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The role of 18F-fluorodeoxyglucose (FDG) positron emission tomography (18F-FDG PET) in the diagnosis of large vessel vasculitis (LVV) is well established. It permits us to assess the extent and the grade of vascular involvement and to rule out the other causes in clinical scenarios characterized by less specific symptoms. The advantages of 18F-FDG PET are far less clear in monitoring disease activity over time. Studies looking for the role of 18F-FDG PET as a potential biomarker had conflicting results and whether and when to repeat it during follow-up is based on clinical experience. A comprehensive assessment, including clinical, laboratory and morphological imaging is still required to monitor patients with large-vessel vasculitis over time. The aim of this review is to present more recent data about the utility of 18 F-FDG PET in the diagnosis and follow-up of LVV. [ABSTRACT FROM AUTHOR]

Response to cardiac resynchronization therapy (CRT) is reduced in patients with high left ventricular (LV) scar burden, in particular when scar is located in the LV lateral wall or septum. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) can identity scar, but is not feasible in all patients. This study investigates if myocardial metabolism by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contractile function by echocardiographic strain are alternatives to LGE-CMR. In a prospective multicenter study, 132 CRT candidates (91% with left bundle branch block) were studied by speckle tracking strain echocardiography, and 53 of these by FDG-PET. Regional myocardial FDG metabolism and peak systolic strain were compared to LGE-CMR as reference method. Reduced FDG metabolism (<70% relative) precisely identified transmural scars (≥50% of myocardial volume) in the LV lateral wall, with area under the curve (AUC) 0.96 (95% confidence interval (CI) 0.90–1.00). Reduced contractile function by strain identified transmural scars in the LV lateral wall with only moderate accuracy (AUC = 0.77, CI 0.71–0.84). However, absolute peak systolic strain >10% could rule out transmural scar with high sensitivity (80%) and high negative predictive value (96%). Neither FDG-PET nor strain identified septal scars (for both, AUC < 0.80). In CRT candidates, FDG-PET is an excellent alternative to LGE-CMR to identify scar in the LV lateral wall. Furthermore, preserved strain in the LV lateral wall has good accuracy to rule out transmural scar. None of the modalities can identify septal scar. The present study is part of the clinical study "Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy (CRID–CRT)", which was registered at clinicaltrials.gov (identifier NCT02525185). The ability of peak systolic strain by echocardiography and glucose metabolism by FDG-PET to identify transmural LV lateral and septal scar in CRT candidates compared to LGE-CMR, illustrated in three representative patients. LGE-CMR (left images) allows for direct scar identification independent of wall motion, and was used as reference standard for scar. Peak systolic strain by echocardiography (middle images) was generally inconclusive of scar, but absolute strain >10% in the LV lateral wall implies that transmural scar in this region is unlikely. Glucose metabolism by FDG-PET (right images) accurately identified transmural LV lateral wall scar, but was unable to distinguish transmural septal scar from septal hypo-metabolism due to left bundle branch block in itself. FDG-PET = 18F-fluorodeoxyglucose Positron Emission Tomography; LV = left ventricular; CRT = cardiac resynchronization therapy; LGE = late gadolinium enhancement; CMR = cardiac magnetic resonance. [Display omitted] • FDG-PET is a good alternative to CMR to identify transmural left ventricular lateral wall scars in patients referred for CRT. • Strain by echocardiography is only moderately accurate, but relatively preserved strain (>10%) in the lateral wall strain means that transmural scar in this region is unlikely. • Contrary to preserved strain, reduced strain in the lateral wall is inconclusive with regard to scar. • Neither FDG-PET nor echocardiographic strain identifies septal scar. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the accuracy of PET/CT and of PET vascular activity score (PETVAS) in assessing disease activity and the ability of PETVAS in predicting relapses in a large single-centre cohort of patients with large vessel vasculitis (LVV). Methods We conducted a retrospective cohort study of prospectively collected data of consecutive patients diagnosed with LVV who underwent at least one PET/CT scan between 2007 and 2020. The nuclear medicine physician's interpretation of each PET/CT scan (active/inactive vasculitis) was compared with disease activity clinical judgement (active disease/remission). For each PET/CT scan, the PETVAS score was calculated and its accuracy in assessing disease activity was evaluated. The ability of PETVAS in predicting subsequent relapses was evaluated. Results A total of 100 consecutive LVV patients (51 large vessel GCA, 49 Takayasu arteritis) underwent a total of 476 PET/CT scans over a mean follow-up period of 97.5 months. Physician-determined PET/CT grading was able to distinguish between clinically active and inactive LVV with a sensitivity of 60% (95% CI 50.9, 68.7) and specificity of 80.1% (95% CI 75.5, 84.1); the area under the curve (AUC)was 0.70 (95% CI 0.65, 0.75). PETVAS was associated with disease activity, with an age and sex–adjusted odds ratio for active disease of 1.15 (95% CI 1.11, 1.19). A PETVAS ≥10 provided 60.8% sensitivity and 80.6% specificity in differentiating between clinically active and inactive LVV; the AUC was 0.73 (95% CI 0.68, 0.79). PETVAS was not associated with subsequent relapses, with an age and sex–adjusted hazard ratio of 1.04 (95% CI 0.97, 1.11). Conclusions The visual PET/CT grading scale and PETVAS had moderate accuracy to distinguish active LVV from remission. PETVAS did not predict disease relapses. [ABSTRACT FROM AUTHOR]

Currently, there are a few detailed guidelines on the overall management of children and adolescents with moderate-severe atopic dermatitis. AD ​​is a complex disease presenting with different clinical phenotypes, which require an individualized and multidisciplinary approach. Therefore, appropriate interaction between primary care pediatricians, pediatric allergists, and pediatric dermatologists is crucial to finding the best management strategy. In this manuscript, members of the Italian Society of Pediatric Allergology and Immunology (SIAIP), the Italian Society of Pediatric Dermatology (SIDerP), and the Italian Society of Pediatrics (SIP) with expertise in the management of moderate-severe atopic dermatitis have reviewed the latest scientific evidence in the field. This narrative review aims to define a pathway to appropriately managing children and adolescents with moderate-severe atopic dermatitis. [ABSTRACT FROM AUTHOR]

Cardiac resynchronization therapy (CRT) is an implant-based therapy applied to patients with a specific heart failure (HF) profile. The identification of patients that may benefit from CRT is a challenging task and the application of current guidelines still induce a non-responder rate of about 30%. Several studies have shown that the assessment of left ventricular (LV) mechanics by speckle tracking echocardiography can provide useful information for CRT patient selection. A comprehensive evaluation of LV mechanics is normally performed using three different echocardioraphic views: 4, 3 or 2-chamber views. The aim of this study is to estimate the relative importance of strain-based features extracted from these three views, for the estimation of CRT response. Several features were extracted from the longitudinal strain curves of 130 patients and different methods of feature selection (out-of-bag random forest, wrapping and filtering) have been applied. Results show that more than 50% of the 20 most important features are calculated from the 4-chamber view. Although features from the 2- and 3-chamber views are less represented in the most important features, some of the former have been identified to provide complementary information. A thorough analysis and interpretation of the most informative features is also provided, as a first step towards the construction of a machine-learning chain for an improved selection of CRT candidates. [ABSTRACT FROM AUTHOR]

