Enrichment of Immune Dysregulation Disorders in Adult Patients with Human Inborn Errors of Immunity.

Human inborn errors of immunity (IEI) comprise a group of diseases resulting from molecular variants that compromise innate and adaptive immunity. Clinical features of IEI patients are dominated by susceptibility to a spectrum of infectious diseases, as well as autoimmune, autoinflammatory, allergic, and malignant phenotypes that usually appear in childhood, which is when the diagnosis is typically made. However, some IEI patients are identified in adulthood due to symptomatic delay of the disease or other reasons that prevent the request for a molecular study. The application of next-generation sequencing (NGS) as a diagnostic technique has given rise to an ever-increasing identification of IEI-monogenic causes, thus improving the diagnostic yield and facilitating the possibility of personalized treatment. This work was a retrospective study of 173 adults with IEI suspicion that were sequenced between 2005 and 2023. Sanger, targeted gene-panel, and whole exome sequencing were used for molecular diagnosis. Disease-causing variants were identified in 44 of 173 (25.43%) patients. The clinical phenotype of these 44 patients was mostly related to infection susceptibility (63.64%). An enrichment of immune dysregulation diseases was found when cohorts with molecular diagnosis were compared to those without. Immune dysregulation disorders, group 4 from the International Union of Immunological Societies Expert Committee (IUIS), were the most prevalent among these adult patients. Immune dysregulation as a new item in the Jeffrey Model Foundation warning signs for adults significantly increases the sensitivity for the identification of patients with an IEI-producing molecular defect.

Cytokine profile levels and their relationship with parasitemia and cardiomyopathy in people with Chagas disease in Spain. A prospective observational study.

Immunoregulatory networks may have a role in controlling parasitemia in the chronic phase of human Chagas disease. The aim was to describe the serum cytokine profile of Trypanosoma cruzi in chronically infected patients and to evaluate its relationship with parasitemia and Chagas cardiomyopathy.This prospective observational study included adult patients with chronic Chagas disease. Demographic and clinical data were collected, and peripheral blood samples were used to perform T. cruzi real-time polymerase chain reaction (RT-PCR) and determine the serum cytokine profile.Fifty-eight patients were included; 17 (29.3%) had positive RT-PCR results. This group had a higher median concentration of TNF-α (p = 0.003), IL-6 (p = 0.021), IL-4 (p = 0.031), IL-1ß (p = 0.036), and IL-17A (p = 0.043) than those with a negative RT-PCR. Patients with cardiac involvement had a higher median concentration of IL-5 (p = 0.016) than those without.These results reinforce the key role that cytokines play in Chagas disease patients with parasitemia and cardiac involvement.

The Accuracy and Absolute Reliability of a Knee Surgery Assistance System Based on ArUco-Type Sensors.

Recent advances allow the use of Augmented Reality (AR) for many medical procedures. AR via optical navigators to aid various knee surgery techniques (e.g., femoral and tibial osteotomies, ligament reconstructions or menisci transplants) is becoming increasingly frequent. Accuracy in these procedures is essential, but evaluations of this technology still need to be made. Our study aimed to evaluate the system's accuracy using an in vitro protocol. We hypothesised that the system's accuracy was equal to or less than 1 mm and 1° for distance and angular measurements, respectively. Our research was an in vitro laboratory with a 316 L steel model. Absolute reliability was assessed according to the Hopkins criteria by seven independent evaluators. Each observer measured the thirty palpation points and the trademarks to acquire direct angular measurements on three occasions separated by at least two weeks. The system's accuracy in assessing distances had a mean error of 1.203 mm and an uncertainty of 2.062, and for the angular values, a mean error of 0.778° and an uncertainty of 1.438. The intraclass correlation coefficient was for all intra-observer and inter-observers, almost perfect or perfect. The mean error for the distance's determination was statistically larger than 1 mm (1.203 mm) but with a trivial effect size. The mean error assessing angular values was statistically less than 1°. Our results are similar to those published by other authors in accuracy analyses of AR systems.

