Conventional Clinical Criteria Research Articles

Diagnostic accuracy of major stroke types in Chinese adults: A clinical adjudication study involving 40,000 stroke cases

SummaryBackgroundWidespread use of brain imaging in suspected stroke cases in Chinese adults has prompted the need for clinical adjudication studies of stroke types. We conducted a clinical adjudication study to assess the reporting and diagnostic accuracy of major stroke types.MethodsThe prospective China Kadoorie Biobank recruited >512,000 adults (mean age 52 years, 59% women) from 10 urban and rural areas in China during 2004–2008, and recorded 45,859 first-ever incident stroke cases during an 11-year follow-up. Medical records were retrieved in ∼85%, and clinical details were recorded using a handheld computer for specialist physician adjudicators who applied conventional WHO clinical criteria for diagnosis of stroke. The positive predictive value (PPV) for reported and adjudicated stroke cases was examined for major stroke types (ischaemic stroke [IS], intracerebral haemorrhage [ICH], subarachnoid haemorrhage [SAH]), calendar year, area, and hospital type.FindingsOf 38,823 cases with retrieved medical records, the PPV for reported strokes was 91%. Among 29,952 adjudicated cases, the PPV for adjudicated cases was 81%, with higher PPV for ICH (n = 3391; 98%) and SAH (364; 98%) than for IS (20,473; 79%). Of 5504 cases with a verified IS diagnosis that was refuted on adjudication, 3763 (68%) had silent lacunar infarcts (LACI). The proportion of cases with silent LACI increased from 7.1% in 2004–2008 to 18.2% in 2016–2017. If cases with silent LACI were classified as IS, as advocated by new International Classification of Diseases (ICD-11) diagnostic criteria for stroke involving imaging and clinical rather than clinical criteria alone, the PPV increased to 93%.InterpretationWhile the overall reporting and diagnostic accuracy of stroke types in Chinese adults is high, the recent implementation of new diagnostic criteria for IS has important implications for contemporary clinical practice and research on stroke in Chinese populations.FundingKadoorie Charitable Foundation, Hong Kong, China, UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), Chinese National Natural Science Foundation (91843302), and the National Key Research and Development Program of China (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904). British Heart Foundation, and UK Medical Research Council, and Cancer Research UK.

Salivary diagnostic biomarker for periodontal disease - A review

Periodontitis is chronic inflammation of the periodontium caused by persistent bacterial infection affecting the connective tissue attachment and supporting bone around the teeth. As the ability to reconstruct the periodontium is limited after alveolar bone loss, early diagnosis and intervention should be paramount goals of periodontal treatment preventing future disease’s progression. Saliva is a physiologic fluid that contains complex mixture of substances as well as inflammatory biomarkers associated with periodontitis. Conventional clinical criteria are often insufficient for determining sites of active disease, for monitoring the response to therapy, or for measuring the degree of susceptibility to future disease progression. Therefore, the use of saliva has provided a substantial addition to the diagnostic armamentarium as an investigative tool for disease processes. With the current technological advances, together with point-of-care detection systems, salivary analysis will be valued much more highly in the near future. Even though saliva is easy to manipulate with low-cost storage, careful attention must be directed to limit variation in specimen integrity. This review focuses on the biomarkers in saliva that appears to be promising in the future for periodontal diagnosis, as well as some contemporary diagnostic tests available.

Enhancing the utility of antroduodenal manometry in pediatric intestinal pseudo-obstruction.

