Search

Background To arthroscopically evaluate the incidence of lateral meniscal root avulsion (LMRA) and associated intra-articular injuries in patients undergoing anterior cruciate ligament (ACL) reconstruction. Materials and Methods From April 2014 to March 2017, 532 consecutive patients were diagnosed as having an ACL injury and underwent arthroscopic ACL reconstruction. The diagnosis of LMRA was made arthroscopically. The effects of gender, activity, grade of laxity, time from injury, and concomitant meniscal lesions were analyzed. Results Among 532 patients, 497 (93.4%) underwent primary ACL reconstruction and 35 (6.5%) underwent revision procedures. 383 were acute or subacute injuries (less than 6 months from injury to surgery) and 149 chronic (more than 6 months). Average age was 30.4 years (DS: ± 11.04); there were 422 (79.3%) males and 110 (20.6%) females. A LMRA associated with the ACL injury was detected in 72 cases (13.5%), with a significant prevalence observed in males ($${\chi ^2}$$ χ 2 = 4.65; P = 0.031, statistically significant). In the 149 patients with a chronic injury, 27 patients had LMRA (18.1%), while 45 of the 383 patients with an acute or subacute injury had LMRA (11.7%). There was a tendency, albeit not significant ($${\chi ^2}$$ χ 2 = 3.721; P = 0.054), for the prevalence to increase with time since the initial ACL injury. LMRA was significantly associated ($${\chi ^2}$$ χ 2 = 7.81; P = 0.006) with a meniscocapsular tear of the posterior horn of the medial meniscus (ramp lesion). No other significant associations, such as with severity of A-P translation (as measured by KT-2000) or activity level, were detected. Conclusion LMRA is a relatively common injury associated with both acute and chronic ACL tears. A relatively high incidence in cases of chronic ACL insufficiency suggests that LMRAs do not heal spontaneously or that they may appear with time, even when absent at the time of the initial injury. Level of evidence Level III, cross-sectional study.

Objective Digital pitting scars (DPS) are frequent, but little studied in SSc to date. Methods An analysis of SSc patients enrolled in the EUSTAR database. Primary objectives were to (i) examine DPS prevalence; (ii) examine whether DPS are associated with digital ulcers (DUs) and active digital ischaemia (DUs or gangrene); and (iii) describe other associations with DPS including internal organ complications. Secondary objectives were whether DPS are associated with (i) functional impairment; (ii) structural microvascular disease; and (iii) mortality. Descriptive statistics and parametric/non-parametric tests were used. Binary logistic regression was used to examine the association between DPS and DUs, active digital ischaemia and mortality. Results A total of 9671 patients were included with reported DPS at any time point (n = 4924) or ‘never’ DPS (n = 4747). The majority (86.9%) were female and mean age was 55.7 years. DPS were associated with longer disease and Raynaud’s duration (both P ≤ 0.001). DPS were associated with interstitial lung disease, pulmonary hypertension, conduction blocks, telangiectases, calcinosis (all P ≤ 0.001) and joint synovitis (P = 0.021). Patients were more likely to have more severe capillaroscopic abnormality and greater hand functional impairment. Multivariable logistic regression analyses showed that DPS were associated (odds ratio) with DUs: 22.03 (19.51–24.87), active digital ischaemia: 6.30 (5.34–7.42) and death: 1.86 (1.48–2.36). Conclusion DPS are associated with a severe disease course including death. The impact of DPS on hand function and ischaemia is significant. The presence of DPS should alert the clinician to a poor prognosis and need to optimize the therapeutic strategy.

Aims The association between hyperglycemia at hospital admission and relevant short- and long-term outcomes in elderly population is known. We assessed the effects on mortality of hyperglycemia, disability, and multimorbidity at admission in internal medicine ward in patients aged ≥ 65 years. Methods Data were collected from an active register of 102 internal medicine and geriatric wards in Italy (RePoSi project). Patients were recruited during four index weeks of a year. Socio-demographic data, reason for hospitalization, diagnoses, treatment, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), renal function, functional (Barthel Index), and cognitive status (Short Blessed Test) and mood disorders (Geriatric Depression Scale) were recorded. Mortality rates were assessed in hospital 3 and 12 months after discharge. Results Of the 4714 elderly patients hospitalized, 361 had a glycemia level ≥ 250 mg/dL at admission. Compared to subjects with lower glycemia level, patients with glycemia ≥ 250 mg/dL showed higher rates of male sex, smoke and class III obesity. These patients had a significantly lower Barthel Index (p = 0.0249), higher CIRS-SI and CIRS-CI scores (p = 0.0025 and p = 0.0013, respectively), and took more drugs. In-hospital mortality rate was 9.2% and 5.1% in subjects with glycemia ≥ 250 and p = 0.0010). Regression analysis showed a strong association between in-hospital death and glycemia ≥ 250 mg/dL (OR 2.07; [95% CI 1.34–3.19]), Barthel Index ≤ 40 (3.28[2.44–4.42]), CIRS-SI (1.87[1.27–2.77]), and male sex (1.54[1.16–2.03]). Conclusions The stronger predictors of in-hospital mortality for older patients admitted in general wards were glycemia level ≥ 250 mg/dL, Barthel Index ≤ 40, CIRS-SI, and male sex.

Leukocytoclastic vasculitis (LCV) is a histopathologic description of a common form of small vessel vasculitis (SVV), that can be found in various types of vasculitis affecting the skin and internal organs. The leading clinical presentation of LCV is palpable purpura and the diagnosis relies on histopathological examination, in which the inflammatory infiltrate is composed of neutrophils with fibrinoid necrosis and disintegration of nuclei into fragments (“leukocytoclasia”). Several medications can cause LCV, as well as infections, or malignancy. Among systemic diseases, the most frequently associated with LCV are ANCA-associated vasculitides, connective tissue diseases, cryoglobulinemic vasculitis, IgA vasculitis (formerly known as Henoch–Schonlein purpura) and hypocomplementemic urticarial vasculitis (HUV). When LCV is suspected, an extensive workout is usually necessary to determine whether the process is skin-limited, or expression of a systemic vasculitis or disease. A comprehensive history and detailed physical examination must be performed; platelet count, renal function and urinalysis, serological tests for hepatitis B and C viruses, autoantibodies (anti-nuclear antibodies and anti-neutrophil cytoplasmic antibodies), complement fractions and IgA staining in biopsy specimens are part of the usual workout of LCV. The treatment is mainly focused on symptom management, based on rest (avoiding standing or walking), low dose corticosteroids, colchicine or different unproven therapies, if skin-limited. When a medication is the cause, the prognosis is favorable and the discontinuation of the culprit drug is usually resolutive. Conversely, when a systemic vasculitis is the cause of LCV, higher doses of corticosteroids or immunosuppressive agents are required, according to the severity of organ involvement and the underlying associated disease.

