Association of an α-Globin Gene Cluster Duplication and Heterozygous β-Thalassemia in a Patient with a Severe Thalassemia Syndrome

Abstract

We describe a new case of a β-thalassemia (β-thal) heterozygote with the mutation IVS-II-654 (C>T) presenting with a transfusion-dependent phenotype. Multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (CGH) analyses of the α-globin gene cluster revealed a full duplication of the α-globin genes including the upstream regulatory element. The duplicated allele and the normal allele in trans resulted in a total of six active α-globin genes. The severe clinical phenotype seemed to be related to the considerable excess of the α- and β-globin deficit caused by the presence of the β-thal. α-Globin cluster duplication should be considered in patients heterozygous for β-thal who show a more severe phenotype than β-thal trait.     

Comparison of iohexol and lactulose-mannitol tests as markers of disease activity in patients with inflammatory bowel disease

Increased intestinal permeability has been proposed as one aetiological factor for inflammatory bowel diseases (IBD). We have previously found that intestinal permeability of a water-soluble contrast medium, iohexol, correlates with disease activity. The objective was to compare the iohexol test with the lactulosemannitol ratio, which is a more extensively studied permeability marker, in patients with active IBD. Urinary excretion of iohexol was compared to the lactulose-mannitol ratio in 22 patients with an exacerbation of IBD and in 10 healthy controls. Median intestinal absorption of iohexol was 0.64% (range 0.13 - 3.8%) in the 22 patients and 0.3% (range 0.15 - 0.54%) in the controls (p~0.016), whereas the median lactulose-mannitol ratio was 0.037 (range 0.01 0.260) in patients and 0.03 (range 0.004 - 0.063) in controls (N.S.). Correlation between urinary excretion of iohexol and lactulose-mannitol ratio was positive (R~z0.41, p~0.018). The urinary excretion of iohexol correlated positively with endoscopic disease activity (R~z0.74, p<0.001) and the modified HarveyBradshaw index (R~z0.44, p~0.04). The lactulose-mannitol ratio correlated positively with endoscopic disease activity (R~z0.44, p~0.05), but correlations with clinical index or c-reactive protein were poor. In conclusion, the iohexol test is a superior activity marker compared to the lactulose-mannitol ratio which probably reflects, instead, some pathogenic property of IBD.     

A Review of Sensitivity,Specificity, and Likelihood Ratios: Evaluating the Utility of the Electrocardiogram as a Screening Tool in Hypertrophic Cardiomyopathy

Appropriate interpretation of a screening test's validity poses a challenge to the clinician. The purpose of this review is to revisit the terms sensitivity, specificity, likelihood ratio, and pre‐ and posttest probability and their application to the clinical setting. For illustration, we use a recently published article in the American Journal of Cardiology that investigates the false negative rate of electrocardiograms in athletic preparticipation screening for hypertrophic cardiomyopathy.     

Novel analysis of clinically relevant diagnostic errors in point‐of‐care devices

Summary. Background: To ensure proper clinical decision‐making and avoid preventable harm, the quality of point‐of‐care (POC) device measures is routinely assessed. Traditional analyses may not reveal clinically important diagnostic errors. Objectives: To compare results between a novel analytic framework and traditional analyses. Methods: Patients in four anticoagulation clinics provided two measures of the International Normalized Ratio (INR) at the same visit as part of routine quality assurance: one via a venous sample and one fingerstick. These were assessed with Hemochron POC devices. Traditional, quarterly, quality assurance assessments emphasized correlation analysis. The novel analysis used enhanced graphics and a validated assessment of clinical decision‐making. Results: 1518 paired INRs were analyzed. The correlation between the POC and laboratory assessments ranged between 0.84 and 0.91. Traditional quality assurance showed that the Hemochron devices were acceptable for continued use in each quarterly analysis. Enhanced graphical analysis demonstrated that the Hemochron devices never reported seven common INR values. The Hemochron devices systematically inflated values < 3 and deflated values > 4, biasing results towards the target INR range. Consequently, the Hemochron devices lead to a different clinical decision than the clinical laboratory measure in 31% of cases (458/1466; 95% confidence interval [CI] 29–34). When the reference INR was low, the Hemochron devices would not result in appropriate dose increases in 52% of cases (95% CI 48–56), placing these patients at risk for a significant adverse drug event. Conclusions: Our novel, clinically relevant analysis revealed previously undetected deficiencies in our POC INR devices, and our approach should be adopted by industry, regulators, and institutions.     

