Detection of sieric BAG3 in patients affected by cardiovascular diseases: State of art and perspectives.

BAG3 is highly expressed in the heart and its functions are essential in maintaining cardiac muscle cells homeostasis. In the past, BAG3 was detected in serum from advanced heart failure patients and its higher levels were correlated to an increased death risk. Moreover, it has also been reported that BAG3 levels in serum are increased in patients with hypertension, a known cardiovascular risk marker. Evidence from different laboratories suggested the possibility to use BAG3-based strategies to improve the clinical outcome of cardiovascular disease patients. This review aims to highlight the biological roles of intracellular or secreted BAG3 in myocardiocytes and propose additional new data on the levels of sieric BAG3 in patients with acute myocardial infarction (AMI), never assessed before. We evaluated BAG3 serum levels in relation to cardiovascular risk parameters in 64 AMI patients aged ≥18 years of either sex. We observed significant (p < .01) correlations of BAG3 positivity with dyslipidemic status and diabetic disease. We did not observe any significant correlations of BAG3 levels with smoking habit, hypertension or familiarity for AMI, although BAG3-positive seemed to be more numerous than BAG3-negative patients among hypertensives and among patients with familiarity for AMI. Furthermore, a significant (p < .001) correlation of BAG3 positivity with diuretics assumption was also noted. In conclusion, 32.8% of the patients were BAG3-positive and were characterized by some particular features as comorbidity presence or concomitant therapies. The significance of these observations needs to be verified by more extensive studies and could help in the validation of the use of BAG3 as a biomarker in heart attack risk stratification.

Multidimensional Prognostic Index Predicts Clinical Outcome and Mortality in Hospitalised Older Patients with Diverticular Disease.

INTRODUCTION: The Multidimensional Prognostic Index (MPI) is a validated tool for assessing mortality risk in hospitalised patients. We aimed to evaluate whether the MPI predicted mortality and the risk of developing diverticular disease (DD) complications in older patients. METHODS: This is a multicentre study conducted in January 2016-March 2018. All patients with DD aged 65 years and older were included. Patients were stratified into three groups according to MPI groups (1, low risk; 2, moderate risk; 3, high risk). Risk of developing DD complications and mortality rate were assessed. Bivariate models were fitted. RESULTS: One hundred hospitalised patients with DD (mean age 77.9 ± 10.6 years, 53 female patients) were included. Patients with higher MPI groups were more likely to develop DD complications. In particular, 12 (46.2%), 21 (52.5%), and 28 (82.4%) patients with complicated DD were distributed to the MPI 1, MPI 2, and MPI 3 groups (p = 0.0063), respectively. Two patients died in the MPI 1, 4 in the MPI 2, and 29 in the MPI 3 group, with mortality rates of 4.0 per 100 person-year (95% confidence interval [CI] 1.0-15.9), 5.6 (95% CI 2.1-15.0), and 89.2 (95% CI 62-130), respectively (log-rank test p < 0.001). In bivariate analysis, after adjustment for age >80 years, Charlson Comorbidity Index >4, DD complications, and the presence of thromboembolism, higher MPI group was independently associated with higher mortality. Those in the MPI 3 group experienced a greater risk of 1-year hospital readmission (p < 0.001). CONCLUSION: MPI predicted mortality in patients with DD and also correlated with the risk of developing DD complications. Studies focussing on possible pathophysiological mechanisms between DD complications and MPI are needed.

[Remote functional evaluation after reconstruction of the anterior cruciate ligament in amateur sportsmen with sedentary work]. / Valutazione funzionale a distanza dopo ricostruzione del LCA in sportivi amatoriali con lavoro sedentario.