Background: Treatment strategy for low‐gradient (LG) aortic stenosis (AS) remains an unresolved issue. The presence of a low aortic gradient and preserved left ventricular ejection fraction (LVEF) might lead toward the underestimation of aortic stenosis severity and a more conservative management. We sought (a) to describe the nature and timing of intervention according to flow/gradient subgroups in patibents with LG‐AS, (2) to determine the factors associated with the decision to intervene, and (c) to describe prognosis. Methods and Results: One hundred and ten patients prospectively included in this study underwent a standardized clinical and imaging evaluation at inclusion and at 1‐year follow‐up. According to aortic flow, gradient and LVEF, patients were divided into 4 groups: LG‐normal flow [n = 27], LG‐low flow‐low LVEF [n = 27], LG‐low flow‐normal LVEF [n = 16], and high gradient (HG) [n = 40]). 73% of patients underwent AVR 86 ± 59 days after the initial assessment. The HG subgroup had significantly higher intervention rates (P <.001). In multivariable analysis, four parameters were associated with the AVR: aortic gradient (HR 1.52 [1.10‐2.11], P =.012), LVEF (HR 0.58 [0.40‐0.85], P =.006), atrial fibrillation (HR 0.43 [0.021‐0.87], P =.019), and NT‐proBNP (HR 0.92[0.86‐0.98), P =.008]. Patients operated earlier had better outcomes than those having a delayed AVR (P =.042). LG‐AS patients had worse outcomes than HG‐AS patients (P <.001). Conclusion: Compared to HG‐AS, LG‐AS is less likely to benefit from an AVR and had a significantly worse outcome. Further interventional studies are needed to investigate the timing of AVR in these patients. [ABSTRACT FROM AUTHOR]

Aims: Functional mitral regurgitation (FMR) is associated with poor outcome in systolic heart failure (HF) patients. Percutaneous edge‐to‐edge mitral valve repair (PMVR) in Mitra‐Fr study failed to prove any beneficial effect over optimal medical treatment (OMT) but win in COAPT study. Nevertheless, little is known about the effect of PMVR on LV performance and mechanics in HF patients with severe secondary MR. Method and results: Thirty‐seven patients with severe FMR undergoing PMVR were included and compared (according to indices of LV myocardial function and the relationship between LV‐size and the degree of regurgitation) to nineteen patients with FMR treated by OMT. Both groups were clinically comparable. At 6‐month follow‐up, cardiac index such as LV global constructive work (GCW) improved significantly in both groups (1.86 vs 2.13 L/min/m2, P = .02, 1.73 vs 2.28 L/min/m2P = .002 and 977 vs 1101 mm Hg.%, P = .003, 967 vs 1110 mm Hg.%, P = .002 for PMVR and OMT groups, respectively) whereas left ventricular (LV) end‐systolic volume index, LV ejection fraction, and global longitudinal strain were not different. Receiver operating characteristics in PMVR with LVEF ≤ 35% subgroup analysis demonstrated that global work index (GWI) had the best ability to identify patients with worse evolution (AUC = 0.882; P = .009), confirmed by univariable logistic regression, particularly for patients with GWI < 482 mm Hg.%. Conclusion: Echocardiographic characteristics at 6‐month follow‐up are not different when compare PMVR and OMT for HF patients with severe FMR. A low global work index might be a tool for discouraging the implantation of clips for this indication. [ABSTRACT FROM AUTHOR]

Background: Myocardial work (MW) estimation by pressure‐strain loops (PSL) allows the non‐invasive assessment of myocardial performance. Aim of this study is to provide the reference values for global myocardial work index (WI), constructive work (CW), wasted work (WW), and work efficiency (WE) in a group of healthy volunteers accounting for age and gender. Methods and results: 2D standard and speckle‐tracking echocardiography were performed in 115 healthy volunteers (median age 36.3 [18–69] years, males: 67%). PSLs were used to assess MW. Mean ± standard deviation or median and inter‐quartile range, 5° and 95° percentile values for global myocardial WI, CW, WW, and WE in the whole population were 1926 ± 247 mm Hg, (1534–2356); 2224 ± 229 mm Hg, (1894–2647); 90 (61–123) mm Hg%, (38–195); and 96 (94–97)%, (91–98), respectively. Global WI (2031 ± 247 vs 1874 ± 232 mm Hg%, P = .001) and global CW (2289 ± 261 vs 2194 ± 207 mm Hg%, P = .04) were higher in women than in men. Age did not affect MW parameters. The segmental analysis showed that myocardial WI, CW, and WE were lower in the left ventricular basal segments than in the apex. The apex‐to‐base gradient was inverted for WW (all P < .0001). Conclusions: The assessment of MW is feasible in normal subjects. The presented referral ranges of global myocardial WI, CW, WW, and WE were not affected by age. An apex‐to‐base gradient was observed for all MW parameters. Nevertheless, the wide variability of MW parameters prevents for the moment the application of this technique in the routine clinical setting. [ABSTRACT FROM AUTHOR]

The manuscript is very attractive and should push forward the heart failure specialists to use more ultrasounds for solving their issues about the management of heart failure patients. Cardiologists, heart failure specialists are not familiar enough with the great value of echocardiography for optimizing, daily, the treatment of heart failure patients. In that regard, congestion imaging likely fits in the point of care and focused cardiac ultrasound (FoCUS) approaches.18,19 Relatively easy to learn, this approach is also attractive and beneficial for non-cardiologists such as intensivists, anaesthesiologists, emergency department physicians and even heart failure nurses. [Extracted from the article]

Background: The estimation of myocardial work by pressure strain loops (PSLs) is a totally new non‐invasive approach to assess myocardial performance, and its role in patients with hypertrophic cardiomyopathy is unknown. The aims of the present study are therefore: (a) to compare myocardial work in patients with non‐obstructive hypertrophic cardiomyopathy (HCM) and in a subset of age‐matched healthy controls and (b) to assess the correlation between myocardial work and left ventricular (LV) fibrosis. Design: Eighty‐two patients with non‐obstructive HCM (58 ± 14 years) and 20 age‐matched healthy subjects (58 ± 7 years, P = 0.99) underwent standard and speckle‐tracking echocardiography to assess myocardial dimensions and deformation parameters. PSLs analysis was used to estimate global myocardial constructive work (GCW) and wasted work (GWW). LV fibrosis was estimated at cardiac magnetic resonance (CMR) by qualitative assessment of late gadolinium enhancement (LGE), and significant fibrosis was defined as LGE in ≥2 LV segments. Results: Global constructive work (1599 ± 423 vs 2248 ± 249 mm Hg%, P < 0.0001) was significantly reduced in HCM compared to the control group. No difference was observed in GWW (141 ± 125 vs 101 ± 88 mm Hg%, P = 0.18) and LV ejection fraction (LVEF) (63 ± 13 vs 66 ± 4% P = 0.17) between the two groups. In HCM, GCW was the only predictor of LV fibrosis at multivariable analysis (OR 1.01, 95% CI: 0.99–1.08, P = 0.04). A cutoff value of 1623 mm Hg% (AUC 0.80, 95% CI: 0.66–0.93, P < 0.0001) was able to predict myocardial fibrosis with a good sensitivity and fair specificity (82% and 67%, respectively). Conclusions: Global constructive work is significantly reduced in HCM despite normal LVEF and is associated with the LV fibrosis as assessed by LGE. [ABSTRACT FROM AUTHOR]