Contemporary treatment of keloids: A 10-year institutional experience with medical management,surgical excision,and radiation therapy

IntroductionWe evaluate a single center’s, decade-long experience utilizing 3 approaches to keloid treatment: corticosteroid medical management (MM), surgical excision (SE), and surgical excision + radiation therapy (SE + RT).Study designPatients undergoing keloid treatment were identified (2008–2017). Outcomes were symptomatology/cosmesis for MM, and recurrence and complications for SE and SE + RT. Logistic regression was used to determine factors associated with recurrence and complications.Results284 keloids (95 MM, 94 SE, 95 S E + RT) corresponded to patients with a median age of 39.1 (IQR: 26.1–53), 68.1% Black, and followed-up for 15.4 months (IQR: 5.6–30.7). For MM, 84.6% and 72.5% reported improvement in cosmesis and symptoms, respectively. SE and SE + RT recurrence were 37.2 and 37.9%, respectively. In adjusted analyses, higher radiation doses were associated with decreased recurrence whereas male gender (OR 3.3) and postoperative steroids (OR 9.5) were associated with increased recurrence (p < 0.01). There were more complications in the SE + RT group.ConclusionsMM resulted in at least some improvement. Recurrence rates after SE and SE + RT were similar. Female sex is protective, race does not affect outcomes.     

Association between Diet and Lifestyle Habits and Irritable Bowel Syndrome: A Case-Control Study

Background/AimsRecent papers have highlighted the role of diet and lifestyle habits in irritable bowel syndrome (IBS), but very few population-based studies have evaluated this association in developing countries. The aim of this study was to evaluate the association between diet and lifestyle habits and IBS.MethodsA food frequency and lifestyle habits questionnaire was used to record the diet and lifestyle habits of 78 IBS subjects and 79 healthy subjects. Cross-tabulation analysis and logistic regression were used to reveal any association among lifestyle habits, eating habits, food consumption frequency, and other associated conditions.ResultsThe results from logistic regression analysis indicated that IBS was associated with irregular eating (odds ratio [OR], 3.257), physical inactivity (OR, 3.588), and good quality sleep (OR, 0.132). IBS subjects ate fruit (OR, 3.082) vegetables (OR, 3.778), and legumes (OR, 2.111) and drank tea (OR, 2.221) significantly more frequently than the control subjects. After adjusting for age and sex, irregular eating (OR, 3.963), physical inactivity (OR, 6.297), eating vegetables (OR, 7.904), legumes (OR, 2.674), drinking tea (OR, 3.421) and good quality sleep (OR, 0.054) were independent predictors of IBS.ConclusionsThis study reveals a possible association between diet and lifestyle habits and IBS.     

Speaking rate and its components in dysarthric speakers

We studied speaking rate and its components in a total of 72 patients with a variety of dysarthria: six with the flaccid type; 16 with spastic type; 17 ataxic type; 8 hypokinetic type; 2 hyperkinetic type; 12 mixed type; and 11 with the unilateral upper motor neuron type. We measured speaking rate, articulation rate, and speech/pause ratio. All patients except one showed a slower speaking rate, and all of the dysarthric groups showed significantly slower rates as compared to the control group. The present data indicate that speaking rate is a sensitive measure of abnormal motor speech performance in all types of dysarthria. However, abnormality in articulation rate was not found in flaccid and hypokinetic dysarthria. In addition, the relationship between speaking rate and articulation rate was not significant in these two groups. These results indicate that speaking rate is not necessarily related to articulation rate in some types of dysarthria, and the clinical measurement of speaking rate needs to include both articulation rate and speech/pause ratio. Based on these findings, clinical strategy in the use of the speaking rate control approach was discussed.