SUMMARY: The anterior cruciate ligament (ACL) is the most commonly injured knee ligament. Currently there are two commonly used surgical procedures: middle third patellar tendon grafts (bone-patellar tendon-bone: BTB) and semitendinosus autografts or semitendinosus combined with gracilis tendon autografts (ST/G). Purpose. The aim of this study is to compare the rehabilitation results over time of amateur sportsmen who have undergone anterior cruciate ligament (ACL) reconstruction surgery by means of one of the two most commonly used procedures: middle third patellar tendon grafts (bone-patellar tendon-bone: BTB) and semitendinosus and gracilis tendon autografts (ST/G). Method. 30 subjects divided into two groups, (15 BTB and 15 ST / G), were evaluated during rehabilitation and at three follow-up periods (16 weeks, 24 weeks, 2 years). Evaluation involved clinical examination, isokinetic tests, and functional rating scales: Lysholm and IKDC. Results. The clinical evaluation resulted in the following mean values: the value of the Lysholm score was 78 in both group at 16 weeks, 91 in group A and 94 in group B at 24 weeks, 98 in group A and 99 in group B at 2 years; the value of the IKDC score was 14 in group A and 15 in group B at 16 weeks, 12 in group A and 14 in group B at 24 weeks, 14 in group A and 15 in group B at 2 years. No major complications occurred during rehabilatation Conclusions. Subjects in both groups showed good neoligament stability up to the 24-week follow up. At the 2-year follow-up the subjects of group B showed poor neoligament stability that prevented the return to the previous level of sporting activity; all the subjects with high intensity sports activity needed a greater muscle strengthening. No statistically significant differences between the two groups are seen.

A new algorithm shows superior ability to discriminate liver fibrosis stages in chronic hepatitis C.

Previous evidence suggests that sialic acid-binding Ig-like lectin 7 (Siglec-7) protein is significantly increased in patients with chronic hepatitis C virus (HCV) infection and directly correlates with clinical parameters of liver inflammation and fibrosis. The aim of this study was to determine the diagnostic value of Siglec-7 as a non-invasive tool to assess liver fibrosis in patients with chronic hepatitis C in a cross-sectional study. Serum levels of Siglec-7 were retrospectively tested in 1007 consecutive patients with chronic HCV infection recruited at three different European sites and data examined by the 'imperfect gold-standard' statistical analysis. Liver stiffness obtained by transient elastography (TE) was considered the standard reference. Liver fibrosis was staged according to published cut-offs of liver stiffness measurement by TE. Accuracy of detection of liver fibrosis stage was not increased by Siglec-7 alone. However, we developed a new index (SiGAP) including Siglec-7, γ-glutamyl transferase, age and platelet count which showed increased sensitivity and specificity in predicting fibrosis compared with APRI or FIB4 indices. The AUROC of SiGAP for the diagnosis of significant (≥F2) and advanced liver fibrosis (≥F3) showed significantly higher values than those of APRI and FIB-4. Siglec-7 may be useful as a complementary tool to assess liver fibrosis stage in patients with chronic hepatitis C when included in a specifically designed algorithm, which showed high level of accuracy in the detection of F2 and F3 fibrosis stage.

Performance of the Attenuation Imaging Technology in the Detection of Liver Steatosis.

OBJECTIVES: The main aim was to assess the performance and cutoff value for the detection of liver steatosis (grade S > 0) with the Attenuation Imaging-Penetration (ATI-Pen) algorithm available on the Aplio i-series ultrasound systems (Canon Medical Systems, Otawara, Japan). The magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) was used as the reference standard. Secondary aims were to compare the results to those obtained with the previous ATI algorithm (Attenuation Imaging-General [ATI-Gen]) and with the controlled attenuation parameter (CAP) and to generate a regression equation between ATI-Pen and ATI-Gen values. METHODS: Consecutive adult patients potentially at risk of liver steatosis were prospectively enrolled. Each patient underwent ultrasound quantification of liver steatosis with ATI-Pen and ATI-Gen and a CAP assessment with the FibroScan system (Echosens, Paris, France). The MRI-PDFF evaluation was performed within a week. The correlations between ATI-Pen, ATI-Gen, the CAP, and the MRI-PDFF were analyzed with the Pearson rank correlation coefficient. The diagnostic performance of ATI-Pen, ATI-Gen, and the CAP was assessed with receiver operating characteristic curves and an area under the receiver operating characteristic curve (AUROC) analysis. RESULTS: Seventy-two individuals (31 male and 41 female) were enrolled. Correlation coefficients of ATI-Pen, ATI-Gen, and the CAP with the MRI-PDFF were 0.78, 0.83, and 0.58, respectively. The AUROCs of ATI-Pen, ATI-Gen, and the CAP for detecting steatosis (S > 0) were 0.90 (95% confidence interval, 0.81-0.96), 0.92 (0.82-0.98), and 0.85 (0.74-0.92), and the cutoffs were greater than 0.69 dB/cm/MHz, greater than 0.62 dB/cm/MHz, and greater than 273 dB/m. The regression equation between ATI-Pen and ATI-Gen was ATI-Pen = 0.88 ATI-Gen + 0.13. CONCLUSIONS: Attenuation Imaging is a reliable tool for detecting liver steatosis, showing an excellent correlation with the MRI-PDFF and high performance with AUROCs of 0.90 or higher.

