The added value of artificial intelligence to LI-RADS categorization: A systematic review.

PURPOSE: The objective of this systematic review was to critically assess the available literature on deep learning (DL) and radiomics applied to the Liver Imaging Reporting and Data System (LI-RADS) in terms of 1) automatic LI-RADS classification of liver nodules; 2) the contribution of DL and radiomics to human evaluation in the classification of liver nodules following LI-RADS protocol. MATERIALS AND METHODS: A literature search was conducted to identify original research studies published up to April 2021. The inclusion criteria were: English language, focus on computed tomography (CT) and/or magnetic resonance (MR) with specified number of patients and lesions, adoption of LI-RADS classification for the detected hepatic lesions, and application of AI in the classification of liver nodules. Review articles, conference papers, editorials and commentaries, animal studies or studies with absence of AI and/or LI-RADS were excluded. After screening 221 articles, 11 studies were included in this review. RESULTS: All the included studies proved that DL and radiomics have high performances in liver nodules classification, sometimes similar or better than human evaluation. The best performances of DL was an AUC of 0.95 on MR and the best performance of radiomics was AUC of 0.98 either on CT and MR, while the lower ones were respectively AUC of 0.63 either on CT and MR for DL and AUC of 0.70 on CT for radiomics. CONCLUSION: DL and radiomics could be a useful tool in assisting radiologists in the diagnosis and classification of liver nodules according to LI-RADS.

Non-adherence and discontinuation rate for oral and parenteral methotrexate: A retrospective-cohort study in 8,952 patients with psoriatic arthritis.

BACKGROUND AND AIMS: Treatment options for PsA, following non-steroidal anti-inflammatory drugs (NSAIDs), include conventional synthetic disease modifying anti-rheumatic drugs (csDMARDS), particularly methotrexate (MTX). The present study was performed to determine the non-adherence and discontinuation rates of different methotrexate (MTX) formulations in psoriatic arthritis (PsA). APPROACH AND RESULTS: We performed a retrospective-cohort study on patients with PsA identified by disease-specific code in the administrative-health-databases of a Northern Italian region (Lombardy) between 2004 and 2015. Subjects were defined as non-adherent if less than 80% of the prescribed MTX dose was taken based on the time between each prescription. Discontinuation rates were calculated using the time between the first and the last MTX prescription over an observation period of 120 months. Among 8952 patients with PsA, 33% were treated with MTX (mean dosage 10 mg/week ± 2.5 mg standard deviation), more frequently (59%) in its parenteral formulation at a 10 mg weekly dosage (35%). Oral glucocorticoids were prescribed to 21% of patients, while non-steroidal anti-inflammatory drugs to 45%. Approximately 37% of patients with PsA were defined as non-adherent to MTX, with the oral formulation associated with an increased risk of non-adherence (hazard ratio 2.08, 95% confidence interval 1.84-2.35, p < 0.001) compared with parenteral 10-15 mg weekly doses. Oral MTX was discontinued in 52% of cases without a significantly increased risk of discontinuation compared to parenteral formulations which, at higher dosages, had a more favorable retention rate. CONCLUSION: Oral MTX formulation is associated with a 2-fold risk of non-adherence compared to MTX parenteral route in PsA.

Risk of hospitalization for heart failure in rheumatoid arthritis patients treated with etanercept and abatacept.

To estimate biologic influence on heart failure (HF) risk in rheumatoid arthritis. Retrospective cohort (RECORD Study of Italian Society for Rheumatology) study on administrative healthcare databases. We identified 2527 patients treated with either etanercept (n = 1690) or abatacept (n = 837). HF incidence rate was higher in the abatacept cohort than in the etanercept cohort with a 2.38 (95% CI 1.08-5.27) crude competing risk HR (SHR) for abatacept of developing HF, not confirmed after adjustment for prespecified confounders (SHR 1.43; 95% CI 0.51-3.98). Abatacept, compared to etanercept, is prescribed to patients with a worse cardiovascular profile but does not increase the risk of developing HF, when confounding factors are accounted for.

HCV-negative mixed cryoglobulinemia and kidney involvement: in-depth review on physiopathological and histological bases.

