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Background: Glucocorticoids (GCs) represent the mainstay therapy for asthmatics. A subset of severe asthmatics fails to respond to steroid-based therapies, leading to important healthcare costs. Single nucleotide polymorphisms (SNPs) of glucocorticoid receptor genes were associated with a response to GC. We evaluate the possible relation of BclI and A3669G SNPs to clinical, biological and functional characteristics of asthmatics. Methods: We recruited 172 mild-to-severe asthmatic outpatients referring to the Severe Asthma and Rare Lung Disease Unit at San Luigi University Hospital. Clinical data were obtained at recruitment when spirometry tests and peripheral blood sampling were performed. Patients were genotyped for BclI and A3669G through the pyrosequencing assay results. Results: Patients with the A3669G AG genotype were younger, allergic and had higher IgE levels compared to AA genotype (p < 0.05). Moreover, asthmatics with the AA genotype had a lower post-bronchodilator FEV1/FVC ratio than the GG genotype (p < 0.05), and a higher RV/TLC ratio than the AG genotype (p < 0.05). Conclusions: The A3669G AG genotype might be related to type-2 allergic asthma; in particular, allele A of A3669G SNP was associated with GC response in our asthmatics. In conclusion, this observational cross-sectional study suggests a possible role of A3669G SNP as a predictor of asthma severity and phenotype.

PTEN hamartoma tumor syndrome (PHTS), is a spectrum of disorders caused by mutations of PTEN, in which non-cancerous growths, called hamartomas, develop in different areas of the body, often including the oral mucosa. PHTS also implies a recognized increased risk of malignancies, as PTEN is a tumor suppressor gene capable of inhibiting progression of several cancers. One of the main and most common clinical manifestation of PHTS are gingival overgrowths presenting as warty lumps. The current study describes patients with gingival or mucosal enlargements leading to the diagnosis of PHTS associated to novel PTEN pathogenic variants. Patients referred to us for gingival lumps suggestive of PHTS associated overgrowths were submitted to genetic analysis in the PTEN gene. Two related and two unrelated patients were investigated. PTEN novel pathogenic variant was found in all of them. Two patients also fulfilled diagnostic criteria of Cowden syndrome (CS). Mucocutaneous lesions, and particularly diffuse gingival overgrowths, are both early and major clinical signs revealing a potential diagnosis of PHTS. Further genetic and clinical assessments are needed in order to confirm and clarify the diagnosis within the PHTS spectrum, including, among others, the CS. A correct interpretation of oral clinical features potentially associated to PHTS is mandatory for diagnosis and a surgical approach can be useful just in case of impairment of periodontal health or for aesthetic needs. The increased risk of malignancies associated to PHTS makes a correct diagnosis pivotal to set up an appropriate lifelong surveillance, aiming at secondary cancer prevention.

Study objective Accurate diagnostic testing to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical. Although highly specific, SARS-CoV-2 reverse transcriptase–polymerase chain reaction (RT-PCR) has been shown in clinical practice to be affected by a noninsignificant proportion of false-negative results. This study seeks to explore whether the integration of lung ultrasonography with clinical evaluation is associated with increased sensitivity for the diagnosis of coronavirus disease 2019 pneumonia, and therefore may facilitate the identification of false-negative SARS-CoV-2 RT-PCR results. Methods This prospective cohort study enrolled consecutive adult patients with symptoms potentially related to SARS-CoV-2 infection who were admitted to the emergency department (ED) of an Italian academic hospital. Immediately after the initial assessment, a lung ultrasonographic evaluation was performed and the likelihood of SARS-CoV-2 infection, based on both clinical and lung ultrasonographic findings (“integrated” assessment), was recorded. RT-PCR SARS-CoV-2 detection was subsequently performed. Results We enrolled 228 patients; 107 (46.9%) had SARS-CoV-2 infection. Sensitivity and negative predictive value of the clinical–lung ultrasonographic integrated assessment were higher than first RT-PCR result (94.4% [95% confidence interval {CI} 88.2% to 97.9%] versus 80.4% [95% CI 71.6% to 87.4%] and 95% [95% CI 89.5% to 98.2%] versus 85.2% [95% CI 78.3% to 90.6%], respectively). Among the 142 patients who initially had negative RT-PCR results, 21 tested positive at a subsequent molecular test performed within 72 hours. All these false-negative cases were correctly identified by the integrated assessment. Conclusion This study suggests that, in patients presenting to the ED with symptoms commonly associated with SARS-CoV-2 infection, the integration of lung ultrasonography with clinical evaluation has high sensitivity and specificity for coronavirus disease 2019 pneumonia and it may help to identify false-negative results occurring with RT-PCR.

