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Objectives To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. Methods SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality. Results We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s.d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc but lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. The risk of any organ involvement, PMI and PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. Conclusion ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting careful screening for ILD in this subgroup.

Grounded in the interdisciplinary crosstalk among physics and biological sciences, precision medicine-based diagnosis and treatment strategies have recently gained great attention for the actual applicability of new engineered approaches in many medical fields, particularly in oncology. Within this framework, the use of ultrasounds employed to attack cancer cells in tumors to induce possible mechanical damage at different scales has received growing attention from scholars and scientists worldwide. With these considerations in mind, on the basis of ad hoc elastodynamic solutions and numerical simulations, we propose a pilot study for in silico modeling of the propagation of ultrasound waves inside tissues, with the aim of selecting proper frequencies and powers to be irradiated locally through a new teragnostic platform based on Lab-on-Fiber technology, baptized as a hospital in the needle and already the object of a patent. It is felt that the outcomes and the related biophysical insights gained from the analyses could pave the way for envisaging new integrated diagnostic and therapeutic approaches that might play a central role in future applications of precise medicine, starting from the growing synergy among physics, engineering and biology.

We described nailfold videocapillaroscopy (NVC) findings and estimated the prevalence of serum anti-nuclear (ANA) and extractable nuclear antigen autoantibodies (ENA) in a cohort of sarcoidosis patients, comparing them with adequate healthy controls (HCs) and with primary Raynaud’s phenomenon patients (PRPs). NVC findings were also correlated with the occurrence of autoantibodies, current treatment, laboratory parameters, variables of lung function and whole-body imaging data. Twenty-six patients with sarcoidosis were assessed through NVC, laboratory parameters, pulmonary function tests, chest-X ray and 18- fluorodeoxyglucose positron emission tomography/computed tomography. The NVC parameters and ANA/ENA dosage were recorded also in 30 PRPs and 30 HCs. Sarcoidosis patients showed a higher rate of capillary dilations and nonspecific abnormalities and a lower mean capillary absolute number than PRPs and HCs (p p p

Newly developed Doppler techniques enable the sampling of slow vascular flows and the extrapolation of spectral parameters in distal arterioles. The aim of this study was to investigate the role of spectral analysis performed by means of ultra-high frequency ultrasound (US) in the evaluation of the peripheral vascular bed of systemic sclerosis (SSc) patients.Both hands of 33 patients affected by diffuse cutaneous SSc and 34 volunteers were evaluated with a US machine equipped with 33-9 MHz and 18-5 MHz transducers. Proximal resistive index and the peak systolic velocity (pRI and pPSV, respectively), were calculated at the level of the second interdigital artery. The distal resistive index (dRI) was calculated at the level of a nailfold arteriole of the third finger. All SSc patients had been previously divided into 4 subgroups according to their nailfold videocapillaroscopic (NVC) patterns following accepted criteria.SSc patients showed a significantly slower systolic velocity at the level of the second interdigital artery (pPSV [SD] = 8.38 [3] cm/s vs pPSV [SD] = 11.14 [4.5] cm/s; P = .005) and a higher dRI (dRI [SD] = 0.65 (0.14) vs dRI [SD] = 0.57 [0.11); P = .0115). No differences were found between the pRI values measured in the SSc patients and those of the controls (pRI [SD] = 0.76 [0.11] vs pRI [SD] = 0.73 [0.12]; P = .359]. The subgroup analysis did not show any significant difference when pPSV, pRI and dRI were compared among NVC morphological patterns.High-resolution Doppler analysis of digital distal arterioles may disclose subtle abnormalities in the downstream microvasculature of SSc patients that could be missed when the examination is performed at a more proximal level and/or using lower Doppler frequencies.

To report a case of hyphema after a bleb needling revision in a PreserFlo MicroShunt implantation.An 87-year-old man suffering from bilateral open angle glaucoma was referred to our hospital with a diagnosis of unsatisfactory intraocular pressure (IOP) control in the right eye, despite the maximally tolerated medical therapy. The patient underwent PreserFlo MicroShunt implantation in his right eye. About 2 months after the surgical procedure, the IOP was raised because of bleb failure for subconjunctival scarring. A needling revision was performed at the slit lamp. During the procedure blood reflux through a PreserFlo MicroShunt device from a filtering bleb to the anterior chamber was observed, causing an IOP rise. Treatment with oral acetazolamide, topical steroid, and antibiotic resulted in the complete resolution of the hyphema in 2 weeks and a significant lowering in IOP.This is the first reported case of blood reflux to the anterior chamber through a PreserFlo MicroShunt implant after a needling procedure.

© Copyright Clinical and Experimental Rheumatology 2022, Objectives: Relapsing polychondritis (RP) evolves with variable and intermittent involvement of cartilage and proteoglycan-rich structures. Ocular manifestations are present in up to two-thirds of RP patients. Necrotising scleritis (NS) and peripheral ulcerative keratitis (PUK) may be inaugural and may lead to eye perforation and vision loss. We aimed to review NS and PUK in RP, in order to characterise them, to identify successful treatment options and unmet needs. Methods: A systematic review of the currently available evidence in PubMed, EMBASE and Scopus was performed according to PRISMA, including observational studies, single case reports and case series of NS/PUK in RP. Study design, number of patients, age, gender, treatment and outcome, were extracted. Two RP patients also provided their opinion. Results: Five case reports and two case series were eligible for inclusion. We identified 10 RP patients with eye-threatening complications (NS and/or PUK), 9 adults (2 males, 7 females, aged 35-72, median age 57.6 years) and one paediatric patient (F, 11 years). Apart from glucocorticoids, cyclophosphamide was effective in 4 patients; infliximab, high-dose immunoglobulins, dapsone, or cyclosporine were also successfully employed in a case each. Surgical repair was reported in 2 cases. Conclusions: Ocular inflammation is often bilateral and recurring in RP; NS/PUK are rare complications. All patients who develop NS/PUK should be specifically questioned for RP signs and symptoms. Early institution of immunosuppressive therapies is mandatory. Increasing awareness, physicians' and patients' education and a multidisciplinary approach may help improve the prognosis of these serious complications of RP.

