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Reliable biomarkers allowing early patients’ stratification for the risk of adverse outcomes in COVID-19 are lacking. Gas6, together with its tyrosine kinase receptors named TAM, is involved in the regulation of immune homeostasis, fibrosis, and thrombosis. Our aim was to evaluate whether Gas6, sAxl, and sMerTK could represent early predictors of disease evolution either towards a negative (death or need of ICU admission) or a positive (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. To this purpose, between January and May 2021 (corresponding to third pandemic wave in Italy), 139 consecutive SARS-CoV-2 positive patients were enrolled in a prospective observational study. Plasma levels of these molecules were measured by ELISA at the time of hospitalization and after 7 and 14 days. We observed that higher plasma Gas6 concentrations at hospital admission were associated with a worsening in clinical conditions while lower sMerTK concentrations at baseline and after 7 days of hospitalization were associated with a more favorable outcome. At multivariate analysis, after correction for demographic and COVID-19 severity variables (NEWS2 and PiO2/FiO2), only Gas6 measured at baseline predicted an adverse prognosis with an odds ratio of 1.03 (C.I. 1.01-10.5). At ROC curve analysis, baseline Gas6 levels higher than 58.0 ng/ml predicted a severe disease evolution with 53.3% sensitivity and 77.6% specificity (area under the curve 0.653, p = 0.01 , likelihood ratio of 2.38, IQR: 1.46-3.87). Taken together, these results support the hypothesis that a dysregulation in the Gas6/TAM axis could play a relevant role in modulating the course of COVID-19 and suggest that plasma Gas6 may represent a promising prognostic laboratory parameter for this condition.

Background. SARS-CoV-2 is responsible for COVID-19, a clinically heterogeneous disease, ranging from being completely asymptomatic to life-threating manifestations. An unmet clinical need is the identification at disease onset or during its course of reliable biomarkers allowing patients’ stratification according to disease severity. In this observational prospective cohort study, patients’ immunologic and laboratory signatures were analyzed to identify independent predictors of unfavorable (either death or intensive care unit admission need) or favorable (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. Methods. Between January and May 2021 (third wave of the pandemic), we enrolled 139 consecutive SARS-CoV-2 positive patients hospitalized in Northern Italy to study their immunological and laboratory signatures. Multiplex cytokine, chemokine, and growth factor analysis, along with routine laboratory tests, were performed at baseline and after 7 days of hospital stay. Results. According to their baseline characteristics, the majority of our patients experienced a moderate to severe illness. At multivariate analysis, the only independent predictors of disease evolution were the serum concentrations of IP-10 (at baseline) and of C-reactive protein (CRP) after 7 days of hospitalization. Receiver-operating characteristic (ROC) curve analysis confirmed that baseline IP − 10 > 4271 pg / mL and CRP > 2.3 mg / dL at 7 days predict a worsening in clinical conditions (87% sensitivity, 66% specificity, area under the curve (AUC) 0.772, p < 0.001 and 83% sensitivity, 73% specificity, AUC 0.826, p < 0.001 , respectively). Conclusions. According to our results, baseline IP-10 and CRP after 7 days of hospitalization could be useful in driving clinical decisions tailored to the expected disease trajectory in hospitalized COVID-19 patients.

Red blood cell distribution width (RDW) has been studied as a prognostic biomarker for different chronic inflammatory diseases. In this paper we aim to evaluate its potential role in the prediction of early relapse in patients affected by polymyalgia rheumatica (PMR). We revised retrospectively clinical records of patients who received a diagnosis of PMR, according to 2012 ACR/EULAR classification criteria, for whom baseline clinical and laboratory data were available. The baseline RDW variation coefficient was correlated to the risk of relapse, in the first 6 months of the disease. We identified 44 patients [females 15 (34.0%)/males 29 (66.0%); median age 80 (72-83)], 9 of whom had an early relapse. These patients showed a larger median RDW than patients who did not relapse [13.7 (13.5-14.9)% vs 13.5 (12.7-14.2)%; p=0.04). The two groups were comparable for all the other clinical and laboratory parameters considered. Interestingly, patients in the higher half of the RDW distribution showed a shorter relapse-free survival (p

