BackgroundIdiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders characterized by muscle inflammation frequently associated with the involvement of other organ systems. Due to variety of presentations and severity degree, treatment of inflammatory myopathies is challenging. Considering the immunopathogenic role of B cell in myositis, Rituximab (RTX), as B cell depleting agent, could be an effective therapy in patients refractory to others immunomodulatory drugs.ObjectivesThe aim of the present study is to demonstrate the efficacy of RTX for the treatment of idiopathic inflammatory myopathies in multi refractory patients. We also considered the effectiveness of a low-dose RTX as a remission-maintenance therapy.MethodsFrom a monocentric cohort of patients with inflammatory myopathies, we considered all patients who have been treated with RTX (2 infusions of 1 gram, week 0-2). We also considered low-dose RTX as a single dose of 1g every 6 months. The response to RTX was considered based on physician judgement (complete CR, partial PR, no-response NR), focused on muscle and lung manifestations. Improvement in muscle involvement was based on reduction of 30% of creatine kinase levels and/or an increase in Manual Muscle Test score (MMT-8) of 20%. Interstitial Lung disease (ILD) was evaluated by pneumologist judgement based on chest computer tomography and spirometry. A response was considered partial if it was maintained less than 6 months from RTX administration and complete if it persisted more than 6 months.ResultsThirty-six patients were included, 15 with diagnosis of polymyositis, 13 with antisynthetase syndrome, 6 with dermatomyositis, 1 with inclusion body myositis and 1 with necrotizing myopathy. Anti-Jo1 autoantibodies were found in 12 patients, anti-SSA in 9, anti-SRP in 5, anti-PM/Scl 75 in 2, anti-Mi2 in 2, anti-PL7 in 1, anti-PL 12 in 1, anti-SSB in 1, anti-TIF1-γ in 1, anti Ku in 1 and anti Sp100 in 1. Most patients (50 %, n=18) were treated with RTX for muscle involvement, 17 % (n= 6) for ILD, 33 % (n=12) for both muscular and lung disease. All patients received oral glucocorticoid before starting RTX administration. The others previous therapies were: methotrexate in 72% of patients, mycophenolate mofetil in 50%, IVIG in 27%, azathioprine in 22%, hydroxychloroquine in 14%, cyclosporine in 14%, leflunomide in 11%, tacrolimus in 3%, cyclophosphamide in 3%. We observed CR to RTX in 70% of patients, PR in 19%, NR in 11%. In the subgroup treated for muscle involvement (n=18), we found a CR in 10 patients, a PR in 5 and NR in 3. In patients with ILD, 5 patients got a CR and 1 PR. In the group of patients with both lung and muscle manifestations, we observed 10 CR, 1 with PR and 1 with NR. Five patients were treated with a low dose maintenance therapy after having achieved remission with standard dose. Three patients had a diagnosis of polymyositis, one of dermatomyositis and one of antisynthetase syndrome. Patients received a minimum of 3 infusions and a maximum of 5 infusions of low dose RTX.Therapy was administrated for an average of 3 years. All of them maintained a CR to RTX.ConclusionIn our cohort, RTX was effective in 89% multi-drug refractory patients and the low-dose was efficacious as a maintenance therapy in all cases.References[1]Oddis CV et. al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. 2013 Feb;65(2):314-24. doi: 10.1002/art.37754. PMID: 23124935; PMCID: PMC3558563. [2]Schmidt J. Current Classification and Management of Inflammatory Myopathies. J Neuromuscul Dis. 2018;5(2):109-129. doi: 10.3233/JND-180308. PMID: 29865091; PMCID: PMC6004913Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Background: IPF remains a deadly and unpredictable disease. Loss of muscle mass (LOM) seems to be associated with poor prognosis in chronic illnesses but its significance in IPF remains unexplored. Thus, we aimed to investigate the role of muscle loss in patients with IPF under antifibrotic treatment. Methods: 88 patients with IPF (16 females, 72 males) were retrospectively enrolled between March 2014 and December 2021. Demographic, functional and radiological data were collected at diagnosis. We recorded the mean Hounsfield Unit (Hu) value of the right paravertebral muscle at the level of the 12th thoracic vertebra and defined loss of muscle mass (LOM) as MeanHu < 30. Survival and Cox regression analysis were applied to assess the prognostic significance. Results: the prevalence of LOM at the time of diagnosis was 47% (41 out of 88). Patients with LOM were older (74 vs 67 years; <0.0001) and presented less metabolic comorbidities (39% vs 62%; p=0.03) compared with not-LOM patients. Indeed, male patients with LOM had a lower survival rate at two-years compared to males without loss of muscle mass [HR 5.3 (95%CI 1.4 - 20); p=0.02]. By Cox regression analysis, low HighGreyLevelRunEmphasis at baseline and the need of oxygen therapy at rest were both independent risk factors of death at 2 years. The optimal cut-off of HighGreyLevelRunEmphasis, in male patients was 13.4 (sens67% and spec81%; AUC 0.79; p=0.005). Conclusion: loss of muscle mass is highly prevalent in IPF patients at the time of diagnosis. Moreover, male patients with muscle loss presented a reduction in survival rate at two years. Low HighGreyLevelRunEmphasis at baseline and oxygen need at rest are independent predictors of mortality.