© Copyright Clinical and Experimental Rheumatology 2022., Objectives: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. Methods: We conducted a multicentre, international, retrospective cohort study. Results: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. Conclusions: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Background/objectives: To compare the number of eye surgical procedures performed in Italy in the 2 months following the beginning of lockdown (study period) because of COVID-19 epidemic with those performed in the two earlier months of the same year (intra-year control) and in the period of 2019 corresponding to the lockdown (inter-year control). Methods: Retrospective analysis of surgical procedures carried out at 39 Academic hospitals. A distinction was made between elective and urgent procedures. Intravitreal injections were also considered. Percentages for all surgical procedures and incidence rate ratios (IRR) for rhegmatogenous retinal detachment (RRD) events were calculated. A p value Results: A total of 20,886 versus 55,259 and 56,640 patients underwent surgery during the lockdown versus intra-and inter-year control periods, respectively. During the lockdown, only 70% of patients for whom an operation/intravitreal injection was recommended, finally underwent surgery; the remaining patients did not attend because afraid of getting infected at the hospital (23%), taking public transportation (6.5%), or unavailable swabs (0.5%). Elective surgeries were reduced by 96.2% and 96.4%, urgent surgeries by 49.7% and 50.2%, and intravitreal injections by 48.5% and 48.6% in the lockdown period in comparison to intra-year and inter-year control periods, respectively. IRRs for RRDs during lockdown dropped significantly in comparison with intra- and inter-year control periods (CI: 0.65–0.80 and 0.61–0.75, respectively, p Conclusion: This study provides a quantitative analysis of the reduction of eye surgical procedures performed in Italy because of the COVID-19 epidemic.

We aimed to evaluate joint and vessel uptake in patients with polymyalgia rheumatica (PMR) by FDG-PET and correlate it with clinical findings.Consecutive PMR patients, without clinical signs of giant cell arteritis, underwent a standardised clinical examination and FDG-PET/CT. Controls were consecutive subjects undergoing FDG-PET for the suspicion of neoplasm not confirmed by the examination. Uptake was evaluated by a qualitative visual score, using the liver uptake as reference and by the semi-quantitative mean standardised uptake value (SUV) and target-to-background ratio (TBR) methods.Eighty-four patients and 84 controls (55 women, median age 73 years, range 50-92 years in both groups) were studied. Sixteen patients were taking glucocorticoids (GC). PMR patients showed a higher articular uptake than controls. GC-treated patients showed uptake lower than GC-naïve patients, but still higher than controls. PMR patients showed a higher vascular uptake than controls in all districts except in the carotid arteries, when evaluated by the visual score. Conversely, the semi-quantitative approach yielded no significant differences. Forty-two patients (50%) showed PET evidence of large-vessel vasculitis (LVV), defined as uptake ≥ than that of the liver, and 11.9% showed LVV with vascular uptake higher than that of the liver. The correlation between clinical findings and uptake was scarce. Neither clinical nor laboratory findings could predict the presence of LVV.Patients with PMR show a typical joint pattern at FDG-PET. There are no clinical or laboratory predictors of LVV. Imaging appears to be the only tool to assess LVV in these patients.

Early diagnosis and treatment is paramount in rheumatoid arthritis (RA). Nowadays, there is a need for quick and non-invasive imaging modalities, for which laser speckle contrast analysis (LASCA), a technique that assesses the peripheral blood perfusion (PBP) on a microvascular level, seems to be a promising candidate. The goal of this pilot study was to examine whether the expected increased PBP in active synovitis in RA patients can be detected by LASCA.Thirty RA patients with active synovitis in a finger joint and 44 healthy controls (HC) underwent LASCA examination. The PBP measured over the finger joints was expressed in perfusion units (PU). For the final analysis, all 30 RA patients were matched by age and gender to 30 HC. For the primary analysis the mean difference in PU between joints with active synovitis compared to matched HC, adjusted for type of joint (MCP/PIP), finger, surface and side of hand and for the matching variables (age and gender), was calculated using a multilevel linear model. For the secondary analysis this mean difference in PU was calculated on a monoarticular level.The primary analysis showed an estimated mean difference of 8.79 PU (95%CI -7.79-25.37 PU; p=0.299). For the secondary analysis on a monoarticular level, none of the estimated mean differences differed significantly.In this pilot study examining the use of LASCA in RA, no significant difference in estimated mean PBP between joints with active synovitis in RA and joints without active synovitis in HC could be detected.

BACKGROUND/OBJECTIVE The aim of this study was to explore the associations between nailfold videocapillaroscopy (NVC) and pulmonary function tests (PFTs) in systemic sclerosis (SSc) patients. METHODS This was a longitudinal study with follow-up of unselected Brazilian SSc patients. Baseline clinical examination, serological workup, high-resolution chest tomography, and NVC were performed. Pulmonary function test was performed at baseline and after 24 months. Pulmonary function test worsening over time was defined as either a ΔFVC decline ≥10% or a ΔFVC decline ≥5% and

ObjectiveFibromyalgia (FM) is a chronic musculoskeletal pain syndrome of unknown aetiopathogenesis. Its development and maintenance are related to the interplay of biological, psychological, and contextual factors. Among the contextual factors, sociodemographic aspects are poorly elucidated. This study aimed to evaluate the relationships between sociodemographic/ clinical factors and symptom severity measures using a web-based registry of patients with FM.MethodsAdult patients with an ACR 2010/2011 diagnosis of FM underwent a clinical evaluation and were asked to complete questionnaires covering their sociodemographic data (gender, age, marital status, educational level), and disease-specific measures (the revised Fibromyalgia Impact Questionnaire (FIQR), and the Polysymptomatic Distress Scale (PDS)).ResultsData relating to 3,221 patients (3001 women and 220 men) was collected. The ANOVA showed significant difference in mean FIQR scores when the five marital conditions (cohabiter, married, separated/divorced, single, widowed) were compared ( F 3.321, p< 0.01). While males and females were found to have comparable FIQR scores, the interaction between gender and marital status indicated that separated/divorced males have higher FIQR scores (F 5.684, p=0.001). The multiple regression analysis demonstrated that patients who reported lower educational level experienced more severe FM symptoms, as scored with FIQR (p

Cardiovascular diseases (CVDs) are among the most common causes of access to the Emergency Department and among the leading causes of death worldwide. Accurate diagnostic algorithms are mandatory to ensure a rapid life-saving treatment. However, non-specific clinical presentation and unnecessary referrals to other subspecialties may lead to misinterpretation of the diagnosis and delays. In recent years, the development of imaging technologies has allowed Computed Tomography (CT) to play a prominent role in the concepts of CVD rule-in and rule-out. An optimization strategy for CT protocols is needed to reduce variability and improve image quality. A correct diagnostic suspicion is crucial, as different districts (i.e., heart, aorta and pulmonary circulation) may require different investigation techniques. Additionally, the CVD pre-test probability assessment is highly correlated with CT accuracy. The purpose of this narrative review is to analyze the current role of CT in the approach to the CVDs in the ED, and to analyze the main strategies of CT optimization.