Red cell distribution width (RDW) is an unconventional biomarker of inflammation. We aimed to explore its role as a predictor of treatment response in rheumatoid arthritis (RA). Eighty-two RA patients (55 females), median age [interquartile range] 63 years [52-69], were selected by scanning the medical records of a rheumatology clinic, to analyze the associations between baseline RDW, disease activity scores and inflammatory markers, as well as the relationship between RDW changes following methotrexate (MTX) and treatment response. The lower the median baseline RDW, the greater were the chances of a positive EULAR response at three months, 13.5% [13.0-14.4] being among those with good response, vs 14.0% [13.2-14.7] and 14.2% [13.5- 16.0] (p=0.009) among those with moderate and poor response, respectively. MTX treatment was followed by a significant RDW increase (p

Giant cell arteritis (GCA) is characterized by two subsets: cranial GCA and large-vessel GCA (LV-GCA); positron emission tomography (PET) is an essential tool in the diagnosis of LV-GCA. In this study, we aimed to investigate its potential prognostic value in the stratification of relapse risk. We retrospectively revised all the clinical records of patients who received a diagnosis of GCA at an immuno-rheumatology clinic of a University Hospital along 6 years and who underwent to a PET-CT examination at diagnosis. Clinical, laboratory, and imaging data were collected. Relapses were recorded. The study population included 19 patients (10 females, 52.6%; median age 74.0 [65.5-76.0] years), 12 with typical cranial GCA (63%) and 7 (37%) with LV-GCA. Based on PET findings, a diagnosis of aortitis was made in 15/19 patients, including 8/12 patients with a classical cranial GCA (58%). Along a median follow-up of 15 months [4.5-26.5], 4 relapses were observed. All relapsers were male; indeed, the difference in gender distribution was the only variable reaching statistical difference between relapsers and non-relapsers. Specifically, aortitis was not more frequent among relapsers. Our study confirms PET as a valid tool in the identification of LV-GCA with no cranial involvement. We failed to demonstrate a role for PET in the prognostic stratification of GCA, while male gender is suggested as a potential risk factor for GCA relapse.Key Points• A significant proportion of patients with GCA presents with non-cranial disease, the identification of which requires imaging studies, among which PET is particularly useful.• Aortitis might be detected also in patients with the classical, cranial GCA type but does not seem to have prognostic implications, at least in terms of relapse risk.• Male gender is suggested as a risk factor for relapse in GCA.

BACKGROUND: COVID-19 has been mainly investigated concerning the acute and subacute phase implications and management. Meanwhile, few studies focused on the midterm sequelae, which still remain largely unknown. AIM: To assess the physical performance of COVID-19 survivors at 3 to 6 months from Hospital discharge. DESIGN: A cross-sectional study focused on mid-term functional outcomes evaluation in COVID-19 survivors. SETTING: Outpatients who had been previously hospitalized due to COVID-19 from March to May 2020 at the University Hospital of Novara, Italy. POPULATION: We enrolled 204 patients, of which 60% were men, with the mean age of 57.9 years. METHODS: Patients firstly underwent the short physical performance battery test (SPPB), which is composed of a series of physical tests assessing the lower limb function and the functional status of the subjects. Subsequently, based on SPPB results, patients' cardiorespiratory fitness performance was further investigated. Patients with normal SPPB score (SPPB>10) underwent the 2-minute walking test (2MWT) whereas, in order to safely test the cardiorespiratory function, in patients with abnormal SPPB score (SPPB≤10) the 1-minute sit-to-stand test (1MSTST) was performed. It should be noted that the 1MSTST can be safely performed even by subjects with compromised walking ability. RESULTS: Overall, 66 patients (32% of our sample) showed an impaired physical performance at 3 to 6 months after hospital discharge. In particular, 29 patients presented an SPPB score ≤10, and the 1MSTST confirmed this status in the whole group (100%) compared to the reference values for age and sex. Besides, among patients with a normal SPPB score, 37 showed a lower sex- and age-matched 2MWT score. Finally, a significant association between Intensive Care Unit hospitalization or mechanical ventilation and physical impairment was observed together with a significant association between the walking ability (measured with SPPB and 2MWT) and the number of comorbidities. CONCLUSIONS: A residual physical and functional impairment was observed in COVID-19 survivors at mid-term evaluation after hospitalization. CLINICAL REHABILITATION IMPACT: Considering the current COVID-19 epidemiology, we might expect a tremendous burden of disability in the next future. Thus, an appropriate clinical rehabilitation pathway must be implemented.