Rapid detection of bacteria in bloodstream infections using a molecular method: a pilot study with a neonatal diagnostic kit.

Neonatal sepsis is a life-threatening condition and its early diagnosis is crucial for infant survival. Identifying responsible pathogens is a key step. Blood culture (BC) is the gold standard, but more rapid and specific diagnostic methods are needed. We evaluated the reliability and utility of 3 h turnaround time diagnostic molecular kit, "EuSepScreen lattanti "CE IVD marked, (EuSepScreen lattanti, Eurospital Spa Trieste, Italy) specifically targeted to detect 4 pathogens in neonatal sepsis: Klebsiella pneumoniae (KP), Escherichia coli (EC), Streptococcus agalactiae (GBS), and Lysteria monocytogenes. We evaluated 69 neonates, 40 full term and 29 preterm infants, with suspected bloodstream infection, who, overall the routine clinical procedures, were tested using the molecular kit. Kit results were compared to BC outcomes. Nineteen cases for early onset sepsis (EOS) were evaluated, 2 of them resulted positive to a molecular kit and to BC (both for GBS and EC). In the 50 cases of suspected late onset sepsis (LOS), 7 infants reported positive and coincident results to both the methods, in 3 further cases the molecular kit identified pathogens (EC) in neonates with negative BC result; in 10 cases BC revealed etiological pathogens exceeding the molecular kit possibility of identification. In case of EOS, results of the molecular kit were coincident to these of BC, but available in 3 h turnaround time, which is an advantage, so the kit may actually be an "add-on tool" for EOS, with reference to EC and GBS, but a larger study with a greater number of EOS cases are needed to validate its usefulness in the NICU. Regarding LOS the restricted panel of identifiable microorganisms failed to provide timely information for sepsis diagnosis, highlighting the need of enlarged number microorganisms for the diagnosis of LOS.Trial registration number: NCT03884894.

Radiation-induced circulating miRNA expression in blood of head and neck cancer patients.

In recent years, scientists have found evidence confirming the aberrant expression of miRNAs in cancer patients compared to healthy individuals. The growing interest in the identification of non-invasive and specific diagnostic and prognostic molecular markers has identified microRNAs as potential candidates in cancer diagnosis, prognosis and treatment response. In the present study, we have analyzed the expression profile of circulating miR-21, -191 and -421 in peripheral blood of head and neck cancer patients (HNC) to investigate a possible modulation of mRNA levels by radiation and to identify the role of mRNA as biomarkers of cancer prognosis. Results showed a modulation of the microRNA expression at different time points after radiotherapy, suggesting that treatment may influence the release of circulating miRNAs depending also on the time interval elapsed since radiotherapy. The expression levels of miR-21, -191 and -421 were higher in blood of patients treated with radiotherapy alone after 6 months from the end of therapy and high levels of them seemed to correlate with the remission of the disease. The trends shown in this study confirmed that miRNAs could be useful prognosis markers and could provide preliminary data for further evaluation in predicting patients' response to radiotherapy by developing miRNA-based treatments to improve the sensitivity of cancer cells to radiotherapy.

Postural analysis in a pediatric cohort of patients with Ehlers-Danlos Syndrome: a pilot study.