Type II mixed cryoglobulinemia without evidence of HCV infection but rather with renal involvement has been occasionally described. The pathogenesis of cryoglobulinemic kidney disease is most likely related to immune complex deposition including cryoglobulins, and cryoaggregation after cold exposure could play a pivotal role in clinical expression of cryoglobulinemia. In these cases, acute kidney injury and proteinuria remain the most frequent clinical expression of a cryoglobulinemic glomerulonephritis. Type II cryoglobulinemia with the laboratory finding of both monoclonal and polyclonal cryoglobulins is the most prevalent bio-humoral pattern among HCV-negative phenotypes with renal involvement, while type III cryoglobulinemia with polyclonal Ig is rare. Histological data in renal biopsies support the hypothesis that regardless of the HCV status cryoglobulinemia vasculitis share the same frequent pathological finding of membranoproliferative glomerulonephritides, but other histological patterns have also been observed in a minority of cases. In HCV-negative mixed cryoglobulinaemia, the paraneoplastic origin of the immune dysfunction should be ruled out and sporadic cases have been reported, while there is no cumulative evidence on the prevalence of these tumour-associated manifestations. Moving from the classification criteria and the etiopathogenesis of mixed cryoglobulinaemia, we provide a comprehensive review of the literature on the appearance of the disease with kidney injury in association with malignancies or autoimmune disorders without HCV coexistence.

One year in review 2018: novelties in the treatment of rheumatoid arthritis.

The current approach to treatment of rheumatoid arthritis (RA) includes early and aggressive intervention aiming to reach early and persistent low disease activity and remission. New drugs have improved the therapeutic armamentarium of rheumatologists, providing new options for patients. Beyond these innovations, new evidence has improved the safety of therapies and provided tools for the optimisation of long-term management of RA. This paper reviews the most relevant studies published over the last year in the field of treatment of RA.

Cutaneous and Mucosal Manifestations of Sjögren's Syndrome.

Sjögren's syndrome is currently considered an "autoimmune epithelitis," as exocrine glands, especially salivary and lacrimal, are progressively destructed by an immune-mediated process associated with specific serum autoantibodies and local lymphocyte infiltrate. Xerostomia remains a key complain in patients with Sjögren's syndrome but should be evaluated also for other causes such as xerogenic medications, followed by radiation and chemotherapy for head and neck cancers, hormone disorders, infections, or other connective tissue diseases. Further, xerophtalmia (also known as dry eye) frequently associated with keratoconjunctivitis sicca cumulatively affects approximately 10-30% of the general population with increasing incidence with age and is more frequently secondary to non-autoimmune diseases. On the other hand, numerous patients with Sjögren's syndrome manifest signs of systemic dryness involving the nose, the trachea, the vagina, and the skin, suggesting that other glands are also affected beyond the exocrine epithelia. Skin involvement in Sjögren's syndrome is relatively common, and various manifestations may be present, in particular xeroderma, eyelid dermatitis, annular erythema, and cutaneous vasculitis. Additional skin non-vasculitic manifestations include livedo reticularis which may occur in the absence of vasculitis, and localized nodular cutaneous amyloidosis possibly representing lymphoproliferative diseases related to Sjögren's syndrome. The treatment of skin and mucosal manifestations in Sjögren's syndrome is similar regardless of the cause, starting from patient education to avoid alcohol and tobacco smoking and to pursue dental hygiene. In conclusion, a strict collaboration between the dermatologist and the rheumatologist is essential in the adequate management of Sjögren's syndrome skin and mucosal manifestations.

Personalized medicine in rheumatology: the paradigm of serum autoantibodies.