Spanish cohort of VEXAS syndrome: clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism.

BACKGROUND: The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. OBJECTIVES: To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. METHODS: Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. RESULTS: Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. CONCLUSION: Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms.

Rationale for combined therapies in severe-to-critical COVID-19 patients.

An unprecedented global social and economic impact as well as a significant number of fatalities have been brought on by the coronavirus disease 2019 (COVID-19), produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute SARS-CoV-2 infection can, in certain situations, cause immunological abnormalities, leading to an anomalous innate and adaptive immune response. While most patients only experience mild symptoms and recover without the need for mechanical ventilation, a substantial percentage of those who are affected develop severe respiratory illness, which can be fatal. The absence of effective therapies when disease progresses to a very severe condition coupled with the incomplete understanding of COVID-19's pathogenesis triggers the need to develop innovative therapeutic approaches for patients at high risk of mortality. As a result, we investigate the potential contribution of promising combinatorial cell therapy to prevent death in critical patients.

Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia.

X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4-dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8-207.8, P < 0.001). The patients' susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.

Percutaneus intermetatarsal ligament release and minimally invasive distal metatarsal osteotomy for treatment second intermetatarsal space syndrome.

BACKGROUND AND OBJECTIVE: Since the description of the syndrome of the second intermetatarsal space, this is a common diagnosis among foot and ankle surgeons. However, no series have been published that consider this syndrome as its own entity. The objective of this study is to evaluate the clinical and radiological results of the release of the intermetatarsal ligament and minimally invasive distal metatarsal osteotomy in patients diagnosed with second space syndrome. MATERIALS AND METHODS: An observational, longitudinal, retrospective study was carried out in patients with a clinical diagnosis of second space syndrome operated on using a minimally invasive technique. For the clinical results, the visual analog scale (VAS) for subjective pain, the Manchester-Oxford Foot Questionnaire (MOXFQ) and the scale for minor metatarsals and interphalangeals of the American Orthopedic Foot and Ankle Society (AOFAS-LMTS) were used for clinical-functional assessment. Consolidation or not of osteotomies was recorded and complications were recorded. RESULTS: Twenty-nine feet in 29 patients were included in the study. After a mean follow-up of 39 months (25-50), clinically and statistically significant improvement was obtained in the scores: pain VAS, scales and subscales of the MOXFQ and the AOFAS-LMTS (p < 0.0001). All osteotomies healed at the end of follow-up and no major complications were recorded. CONCLUSIONS: Percutaneous or minimally invasive surgery, in patients with second intermetatarsal space syndrome, obtains good clinical, functional and subjective results, with few complications. Therefore, we consider it an effective, safe and recommended technique in the hands of experienced surgeons.

Does delaying surgery for "healthy" hip fracture patients have increased complications and mortality?

INTRODUCTION: Surgical delay is one of the risk factors for mortality and morbidity in patients with HF. One of the causes of delay is due to admission on Thursday-Friday, weekends, holidays or previous periods. The final objective of this study is to analyze administrative-organizational delay in complication and mortality rates. MATERIAL AND METHODS: A total of 607 cases of surgically operated hip fractures were analyzed. Two groups were established, one of them operated on in < 48 h (ND group) and the other surgically delayed for administrative organizational reasons (AA group). Demographic variables related to treatment and fracture were analyzed in both groups, as well as the rates of surgical wound complications, general complications and mortality rate in the first 30 days, in the first year and more than one year after surgery. RESULTS: We observed a surgical wound seroma and staining rate of 15.7% in the AA group and 9.6% in the ND group; and a surgical wound surface infection rate of 1.9% in the AA group and 0.8% in the ND group (p = 0.275). General complications occurred in 34.4% (AA group) and 29% (ND group). The 30-day mortality rate was 4.8% in the AA group and 1.9% in the ND group (p = 0.081). CONCLUSION: We found no statistically significant differences in patients delayed for administrative reasons in terms of mortality and surgical wound and general complication rates. Although the proportion of surgical wound complications and 30-day mortality was higher in the AA group versus the ND group.