BACKGROUND: The Ehlers-Danlos Syndrome (EDS) is a rare disorder affecting the connective tissue. EDS patients may suffer of proprioception and balance impairment but all the studies dealing with such symptoms have been addressed to adult subjects. The Study of such impairment in younger patients may lead to a better awareness of own motor abilities and to a focused rehabilitative intervention. Therefore, our work aims to assess the occurrence of these alterations in a pediatric cohort of EDS patients. METHODS: The Research was designed as a cross-sectional study with a matching control group and performed on a pediatric cohort of 12 subjects with Ehlers-Danlos Syndrome (Classic and Hypermobility type) and on 12 healthy controls, during a follow-up visit at the Department of Pediatrics and at the Rehabilitation Unit of the Foundation IRCCS Policlinico San Matteo, in Pavia from April 2015 to October 2015. A square forceplatform was used to obtain the CoP (center of pressure) displacement during quiet standing during an open and a closed eyes trials. The comparisons between EDS and control group were performed using a t-test for independent data. P<0.05 was considered statistically significant. All tests were two-sided. RESULTS: All the postural parameters considered raised at closed eyes, no significant modifications without vision were found only for the standard deviation along the antero-posterior (AP) axis for the two groups. Both at open eyes and at closed eyes, Patients with EDS showed the postural parameters significantly greater than controls (P≤0.05) and this observation was most notably for the Sway. CONCLUSIONS: According to our results, a planned monitoring of age-related changes in postural parameters of patients with EDS could be really interesting to provide a perspective of the development of postural control in these patients. In fact, considering our results, it could be interesting to apply rehabilitative strategies to enhance motor coordination and postural reflexes so improving their postural control as soon as possible. Further studies about the postural control in EDS children and adolescents are required to confirm our results.

An immune-molecular hypothesis supporting infectious aetiopathogenesis of Kawasaki disease in children.

The competitive binding between CpG-ODN (single-stranded DNA from pathogens) and HLA-B and HLA-A ligands for the inhibitory Killer Immunoglobulin-like Receptors (KIR)3DL1/2 may lead to possible hypo-sensing of pathogens and ineffective clearance. We observed an overabundance of HLA ligands for inhibitory KIR with three domains in KD subjects.

A Trained Pulmonologist Can Reliably Assess Endosonography-Derived Lymph Node Samples during Rapid On-Site Evaluation.

BACKGROUND: The widespread use of rapid on-site evaluation is hampered by constraints related to time and resources, inadequate reimbursement, and evidence from randomized trials that show a lack of increase in diagnostic yield and specimen adequacy associated with its usage. OBJECTIVE: We aimed to verify whether a pulmonologist can assess endosonography-derived lymph node samples after a comprehensive and reproducible training provided by a specialist pathologist. METHODS: Prospective, observational trial structured in three phases. In the first (training) phase, a pathologist critically evaluated the smears from 150 archival endosonography cases with a pulmonologist. In the second (test) phase, the pulmonologist was asked to assess 50 archival endosonography-derived samples. In the last (real-life) phase, the pulmonologist classified the samples from 200 patients during the endosonography. The overall agreement between pulmonologist and pathologist (gold standard), assessed through κ-statistics, was the primary outcome. The agreement for the identification of specific cytological categories was the secondary outcome. RESULTS: The overallagreement between pulmonologist and pathologist was 84% (κ0.765, 95% CI 0.732-0.826) in the test phase and 89.7% (κ 0.844, 95% CI 0.799-0.881) in the real-life phase. The agreement for specific cytological categories was 92.7% (95% CI 0.824-0.980) for inadequate samples, 90.3% (95% CI 84.5-94.5%) for reactive lymphadenopathies, 90.5% (95% CI 0.845-0.946) for malignancy, and 73% (95% CI 0.515-0.897) for granulomatous samples. CONCLUSIONS: A trained pulmonologist can reliably assess adequacy and malignancy for endosonography-derived samples, which could be useful in institutions where a cytopathologist/cytotechnician is not available regularly.

Focused extracorporeal shock wave therapy for greater trochanteric pain syndrome with gluteal tendinopathy: a randomized controlled trial.