© 2022Background: The GLORIA placebo-controlled trial found a favorable balance of benefit and harm for two years of prednisolone (5 mg/day) as add-on treatment for rheumatoid arthritis (RA) patients aged 65+. This study evaluated the cost-effectiveness of low-dose prednisolone in the treatment of RA. Methods: The economic evaluation had a societal perspective with a time horizon of two years. Cost data were collected with questionnaires and from recorded events, and valued with standard Dutch unit prices of 2017. The primary effectiveness outcome was the disease activity score in 28 joints (DAS28). For cost-utility, quality-adjusted life years (QALYs) were estimated from the EuroQol-5 Dimension (EQ-5D) questionnaire. Bootstrapping assessed the uncertainty around the average differences in costs and health outcomes. Results: In total, 444 of 451 randomized patients were included in the modified intention-to-treat analysis. Patients had median four active comorbidities at baseline. Mean total costs over two years were k€10.8 in the prednisolone group, k€0.5 (95% CI –4.0; 1.8) lower than in the placebo group. Total direct medical costs were k€0.5 (95% CI –4.0; 1.5) lower in the prednisolone group. The mean number of QALYs was similar in both groups (difference 0.02 [–0.03; 0.06] in favor of prednisolone). The DAS28 was 0.38 lower in the prednisolone group than in the placebo group (0.19; 0.56). Conclusion: With greater effectiveness (DAS28) at non-significantly lower costs, low-dose, add-on prednisolone is cost-effective for RA compared to placebo over two years. QALYs were equal in both groups, most likely due to the impact of multiple comorbidities.

Osteoarthritis (OA) is the most common joint condition and, with a burgeoning ageing population, is due to increase in prevalence. Beyond conventional medical and surgical interventions, there are an increasing number of ‘alternative’ therapies. These alternative therapies may have a limited evidence base and, for this reason, are often only afforded brief reference (or completely excluded) from current OA guidelines. Thus, the aim of this review was to synthesize the current evidence regarding autologous chondrocyte implantation (ACI), mesenchymal stem cell (MSC) therapy, platelet-rich plasma (PRP), vitamin D and other alternative therapies. The majority of studies were in knee OA or chondral defects. Matrix-assisted ACI has demonstrated exceedingly limited, symptomatic improvements in the treatment of cartilage defects of the knee and is not supported for the treatment of knee OA. There is some evidence to suggest symptomatic improvement with MSC injection in knee OA, with the suggestion of minimal structural improvement demonstrated on MRI and there are positive signals that PRP may also lead to symptomatic improvement, though variation in preparation makes inter-study comparison difficult. There is variability in findings with vitamin D supplementation in OA, and the only recommendation which can be made, at this time, is for replacement when vitamin D is deplete. Other alternative therapies reviewed have some evidence (though from small, poor-quality studies) to support improvement in symptoms and again there is often a wide variation in dosage and regimens. For all these therapeutic modalities, although controlled studies have been undertaken to evaluate effectiveness in OA, these have often been of small size, limited statistical power, uncertain blindness and using various methodologies. These deficiencies must leave the question as to whether they have been validated as effective therapies in OA (or chondral defects). The conclusions of this review are that all alternative interventions definitely require clinical trials with robust methodology, to assess their efficacy and safety in the treatment of OA beyond contextual and placebo effects. Electronic supplementary material The online version of this article (10.1007/s40520-020-01515-1) contains supplementary material, which is available to authorized users.

Objectives To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). Methods SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). Results Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06–4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65–3.95). Adjusting for arterial hypertension resulted in a HR of 2.04 (95%CI 1.29–3.24). There was no evidence for an interaction of ACEi and arterial hypertension (HR 0.83, 95%CI 0.32–2.13, p = 0.69). Calcium channel blockers (CCB), angiotensin receptor blockers (ARB), endothelin receptor antagonists, and GC—mostly in daily dosages below 15 mg of prednisolone—did not influence the hazard for SRC. Conclusions ACEi in SSc patients with concomitant arterial hypertension display an independent risk factor for the development of SRC but are still first choice in SRC treatment. ARBs might be a safe alternative, yet the overall safety of alternative antihypertensive drugs in SSc patients needs to be further studied.

PRCIS Automated gonioscopy is a recent method of recording angle pictures. Our study shows that agreement between observers is moderate in most categories used in clinical practice, underlying its clinical usefulness but also room for improvement. INTRODUCTION Iridocorneal angle (ICA) imaging methods have been recently developed to record gonioscopic images. The purpose of this study was to perform an interrater agreement analysis of ICA photographs. METHODS Multicentric cross-sectional observational study. Consecutive patients in 2 ophthalmology departments underwent automated gonioscopy. One picture per quadrant from each eye was selected for randomization. Pictures were graded and analyzed by 4 masked glaucoma specialists regarding angle opening, width, Shaffer and Spaeth gradings and other findings. Fleiss' κ statistics was performed to assess interrater agreement. RESULTS A total of 50 patients were recruited, with the sample containing a variety of diagnosis including pseudoexfoliation (22%), angle-closure suspect (12%), and pigmentary glaucoma (4%). The sample included phakic (68%) and pseudophakic patients, as well as cases with gonio-implanted surgical devices (10%). There was moderate agreement on angle opening, angle width, presence of angle vessels, and peripheral anterior synechiae (κ=0.435, 0.511, 0.558, 0.488, respectively; P

Cardiovascular diseases are still the main cause of death among women despite the improvements in treatment and prognosis achieved in the last 30 years of research. The determinant factors and causes have not been completely identified but the role of "gender" is now recognized. It is well known that women tend to develop cardiovascular disease at an older age than men, and have a high probability of manifesting atypical symptoms not often recognized. Other factors may also co-exist in women, which may favor the onset of specific cardiac diseases such as those with a sex-specific etiology (differential effects of estrogens, pregnancy pathologies, etc.) and those with a different gender expression of specific and prevalent risk factors, inflammatory and autoimmune diseases and cancer. Whether the gender differences observed in cardiovascular outcomes are influenced by real biological differences remains a matter of debate.This ANMCO position paper aims at providing the state of the research on this topic, with particular attention to the diagnostic aspects and to care organization.

Patient-specific templates (PST) have become a useful tool for guiding osteotomy in complex surgical scenarios such as pelvic resections. The design of the surgical template results in sharper, less jagged resection margins than freehand cuts. However, their correct placement can become difficult in some anatomical regions and cannot be verified during surgery. Conventionally, pelvic resections are performed using Computer Assisted Surgery (CAS), and in recent years Augmented Reality (AR) has been proposed in the literature as an additional tool to support PST placement. This work presents an AR task to simplify and improve the accuracy of the positioning of the template by displaying virtual content. The focus of the work is the creation of the virtual guides displayed during the AR task. The system was validated on a patient-specific phantom designed to provide a realistic setup. Encouraging results have been achieved. The use of the AR simplifies the surgical task and optimizes the correct positioning of the cutting template: an average error of 2.19 mm has been obtained, lower than obtained with state-of-the-art solutions. In addition, supporting PST placement through AR guidance is less time-consuming than the standard procedure that solely relies on anatomical landmarks as reference.