Objective To analyse the available evidence about the use of rituximab (RTX) and other biologic agents in eosinophilic granulomatosis with polyangiitis (EGPA) patients and to provide useful findings to inform the design of future, reliable clinical trials. Methods A systematic review was performed. A systematic search was conducted in PubMed/MEDLINE, Scopus, Web of Science and the Cochrane library databases on RTX, and an extensive literature search was conducted on other biologic agents. Results Forty-five papers pertinent to our questions were found: 16 retrospective cohort studies, 8 case series, 3 prospective cohort studies and 18 single case reports, for a total of 368 EGPA patients. More than 80% of evaluable patients achieved complete or partial remission with a tendency towards a higher rate of complete response in the pANCA-positive subgroup. Conclusion Although the majority of the evaluable EGPA patients treated with RTX appears to achieve complete remission, we strongly believe that a number of sources of heterogeneity impair a clear interpretation of results and limit their transferability in clinical practice. Differences in design, enrolment criteria, outcome definition and measurement make a comparison among data obtained from studies on RTX and other biologic agents unreliable.

Background: Psoriatic Arthritis (PsA) is the most common extracutaneous manifestation of psoriasis. This chronic inflammatory arthritis is burdened with significant morbidity, leading to irreversible joint damage and disability. In recent years, a deeper understating of its pathogenesis has led to the development of several new drugs targeting different pathways. Objectives: This review aims to highlight the clinical efficacy and safety of the novel agents that have become recently available for the treatment of PsA, as well as new promising therapeutic targets that are being evaluated in clinical trials. Methods: For the purpose of this narrative review, we searched in the MEDLINE and ClinicalTrials. gov databases. Results: After the introduction of the first biological drugs targeting Tumor Necrosis Factor (TNF), several other drugs with different targets have been developed, including anti-Interleukin (IL) 12/23p40, anti-IL17, and, more recently, anti-IL23p19 agents. Conclusions: Data supporting the efficacy of different agents in the major domains of PsA, as well as their safety issues, are summarized here. Finally, the current pipeline, including several novel nonbiological small molecules, such as Janus kinase (JAK) inhibitors, that are currently being evaluated in clinical trials are also presented. Discussion: The availability of newer therapeutic agents has substantially changed the treatment strategy for PsA. In the future, a personalized treatment approach will probably achieve better control of disease manifestations.

Systemic sclerosis (scleroderma, SSc) is a systemic disease characterized by vascular lesions, fibrosis, and circulating autoantibodies. A complex interplay between innate and adaptive immunity, and with regard to the latter, between humoral and cellular immunity, is believed to be involved in SSc pathogenesis. Lately, close attention has been paid to the role of B cells which, once activated, release profibrotic cytokines, promote profibrotic Th2 differentiation, and produce autoantibodies. Several novel interesting autoantibodies, targeting antigens within the extracellular matrix or on the cell surface, rather than the nuclear antigens of canonical SSc-autoantibodies, have been recently described in patients with SSc. As they show stimulatory or inhibitory activity or react with structures involved in the pathogenesis of SSc lesions, they can be considered as potentially pathogenic. In this paper, we will review those which have been better characterized.

Background The aim of this study was to evaluate and compare the internal and external responsiveness of a computed-aided method (CaM) with a conventional visual reader-based score (CoVR) to measure interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) on high resolution computed tomography (HRCT). Methods Forty-five patients were evaluated in this retrospective cohort. HRCTs were collected at baseline and after 1 year. HRCT abnormalities were evaluated according to a CoVR (Warrick's method) and a quantitative CaM. Internal 1-year responsiveness was tested with a standardized mean response (SRM). Analyses of the receiver operating characteristic curves (ROCs) evaluated the sensitivity and specificity of the two methods to discriminate between clinically relevant progression and no relevant progression, using expert judgment as the gold standard (external responsiveness). Results In one year, lung involvement was stable/improved in 17 of the 45 patients (37.8%) and worsened in 28 patients (62.2%). HRCT scores changed moderately over the follow-up period. Using SFM, CaM was significantly more responsive in detecting changes due to treatment than the CoVR method. Likewise, in the analysis of the ROC curve, CaM scores showed the highest performance (AUC ROC CaM vs. CoVR, 0.951 vs. 0.807; p = 0.0065). Conclusion Quantitative analysis of CaM was more responsive than the CoVR method to accurately evaluate and monitor SSc-ILD progression or response to therapy.

Significance: A systematic approach to develop experts-based recommendations could have a favorable impact on clinical problems characterized by scarce and low-quality evidence as heel pressure ulcers. Recent Advances: A systematic approach was used to conduce a formal consensus initiative. A multidisciplinary panel of experts identified relevant clinical questions, performed a systematic search of the literature, and created a list of statements. GRADE Working Group guidelines were followed. An independent international jury reviewed and voted recommendations for clinical practice. Consent was developed according to Delphi rules and GRADE method was used to attribute grade of strength. Critical Issues: The extensive search of the literature retrieved 42 pertinent articles (26 clinical studies, 7 systematic reviews or meta-analysis, 5 other reviews, 2 consensus-based articles, and 2 in vitro studies). Thirty-five recommendations and statements were created. Only 1 of 35, concerning ankle–brachial pressure index reliability in diabetic patients, was rejected by the panel. No sufficient agreement was achieved on toe brachial index test to rule out the orphan heel syndrome, removing dry eschar in adult patients without vascular impairment, and using an antimicrobial dressing in children with infected heel pressure injuries. Eleven recommendations were approved with a weak grade of strength. Experts strongly endorsed 20 recommendations. Offloading, stages I and II pressure injuries, and referral criteria were areas characterized by higher level of agreement. Future Directions: We believe that the results of our effort could improve practice, especially in areas where clear and shared opinions emerged. Barriers and limits that could hinder implementation are also discussed in the article.