Antroduodenal manometry (ADM) and histopathology are currently employed to aid the diagnosis of pediatric intestinal pseudo-obstruction (PIPO). Limited data are available on the reliability of ADM analysis and its correlation with histopathology. We aimed to develop a protocol for enhanced analysis of ADM contractile patterns, including a scoring system, and explore whether this provided better correlation with histopathology. Children referred with suspected PIPO between April 2012-December 2019 who underwent both ADM and full-thickness biopsies were included. ADM tracings were analyzed using both standard (conventional ADM) and novel (enhanced ADM) motility parameters. A novel ADM score (GLASS score) was generated based on the enhanced ADM analysis. Conventional and enhanced ADM analyses were then correlated with histopathology. Forty patients were included. Using conventional clinical criteria, 29 of these were diagnosed with PIPO and the other 11 with non-PIPO diagnoses. Twenty-three of the PIPO patients had abnormal histopathology: 6 myopathy, 4 neuropathy, 3 neuro-myopathy, and 10 non-specific changes. No agreement in diagnosis was found between conventional ADM analysis and histopathology (ϰ=0.068; p=0.197), whereas the latter significantly correlated with enhanced ADM analysis (ϰ=0.191; p=0.003). The enhanced ADM score was significantly higher in PIPO versus non-PIPO (16.0 vs. 8.0; p<0.001). As opposed to conventional analysis protocols, the newly developed enhanced ADM analysis and associated score is not only able to discriminate between PIPO and non-PIPO patients, but also between distinct histopathological pathologies. Further studies are required to assess the utility of enhanced ADM analysis in larger populations.

Mild parkinsonian signs: the interface between aging and Parkinson’s disease

Mild Parkinsonian Signs (MPS) describe a spectrum that exists between the expected motor decline of normal aging and a more serious motor deterioration resulting from Parkinson’s disease (PD) and neurodegeneration. Although MPS are a feature of the prodromal stage of PD, their formal definition is unclear and still relies somewhat on conventional clinical criteria for PD. This review will summarise the early motor features of PD and methods of assessment, from conventional clinical scales to advances in quantitative measures. Finally, the boundaries of motor decline as part of normal aging and pathological neurodegeneration will be discussed.

A Machine Learning Approach for the Differential Diagnosis of Alzheimer and Vascular Dementia Fed by MRI Selected Features.

Among dementia-like diseases, Alzheimer disease (AD) and vascular dementia (VD) are two of the most frequent. AD and VD may share multiple neurological symptoms that may lead to controversial diagnoses when using conventional clinical and MRI criteria. Therefore, other approaches are needed to overcome this issue. Machine learning (ML) combined with magnetic resonance imaging (MRI) has been shown to improve the diagnostic accuracy of several neurodegenerative diseases, including dementia. To this end, in this study, we investigated, first, whether different kinds of ML algorithms, combined with advanced MRI features, could be supportive in classifying VD from AD and, second, whether the developed approach might help in predicting the prevalent disease in subjects with an unclear profile of AD or VD. Three ML categories of algorithms were tested: artificial neural network (ANN), support vector machine (SVM), and adaptive neuro-fuzzy inference system (ANFIS). Multiple regional metrics from resting-state fMRI (rs-fMRI) and diffusion tensor imaging (DTI) of 60 subjects (33 AD, 27 VD) were used as input features to train the algorithms and find the best feature pattern to classify VD from AD. We then used the identified VD–AD discriminant feature pattern as input for the most performant ML algorithm to predict the disease prevalence in 15 dementia patients with a “mixed VD–AD dementia” (MXD) clinical profile using their baseline MRI data. ML predictions were compared with the diagnosis evidence from a 3-year clinical follow-up. ANFIS emerged as the most efficient algorithm in discriminating AD from VD, reaching a classification accuracy greater than 84% using a small feature pattern. Moreover, ANFIS showed improved classification accuracy when trained with a multimodal input feature data set (e.g., DTI + rs-fMRI metrics) rather than a unimodal feature data set. When applying the best discriminant pattern to the MXD group, ANFIS achieved a correct prediction rate of 77.33%. Overall, results showed that our approach has a high discriminant power to classify AD and VD profiles. Moreover, the same approach also showed potential in predicting earlier the prevalent underlying disease in dementia patients whose clinical profile is uncertain between AD and VD, therefore suggesting its usefulness in supporting physicians' diagnostic evaluations.