In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients. It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.

ObjectiveThe role of age in influencing the severity of fibromyalgia (FM) is still controversial. The aim of this study is to define the contribution of age in the severity of FM from data from a large national database.MethodsThis cross-sectional study included adult patients with FM diagnosed according to the 2010/2011 American College of Rheumatology criteria. Disease severity was assessed with the revised Fibromyalgia Impact Questionnaire (FIQR) and the modified Fibromyalgia Assessment Status (FAS 2019mod). Patients were grouped into five age categories (between 18-40 years, between 41- 50 years, between 51-60 years, between 61-70 years, and =71 years). Differences in disease severity between groups were assessed by one-way analysis of variance (ANOVA).ResultsThe study included 2889 patients (199 males and 2690 females), mean age of 52.58 (+/- 11.82) years, with a mean FIQR score of 59.22 (+/- 22.98) and a mean FAS 2019mod of 25.50 (+/- 8.66). Comparing the mean values of the various indices between age categories, there were no statistically significant differences between the groups for FIQR total score and FAS 2019mod. However, the 60-70 years category showed the lowest scores for both scales. The main difference emerged for the FIQR physical function subscale, where the =71 years category showed significantly higher scores (p

Today, neuronavigation is widely used in daily clinical routine to perform safe and efficient surgery. Augmented reality (AR) interfaces can provide anatomical models and preoperative planning contextually blended with the real surgical scenario, overcoming the limitations of traditional neuronavigators. This study aims to demonstrate the reliability of a new-concept AR headset in navigating complex craniotomies. Moreover, we aim to prove the efficacy of a patient-specific template-based methodology for fast, non-invasive, and fully automatic planning-to-patient registration. The AR platform navigation performance was assessed with an in-vitro study whose goal was twofold: to measure the real-to-virtual 3D target visualization error (TVE), and assess the navigation accuracy through a user study involving 10 subjects in tracing a complex craniotomy. The feasibility of the template-based registration was preliminarily tested on a volunteer. The TVE mean and standard deviation were 1.3 and 0.6 mm. The results of the user study, over 30 traced craniotomies, showed that 97% of the trajectory length was traced within an error margin of 1.5 mm, and 92% within a margin of 1 mm. The in-vivo test confirmed the feasibility and reliability of the patient-specific template for registration. The proposed AR headset allows ergonomic and intuitive fruition of preoperative planning, and it can represent a valid option to support neurosurgical tasks.

Objectives To investigate the reliability of high frequency ultrasound (HFUS) in measuring skin fibrosis in SSc. Methods First, a systematic review (according to PRISMA) was conducted to identify studies that documented HFUS’ reliability in SSc as a primary outcome. Then, in an additional pilot study, the inter- and intra-rater reliability of two investigators performing HFUS for dermal thickness (DT) measurements in a standardized manner across all 17 areas of the modified Rodnan Skin Score was evaluated in a group of 59 SSc patients and descriptively in 44 healthy controls (HC). As an external validation, DT measurements by HFUS were performed in a separate group of 30 SSc patients by the same first and another third investigator. Results The systematic review retained few (4/1719 unique records) small-scale studies, with mixed study populations (combining SSc and HC). The reported data herein are suggestive of the inter-/intra-rater reliability of HFUS (intra-class correlation coefficient [ICCs] ranging 0.65–0.94/0.55–0.96, respectively). Additionally, in our pilot study, inter-/intra-rater reliability was good-to-excellent in both SSc groups and HC (ICCs ranging 0.70–0.97/0.70–0.98 and 0.65–0.95/0.63–0.96, respectively). Conclusion The identified small-scale studies were not only combining data from SSc and HC, they were also heterogeneous in terms of technical aspects (probes and frequency), image acquisition methods ([number of] areas assessed) and definitions used for skin thickness, which prevents drawing unequivocal conclusions. Despite these limitations, our standardized pilot study corroborated the findings in literature, paving the way for the applicability of HFUS as a reliable (complementary) tool to quantify skin fibrosis in SSc.

Background The Brazilian population has a tri-hybrid composition with a high degree of ethnic admixture. We hypothesized that Brazilian individuals with CF from different Brazilian regions have a specific distribution of CFTR variants. Methods Individuals with CF with data available in the Patient Registry and without an established genotype were submitted to CFTR sequencing by Next Generation Sequencing (NGS) methodology, and results were anonymously incorporated to the Registry Database. Genotyping results were expressed as ‘positive’, ‘inconclusive’ or ‘negative’. Logistic regression models were performed to investigate the association between demographic/clinical variables and genotyping results. Mediation analysis was conducted to estimate direct and indirect effects of Brazilian region on a binary positive genotyping response. Results In October 2017, data from 4,654 individuals with CF were available, and 3,104(66.7%) of them had a genotyping result. A total of 236 variants (114 new variants) were identified, with F508del identified in 46% of the alleles tested. Genotyping revealed 2,002(64.5%) individuals positive, 757(24.4%) inconclusive and 345(11.1%) negative. Distribution of genotype categories was markedly different across Brazilian Regions, with greater proportions of negative individuals in the North (45%) and Northeast (26%) regions. Newborn screening (CF-NBS) and age at diagnosis were identified as mediators of the effect of Brazilian region on a positive genotyping result. Conclusions This large initiative of CFTR genotyping showed significant regional discrepancies in Brazil, probably related to socio-economic conditions, lack of adequate CF-NBS and poor access to reliable sweat testing. These results may be useful to indicate Regions where CF care demands more attention.

Objective In the SENSCIS trial in subjects with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib reduced the rate of decline in forced vital capacity (FVC) over 52 weeks by 44% versus placebo. This study was undertaken to investigate the effects of nintedanib on categorical changes in FVC and other measures of ILD progression. Methods In post hoc analyses, we assessed the proportions of subjects with categorical changes in FVC % predicted at week 52 and the time to absolute decline in FVC of ≥5% predicted or death and absolute decline in FVC of ≥10% predicted or death. Results A total of 288 subjects received nintedanib and 288 subjects received placebo. At week 52, in subjects treated with nintedanib and placebo, respectively, 55.7% and 66.3% had any decline in FVC % predicted, 13.6% and 20.1% had a decline in FVC of >5% to ≤10% predicted, and 3.5% and 5.2% had a decline in FVC of >10% to ≤15% predicted; 34.5% and 43.8% had a decrease in FVC of ≥3.3% predicted (proposed minimal clinically important difference [MCID] for worsening of FVC), while 23.0% and 14.9% had an increase in FVC of ≥3.0% predicted (proposed MCID for improvement in FVC). Over 52 weeks, the hazard ratio (HR) for an absolute decline in FVC of ≥5% predicted or death with nintedanib versus placebo was 0.83 (95% confidence interval [95% CI] 0.66-1.06) (P = 0.14), and the HR for an absolute decline in FVC of ≥10% predicted was 0.64 (95% CI 0.43-0.95) (P = 0.029). Conclusion These results suggest that nintedanib has a clinically relevant benefit on the progression of SSc-ILD.