Background: The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic, causing COVID‐19, is rapidly spread across the world, by posing novel challenges for all physicians. Cutaneous manifestations of COVID‐19 may be present in 20% of patients, but they are still now poorly characterized. Methods: We search literature to describe all the various cutaneous manifestation observed during COVID‐19 pandemic. Results: Different cutaneous clinical patterns were described, showing a wide polymorphism. Conclusion: We provided an overview of all the various cutaneous manifestations of COVID‐19 described in the literature today, to improve our knowledge and lead a more prompt and accurate diagnosis, especially in asymptomatic or paucisymptomatic cases. [ABSTRACT FROM AUTHOR]

Background In aortic stenosis ( AS), the left ventricle ( LV) should face an increased afterload that is due to both the stenotic aortic valve and the peripheral vascular resistance ( PVR). Valvulo-arterial impedance ( ZVa) is a recently introduced parameter, which permits the evaluation of global LV afterload in AS. Aim of this study was to assess the influence of increasing ZVa on the longitudinal, circumferential, and radial components of LV mechanics. Methods A total of 126 patients (mean age: 80.1±12.0 years, males: 47%) with severe AS (aortic surface <1 cm2 or <0.6 cm2/m2) underwent standard echocardiography to characterize aortic valve gradients, LV function, and ZVa. 2D speckle tracking echocardiography was used to estimate global longitudinal ( GLS), circumferential ( GCS), and radial ( GRS) LV strain. Results The population was divided into four groups according to ZVa quartiles: Q1 ( ZVa≤3.43 mm Hg/mL/m2), Q2 (3.43< ZVa≤4.1 mm Hg/mL/m2), Q3 (4.1< ZVa≤5.1 mm Hg/mL/m2), ad Q4 ( ZVa>5.1 mm Hg/mL/m2). ZVa increase from Q1 to Q4 was associated with a progressive reduction in GLS and GCS ( ANOVA, both P<.0001). GRS was relatively insensitive to ZVa increase, a significant reduction of GRS appearing only in Q4 patients with respect to Q1 (29.7±16.4 vs 20.7±13.2%, P=.01). Conclusions Left ventricle myocardial fibers show a different response to afterload increase. Subendocardial fibers function is impaired earlier, whereas mid-wall circumferential fibers remain substantially unaffected, providing interesting insights into the mechanisms of LV dysfunction in AS. [ABSTRACT FROM AUTHOR]

Functional tricuspid regurgitation (FTR) is an independent risk factor for morbidity and mortality. New pathophysiological concepts but also new therapeutic options are justifying new knowledges for characterizing FTRs and their prognoses. Aim: To study echocardiographic criteria associated with prognosis in FTR-patients using a clustering method in two cohorts. Two hundred forty-one patients with at least severe (≥grade 3) TR were enrolled: 92 in the retrospective cohort (mean age 77.9 ± 13 years) and 149 in the prospective validation cohort. Hierarchical clustering analysis was conducted. Four parameters explained the clustering categorization according to a multinomial regression (right ventricular (RV) end-diastolic mid-cavity diameter, RV free-wall strain, right atrial (RA) volume index, RA strain; p = 0.0039). Three clusters were identified in the retrospective cohort: Cluster 1 had better right ventricular, left ventricular, and right atrial function than Cluster 2 (reduced RV and RA strain despite similar sizes). Cluster 3 included patients with severely dilated heart chambers associated to RV and RA dysfunctions. When applying the model in the validation (external) cohort, the rate of the primary endpoint (hospitalization for heart failure and/or death from any cause) was lowest in Cluster 1 (30.8% versus 48% and 58.8% in Clusters 2 and 3, respectively; p < 0.05). In FTR patients, different profiles of RV and RA remodeling are associated with different outcomes. Therefore, the diagnostic work-up in this clinical setting should include RV and RA characteristics. Under noninterventional management, the phenotype corresponding to preserved RV size and preserved RA and RV functions appears to have a better prognosis. [Display omitted] • In patients with a Functional Tricuspid Regurgitation, different profiles of RV and RA remodeling are associated with different outcomes. • Not only the right ventricular size or function are important, both should be consider. • Do not forget the right atrium. [ABSTRACT FROM AUTHOR]

The article focuses on the challenges of assessment of myocardial function in the context of valvular heart disease. Topics discussed include clinical use of the left ventricular (LV) pressure–strain loops (PSL) for the same; a study conducted in cardiac resynchronization therapy (CRT) candidates and in patients with ischaemic heart disease related to same; and preliminary assessment of PLS as an index of LV myocardial function on patients undergoing aortic valve replacement.

Objectives To assess the impact of tocilizumab (TCZ) monotherapy after ultra-short-pulse glucocorticoids (GCs) on clinical manifestations, and vessel inflammation and damage in large vessel-GCA (LV-GCA). Methods In this prospective observational study, we enrolled patients with active LV-GCA. All patients received 500 mg per day i.v. methylprednisolone for three consecutive days and weekly s.c. TCZ injections from day 4 until week 52. PET/CT was performed on all patients at baseline and at weeks 24 and 52. The primary end points were the reduction in the PET vascular activity score (PETVAS) at weeks 24 and 52 compared with baseline, and the proportion of patients with relapse-free remission at weeks 24 and 52. The secondary end point was the proportion of patients with new aortic dilation at weeks 24 and 52. Results A total of 18 patients were included (72% female, mean age 68.5 years). Compared with the baseline value, a significant reduction in the PETVAS was observed at weeks 24 and 52, mean (95% CI) reductions –8.6 (–11.5 to –5.7) and –10.4 (–13.6 to –7.2), P  = 0.001 and 0.002, respectively. The proportion of patients with relapse-free remission at weeks 24 and 52 was 10/18 (56%, 95% CI 31–78) and 8/17 (47%, 95% CI 23–72), respectively. At weeks 24 and 52, no patient had shown new aortic dilation. However, 4 patients who had shown aortic dilation at baseline showed a significant increase in aortic diameter (≥5 mm) at week 52. Conclusion TCZ monotherapy after ultra-short-pulse GCs controlled the clinical symptoms of GCA and reduced vascular inflammation. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT05394909. [ABSTRACT FROM AUTHOR]