Clinical chorioamnionitis criteria are not sufficient for predicting intra-amniotic infection

Aim To evaluate the diagnostic performance of three conventional clinical chorioamnionitis criteria; including Gibbs, Lencki, and suspected triple I; for the prediction of intra-amniotic infection. Methods A retrospective cohort study was conducted using data from three perinatal centers from 2014 to 2018. Patients with preterm labor or premature prelabor rupture of membranes between 22 and 33 weeks of gestation and those who underwent transabdominal amniocentesis to detect intra-amniotic infection were selected. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms, including genital mycoplasmas, plus low glucose level or leukocytosis in amniotic fluid. Sensitivity, specificity, and positive and negative likelihood ratios were calculated to determine the diagnostic performance of each criterion in predicting intra-amniotic infection. Results Of 99 pregnant women who met the study inclusion criteria, 13 (13.1%) had intra-amniotic infection confirmed by amniocentesis and 86 (86.9%) had no intra-amniotic infection. Maternal characteristics were not significantly different between groups, except for the higher incidence of preterm, prelabor rupture of membranes in pregnant women with intra-amniotic infection (53.8 versus 14%, p < .01). The incidences of clinical chorioamnionitis in the non-IAI and IAI groups were 1 of 86 (1.2%), 1 of 86 (1.2%), 0 of 86 (0%) and 2 of 13 (15.4%), 2 of 13 (15.4%), 2 of 13 (15.4%) according to Gibbs, Lenki, and suspected triple I criteria, respectively. The specificity of the three criteria ranged from 98.8 to 100%; however, the sensitivity was low (15.4%). The positive likelihood ratio was significant for three criteria from 13.2 (95% confidence interval [CI], 1.29–135) to infinite. However, the negative likelihood ratio was not low enough and not significant for the three criteria (0.85 [95% CI, 0.67–1.07] to 0.86 [95% CI, 0.68–1.08]). Conclusion The conventional clinical chorioamnionitis criteria are not sensitive for the prediction of intra-amniotic infection in pregnant women with preterm labor and/or preterm prelabor rupture of membranes.

Serum omentin-1 as a predictor of activity in Crohn\u2019s disease

Background and aimCrohn’s disease (CD) is associated with alterations in fat mass and fat distributions, with changed productions of adipokines, including omentin-1. Omentin-1 may be involved in the pathogenesis of inflammatory bowel disease. The aim was to determine the serum and mucosal omentin-1 levels in CD patients and to evaluate its potential as a marker for disease activity.Patients and methodsSeventy-five adult consecutive outpatients, with a confirmed diagnosis of CD, and 45 age-matched, sex-matched, and BMI-matched healthy volunteers were enrolled in this study after written conscious consent and approval by the Institutional Review Board of Mansoura University. CD was diagnosed by conventional clinical, radiological, endoscopic, and histopathological criteria. Serum levels and mucosal mRNA expression of omentin-1 were measured by commercially available kits according to the manufacturer’s protocols.ResultsSerum omentin-1 and its mucosal gene expression were significantly lower in patients with CD (53.3±12.8) than in healthy controls (72.7±16.8, P<0.0001). Moreover, serum omentin-1 levels were significantly lower in patients with active CD (36.2±9.6) than in patients in remission (69.2±14.4, P≤0.0001). No significant differences were demonstrated between patients in remission and healthy controls (P>0.05). In CD patients, the decrease in serum omentin-1 was associated with a significantly higher BMI, C-reactive protein, erythrocyte sedimentation rate, Crohn’s disease activity index, simplified endoscopic score for CD and inflammation scores (P≤0.05). Moreover, omentin-1 was much superior to C-reactive protein in predicting CD activity and severity.ConclusionSerum and mucosal expression of omentin-1 might be a reliable surrogate noninvasive marker of disease activity in CD with significantly high sensitivity, specificity, and diagnostic accuracy.

Maturity Onset Diabetes of the Young is Not Necessarily Associated with Autosomal Inheritance: Case Description of a De Novo HFN1A Mutation.

Maturity onset diabetes of the young (MODY) accounts for up to 4% of all cases of diabetes in pediatric patients. MODY is usually characterized by autosomal dominant inheritance, impaired insulin secretion, and an average age at diagnosis of 18–26 years. Mutations in the hepatocyte nuclear factor 1-alpha (HNF1A), glucokinase, hepatocyte nuclear factor 4-alpha, and hepatocyte nuclear factor 1-beta genes are the mutations most frequently observed in cases of MODY. We herein report a case of HNF1A-MODY characterized by an early onset of diabetes. Genetic investigations revealed a de novo heterozygous substitution, N237D (HNF1A c.709A>G), in exon 3 of the HNF1A gene. Our case supports the hypothesis that de novo mutations are more frequent than expected. This recent evidence may suggest that conventional clinical diagnostic criteria for MODY should be revised and personalized according to the individual patient.Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-019-0633-3) contains supplementary material, which is available to authorized users.