Performance of a flow cytometry-based immunoassay for detection of antibodies binding to SARS-CoV-2 spike protein.

The performance of a laboratory-developed IgG/IgA flow cytometry-based immunoassay (FCI) using Jurkat T cells stably expressing full-length native S protein was compared against Elecsys electrochemiluminiscent (ECLIA) Anti-SARS-CoV-2 S (Roche Diagnostics, Pleasanton, CA, USA), and Liaison SARS-CoV-2 TrimericS IgG chemiluminiscent assay (CLIA) (Diasorin S.p.a, Saluggia, IT) for detection of SARS-CoV-2-specific antibodies. A total of 225 serum/plasma specimens from 120 acute or convalescent COVID-19 individuals were included. Overall, IgG/IgA-FCI yielded the highest number of positives (n = 179), followed by IgA-FCI (n = 177), Roche ECLIA (n = 175), IgG-FCI (n = 172) and Diasorin CLIA (n = 154). For sera collected early after the onset of symptoms (within 15 days) IgG/IgA-FCI also returned the highest number of positive results (52/72; 72.2%). Positive percent agreement between FCI and compared immunoassays was highest for Roche ECLIA, ranging from 96.1 (IgG/IgA-FCI) to 97.7% (IgG-FCI), whereas negative percent agreement was higher between FCI and Diasosin CLIA, regardless of antibody isotype. The data suggest that FCI may outperform Roche ECLIA and Diasorin CLIA in terms of clinical sensitivity for serological diagnosis of SARS-CoV-2 infection.

Drug reexposure in children with severe mucocutaneous reactions.

In pediatric patients, severe cutaneous adverse reactions (SCARs) frequently occur in the course of acute illnesses, mostly infections, which are usually treated with antibiotics or analgesics. The drug provocation test (DPT) is contraindicated in such situations, due to the risk of triggering a new severe reaction. As a consequence, lifelong avoidance is recommended. However, causation is uncertain in most cases. The dilemma arises when avoiding the drug is not harmless for the patient. We have attended three patients who were referred to our pediatric allergy unit with a history of SCAR related in time to simultaneous use of paracetamol and ibuprofen. Medical records and images of the patients were reviewed with the assistance of a dermatologist, and alternative diagnoses were considered in both cases. The ALDEN score for implicated drugs was calculated. After considering a high probability of ibuprofen tolerance and obtaining informed consent from the patients, we performed a sequential allergy workup including in vitro tests, skin tests, and finally DPT in two of the patients, confirming ibuprofen tolerance. In conclusion, although generally contraindicated, DPT may be considered for some useful drugs after careful evaluation of the risk-benefit balance, preceded by a sequential study including in vitro and skin tests.

The age again in the eye of the COVID-19 storm: evidence-based decision making.

BACKGROUND: One hundred fifty million contagions, more than 3 million deaths and little more than 1 year of COVID-19 have changed our lives and our health management systems forever. Ageing is known to be one of the significant determinants for COVID-19 severity. Two main reasons underlie this: immunosenescence and age correlation with main COVID-19 comorbidities such as hypertension or dyslipidaemia. This study has two aims. The first is to obtain cut-off points for laboratory parameters that can help us in clinical decision-making. The second one is to analyse the effect of pandemic lockdown on epidemiological, clinical, and laboratory parameters concerning the severity of the COVID-19. For these purposes, 257 of SARSCoV2 inpatients during pandemic confinement were included in this study. Moreover, 584 case records from a previously analysed series, were compared with the present study data. RESULTS: Concerning the characteristics of lockdown series, mild cases accounted for 14.4, 54.1% were moderate and 31.5%, severe. There were 32.5% of home contagions, 26.3% community transmissions, 22.5% nursing home contagions, and 8.8% corresponding to frontline worker contagions regarding epidemiological features. Age > 60 and male sex are hereby confirmed as severity determinants. Equally, higher severity was significantly associated with higher IL6, CRP, ferritin, LDH, and leukocyte counts, and a lower percentage of lymphocyte, CD4 and CD8 count. Comparing this cohort with a previous 584-cases series, mild cases were less than those analysed in the first moment of the pandemic and dyslipidaemia became more frequent than before. IL-6, CRP and LDH values above 69 pg/mL, 97 mg/L and 328 U/L respectively, as well as a CD4 T-cell count below 535 cells/µL, were the best cut-offs predicting severity since these parameters offered reliable areas under the curve. CONCLUSION: Age and sex together with selected laboratory parameters on admission can help us predict COVID-19 severity and, therefore, make clinical and resource management decisions. Demographic features associated with lockdown might affect the homogeneity of the data and the robustness of the results.

