Full Spectrum Of Disease Severity Research Articles

A pro-inflammatory gut mucosal cytokine response is associated with mild COVID-19 disease and superior induction of serum antibodies

The relationship between gastrointestinal tract infection, the host immune response, and the clinical outcome of disease is not well understood in COVID-19. We sought to understand the effect of intestinal immune responses to SARS-CoV-2 on patient outcomes including the magnitude of systemic antibody induction. Combining two prospective cohort studies, International Severe Acute Respiratory and emerging Infections Consortium Comprehensive Clinical Characterisations Collaboration (ISARIC4C) and Integrated Network for Surveillance, Trials and Investigations into COVID-19 Transmission (INSTINCT), we acquired samples from 88 COVID-19 cases representing the full spectrum of disease severity and analysed viral RNA and host gut cytokine responses in the context of clinical and virological outcome measures. There was no correlation between the upper respiratory tract and faecal viral loads. Using hierarchical clustering, we identified a group of fecal cytokines including Interleukin-17A, Granulocyte macrophage colony-stimulating factor, Tumor necrosis factorα, Interleukin-23, and S100A8, that were transiently elevated in mild cases and also correlated with the magnitude of systemic anti-Spike-receptor-binding domain antibody induction. Receiver operating characteristic curve analysis showed that expression of these gut cytokines at study enrolment in hospitalised COVID-19 cases was associated negatively with overall clinical severity implicating a protective role in COVID-19. This suggests that a productive intestinal immune response may be beneficial in the response to a respiratory pathogen and a biomarker of a successful barrier response.

THE ASSESSMENT OF MRE FINDINGS ACCORDING TO CDAI SCORE IN PATIENTS WITH CROHN’S DISEASE

Abstract INTRODUCTION Crohn’s disease (CD) is a chronic inflammatory bowel disease of the gastrointestinal tract. One of the diagnostic steps is to perform a magnetic resonance enterography (MRE). The purpose of the study was to compare MRE findings with clinical index of the disease activity - CDAI score, in order to verify the usefullness of magnetic resonance enterography. SUBJECTS/METHODS The study included 46 patients who underwent MRE according to a standard protocol, with dynamic contrast-enhanced sequences. All studies were performed in prone position, using mannitol as a positive oral contrast agent. The MRE severity grading was performed according to the consensus recommendations. CDAI score was assessed prior to examination by a specialist. RESULTS 32 patients had multifocal lesions, 14 presented with unilocular lesions and 14 had a history of previous bowel resection. Penetrating disease was diagnosed in 15 subjects. The results indicate for good correlation between MRE and CDAI assessment in groups of patients with moderate and severe clinical symptoms. However, there is a significant discrepancy in MRE findings in the group of patients with mild disease activity according to CDAI. Out of 23 patients with clinically mild symptoms, 1 exhibited MRE characteristics of severe, 9 of moderate and 7 of mild inflammatory intestinal lesions. CONCLUSION There is good accordance between MRE and clinical findings in patients with prominent disease symptoms, indicating that MR enterography might be a promising modality in terms of lesion activity grading. Nonetheless, there exist a significant group of patients with mild disease symptoms, in whom MRE tends to show full spectrum of disease severity.

Evolution of Coronavirus Disease 2019 (COVID-19) Symptoms During the First 12 Months After Illness Onset.

BackgroundFew robust longitudinal data on long-term coronavirus disease 2019 (COVID-19) symptoms are available. We evaluated symptom onset, severity and recovery across the full spectrum of disease severity, up to one year after illness onset.MethodsThe RECoVERED Study is a prospective cohort study based in Amsterdam, the Netherlands. Participants aged ≥18 years were enrolled following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis via the local public health service and from hospitals. Standardized symptom questionnaires were completed at enrollment, 1 week and month later, and monthly thereafter. Clinical severity was defined according to World Health Organization (WHO) criteria. Kaplan-Meier methods were used to compare time from illness onset to symptom recovery, by clinical severity. We examined determinants of time to recovery using multivariable Cox proportional hazards models.ResultsBetween 11 May 2020 and 1 May 2021, 342 COVID-19 patients (192 [56%] male) were enrolled, of whom 99/342 (29%) had mild, 145/342 (42%) moderate, 56/342 (16%) severe, and 42/342 (12%) critical disease. The proportion of participants who reported at least 1 persistent symptom at 12 weeks after illness onset was greater in those with severe/critical disease (86.7% [95% confidence interval {CI} = 76.5–92.7%]) compared to those with mild or moderate disease (30.7% [95% CI = 21.1–40.9%] and 63.8% [95% CI = 54.8–71.5%], respectively). At 12 months after illness onset, two-fifths of participants (40.7% [95% CI = 34.2–7.1]) continued to report ≥1 symptom. Recovery was slower in female compared to male participants (adjusted hazard ratio [aHR] 0.65 [95% CI = .47–.92]) and those with a body mass index [BMI] ≥30kg/m2 compared to BMI <25kg/m2 (hazard ratio [HR] 0.62 [95% CI = .39–.97]).ConclusionsCOVID-19 symptoms persisted for one year after illness onset, even in some individuals with mild disease. Female sex and obesity were the most important determinants of speed of recovery from symptoms.