OBJECTIVES:: To investigate if focused extracorporeal shock wave therapy (f-ESWT) is an effective treatment in a population affected by greater trochanteric pain syndrome (GTPS). DESIGN:: Randomized controlled trial, with blind outcome assessors. SETTING:: Outpatients, University Hospital. SUBJECTS:: A total of 50 patients affected by GTPS with gluteal tendinopathy. INTERVENTIONS:: The study group was assigned to receive f-ESWT, the control group received ultrasound therapy (UST). MAIN MEASURES:: We assessed hip pain and lower limb function by means of a numeric rating scale (p-NRS) and the Lower Extremity Functional Scale (LEFS scale), respectively. The first follow-up evaluation (2M-FUP) was performed two months after the first treatment session, the second (6M-FUP) was carried out six months later. RESULTS:: The mean age of the population was 61.24 (9.26) years. A marked prevalence of the female sex was recorded (44 subjects, 86%). The statistical analysis showed a significant pain reduction over time for the study group and the control group, the f-ESWT proving to be significantly more effective than UST ( P < 0.05) at the 2M-FUP (2.08 vs 3.36) and at the 6M-FUP (0.79 vs 2.03). A marked improvement of the LEFS total score was observed in both groups as well, but we found no statistical differences in the comparisons between groups. CONCLUSION:: Our findings support the hypothesis that f-ESWT is effective in reducing pain, both in the short-term and in the mid-term perspective. We also observed a functional improvement in the affected lower limb, but, in this case, f-ESWT showed not to be superior to UST.

A shared protocol for porcine surfactant use in pediatric acute respiratory distress syndrome: a feasibility study.

BACKGROUND: Pediatric ARDS still represents a difficult challenge in Pediatric Intensive Care Units (PICU). Among different treatments proposed, exogenous surfactant showed conflicting results. Aim of this multicenter retrospective observational study was to evaluate whether poractant alfa use in pediatric ARDS might improve gas exchange in children less than 2 years old, according to a shared protocol. METHODS: The study was carried out in fourteen Italian PICUs after dissemination of a standardized protocol for surfactant administration within the Italian PICU network. The protocol provides the administration of surfactant (50 mg/kg) divided in two doses: the first dose is used as a bronchoalveolar lavage while the second as supplementation. Blood gas exchange variations before and after surfactant use were recorded. RESULTS: Sixty-nine children, age 0-24 months, affected by Acute Respiratory Distress Syndrome treated with exogenous porcine surfactant were enrolled. Data collection consisted of patient demographics, respiratory variables and arterial blood gas analysis. The most frequent reasons for PICU admission were acute respiratory failure, mainly bronchiolitis and pneumonia, and septic shock. Fifty-four children (78.3%) had severe ARDS (define by oxygen arterial pressure and inspired oxygen fraction ratio (P/F) < 100), 15 (21.7%) had moderate ARDS (100 < P/F < 200). PO2, P/F, Oxygenation Index (OI) and pH showed a significant improvement after surfactant use with respect to baseline (p < 0.001 at each included time-point for each parameter). No significant difference in blood gas variations were observed among four different subgroups of diseases (bronchiolitis, pneumonia, septic shock and others). Overall, 11 children died (15.9%) and among these, 10 (90.9%) had complex chronic conditions. Two children (18.2%) died while being treated with Extracorporeal Membrane Oxygenation (ECMO). Mortality for severe pARDS was 20.4%. CONCLUSION: The use of porcine Surfactant improves oxygenation, P/F ratio, OI and pH in a population of children with moderate or severe pARDS caused by multiple diseases. A shared protocol seems to be a good option to obtain the same criteria of enrollment among different PICUs and define a unique way of use and administration of the drug for future studies.

Diagnostic Performance and Accuracy of the 3 Interpreting Methods of Breast Strain Elastography: A Systematic Review and Meta-analysis.

There are 3 methods of interpreting breast strain elastography: the elastographic-to-B-mode length ratio (E/B), a 5-point color scale (5P), and the strain ratio (SR). This meta-analysis assessed which method is superior to the others. A systematic search of the medical literature was performed in July 2017. Studies were eligible for inclusion if they fulfilled the following criteria: (1) had biopsy-proven or long-term stability as the reference standard; (2) used either the E/B, 5P, or SR to interpret results; and (3) had at least 50 cases. A total of 220 records were retrieved; 60 full-text articles were examined, and 46 were included in the meta-analysis. Publication years ranged from 2007 and 2017. The quality of studies was generally high. The mean age of women was 48 years; 12,398 lesions (4242 malignant) were analyzed. For the 5P method, the sensitivity was 77%; specificity, 87%; positive likelihood ratio (LR), 5.3; and negative LR, 0.24. For the SR method, sensitivity was 87%; specificity, 81%; positive LR, 4.8; and negative LR, 0.16. For the E/B method, sensitivity was 96%; specificity, 88%; positive LR, 7.1; and negative LR, 0.03. Of the 3 methods, the E/B had the highest sensitivity, and the E/B and 5P had the highest specificity. With a negative LR of 0.03, the E/B method can downgrade lesions with a pretest probability of 50% to a 2% probability of malignancy.