A significant decline in the admission to intensive cardiac care unit (ICCU) has been noted in Italy during the COVID-19 outbreak. Previous studies have provided data on clinical features and outcome of these patients, but information is still incomplete. In this multicenter study conducted in six ICCUs, we enrolled consecutive adult patients admitted to ICCU in three specific time intervals: from February 8 to March 9, 2020 [before national lockdown (pre-LD)], from March 10 to April 9, 2020 [during the first period of national lockdown (in-LD)] and from May 18 to June 17, 2020 [soon after the end of all containment measures (after-LD)]. Compared to pre-LD, in-LD was associated with a significant drop in the admission to ICCU for all causes (− 35%) and acute coronary syndrome (ACS; − 49%), with a rebound soon after-LD. The in-LD reduction was greater for women (− 49%) and NSTEMI (− 61%) compared to men (− 28%) and STEMI (− 33%). Length-of-stay, and in-hospital mortality did not show any significant change from to pre-LD to in-LD in the whole population as well as in the ACS group. This study confirms a notable reduction in the admissions to ICCUs from pre-LD to in-LD followed by an increment in the admission rates after-LD. These data strongly suggest that people, particularly women and patients with NSTEMI, are reluctant to seek medical care during lockdown, possibly due to the fear of viral infection. Such a phenomenon, however, was not associated with a rise in mortality among patients who get hospitalization. Supplementary Information The online version contains supplementary material available at 10.1007/s11739-021-02718-8.

Objectives To investigate the reliability of durometry in systemic sclerosis (SSc), by means of a systematic review and additional pilot study. Methods Literature was systematically reviewed according to the PRISMA guidelines to identify all original studies assessing the reliability of durometry in SSc. Additionally, in the pilot study, intra-rater reliability was evaluated in a first cohort of 74 SSc patients (61 female, 13 LSSc/53 LcSSc/8 DcSSc). In a second separate set of 30 SSc patients (21 female, 4 LSSc/20 LcSSc/6 DcSSc), intra- and inter-rater reliability were evaluated. Results Only two unique records identified through the systematic review were qualified to generate conclusions. Regarding intra-rater reliability, Kissin reported excellent intra-class correlation coefficient values (ICC, 0.86–0.94) for measurements at nine skin sites in two DcSSc patients. Merkel and Kissin described, both in five DcSSc patients, good to excellent inter-rater reliability (ICC, 0.82–0.96 and 0.61–0.85) for measurements at respectively, six and nine skin sites. In our pilot study, ICC for intra-rater reliability at 17 standardized skin sites were excellent in both cohorts, ranging 0.93–0.99 and 0.78–0.98, respectively. ICC for inter-rater reliability at 17 standardized skin sites were good to excellent 0.63–0.93, except for the feet (0.48 and 0.52). Conclusion The preliminary findings in the literature are supported by our pilot study in which we have attested the reliability of durometry in SSc patients. However, prior to including durometry as an (additional) outcome measure in SSc clinical trials, its validation status in the assessment of skin fibrosis needs to be completely attested.

Objective To establish optimal cut-off values for the scores of the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromialgia Assessment Scale (FAS 2019mod), and the Polysymptomatic Distress Scale (PDS) in order to distinguish five levels of FM disease severity. Methods Consecutive FM patients were evaluated with the three clinimetric indices, and each patient was required to answer the anchor question: ‘In general, would you say your health is 1 = very good, 2 = good, 3 = fair, 4 = poor, or 5 = very poor?’—which represented the external criterion. Cut-off points were established through the interquartile reconciliation approach. Results The study sample consisted of 2181 women (93.2%) and 158 men (6.8%), with a mean age of 51.9 (11.5) years, and mean disease duration was 7.3 (6.9) years. The overall median FIQR, FAS 2019 mod and PDS scores (25th–75th percentiles) were respectively 61.16 (41.16–77.00), 27.00 (19.00–32.00) and 19.0 (13.00–24.00). Reconciliation of the mean 75th and 25th percentiles of adjacent categories defined the severity states for FIQR: 0–23 for remission, 24–40 for mild disease, 41–63 for moderate disease, 64–82 for severe disease and >83 for very severe disease; FAS 2019 mod: 0–12 for remission, 13–20 for mild disease, 21–28 for moderate disease, 29–33 for severe disease and >33 for very severe disease; PDS: 0–5 for remission, 6–15 for mild disease, 16–20 for moderate disease, 21–25 for severe disease and >25 for very severe disease. Conclusions Disease severity cut-offs can represent an important improvement in interpreting FM.

Background: The present study aimed to examine longitudinal trends in hospitalizations for acute coronary syndrome (ACS) before and during the COVID-19 pandemic, by reviewing the data from 13 hospitals of the Veneto Region, in the north-east of Italy. Methods: We performed a multicenter, retrospective analysis including all the consecutive patients presenting with ACS and other acute cardiovascular (CV) conditions (defined as heart failure, arrhythmias, cardiac arrest and venous thromboembolism) hospitalized in 13 different hospitals of the Veneto Region covering a population of 2,554,818 inhabitants, during the first (between 15 March 2020 and 30 April 2020) and second (between 15 November 2020 and 30 December 2020) COVID-19 pandemic waves (the 2020 cohort). Data were compared with those obtained at the same time-windows of years 2018 and 2019 (the historical cohorts). Results: Compared to the historical cohorts, a significant decrease in the number of ACS cases was observed in 2020 (−27.3%, p = 0.01 and −32%, p < 0.001, comparing 2018 versus 2020 and 2019 and 2020, respectively). The proportion of patients hospitalized for acute CV conditions decreased during the first and second wave COVID-19 pandemic when compared to the historical cohorts (−36.5%, p < 0.001 and −40.6%, p < 0.001, comparing 2018 versus 2020 and 2019 and 2020, respectively). Pearson’s correlation evidenced a significant inverse relationship between the number of COVID-19 cases and both ACS hospital admissions (r = −0.881, p = 0.005) and hospitalizations for acute CV conditions (r = −0.738, p = 0.01), respectively. Conclusions: The decrease in hospitalizations for ACS and other acute CV conditions will strongly affect future patients’ management since undiagnosed nonfatal CV events represent a source of increased (and unknown) CV morbidity and mortality.

