@ERSpublications IPAF retrospective cohorts show numerous differences between them. We propose some ideas to improve IPAF criteria http://ow.ly/eubC30jlGJO ABSTRACT The term interstitial pneumonia with autoimmune features (IPAF) has been proposed to define patients with interstitial lung disease (ILD) associated with autoimmune signs not classifiable for connective tissue diseases (CTDs). This new definition overcomes previous nomenclatures and provides a uniform structure for prospective studies through specific classification criteria.This work evaluates the characteristics of IPAF patients reported in the literature, to highlight potential limits through a comparative analysis and to suggest better performing classification criteria.Four retrospective studies on the IPAF population have been considered. The study subjects differed in age, sex, smoking habit, ILD pattern and outcomes. Another important difference lies in the diverse items considered in the classification criteria. The retrospective design of the studies and the absence from some of them of a rheumatologist clearly involved in the diagnosis may have influenced the data, but current IPAF criteria seem to include a rather heterogeneous population. To overcome these discrepancies, this review suggests a limitation in the use of single items and the exclusion of extremely specific CTD criteria. This should avoid the definition of IPAF for those diseases at different stages or at early onset. The investigation of a functional or morphological cut-off of pulmonary involvement would be useful.

Digital ulcers (DUs) are a rather frequent and invalidating complication in systemic sclerosis (SSc), often showing a very slow or null tendency to heal, in spite of the commonly used systemic and local therapeutic procedures. Recently, stem cell therapy has emerged as a new approach to accelerate wound healing. In the present study, we have tentatively treated long-lasting and poorly responsive to traditional therapy SSc-related DUs by implantation of autologous adipose tissue-derived cell (ATDC) fractions. Fifteen patients with SSc having a long-lasting DU in only one fingertip who were unresponsive to intensive systemic and local treatment were enrolled in the study. The grafting procedure consisted of the injection, at the basis of the corresponding finger, of 0.5-1 ml of autologous ATDC fractions, separated by centrifugation of adipose tissue collected through liposuction from subcutaneous abdominal fat. Time to heal after the procedure was the primary end point of the study, while reduction of pain intensity and of analgesic consumption represented a secondary end point. Furthermore, the posttherapy variation of the number of capillaries, observed in the nailfold video capillaroscopy (NVC) exam and of the resistivity in the digit arteries, measured by high-resolution echocolor-Doppler, were also taken into account. A rather fast healing of the DUs was reached in all of the enrolled patients (mean time to healing 4.23 weeks; range 2-7 weeks). A significant reduction of pain intensity was observed after a few weeks (p < 0.001), while the number of capillaries was significantly increased at 3- and 6-month NVC assessment (p < 0.0001 in both cases). Finally, a significant after-treatment reduction of digit artery resistivity was also recorded (p < 0.0001). Even with the limitations related to the small number of patients included and to the open-label design of the study, the observed strongly favorable outcome suggests that local grafting with ATDCs could represent a promising option for the treatment of SSc-related DUs unresponsive to more consolidated therapies.

Autologous fat tissue grafting (AFTG) has been successfully used in the treatment of different sclerotic conditions, including localized scleroderma. Patients with advanced systemic sclerosis (SSc)-related perioral thickening and mouth opening limitation are candidates for this therapeutic approach. AFTG of the lips was performed to improve mouth opening in patients with SSc. We enrolled in the study 20 female patients with diffuse SSc (median age 35 ± 15 years and 11 ± 10 years of disease duration). Two-milliliter fractions of autologous fat drawn from trochanteric or periumbilical areas were injected in eight different sites around the mouth. Baseline and after-treatment mouth opening changes were assessed by measuring interincisal distance and oral perimeter, while skin hardness was tested by digital durometer. Pre-and posttreatment modifications of microvascular architecture were assessed by counting capillaries in the inferior lip videocapillaroscopy (VC) images and by scoring the microvascular density (MVD) in anti-CD34/CD31 immunohistochemical (IH) stained perioral skin biopsy sections. Similarly, histological sections were examined to evaluate dermoepidermic junction (DEJ) modifications. Three months after treatment, both the interincisal distance and oral perimeter significantly increased (p < 0.001). At the same time, a significant skin neovascularization became evident, both considering the VC images (p < 0.001) and MVD scores in IH sections (p < 0.0001). Finally, some skin histological aspects also improved, as shown by the significant changes in DEJ flattening scores (p < 0.0001). The present study suggests that, in patients with SSc, AFTG can improve mouth opening and function, induce a neovascularization, and partially restore the skin structure.

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Background: The term Interstitial Pneumonia with Autoimmune Features (IPAF) describes patients with Interstitial Lung Diseases (ILDs) and clinical or serological features of autoimmune diseases insufficient to reach a specific classification of a Connective Tissue Disease (CTD). Currently, retrospective studies on IPAF patients have proven to be heterogeneous in general characteristics, outcomes and High-Resolution Computed Tomography (HRCT) pattern. This study aims to describe for the first time the clinical, serological and radiological features of a prospective cohort of IPAF patients. This cohort is then compared to a group of patients with Idiopathic Pulmonary Fibrosis (IPF). Material and methods: From 626 consecutive ILD patients evaluated, 45 IPAF and a comparison cohort of 143 IPF patients were enrolled. All patients underwent clinical assessment with rheumatologic and respiratory evaluation, HRCT, Pulmonary Function Tests and Nailfold Videocapillaroscopy. Results: The IPAF patients had a predominance of female gender (62.12%) with a median age of 66 years. The most common findings were: Nonspecific Interstitial Pneumonia (NSIP, 68.89%), Antinuclear Antibody positivity (17.77%) and Raynaud Phenomenon (31.11%). In comparison with IPF, IPAF patients showed younger age, better performances in Pulmonary Function Tests, less necessity of O 2 support and predominance of female sex and NSIP pattern. Discussion: This is the first report of a prospective cohort of IPAF patients. IPAF patients seem to have a less severe lung disease than IPF. IPAF criteria probably need to be revisited and validated, but their capacity to recruit patients with incomplete forms or early onset of CTD could be useful for further research.