Influence of weight status on bone mineral content measured by DXA in children.

INTRODUCTION: Childhood obesity is a public health problem with repercussions in later life. As tissue formation peaks in childhood we determined how weight status influences bone mineral content. MATERIAL AND METHODS: We studied 553 children aged 4-18 years over 10 years (46.8% girls). We measured age, weight, height and through bone densitometry (DXA), bone mineral content (BMC), bone mineral density (BMD), and waist, arm and hip circumferences. The patients were divided into groups using the body mass index z-score: underweight, normal weight, overweight, obese and very obese. RESULTS: BMC and BMD values were highest in the normal-weight and overweight groups. Logistic regression showed bone mineralization was inversely associated with waist circumference, the association being positive for weight and age. No differences were found according to sex. DISCUSSION: Studies of the relationship between weight and bone mineralization report contradictory results, often because of different study designs. Moreover, studies in children are either few or with small samples. Our findings in a large sample show the importance of weight status in bone mineralization given the risk of bone fractures or osteoporosis. CONCLUSIONS: Weight status influenced bone mineralization. BMC and BMD decreased in children with a higher degree of obesity. Waist circumference correlated negatively with bone mineralization.

Non-alcoholic fatty liver disease is associated with bacterial translocation and a higher inflammation response in psoriatic patients.

Psoriasis and non-alcoholic fatty liver disease (NAFLD) are both inflammatory diseases. The study objective was to estimate the risk of NAFLD, non-alcoholic steatohepatitis, and liver fibrosis (by liver stiffness and liver biopsy) in patients with psoriasis and to determine the epidemiological, clinical, immunological (TNF-α, IL-2, IL-6, IL-12, IL-17, IL-23, and TGF-ß) characteristics, and bacterial translocation. Of the 215 psoriatic patients included, 91 presented NAFLD (prevalence: 42.3%). Compared to patients with psoriasis alone, those with NAFLD were significantly more likely to have metabolic syndrome, diabetes, dyslipidemia, body mass index ≥ 30 kg/m2, homeostatic model assessment of insulin resistance ≥ 2.15, and greater psoriasis area severity index. NAFLD patients also had significantly higher levels of TNF-α (p = 0.002) and TGF-ß (p = 0.007) and a higher prevalence of bacterial translocation (29.7% vs. 13.7%; p = 0.004). Liver stiffness measurement was over 7.8 kPa in 17.2% (15/87) of NAFLD patients; 13 of these underwent liver biopsy, and 5.7% (5/87) had liver fibrosis, while 1.1% (1/87) had advanced fibrosis or non-alcoholic steatohepatitis. In conclusion the prevalence of NAFLD in patients with psoriasis is high and associated with a higher prevalence of metabolic syndrome features, bacterial translocation and a higher pro-inflammatory state. It is worth mentioning that liver fibrosis and non-alcoholic steatohepatitis are not frequent in this population of patients.

Insulin Resistance as a Diagnostic Criterion for Metabolically Healthy Obesity in Children.