Evaluation of Inter-System Variability in Liver Stiffness Measurements.

AIM: The primary aim of this study was to determine the inter-system variability of liver stiffness measurements (LSMs) in patients with varying degrees of liver stiffness. The secondary aim was to determine the inter-observer variability of measurements. MATERIALS AND METHODS: 21 individuals affected by chronic hepatitis C and 5 healthy individuals were prospectively enrolled. The assessment of LSMs was performed using six ultrasound (US) systems, four of which with point shear wave elastography (p-SWE) and two with 2 D shear wave elastography (2D-SWE) systems. The Fibroscan (Echosens, France) was used as the reference standard. Four observers performed the measurements in pairs (A-B, C-D). The agreement between different observers or methods was calculated using Lin's concordance correlation coefficient. The Bland-Altman limits of agreement (LOA) were calculated as well. RESULTS: There was agreement above 0.80 for all pairs of systems. The mean difference between the values of the systems with 2D-SWE technique was 1.54 kPa, whereas the maximum mean difference between the values of three out of four systems with the pSWE technique was 0.79 kPa. The intra-patient concordance for all systems was 0.89 (95 % CI: 0.83 - 0.94). Inter-observer agreement was 0.96 (95 % CI: 0.94 - 0.98) for the pair of observers A-B and 0.93 (95 % CI: 0.89 - 0.96) for the pair of observers C-D. CONCLUSION: The results of this study show that the agreement between LSMs performed with different US systems is good to excellent and the overall inter-observer agreement in "ideal conditions" is above 0.90 in expert hands.

Anatomic variations of the round window niche: radiological study and related endoscopic anatomy.

PURPOSE: In the last decades, literature has shown an increasing interest in round windows (RW) anatomy due to its pivotal role in deafness surgery. The high variability of this anatomical region, with particular regard to the round windows niche (RWN), has been studied by several authors through different methods of investigation. The aim of the present research was to radiologically examine the morphological variability of the RWN and to link the imaging findings to the endoscopic view. METHODS: High-resolution CT scans of 300 temporal bones without neuro-otological pathologies were retrospectively reviewed by 2 neuroradiologist and 1 ENT surgeon who independently evaluated the RWN morphological variations. To link the radiological to the endoscopic data, 45 cadaveric human temporal bones were submitted to a radiological evaluation and to an otoendoscopy conducted through a posterior tympanotomy approach. RESULTS: Three variants of the RWN were detected on coronal CT scan reconstructions: 155 "cylindrical-type", 97 "j-type" and 48 "truncated cone-type". For each radiological type the endoscopic findings showed a specific endoscopic position of the RW chamber, which results in different degrees of RW membrane visibility when analysed through a posterior tympanotomy approach. CONCLUSIONS: To the best of our knowledge, this is the first description of the above-mentioned RWN radiological variations supported by endoscopic data. This study suggests an additional anatomical evaluation that could be useful to predict the RW membrane visibility through a posterior tympanotomy approach. Further studies are required to support the clinical implications of our observations.

Relevance of HLA-DQB1*02 Allele in the Genetic Predisposition of Children with Celiac Disease: Additional Cues from a Meta-Analysis.