Background: limited data exist on the prevalence of radiographic abnormalities after COVID-19 pneumonia, and the extent to which High Resolution CT (HRCT) features correlate with symptoms and function after 12-month from hospitalization remains unclear. Aims: To prospectively assess and characterize, among all discharged patients with COVID-19, those with persisting pulmonary sequalae after 12-month follow-up. Methods: 354 patients were evaluated in our post-COVID-clinic from June 2020 to January 2021. Symptoms and functional parameters were recorded. According to the absence or presence of HRCT abnormalities after 12-months, patients were categorized as recovered (REC) or not recovered (NOT-REC) and the extension of radiographic changes was scored. Results: 296/354 patients(84%) completed the 12-month follow up. 21/296(7%) presented pulmonary sequelae with a mean extension of interstitial changes of 11% of the whole lung. REC displayed a median full recovery time of 131(60-203) days. Compared to REC, NOT-REC were mainly current smokers [3(14%) vs.12(4%);p=0.05], with a longer in-hospital stay [13 (7.5–40.5) vs.10.0(6.0–16.0);p=0.02], need for a higher maximal FiO2 during hospitalization [60(29–100) vs. 33 (21–65);p<0.004] and higher intensity medical care [10(48%) vs.48(17%);p<0.001]. Conversely, lung function did not differ [FVC 97%(88-109) vs.93(82-105),p=0.32; FEV1 102%(86–116) vs. 96(85-106);p=0.11]. Conclusion: A low percentage of patients discharged for COVID-19 pneumonia showed fibrotic-like changes at 12-month follow-up, yet with preserved lung function. They are mainly current smokers, with a higher level of medical care during hospitalization and a prolonged in-hospital stay.

Background: Patients with ILD may display a progressive fibrosing behavior despite treatment. The phenotype and clinical characteristics of progressive IIM-ILDs still remain to be deeply investigated. Aim: To explore clinical and serological characteristics of progressive IIM-ILD patients in a multicentric population. Methods: We collected clinical, serological and radiological data of 125 IIM-ILD patients at diagnosis and during follow-up. Progression was defined when forced vital capacity (FVC) %pred. decline was ≥ 5% or when a high-resolution CT scan worsens over one-year follow-up. Results: In 79/125(63%) IIM-ILDs patients (age 64±11.5;24M,55F) functional and radiological date were available after one-year follow-up. 65(82%) were classified as stables (S) and 14(18%) as progressors (P). Sex, age and functional data at ILD diagnosis and the mortality rate (7vs.3%) did not differ among P and S. Compared to S, P displayed a significantly higher prevalence of anti-MDA5 antibodies (29vs.6%;p=0.03), heliotropic rash (29vs.5%;p=0.02), xerostomia (29vs.5%;p=0.02) and xerophthalmia (36vs.6%;p=0.007). Anti-MDA5 antibodies [HR6.10 95%CI(1.30–28.4);p=0.002], heliotropic rash [8.00(1.55–41.23);p=0.01], xerostomia [8.19 (1.84 – 36.36);p=0.006] and xerophthalmia [8.00 (1.55 – 41.2);p=0.01] were confirmed as progression-associated factors at univariate but not at multivariate analysis. Conclusions: Serological and clinical features at diagnosis may predict progression in IIM-ILD patients. Anti-MDA5 antibodies, heliotropic rash, xerostomia and xerophthalmia are prevalent in progressive IIM-ILD population, but their role as independent predictors need to be further investigated.

