti-Jo1-positive patients]. For each patient, we examined number of capillaries, giant capillaries, microhemorrhages, avascular areas, ramified capillaries, and the presence of systemic sclerosis (SSc)-like pattern. Finally, we correlated NVC features with clinical and serological findings of patients with AS. Concomitantly, a historical cohort of 75 patients with antinuclear antibody-negative primary Raynaud phenomenon (RP) and longterm followup was used as a control group (female/male ratio 4.13/1, mean age 53.9 ± 17.6 yrs) for NVC measures. Results. NVC abnormalities were observed in 62.1% of AS patients compared with 29.3% of primary RP group (p < 0.001). An SSc-like pattern was detected in 67 patients (35.3%) and it was associated with anti-Jo1 antibodies (p = 0.002) and also with a longer disease duration (p = 0.004). Interestingly, there was no significant correlation between the presence of SSc-like pattern and RP, and only 47% of patients with SSc-like pattern had RP. Conclusion. NVC abnormalities are commonly observed in AS, independently from the occurrence of RP. The presence of an SSc-like pattern could allow identification of a more defined AS subtype, and prospective studies could confirm the association with clinical and serological features of AS.

Pearl-farming is the second most important source of income in French Polynesia. However, tropical lagoons are fragile ecosystems with regard to anthropogenic pressures like plastic pollution, which threaten marine life and the pearl oyster-related economy. Here, we investigated the spatial distribution of microplastics (MP) and concentrations in surface water (SW), water column (WC) and cultivated pearl oyster (PO) from three pearl-farming atolls with low population and tourism. Microplastics were categorized by their size class, shape, colour and polymer type identified using FTIR spectroscopy. Widespread MP contamination was observed in every study site (SW, 0.2–8.4 MP m–3; WC, 14.0–716.2 MP m–3; PO, 2.1–125.0 MP g–1 dry weight), with high contamination in the WC highlighting the need to study the vertical distribution of MP, especially as this compartment where PO are reared. A large presence of small (< 200 µm) and fragment-shaped (> 70%) MP suggests that they result from the breakdown of larger plastic debris. The most abundant polymer type was polyethylene in SW (34–39%), WC (24–32%), while in PO, polypropylene (14–20%) and polyethylene were more evenly distributed (9–21%). The most common MP identified as black-grey polyethylene and polypropylene matches the polymer and colour of ropes and collectors questioning a pearl-farming origin.

Pearl-farming is the second most important source of income in French Polynesia. However, tropical lagoons are fragile ecosystems with regard to anthropogenic pressures like plastic pollution, which threaten marine life and the pearl oyster-related economy. Here, we investigated the spatial distribution of microplastics (MP) and concentrations in surface water (SW), water column (WC) and cultivated pearl oyster (PO) from three pearl-farming atolls with low population and tourism. Microplastics were categorized by their size class, shape, colour and polymer type identified using FTIR spectroscopy. Widespread MP contamination was observed in every study site (SW, 0.2–8.4 MP m–3; WC, 14.0–716.2 MP m–3; PO, 2.1–125.0 MP g–1 dry weight), with high contamination in the WC highlighting the need to study the vertical distribution of MP, especially as this compartment where PO are reared. A large presence of small (< 200 µm) and fragment-shaped (> 70%) MP suggests that they result from the breakdown of larger plastic debris. The most abundant polymer type was polyethylene in SW (34–39%), WC (24–32%), while in PO, polypropylene (14–20%) and polyethylene were more evenly distributed (9–21%). The most common MP identified as black-grey polyethylene and polypropylene matches the polymer and colour of ropes and collectors questioning a pearl-farming origin.

Early life stages (ELS) of numerous marine invertebrates mustcope with man-made contaminants, including plastic debris, during their pelagic phase. Among the diversity of plastic particles, nano-sized debris, known as nanoplastics, can induce effects with severe outcomes in ELS of various biological models, including the Pacific oyster Crassostrea gigas. Here, we investigated the effects of a sub-lethal dose (0.1 µg mL−1) of 50 nm polystyrene nanobeads (nano-PS) with amine functions on oyster embryos (24 h exposure) and we assessed consequences on larval and adult performances over two generations of oysters. Only a few effects were observed. Lipid analyses revealed that first-generation (G1) embryos exposed to nano-PS displayed a relative increase in cardiolipin content (+9.7%), suggesting a potential modification of mitochondrial functioning. G1-larvae issued from exposed embryos showed decreases in larval growth (−9%) and lipid storage (−20%). No effect was observed at the G1 adult stage in terms of growth, ecophysiological parameters (clearance and respiration rates, absorption efficiency), or reproductive outputs (gonadic development, gamete quality). Second generation (G2) larvae issued from control G1 displayed a significant growth reduction after G2 embryonic exposure to nano-PS (−24%) compared to control (as observed at the first generation), while no intergenerational effect was detected on G2 larvae issued from G1 exposed embryos. Overall, the present experimental study suggests a low incidence of a short embryonic exposure to nano-PS on oyster phenotypes along the entire life cycle until the next larval generation.

Pearl-farming is the second most important source of income in French Polynesia. However, tropical lagoons are fragile ecosystems with regard to anthropogenic pressures like plastic pollution, which threaten marine life and the pearl oyster-related economy. Here, we investigated the spatial distribution of microplastics (MP) and concentrations in surface water (SW), water column (WC) and cultivated pearl oyster (PO) from three pearl-farming atolls with low population and tourism. Microplastics were categorized by their size class, shape, colour and polymer type identified using FTIR spectroscopy. Widespread MP contamination was observed in every study site (SW, 0.2–8.4 MP m–3; WC, 14.0–716.2 MP m–3; PO, 2.1–125.0 MP g–1 dry weight), with high contamination in the WC highlighting the need to study the vertical distribution of MP, especially as this compartment where PO are reared. A large presence of small (< 200 µm) and fragment-shaped (> 70%) MP suggests that they result from the breakdown of larger plastic debris. The most abundant polymer type was polyethylene in SW (34–39%), WC (24–32%), while in PO, polypropylene (14–20%) and polyethylene were more evenly distributed (9–21%). The most common MP identified as black-grey polyethylene and polypropylene matches the polymer and colour of ropes and collectors questioning a pearl-farming origin.