Background and Objectives: Celiac disease (CD) is a multifactorial immune-mediated disorder, triggered by the ingestion of gluten in genetically-predisposed subjects carrying MHC-DQ2 and -DQ8 heterodimers, which are encoded by four HLA-DQ allelic variants, overall. This meta-analysis aims at providing further epidemiological support to the predominant relevance of one specific allele, namely HLA-DQB1*02, in the predisposition and genetic risk of CD. Materials and Methods: We performed a search of MEDLINE/PubMed, Embase, Web of Science, and Scopus, retrieving all publications (case-control study, cross-sectional, and retrospective cohort study) on the association between HLA class II polymorphisms and first-degree relatives (FDRs) of children with CD. After a critical reading of the articles, two investigators independently performed data extraction according to the following inclusion criteria: HLA class II genes, any DQ and DR molecules, and CD diagnosed following the current clinical guidelines. A third participant was consulted for discussion to reach an agreement concerning discrepancies. Results: Our search strategy selected 14 studies as being eligible for inclusion, and those were submitted for data extraction and analysis. These studies were published between 1999 and 2016 and, collectively, enrolled 3063 FDRs. Positive and negative likelihood ratios (LR+ and LR-, respectively) for CD diagnosis, according to the presence of the HLA-DQ genotype coding a complete MHC-DQ2 and/or MHC-DQ8 molecules, were 1.449 (CI 1.279-1.642) and 0.187 (CI 0.096-0.362), respectively. If only the isolated presence of HLA-DQB1*02 allele is considered, the pooled estimation of LR+ was 1.659 (CI 1.302-2.155) and, importantly, the LR- still showed a very good discriminatory power of 0.195 (CI 0.068-0.558). Conclusions: Through our differential meta-analysis, comparing the presence of the genotype coding the full MHC-DQ2 and/or DQ8 molecules with the isolated presence of HLA-DQB1*02 allelic variant, we found that the LR- of the latter analysis maintained the same value. This observation, along with previous evidences, might be useful to consider potential cost-effective widened screening strategies for CD in children.

HLA-DQ genetics in children with celiac disease: a meta-analysis suggesting a two-step genetic screening procedure starting with HLA-DQ ß chains.

BackgroundSpecific HLA-DQ genes have been recognized as necessary - but not sufficient - factors for the occurrence of Celiac Disease (CD). Through a meta-analysis, evaluating the distribution of CD-related HLA genotypes in children, we aimed at providing insights for a potential widened screening strategy.MethodsAfter a systematic search on the association between class II HLA genes and CD in children, 46 publications were obtained and assessed for eligibility. A total of 13 eligible studies were submitted to data extraction and analysis (10 case-control studies and 3 cohort studies). Case-control studies collectively enrolled 740 CD patients and 943 controls.ResultsIn the population-stratified analysis, the following alleles conferred a significantly increased risk for CD: HLA-DQB1*02 (odds ratio [OR]=10.28) and HLA-DQB1*03:02 (OR=2.24). By drafting a risk gradient to develop CD according to HLA genetic background, the highest risk is confirmed to exist for DQ2/DQ2 homozygous subjects, regardless of the ethnicities (OR=5.4). Actually, the genotype DQ2/ß2 showed basically the same risk (OR=5.3). Indeed, no differences have been found in CD risk between DQ2/ß2 and DQ2/DQ2, as well as between DQ8/ß2 and DQ2/DQ8, and between ß2/DQX and DQ2/X.ConclusionThe HLA-DQB1*02:01 allele is present in more than 90% CD children. In the perspective of a widened pediatric population screening for CD, a double-step process might be suggested: HLA-DQB1*02:01 might be investigated first and, only if this result is positive, children might be candidate for a prospective serologic screening, as a second step.

Percutaneous Transanastomotic Stent Graft Deployment to Salvage Dysfunctional Native Forearm Radiocephalic Fistulae: Feasibility and Primary Patency at 12 Months.

PURPOSE: To evaluate feasibility and efficacy of transanastomotic self-expandable polytetrafluoroethylene stent graft placement for salvage of radiocephalic arteriovenous fistulae (RCAVFs). MATERIALS AND METHODS: From 2008 to 2016, 26 patients (21 male; age, 38-80 y) with dysfunctional RCAVFs for juxtaanastomotic lesions that were unresponsive to angioplasty underwent transanastomotic stent graft placement. Stenotic and thrombotic lesions were included. All were deemed unsuitable for surgical revision. Patency rates were calculated per Kaplan-Meier method. A Cox analysis was used to identify influencing factors. RESULTS: Thirty-two stent grafts (6 patients had 2 stents) were deployed. Anatomic and clinical success were achieved in all patients; no major complications occurred. Mechanical and/or pharmacologic thrombolysis was performed in 6 cases before stent graft deployment. During follow-up (median, 34.7 mo; range, 1.9-102.7 mo), 17 repeat interventions were required in 10 patients (43 procedures overall), for an endovascular intervention rate of 0.27 per year. At 3, 6, 12, and 24 months, primary patency (PP) rates were 96% ± 4 (95% CI, 75%-99%), 83% ± 7 (95% CI, 61%-93%), 78% ± 8 (95% CI, 55%-90%), and 69% ± 10 (95% CI, 46%-84%). The corresponding assisted PP rates were 96% ± 4 (95% CI, 76%-99%), 96% ± 4 (95% CI, 76%-99%), 92% ± 5 (95% CI, 71%-98%), and 82% ± 8 (95% CI, 60%-93%). Five AVFs were ultimately abandoned. Per Cox analysis, arterial diameter ≥ 4 mm was associated with better PP (P = .032). CONCLUSIONS: Transanastomotic stent graft placement for RCAVF salvage is feasible and safe, providing patency rates comparable with historical endovascular and surgical data. Its role should be evaluated in larger studies.