The sequencing of the human genome is now well recognized as the starting point of personalized medicine. Nonetheless, everyone is unique and can develop different phenotypes of the same disease, despite identical genotypes, as well illustrated by discordant monozygotic twins. To recognize these differences, one of the easiest and most familiar examples of biomarkers capable of identifying and predicting the outcome of patients is represented by serum autoantibodies. In this review, we will describe the concept of personalized medicine and discuss the predictive, prognostic and preventive role of antinuclear antibodies (ANA), anti-citrullinated peptide antibodies (ACPA), rare autoantibodies and anti-drug antibodies (ADA), to evaluate how these can help to identify different disease immune phenotypes and to choose the best option for treating and monitoring rheumatic patients in everyday practice. The importance of ANA resides in the prediction of clinical manifestations in systemic sclerosis and systemic lupus erythematosus and their association with malignancies. ACPA have a predictive role in rheumatoid arthritis, they are associated with the development of a more aggressive disease, extra-articular manifestations and premature mortality in RA patients; moreover, they are capable of predicting therapeutic response. Rare autoantibodies are associated with different disease manifestations and also with a greater incidence of cancer. The determination of ADA levels may be useful in patients where the clinical efficacy of TNF-α inhibitor has dropped, for the assessment of a right management. The resulting scenario supports serum autoantibodies as the cornerstone of personalized medicine in autoimmune diseases.

Recommendations for infectious disease screening in migrants to Western Europe with inflammatory arthropathies before starting biologic agents. Results from a multidisciplinary task force of four European societies (SIR, SER, SIMET, SEMTSI) facing the largest impact of the flow of migrants today.

OBJECTIVES: Inflammatory arthritis needs infectious disease screening before starting a biologic agent, however, few data are known about migrant patients, who represent a peculiar population which requires a multidisciplinary approach among international health specialists and should also be considered by health authorities. For this reason, the Italian and Spanish Societies of Rheumatology (SIR and SER) and Tropical Medicine (SIMET and SEMTSI) promoted a multidisciplinary task force in order to produce specific recommendations about screening and advices to be considered in migrant patients with inflammatory arthritis candidate to receive biological therapy, according to their geographical origin. METHODS: The experts provided a prioritised list of research questions and the eligible spectrum of inflammatory arthritis, biologic drugs and infectious disease were defined in order to perform a systematic literature review. A search was made in Medline, Embase and Cochrane library, updated to March 2015. Ubiquitous infections and HBV, HCV, HIV and tuberculosis that are already considered in national and international recommendations, were not included. The strength of each recommendation was determined. RESULTS: The task force members agreed on 7 overarching principles. The risk of reactivation of selected potentially latent infectious disease was addressed in migrants with inflammatory arthritis candidates for biologics was considered and 15 potentially relevant infections were identified. CONCLUSIONS: Fifteen disease-specific recommendations were formulated on the basis of high level of agreement among the experts panel.

Safety profile of biologic agents for Behçet's disease in a multicenter observational cohort study.

AIM: The primary aim of this study was to explore the safety profile of biologic treatments in Behçet's disease (BD), based on their mechanism of action; the secondary aim was to study any potential variation in terms of retention rate according to each single drug. METHOD: We studied a total of 85 treatment regimens with biologic agents from 64 patients. The total follow-up was calculated as 8640 patient-years (anti-tumor necrosis factor [TNF]-alpha 7.020, anti-interleukin [IL]-beta 1.368). Cumulative rates of drug retention were studied using the Kaplan-Meier plot and covariates in the regression model included the mechanism of action of the biologic agent, other concomitant therapies, disease duration, sex, age at start of drug therapy; for each confounding factor hazard ratios (HR) were calculated. RESULTS: The most frequently prescribed biologic treatments were anti-TNF-alpha agents (79%), while anti-IL1-beta was used in the remaining regimens. Concomitant disease-modifying antirheumatic drugs were prescribed in 36% of patients, mainly cyclosporine and methotrexate, while in 35/85 regimens low-dose glucocorticoids were associated. During the follow-up, in all but one regimen the safety profile was free of any adverse events or serious adverse events; we observed only one case of endocarditis, reported during the 10th month of etanercept. CONCLUSION: Data from a large multicenter cohort suggest that anti-TNF-alpha and anti-IL1-beta agents are characterized by an excellent safety profile in BD.

Myositis-specific autoantibodies and their association with malignancy in Italian patients with polymyositis and dermatomyositis.