The concern about the offspring’s health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.

Objective Arthritis is the most frequent extra-intestinal manifestation in patients with inflammatory bowel diseases (IBD). The coexistence of intestinal and articular inflammation advocates the need for a multidisciplinary management of patients with IBD-associated spondyloarthritis. Methods Consecutive IBD patients were evaluated jointly by the gastroenterologist and the rheumatologist in a combined clinic. All the patients were assessed and screened for articular involvement, disease activity and health related quality of life. After the prescription of a shared treatment, patients with spondyloarthritis were followed up for 24 months. Results Two hundred sixty-two IBD patients, including 80 who were classified as affected by spondyloarthritis according to the ASAS criteria, were included in the study. At baseline, patients with both IBD and spondyloarthritis showed worse quality of life in both the physical and mental domains. The multidisciplinary management provided a significant improvement of gastrointestinal and articular manifestations, as well as the health-related quality of life. Moreover, global and gastrointestinal-specific quality of life significantly correlated with articular disease activity. Conclusion The multidisciplinary management significantly improves both articular and gastrointestinal disease activities and the quality of life of patients with IBD-associated spondyloarthritis. An appropriate screening strategy and the integrated management of these patients should be encouraged and employed in clinical practice.

Background: Belimumab was recently approved for treatment of lupus glomerulonephritis (LN). Aim: To evaluate renal response and its predictors in LN patients receiving belimumab in real-life. Patients and methods: We considered all patients fulfilling the SLEDAI-2K renal items and/or having estimated glomerular filtration rate (eGFR)≤60 ml/min/1.73 m2, with positive anti-dsDNA and/or low C3/C4 enrolled in the multicentre Italian lupus cohort BeRLiSS (BElimumab in Real LIfe Setting Study), treated with monthly IV Belimumab 10 mg/kg over standard treatment. Primary efficacy renal response (PERR), defined as proteinuria ≤0.7 g/24 h, eGFR≥60 ml/min/1.73 m2 without rescue therapy, was considered as primary outcome. Complete renal response (CRR; proteinuria

Highlights • Tocilizumab (TCZ) is currently being tested in COVID‐19‐induced cytokine storm. • COVID-19 patients responding to TCZ have higher post-treatment levels of circulating miR-146a. • Low levels of miR-146a are associated with death in COVID-19 patients not responding to TCZ. • MicroRNAs can represent biomarkers of response to anti-inflammatory interventions in COVID-19., Current COVID-19 pandemic poses an unprecedented threat to global health and healthcare systems. The most amount of the death toll is accounted by old people affected by age-related diseases that develop a hyper-inflammatory syndrome. In this regard, we hypothesized that COVID-19 severity may be linked to inflammaging. Here, we examined 30 serum samples from patients enrolled in the clinical trial NCT04315480 assessing the clinical response to a single-dose intravenous infusion of the anti-IL-6 receptor drug Tocilizumab (TCZ) in COVID-19 patients with multifocal interstitial pneumonia. In these serum samples, as well as in 29 age- and gender-matched healthy control subjects, we assessed a set of microRNAs that regulate inflammaging, i.e. miR-146a-5p, miR-21-5p, and miR-126-3p, which were quantified by RT-PCR and Droplet Digital PCR. We showed that COVID-19 patients who did not respond to TCZ have lower serum levels of miR-146a-5p after the treatment (p = 0.007). Among non-responders, those with the lowest serum levels of miR-146a-5p experienced the most adverse outcome (p = 0.008). Our data show that a blood-based biomarker, such as miR-146a-5p, can provide clues about the molecular link between inflammaging and COVID-19 clinical course, thus allowing to better understand the use of biologic drug armory against this worldwide health threat.

Objectives Gut microbiota has been widely reported to be involved in systemic inflammation through microbial translocation and T cell activation in several diseases. In this work we aimed to investigate bacterial infiltration and epithelial impairment in the gut of patients with IBD-associated SpA (SpA-IBD), as well as the relationship of microbial translocation with immune system activation and their putative role in the pathogenesis of joint inflammation in IBD patients. Methods Tight-junction proteins (TJPs) occludin and claudin-1/-4 and bacteria were assessed by real-time PCR analysis and immunohistochemical staining of the ileum. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharides (LPS), soluble CD14 (sCD14), sclerostin and anti-sclerostin antibodies (anti-sclerostin-IgG) were assayed with ELISAs and peripheral mononuclear blood cells with flow cytometry. LPS and sCD14 were used in vitro to stimulate a human osteoblast cell line. Results Compared with IBD, ileal samples from SpA-IBD patients showed bacterial infiltration, epithelial damage and downregulation of TJPs. In sera, they showed higher serum levels of I-FABP, LPS, sCD14 (the latter correlating with sclerostin and anti-sclerostin-IgG) and higher CD80+/CD163+ and lower CD14+ mononuclear cells. In vitro experiments demonstrated that only the LPS and sCD14 synergic action downregulates sclerostin expression in osteoblast cells. Conclusion SpA-IBD patients are characterized by gut epithelium impairment with consequent translocation of microbial products into the bloodstream, immune system activation and an increase of specific soluble biomarkers. These findings suggest that gut dysbiosis could be involved in the pathogenesis of SpA-IBD and it could hopefully prompt the use of these biomarkers in the follow-up and management of IBD patients.

Gastric antral vascular ectasia (GAVE), or watermelon stomach, is a rare acquired vascular disorder, characterized by multiple longitudinal stripes of red vessels originating from the pylorus and involving the antrum. In recent years, GAVE emerged as a potential gastrointestinal complication in patients with systemic sclerosis, with an estimated prevalence that ranges between 1% and 22.3%. GAVE usually presents with a refractory iron-deficiency anemia, that may require repeated blood transfusions, due to recurring gastrointestinal bleeding. Given the close association between GAVE and anti-RNA polymerase III antibodies, screening these high risk patients with endoscopy should be considered even in absence of anemia or gastric-related symptoms. Endoscopic methods, including thermal and mechanical techniques, are the treatment of choice for GAVE-related bleeding. In patients with GAVE and systemic sclerosis that are refractory to endoscopic therapy, cyclophosphamide and autologous hematopoietic stem cell transplantation may be an effective treatment option.