Key Points Question What respiratory, functional, and psychological sequalae are associated with recovery from coronavirus disease 2019 (COVID-19)? Findings In this cohort study of 238 patients with COVID-19 hospitalized in an academic hospital in Northern Italy, more than half of participants had a significant reduction of diffusing lung capacity for carbon monoxide or measurable functional impairment and approximately one-fifth of patients had symptoms of posttraumatic stress 4 months after discharge. Meaning These findings suggest that despite virological recovery, a sizable proportion of patients with COVID-19 experienced respiratory, functional, or psychological sequelae months after hospital discharge., This cohort study examines prevalence and risk factors associated with lung function or physical impairment or posttraumatic stress symptoms among survivors of severe coronavirus disease 2019 (COVID-19)., Importance Although plenty of data exist regarding clinical manifestations, course, case fatality rate, and risk factors associated with mortality in severe coronavirus disease 2019 (COVID-19), long-term respiratory and functional sequelae in survivors of COVID-19 are unknown. Objective To evaluate the prevalence of lung function anomalies, exercise function impairment, and psychological sequelae among patients hospitalized for COVID-19, 4 months after discharge. Design, Setting, and Participants This prospective cohort study at an academic hospital in Northern Italy was conducted among a consecutive series of patients aged 18 years and older (or their caregivers) who had received a confirmed diagnosis of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection severe enough to require hospital admission from March 1 to June 29, 2020. SARS-CoV-2 infection was confirmed via reverse transcription–polymerase chain reaction testing, bronchial swab, serological testing, or suggestive computed tomography results. Exposure Severe COVID-19 requiring hospitalization. Main Outcomes and Measures The primary outcome of the study was to describe the proportion of patients with a diffusing lung capacity for carbon monoxide (Dlco) less than 80% of expected value. Secondary outcomes included proportion of patients with severe lung function impairment (defined as Dlco

Staphylococcus condimenti (S. condimenti) is a coagulase-negative bacterium, generally regarded as not pathogenic. Indeed, S. condimenti owes its name to having been isolated from starter cultures of fermented sausage, as well as from fish and soy sauces. To the best of our knowledge, only two cases of human infection caused by this bacterium have been reported. Here, we present a case of meningitis by S. condimenti in a 65-year-old woman who was brought to hospital after having been found unconscious at home. At her arrival, she had a Glasgow coma scale = 3, fever, and hypoxic-normocapnic respiratory failure. Examination of her cerebrospinal fluid showed a slightly increased white blood cell count, normal glucose and protein concentrations. Paired cultures on blood and liquor samples yielded S. condimenti. Targeted antibiotic treatment with ceftriaxone led to a complete recovery. This unique case expands our knowledge on S. condimenti as a pathogenic bacterium.

Background: Red blood cell distribution width (RDW) has recently emerged as a possible surrogate biomarker of inflammation. Its potential role as prognostic biomarker has not been evaluated yet in Rheumatoid Arthritis (RA). Objectives: The following study aims to evaluate the potential prognostic role of RDW in the prediction of early response to methotrexate (MTX). Methods: We performed a retrospective analysis of clinical records of patients affected by RA, according to ACR/Eular classification Criteria. The baseline RDW was recorded and correlated with disease activity scores and inflammatory markers. The response to treatment was evaluated at the 3-months follow-up visit according to Eular response criteria. Results: We selected 88 patients (58 females, 65.9%), with a median age of 62 [52-69] years. 61 patients were positive for Rheumatoid Factor (RF) and/or anticitrullinated antibodies – anti-CCP (69.3%). The median DAS28 for Erythrocyte sedimentation rate (DAS28ESR) at the diagnosis was 4.16 [3.33-5.00] while the median RDW was 14.0 [13.1-14.9]%. The baseline RDW was directly associated to CRP (ρ= 0.250; p=0.02), but not with ESR (p=0.32) or DAS28ESR (p=0.40). All the patients received methotrexate (MTX) at a median dose of 10 [10-15] mg/week, 79 (89.8%) also received prednisone (median dose 5 [5-10] mg/day) and 20 hydroxychloroquine in addition to MTX. A significant trend towards a larger RDW was reported from patients with a good Eular response at three months (13.5 [13.0-14.4]%) to those with a moderate response (14.0 [13.2-14.7]%) and finally to those with a poor response (14.6 [13.6-16.0]%; p=0.004). At logistic regression, RDW (p=0.02), but not CRP or ESR (p=0.70 and p=0.37 respectively), was a predictor of a good Eular response. Moreover, in a further logistic regression model, baseline RDW (p=0.03) and baseline DAS28ESR (p=0.0009) were the only predictors of a good Eular response at three months, while age, gender, MTX and prednisone dosage and seropositivity did not fit the model. After the treatment RDW significantly increases (14.7 [14.0-15.7]%) and the variation of RDW from baseline is inversely related to the variation of DAS28ESR (ρ= -0.263; p=0.02). The increase of RDW is significantly higher in patients with a good Eular response, with a trend towards a smaller increase in case of moderate and poor response (0.95 [0.35-1.35]% vs. 0.65 [0.1-1.9]% vs. 0.2 [-0.62-0.77]%; p=0.015). Conclusion: RDW is a promising predictor of early response to MTX in RA; in this context, it performs better than classical inflammatory markers. Moreover, RDW significantly increases after MTX initiation, proportionately to response to treatment, suggesting a potential role for RDW as a marker of MTX effectiveness. Disclosure of Interests: None declared