Background: Acute aortic syndromes (AASs) are rare and severe cardiovascular emergencies with unspecific symptoms. For AASs, both misdiagnosis and overtesting are key concerns, and standardized diagnostic strategies may help physicians to balance these risks. D-dimer (DD) is highly sensitive for AAS but is inadequate as a stand-alone test. Integration of pretest probability assessment with DD testing is feasible, but the safety and efficiency of such a diagnostic strategy are currently unknown. Methods: In a multicenter prospective observational study involving 6 hospitals in 4 countries from 2014 to 2016, consecutive outpatients were eligible if they had ≥1 of the following: chest/abdominal/back pain, syncope, perfusion deficit, and if AAS was in the differential diagnosis. The tool for pretest probability assessment was the aortic dissection detection risk score (ADD-RS, 0–3) per current guidelines. DD was considered negative (DD−) if Results: A total of 1850 patients were analyzed. Of these, 438 patients (24%) had ADD-RS=0, 1071 patients (58%) had ADD-RS=1, and 341 patients (18%) had ADD-RS >1. Two hundred forty-one patients (13%) had AAS: 125 had type A aortic dissection, 53 had type B aortic dissection, 35 had intramural aortic hematoma, 18 had aortic rupture, and 10 had penetrating aortic ulcer. A positive DD test result had an overall sensitivity of 96.7% (95% confidence interval [CI], 93.6–98.6) and a specificity of 64% (95% CI, 61.6–66.4) for the diagnosis of AAS; 8 patients with AAS had DD−. In 294 patients with ADD-RS=0/DD−, 1 case of AAS was observed. This yielded a failure rate of 0.3% (95% CI, 0.1–1.9) and an efficiency of 15.9% (95% CI, 14.3–17.6) for the ADD-RS=0/DD− strategy. In 924 patients with ADD-RS ≤1/DD−, 3 cases of AAS were observed. This yielded a failure rate of 0.3% (95% CI, 0.1–1) and an efficiency of 49.9% (95% CI, 47.7–52.2) for the ADD-RS ≤1/DD− strategy. Conclusions: Integration of ADD-RS (either ADD-RS=0 or ADD-RS ≤1) with DD may be considered to standardize diagnostic rule out of AAS. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02086136.

Acute aortic syndromes (AAS) are cardiovascular emergencies with unmet diagnostic needs. Copeptin is released upon stress conditions and is approved for rule-out of myocardial infarction (MI). As MI and AAS share presenting symptoms, stress mechanisms and necessity for rapid diagnosis, copeptin appears as an attractive biomarker also for AAS. We thus performed a diagnostic and observational study in Emergency Department (ED) outpatients. Inclusion criteria were chest/abdominal/back pain, syncope and/or perfusion deficit, plus AAS in differential diagnosis. Blood samples were obtained in the ED. 313 patients were analyzed and 105 (33.5%) were diagnosed with AAS. Median copeptin was 38.91 pmol/L (interquartile range, IQR, 16.33–173.4) in AAS and 7.51 pmol/L (IQR 3.58–15.08) in alternative diagnoses (P

Pre-test probability assessment is key in the approach to suspected acute aortic syndromes (AASs). However, most patients with AAS-compatible symptoms are classified at low probability, warranting further evaluation for decision on aortic imaging. White blood cell count, platelet count and fibrinogen explore pathophysiological pathways mobilized in AASs and are routinely assayed in the workup of AASs. However, the diagnostic performance of these variables for AASs, alone and as a bundle, is unknown. We tested the hypothesis that white blood cell count, platelet count and/or fibrinogen at presentation may be applied as additional tools to standard clinical evaluation for pre-test risk assessment in patients at low probability of AAS.This was a retrospective observational study conducted on consecutive patients managed in our Emergency Department from 2009 to 2014 for suspected AAS. White blood cell count, platelet count and fibrinogen were assayed during evaluation in the Emergency Department. The final diagnosis was obtained by computed tomography angiography. The pre-test probability of AAS was defined according to guidelines. Of 1210 patients with suspected AAS, 1006 (83.1%) were classified at low probability, and 271 (22.4%) were diagnosed with AAS. Within patients at low probability, presence of at least one alteration among white blood cell count9*10In addition to standard clinical evaluation, white blood cell count and platelet count may be used in patients at low pre-test probability to fine-tune risk assessment of AAS.