Clinical Characteristics of Coronavirus Disease 2019 in a Cohort of Iranian Patients: Olfactory Dysfunction as a Frequent Clinical Presentation

Background: Since its outbreak, the 2019 novel coronavirus (SARS-CoV-2) has been associated withcoronavirus disease 2019 (COVID-19). The full spectrum of disease severity of COVID-19 is still unknown.In this study which is the first report from Iran, we showed that olfactory dysfunction is a frequent clinicalmanifestation among COVID-19 patients.Methods: All patients with suspected SARS-CoV-2 infection were admitted to Arak hospitals in Iran. Weretrospectively collected and analyzed data on patients with either laboratory-confirmed SARS-CoV-2infection by real-time RT-PCR and/or chest CTResults: Most patients in our cohort had mild COVID-19 (104 [60.4%] of 172) . Common symptoms atthe onset of disease included (subjective) fever (131 [76%] of 172 patients), cough (130 [75.5%]), myalgia(107 [62%]) dyspnea (92 [53.5%]), chills (96 [55.8%]), and headache (94 [54.6%]). Olfactory dysfunction(OD), including anosmia, hyposmia, hyperosmia, and dysosmia, were reported by 61 ([36.5%] of 167)patients. The most common concurrent symptoms beside the olfactory dysfunctions, were fever (39 [69.6%]of 56 patients) and chills (26 [46.4%]), respectively. For the most part, the patient’s condition worsenedafter the notice of anosmia/dysgeusia (48 [85.7%] of 56 patients). The majority of anosmic patients wererecovered from COVID-19 (50 [89.3%] of 56 patients). The anosmia/dysgeusia was resolved in 42 [75%]of 56 patients after two weeks.Conclusion: Taken together, this study reports the disease spectrum of SARS-CoV-2 infection in a cohort of172 Iranian adult patients. To the best of our knowledge, this is the first report from Iran.

Presenting characteristics and clinical outcome of patients with COVID-19 in South Korea: A nationwide retrospective observational study

BackgroundMore than 13,000 cases were reported to be infected with COVID-19 by RT-PCR in South Korea. Most studies report clinical characteristics of hospitalized patients with COVID-19; the full spectrum of disease severity has thus not yet been well described. MethodsUsing retrospective observational methods, this study analyzed factors affecting early clinical symptoms, clinical progress, and severity of disease for COVID-19 positive patients released from quarantine to provide information on establishing optimized care for new patients. The medical data of 7803 laboratory-confirmed patients who had been discharged or died by April 30, 2020 were analyzed using multivariate logistic regression analysis. FindingsOn admission, 7383 (94•5%) patients were asymptomatic or showed mild illness, and 372 (4•8%) patients were severe illness. Also, 48 (0 0•6%) were hospitalized with critically ill when diagnosed. Most patients with asymptomatic or mild illness on admission remained mild until discharge, 253 (3•4%) progressed to severe illness, and 83 (1•1%) died in hospital. However, the case fatality were 29•8% and 62•5% in severe and critically ill patients, respectively. At admission, 73•0% of hospitalized patients had symptoms; most common were cough (42•5%), sputum (28•8%), and fever (20•1%). Only 35•2% of laboratory confirmed patients admitted to the temporary care facility complained of symptoms. Increasing odds of being critically ill was associated with older age (OR 28•93, 95% CI 13•34–62•75 for age >70y, vs. age <50 y; p<0•0001), being male (OR 2•15, 95% CI1•59–2•89; p<0•0001), fever (OR 2•52, 95% CI 1.84–3•45; p<0•0001), and shortness of breath (OR 7•40, 95% CI 5•37–10•19; p<0•0001). Comorbid illness significantly increased risk of critical illness or death. InterpretationMost cases were discharged as asymptomatic or recovered from mild illness, and only 9•7% developed severe disease requiring oxygen therapy or more. Case fatality rate was 2•9%, and markedly increased in those over age 50. Risk factors such as age, sex, fever, shortness of breath, and underlying disease can be useful in predicting future clinical severity. Additionally, the number of confirmed asymptomatic COVID-19 patients significantly contribute to continued spread. Fundingnone.