Background and objectiveSystemic small vessel vasculitides carry an increased risk of acute arterial and venous thromboembolic events (AVTE); however, this risk has not been systematically explored in Eosinophilic Granulomatosis with Polyangiitis (EGPA). This study assessed the occurrence and main risk factors of AVTE among EGPA patients as compared to the general community from the population-based Bruneck cohort.MethodsWe conducted a retrospective multicenter cohort study on 573 EGPA patients. Clinical and serological data were collected at diagnosis. Occurrence of AVTE and time to the first AVTE after EGPA diagnosis were recorded. Age-standardized event rate (SER) of AVTE as compared to the reference cohort was assessed. Cox regression was applied to identify AVTE predictors.Results129 EGPA patients (22.5%) had AVTE, considered as potentially life-threatening in 55.8%. Seventy patients experienced an AVTE prior to diagnosis (of whom 58.6% in the two years before diagnosis) and 75 following EGPA diagnosis, of whom 56% in the two subsequent years. The SER of AVTE as compared to the reference cohort was 2.10 (95% CI 1.67-2.63). This risk was particularly increased in patients with history of AVTE and with a Birmingham Vasculitis Activity Score ≥20 at diagnosis. Patients receiving immunosuppression within 2 months of diagnosis were at lower risk, while antiplatelet or anticoagulant treatment did not confer measurable benefit.ConclusionEGPA is associated with AVTE in approximately one quarter of patients, particularly around diagnosis. Immunosuppressants seemed to exert a protective effect, while anticoagulant and antiplatelet agents did not.

Background Cardiac involvement in SSc is frequent, mostly subclinical and represents a negative prognostic factor. Speckle tracking derived measurement global longitudinal strain (GLS) has been able to identify primary heart involvement in patients with SSc and no overt cardiac disease. SSc-related cardiomyopathy, defined as a condition affecting the heart primarily and globally, has been proven to progress over time and seems to be correlated to cardiac arrhythmias. Nonetheless, cardiac arrhythmias represent 6% of the overall causes of death in SSc patients. Purpose The aim of our study was to assess the incidence of cardiac arrhythmias in SSc patients with no overt cardiac disease and to identify potential predictors. Methods Prospective longitudinal study enrolling all consecutive patients with a diagnosis of SSc and no overt cardiac disease or pulmonary hypertension. Echocardiographic parameters and GLS were obtained at baseline and at each follow up. Presence of atrial fibrillation (AF), atrial tachycardia (AT), ventricular ectopic beats >1000/24 h (VEB), supraventricular ectopic beats (SVEB), bundle branch block (BBB) and atrioventricular block (AVB) was assessed through clinical history, ECG and 24-Holter monitoring over time. Results Among 67 consecutive patients with SSc, 11 (16.7%) had at least one episode of AF or AT. Moreover, respectively 12 (17.9%) and 16 (23.9%) had a significant amount of SVEB and VEB at Holter monitoring. Conduction defects were common, with 4 (4.6%) of all patients with grade I AVB, 1 (1.5%) with grade II AVB and 1 (1.5%) with complete heart block. Complete right BBB was seen in 6 (6.9%) of patients. Four patients (4.6%) experienced a sudden cardiac death during follow-up (median 20 months, 1st-3rd quartile 12–24 months). Years from SSc diagnosis (RR 1.10; 95% CI 1.02–1.23; p=0.047) and indexed right atrial volume (iRAV; RR 1.22; 95% CI 1.07–1.39; p=0.004), but not indexed left atrial volume were independently correlated with the diagnosis of AF/AT. The same two variables were independently correlated with any degree of AV block (years from SSc diagnosis: RR 1.11; 95% CI 1.01–1.23; p=0.004; iRAV: RR 1.14; 95% CI 1.02–1.27; p=0.019). Due to the low sample size, we were unable to detect any clinical predictors of sudden cardiac death in our population, however those who died experienced a larger worsening in left ventricle GLS values (4.0±1.6 vs. 0.9±0.4, p=0.056). Conclusions Supraventricular arrhythmias and conduction defects are common in patients with SSc. Time from diagnosis and right atrial volumes are able to predict the incidence of such conditions, supporting the hypothesis that a long-lasting disease and the anatomical remodelling of the right atrium could contribute to the developing of tachy- and bradyarrhythmias in this population. Funding Acknowledgement Type of funding source: None

The rarity of systemic sclerosis (SSc) and its widely heterogeneous presentation and disease course are the main limitations for clinical research. The European Scleroderma Trials and Research group (EUSTAR) was launched in 2004, aiming to unify research efforts in the field of SSc. The central EUSTAR database has grown exponentially over the years, promoting new research and clinical trials, shedding new light on SSc diagnosis, its clinical course and providing new ideas for state-of-the-art therapy.Areas covered: The authors summarized key findings of the main EUSTAR studies by reviewing PubMed and Web-of-Science databases through July 2020. The authors focused on the very early diagnosis of SSc, the prediction of disease course and mortality, the evaluation of disease activity and quality of life, the general management and therapy.Expert opinion: The findings elucidated in EUSTAR studies have substantially improved the diagnostic and therapeutic approach to SSc in the last fifteen years. Further efforts are warranted to identify early prognostic markers of the disease and stratify patients who may benefit most from vasoactive, immunosuppressive, and/or antifibrotic therapy. This will be particularly important in leading the future of SSc towards precision medicine and to promote more targeted clinical trials.