The aortic dissection detection (ADD) risk score has been proposed by guidelines to standardise the approach to patients with suspected acute aortic dissection (AD). However, the ADD risk score has not been validated so far.Patients with suspected AD from two clinical centres were prospectively enrolled in a registry from 2008 to 2012. The ADD risk score was calculated retrospectively by review of medical charts, according to the number of risk categories where patients met criteria. Of 1328 patients, 291 (21.9%) were diagnosed with AD. The ADD risk score was=0 in 439 (33.1%) patients, =1 in 646 (48.6%) patients and1 in 243 (18.3%) patients. The incidence of AD was 5.9%, 27.3% and 39.1% respectively in patient groups identified by ADD risk score=0, =1 and1. ADD risk score0 had a sensitivity of 91.1% (95% confidence interval (CI) 87.2-94.1%) and a specificity of 39.8% (95% CI 36.8-42.9%) for the diagnosis of AD, while ADD risk score1 had a sensitivity of 32.7% (95% CI 27.3-38.4%) and a specificity of 85.7% (95% CI 83.5-87.8%). Among patients with ADD risk score=0, mediastinum widening on chest X-ray had a sensitivity of 16.7% (95% CI 3.6-41.4%) and a specificity of 86.3% (95% CI 81.9-90.0%).The ADD risk score stratifies patients for the risk of AD. ADD risk score0 is highly sensitive and poorly specific for the diagnosis in AD. The presence of ADD risk score=0 per se does not accurately exclude AD. In patients with ADD risk score=0, chest X-ray provides limited diagnostic information.

Purpose: The diagnosis of acute aortic dissection (AoD) constitutes a major challenge. To assist physicians, the American Heart Association (AHA) has proposed a detection risk score based on high-risk predisposing conditions, pain features and physical examination. Such score identifies patients at low, intermediate and high risk of AoD. In the low-risk group, absence of a widened mediastinum on chest X-ray has been suggested as a mean to safely rule out AoD without further aortic imaging. However, the AHA risk score and derived diagnostic algorithm is awaiting validation. The aim of our study was to evaluate the diagnostic performance of the AoD AHA risk score in the emergency department (ED). Methods: Consecutive adult patients suspected of AoD from 2 EDs were included in a prospective registry from January 2008 to December 2012. Patients were classified according to the AHA risk score and the prevalence of AoD was calculated in each risk group. Furthermore, we estimated the prevalence of AoD in low-risk patients with a not-widened mediastinum on chest X-ray (CXR). The final diagnosis of AoD was obtained with computed tomography, angiography, surgery or autopsy. Results: Among the 1279 patients (mean age 68 years) included in the study, 236 (18.4%) were diagnosed with AoD; 365 (28.5%) patients presented at least one predisposing high-risk condition, 358 (27.9%) a high-risk pain feature and 342 (26.7%) a high-risk physical examination finding. 461 (36%) patients were classified as low-risk, 595 (46.5%) as intermediate-risk and 223 (17.4%) as high-risk. The respective prevalence of AoD was 10.1%, 18.9% and 34% in the 3 groups. Among the 420 (91%) low-risk patients with available CXR, the mediastinum was not-widened in 28 (60%) of 47 patients with AoD. Hence, 6.6% of low-risk patients with a not-widened mediastinum on CXR had AoD. Conclusion: The AHA risk score correctly stratifies patients for AoD prevalence in the ED. However AoD can not safely be rule out in the low risk patients even if a not-widened mediastinum is detected at CXR.

Introduction Matrix metalloproteinases (MMPs) are involved in aortic pathophysiology. Preliminary studies have detected increased plasma levels of MMP8 and MMP9 in patients with acute aortic dissection (AAD). However, the performance of plasma MMP8 and MMP9 for the diagnosis of AAD in the emergency department is at present unknown. Methods The levels of MMP8 and MMP9 were measured by ELISA on plasma samples obtained from 126 consecutive patients evaluated in the emergency department for suspected AAD. All patients were subjected to urgent computed tomography (CT) scan for final diagnosis. Results In the study cohort (N = 126), AAD was diagnosed in 52 patients and ruled out in 74 patients. Median plasma MMP8 levels were 36.4 (interquartile range 24.8 to 69.3) ng/ml in patients with AAD and 13.2 (8.1 to 31.8) ng/ml in patients receiving an alternative final diagnosis (P