Background: The response to cardiac resynchronization therapy (CRT) depends on septal viability and correction of abnormal septal motion. This study investigates if cardiac magnetic resonance (CMR) as a single modality can identify CRT responders with combined imaging of pathological septal motion (septal flash) and septal scar. Methods: In a prospective, multicenter, observational study of 136 CRT recipients, septal scar was assessed using late gadolinium enhancement (LGE) (n = 127) and septal flash visually from cine CMR sequences. The primary endpoint was CRT response, defined as ≥15% reduction in LV end-systolic volume with echocardiography after 6 months. The secondary endpoint was heart transplantation or death of any cause assessed after 39 ± 13 months. Results: Septal scar and septal flash were independent predictors of CRT response in multivariable analysis (both p < 0.001), while QRS duration and morphology were not. The combined approach of septal scar and septal flash predicted CRT response with an area under the curve of 0.86 (95% confidence interval (CI): 0.78–0.94) and was a strong predictor of long-term survival without heart transplantation (hazard ratio 0.27, 95% CI: 0.10–0.79). The accuracy of the approach was similar in the subgroup with intermediate (130–150 ms) QRS duration. The combined approach was superior to septal scar and septal flash alone (p < 0.01). Conclusions: The combined assessment of septal scar and septal flash using CMR as a single-image modality identifies CRT responders with high accuracy and predicts long-term survival. [ABSTRACT FROM AUTHOR]

The article offers the author's insights on the value of B-type natriuretic peptides (BNP) in the prognosis of heart failure (HF) with reduced or preserved ejection fraction (EF). Topics mentioned include the published guidelines by European Society of Cardiology (ESC) which incorporated BNP as diagnosis and prognosis tool, the use of multicenter cohort in Korean HF registry, and the issue on the impact of NP to treatment strategy.

This paper proposes a model-based estimation of left ventricular (LV) pressure for the evaluation of constructive and wasted myocardial work of patients with aortic stenosis (AS). A model of the cardiovascular system is proposed, including descriptions of i) cardiac electrical activity, ii) elastance-based cardiac cavities, iii) systemic and pulmonary circulations and iv) heart valves. After a sensitivity analysis of model parameters, an identification strategy was implemented using a Monte-Carlo cross-validation approach. Parameter identification procedure consists in two steps for the estimation of LV pressures: step 1) from invasive, intraventricular measurements and step 2) from non-invasive data. The proposed approach was validated on data obtained from 12 patients with AS. The total relative errors between estimated and measured pressures were on average 11.9% and 12.27% and mean R2 were equal to 0.96 and 0.91, respectively for steps 1 and 2 of parameter identification strategy. Using LV pressures obtained from non-invasive measurements (step 2) and patient-specific simulations, Global Constructive (GCW), Wasted (GWW) myocardial Work and Global Work Efficiency (GWE) parameters were calculated. Correlations between measures and model-based estimations were 0.88, 0.80, 0.91 respectively for GCW, GWW and GWE. The main contributions concern the proposal of the parameter identification procedure, applied on an integrated cardiovascular model, able to reproduce LV pressure specifically to each AS patient, by non-invasive procedures, as well as a new method for the non-invasive estimation of constructive, wasted myocardial work and work efficiency in AS. [ABSTRACT FROM AUTHOR]

Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74–0.88) and 0.86 (95%CI: 0.79–0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12–0.67) to 0.20 (95%CI: 0.08–0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine. [ABSTRACT FROM AUTHOR]

• Concentrations of IgG subclasses decrease in human from IgG1 to IgG4. • 3′RR1 positional cis-effect potentially drives IgG subclasses' serum quantities. • 3′RR hs1.2 enhancer is implicated in autoimmune diseases but not in allergic asthma. Several studies in animal models have demonstrated the role of the 3′ Regulatory Region (3′RR) in the B cell maturation in mammals. In healthy humans, the concentration of each class of circulating immunoglobulins (Igs) has stable but different levels, due to several control mechanisms that also involve a duplicated version of the 3′RR on the chromosome 14 (chr14). The classes' equilibrium can be altered during infections and in other pathological conditions. We studied the concentrations of IgA, IgM, IgG classes and IgG subclasses in a cohort of 1235 people having immunoglobulin concentrations within normal range to determine the presence of any correlation between the Igs serum concentrations, age and ratio among Ig classes and IgG subclasses in healthy humans. Furthermore, we assessed the concentrations of IgE and the allelic frequency of 3′RR1 hs1.2 enhancer in a group of 115 subjects with high levels of circulating IgE due to acute exacerbation of allergic asthma and in a control group of 118 healthy subjects. In both children and adult subjects, the concentrations of the four IgG subclasses decreased from IgG1 to IgG4. Furthermore, the 3′RR1 enhancer hs1.2 alleles contribute to the control of the IgG subclasses levels, but it does not affect the IgE levels. The 3′RR1 controls IgG and IgE through different mechanisms, only in the IgG case involving the hs1.2 alleles. Thus, considering the IgH constant genes loci on the chromosome 14 and the multiple steps of switch that rearrange the whole region, we found that in humans the classes of Igs are modulated by mechanisms involving a complex interaction and transition between 3′RR1 and 3′RR2, also in physiological conditions. [ABSTRACT FROM AUTHOR]

By the April 12, 2022, the COVID‐19 pandemic had resulted in over half a billion people being infected worldwide. There have been 6.1 million deaths directly due to the infection, but the pandemic has had many more short‐ and long‐term pervasive effects on the physical and mental health of the population. Allergic diseases are among the most prevalent noncommunicable chronic diseases in the pediatric population, and health‐care professionals and researchers were seeking answers since the beginning of pandemic. Children are at lower risk of developing severe COVID‐19 or dying from infection. Allergic diseases are not associated with a higher COVID‐19 severity and mortality, apart from severe/poorly controlled asthma. The pandemic disrupted routine health care, but many mitigation strategies, including but not limited to telemedicine, were successfully implemented to continue delivery of high‐standard care. Although children faced a multitude of pandemic‐related issues, allergic conditions were effectively treated remotely while reduction in air pollution and lack of contact with outdoor allergens resulted in improvement, particularly respiratory allergies. There is no evidence to recommend substantial changes to usual management modalities of allergic conditions in children, including allergen immunotherapy and use of biologicals. Allergic children are not at greater risk of multisystem inflammatory syndrome development, but some associations with Long COVID were reported, although the data are limited, and further research is needed. This statement of the EAACI Section on Pediatrics provides recommendations based on the lessons learnt from the pandemic, as available evidence. [ABSTRACT FROM AUTHOR]

Objective: To identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic syndrome) from a single‐center cohort of Italian patients with vasculitis, using a clinically oriented phenotype‐first approach. Methods: We retrospectively reviewed the clinical records of 147 consecutive male patients followed up in our vasculitis clinic from 2013 to date. All patients with a diagnosis of vasculitis and treatment‐resistant manifestations of inflammation, persistently elevated inflammation markers, and hematologic abnormalities were identified. Bone marrow aspirates were examined for the presence of vacuoles. Sequencing of ubiquitin‐activating enzyme E1 (UBA‐1) was performed using genomic DNA from peripheral blood leukocytes or bone marrow tissue. Results: Seven patients with vasculitis and concomitant features of VEXAS syndrome were identified. A final diagnosis of VEXAS syndrome was made in 3 of the 5 patients who underwent sequencing of UBA‐1 (diagnosis was made postmortem for 1 patient). In all 3 patients, examination of the bone marrow aspirate revealed vacuoles characteristic of VEXAS syndrome, and all 3 patients met the definitive World Health Organization criteria for myelodysplastic syndrome. Cytogenetic analysis showed normal karyotypes in all 3 patients. Conclusion: To our knowledge, this is the first report of VEXAS syndrome associated with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. Our data emphasize the need to consider VEXAS syndrome when evaluating patients with various forms of systemic vasculitis. The novel association between VEXAS syndrome and ANCA‐associated vasculitis reported herein warrants further investigation. [ABSTRACT FROM AUTHOR]