Introduction: Abnormal liver function tests at hospital admission are frequently reported in patients with coronavirus disease 2019 (COVID-19), but their prognostic significance deserves further investigation. Aim: To assess whether aspartate aminotransferase (AST) and alanine aminotransferase (ALT) abnormalities at admission predict disease course in patients hospitalized for COVID-19. Methods: In this single-center retrospective study, data of 188 patients admitted to the Infectious Disease Unit of the Padova University Hospital between February and May 2020 were collected. Patients were considered to have transaminases abnormalities when AST, ALT or both were above the upper limit of normal (ULN). The disease was considered as severe in case of intensive care unit (ICU) patient admission or death. Results: At admission, 98 patients (52.1%) had abnormal transaminases, but only 12 patients (6.4%) showed levels above 3 x ULN. Patients with severe disease showed higher AST (50 [IQR, 37-77] vs. 30 [IQR, 24-43] U/L, p<0.0001) and a trend to higher ALT (32 [IQR, 20-56] vs. 25 [IQR, 18-39] U/L, p=0.07) levels. Altered transaminases at baseline were associated with a higher probability of ICU transfer (40.8% vs. 15.6%, p=0.0002), mechanical ventilation (19.4% vs. 3.3%, p=0.0005), non-invasive ventilation (12.2% vs. 4.4%, p=0.07), and longer hospital stay (9 vs. 7 days, p=0.002). The risk of severe disease (transfer to ICU or death) was remarkably higher in patients with altered transaminases at admission (46.9% vs. 15.6%; p<0.0001) (Figure), and this was confirmed on multivariable logistic regression analysis after adjusting for sex, age, comorbidities, circulating inflammatory markers (neutrophil-to-lymphocyte ratio and C-reactive protein) and albumin levels with a five-fold higher risk (OR=5.17, 95% CI 1.81-14.70; p=0.002). Conclusion: Hospitalized COVID-19 patients have frequently transaminases abnormalities at admission, and these alterations are able to independently predict a severe disease course.

Interstitial lung diseases (ILDs) are a heterogeneous group of disorders affecting lung interstitium. A multidisciplinary team (MdT) is required for a confident diagnosis. Transbronchial biopsy (TBB) receives weak recommendations in the current diagnostic guidelines. Few recent papers have underlined the contributive diagnostic value of TBB, thus the main goal of our study was to evaluate the principal factors which can impact on its adequacy. We evaluated 51 patients with clinical/radiological suspicious of ILD, that underwent TBB in our center in one year. The number and the surface area of the samples were morphometrically evaluated. Crushing and blood extravasation artifacts were also scored based on the partial or extensive sample involvement. Inadequate specimens were considered those tissues mainly consisting of bronchial wall, pleura fragments and vessels. A one-year follow up was available in all patients for final confirmation of MdT diagnosis. 44/51 (86%) samples were adequate and 7/51 (14%) were inadequate. In adequate TBBs, a confident diagnosis was obtained in 68%. Sample number was similar but area seemed to be lower in inadequate than in adequate TBBs (median: 4 vs 5mm2). Concerning the artifacts, a trend was found when considering crushing: it was present in all inadequate samples (extensive crush) and in 77% of adequate samples (p=0.067). Among the adequate cases, the most frequent diagnoses were UIP (34%) and OP (38%). Adequate TBB could be successful to achieve a confident diagnosis when the ILD is strongly suspected. Crushing is the parameter that seems to have the major impact, but larger case studies are required.

Lung transplant (LT) recipients are at high risk to be affected by cytomegalovirus (CMV) infection or to die from CMV disease. Two strategies are usually adopted in the clinical management of transplant recipients: antiviral prophylaxis and pre-emptive therapy. The benefit of combined CMV prophylaxis after LT still remains unclear. The aim of this study was to investigate the effect of combined prophylaxis using gancyclovir or valgancyclovir and CMV immunoglobulins in our LT recipients. 60 recipients (transplanted in our Centre from 2007 to 2010) were randomly assigned to combined CMV prophylaxis (group 1), pre-emptive therapy (group 2) and single gancyclovir prophylaxis (group 3). All had a minimum follow-up of 1 year posttransplant. The three groups did not differ significantly in demographic, immunological characteristics, CMV serostatus or initial immunosuppressive therapy. Viral (CMV and other herpesviruses) infection index, acute rejection index and CMV associated pneumonia were evaluated in 261 scheduled bronchoalveolar lavage (viral infection) and in 335 scheduled tranbronchial biopsies (acute rejection and CMV pneumonia). Bronchiolitis Obliterans Syndome (BOS) and cumulative survival were also analysed. Significant reduced viral infection index was observed in group 1 compared to group 2 and 3 (p=0.004). Less acute rejection index, particularly grade A3 and reduced first-year CMV pneumonia both with marginal statistical significance (p=0.08 and 0.09 respectively) were seen in group 1 compared to group 2 and 3. The difference in the BOS grades between the groups was not statistically significant. Three-year survival was significantly higher in group 1 than group 2 and 3 (p=0.003). Our data underline the strong efficacy of combined CMV prophylaxis in reducing viral infection. Better survival may result from improved viral infection prevention, although multicentre randomized trials are warranted.

