Hb Marineo [beta70(E14)Ala-->Val]: a silent hemoglobin variant with a mutation within the heme pocket

We report a new hemoglobin (Hb) variant, Hb Marineo [beta70(E14)Ala --> Val], found in three generations of a family from West Sicily. The mutation is due to a GCC --> GTC substitution at codon 70 of the beta-globin gene. To date, three mutations at codon 70 of the beta-globin gene have been described, presenting with hemolytic anemia. In our case, no anemia or other alteration of hematological indices were found. Cation exchange high performance liquid chromatography (HPLC) showed a peak in the P2 window (VARIANT I), while a peak was detected by VARIANT II HPLC in the P3 window. Reversed phase HPLC analysis showed an abnormal chain amounting to about 40% of the total beta chains.     

Pyrosequencing for Rapid Detection of Extensively Drug-Resistant Mycobacterium tuberculosis in Clinical Isolates and Clinical Specimens

Treating extensively drug-resistant (XDR) tuberculosis (TB) is a serious challenge. Culture-based drug susceptibility testing (DST) may take 4 weeks or longer from specimen collection to the availability of results. We developed a pyrosequencing (PSQ) assay including eight subassays for the rapid identification of Mycobacterium tuberculosis complex (MTBC) and concurrent detection of mutations associated with resistance to drugs defining XDR TB. The entire procedure, from DNA extraction to the availability of results, was accomplished within 6 h. The assay was validated for testing clinical isolates and clinical specimens, which improves the turnaround time for molecular DST and maximizes the benefit of using molecular testing. A total of 130 clinical isolates and 129 clinical specimens were studied. The correlations between the PSQ results and the phenotypic DST results were 94.3% for isoniazid, 98.7% for rifampin, 97.6% for quinolones (ofloxacin, levofloxacin, or moxifloxacin), 99.2% for amikacin, 99.2% for capreomycin, and 96.4% for kanamycin. For testing clinical specimens, the PSQ assay yielded a 98.4% sensitivity for detecting MTBC and a 95.8% sensitivity for generating complete sequencing results from all subassays. The PSQ assay was able to rapidly and accurately detect drug resistance mutations with the sequence information provided, which allows further study of the association of drug resistance or susceptibility with each mutation and the accumulation of such knowledge for future interpretation of results. Thus, reporting of false resistance for mutations known not to confer resistance can be prevented, which is a significant benefit of the assay over existing molecular diagnostic methods endorsed by the World Health Organization.     

Safety and feasibility of iliac endovascular interventions with a radial approach. Results from a multicenter study coordinated by the Italian Radial Force

Background

Percutaneous angioplasty of lower limb disease is commonly performed with a transfemoral access. In the coronary field, a transradial approach has shown to reduce access-site bleeding and adverse clinical events. This route has not yet been well studied for the majority of peripheral interventions, like those involving the iliac arteries. In this study we sought to evaluate the feasibility and safety of this approach for iliac interventions.

Methods

Multicenter study was performed at high-volume centers with experience in transradial percutaneous interventions. Primary endpoint of the study was procedural success; secondary endpoints included in-hospital bleeding, 1-month freedom from adverse events and the rate of radial occlusion. Feasibility of this technique was evaluated by recording procedural and fluoroscopy time and contrast load.

Results

A total of 149 patients from 5 centers were enrolled. The population had a medium risk profile, with 48% of patients having TASC 2 or 3 lesions. Procedural success was achieved in 98.7% of the population, and we did not register in-hospital complications, including both vascular access site and procedural-related complications. An ancillary transfemoral approach was used in 13% of patients. One-month freedom from symptoms was achieved in 97.3% of patients, and the rate of radial occlusion was 2.7%. Major determinants of an unsuccessful procedure were the use of normal 6 or 7-Fr introducer with guiding catheter, TASC D lesion attempt, lesion length > 30 mm and total occlusion.

Conclusions

A transradial approach for iliac disease may be a feasible and safe alternative to the transfemoral route in experienced hands, in the light of significant technical improvements and dedicated devices.     