Background: During the COVID-19 pandemic, the risk of SARS-CoV-2 infection, the public health measures of social distancing, the freedom limitations, quarantine, and the enforced homeworking under the lockdown period, as well as medical causes including COVID-19 infection per se, may have caused major emotional distress, especially in the most vulnerable patients. We aimed to evaluate the variations in the number of admissions due to Takotsubo syndrome (TTS) during the COVID-19 pandemic in the Veneto region. Methods: We retrospectively reviewed and analyzed the number of admissions because of TTS in 13 Divisions of Cardiology located in the Veneto region, the northeastern area of Italy, covering a population of more than 2.5 million inhabitants, during the two major pandemic waves of COVID-19 (the first between 15 March and 30 April 2020 and the second between 15 November and 30 December 2020) that occurred in 2020. Results: In total, 807 acute coronary syndromes were admitted in the 13 enrolling hospitals. Among these, 3.9% had TTS. Compared to the corresponding 2018 and 2019 time periods, we observed a significant increase in the number of TTS cases (+15.6%, p = 0.03 and +12.5%, p = 0.04, comparing 2018 to 2020 and 2019 to 2020, respectively). Geographical distribution of the TTS cases reflected the broad spread of the SARS-CoV-2 infection with a significant direct relationship between TTS incidence and the number of COVID-19 infections according to Pearson’s correlation (r = 0.798, p < 0.001). Conclusions: The higher incidence of TTS during the 2020 COVID-19 pandemic waves, especially in the areas that were hit hardest in terms of morbidity and mortality by the SARS-CoV-2 infection, suggest a strong direct and/or indirect role of COVID-19 in the pathogenesis of TTS.

Patients presenting to the emergency with thoracic symptoms could have a wide variety of causes, even if the traumatic and vascular causes are excluded. Therefore, the diagnosis is often a challenge for emergency physicians. Anamnesis, physical examination and laboratory testing need to be integrated with imaging to get a rapid diagnosis and to distinguish among the potential causes. This review discusses the role of diagnostic imaging studies in the emergency setting in patients with non-traumatic non-cardiovascular thoracic symptoms. The use of chest x-ray, bedside lung Ultrasound and Computed Tomography in the diagnosis and care of these patients have been reviewed as well as the common findings on imaging.

Innate and adaptive immunity represent a harmonic counterbalanced system involved in the induction, progression, and possibly resolution of the inflammatory reaction that characterize autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis (RA). Although the immunopathophysiological mechanisms of the ARDs are not fully clarified, they are often associated with an inappropriate macrophage/T-cell interaction, where classical (M1) or alternative (M2) macrophage activation may influence the occurrence of T-helper (Th)1 or Th2 responses. In RA patients, M1/Th1 activation occurs in an inflammatory environment dominated by Toll-like receptor (TLR) and interferon (IFN) signaling, and it promotes a massive production of pro-inflammatory cytokines [i.e., tumor necrosis factor-α (TNFα), interleukin (IL)-1, IL-12, IL-18, and IFNγ], chemotactic factors, and matrix metalloproteinases resulting in osteoclastogenesis, erosion, and progressive joint destruction. On the other hand, the activation of M2/Th2 response determines the release of growth factors and cytokines [i.e., IL-4, IL-10, IL-13, and transforming growth factor (TGF)-β] involved in the anti-inflammatory process leading to the clinical remission of RA. Several subtypes of macrophages have been described. Five polarization states from M1 to M2 have been confirmed in in vitro studies analyzing morphological characteristics, gene expression of phenotype markers (CD80, CD86, TLR2, TLR4, or CD206, CD204, CD163, MerTK), and functional aspect, including the production of reactive oxygen species (ROS). An M1 and M2 macrophage imbalance may induce pathological consequences and contribute to several diseases, such as asthma or osteoclastogenesis in RA patients. In addition, the macrophage dynamic polarization from M1 to M2 includes the presence of intermediate polarity stages distinguished by the expression of specific surface markers and the production/release of distinct molecules (i.e., nitric oxide, cytokines), which characterize their morphological and functional state. This suggests a “continuum” of macrophage activation states playing an important role during inflammation and its resolution. This review discusses the importance of the delicate M1/M2 imbalance in the different phases of the inflammatory process together with the identification of specific pathways, cytokines, and chemokines involved, and its clinical outcomes in RA. The analysis of these aspects could shed a light on the abnormal inflammatory activation, leading to novel therapeutical approaches which may contribute to restore the M1/M2 balance.

BackgroundNailfold videocapillaroscopy (NVC) non-specific abnormalities may be present in subjects with isolated Raynaud’s phenomenon (RP) before the potential transition to systemic sclerosis (SSc) specific microvascular alterations (‘scleroderma pattern’). This study aims to investigate NVC non-specific abnormalities, notably capillary dilations, in RP patients, as possible forerunners of the ‘scleroderma pattern’.MethodsA 10-year retrospective NVC-based investigation evaluated 55 RP patients sorted into 3 sex-matched and age-matched groups according to clinical evolution: 18 later developing SSc (cases), 19 later developing other connective tissue disease and 18 maintaining primary RP at long-term follow-up (controls). All patients had a basal NVC showing non-specific abnormalities, namely non-specific >30 µm dilated capillaries (30–50 μm diameter). Sequential NVCs were longitudinally evaluated using current standardised approach. Statistical analysis assessed the risk for developing a ‘scleroderma pattern’.ResultsSignificantly larger capillary diameters were observed in cases versus controls both at basal NVC and during follow-up NVC (p=30 µm dilated capillaries/mm at basal NVC was the strongest single predictor of ‘scleroderma pattern’ evolution with 24% increased risk per each dilated capillary (OR 1.24, 95% CI 1.17,1.32). Additionally, a tree-based analysis suggested the efferent (venous) diameter of the most dilated capillary on basal NVCas a variable of interest to identify patients maintaining primary RP.ConclusionThis is the first study to describe an NVC ‘prescleroderma signature’ to potentially identify RP patients later developing a ‘scleroderma pattern’.