Background: Multiple studies have been conducted to investigate Tocilizumab in patients with cOVID-19 pneumonitis. However, published reports show conflicting results, largely due to weak retrospective designs and heterogeneity in critical methodological issues.Methods: This open-label trial was structured according to the Simon’s optimal two-stage design in order to clarify which patients could really benefit from anti-IL6 strategies and how a future randomized trial should be designed to provide reliable and unequivocal results. 46 patients received a single infusion of Tocilizumab. Inclusion criteria were: SARS-CoV2 infection diagnosed by rt-PCR, multifocal interstitial pneumonia, need of oxygen therapy (FiO2 50%) to maintain SO2 >93%, recent (within the last 24 hours) worsening of lung function. Clinical outcomes were established a priori to assess whether a patient responded to treatment. A low number of carefully chosen clinical and biological markers was measured in order to test their predictive values. Primary end point was early and sustained clinical response. Results: Twenty-one (46%) patients fulfilled pre-defined response criteria. Lower levels of IL-6 at 24 hours after tocilizumab infusion (p=0.049) and higher baseline values of PaO2/FiO2 (p=0.008) predicted a favorable clinical response. Patients not improving at 72 hours were also non-responder at day 7. 11/25 of non-responder patients were intubated and 7 died. High levels of vWF were detected in all sera, with a tendency towards higher concentrations in the non-responder group. Conclusions: Objective clinical response rate overcame the pre-defined threshold of 30%. Efficacy of tocilizumab to improve respiratory function in selected patients with severe COVID-19 pneumonitis warrants investigations in randomized trials. Trial registration: NCT 04315480

BackgroundCurrent COVID-19 pandemic poses an unprecedented threat to global health and healthcare systems. At least in western countries, the most amount of the death toll is accounted by old people affected by age-related diseases. In this regard, we proposed that COVID-19 severity may be tightly related to inflammaging, i.e. the age-related onset of inflammation, which is responsible for age-related diseases. It has been reported that systemic hyper-inflammation may turn to be detrimental in COVID-19 patients.ObjectiveHere, we exploited a recently closed clinical trial (NCT04315480) on the anti-IL-6 drug tocilizumab to assess whether microRNAs regulating inflammaging can be assessed as biomarkers of drug response and outcome.MethodsSerum levels of miR-146a-5p, −21-5p, and −126-3p were quantified by RT-PCR and Droplet Digital PCR by two independent laboratories on 30 patients with virologically confirmed COVID-19, characterized by multifocal interstitial pneumonia confirmed by CT-scan and requiring oxygen therapy, and 29 age- and gender-matched healthy control subjects. COVID-19 patients were treated with a single-dose intravenous infusion of 8 mg/kg tocilizumab and categorized into responders and non-responders.ResultsWe showed that COVID-19 patients who did not respond to tocilizumab have lower serum levels of miR-146a-5p after the treatment (p=0.007). Moreover, among non-responders, those with the lowest serum levels of miR-146a-5p experienced the most adverse outcome (p=0.008).ConclusionOur data show that blood-based biomarkers, such as miR-146a-5p, can provide a molecular link between inflammaging and COVID-19 clinical course, thus allowing to enlarge the drug armory against this worldwide health threat.

Impaired hand function is a major contributor to overall disability and reduced health-related quality of life in scleroderma patients. A relevant issue concerns interaction of scleroderma subjects with touchscreen interfaces. This study aims at investigating this problem assessing scleroderma patients’ performance with a novel, aptly designed, touchscreen application in order to identify critical items of touchscreen technology which may impair or facilitate the use by scleroderma subjects. Eighty scleroderma patients performed this novel application including three games, each of which tested a different gesture: tapping, dragging/dropping, and pinching-to-zoom. Eighty healthy subjects without hand impairments were recruited as controls. Scleroderma patients performed worse than healthy users in each game, and statistically significant negatively impacting items were identified. In the second phase of the study, the 10 worst touchscreen performers within the scleroderma cohort were recruited for a physio-rehabilitation trial based on the daily use at home of a modified version of the software application downloaded into the personal devices of patients. The results of this study allow introduction of guidelines to design accessible touchscreen interfaces for subjects with scleroderma and suggest that touchscreen technology may be included in self-administered physio-rehabilitation programs for scleroderma hand.

Aims Cardiac involvement in patients with systemic sclerosis (SSc) is frequent and represents a negative prognostic factor. Recent studies have described subclinical heart involvement of both the right ventricle (RV) and left ventricle (LV) via speckle-tracking-derived global longitudinal strain (GLS). It is currently unknown if SSc-related cardiomyopathy progresses through time. Our aim was to assess the progression of subclinical cardiac involvement in patients with SSc via speckle-tracking-derived GLS. Methods This was a prospective longitudinal study enrolling 72 consecutive patients with a diagnosis of SSc and no structural heart disease nor pulmonary hypertension. A standard echocardiographic exam and GLS calculations were performed at baseline and at follow-up. Results Traditional echocardiographic parameters did not differ from baseline to 20-month follow-up. LV GLS, despite being already impaired at baseline, worsened significantly during follow-up (from –19.8 ± 3.5% to –18.7 ± 3.5%, p = .034). RV GLS impairment progressed through the follow-up period (from –20.9 ± 6.1% to –18.7 ± 5.4%, p = .013). The impairment was more pronounced for the endocardial layers of both LV (from –22.5 ± 3.9% to –21.4 ± 3.9%, p = .041) and RV (–24.2 ± 6.2% to –20.6 ± 5.9%, p = .001). A 1% worsening in RV GLS was associated with an 18% increased risk of all-cause death or major cardiovascular event (p = .03) and with a 55% increased risk of pulmonary hypertension (p = .043). Conclusion SSC-related cardiomyopathy progresses over time and can be detected by speckle-tracking GLS. The highest progression towards reduced deformation was registered for the endocardial layers, which supports the hypothesis that microvascular dysfunction is the main determinant of heart involvement in SSc patients and starts well before overt pulmonary hypertension.

Introduction Spondyloarthrits (SpA) share clinical, genetic and immunological features with Inflammatory Bowel Diseases (IBD), and enteropathic SpA (eSpA) represent the clinical evidence of the association between gut and joint diseases. This cross-sectional study aimed to report data of eSpA patients collected from the first Italian database. Patients and methods A specific web-based interface has been created to insert and collect the main clinical, serologic and imaging data from patients with eSpA, as well as disease activity, comorbidities and treatment, in a real-life scenario. Results Data were collected in 14 Italian centers (7 rheumatology and 7 gastroenterology units). A total of 347 eSpA patients were enrolled in the study. Type 1 peripheral eSpA was the most frequent form. Crohn’ Disease (CD) was the most represented IBD. CD activity was similar among eSpA, whereas UC activity was slightly higher in the axial and mixed form than in the peripheral eSpA. The disease was active in less than half of axial eSpA patients and in only 18% of patients with peripheral eSpA. Furthermore, most of the patients had an inactive IBD. Nineteen percent of the total eSpA patients were free of therapy at the time of the enrollment and 61% of the patients were receiving biotechnological agents. Conclusions The multidisciplinary management of eSpA patients, favored by this ad hoc created web-based platform, allowed to obtain data from the largest eSpA cohort. The information coming of this database might advance knowledge of eSpA and improve their standard of care.