Analysis of steatosis biomarkers and inflammatory profile after adding on PCSK9 inhibitor treatment in familial hypercholesterolemia subjects with nonalcoholic fatty liver disease: A single lipid center real-world experience

Background and aimsNonalcoholic fatty liver disease (NAFLD) may be crucial in subjects with familial hypercholesterolemia (FH). We aimed to evaluate the effect of the inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9-i) on steatosis biomarkers such as triglyceride-glucose index (TyG) and hepatic steatosis index (HSI) and analyse the role of TG/HDL in this population before and after adding-on PCSK9-i.Methods and resultsIn this observational study, we evaluated 26 genetically confirmed FH patients with NAFLD and an LDL-C off-target despite high-intensity statins plus ezetimibe. All patients added PCSK9-i treatment and obtained biochemical analysis and TyG and HSI evaluation at baseline and after six months of PCSK9-i. No difference of steatosis biomarkers was found after adding-on PCSK9-i therapy. In a secondary analysis, we divided the study population in two groups according to TG/HDL median value: high TG/HDL group (H-TG/HDL) and low TG/HDL group (L-TG/HDL). TyG and HSI were significantly lower in the L-TG/HDL than H-TG/HDL group (for TyG 9.05 ± 0.34 vs 9.51 ± 0.32; for HSI 38.43 ± 1.35 vs 41.35 ± 1.83, p value for both < 0.05). After six months of PCSK9-i therapy, TyG and HSI were significantly reduced in the L-TG/HDL group after PCSK9-i therapy (?7.5% and ?8.4% respectively, p value for both < 0.05) and these biomarkers were lower compared to H-TG/HDL group (for TyG 8.37 ± 0.14 vs 9.19 ± 0.12; for HSI 35.19 ± 1.32 vs 39.48 ± 1.33, p value for both < 0.05).ConclusionIn conclusion, PCSK9-i therapy significantly ameliorate steatosis biomarkers in FH patients with low TG/HDL; our results appear to be consistent with a beneficial role of PCSK9-i on steatosis biomarkers in FH subjects with NAFLD.     

The paraoxonase promoter polymorphism (-107)T>C is not associated with carotid intima-media thickness in Sicilian hypercholesterolemic patients

BACKGROUND AND OBJECTIVES: Increased plasma low-density lipoprotein-cholesterol (LDL-C) levels in hypercholesterolemic subjects are associated with enhanced LDL oxidation that represents an additional risk for atherosclerotic disease. Human serum paraoxonase (PON1), a high-density lipoprotein (HDL) associated enzyme, has been shown to protect LDL from oxidation, thus playing an important role in reducing the risk of atherosclerosis. PON1 gene polymorphisms have been found to be associated with the variations in serum PON1 levels and activities, and with the risk for coronary artery disease (CAD). This study was performed to evaluate the contribution of the PON1 promoter (-107)T>C and the coding region Gln 192 Arg (Q192R) and Leu 55 Met (L55M) polymorphisms to the presence of carotid atherosclerosis in 208 Sicilian subjects with primary hypercholesterolemia. METHODS: Carotid artery intima-media wall thickness (IMT) was measured as an indicator of early atherosclerotic disease. The subjects were classified according to whether they have a normal (1 mm) IMT. Subjects were also investigated for physical and biochemical parameters, including PON1 activity. RESULTS: No significant differences were detected among the PON1 genotypes with respect to age, sex, BMI, plasma lipids, systolic blood pressure in both groups of patients. There were significant differences between PON1 genotypes with respect to PON1 activity. The 192QQ, 55MM and (-107)TT genotypes showed lower PON1 activity compared to the RR, LL and CC genotypes. The PON1 (-107)T>C genotype distribution in both IMT groups showed no significant differences in percentage of TT, CT and CC genotypes. Similar results were obtained analyzing the Q192R and L55M genotype frequencies. Stepwise forward logistic regression analysis confirmed the lack of association between PON1 genotypes and carotid abnormalities. CONCLUSIONS: In conclusion, our data provided no evidence of a significant association between either PON1 promoter (-107)T>C or coding region, Q192R and L55M, polymorphisms and early carotid atherosclerosis in Sicilian hypercholesterolemic subjects.     

Disability, Driving Licence and Driving Technology: the Italian Experience

Through norms,concessions,assessment and training,the article shows the importance of the rehabilitation approach to identify the ways in which to help the disabled person achieve his driving licence and,therefore drive a vehicle.It shows the number of variants that exist for each system allowing the adaptation of various automobile functions to the needs of disabled people and in this way we can understand how even seriously disabled people with very complex situations can drive when the correct adaptations are identified.     