This study aims to characterize myositis-specific antibodies in a well-defined cohort of patients with idiopathic inflammatory myopathy and to determine their association with cancer. Sera from 40 patients with polymyositis, dermatomyositis, and controls were tested by protein and RNA immunoprecipitation to detect autoantibodies, and immunoprecipitation-Western blot was used for anti-MJ/NXP-2, anti-MDA5, and anti-TIF1γ/α identification. Medical records were re-evaluated with specific focus on cancer. Anti-MJ/NXP-2 and anti-TIF1γ/α were the most common antibodies in dermatomyositis. In six dermatomyositis cases, we found five solid forms of cancer and one Hodgkin's lymphoma in long-term remission. Among patients with cancer-associated dermatomyositis, three were positive for anti-TIF1γ/α, two for anti-Mi-2, and one for anti-MJ/NXP-2. The strongest positivity of anti-TIF1γ was seen in two active forms of cancer, and this antibody was either negative or positive at low titers in the absence of cancer or in the 7-year remission Hodgkin's lymphoma. Four out of twenty (20 %) patients with polymyositis had solid cancer, but no specific association with autoantibodies was identified; further, none of the four cases of antisynthetase syndrome had a history of cancer. No serum myositis-associated autoantibody was observed in control sera, resulting in positive predictive value 75 %, negative predictive value 78.5 %, sensitivity 50 %, specificity 92 %, and area under the ROC curve 0.7083 for the risk of paraneoplastic DM in anti-TIF1γ/α (+) patients. Myositis-specific autoantibodies can be identified thanks to the use of immunoprecipitation, and their association with cancer is particularly clear for anti-TIF1γ/α in dermatomyositis. This association should be evaluated in a prospective study by immunoprecipitation in clinical practice.

Sex Differences in the Treatment of Psoriatic Arthritis: A Systematic Literature Review.

Psoriatic arthritis (PsA) is a chronic inflammatory condition associated with skin psoriasis and manifests a wide clinical phenotype, with proposed differences between sexes. Current treatments are based on traditional disease-modifying anti-rheumatic drugs (DMARD), and biologic agents and studies have reported different clinical response patterns depending on sex factors. We aimed to identify sex differences in drug retention rate in patients with PsA and performed a systematic research on MEDLINE, EMBASE and Cochrane databases (1979 to June 2015) for studies regarding effectiveness (measured as drug retention rate) in PsA in both traditional DMARDs and biologics. Demographic data as well as retention rates between sexes were extracted. From a total 709 retrieved references, we included 9 articles for the final analysis. Only one study reported data regarding DMARDs, while eight studies reported retention rate for anti-tumor necrosis factor (TNF) biologics, mainly infliximab, adalimumab and etanercept. No differences were reported in retention rates between sexes for methotrexate, while women manifested lower retention rates compared to men with regard to anti-TNF. We highlight the need to include sex differences in the management flow chart of patients with PsA.

Medical Complications of Tattoos: A Comprehensive Review.

Tattoos are defined as the introduction of exogenous pigments into the dermis in order to produce a permanent design. This process may occur unintentional or may be deliberately administered for cosmetic or medical reasons. Tattoos have been around for over 5000 years and over time have evolved to represent a common cosmetic practice worldwide. Currently, adverse reactions are relatively rare and generally unpredictable and predominantly include immune-mediated reactions and skin infections. Along with better healthcare standards and more stringent public health mandates such as the provision of disposable needles, major infectious complications related to hepatitis and human retroviral infections have decreased significantly. When they do occur, skin infections are most frequently associated with Staphylococcus aureus or Streptococcus pyogenes. The aim of this study is to review the types and rates of medical complications of permanent tattoos. PubMed search and search dates were open ended. Acute local inflammation is the most common complication, but infections, allergic contact dermatitis, and other inflammatory or immune responses that are not well-characterized may occur. As many patients with immune reactions to tattoos do not react on skin or patch testing, it is postulated that the antigens contained in dyes or pigments are such small molecules that they need to be haptenized in order to become immunogenic. Red ink is associated more frequently with long-term reactions, including granulomatous and pseudolymphomatous phenomena or morphea-like lesions and vasculitis. Exacerbation of preexisting psoriasis, atopic dermatitis, and pyoderma gangrenosum may occur after tattooing. There is no well-defined association between cancer and tattoos. The treatment of tattoo-related complications may include local destructive measures (cryotherapy, electro-surgery, dermabrasion, chemical destruction, ablative laser destruction), surgical excision, and thermolysis of the pigment using Q-switched laser therapy.