Giant cell arteritis (GCA) is the most common form of vasculitis of the adult. General practitioners (GPs) are usually the first physicians who take care of GCA patients. In this study, the awareness of GPs from Genoa, Italy, regarding GCA was investigated by a web-based survey. A web-based questionnaire was sent by mail to 775 Italian GPs. It included 12 multiple choice questions regarding practice seniority, practice population size, number of GCA patients followed, and GPs’ diagnostic and therapeutic approach. Of the 775 GPs involved, 76 (9.8%) answered. Thirty-three/75 (44%) declared that they did not see patients with GCA and the remaining 42 (56%) that they diagnose between one and two patients per year. New headache onset was the presenting feature of GCA for the majority of GPs (78.3%). GCA was diagnosed on the basis of clinical presentation alone by 35.2% of them, of temporal artery biopsy by 49.3%, and by imaging, including ultrasound and magnetic resonance imaging, by 15.5%. The referral pattern was mainly toward rheumatologists (68.5%). Only 27.8% GPs declared they start treatment at the first clinical suspicion, with the others waiting for laboratory and imaging examinations or specialist consultation. The doses of glucocorticoids used were in keeping with current guidelines. The management of GCA by GPs from Genoa is in general correct, with the exceptions of excessive confidence in headaches for diagnosis and of the timing of GC initiation. These points suggest that a program of information and education for GPs is warranted.

Objectives To investigate the validation status of laser Doppler flowmetry (LDF) in systemic sclerosis (SSc) according to the ‘Outcome Measures in Rheumatologic Clinical Trials’ (OMERACT) filter. Methods The literature was systematically reviewed to identify all reports assessing the microcirculatory flow in SSc patients. The OMERACT filter –including the domains of truth, discrimination and feasibility– was applied and a quality assessment was done by the ‘Good Methods Checklist’. To ease the comparison between studies the results were grouped per dynamic test situation: basal, cold/heat challenge and occlusion. Results The literature search resulted in 4332 hits. Based on title and abstract screening 243 hits were retained and of these, 52 full texts described an assessment by LDF in SSc patients. Finally, 18 studies passed the quality assessment and form the object of this review. The review reveals that expert consensus is lacking on the face and content validity of LDF in SSc. The construct validity of LDF, on the other hand is partially validated. Conflicting results exist on the discriminant capacity of LDF in distinguishing healthy from diseased patients, primary from secondary Raynaud's phenomenon and in differentiating between disease subsets. Yet, complementing an LDF-measurement with a heat challenge, as well as the evaluation of the post-occlusive hyperaemic response, has the potential to elicit a difference between healthy and diseased patients. Lastly, data on the feasibility of LDF in SSc is lacking in the identified literature. Conclusion This systematic review emphasizes the very preliminary validation status of LDF in the assessment of the microcirculatory flow in SSc.

Abdominal acute pain is a manifestation of heterogeneous medical conditions, with difficult clinical-laboratory assessment. Multi-detector CT (MDCT) is the gold standard imaging technique for evaluating adult patients with acute abdominal pain. Due to its fast execution and the high spatial resolution, CT is fundamental in the diagnostic and therapeutic work-up of patients with time-dependent pathology that could require surgical treatment, reducing mortality and morbidity. However, the radiological risk connected to the ionizing radiation use should not be underestimated, especially in young patients. The aim of this study is to identify optimized CT protocols to apply in the management of non-traumatic acute abdomen. In particular, this review is focused on the main emergency settings: acute pancreatitis, small bowel obstruction, acute appendicitis and acute diverticulitis. This survey would not be complete without mentioning Dual-Energy CT (DECT) technique, one of the last frontiers in CT, achieving encouraging results also in acute abdominal conditions.

Background Uveitis is one of the most frequent ophthalmologic manifestations in rheumatology. Uveal inflammation can underlie a systemic inflammatory rheumatic disease (SIRD) in approximately 30% of cases with a significant burden on the quality of life since it represents a cause of blindness in up to 20% of cases in Western countries. Methods In this review, we provide a comprehensive overview of the pathophysiology of uveitis associated with SIRDs. According to our literature survey on the epidemiology of uveitis among SIRDs, spondyloarthritides, Behcet's disease and sarcoidosis get the major impact. Results In Behcet's uveitis, the key players are highly polarized Th1 and Th17 lymphocytes, natural killer T cells and gamma delta T cells. All contribute to a great destructive inflammatory environment with the most serious visual damage resulting from the involvement of the posterior segment of the eye. In contrast, spondyloarthritides-related uveitis derives from a complex interaction between genetic background and extra-ocular inflammatory mediators originating from enthesitis, arthritis, psoriatic lesions and microbiome pro-inflammatory alterations. In such conditions, the immune infiltration of CD4+ T cells, Th17 and natural killer cells along with pro-inflammatory cytokines, TNF-alpha among all, leads to intraocular inflammation. Lastly, granuloma formation represents the primary hallmark lesion in sarcoid uveitis. This suggests a profound link between the innate system that mainly recruits activated macrophages and adaptive system involving by Th1, Th17 and Th17.1 cells. Conclusions Awareness among rheumatologists of a potential severe ocular involvement generates new insights into targeted therapeutic approaches and personalized treatments for each patient.

To assess the efficacy of radiomics features obtained by T2-weighted sequences to predict clinical outcomes following liver resection in colorectal liver metastases patients.This retrospective analysis was approved by the local Ethical Committee board and radiological databases were interrogated, from January 2018 to May 2021, to select patients with liver metastases with pathological proof and MRI study in pre-surgical setting. The cohort of patients included a training set and an external validation set. The internal training set included 51 patients with 61 years of median age and 121 liver metastases. The validation cohort consisted a total of 30 patients with single lesion with 60 years of median age. For each volume of interest, 851 radiomics features were extracted as median values using PyRadiomics. Nonparametric test, intraclass correlation, receiver operating characteristic (ROC) analysis, linear regression modelling and pattern recognition methods (support vector machine (SVM), k-nearest neighbours (KNN), artificial neural network (NNET) and decision tree (DT)) were considered.The best predictor to discriminate expansive versus infiltrative front of tumour growth was obtained by wavelet_LHL_gldm_DependenceNonUniformityNormalized with an accuracy of 82%; to discriminate high grade versus low grade or absent was the wavelet_LLH_glcm_Imc1 with accuracy of 88%; to differentiate the mucinous type of tumour was the wavelet_LLH_glcm_JointEntropy with accuracy of 92% while to identify tumour recurrence was the wavelet_LLL_glcm_Correlation with accuracy of 85%. Linear regression model increased the performance obtained with respect to the univariate analysis exclusively in the discrimination of expansive versus infiltrative front of tumour growth reaching an accuracy of 90%, a sensitivity of 95% and a specificity of 80%. Considering significant texture metrics tested with pattern recognition approaches, the best performance was reached by the KNN in the discrimination of the tumour budding considering the four textural predictors obtaining an accuracy of 93%, a sensitivity of 81% and a specificity of 97%.Ours results confirmed the capacity of radiomics to identify as biomarkers, several prognostic features that could affect the treatment choice in patients with liver metastases, in order to obtain a more personalized approach.