The prediction of ventricular arrhythmia (VA) in hypertrophic cardiomyopathy (HCM) remains challenging. We sought to characterize the VA risk profile in HCM patients through clustering analysis combining clinical and conventional imaging parameters with information derived from left ventricular longitudinal strain analysis (LV-LS). A total of 434 HCM patients (65% men, mean age 56 years) were included from two referral centers and followed longitudinally (mean duration 6 years). Mechanical and temporal parameters were automatically extracted from the LV-LS segmental curves of each patient in addition to conventional clinical and imaging data. A total of 287 features were analyzed using a clustering approach (k-means). The principal endpoint was VA. 4 clusters were identified with a higher rhythmic risk for clusters 1 and 4 (VA rates of 26%(28/108), 13%(13/97), 12%(14/120), and 31%(34/109) for cluster 1,2,3 and 4 respectively). These 4 clusters differed mainly by LV-mechanics with a severe and homogeneous decrease of myocardial deformation for cluster 4, a small decrease for clusters 2 and 3 and a marked deformation delay and temporal dispersion for cluster 1 associated with a moderate decrease of the GLS (p < 0.0001 for GLS comparison between clusters). Patients from cluster 4 had the most severe phenotype (mean LV mass index 123 vs. 112 g/m2; p = 0.0003) with LV and left atrium (LA) remodeling (LA-volume index (LAVI) 46.6 vs. 41.5 ml/m2, p = 0.04 and LVEF 59.7 vs. 66.3%, p < 0.001) and impaired exercise capacity (% predicted peak VO2 58.6 vs. 69.5%; p = 0.025). Processing LV-LS parameters in HCM patients 4 clusters with specific LV-strain patterns and different rhythmic risk levels are identified. Automatic extraction and analysis of LV strain parameters improves the risk stratification for VA in HCM patients. [Display omitted] • Ventricular arrhythmia risk profile in Hyerptrophic cardiomyopathy patients remains a challenge despite new guidelines. Clustering analysis combining clinical and conventional imaging parameters with information derived from left ventricular longitudinal strain analysis have been successfully applied [ABSTRACT FROM AUTHOR]

Objectives: EULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of rheumatoid arthritis (RA). In particular, few data are available regarding the effectiveness of a second-line bDMARD after failure of abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX). The aim of this study was to analyze the retention rate of a second line with tumor necrosis factor inhibitors (TNFi) or other mechanisms of action (MoAs), after the failure of either RTX, TCZ, or ABA. Methods: Two hundred and seventy-eight RA patients from the Italian GISEA registry were included in the study. RTX was the first bDMARD in 18% of patients, ABA in 45.7%, and TCZ in 36.3%, while the second bDMARD was a TNFi (group 1) in 129 patients and an agent with a different MoA (group 2) in 149. Results: During a median follow-up of 22 months (IQR 68), 129 patients discontinued their treatment; patients of group 1 discontinued the treatment more frequently than patients of group 2 (p<0.001) with retention rates of 33.6±5.7% and 63.6±4.6% after 104 weeks for group 1 and group 2, respectively (p<0.001). At multivariate analysis, the mechanism of action was the only predictor for the maintenance in therapy. Conclusions: According to our data, ABA, RTX, and TCZ seem to maintain a good retention rate also when used as a second-line therapy, suggesting their use after the failure of a non-TNFi as first-line therapy. However, specifically designed studies are needed to evaluate the more appropriate therapeutic strategies in RA, according to the first-line drug, including new targeted synthetic DMARDs. Key Points • A large proportion of rheumatoid arthritis patients fail the first biologic DMARD. • Few data are available about the efficacy of biologic DMARD after the failure of a non-TNF inhibitor. • Abatacept, rituximab, or tocilizumab seem to maintain a good retention rate after the failure of a first-course therapy with a non-TNF inhibitor. [ABSTRACT FROM AUTHOR]

Objectives Efficacy evaluation of GCA treatment is primarily based on non-specific symptoms and laboratory markers. We aimed to assess the change in vascular inflammation in patients with large vessel (LV)-GCA under different treatments using [18F]FDG PET/CT. Methods Observational study on patients with new-onset, active LV-GCA starting treatment with either prednisolone monotherapy (PRED) or combination with MTX or tocilizumab (TOC). All patients underwent baseline and follow-up PET/CT. The aorta and its major branches were assessed using PET vascular activity score (PETVAS) by independent readers. Cumulative glucocorticoid doses and cessation of glucocorticoid treatment were documented in all patients. Results We included 88 LV-GCA patients, 27 were treated with PRED, 42 with MTX and 19 with TOC. PETVAS decreased from 18.9–8.0 units at follow-up in the overall population (P <0.001). PETVAS changes were numerically higher in patients receiving MTX (−12.3 units) or TOC (−11.7 units) compared with PRED (−8.7). Mean cumulative prednisolone dosages were 5637, 4418 and 2984 mg in patients treated with PRED, MTX and TOC (P =0.002). Risk ratios for glucocorticoid discontinuation at the time of follow-up PET/CT were 6.77 (95% CI: 1.01, 45.29; P =0.049) and 16.25 (95% CI: 2.60, 101.73; P =0.003) for MTX and TOC users compared with PRED users. Conclusion Treatment of LV-GCA inhibits vascular inflammation in the aorta and its major branches. While similar control of vascular inflammation was achieved with PRED, MTX and TOC treatments, TOC showed a strong glucocorticoid sparing effect, supporting the concept of initial combination therapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the susceptibility to coronavirus disease 2019 (COVID‐19) in patients with autoimmune conditions treated with antimalarials in a population‐based study. Methods: All residents treated with chloroquine (CQ)/hydroxychloroquine (HCQ) from July through December 2019 and living in 3 provinces of Regione Emilia‐Romagna were identified by drug prescription registries and matched with the registry containing all residents living in the same areas who have had swabs and tested positive for severe acute respiratory syndrome coronavirus 2 (SARS–CoV‐2). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results: A total of 4,408 patients were identified. The prevalence of patients receiving antimalarials was 0.85 per 1,000 men and 3.3 per 1,000 women. The cumulative incidence of testing during the study period was 2.7% in the general population and 3.8% among those receiving CQ or HCQ, while the cumulative incidence of testing positive was 0.55% in the general population and 0.70% among those receiving CQ/HCQ. Multivariate models showed that those receiving CQ/HCQ had a slightly higher probability of being tested compared to the general population (OR 1.09 [95% CI 0.94–1.28]), the same probability of being diagnosed as having COVID‐19 (OR 0.94 [95% CI 0.66–1.34]), and a slightly lower probability of being positive once tested (OR 0.83 [95% CI 0.56–1.23]). None of the differences were significant. Conclusion: Our findings do not support the use of antimalarials as a prophylactic treatment of COVID‐19. [ABSTRACT FROM AUTHOR]