Serum chromogranin-A in hepatocellular carcinoma： Diagnostic utility and limits

AIM: The utility of serum alpha-fetoprotein (α-FP) for the detection of hepatocellular carcinoma (HCC) is questionable. High serum levels of chromogranin-A (CgA) have recently been reported in HCC. Impaired hepatic, renal, and heart functions influence circulating CgA. The aim of this study was to assess sensitivity and specificity of serum CgA as a marker of HCC in patients with liver cirrhosis (LC). METHODS: Serum CgA levels were measured by RIA in 339 patients of which 54 HCC, 132 LC, 45 chronic hepatitis (CH), 27 chronic heart failure (CHF), 36 chronic renal failure (CRF), 45 chronic inflammatory bowel disease (IBD) as disease controls and in 75 healthy controls. Patients with liver disease or IBD and concomitant renal and/or heart failure were excluded. Pearson correlation, non-parametric combination test and confidence interval analysis were used for statistical analysis. RESULTS: Serum CgA above normal values (100 ng/mL) were found in 83% of HCC patients, in 48% of LC patients, in 20% of CH patients, in 33% of IBD patients, in 92% of CRF patients, in 100% of CHF patients, and in none of the healthy controls. The mean CgA values in HCC (769±1046), in LC (249±369), in CH (87±94), in CRF (1390±1401), in CHF (577±539), in IBD (146±287) were significantly higher than those in healthy controls (48±18). HCC patients had higher CgA values (P<0.01) than LC, CH, and IBD patients but did not differ from those with CRF or CHF. The 95% CI for the mean (250-1289 ng/mL) in HCC patients was selected as a CgA range and the lower value of such range was assumed as cut-off. Sensitivity and specificity of CgA, calculated in relation to the cut-off in patients with cirrhosis and HCC, were respectively 61% (CI 48-73%) and 82% (CI 75-88%). Serum a-FP values were >200 ng/mL in 21% of the HCC patients and in none of the LC patients. No significant correlation was found between a-FP and CgA in patients with HCC and in patients with cirrhosis. CONCLUSION: When HCC is suspected and a-FP is normal or <200 ng/mL, CgA serum values represent a complementary diagnostic tool, unless kidney or heart failure is present.     

Non Invasive Assessment of Lung Disease in Ataxia Telangiectasia by High-Field Magnetic Resonance Imaging

Purpose

A sensitive imaging technique that assesses ataxia telangiectasia (AT) lung disease without ionizing radiation is highly desirable. We designed a study to evaluate lung changes using magnetic resonance imaging (MRI), and to investigate the relationships among severity and extent of pulmonary abnormalities and clinical, microbiological and functional data in children and young adults with AT.

Methods

Fifteen AT patients (age, 11.3 years; range, 6–31) underwent 3.0-T MRI, spirometry, and deep throat or sputum culture. Images were scored using a modified Helbich score.

Results

Although only 8 patients (53 %) had recurrent/chronic respiratory symptoms, MRI identified lung abnormalities in all. Bronchiectasis, peribronchial thickening, mucous plugging, and collapse/consolidation were present in 60 %, 87 %, 67 %, and 13 % of cases, respectively, with no difference between subjects with or without respiratory symptoms. No difference in changes of specific scores was found between the two groups, but the total MRI score was higher in patients with respiratory symptoms (6.5 versus 5, respectively; p?=?0.02). Total or specific MRI scores were not associated with patients’ age. Of all scores, only mucous plugging subscore appeared significantly related to FEV₁ (r?=?0.7, p?=?0.04) and FEF_25–75% (r?=?0.9, p?=?0.001). MRI scores from patients with positive (n?=?5) or negative (n?=?10) sputum culture were not significantly different.

Conclusions

MRI is valuable in the assessment of extent and severity of pulmonary changes in children and adults with AT. It represents an helpful tool for the longitudinal evaluation of patients and may be also used as an outcome surrogate to track the effects of medications.     

Skeletal and Dental Effectiveness of Treatment of Class II Malocclusion With Headgear: A Systematic Review and Meta-analysis

Objective

To evaluate the skeletal and dental effects of headgear treatment by systematically reviewing the best available scientific evidence.