Biomarkers in psoriatic arthritis: a systematic literature review.

Psoriatic arthritis (PsA) is characterized by chronic inflammation of peripheral joints and axial skeleton, associated with a strong genetic background. Clinics include enthesitis or dactylitis and extra-articular involvement as uveitis or inflammatory bowel disease, while treatment options range from nonsteroidal anti-inflammatory drugs (NSAIDs) to biologics, targeting TNF α or Th17. No serum autoantibody is associated with PsA, while other biomarkers have been proposed for early diagnosis or to predict treatment response. To better discuss this area of growing interest we performed a systematic review of the literature on biomarkers in PsA. Our research retrieved 408 papers, and 38 were included in the analysis. Based on the available literature, we draw some recommendations for the use of biomarkers in the management of patients with PsA.

Serum antinuclear and extractable nuclear antigen antibody prevalence and associated morbidity and mortality in the general population over 15 years.

The prevalence of ANA and anti-ENA in the general population is not well established, especially their clinical significance in healthy subjects. We herein determined the prevalence and predictive value of serum ANA and anti-ENA for connective tissue diseases (CTD), cancer, and mortality. We took advantage of a randomly selected sample of the 1998 general population (Isola I) consisting of 2828 subjects (53% women, age 43±13 years) from a well-defined Northern Italian area. Serum ANA and anti-ENA were tested on the 2690 samples available in 2012 (Isola II, 50% women, age 58±13 years). Administrative databases were searched for CTD, cancer diagnosis, and death cases occurring between enrollment and December 31, 2013. The hazard ratio (HR) was calculated for incident cases. Serum ANA is positive in 18.1% for any titer and 6.1% for titers ≥1:160, 23% in subjects over 50 years and 13.1% and 6.1% for any titer and titers ≥1:160, respectively, in women. The HR for CTD development was significantly high for all ANA titers, with the highest for ANA ≥1:160 (HR 14.19, 95% CI 3.07-65.68). ANA positivity was not associated with cancer (HR 1.03; 95% CI 0.75-1.43), or with mortality (HR adjusted for age and sex 1.40; 95% CI 0.94-2.09). Serum anti-ENA is positive in a minority of subjects with highest figures for anti-nucleosome (1.9%), -histone (1.6%) and -PM/Scl (1.5%). In conclusion, serum ANA prevalence in the general population is highest in senior subjects and in women, while the female predominance is significantly lower compared to overt CTD. Serum ANA is associated with an increased probability of CTD development over time, but does not influence survival or cancer risk.

Seronegative reactive spondyloarthritis and the skin.

Spondyloarthritidies represent a group of conditions affecting the axial and peripheral muscoloskeletal apparatus and are often associated with psoriasis, infections, and inflammatory bowel diseases. Other diseases included in this category are psoriatic arthritis, ankylosing spondylitis, and enteropathic arthritis. Reactive arthritis is an elusive spondyloarthritis, commonly occurring 1 to 3 weeks after a digestive or a genitourinary tract infection, in which microorganisms do not infect the joint directly. Reactive arthritis is classically characterized by large-joint arthritis, urethritis in men and cervicitis in women, and eye inflammation (usually conjunctivitis or uveitis) but encompasses numerous other symptoms and signs, including manifestations of dermatologic interest such as keratoderma blenorrhagicum and circinate balanitis. The diagnosis of reactive arthritis is clinical, and the infectious agent cannot always be identified due to disease latency after the infection. Most cases are self-limiting, but reactive arthritis may become chronic in 30% of cases. Treatment options include anti-inflammatory drugs, steroids, and sulfasalazine; biologic agents, such as tumor necrosis factor α (TNF-α) blockers, have been recently used, but there are only a few randomized clinical trials on the treatment of reactive arthritis. The effectiveness of antimicrobials needs further evaluation.