Obestatin/Ghrelin Ratio as a New Activity Index in Ulcerative Colitis

Background and Aim: Ulcerative colitis (UC) is an immune-mediated systemic inflammatory process that destroys the intestinal mucosa. Ghrelin, an appetite-regulatory hormone, has anti-inflammatory effects including a decrease in circulating cytokines. Some reports demonstrated a strong relationship between the serum ghrelin level and the severity of mucosal inflammation in the gastrointestinal tract. The aim is to investigate serum levels and colonic mucosal mRNA expression of ghrelin, obestatin, and obestatin/ghrelin ratio in patients with UC and to determine their potential as markers for UC disease activity. Patients and Methods: seventy-five outpatients with UC and 45 age- and sex-matched healthy volunteers were enrolled in this study after written conscious consent and approval by the Institutional Review Board of Mansoura University. UC was diagnosed by conventional clinical, radiological, endoscopic, and histopathological criteria. Serum ghrelin, obestatin levels, and their mucosal mRNA expression were measured by ELISA kits and a real-time quantitative reverse transcriptase polymerase chain reaction according to the manufacturer’s protocols. Results: Serum levels and mucosal mRNA expression of ghrelin were significantly higher in patients with active UC than patients in remission p˂0.0001). Obestatin/ghrelin ratio was significantly lower in patients with active UC (0.26±0.08) than those in remission (0.523±0.16; p˂0.0001). Obestatin/ghrelin ratio was negatively and significantly correlated with inflammation and endoscopic scores, colitis activity index, serum ghrelin level, and its mucosal mRNA expression (p˂0.05). Conclusion: obestatin/ghrelin ratio might be a reliable surrogate non-invasive marker of disease activity in UC with significantly high sensitivity, specificity, predictive values, and diagnostic accuracy.

Quantitative assessment of pericardial delayed hyperenhancement helps identify patients with ongoing recurrences of pericarditis

ObjectivesRecurrences of pericarditis (RP) are often difficult to diagnose due to lack of clinical signs and symptoms during subsequent episodes. We aimed to investigate the value of quantitative assessment of...

Examining differences in neuropsychiatric symptom factor trajectories in empirically derived mild cognitive impairment subtypes

The aim of this study was to examine neuropsychiatric symptom (NPS) factor severity progression over time in empirically derived (ED) mild cognitive impairment (MCI) subtypes. Participants in the Alzheimer's Disease Neuroimaging Initiative study diagnosed with MCI by Alzheimer's Disease Neuroimaging Initiative protocol using conventional clinical (CC) criteria (n=788) were reclassified using cluster analysis as amnestic, dysnomic, dysexecutive MCI, or cluster-derived normal (CC-Normal) using empirical criteria. Cognitively normal (CN) participants (n=207) were also identified. The Neuropsychiatric Inventory-Questionnaire (NPI-Q) was administered from baseline through 48-month follow-up. Exploratory factor analysis was completed to determine the NPI-Q factor structure at 6-month follow-up. Multilevel modeling was used to determine NPI-Q symptom severity factor and apathy symptom progression over time by cognitive subtype. The exploratory factor analysis revealed that the NPI-Q consisted of 2 factors: hyperactivity/agitation and mood symptoms. Using clinical and empirical criteria, all MCI groups were identified as having more severe hyperactivity/agitation symptoms than CN participants. However, only the amnestic MCI group identified using empirical criteria showed an increase in symptom severity over time relative to CN participants. Mood factor and apathy symptoms were found to be more severe in dysexecutive and amnestic groups in both models. Similarly, both models identified a significant worsening of mood and apathy symptoms over time for dysexecutive and amnestic groups relative to CN participants. This study provides further support that empirical criteria aid in examining the progression of clinical characteristics associated with MCI. Further, it helps to identify which MCI subtypes may be at higher risk for NPS progression.

Incomplete Distal Renal Tubular Acidosis and Kidney Stones.