Clinical course and potential predictive factors for pneumonia of adult patients with Coronavirus Disease 2019 (COVID-19): A retrospective observational analysis of 193 confirmed cases in Thailand.

Clinical spectrum of Coronavirus Disease 2019 (COVID-19) remains unclear, especially with regard to the presence of pneumonia. We aimed to describe the clinical course and final outcomes of adult patients with laboratory-confirmed COVID-19 in the full spectrum of disease severity. We also aimed to identify potential predictive factors for COVID-19 pneumonia. We conducted a retrospective study among adult patients with laboratory-confirmed COVID-19 who were hospitalized at Bamrasnaradura Infectious Diseases Institute, Thailand, between January 8 and April 16, 2020. One-hundred-and-ninety-three patients were included. The median (IQR) age was 37.0 (29.0-53.0) years, and 58.5% were male. The median (IQR) incubation period was 5.5 (3.0-8.0) days. More than half (56%) of the patients were mild disease severity, 22% were moderate, 14% were severe, and 3% were critical. Asymptomatic infection was found in 5%. The final clinical outcomes in 189 (97.9%) were recovered and 4 (2.1%) were deceased. The incidence of pneumonia was 39%. The median (IQR) time from onset of illness to pneumonia detection was 7.0 (5.0-9.0) days. Bilateral pneumonia was more prevalent than unilateral pneumonia. In multivariable logistic regression, increasing age (OR 2.55 per 10-year increase from 30 years old; 95% CI, 1.67-3.90; p<0.001), obesity (OR 8.74; 95%CI, 2.06-37.18; p = 0.003), and higher temperature at presentation (OR 4.59 per 1°C increase from 37.2°C; 95% CI, 2.30-9.17; p<0.001) were potential predictive factors for COVID-19 pneumonia. Across the spectrum of disease severities, most patients with COVID-19 in our cohort had good final clinical outcomes. COVID-19 pneumonia was found in one-third of them. Older age, obesity, and higher fever at presentation were independent predictors of COVID-19 pneumonia.

High adherence and low dropout rate in a virtual clinical study of atopic dermatitis through weekly reward-based personalized genetic lifestyle reports.

IntroductionClinical trials often suffer from significant recruitment barriers, poor adherence, and dropouts, which increase costs and negatively affect trial outcomes. The aim of this study was to examine whether making it virtual and reward-based would enable nationwide recruitment, identify patients with variable disease severity, achieve high adherence, and reduce dropouts.MethodsIn a siteless, virtual feasibility study, individuals with atopic dermatitis (AD) were recruited online. During the 8-week study, subjects used their smartphones weekly to photograph target AD lesions, and completed patient-oriented eczema measure (POEM) and treatment use questionnaires. In return, subjects were rewarded every week with personalized lifestyle reports based on their DNA.ResultsOver the course of the 11 day recruitment period, 164 (82% women and 18% men) filled in the form to participate, of which 65 fulfilled the inclusion criteria and signed the informed consent. Ten were excluded as they did not complete the mandatory study task of returning the DNA sample. 55 (91% women, 9% men) subjects returned the DNA sample and were enrolled throughout Denmark, the majority outside the Copenhagen capital region in rural areas with relatively low physician coverage. The mean age was 28.5 (SD ±9.5 years, range 18–52 years). The baseline POEM score was 14.5±5.6 (range 6–28). Based on the POEM, 7 individuals had mild, 28 had moderate, 17 had severe, and 3 had very severe eczema. The retention rate was 96% as 53 out of 55 enrolled completed the study. The adherence was very high, and more than 90% of all study tasks were completed. Follow up of 41 subjects showed that 90% would take part again or continue if the study had been longer.ConclusionA virtual trial design enables recruitment with broad geographic reach and throughout the full spectrum of disease severity. Providing personalized genetic reports as a reward seems to contribute to high adherence and retention.

A Systematic Review Examining the Oral Health Status of Persons with Dementia.