OBJECTIVES: In recent years, a subgroup of individuals with obesity has been described as having a lower risk of metabolic and cardiovascular complications. These individuals have what is referred to as metabolically healthy obesity (MHO), which has a favorable metabolic profile and a lower probability of long-term complications. The definition of this subtype in children is not clear. The aim of the present study was to determine whether Homeostasis Model Assessment (HOMA) above a set threshold could be the marker of metabolically unhealthy obesity (MUO) in children, or a parameter that can be used in the overall assessment. It is intended to compare the International Diabetes Federation (IDF) criteria against HOMA in the diagnosis of MUO. METHODS: This observational, retrospective, cohort study included children with obesity and analyzed their metabolic state by means of blood testing and dual-energy X-ray absorptiometry. RESULTS: A total of 96 patients were included, 44.8% boys and 55.2% girls, ages 6-17 years. The patients with MHO according to the HOMA criterion were younger (P = 0.001), had a lower body mass index (BMI) z score (P = 0.006), waist-height index (P = 0.009), hip-height index (P = 0.010), blood glucose (P = 0.003), insulin (P < 0.001), and lower percentages of total fat (P = 0.002), trunk fat (P = 0.001), and android fat (P = 0.009) than those with MUO. The logistic regression analysis according to IDF criteria detected an area under the receiver operating characteristic (ROC) curve of 0.659 (95% CI 0.546-0.771; P = 0.009) versus the area under the ROC curve of 0.854 (95% CI 0.777-0.931; P < 0.001) for the HOMA definition. Therefore, the determination of the metabolic state according to HOMA has greater sensitivity and specificity than the IDF criteria. The multivariate analysis in children classified according to HOMA revealed that the percentage of total fat and gynoid fat distributions and triglyceride level could be markers of a healthy or unhealthy metabolic state in children with obesity (P < 0.001). CONCLUSIONS: The use of HOMA as a single criterion was demonstrated to be an effective and simple detector of adiposity, which predicts the metabolically healthy obesity in children.

COVID-19: age, Interleukin-6, C-reactive protein, and lymphocytes as key clues from a multicentre retrospective study.

BACKGROUND: The SARS-CoV-2 infection has widely spread to become the greatest public health challenge to date, the COVID-19 pandemic. Different fatality rates among countries are probably due to non-standardized records being carried out by local health authorities. The Spanish case-fatality rate is 11.22%, far higher than those reported in Asia or by other European countries. A multicentre retrospective study of demographic, clinical, laboratory and immunological features of 584 Spanish COVID-19 hospitalized patients and their outcomes was performed. The use of renin-angiotensin system blockers was also analysed as a risk factor. RESULTS: In this study, 27.4% of cases presented a mild course, 42.1% a moderate one and for 30.5% of cases, the course was severe. Ages ranged from 18 to 98 (average 63). Almost 60 % (59.8%) of patients were male. Interleukin 6 was higher as severity increased. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19, and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of angiotensin-converting enzyme inhibitors was associated with a better prognosis. The angiotensin II receptor blocker use was associated with a more severe course. CONCLUSIONS: Age and age-related comorbidities, such as dyslipidaemia, hypertension or diabetes, determined more frequent severe forms of the disease in this study than in previous literature cohorts. Our cases are older than those so far reported and the clinical course of the disease is found to be impaired by age. Immunosenescence might be therefore a suitable explanation for the hampering of immune system effectors. The adaptive immunity would become exhausted and a strong but ineffective and almost deleterious innate response would account for COVID-19 severity. Angiotensin-converting enzyme inhibitors used by hypertensive patients have a protective effect in regards to COVID-19 severity in our series. Conversely, patients on angiotensin II receptor blockers showed a severer disease.