Renal tubular acidosis (RTA) is comprised of a diverse group of congenital or acquired diseases with the common denominator of defective renal acid excretion with protean manifestation, but in adults, recurrent kidney stones and nephrocalcinosis are mainly found in presentation. Calcium phosphate (CaP) stones and nephrocalcinosis are frequently encountered in distal hypokalemic RTA type I. Alkaline urinary pH, hypocitraturia, and, less frequently, hypercalciuria are the tripartite lithogenic factors in distal RTA (dRTA) predisposing to CaP stone formation; the latter 2 are also commonly encountered in other causes of urolithiasis. Although the full blown syndrome is easily diagnosed by conventional clinical criteria, an attenuated forme fruste called incomplete dRTA typically evades clinical testing and is only uncovered by provocative acid-loading challenges. Stone formers (SFs) that cannot acidify urine of pH<5.3 during acid loading are considered to have incomplete dRTA. However, urinary acidification capacity is not a dichotomous but rather a continuous trait, so incomplete dRTA is not a distinct entity but may be one end of a spectrum. Recent findings suggest that incomplete dRTA can be attributed to heterozygous carriers of hypofunctional V-ATPase. The value of incomplete dRTA diagnosis by provocative testing and genotyping candidate genes is a valuable research tool, but it remains unclear at the moment whether they alter clinical practice and needs further clarification. No randomized controlled trials have been performed in SFs with dRTA or CaP stones, and until such data are available, treatment of CaP stones are centered on reversing the biochemical abnormalities encountered in the metabolic workup. SFs with type I dRTA should receive alkali therapy, preferentially in the form of K-citrate delivered judiciously to treat the chronic acid retention that drives both stone formation and bone disease.

Withdrawal of immunosuppressant or biologic therapy for patients with quiescent Crohn's disease.

Withdrawal of immunosuppressant or biologic therapy for patients with quiescent Crohn's disease.

IMPROVEMENT OF POSSIBILITIES OF TREATING PNEUMONIAS IN PATIENTS ON THE BACKGROUND OF ACUTE MYELOBLAST LEUCOSIS IN THE ASPECT OF IMMUNORESISTANCE MECHANISMS

Aim: to analyze the influence of the immunomodeling preparation glutamyl-cysteinyl-glycine disodium (glutoxim) on indices of cellular and humoral immunity in patients with pneumonias on the background of acute myeloblast leucosis to form new approaches to the improvement of treating pneumonias in patients with immunity disorders. Materials and methods. The research group - 37 patients with pneumonia on the background of acute myeloblast leucosis, who underwent the program treatment on the base of the hematological center “MI city multi-profile clinical hospital №4” Dnipro city, 2014-2015. The age of patients from 23 to 45 years old; 10 women and 27 men. The diagnosis of leucosis and pneumonia forms was verified corresponding to modern conventional clinical and morphological criteria. Patients from the main research group (n = 18) were prescribed with glutamyl-cysteinyl-glycine disodium by the scheme 2 ml of 3 % (60 mg) i/v № 10 in mornings, summary dose - 300 mg. Indications of immunograms were studied: Т-lymphocytes, В-lymphocytes and their subpopulation composition (CD3 +, CD4 +, CD8 +, CD19 +, CD19-, CD16 +, CD56+) using the flowing laser cytofluorimetry. Immunoglobulin levels were determined by the method of immunoturbometry. Indications of immunograms were assessed in the treatment dynamics. The statistical processing – using packages of applied programs «Excel» and «Statistic 10». Results. According to the analysis of indices of the cellular and humoral immunity of patients with pneumonia on the background of acute myeloblast leucosis, the process of glutamyl-cysteinyl-glycine disodium use proved the statistically reliable activation of phagocytosis and anti-infectious defense indices. The dynamics of humoral immunity indices also proved the positive influence on the state of the immune reactivity of the organism with the reliable increase of ІgА and Іg М, responsible for neutralization of infectious agents and bacterial toxins. Conclusions: The use of the ummunomodeling preparation glutamyl-cysteinyl-glycine disodium (glutoxim) in patients with pneumonia on the background of acute myeloblast leucosis results in the improvement of indices of cellular and humoral immunity and phagocytosis activation. The research results prove the possibility of optimization of approaches to treating pneumonias in patients with severe immunity disorders by using immunomedeling therapy by glutamyl-cysteinyl-glycine disodium (glutoxim). KEYWORDS

Histologic scoring indices for evaluation of disease activity in Crohn's disease.