Raynaud phenomenon (RP), typically, precede the clinical onset of systemic manifestations in several connective tissue diseases (CTDs). These autoimmune disorders usually share a microvascular damage whose alterations can be detected by nailfold videocapillaroscopy (NVC). The aim of the study was to compare the NVC microvascular status in Mixed Connective Tissue Disease (MCTD) versus the Undifferentiated Connective Tissue Disease (UCTD), and to search correlations between NVC findings and specific autoantibodies in UCTD patients.Clinical data and NCV patterns were retrospectively obtained from the files of 46 MCTD patients, 47 stable UCTD patients and 51 individuals with primary RP (PRP) as controls collected in a central database (VideoCap®, DS Medica, Milan, Italy). ANA and ENA Abs were tested respectively by indirect immunofluorescence and enzyme-linked immunosorbent assay."Scleroderma-like" (SSc-like) NVC pattern was significantly more frequent in MCTD than in UCTD patients (48% vs 11%, p 0.001). Giant capillaries, abnormal shapes (i.e. neoangiogenesis) and lower capillary density were predominantly detected among MCTD versus UCTD patients (48% vs 11%, 49% vs 13%, 52% vs 9%, respectively, p 0.001). The absolute number of capillaries was significantly lower in MCTD versus UCTD patients (mean 7 ± 1.7 SD vs mean 9.2 ± 1.3 SD, respectively, p 0.001). Fully normal NVC pattern and non-specific NVC alterations were respectively observed in 6% and 46% of MCTD and in 6% and 83% of UCTD. Moreover, PRP patients showed normal NVC pattern and non-specific capillary abnormalities in 23% and in 77%, respectively. No statistically significant correlations were observed between NVC patterns and ANA patterns/specific ENA-Abs among the UCTD patients.The significant presence of the SSc-like NVC pattern and reduced number of capillaries seem the most typical NVC findings in MCTD in comparison to UCTD patients, suggesting a reflection of more complex and severe disease in MCTD ones.

COVID-19 is a multisystem disease that causes endothelial dysfunction and organ damage. Aim of the study was to evaluate the microvascular status in COVID-19 survivors with past different disease severity, in comparison with age and sex-matched primary Raynaud's phenomenon (PRP) patients and control subjects (CNT), including possible effects of concomitant therapies.Sixty-one COVID-19 survivors (mean age 58 ± 13 years, mean days from disease onset 126 ± 53 and mean days from recovery 104 ± 53), thirty-one PRP patients (mean age 59 ± 15 years, mean disease duration 11 ± 10 years) and thirty CNT (mean age 58 ± 13 years) underwent nailfold videocapillaroscopy (NVC) examination. The following capillaroscopic parameters were searched and scored (0-3): dilated capillaries, giant capillaries, isolated microhemorrhages, capillary ramifications (angiogenesis) and capillary number, including absolute capillary number per linear millimeter at the nailfold bed.The mean nailfold capillary number per linear millimeter was significantly lower in COVID-19 survivors when compared with PRP patients and CNT (univariate and multivariate analysis p 0.001). On the contrary, COVID-19 survivors showed significantly less isolated microhemorrhages than PRP patients and CNT (univariate and multivariate analysis, p = 0.005 and p = 0.012, respectively). No statistically significant difference was observed between COVID-19 survivors and control groups concerning the frequency of dilated capillaries and capillary ramifications. COVID-19 selective therapies showed a promising trend on preserving capillary loss and deserving further investigations.SARS-CoV-2 seems to mainly induce a significant loss of capillaries in COVID-19 survivors at detailed NVC analysis in comparison to controls. The presence of a significant reduced score for isolated microhaemorrhages in COVID-19 survivors deserves further analysis.

Objective. Health-Related Quality of Life (HRQoL) in adult patients with mixed connective tissue disease (MCTD) has not been described so far. Therefore, we performed an explorative study to evaluate HRQoL in MCTD patients.Methods. MCTD patients fulfilling the Kahn criteria and participating in the prospective follow-up cohort for MCTD of the Leiden University Medical Center were included; and matched to systemic sclerosis (SSc) patients based on age, sex and disease duration. Data on disease characteristics and HRQoL (SF36 and EQ-5D) were collected annually. HRQoL was compared between MCTD and SSc patients at baseline. Factors associated with HRQoL in MCTD were identified using linear regression and change in HRQoL over 3 years using linear mixed models.Results. Thirty-four MCTD patients (121 visits) and 102 SSc patients (424 visits) were included. At baseline, MCTD patients presented with interstitial lung disease, cardiac involvement, synovitis and myositis more frequently compared to SSc patients, while use of immunosuppressive medication was less frequent. In both groups, mean SF36 scores were lower than in the general Dutch population. The SF36 subscore "general health perception" was impacted most in both groups (MCTD: 38.5 [SD:7.0], SSc: 39.9 [SD:8.9]). During follow-up, SF36 scores improved in MCTD patients, while EQ5DNL remained stable. No specific characteristics were identified that associated with baseline HRQoL or change in HRQol over time.Conclusion. Like in SSc, HRQoL in MCTD is significantly impaired, especially the general health perception of patients. Evaluation in larger prospective cohorts is needed to identify characteristics that impact HRQol most.

Microvascular remodeling is one major responsible for vascular adaptation in pregnancy, still it is not routinely evaluated in the obstetric field. This pilot study aimed to explore the role of nailfold capillaroscopy (NCV) in detecting microvascular changes during normal pregnancy.A population of 30 healthy pregnant women was longitudinally followed performing clinical assessment and NVC evaluation at each trimester and post-partum. Thirty non-pregnant age-matched healthy women having received at least two NVCs with a minimum 9 to 12-month interval were selected as controls. All NVC images were evaluated by a qualitative and semi-quantitative assessment using current standardised approach. Statistical analyses were conducted to assess NVC trend throughout gestation and its possible association with pregnancy course.A progressive significant increase of NVC neoangiogenesis and a specular reduction in capillary dilations was observed during pregnancy (p 0.05). These variations were not found in age-matched controls, who showed stable NVC parameters over a similar time frame (p 0.05). Additionally, a significant inverse correlation was found between NVC neoangiogenesis rate and maternal systemic BP (rho = -0.72, p 0.005).This first comprehensive longitudinal NVC evaluation during normal pregnancy reports significant but physiological microvascular variations throughout gestation, suggesting NVC as a safe and promising technique for further investigate and define patterns of microvascular changes also in pathological pregnancies.