Clinica Medica and Ematologica in Ancona stemmed some 30 years ago from one originator medical team dedicated to Internal Medicine practice with a special interest towards immunological and hematological studies. This original scientific interest has spread over a multitude of fellows, some of whom have reached outstanding academic and clinical results, maintaining and extending the excellent reputation of the founding group over the years and until the present time. The best scientific achievements have been obtained in the field of systemic sclerosis and chronic graft versus host disease, whereas the clinical activity has been successfully dedicated to the management of autoimmune diseases and hematological disorders, with particular attention to innovative immunomodulatory therapies and stem cell transplantation.

Gastrointestinal (GI) involvement is almost universal in patients with systemic sclerosis (SSc) and is associated with significant disease-related morbidity and mortality.1 The entire GI tract can be involved and other disease features (eg, low mood, terminal organ failure and functional hand impairment) can result in significant nutritional impairment. Severe GI involvement has been reported to occur in ~10% of patients with SSc and often occurs early in the course of the disease.2 However, identification of patients at high risk of clinically significant weight loss is extremely challenging, including from the high prevalence of GI symptoms in patients with SSc. Therefore, there is a need to understand high-risk patients including potentially modifiable risk factors, with a view to early intervention strategies. Against this background, the aim of this study was to examine potential clinical risk factors of significant weight loss in patients with SSc. We performed an analysis of patients with SSc enrolled in the multinational, longitudinal European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) database. In our study, we defined significant weight loss as 4.5 kg and/or least 5% of their body weight at 5 months onwards.3 Patients with a recorded second visit after 3 months and before 12 months were included in the analysis. We adopted a pragmatic approach (relevant to clinical practice) in …

Objective To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus (SLE) who were treated with belimumab. Methods In this retrospective study of a multicenter cohort of SLE patients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to the SLE Responder Index 4 (SRI-4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was used to score disease damage yearly over the follow-up. Predictors of outcomes were analyzed by multivariate logistic regression with the results expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Results The study included 466 patients with active SLE from 24 Italian centers, with a median follow-up period of 18 months (range 1-60 months). An SRI-4 response was achieved by 49.2%, 61.3%, 69.7%, 69.6%, and 66.7% of patients at 6, 12, 24, 36, and 48 months, respectively. Baseline predictors of response at 6 months included a score of ≥10 on the SLE Disease Activity Index 2000 (SLEDAI-2K) (OR 3.14 [95% CI 2.033-4.860]) and a disease duration of ≤2 years (OR 1.94 [95% CI 1.078-3.473). Baseline predictors of response at 12 months included a score of ≥10 on the SLEDAI-2K (OR 3.48 [95% CI 2.004-6.025]) and an SDI score of 0 (OR 1.74 [95% CI 1.036-2.923]). Baseline predictors of response at 24 months included a score of ≥10 on the SLEDAI-2K (OR 4.25 [95% CI 2.018-8.940]) and a disease duration of ≤2 years (OR 3.79 [95% CI 1.039-13.52]). Baseline predictors of response at 36 months included a score of ≥10 on the SLEDAI-2K (OR 14.59 [95% CI 3.54-59.79) and baseline status of current smoker (OR 0.19 [95% CI 0.039-0.69]). Patients who were in remission for ≥25% of the follow-up period (44.3%) or who had low disease activity for ≥50% of the follow-up period (66.1%) accrued significantly less damage (P = 0.046 and P = 0.007). A baseline SDI score of 0 was an independent predictor of achieving low disease activity in ≥50% of the follow-up period and remission in ≥25% of the follow-up period. Our findings suggest that the lower the baseline damage, the greater the probability of achieving remission over the course of ≥25% of the follow-up. Further, there was a negative association between the number of flares reported prior to belimumab initiation and the frequency of belimumab discontinuation due to inefficacy (P = 0.009). Conclusion In patients with active SLE and low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real-life setting.

Objectives The prevalence and clinical implications of small airways involvement in SSc are still to be fully elucidated. The goal of the present work is to assess the prevalence of small airways dysfunction by impulse oscillometry and to determine whether it correlates with selected disease-related features and respiratory-related quality of life. Methods Ninety-four SSc patients and 93 healthy controls were studied by impulse oscillometry measurements. Small airways dysfunction was defined as the difference between resistance at low frequency, i.e. 5 Hz, and resistance at high frequency, i.e. 20 Hz, termed ‘R5-R20’, ⩾0.07 kPa/l/s. The St George’s Respiratory Questionnaire was used to measure health impairment in SSc patients. Radiological features of small airways disease and parenchymal abnormalities on high resolution CT chest scans were jointly assessed by two thoracic radiologists. Results Small airways dysfunction was present in 21.5% of the SSc patient cohort, with a prevalence almost 5-fold higher compared with controls, and it was significantly associated with worse respiratory-related quality of life. Radiological features consistent with small airways abnormalities were detected in 25% of SSc patients, mostly in the absence of interstitial lung changes. Combining functional and radiological evaluations, one-third of the SSc cohort showed at least one feature of small airways involvement, which was associated with the lcSSc phenotype and with longer disease duration. Conclusion The current study strengthens the hypothesis that small airway dysfunction might be a feature of SSc-related lung involvement, providing the first data on its significant impact on respiratory-related quality of life. A full assessment of lung function in SSc patients should include impulse oscillometry as a complementary technique, due to potential clinical and therapeutic implications.