While the world is facing an unprecedented pandemic with COVID‐19, patients with chronic diseases need special attention and if warranted adaptation of their regular treatment plan. In children, allergy and asthma are among the most prevalent non‐communicable chronic diseases, and healthcare providers taking care of these patients need guidance. At the current stage of knowledge, children have less severe symptoms of COVID‐19, and severe asthma and immunodeficiency are classified as risk factors. In addition, there is no evidence that currently available asthma and allergy treatments, including antihistamines, corticosteroids, and bronchodilators, increase the risk of severe disease from COVID‐19. Most countries affected by COVID‐19 have opted for nationwide confinement, which means that communication with the primary clinician is often performed by telemedicine. Optimal disease control of allergic, asthmatic, and immunodeficient children should be sought according to usual treatment guidelines. This statement of the EAACI Section on Pediatrics puts forward six recommendations for the management of childhood allergies and immunodeficiencies based on six underlying facts and existing evidence. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic. Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases. [ABSTRACT FROM AUTHOR]

Abstract Aims The current algorithm in transthoracic echocardiography (TTE) proposed in the 2016 ASE/EACVI recommendation for the estimation of left ventricular filling pressure (LVFP) is quite complex and time-consuming. B-lines, in lung ultrasonography (LUS), could constitute an interesting tool for LVFP evaluation in clinical practice, although data regarding their association with invasive haemodynamics are lacking. The purpose of this study was to explore the diagnostic accuracy of B-lines in identifying elevated left ventricular end-diastolic pressure (LVEDP). Method and results 81 adults with significant dyspnoea (NYHA ≥ 2) were prospectively analyzed by LUS in four areas in each hemithorax and a complete TTE within four hours prior to coronary angiography. Twenty-eight patients had elevated LVEDP. Clinical variables yielded a C-index of 79% to identify elevated LVEDP. The number of total B-lines was higher in the elevated LVEDP group (1.0vs17.0, p < 0.0001) and significantly increased the diagnostic accuracy (C-index increase = 10.5%, p = 0.002) and net reclassification index (NRI = 145.4, 113.0–177.9, p < 0.0001) on top of clinical variables. Conclusion This study demonstrates the substantial diagnostic capacity of B-lines to identify elevated LVEDP, which appears superior to that of classical echocardiographic strategies. This tool should be considered in a multi-parametric approach in patients with heart failure. Highlights • ASE/EACVI recommendation for the estimation of left ventricular filling pressure is quite complex and time consuming. • B-lines, in lung ultrasound, could constitute an interesting tool for LVFP evaluation in clinical practice, but data regarding their association with invasive hemodynamics are lacking. • Clinical variables had a C-index of 79% to identify elevated LVEDP. • Total B-lines number was higher in the elevated LVEDP group (1.0vs17.0, p < 0.0001) and significantly increased diagnostic accuracy (C-index increase = 15.5%, p = 0.004) and a net reclassification index (NRI = 142.0, 108.5–175.6, p < 0.0001) on top of clinical variables. • In contrast, the 2016 ASE/EACVI recommendations did not significantly increase neither the reclassification nor the diagnostic accuracy. There is an important diagnostic capacity of B-lines to identify elevated filling pressure and that is probably something to consider in our clinical routine. [ABSTRACT FROM AUTHOR]

To assess the efficacy and safety of Rituximab (RTX) in adult primary central nervous system vasculitis (PCNSV). We retrospectively assessed the effect of RTX in 6 patients with PCNSV. Five of the 6 were refractory to high dose glucocorticoids (GCs) and/or conventional immunosuppressants (IS). The sixth was newly diagnosed and received RTX in combination with GCs. Clinical evaluation, laboratory tests, and imaging modalities were performed at initial RTX administration and during the follow-up. Treatment response was assessed using the treating physician's global opinion regarding response and the degree of disability using the modified Rankin scale (mRS). We also performed a literature review for previous use of RTX in PCNSV using PubMed, Ovid Medline, and the Cochrane library. The six patients (3 females) had a median age at diagnosis of 50.5 years (range 17–68 years). All had active disease when RTX was started. In 4 patients, RTX administration was associated with a marked reduction in the number of flares (from 18 before starting RTX to 3 after). One patient, after an initial improvement, had 2 flares when B cells were depleted and he was not able to reduce prednisone below 20 mg/day. A 6th patient had a flare when B cells recovered and retreatment with RTX re-induced and maintained remission. The median mRS score at last visit (median: 2; range 0–4) was lower than that prior to treatment (median 3; range 1–5). The median prednisone daily dose before RTX administration was significantly higher than that at last follow-up (p =.006). In the literature review, we identified 5 papers describing 7 patients treated with RTX. Six patients responded to RTX with clinical and MRI improvement with no reported flares after RTX treatment. Our data support a potential role for RTX treatment in selected patients with PCNSV. • In PCNSV there is the need to identify effective therapeutic agents • B-cell depletion in PCNSV maintains disease remission and reduces the number of flares and GC dosage • Rituximab is effective and safe in PCNSV refractory to traditional immunosuppressive agents • Rituximab could have a role as a first line therapy for PCNSV patients with less favorable prognosis [ABSTRACT FROM AUTHOR]

Background: The 2010 Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines are the only Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines for cow's milk allergy (CMA). They indicate oral food challenge (OFC) as the reference test for diagnosis, and suggest the choice of specific alternative formula in different clinical conditions. Their recommendations are flexible, both in diagnosis and in treatment. Objectives & methods: Using the Scopus citation records, we evaluated the influence of the DRACMA guidelines on milk allergy literature. We also reviewed their impact on successive food allergy and CMA guidelines at national and international level. We describe some economic consequences of their application. Results: DRACMA are the most cited CMA guidelines, and the second cited guidelines on food allergy. Many subsequent guidelines took stock of DRACMA's metanalyses adapting recommendations to the local context. Some of these chose not to consider OFC as an absolute requirement for the diagnosis of CMA. Studies on their implementation show that in this case, the treatment costs may increase and there is a risk of overdiagnosis. Interestingly, we observed a reduction in the cost of alternative formulas following the publication of the DRACMA guidelines. Conclusions: DRACMA reconciled international differences in the diagnosis and management of CMA. They promoted a cultural debate, improved clinician's knowledge of CMA, improved the quality of diagnosis and care, reduced inappropriate practices, fostered the efficient use of resources, empowered patients, and influenced some public policies. The accruing evidence on diagnosis and treatment of CMA necessitates their update in the near future. [ABSTRACT FROM AUTHOR]