Background Giant cell arteritis (GCA) is a large vessel vasculitis that affects the aorta and/or its major branches including the superficial temporal artery. Together to cranial symptoms such as headache and visual disturbances, extra cranial manifestations have been widely reported, sometimes as unique clinical presentation. Several imaging modalities are available to evaluate aortic involvement including fluorodeoxyglucose (FDG) positron emission tomography (PET), however there are few reports that analyzed the impact of the findings of this advanced imaging in predicting outcomes of the disease. Objectives To assess the utility of PET in disease extension assessment to predict, together to clinical manifestations, the disease evolution. Methods We retrospectively reviewed all the clinical records of patients receiving a diagnosis of large vessel vasculitis from 1st January 2010 to 1st January 2016 at a tertiary immunorheumatology clinic of a university Hospital, who underwent a PET. Clinical, laboratory, and imaging data were collected. Non-parametric analysis was performed. Results We recruited 19 patients (10 females, 52.6%). The median age was 74.0 [65.5-76.0]; at the diagnosis, the median erythrocyte sedimentation rate (ESR) was 65.5 [49.0-86.0], while C-reactive protein (CRP) was 8.5 [5.5-14.0]. 12 patients showed a typical cranial GCA (63.2%), while 7 (36.8%) were diagnosed with extracranial GCA. The two groups were comparable at diagnosis for age, gender, median ESR and CRP. Interestingly, the PET was significative for aortitis not only in the 7 patients with extracranial involvement, but also in 7/12 patients with cranial GCA (58.3%). Along a median follow-up of 15 months [4.5-26.5], 4 relapses were reported. Notably, all the relapsers were males and showed both aortic and cranial involvement. In a multivariate model, male gender was the only predictor of relapse (p=0.02), while age at onset, clinical subset (cranial vs. extracranial) and steroid dose did not fit the model Conclusion The use of PET in GCA is relevant in the assessment of extension of disease since a significative number of patients without cranial symptoms in the end resulted to have large vessel involvement. In addition, PET is useful in identifying patients with cranial involvement that have also aortic inflammation since they seems to have worse prognosis. Disclosure of Interests None declared

Background: Different neurological manifestations have been observed in 20-25% of patients affected by Sjogren’s syndrome (SS). Among them, CNS demyelinating diseases, Neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSD) with anti-aquaporin4 antibodies (anti-AQP4) positivity have been described. Objectives: The aim of the present study was to assess the clinical charachteristics and seroimmunological correlations in patients with Ro-SSA antibodies and Central and peripheral nervous system (CNS and PNS) involvement. Methods: We retrospectively reviewed clinical records, laboratory and Magnetic Resonance Imaging (MRI) reports of patients followed-up at a tertiary level immunorheumatology and neuroimmunology clinic. We included patients showing an anti-SSA antibodies positivity and concomitant neurological symptoms at diagnosis. We excluded patients fulfilling SLICC criteria for SLE. We recorded clinical and laboratory and MRI data for all patients. Results: Out of 9598 clinical records reviewed, we identified 511 patients with anti Ro/SSA positivity. 11 patients had prevalent neurological manifestations. 8 (72.7%) patients were women. The median age was 56 [IQR 31] years. CNS involvemente was the main clinical feature in 7 patients (63.6%); 3 of them (27.3%) also had PNS manifestations. 4 patients showed exclusively PNS involvement. 3 subjects fulfilled criteria for SS while 8 patients were classified as undifferentiated connective tissue disease. 7 patients underwent spinal tap which reported inflammatory alterations (high levels of CSF proteins in 2 subjects and oligoclonal bands in 4 patients). Median Erythrocyte sedimentation rate (ESR) was 12 mm/h [IQR 18] while median C- Reactive protein was 0.34 mg/dL [IQR 0.32]. There was not complement deficiency in any patient. With regard to the tested autoantibodies, 2 subjects showed also anti-La positivity. Out of the 4 patients tested for anti-AQP4 none was positive, even if 2 patients had NMODSD. Conclusion: Anti-SSA positive may show a wide spectrum of neurological manifestations; CNS involvement was not associated to anti-AQP4 positivity in our cohort, even in patients with NMO/NMOSD. Further investigations are required to better disclose this association and to search for novel autoantibodies. Disclosure of Interests: None declared