Background Immune checkpoint inhibitors are a new promising class of antitumor drugs that have been associated with a number of immune-related Adverse Events (AEs), including musculoskeletal and rheumatic disease. Methods We searched Medline reviewing reports of musculoskeletal and rheumatic AEs induced by immune checkpoint inhibitors. Results Several musculoskeletal and rheumatic AEs associated with immune checkpoint inhibitors treatment are reported in the literature. In particular, arthralgia and myalgia were the most common reported AEs, whereas the prevalence of arthritis, myositis and vasculitis is less characterized and mainly reported in case series and case reports. Other occasionally described AEs are sicca syndrome, polymyalgia rheumatica, systemic lupus erythematosus and sarcoidosis. Conclusion Newly induced musculoskeletal and rheumatic diseases are a frequent adverse event associated with immune checkpoint inhibitors treatment.

In our study, we aimed to demonstrate whether a complex iatrogenic clubfoot really exists; identify the causative mechanisms; and determine the outcome if properly treated. We observed 54 clubfeet previously treated unsuccessfully by manipulation and casting elsewhere. All the feet had been classified at diagnosis as typical clubfeet. In 26 cases, the cast had slipped down, entrapping the foot in a plantar-flexed position. Nine clubfeet out of those 26 cases presented the clinical features of a complex iatrogenic deformity. These were treated with the modified Ponseti protocol and evaluated at follow-up according to the International Clubfoot Study Group Score. The length of follow-up averaged 7.2 years. Two feet showed an excellent result, five feet showed a good result, and two feet showed a fair result. The relapse rate was 55% in complex clubfeet. Relapsed clubfeet were treated by Achilles tenotomy or lengthening and anterior tibial tendon transfer. We believe that faulty manipulation and a poor casting technique may convert a typical clubfoot into a complex iatrogenic deformity. Risk factors include severe clubfoot, short and stubby foot, and unmolded casts slipping down.

Psoriatic arthritis (PsA) is a chronic inflammatory autoimmune arthritis, occurring in patients with psoriasis (Pso), that may affect the whole musculoskeletal system but also nails, eye, and gastrointestinal tract. Dermatologists and rheumatologists usually manage Pso and PsA separately, but early diagnosis and integrated management could achieve better outcomes of both skin and musculoskeletal manifestations, thus improving the health-related quality of life (HRQoL) of patients. In this work, we have described a model of integrated dermo-rheumatologic approach for the early diagnosis of PsA and to present the outcomes of the multidisciplinary management of PsA patients after 48 weeks of follow-up. Pso patients complaining musculoskeletal symptoms were enrolled in a DErmo-Rheumatologic Clinic (DERC) in order to screen, classify, and treat patients with PsA, employing an operative working procedure and a specific flowchart. The integrated dermatologic and rheumatologic management of PsA patients allowed a prompt establishment of the diagnosis and the best therapeutic approach in these patients, with a significant improvement of skin and articular diseases and, eventually, a consistent amelioration of HRQoL. Dermatologists and rheumatologists usually manage the "psoriatic disease" in separated outpatient clinics. In our study, we have demonstrated that a combined DERC, by means of a tight cooperation between the dermatologist and the rheumatologist, which use a specific working procedure and treatment flowchart, may achieve the optimal clinical management of these patients, with a consistent clinical remission of the disease and a significant amelioration of the HRQoL.

Background Systemic sclerosis is characterised by progressive cutaneous and organ fibrosis. Among all organs, a subclinical heart involvement is difficult to detect through conventional imaging. Design We evaluated whether speckle tracking-derived global longitudinal strain could help detect early subclinical systolic dysfunction in systemic sclerosis patients without overt clinical involvement. Methods A case–control, single-centre study on 52 systemic sclerosis patients and 52 age and gender-matched controls. Patients with structural heart disease, heart failure, atrial fibrillation and pulmonary hypertension were excluded. For every patient, standard echocardiographic and speckle tracking-derived variables for the systolic and diastolic function of the left ventricle and right ventricle were acquired. Results Traditional parameters of left and right systolic function did not differ between systemic sclerosis patients and controls (all P = ns). Left and right ventricular global longitudinal strain was significantly impaired in patients with systemic sclerosis when compared to controls (–19.2% vs. –21.1%; P = 0.009 and –18.2% vs. –22.3%; P = 0.012, respectively). Systemic sclerosis patients had a 2.5-fold increased risk of subclinical left ventricular systolic impairment (odds ratio 2.5, 95% confidence interval 1.1–5.5; P = 0.027) and a 3.3-fold increased risk of subclinical right ventricular systolic impairment when compared to controls (odds ratio 3.3, 95% confidence interval 1.4–7.7; P = 0.004). Alterations in the myocardial deformation pattern of systemic sclerosis patients were homogeneous in the right ventricle and eccentric in the left ventricle. Conclusions While traditional echocardiographic parameters are ineffective in detecting subclinical systolic impairment, reduced global longitudinal strain is common in patients with systemic sclerosis and significant for both ventricles. Global longitudinal strain could become a low-cost, non-invasive and reliable tool in order to detect early cardiac involvement in systemic sclerosis patients.

Systemic sclerosis (SSc) is an autoimmune disease of unknown aetiology characterized by vascular lesions, immunological alterations and diffuse fibrosis of the skin and internal organs. Since recent evidence suggests that there is a link between metabolomics and immune mediated disease, serum metabolic profile of SSc patients and healthy controls was investigated by 1H-NMR and GC-MS techniques. The results indicated a lower level of aspartate, alanine, choline, glutamate, and glutarate in SSc patients compared with healthy controls. Moreover, comparing patients affected by limited SSc (lcSSc) and diffuse SSc (dcSSc), 6 discriminant metabolites were identified. The multivariate analysis performed using all the metabolites significantly different revealed glycolysis, gluconeogenesis, energetic pathways, glutamate metabolism, degradation of ketone bodies and pyruvate metabolism as the most important networks. Aspartate, alanine and citrate yielded a high area under receiver-operating characteristic (ROC) curves (AUC of 0.81; CI 0.726–0.93) for discriminating SSc patients from controls, whereas ROC curve generated with acetate, fructose, glutamate, glutamine, glycerol and glutarate (AUC of 0.84; CI 0.7–0.98) discriminated between lcSSc and dcSSc. These results indicated that serum NMR-based metabolomics profiling method is sensitive and specific enough to distinguish SSc from healthy controls and provided a feasible diagnostic tool for the diagnosis and classification of the disease.