Early morpho-functional changes in patients treated with hydroxychloroquine: a prospective cohort study.

PURPOSE: We aimed to find earlier morphological and functional alterations in the retinas of patients treated with hydroxychloroquine (HCQ). This was a prospective cohort study. METHODS: We examined 33 patients (mean age, 57.14 [SD, 11.02] years) who were affected by various types of rheumatic diseases. The mean treatment period was 124.7 [SD, 99.4] months, and the mean total drug intake was 5.41 [SD, 3.34] g daily at baseline. The control group consisted of 28 subjects with a mean age of 61.25 [SD, 2.16 years]. The set of tests encompassed best-corrected visual acuity (BCVA), a multifocal electroretinogram (mfERG), spectral-domain optical coherence tomography (SD-OCT), fundus auto fluorescence (FAF), the 10-2 automated visual field (VF) test (10-2 VF), and frequency-doubling technology (FDT). RESULTS: The mfERG P1 wave density amplitudes decreased in all the rings, from 31.10 to 28.02 (p = 0.008) in the first ring, and from 18.29 to 16.55 [p < 0.001], from 12.050 to 10.91 [p = 0.002], from 9.53 to 8.69 [p = 0.003], and from 8.25 to 7.48 [p = 0.001] nanovolts/degree2 in rings 2, 3, 4, and 5, respectively. A significant reduction was found also in the N1 wave in the second ring. The SD-OCT retinal thickness measurement revealed significant thinning in five sectors, including the outer and inner nasal sectors, the outer and inner temporal sectors, and the inner superior sector. The 10-2 VF mean deviation paradoxically improved, while minimal FAF alterations in the retinal pigment epithelium were found in eight eyes. CONCLUSIONS: mfERGs and SD-OCT were altered in our patients before significant retinal changes occurred.

High-Frame Rate Vector Flow Imaging of the Carotid Bifurcation in Healthy Adults: Comparison With Color Doppler Imaging.

OBJECTIVES: To evaluate the carotid bifurcation in healthy adults using a commercial system equipped with high-frame rate vector flow imaging (VFI) based on the plane wave and to compare VFI with color Doppler imaging. METHODS: Carotid bifurcation diameters and flow characteristics of 60 vessels in 60 healthy volunteers were evaluated quantitatively and qualitatively to assess complex flow patterns and their extension and duration. RESULTS: Complex flow in the internal carotid artery (ICA) was associated with a statistically significant difference in the ΔICA sinus-to-common carotid artery (CCA) diameter ratio (the relative change in diameter between the CCA and ICA sinus.) Vector flow imaging and color Doppler imaging were in accordance when detecting complex flow in 96.7% of cases; in 3.3% of cases, only VFI identified small recirculation areas of short duration. Vector flow imaging highlighted a larger extension of the complex flow (mean ± SD, 47.7 ± 28.5 mm2 ; median, 45.5 mm2 ) compared with color Doppler imaging (mean, 29.2 ± 19.9 mm2 ; median, 29.5 mm2 ) and better depicted different complex flow patterns; a strong correlation (r = 0.84) was found between the ΔICA sinus-to-CCA diameter ratio and the complex flow extension. Vector flow imaging showed a longer duration of the flow disturbances (mean, 380 ± 218 milliseconds; median, 352.5 milliseconds) compared with color Doppler imaging (mean, 325 ± 206 milliseconds; median, 333 milliseconds), and there was a strong correlation (r = 0.92). CONCLUSIONS: Vector flow imaging is as effective as color Doppler imaging in the detection of flow disturbances, but it is more powerful in the assessment of complex flow patterns.