Histologic assessment of mucosal disease activity has been increasingly used in clinical trials of treatment for Crohn's disease. However, the operating properties of the currently existing histologic scoring indices remain unclear. A systematic review was undertaken to evaluate the development and operating characteristics of available histologic disease activity indices in Crohn's disease. Electronic searches of MEDLINE, EMBASE, PubMed, and the Cochrane Library (CENTRAL) databases from inception to 20 July 2016 were supplemented by manual reviews of bibliographies and abstracts submitted to major gastroenterology meetings (Digestive Disease Week, United European Gastroenterology Week, European Crohn's and Colitis Organisation). Any study design (e.g. randomised controlled trial, cohort study, case series) that evaluated a histologic disease activity index in patients with Crohn's disease was considered for inclusion. Study participants included adult patients (> 16 years), diagnosed with Crohn's disease using conventional clinical, radiographic or endoscopic criteria. Two authors independently reviewed the titles and abstracts of the studies identified from the literature search. The full text of potentially relevant citations were reviewed for inclusion and the study investigators were contacted as needed for clarification. Any disagreements regarding study eligibility were resolved by discussion and consensus with a third author.Two authors independently extracted and recorded data using a standard form. The following data were recorded from each eligible study: number of patients enrolled; number of patients per treatment arm; patient characteristics: age and gender distribution; description of histologic disease activity index utilized; and outcomes such as content validity, construct validity, criterion validity, responsiveness, intra-rater reliability, inter-rater reliability, and feasibility. Sixteen reports of 14 studies describing 14 different numerical histological indices fulfilled the inclusion criteria.Inter-rater reliability was assessed in one study. For the Naini and Cortina Score, estimates of correlation were 'almost perfect', ranging from r = 0.94 to 0.96. The methodological quality of this study with respect to reliability was 'good'.With respect to validity, correlation estimates between various histological scoring systems and Crohn's disease activity as measured by objective markers of inflammation (including C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin and fecal lactoferrin); endoscopic disease activity scores; clinical disease activity scores; and quality of life questionnaires were reported. Comparisons between histologic scoring indices and endoscopic scoring indices ranged from no correlation to 'substantial' (r = 0.779). The methodological quality of the studies that explored validity ranged form 'poor' to 'good'.Responsiveness data were available in seven studies. After subjects were administered a treatment of known efficacy, statistically significant change in the index score was demonstrated in five studies with respect to six indices. Two studies failed to indicate whether there was statistically significant change in the index score post-treatment. With regard to methodological quality, six of the studies were rated as 'poor' and one of the studies was rated as 'fair'.Feasibility was assessed by one study. The Naini and Cortina Score was shown to be simple to use and feasible for every given case. Currently there is no fully validated histological scoring index for evaluation of Crohn's disease activity. Development of a validated histological scoring index for Crohn's disease is a clinical and research priority.

Use of bio-informatics assessment schema (BIAS) to improve diagnosis and prognosis of myocardial perfusion data: results from the NHLBI-sponsored women's ischemia syndrome evaluation (WISE).