While the oral health of persons with dementia has been shown to be poor, no systematic reviews have been published that examined the topic in depth, including participants with dementia representing the full spectrum of disease severity, and evaluating a broad scope of oral health assessments. The aim of this study was to conduct a current literature review to fill this gap in knowledge. A systematic search of 5 databases (CINAHL, PubMed, EMBASE, Scopus, and ISI Web of Science) was conducted to identify all relevant studies published up to May 2016. There were no exclusions related to study type, severity of dementia, dentate status, or living arrangements. Results were reported descriptively and summarized. Meta-analyses were performed where possible and reported as mean difference (MD) or standardized mean difference (SMD), with a 95% confidence interval (CI). Twenty-eight studies were identified. Assessments were conducted of tooth status, active dental caries, hygiene (plaque/calculus) of natural and artificial teeth, periodontal diseases, denture status (retention, stability, denture-related mucosal lesions), and oral health-related quality of life. Across all evaluations, persons with dementia generally had scores/results suggestive of poor oral health. In meta-analyses, compared with persons without dementia, those with dementia had a significantly fewer number of teeth (MD, -1.52; 95% CI, -0.2.52 to -0.52; P = 0.003; n = 13 studies), more carious teeth (SMD, 0.29; 95% CI, 0.03 to 0.48; P = 0.028; n = 9), significantly worse oral hygiene evaluated using a broad range of assessment tools (SMD, 0.88; 95% CI, 0.57 to 1.19, P < 0.0001; n = 7), and significantly poorer periodontal health (SMD, 0.38; 95% CI, 0.06 to 0.70; P = 0.02; n = 6 studies). The oral health status of persons with mild to severe forms of dementia, who were living in both the community and residential care facilities, was found to be poor across a broad range of dental assessments. Knowledge Transfer Statement: The results of this study define the scope of oral issues and quantify the degree of impairment in individuals with dementia, evaluated using a variety of oral health measures. The results revealed that poor oral health is associated with dementia.

Polypharmacy and inappropriate medication use in patients with dementia: an underresearched problem.

Multimorbidity and polypharmacy are increasingly prevalent across healthcare systems and settings as global demographic trends shift towards increased proportions of older people in populations. Numerous studies have demonstrated an association between polypharmacy and potentially inappropriate prescribing (PIP), and have reported high prevalence of PIP across settings of care in Europe and North America and, as a consequence, increased risk of adverse drug reactions, healthcare utilization, morbidity and mortality. These studies have not focused specifically on people with dementia, despite the high risk of adverse drug reactions and PIP in this patient cohort. This narrative review considers the evidence currently available in the area, including studies examining prevalence of PIP in older people with dementia, how appropriateness of prescribing is assessed, the medications most commonly implicated, the clinical consequences, and research priorities to optimize prescribing for this vulnerable patient group. Although there has been a considerable research effort to develop criteria to assess medication appropriateness in older people in recent years, the majority of tools do not focus on people with dementia. Of the limited number of tools available, most focus on the advanced stages of dementia in which life expectancy is limited. The development of tools to assess medication appropriateness in people with mild to moderate dementia or across the full spectrum of disease severity represents an important gap in the research literature and is beginning to attract research interest, with recent studies considering the medication regimen as a whole, or misprescribing, overprescribing or underprescribing of certain medications/medication classes, including anticholinergics, psychotropics, antibiotics and analgesics. Further work is required in development and validation of criteria to assess prescribing appropriateness in this vulnerable patient population, to determine prevalence of PIP in large cohorts of people with the full spectrum of dementia variants and severities, and to examine the impact of PIP on health outcomes.

Recurrent purple urine bag syndrome presenting with full spectrum of disease severity: case report and review of literature.

Purple urine bag syndrome (PUBS) is a unique phenomenon characterized by purple discoloration of the urinary catheter bag and tubing following urinary catheterization lasting for hours to days. The purple discoloration is a mixture of indirubin dissolved in plastic with indigo on its surface. PUBS is most commonly associated with urinary tract infection (UTI) caused by bacteria with indoxyl phosphatase/sulfatase activity. It occurs predominantly in chronically catheterized, constipated elderly female patients. It usually appears to be asymptomatic and harmless, but rarely it can present as a severe illness. We report on a 29-year-old female with urinary ileal diversion presenting with multiple episodes of PUBS each with an asymptomatic state of varying severity, symptomatic UTI and severe sepsis requiring intensive care. To our knowledge, this is the first report where a single young patient had recurrent PUBS which presented with a full spectrum of disease severity at different occasions.