Idiopathic pulmonary fibrosis (IPF) is a rare chronic and ultimately fatal disease resulting in an aberrant scarring and thickening of lung tissue. Molecular pathogenetic mechanisms of IPF are still unknown and till now no effective therapy is known to really improve disease's outcome. A deeper understanding of IPF biology is now mandatory to clarify IPF origin in order to identify actionable targets. Here we discuss and analyze the data presented by a recent paper published by De Pianto et al. on the prestigious respiratory journal Thorax. The work is focused on how gene expression analysis can be applied to stratify IPF cases based on their risk of disease progression. Moreover they tried to match genetic and phenotypic profiles in order to predict therapeutic response and patients' prognosis.

Idiopathic pulmonary fibrosis (IPF), the commonest form of the interstitial lung diseases identifies a specific form of chronic, progressive fibrosing interstitial pneumonia, occurring primarily in older adults, and limited to the lungs. IPF represents an unsolved health problem with an urgent medical need due to lack of effective therapies. Although precise IPF etiology remains elusive, during the past decade there has been a shift away from the pathogenetic theory of generalized inflammation progressing to a paradigm of disordered fibroproliferation and alveolar epithelial cell function. A better understanding of the molecular mechanisms driving IPF fibroblasts proliferation is mandatory to provide insights into the pathogenesis, and to identify highly reproducible biomarkers for disease onset and progression. In this review we aim to discuss and analyze the findings recently published by Yang et al. on Thorax, which reported a strong molecular signature as-sociated with the expression of cilium genes that divides IPF/ usual interstitial pneumonia into two subtypes, one with increased cilium gene expression and one with low expression of cilium genes. The study presents a number of methodology limitations, mainly related to samples characterization and to a general overstatement of the conclusions from class clustering analysis. Nevertheless, the study clearly demonstrates ‑ for the first time ‑ that the cilium apparatus is activated in microscopic honeycombing. In such setting, cilia are likely to act as signaling "machine" which cooperates in promoting proliferative and regenerative cellular processes. Although preliminary, these results sustain a rationale to develop further investigations to confirm the impact of cilium gene expression in IPF with the final perspective of therapeutic intervention.

Lung transplantation is a therapeutic option for end stage lung diseases. One of the most important topics in transplant management is the role of viral infections in chronic lung allograft dysfunction (CLAD) and in particular in acute rejection (AR). This review arise from a recent study BY Brideaux et al. that offers the opportunity to investigate deeply the incidence, risk factors, symptomatology and clinical outcome of respiratory viral infections. Although most respiratory viral infections cause self-limited upper respiratory diseases, lung transplant recipients (LTRs) are particularly prone to develop complications. The absence of symptoms is a pivotal problem in managing these patients as it can depend on absence of active replication or on the effect of immunosuppressive regimen. In one word viruses can be just passengers or aggressive drivers in a facilitated environment, and the potential damage is completely different, as the management. PCR samplings give us an idea of the presence but not the certainty of the activity of viruses, and this is another common problem in reading data. In Herpes Virus infections this problem can be overtaken by studying biological samples and immune response, balancing the presence (PCR) and the activity (shell vial) of viruses with specific immune response (elispot). In fact viral presence doesn't mean activity and activity doesn't mean pathology in case of competent immune response. All these data can be matched in every single patient and managed by a tailored approach, either monitoring or treating.

<正>肺高血压是特发性肺间质纤维化(idiopathic pulmonary fibrosis,IPF)的主要并发症,对患者预后有不良影响。目前认为疱疹病毒在IPF的发生发展过程中起致病作用。病毒对IPF相关的肺高血压的影响尚不清楚。该研究重点探讨病毒对IPF患者肺高血压相关方面的影响,同时还对γ疱疹病毒[鼠疱疹病毒68(maus herpesvirus 68,MHV-68)]诱发的肺间质纤维化实验室小鼠模型进行评估。方法:应用分子鉴定

Idiopathic Pulmonary Fibrosis (IPF) is a common indication for lung transplantation (LTX) in most transplant centers. Herpesviruses, particularly EBV, have often been identified in IPF lungs and thought to be a potential cofactor for the development and/or progression of the disease. Viral recurrence, a frequent finding in other solid organ transplants (such as liver) is frequently associated with poor outcome and graft dysfunction. To date it is unknown if viral recurrence can occur in viral IPF recipients.