Autoinflammatory syndromes: diagnosis and management

During the last decades the description of autoinflammatory syndromes induced great interest among the scientific community. Mainly rheumatologists, immunologists and pediatricians are involved in the discovery of etiopathogenesis of these syndromes and in the recognition of affected patients. In this paper we will discuss the most important clues of monogenic and non-genetic inflammatory syndromes to help pediatricians in the diagnosis and treatment of these diseases

CT pulmonary angiography appropriateness in a single emergency department: does the use of revised Geneva score matter?

Purpose: To assess the percentage of computed tomography pulmonary angiography (CTPA) procedures that could have been avoided by methodical application of the Revised Geneva Score (RGS) coupled with age-adjusted D-dimer cut-offs rather than only clinical judgment in Emergency Department patients with suspected pulmonary embolism (PE). Material and methods: Between November 2019 and May 2020, 437 patients with suspected PE based on symptoms and D-dimer test were included in this study. All patients underwent to CTPA. For each patient, we retrospectively calculated the age-adjusted D-dimer cut-offs and the RGS in the original version. Finally, CT images were retrospectively reviewed, and the presence of PE was recorded. Results: In total, 43 (9.84%) CTPA could have been avoided by use of RGS coupled with age-adjusted D-dimer cut-offs. Prevalence of PE was 14.87%. From the analysis of 43 inappropriate CTPA, 24 (55.81%) of patients did not show any thoracic signs, two (4.65%) of patients had PE, and the remaining patients had alternative thoracic findings. Conclusion: The study showed good prevalence of PE diagnoses in our department using only physician assessment, although 9.84% CTPA could have been avoided by methodical application of RGS coupled with age-adjusted D-dimer cut-offs

A diagnostic dilemma: Pedunculated mesenteric lipodystrophy mimicking Meckel's diverticulum. A case report and literature review

Mesenteric lipodystrophy is a rare fibroinflammatory disease of unknown origin with clinical and radiological non specific findings. PRESENTATION OF THE CASE: The case of a 42-years-old man affected by a pedunculated mesenteric lipodystrophy mimicking Meckel's diverticulum is reported. Clinical, imaging and histological findings are discussed. DISCUSSION: Mesenteric lipodystrophy affects the mesenteric fat of the abdomen with a typical diffuse thickening of the mesentery, nodular thickening of the mesenteric root and presence of mass-like lesions. Ultrasound (US) and Multiphasic Computed Tomography (CT) represent the main imaging tools used for diagnosis. Clinical and imaging findings can mimick other pathological conditions affecting the mesenteric fat tissue. Contrast enhanced CT is the most accurate imaging technique for diagnosing mesenteric lipodystrophy due to the high panoramicity and accuracy with multiplanar imaging. Multiphasic technique helps to characterize the lesion and to recognize vascular anatomy. Oral administration of iodinated contrast medium may help to assess the relationship with bowel loops. All these diagnostic elements are crucial for the surgical timing and approach. CONCLUSIONS: Due to the heterogeneous mesenteric involvement, the nonspecific CT findings and the high number of diseases for differential diagnosis, the detection of mesenteric lipodystrophy is challenging and requires early clinical suspicion. An histological examination is always necessary

The Multifaceted COVID-19: CT Aspects of Its Atypical Pulmonary and Abdominal Manifestations and Complications in Adults and Children. A Pictorial Review

Our daily experience in a COVID hospital has allowed us to learn about this disease in many of its changing and unusual aspects. Some of these uncommon manifestations, however, appeared more frequently than others, giving shape to a multifaceted COVID-19 disease. This pictorial review has the aim to describe the radiological aspects of atypical presentations and of some complications of COVID-19 disease in adults and children and provide a simple guide for radiologists to become familiar with the multiform aspects of this disease

Use of Liraglutide in the Real World and Impact at 36 Months on Metabolic Control, Weight, Lipid Profile, Blood Pressure, Heart Rate, and Renal Function