We introduce an algorithmic approach to optimize diagnostic and prognostic value of gated cardiac single photon emission computed tomography (SPECT) and magnetic resonance (MR) myocardial perfusion imaging (MPI) modalities in women with suspected myocardial ischemia. The novel approach: bio-informatics assessment schema (BIAS) forms a mathematical model utilizing MPI data and cardiac metrics generated by one modality to predict the MPI status of another modality. The model identifies cardiac features that either enhance or mask the image-based evidence of ischemia. For each patient, the BIAS model value is used to set an appropriate threshold for the detection of ischemia. Women (n=130), with symptoms and signs of suspected myocardial ischemia, underwent MPI assessment for regional perfusion defects using two different modalities: gated SPECT and MR. To determine perfusion status, MR data were evaluated qualitatively (MRIQL) and semi-quantitatively (MRISQ) while SPECT data were evaluated using conventional clinical criteria. Evaluators were masked to results of the alternate modality. These MPI status readings were designated "original". Two regression models designated "BIAS" models were generated to model MPI status obtained with one modality (e.g., MRI) compared with a second modality (e.g., SPECT), but importantly, the BIAS models did not include the primary Original MPI reading of the predicting modality. Instead, the BIAS models included auxiliary measurements like left ventricular chamber volumes and myocardial wall thickness. For each modality, the BIAS model was used to set a progressive threshold for interpretation of MPI status. Women were then followed for 38±14 months for the development of a first major adverse cardiovascular event [MACE: CV death, nonfatal myocardial infarction (MI) or hospitalization for heart failure]. Original and BIAS-augmented perfusion status were compared in their ability to detect coronary artery disease (CAD) and for prediction of MACE. Adverse events occurred in 14 (11%) women and CAD was present in 13 (10%). There was a positive correlation of maximum coronary artery stenosis and BIAS score for MRI and SPECT (P<0.001). Receiver operator characteristic (ROC) analysis was conducted and showed an increase in the area under the curve of the BIAS-augmented MPI interpretation of MACE vs. the original for MRISQ (0.78 vs. 0.54), MRIQL (0.78 vs. 0.64), SPECT (0.82 vs. 0.63) and the average of the three readings (0.80±0.02 vs. 0.60±0.05, P<0.05). Increasing values of the BIAS score generated by both MRI and SPECT corresponded to the increasing prevalence of CAD and MACE. The BIAS-augmented detection of ischemia better predicted MACE compared with the Original reading for the MPI data for both MRI and SPECT.

Clinical features of familial hypercholesterolemia in Korea: Predictors of pathogenic mutations and coronary artery disease – A study supported by the Korean Society of Lipidology and Atherosclerosis

BackgroundProper screening and diagnosis of familial hypercholesterolemia (FH) is of critical importance for cardiovascular prevention. However, the clinical diagnosis of FH remains difficult partly because its phenotype can vary between different ethnicities. The aim of this study was to determine the clinical features and the best diagnostic approach in Korean FH patients. The predictors of putative pathogenic mutations and coronary artery disease (CAD) were also identified. Methods and ResultsNinety-seven patients with low-density lipoprotein-cholesterol >190 mg/dL and xanthoma or FH-compatible family history were included. Putative pathogenic mutations in LDLR, APOB, or PCSK9 genes were identified in 32% of the enrolled patients. The subjects were classified according to four sets of clinical criteria (Simon Broome, Dutch, MEDPED, Japanese). The mutation rates in definite type FH of Simon Broome or Dutch criteria were 35%–37% and lower in our patients than in those of other countries. The mutation detection rate by MEDPED criteria was 67%–75% and higher than those based on other criteria. The best low-density lipoprotein-cholesterol (LDL-C) threshold for predicting mutations was 225 mg/dL. LDL-C was found to be the only independent predictor of mutation carriers, while hypertension and low high-density lipoprotein-cholesterol were predictive of CAD. ConclusionsThe conventional clinical criteria showed limited mutation detection power and low specificities in Korean FH patients, in whom the best LDL-C threshold for putative mutation was 225 mg/dL. Traditional cardiovascular risk factors were also significantly associated with CAD risk in this population.

DIAGNOSTICS THE SEVERITY OF PELVIC INFLAMMATORY DISEASES BY THE MARKERS OF HEMOSTASIS AND INFLAMMATION

Now pelvic inflammatory disease (PID) is one of the most urgent problems in modern gynecology. Pelvic inflammatory diseases (PID) have a leading position not only in the structure of gynecological morbidity, but also are the most frequent cause of damage to the reproductive health of women, thereby creating health, social and economic problems. In modern conditions, inflammatory diseases of the genitals are characterized by several features: multifocal inflammatory lesion; the lack of specific clinical symptoms; transformation of clinical finding toward obligated and atypical forms which causes significant difficulties in diagnosis. Latent, obligated, indolent, asymptomatic, subclinical, and in English literature - "dumb, atypical or unrecognized" inflammation is 60% of all PID (V.I. Kulakov, 2005, A.P. Nikonov, 2006, Bezbakh I.V., 2006, Lineva O.I., 2006, Kovalev, L.A., 2010, Sweet R.L., 2009 Serov V.N., 2011). In 2012 European Guideline IUSTI / WHO on keeping patients with pelvic inflammatory disease was published. Unfortunately, conventional methods for routine laboratory studies often have a diagnostic value only in patients with severe clinical manifestations of the disease. Thus, to assess the severity of the inflammatory process only by conventional clinical criteria are currently not possible. Search of diagnostic criteria based on objective indicators, is highly relevant [1], [3].