Background: Almost all attempts to improve patient selection for cardiac resynchronization therapy (CRT) using echo-derived indices have failed so far. We sought to assess: the performance of homemade software for the automatic quantification of integral 3D regional longitudinal strain curves exploring left ventricular (LV) mechanics and the potential value of this tool to predict CRT response.Methods: Forty-eight heart failure patients in sinus rhythm, referred for CRT-implantation (mean age: 65 years; LV-ejection fraction: 26%; QRS-duration: 160 milliseconds) were prospectively explored. Thirty-four patients (71%) had positive responses, defined as an LV end-systolic volume decrease ≥15% at 6-months. 3D-longitudinal strain curves were exported for analysis using custom-made algorithms. The integrals of the longitudinal strain signals (I L,peak) were automatically measured and calculated for all 17 LV-segments.Results: The standard deviation of longitudinal strain peak (SDI L,peak ) for all 17 LV-segments was greater in CRT responders than non-responders (1.18% s-1 [0.96; 1.35] versus 0.83% s-1 [0.55; 0.99], p = 0.007). The optimal cut-off value of SDI L,peak to predict response was 1.037%.s-1. In the 18-patients without septal flash, SDI L,peak was significantly higher in the CRT-responders.Conclusions: This new automatic software for analyzing 3D longitudinal strain curves is avoiding previous limitations of imaging techniques for assessing dyssynchrony and then its value will have to be tested in a large group of patients. [ABSTRACT FROM AUTHOR]

Lymphocytes possess an independent cholinergic system. We assessed the expression of muscarinic cholinergic receptors in lymphocytes from 49 asthmatic children and 10 age matched controls using Western blot. We demonstrated that CD4 + and CD8 + T cells expressed M2 and M4 muscarinic receptors which density were significantly increased in asthmatic children in comparison with controls. M2 and M4 receptor increase was strictly related with IgE and fraction of exhaled nitric oxide (FeNO) measurements and with impairment in objective measurements of airway obstruction. Increased lymphocyte muscarinic cholinergic receptor expression may concur with lung cholinergic dysfunction and with inflammatory molecular framework in asthma. [ABSTRACT FROM AUTHOR]

The Italian interest group (IG) on atopic eczema and urticaria ismember of the Italian Society of Allergology and Immunology. The aimof our IG is to provide a platformfor scientists, clinicians, and experts. In this review we discuss the role of skin microbiota not only in healthy skin but also in skin suffering from a topic dermatitis (AD). A Medline and Embase search was conducted for studies evaluating the role of skin microbiota. We examine microbiota composition and its development within days after birth; we describe the role of specific groups of microorganisms that colonize distinct anatomical niches and the biology and clinical relevance of antimicrobial peptides expressed in the skin. Specific AD disease states are characterized by concurrent and anticorrelated shifts in microbial diversity and proportion of Staphylococcus. These organisms may protect the host, defining them not as simple symbiotic microbes but rather asmutualistic microbes. These findings reveal links between microbial communities and inflammatory diseases such as AD and provide novel insights into global shifts of bacteria relevant to disease progression and treatment. This review also highlights recent observations on the importance of innate immune systems and the relationship with normal skin microflora for the maintenance of healthy skin. [ABSTRACT FROM AUTHOR]

To cite this article: Meglio P, Giampietro PG, Carello R, Gabriele I, Avitabile S, Galli E. Oral food desensitization in children with IgE-mediated hen's egg allergy: a new protocol with raw hen's egg. Pediatr Allergy Immunol 2012: 00. Abstract Background: Hen's egg allergy affects young children and can cause severe allergic reactions. Avoidance results in dietary limitations and can affect the quality of life, especially in cases where potentially life-threatening reactions exist. Our objective was to desensitize children with moderate-severe IgE-mediated hen's egg allergy over a 6-month period, by introducing increasing and very gradual daily doses of raw hen's egg in order to enable the children to assume 25ml of this food, or to induce tolerance to the highest possible dose. The protocol foresaw the egg reintroduction in the home setting. Methods: In this randomized, controlled open study, 20 hen's egg allergic children (10 in the active group) were admitted. A convincing history or a positive double-blind placebo-controlled food challenge confirmed the diagnosis. Oral desensitization was performed with increasing doses starting from 0.27 mg of hen's egg proteins (1 drop of raw hen's egg diluted 1:100). We adopted an original, mathematically calculated protocol in order to ensure a constant, daily increment of doses. Results: 8/10 children (80%) in the active group achieved the daily intake of 25ml over a 6-month period. One child (10%) could tolerate up to 2ml/day while another child (10%) failed the desensitization. Six months after enrolment only 2 children in the control group (20%) could tolerate hen's egg. Conclusions: We successfully desensitized 8/10 children with IgE-mediated hen's egg allergy in a 6-month period. The partial outcome in the child who could tolerate 2ml/day reduced the risk of severe reactions after unnoticed introduction of egg. A regular protocol that ensures a daily constant increase of doses helps to reduce possible adverse events, thus improving safety and effectiveness. [ABSTRACT FROM AUTHOR]

Background The diagnostic gold standard of food allergy is the oral food challenge ( OFC). Data on severe reactions and drug use during OFC are scarce. Our aims were (i) to investigate the prevalence and spectrum of reactions' severity during OFC and to assess drug use and epinephrine use in anaphylaxis due to OFC; (ii) to investigate the predictive value of the skin prick test wheal size for the outcome of OFCs. Methods A retrospective charts review of children undergoing OFC at three Allergy Centres between January 2007 and December 2008 was performed. Results A total of 544 OFCs were analysed. Most frequently involved foods were egg, milk and wheat. 254/526 (48.3%) were positive. 167 (65.7%) were defined mild reactions, 81 (31.9%) multiorgan reactions and 6 (2.4%) anaphylaxis. No patients had cardiovascular symptoms. Data on treatments were available in 98.8% OFCs. In half of them antihistamines were used vs. 10% cases in which steroids were preferred. Six children (2.4%) were treated with Epinephrine inhalation, 5 (2%) with beta-2 inhalation, 8 (3.1%) with steroid inhalation. One child was treated with IM Epinephrine + IV fluids. Skin prick tests predictive cut-off were 9 mm for albumen, 7 for yolk, 13 for fresh albumen, 10 for α-lactalbumin, seven for casein, eight for β-lactoglobulin, 20 for cow's milk and 10 for fresh cow's milk. Conclusion OFCs performed in controlled settings by expert Allergists are safe. Consideration needs to be given as to whether the Anaphylaxis' Guideline need to be modified when applied in treating patients undergoing OFC. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) and psoriasis are common skin diseases characterized by cutaneous inflammation and disturbed epidermal differentiation. Genome-wide analyses have shown overlapping susceptibility loci, such as the epidermal differentiation complex on chromosome 1q21. Recently, a deletion on 1q21 (LCE3C_LCE3B-del), comprising LCE3B and LCE3C, two members of the late cornified envelope (LCE) gene cluster, was found to be associated with psoriasis. Although the mechanistic role of LCE proteins in psoriasis has not been identified, these proteins are putatively involved in skin barrier formation and repair. Considering the potential genetic overlap between the two diseases and the recent finding that mutations in the skin barrier protein filaggrin are associated with AD, we investigated a possible association between LCE3C_LCE3B-del and AD. Evaluation of four different cohorts of European ancestry, containing a total of 1075 AD patients and 1658 controls, did not provide evidence for such an association. Subgroup analysis did not reveal an association with concomitant asthma. Our data suggest that the potential roles of skin barrier defects in the pathogenesis of AD and psoriasis are based on distinct genetic causes. [ABSTRACT FROM AUTHOR]