PTU-127 The impact of surgery on health related quality of life in ulcerative colitis

IntroductionSurgery is perceived as curative for ulcerative colitis but may not restore full health. Health-related QoL in ulcerative colitis is often measured using disease-specific instruments (eg, the Inflammatory Bowel Disease...

Treatment Options for Patients with Advanced Pompe Disease

Clinical trials of Myozyme® have demonstrated efficacy in carefully selected cohorts of patients with Pompe disease. Post-licensing, the drug is now being used in patients who have more advanced disease and would not have met the inclusion criteria for clinical trials. Real-life experience in infants has shown that cardiac disease responds well to enzyme replacement therapy (ERT), but babies who are already ventilator-dependent at initiation of therapy are unlikely to become ventilator-independent. In infants, advanced disease is severe disease and prognosis is likely to be correspondingly poor. In adults, even those who are wheelchair-bound or ventilator-dependent can show real improvements in performance with ERT, although these may be difficult to quantify. In adults diagnosed before ERT was available, we see a full spectrum of disease severity. Severity is related to age at symptom onset and older patients may have mild, moderate or severe disease. Adults with advanced disease get real benefit from ERT, although this may be difficult to quantify.

IL-17A in Asthma - A Question of Severity

Allergic asthma is a chronic inflammatory disease of the lung driven by aberrant responses to normally innocuous environmental allergens. Disease is characterized by excessive IgE synthesis, eosinophilic pulmonary inflammation, mucus hypersecretion, and airway remodeling, and airway hyperresponsiveness - all leading to the clinical features of disease - reversible episodes of coughing, shortness of breath and wheezing. While the excessive production of cytokines like IL-4, IL-5 and IL-13 by allergen specific-Th2 cells is sufficient to explain most features of allergic asthma, increasing evidence suggests that the Th2 paradigm does not explain the full spectrum of disease severity. In particular, severe asthmatics represent a small subset of asthmatics, in which disease is associated with more severe airway reactivity, a mixed eosinophilic/neutrophilic infiltrate, and insensitivity to treatment with corticosteroids. Thus, severe asthmatics are not only more susceptible asthma-related complications; they are underserved by currently available therapies. Recent evidence suggests that the development of severe disease may be associated with the development of a mixed Th2/Th17 response. Herein, we will assess the data from human and animal models suggesting a link between a mixed Th2/Th17 response, and the development of severe asthma. A greater understanding of the mechanisms responsible for the development of severe asthma may allow the development of efficacious therapeutics for the treatment of this intractable form of disease.

Approaches to the Study of Drug-Induced Liver Injury

Retrospective studies of administrative databases have led to highly variable estimates of the incidence and natural history of drug-induced liver injury (DILI) and the agents implicated. In contrast, prospective multicenter registry studies allow for more accurate phenotyping of individual patients with DILI, as well as for collection of biological samples for mechanistic studies. In addition to improved diagnostic and prognostic biomarkers, standardized causality assessment tools are needed, as well as population-based studies that represent the full spectrum of disease severity. This would facilitate further research into the pathogenesis of DILI, leading ultimately to the prevention of this condition.

Predictors of Body Mass Index in Patients With Moderate to Severe Emphysema

ABSTRACTPeople with Chronic Obstructive Pulmonary Disease are at risk for low body weight and the subsequent sequelae of cachexia. The goal of this study was to define the relationship between of degree of emphysema as measured by high resolution chest computerized tomography, body mass index and caloric intake. Subjects from San Diego County were recruited to participate in a multi-center randomized clinical trial to test the Feasibility of Retinoids in the Treatment of Emphysema (FORTE). Forty subjects with Chronic Obstructive Pulmonary Disease, participated in a nutrition substudy and were ex-smokers with FEV1 between 20%–80% predicted. Body mass index was correlated with the degree of emphysema as measured by high resolution chest tomography (CT), r2 = 0.171 p < 0.01 across the full spectrum of disease severity. Dietary intake averaged over four days using 24-hour recalls was inversely correlated with BMI, r2 = 0.471, p < 0.001, indicating a higher energy intake in subjects with low BMI. Pulmonary function tests of percent predicated FEV1 was mildly related to BMI (r2 = 0.086, p < 0.06). A regression model was developed to define the relationship of BMI and degree of emphysema and calorie per kilogram body weight, which accounted for 60% of the variability, p < 0.001. Low body weight in the COPD is related to the degree of emphysema, not due to decreased caloric intake. Subjects with low body weight have compensated by increasing their caloric intake and are meeting their nutritional needs.