Oesophageal dilatation (OD) has been implicated in the pathogenesis of interstitial lung disease (ILD) in systemic sclerosis (SSc). The aims of this study were to explore the association of the OD and SSc-ILD on chest high-resolution computed tomography (HRCT), and to establish a cutoff point for the OD suggestive for the presence of a significant lung involvement.The widest oesophageal diameter (WOD) was obtained on axial HRCT images. The parenchymal abnormalities on HRCT were coded and scored according to Warrick method. Patient-centred measures, pulmonary function tests and the single breath carbon monoxide diffusing capacity of the lung (DLco) were also obtained. Multivariate regression analysis was performed to identify factors associated with oesophageal diameter.126 subjects with SSc were included. The mean (± SD) WOD was 13.5 (± 4.2) mm, and in 76 (60.3%) participants WOD was ≥ 11 mm. SSc patients with ILD had larger oesophageal diameters than those without lung disease (19.4 vs. 14.1 mm, p 0.001). We observed a high correlation between WOD and gastro-oesophageal reflux disease questionnaire (GerdQ) (r = 0.886, p 0.001), Borg score (r = 0.705, p 0.001), and Warrick score (r = 0.614, p 0.001). WOD negatively correlated with DLco (r = - 0.508, p 0.001). Multivariate analysis demonstrated positive associations between WOD and GerdQ (p 0.0001), Borg score (p 0.0005), and total Warrick score (p = 0.019).An increased oesophageal diameter ( 11 mm) on chest HRCT is associated with pulmonary and oesophageal symptoms, more severe ILD, and lower DLco.

Background The use of biologic agents in systemic immune-mediated diseases has dramatically increased in recent years, replacing conventional immunosuppressive strategies that are characterized by unspecific mechanisms of action and burdened with serious adverse effects. Biologic drugs have selective action towards specific targets, with considerable steroid-sparing effect. They are used nowadays to induce remission or treat specific organ involvements in systemic autoimmune diseases. Conclusion In this review, we will discuss the scientific evidence supporting the use of biologics in these diseases, with a particular emphasis on their efficacy and safety profile compared to the conventional drugs.

BACKGROUND Biologic drugs, introduced in clinical practice almost twenty years ago, represent nowadays a prominent treatment option in patients with chronic inflammatory arthritis, such as Rheumatoid Arthritis, Psoriatic Arthritis and Spondyloarthritis, that include ankylosing spondylitis and non-radiographic axial spondyloarthritis. METHODS Several compounds targeting different pathways have been marketed and approved for the treatment of inflammatory arthritis, with a significant impact on the clinical outcomes and the natural history of the diseases. RESULTS There are currently seven classes of biologics that are available for the treatment of inflammatory arthritis, each inhibiting a different aspect of the immune-driven inflammatory pathway. They include: • Tumor Necrosis Factor (TNF) inhibitors (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol); • Interleukin-1 (IL-1) receptor antagonists (anakinra); • Interleukin-6 (IL-6) inhibition (tocilizumab); • Interleukin-12/23 (IL23) inhibition (ustekinumab); • Interleukin-17 (IL-17) inhibition (secukinumab); • B-cell inhibition (anti-CD20, rituximab); • T-cell costimulation inhibition (anti-CTLA-4, abatacept). CONCLUSION In this review, we will focus on the role of biologic drugs in the treatment strategies for inflammatory arthritis.

Systemic sclerosis (SSc) is characterized by microangiopathy, excessive fibrosis, and the presence of circulating autoantibodies to several cellular and extracellular components. The role of autoimmunity in generating the clinical and pathologic phenotypes in SSc has been long debated and is still matter of controversy. Distinct specificities of antinuclear antibodies (ANAs) are selectively detected in SSc patients and are associated with unique disease manifestations, but do not have a proven pathogenic role. A new group of autoantibodies reactive with cell surface receptors have been identified in SSc patients. They have been shown to directly activate pathways that may contribute to tissue and vascular damage. As such, they are proposed to have a role as agonistic autoantibodies in SSc. According to Koch's third postulate, the autoantibodies in question should cause disease when introduced into a healthy subject. Therefore, our review will focus on those autoantibodies for which agonistic activity has already been demonstrated not only in vitro, but, at least partly, also in vivo. These include the antibodies anti-endothelial cells (AECA), anti-Platelet-Derived Growth Factor Receptor (PDGFR), anti-Angiotensin II type 1 receptor (AT1R) and anti-endothelin-1 type A receptor (ETaR). In this review, we will discuss also a class of antagonistic autoantibodies, the anti-muscarinic-3 receptor (M3R) antibodies, since they seem to fulfill the aforementioned requirements.

Lartruvo® (olaratumab) is a fully human immunoglobulin G subclass 1 (IgG1) monoclonal antibody that inhibits platelet-derived growth factor receptor alpha (PDGFRα). The antitumor activity of olaratumab has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in cancer cell lines, including glioblastoma and leiomyosarcoma cells. It represents the first-in-class antibody to be approved by regulatory authorities for the treatment of advanced soft-tissue sarcomas (STSs) in combination with doxorubicin, based on the results of the Phase Ib/II trial by Tap et al. The median progression-free survival (PFS), which was the primary end point of the study, was improved for patients treated with olaratumab plus doxorubicin compared to those treated with doxorubicin monotherapy (6.6 vs 4.1 months, respectively; HR 0.672, 95% CI 0.442–1.021, p=0.0615). Moreover, final analysis of overall survival (OS) showed a median OS of 26.5 months with olaratumab plus doxorubicin vs 14.7 months with doxorubicin, with a gain of 11.8 months (HR 0.46, 95% CI 0.30–0.71, p=0.0003). In October 2016, olaratumab was admitted in the Accelerated Approval Program by the US Food and Drug Administration (FDA) for use in combination with doxorubicin for the treatment of adult patients with STSs. In November 2016, the European Medicines Agency (EMA) granted conditional approval for olaratumab in the same indication under its Accelerated Assessment Program. A double-blind, placebo-controlled, randomized Phase III study (ANNOUNCE trial, NCT02451943) is being performed in order to confirm the survival advantage of olaratumab and to provide definitive drug confirmation by regulators. The study is ongoing, but enrollment is closed. The purpose of this review was to evaluate the rationale of olaratumab in the treatment of advanced STSs and its emerging role in clinical practice.