Background: acute recurrent pancreatitis is a complex multigenic disease, the diagnosis is even more difficult when this disease develops in a child. Case Presentation: a 6-years old boy, hospitalized with epigastric pain radiating to the back showed high serum levels of serum amylase, lipase, CRP and erythrosedimentation rate. Several similar milder episodes of pain, followed by quick recovery and complete disappearance of symptoms were reported during the previous 13 months. The child was medically treated and after 7 days with normal clinic and laboratory tests was discharged with a hypolipidic diet. All the known aetiologic hypotheses were excluded by anamnestic investigation, clinical observation and biochemical evaluation, whereas, anatomic abnormality were excluded by a secretin stimulated magnetic resonance (MRI). At the last follow-up visit, (11 months later), the child showed a normal body weight and anthropometric profile, without further abdominal pain. Mutation screening for coding regions of PRSS1, SPINK1, CFTR and the new hereditary pancreatitis-associated chymotrypsin C (CTRC) genes showed a novel variation, c.541A > G (p.S181G), in the exon 4 of PRSS1 gene and the classical CF p.F508del mutation in the CFTR. Both mutations were present in his clinically normal mother and absent in the patient's father. Conclusions: this report extend the spectrum of PRSS1 mutations, however, the absence of family history of pancreatitis leaves the present case without the hallmark of the hereditary origin of pancreatitis. At the present knowledge it can be only stated that the combined genotype CFTR (F508del)/PRSS1 (S181G) is associated to a mild phenotype of acute recurrent pancreatitis in this child without any further conclusion on its pathogenetic role or prediction on the course of the disease. [ABSTRACT FROM AUTHOR]

Until now, the basic treatment for food allergy has been to avoid the offending item. This approach is difficult in the case of common foods and in the case where there is a risk of severe reaction after consuming the offending food, even inadvertently. This is the follow-up of a previous study aimed at desensitizing 21 children with immunoglobulin E (IgE)-mediated cow’s milk (CM) allergy. This protocol was totally or partially successful in 85% of cases, but failed in the remaining 15%. Our aims were to study the long-term effectiveness and safety of oral CM desensitization, and the prognostic value of Skin Prick Test (SPT) and specific serum CM IgE. The 21 children were called back (one dropped out). The allergic history and other information on CM intake over the last 4–5 yr were recorded. Children underwent SPT, and end-point SPT, with casein and α-lactoalbumin. Specific CM IgE was also measured. At follow-up, 14/20 children totally (n = 13, 65%) or partially (n = 1, 5%) tolerated CM. None of the recalled children reported use of emergency care. SPT positivity to casein and/or α-lactoalbumin decreased significantly (p < 0.01), and all the negative SPT referred to the tolerant children. Cutaneous sensitivity to both casein and α-lactoalbumin (end-point SPT) significantly decreased after the 6-month desensitization period of the previous study (p < 0.001), but did not decrease significantly at follow-up. A significant reduction of serum-specific CM IgE was also observed (p < 0.05). Clinical tolerance induced by oral CM desensitization persists in time. Negativization of SPT and reduction of specific CM IgE could be considered prognostic indicators of CM tolerance. Oral CM desensitization seems to be a promising method to treat CM food allergy. This protocol is time-consuming but offers the advantage that it can be performed at home. This methodology must only be used by trained staff. [ABSTRACT FROM AUTHOR]

Cord blood T lymphocytes are immature and their functional defect partially reflects a suboptimal level of costimulatory signals provided by neonatal antigen-presenting cells. Neonatal Vδ2 T lymphocytes, a small component of cellular immunity involved in the response against bacteria, protozoa, virus-infected cells and tumours, are also considered to be immature. Cord blood Vδ2 T lymphocytes are mostly naïve, proliferate poorly and do not produce cytokines in response to the model phosphoantigen isopentenyl pyrophosphate. We cultured cord blood mononuclear cells with the aminobisphosphonate Pamidronate or with live bacille Calmette–Guérin, and showed that both elicit a strong cord blood Vδ2 T-cell proliferative response, inducing the expression of activation markers and promoting the differentiation from naïve to memory cells. Our results suggest that cord blood Vδ2 T cells are not inherently unresponsive and can mount strong responses to aminobisphosphonates and mycobacteria. Neonatal Vδ2 T lymphocytes may be important participants in responses to microbial infections early in life. [ABSTRACT FROM AUTHOR]

A study of the association between mild thyroid dysfunction and higher mortality in cardiac patients. An assessment of cardiac and deaths of 3121 cardiac patients is undertaken in four defined groups: euthyroidism, subclinical hypothyroidism (SCH), subclinical hyperthyroidism (SCT), and low trioodothyronine syndrome (low T3). The investigation revealed that altered status of thyroid is associated with increased mortality risk in cardiac disease patients.

The article presents a study on the sequencing of FLG gene in 220 Italian patients wit atopic eczema (AE). It mentions that AE is the most common chronic inflammatory skin disease with increased transepidermal water loss. In conclusion, there is a small percentage of Italian AE patients which carry mutations in the FLG gene, however, it must not be considered as a major risk factor for AE in the Italian population. It notes that FLG mutations is heterogeneous among European populations.

Background: acute recurrent pancreatitis is a complex multigenic disease, the diagnosis is even more difficult when this disease develops in a child.Case Presentation: a 6-years old boy, hospitalized with epigastric pain radiating to the back showed high serum levels of serum amylase, lipase, CRP and erythrosedimentation rate. Several similar milder episodes of pain, followed by quick recovery and complete disappearance of symptoms were reported during the previous 13 months. The child was medically treated and after 7 days with normal clinic and laboratory tests was discharged with a hypolipidic diet. All the known aetiologic hypotheses were excluded by anamnestic investigation, clinical observation and biochemical evaluation, whereas, anatomic abnormality were excluded by a secretin stimulated magnetic resonance (MRI). At the last follow-up visit, (11 months later), the child showed a normal body weight and anthropometric profile, without further abdominal pain. Mutation screening for coding regions of PRSS1, SPINK1, CFTR and the new hereditary pancreatitis-associated chymotrypsin C (CTRC) genes showed a novel variation, c.541A > G (p.S181G), in the exon 4 of PRSS1 gene and the classical CF p.F508del mutation in the CFTR. Both mutations were present in his clinically normal mother and absent in the patient's father.Conclusions: this report extend the spectrum of PRSS1 mutations, however, the absence of family history of pancreatitis leaves the present case without the hallmark of the hereditary origin of pancreatitis. At the present knowledge it can be only stated that the combined genotype CFTR (F508del)/PRSS1 (S181G) is associated to a mild phenotype of acute recurrent pancreatitis in this child without any further conclusion on its pathogenetic role or prediction on the course of the disease. [ABSTRACT FROM AUTHOR]