Elevated Plasma Reelin Levels in Children With Autism.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders involving age-dependent gene dysregulation. Reelin is a glycoprotein that varies its expression throughout lifetime and controls cortical patterning and synaptogenesis. Brain and plasma reelin levels have been reported to be low in adults with autism; as well as in children with autism, but only when compared to control adults. Therefore, reelin expression levels in children with autism are unclear. For this reason, we compared plasma reelin levels in children with autism and children without autism (non-ASD) of similar ages to evaluate reelin expression in ASD during childhood. Plasma samples from 19 non-ASD (8.9 ± 0.8 years) and 40 children with autism (7.5 ± 0.5 years) were analyzed. We found that 50% of the children with autism displayed similar plasma reelin levels to the non-ASD group. However, the remaining 50% expressed more than 30 times more reelin compared to non-ASD levels. We also show that male children with autism displayed significantly higher reelin levels than females. The clinical presentation of this subgroup could not be distinguished from that of children with autism. Epilepsy or attention-deficit/hyperactivity disorder (ADHD) was not associated to reelin levels. We conclude that the high levels of plasma reelin might be an important hallmark in a subset of children with autism, previously unnoticed. As we could not find any correlation between reelin levels and ASD clinical presentations, our results may indicate transient reelin increases in the plasma or the characterization of a group of ASD individuals with a different pathophysiology.

Spermine Confers Stress Resilience by Modulating Abscisic Acid Biosynthesis and Stress Responses in Arabidopsis Plants.

Polyamines (PAs) constitute a group of low molecular weight aliphatic amines that have been implicated as key players in growth and development processes, as well as in the response to biotic and abiotic stresses. Transgenic plants overexpressing PA-biosynthetic genes show increased tolerance to abiotic stress. Therein, abscisic acid (ABA) is the hormone involved in plant responses to environmental stresses such as drought or high salinity. An increase in the level of free spermine (Spm) in transgenic Arabidopsis plants resulted in increased levels of endogenous ABA and promoted, in a Spm-dependent way, transcription of different ABA inducible genes. This phenotype was only partially reversed by blocking ABA biosynthesis, indicating an ABA independent response mediated by Spm. Moreover, the phenotype was reproduced by adding Spm to Col0 wild-type Arabidopsis plants. In contrast, Spm-deficient mutants showed a lower tolerance to salt stress. These results indicate that Spm plays a key role in modulating plant stress responses.

Nonalcoholic fatty liver disease puts patients with psoriasis at greater cardiovascular risk.

BACKGROUND/OBJECTIVE: Psoriasis and nonalcoholic fatty liver disease (NAFLD) are inflammatory diseases associated with increased cardiovascular risk, but no studies have evaluated cardiovascular risk in patients with both. The objective was to assess cardiovascular risk in patients with psoriasis and NAFLD. MATERIAL AND METHODS: Cross-sectional, single-centre study in patients with moderate to severe psoriasis. Participants underwent liver ultrasound to determine the presence of NAFLD. Cardiovascular risk was evaluated using the calibrated Framingham function and Systematic Coronary Risk Evaluation (SCORE) charts. Statistical analyses included a descriptive analysis, chi-square tests for comparing independent samples and stepwise multiple logistic regression to identify associations with the two risk scores. RESULTS: Psoriatic patients with NAFLD had significantly higher odds of moderate to very high 10-year cardiovascular risk compared to those without NAFLD, according to SCORE (71.5% versus 29.2%; odds ratio [OR] 6.0, 95% confidence interval [CI] 3.3-11.1; P < 0.001). Using both the SCORE and Framingham assessment methods, moderate to very high cardiovascular risk was independently associated with metabolic syndrome (Framingham: adjusted odds ratio [ORa] 5.5, 95% CI 2.3-12.9, P < 0.001; SCORE: ORa 4.7, 95% CI 1.9-11.7, P = 0.001) and systemic treatment (Framingham: ORa 3.4, 95% CI 1.4-8.5, P = 0.009; SCORE: ORa 3.2, 95% CI 1.2-8.2, P = 0.021). Using SCORE, cardiovascular risk was also associated with NAFLD (ORa of 2.8, 95% CI 1.2-6.6, P = 0.014). CONCLUSION: Psoriasis plus NAFLD confers higher cardiovascular risk at 10 years than psoriasis alone. In comorbid patients, more intense diagnostic efforts and follow-up are justified.