PURPOSE: An observational retrospective study was conducted by 2 diabetes clinics in Italy to assess patterns of use and long-term effectiveness of liraglutide on established and emerging parameters. METHODS: Data from 261 patients with type 2 diabetes who started treatment with liraglutide between 2010 and 2014 were collected. Hierarchical linear regression models were applied to assess trends over time of clinical parameters. Factors associated with higher likelihood of dropout were identified through multivariate logistic analysis. FINDINGS: Liraglutide was initiated as a switch in 42.5% of patients and as an add-on in 49.8%; in 7.7% of the patients initiation of liraglutide was associated with a reduction in the number of pharmacologic agents. A statistically significant reduction after 36 months was found for the following parameters (mean change [95% CIs]): glycosylated hemoglobin (HbA1c; -1.01% [1.34% to -0.68%]), fasting blood glucose (-27.5 [-40.6 to -14.4] mg/dL), weight (-2.9 [-4.5 to -1.3] kg), body mass index (-1.13 [-1.76 to -0.50] kg/m2), waist circumference (-1.74 [-3.85 to -0.37] cm), and LDL-C (-24.7 [-36.67 to -12.8] mg/dL). Improvements in systolic (-3.5 mm Hg) and diastolic (-2.3 mm Hg) blood pressures were observed at 24 months. Albuminuria was reduced by -16.6 mg/L during 36 months, although statistical significance was not reached. Glomerular filtration rate and heart rate were unchanged. Reductions in HbA1c between -0.6% and -1.3% were obtained in specific subgroups. Treatment was effective also in patients with >20 years of diabetes duration, although the likelihood of dropout was 6% higher for each additional year of disease duration (RR = 1.06; 95% CI, 1.01-1.12). The likelihood of dropout was almost four times higher for subjects treated with insulin (RR = 3.82; 95% CI, 1.22-11.96) and more than twice for those treated with sulfonylureas (RR = 2.39; 95% CI, 1.16-4.94) compared with patients not treated with these agents. IMPLICATIONS: Liraglutide used in routine clinical conditions maintains its effectiveness on metabolic control and weight after 3 years. Improvements in terms of metabolic control were found when liraglutide was used as both switch and add-on treatment. In addition, improvements were sustained when liraglutide replaced sulfonylureas or insulin. Diabetes duration had no impact on drug efficacy. Long-term benefits relative to blood pressure and LDL-C were also found, which could not be entirely explained by antihypertensive/lipid-lowering treatment intensification. No major effect on renal parameters was documented. Diabetes duration and some concomitant treatments were associated with a higher likelihood of liraglutide discontinuation. These data can contribute to improve appropriateness and cost-effectiveness profile of liraglutide

Clinical and functional characterization of a novel mutation in lamin a/c gene in a multigenerational family with arrhythmogenic cardiac laminopathy.

Mutations in the lamin A/C gene (LMNA) were associated with dilated cardiomyopathy (DCM) and, recently, were related to severe forms of arrhythmogenic right ventricular cardiomyopathy (ARVC). Both genetic and phenotypic overlap between DCM and ARVC was observed; molecular pathomechanisms leading to the cardiac phenotypes caused by LMNA mutations are not yet fully elucidated. This study involved a large Italian family, spanning 4 generations, with arrhythmogenic cardiomyopathy of different phenotypes, including ARVC, DCM, system conduction defects, ventricular arrhythmias, and sudden cardiac death. Mutation screening of LMNA and ARVC-related genes PKP2, DSP, DSG2, DSC2, JUP, and CTNNA3 was performed. We identified a novel heterozygous mutation (c.418_438dup) in LMNA gene exon 2, occurring in a highly conserved protein domain across several species. This newly identified variant was not found in 250 ethnically-matched control subjects. Genotype-phenotype correlation studies suggested a co-segregation of the LMNA mutation with the disease phenotype and an incomplete and age-related penetrance. Based on clinical, pedigree, and molecular genetic data, this mutation was considered likely disease-causing. To clarify its potential pathophysiologic impact, functional characterization of this LMNA mutant was performed in cultured cardiomyocytes expressing EGFP-tagged wild-type and mutated LMNA constructs, and indicated an increased nuclear envelope fragility, leading to stress-induced apoptosis as the main pathogenetic mechanism. This study further expands the role of the LMNA gene in the pathogenesis of cardiac laminopathies, suggesting that LMNA should be included in mutation screening of patients with suspected arrhythmogenic cardiomyopathy, particularly when they have ECG evidence for conduction defects. The combination of clinical, genetic, and functional data contribute insights into the pathogenesis of this form of life-threatening arrhythmogenic cardiac laminopathy

CMR imaging of <i>LMNA</i> mutation-positive family members.

<p>(A) Short-axis cine (a) and LGE sequences in the Short-axis (b) and 2-chambers long-axis views (c). Bulging (arrow in a) and LGE of the RV free wall (arrowheads in b). Linear midwall LGE is localized at the interventricular septum and LV inferior wall (arrowheads in c) (subject III-5). (B) and (C) LGE sequences in the short axis (a) and 4-chambers long axis views (b). LGE with linear midwall pattern is shown on the LV inferior wall and basal interventricular septum (arrowheads) (subjects III-8, and IV-2).</p

Analysis of nuclear envelope integrity under stressing condition in LMNA transfected HL-1 cells.

<p>Nuclear WT LMNA (A) and DUP LMNA (B) signals in control (CTR) and stressing conditions (Hyperosmolarity, Hypoxia, Oxidative stress). The merged signals of LMNA proteins and the RFP nuclear marker are shown in the insets. Confocal XY planar projections are depicted in each experimental condition.</p