Serous effusions complicating the course of lymphomas occur commonly in the pleural space but seldom in the peritoneum, where they most often present as chylous ascites with diagnostic cytology. Almost invariably, in these rare cases, the serum to ascites albumin gradient is low. We describe a 28-year-old woman with anasarca, ascites and a serum to ascites albumin gradient of 1.1 g/dl, consistent with portal hypertension. No tumour cells were detected in the ascitic fluid. However, a CT scan of the chest and abdomen disclosed liver and spleen enlargement and multiple enlarged retroperitoneal lymph nodes, suspicious for a lymphoproliferative disorder. Bone marrow aspiration and biopsy were not diagnostic, so a decision was made to proceed with a splenectomy despite the onset of low-grade disseminated intravascular coagulation. Surgery was uneventful. Diffuse large B cell lymphoma was diagnosed. A liver biopsy taken at the time of surgery demonstrated that the liver parenchyma was massively infiltrated by reactive T lymphocytes surrounding rare large CD20+ tumour cells. This infiltrate had likely led to increased portal pressure attended by ascites formation, which resolved completely after chemotherapy. The case emphasizes the rewards of pursuing a diagnosis supported by a high prior probability even in the presence of apparently discordant laboratory findings, as well as the importance of performing a diagnostic splenectomy in case of splenomegaly with unexplained focal lesions. LEARNING POINTS Lymphomas may present with serous effusion, which is usually chylous and with positive cytology when represented by ascites accumulation; non-chylous effusions can be due to altered lymphatic drainage, extrinsic compression of the portal vein by enlarged lymph nodes as well as massive infiltration of the liver by lymphoma. If the cause of splenomegaly is unclear, diagnostic splenectomy remains a viable option. The diagnosis of lymphoma should always be pursued, even if it requires apparently unwise surgery, since this type of cancer can be treated effectively only if thoroughly characterized pathologically and molecularly. Keywords: Ascites, splenomegaly, lymphoma, disseminated intravascular coagulation, diagnostic splenectomy HOSPITAL GRAND ROUNDS Public University Hospital Maggiore della Carita, Novara, Italy by Editorial Board Member, Prof. Ettore Bartoli The Public University Hospital “Maggiore della Carita”, Novara, Italy, is a 700-bed teaching hospital, with 2700 employees. Approximately 500 of these are medical doctors. It is the home Institution for the Medical School of the “Universita del Piemonte Orientale”. In its early days it was a branch of the University of Turin and it became autonomous in 1998. Today, it admits 150 medical students and 80 interns a year and is strongly committed to pursuing excellence in education and research. In fact, according to the most recent CENSIS survey, it ranks 6th out of the 37 state universities nationwide. Despite its recent history as a university hospital, the roots of the “Maggiore” date back to the Middle Ages. Originally it was a charity institute dedicated to the Archangel Michael - hence the name “Casa di San Michele della Carita”. It was founded in the XI century with the aim of helping the poor, the elderly and the pilgrims. The care activity was addressed to aiding the sick only later, starting from the end of the thirteenth century. In 1482, a Bull of Pope Sixtus IV imposed the union between the Hospital of “S. Michele” with the other seven hospitals in Novara, confirming the importance assumed by this institution in its urban context. Open in a separate window CASE DESCRIPTION A 28-year-old woman was admitted to the internal medicine division of an academic hospital in northern Italy with complaints of progressive abdominal distention and fatigue. She also described substantial weight gain and anorexia over the previous 6 months. At physical examination, the patient appeared chronically ill. She was afebrile and all other vital parameters were normal, but there was anasarca, with marked swelling and erythema of the lower legs. There were no enlarged or palpable lymph nodes, but a protuberant abdomen, with central tympany and flank dullness at percussion, was noted. The remainder of the examination was normal. A full blood count revealed white blood cells (WBC) 7.69 ×109/l (81% neutrophils, 9% lymphocytes), red blood cells (RBC) 3.96×1012/l, haemoglobin 11.2 g/l, and platelets (PLTs) 143×109/l. Examination of a peripheral blood smear did not add significant information. Prothrombin time was 14.4 sec. Serological studies for human immunodeficiency virus, hepatitis B virus and hepatitis C virus were negative. Other laboratory results included lactate dehydrogenase (LDH) 688 IU/l (normal limits, 208–450 IU/l), total serum proteins 3.8 g/dl (6.4–8.3 g/dl), albumin 2.2 g/dl (3.5–5.5 g/dl) and total bilirubin 1.5 mg/dl (0.3–1.2 mg/dl). Renal function tests and electrolyte levels were normal. A paracentesis was performed with aspiration of a yellow-coloured, slightly turbid fluid whose analysis gave the following results: albumin 1.1 g/dl (serum to ascites albumin gradient of 1.1 g/dl), WBC 0.29×109/l, of which 31% were neutrophils and 69% lymphocytes, RBC 1000/μl, LDH 312 U/l (normal 105–245 U/l) and rare epithelial cells. Culture of the ascitic fluid and real time-polymerase chain reaction amplification for Mycobacterium tuberculosis were negative. A computed tomography (CT) scan of the abdomen and chest confirmed massive ascites, liver enlargement without focal lesions, thinning of the inferior vena cava and hepatic veins, enlargement of the spleen (longitudinal diameter, 15 cm) whose parenchymal architecture was distorted by several lesions (the largest being 5.38 cm in diameter), multiple enlarged retroperitoneal lymph nodes above the psoas muscle, small bilateral pleural effusions, and diffuse imbibition of the adipose tissue (Figs. 1 and ​and22). Open in a separate window Figure 1 Coronal view of a contrast-enhanced CT scan of the abdomen and chest, showing a distorted and enlarged spleen and a diffusely enlarged liver with no focal lesions

Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue diseases (CTD). Its early diagnosis is essential to start effective treatment. In the present paper, we aimed to evaluate the role of plasma osteopontin (OPN) as a candidate biomarker of PAH in a cohort of CTD patients. OPN is a pleiotropic protein involved in inflammation and fibrogenesis and, therefore, potentially promising in this specific clinical context. We performed a cross-sectional observational study on a cohort of 113 CTD patients (females N = 101, 89.4%) affected by systemic sclerosis N = 88 (77.9%), mixed connective tissue disease N = 10 (8.8%), overlap syndrome N = 10 (8.8%) or undifferentiated connective tissue disease N = 5 (4.4%). CTD-PAH patients showed significantly higher OPN plasma values than patients with CTD alone (241.0 (188.8–387.2) vs. 200.7 (133.5–281.6) ng/mL, p = 0.03). Although OPN levels were directly correlated with age and inversely with glomerular filtration rate, they remained associated with PAH at multivariate analysis. In conclusion, OPN was significantly associated with PAH among patients with CTD, suggesting it may have a role as a non-invasive disease biomarker of PAH.

The early diagnosis of pulmonary arterial hypertension (PAH) is a major determinant of prognosis in patients affected by connective tissue diseases (CTDs) complicated by PAH. In the present paper we investigated the diagnostic accuracy of cardiopulmonary exercise testing (CPET) in this specific setting. We recorded clinical and laboratory data of 131 patients who underwent a CPET at a pulmonary hypertension clinic. Out of them, 112 (85.5%) had a diagnosis of CTDs, 8 (6.1%) received a diagnosis of CTDs-PAH and 11 (8.4%) were affected PH of different etiology. Among CPET parameters the following parameters showed the best diagnostic performance for PAH: peak volume of oxygen uptake (VO2, AUC: 0.845, CI95% 0.767–0.904), ratio between ventilation and volume of exhaled carbon dioxide (VE/VCO2 slope, AUC: 0.888, CI95%: 0.817–0.938) and end-tidal partial pressures (PetCO2, AUC: 0.792, CI95%: 0.709–0.861). These parameters were comparable among CTDs-PAH and PH of different etiology. The diagnostic performance was even improved by creating a composite score which included all the three parameters identified. In conclusion, CPET is a very promising tool for the stratification of risk of PAH among CTDs patients, the use of composite measures may improve diagnostic performance.