This study aims to assess the peripheral blood cell count “signature” of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) to discriminate promptly between COronaVIrus Disease 19 (COVID-19) and community-acquired pneumonia (CAP). We designed a retrospective case-control study, enrolling 525 patients (283 COVID-19 and 242 with CAP). All patients had a fever and at least one of the following signs: cough, chest pain, or dyspnea. We excluded patients treated with immunosuppressants, steroids, or affected by diseases known to modify blood cell count. COVID-19 patients showed a significant reduction in white blood cells (neutrophils, lymphocytes, monocytes, eosinophils) and platelets. We studied these parameters univariately, combined the significant ones in a multivariate model (AUROC 0.86, Nagelkerke PSEUDO-R2 0.5, Hosmer–Lemeshow p-value 0.9) and examined its discriminative performance in an internally-randomized validation cohort (AUROC 0.84). The cut-off selected according to Youden’s Index (−0.13) showed a sensitivity of 84% and a specificity of 72% in the training cohort, and a sensitivity of 88% and a specificity of 73% in the validation cohort. In addition, we determined the probability of having COVID-19 pneumonia for each Model for possible Early COvid-19 Recognition (MECOR) Score value. In conclusion, our model could provide a simple, rapid, and cheap tool for prompt COVID-19 diagnostic triage in patients with CAP. The actual effectiveness should be evaluated in further, prospective studies also involving COVID-19 patients with negative nasopharyngeal swabs.

IntroductionNailfold videocapillaroscopy (NVC) in systemic sclerosis (SSc) is a procedure commonly used for patient classification and subsetting, but not to define disease activity (DA). This study aimed to evaluate whether the number of micro-haemorrhages (MHE), micro-thrombosis (MT), giant capillaries (GC), and normal/dilated capillaries (Cs) in NVC could predict DA in SSc.MethodsEight-finger NVC was performed in 107 patients with SSc, and the total number of MHE/MT, GC, and the mean number of Cs were counted and defined as number of micro-haemorrhages (NEMO), GC and Cs scores, respectively. The European Scleroderma Study Group (ESSG) index constituted the gold standard for DA assessment, and scores ≥3.5 and =3 were considered indicative of high and moderate activity, respectively.ResultsNEMO and GC scores were positively correlated with ESSG index (R = 0.65, P <0.0001, and R = 0.47, P <0.0001, respectively), whilst Cs score showed a negative correlation with that DA index (R = −0.30, P <0.001). The area under the curve (AUC) of receiver operating characteristic plots, obtained by NEMO score sensitivity and specificity values in classifying patients with ESSG index ≥3.5, was significantly higher than the corresponding AUC derived from either GC or Cs scores (P <0.03 and P <0.0006, respectively). A modified score, defined by the presence of a given number of MHE/MT and GC, had a good performance in classifying active patients (ESSG index ≥3, sensitivity 95.1%, specificity 84.8%, accuracy 88.7%).ConclusionsMHE/MT and GC appear to be good indicators of DA in SSc, and enhances the role of NVC as an easy technique to identify active patients.

BackgroundSome abnormalities in nailfold videocapillaroscopy (NVC), such as the presence of micro-haemorrhages (MHEs), micro-thromboses (MTs), giant capillaries (GCs) and reduction in the number of capillaries (nCs), suggest a disease activity (DA) phase in systemic sclerosis (SSc). In a previous paper, we showed that the number of micro-haemorrhages and micro-thromboses (the so-called NEMO score) was the NVC feature more closely associated with DA. The present study was aimed at validating the NEMO score as a measure of DA in patients with SSc.MethodsTwo cohorts of 122 and 97 patients with SSc who were referred to two different rheumatology units, one in Milan and one in Naples, respectively, constituted the validation cohorts. The NEMO score, the total number of GCs and the mean nCs per digit were the parameters defined in each patient by eight-finger NVC. An expert operator analysed the NVCs in each of the participating units. The European Scleroderma Study Group (ESSG) index was used to define the DA level in each patient at the time of NVC examination.ResultsThe NEMO score was the NVC parameter more strictly correlated with the ESSG score in both the Milan and Naples cohorts (p < 0.0001), and it was the only one among the NVC variables that gave a significant contribution in a logistic model where the ESSG score represented the dependent variable. ROC curve analysis confirmed that the NEMO score had the best performance in measuring DA. The AUC of the NEMO score was significantly greater than the AUCs obtained by plotting the sensitivity and specificity of the number of GCs and the mean nCs (p < 0.0001 in all cases). The NEMO score values that showed the best sensitivity-specificity balance in capturing patients with a relevant DA level were slightly higher in the Naples cohort than in the Milan cohort.ConclusionsThis study confirms that the presence of a certain number of MHEs and MTs in NVC may be considered a strong warning signal of a current phase of DA in patients with SSc.