The reliability of using postero-anterior cephalometry and cone-beam CT to determine transverse dimensions in clinical practice

Abstract Aim: This study primarily aimed to assess the accuracy of classically-advocated reference points for the measurement of transverse jaw-base and dental relationships using conventional Postero-Anterior Cephalometry (PAC) and Cone-Beam Computed Tomography (CBCT). Method: PAC and CBCT images were collected from 31 randomly selected orthodontic patients (12 males, 19 females), all of whom had a full permanent dentition. The transverse widths of the maxilla, mandible and the dentition were measured using reference points on both image modalities. Confidence intervals, intra-class coefficients and Bland Altman plots were used to assess the measurement differences derived from the two acquirement methods. Results: Measurements on PAC and CBCT images demonstrated statistically significant differences in the majority of the assessed variables. The interjugal (J-J) width was one of only two variables which did not demonstrate a statistically significant difference on image comparison. The mean differences of the antegonial width (Ag-Ag) (-4.44mm, 95% CI -5.38 to -3.51) represented the greatest difference between the imaging techniques. The application of these points to a transverse skeletal analysis (J-J/Ag-Ag ratio) revealed that five of the 31 subjects (16%) recorded ‘false positive’ readings according to the derived data. Conclusion: It is recommended that clinicians are cautious when interpreting and making decisions related to transverse dimensions derived from a PAC. The PAC has a higher tendency to falsely identify individuals who require maxillary expansion procedures based on conventional clinical criteria. The errors primarily associated with identifying structures which represent the width of the mandible are significant in both PAC and CBCT techniques and require further investigation. It is postulated that the confounding effects of overlying soft tissues have a significant impact on a clinician’s ability to identify relevant landmarks.

Improved diagnosis and prognosis using Decisions Informed by Combining Entities (DICE): results from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE).

To introduce an algorithmic approach to improve the interpretation of myocardial perfusion images in women with suspected myocardial ischemia. Gated single photon emission computed tomography (SPECT) and magnetic resonance (MR) myocardial perfusion imaging (MPI) approaches have relatively poor diagnostic and prognostic value in women with suspected myocardial ischemia. Here we introduce an approach: Decisions Informed by Combining Entities (DICE) that forms a mathematical model utilizing MPI and cardiac dimensions generated by one modality to predict the perfusion status of another modality. The effect of the model is to systematically incorporate cardiac metrics that influence the interpretation of perfusion images, leading to greater consistency in designation of myocardial perfusion status between studies. Women (n=213), with suspected myocardial ischemia, underwent MPI assessment for regional perfusion defects using two modalities: gated SPECT (n=207) and MR imaging (n=203). To determine perfusion status, MR data were evaluated qualitatively and semi-quantitatively while SPECT data were evaluated using conventional clinical criteria. These perfusion status readings were designated "Original". Four regression models were generated to model perfusion status obtained with one modality [e.g., semi-quantitative magnetic resonance imaging (MRI)] against another modality (e.g., SPECT) and a threshold applied (DICE modeling) to designate perfusion status as normal or low. The DICE models included perfusion status, left ventricular (LV) chamber volumes and myocardial wall thickness. Women were followed for 40±16 months for the development of first major adverse cardiovascular event (MACE: CV death, nonfatal myocardial infarction (MI) or hospitalization for congestive heart failure). Original and DICE perfusion status were compared in their ability to detect high-grade coronary artery disease (CAD) and for prediction of MACE. Adverse events occurred in 25 (12%) women and CAD was present in 34 (16%). In receiver-operator characteristic (ROC) analysis for CAD detection, the average area under the curve (AUC) for DICE vs. Original status was 0.77±0.03 vs. 0.70±0.03, P<0.01. Similarly, in Kaplan-Meier survival analysis the average log-rank statistic was higher for DICE vs. the Original readings (10.6±5.2 vs. 3.0±0.6, P<0.05). While two data sets are required to generate the DICE models no knowledge of follow-up results is needed. DICE modeling improved diagnostic and prognostic value vs. the Original interpretation of the myocardial perfusion status.