Indicators for Measuring Mental Health: Towards Better Surveillance

Accurate measurement and improvement of population mental health requires the recording of indicators that capture the full spectrum of disease severity. This paper describes four different strategies for measuring the prevalence of depression and anxiety in Canada based on data from the 2002 Canadian Community Health Survey - Mental Health and Well-being (Cycle 1.2) and the 2003 Quebec medical services claims database. The use of multiple indicators provides a more comprehensive picture of mental health needs than a single indicator alone. However, the validity of these indicators raises certain challenges and highlights the complexity of obtaining valid and sustainable measurements of mental health problems over time. We include a discussion of problems related to information availability and management.

Kawasaki Disease in a Pediatric Intensive Care Unit: A Case-Control Study

We conducted a case-control study to ascertain the clinical presentations, risk factors, and clinical outcomes of children who had Kawasaki disease and were admitted to the ICU of our children's hospital. We reviewed charts of all children who had a discharge diagnosis of Kawasaki disease and were admitted to the ICU from 1995 through 2007. For each patient, we identified 3 season-matched control subjects who had Kawasaki disease and were not admitted to the ICU. We identified 423 patients with Kawasaki disease. Of those, 14 (3.3%) were admitted to the ICU and met our inclusion criteria. ICU admission diagnoses were most commonly toxic shock or septic shock. Thirteen (92.8%) of 14 patients who were admitted to the ICU met criteria for complete Kawasaki disease before treatment. There was no significant difference in age in ICU patients compared with season-matched control subjects with Kawasaki disease. ICU patients were significantly more likely to be female and to have higher band counts, lower platelet counts, lower albumin levels, and higher C-reactive protein values. Time from admission to treatment with intravenous immunoglobulin was delayed in ICU patients. ICU patients were more likely to have intravenous immunoglobulin-refractory disease and require therapy with a second dose of intravenous immunoglobulin, infliximab, or steroids. We present a case-control study of patients who had Kawasaki disease and presented severely ill, in shock, and requiring admission to the ICU. These patients frequently were misdiagnosed because of failure to appreciate the full spectrum of disease severity seen in patients with Kawasaki disease. These patients' illnesses was often mistaken for toxic or septic shock, leading to a delay in treatment with intravenous immunoglobulin. Patients who have Kawasaki disease and are admitted to the ICU are at increased risk for intravenous immunoglobulin-refractory disease and may be at risk for development of more severe coronary artery disease.

Usefulness of six non-proprietary indirect markers of liver fibrosis in patients with chronic hepatitis C

The aim of the study was to perform a comprehensive diagnostic evaluation of six popular, non-proprietary, indirect markers of liver fibrosis in a cohort of patients with chronic hepatitis C representing the full spectrum of disease severity. A total of 167 consecutive, hepatitis C virus RNA positive, untreated patients with chronic hepatitis C were studied. Liver biopsy with histological evaluation and age/platelet index, aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase to platelet ratio index, Bonacini's discriminant score, Forn's fibrosis index and FibroIndex were assessed in all patients. The area under the receiver operating characteristic curves of the six tests was always greater when performed to discriminate patients with METAVIR score F4 than when assessed to discriminate patients with METAVIR score > or =F2. At step-wise discriminant analysis the only indirect marker of fibrosis entered was FibroIndex, with the following correct classification of the patients: total=52.1, patients with scores F0-F1=62.2, patients with scores F2-F3=26.0 and patients with score F4=68.4. The ability to correctly classify patients using a panel of non-proprietary indirect markers of liver fibrosis is far from being ideal. Among them, FibroIndex appears to possess the best discriminating capacity. The simultaneous use of several indirect markers of liver fibrosis does not improve their diagnostic accuracy.

Plaque development, vessel curvature, and wall shear stress in coronary arteries assessed by X-ray angiography and intravascular ultrasound

The relationships among vascular geometry, hemodynamics, and plaque development in the coronary arteries are complex and not yet well understood. This paper reports a methodology for the quantitative analysis of in vivo coronary morphology and hemodynamics, with particular emphasis placed on the critical issues of image segmentation and the automated classification of disease severity. We were motivated by the observation that plaque more often developed at the inner curvature of a vessel, presumably due to the relatively lower wall shear stress at these locations. The presented studies are based on our validated methodology for the three-dimensional fusion of intravascular ultrasound (IVUS) and X-ray angiography, introducing a novel approach for IVUS segmentation that incorporates a robust, knowledge-based cost function and a fully optimal, three-dimensional segmentation algorithm. Our first study shows that circumferential plaque distribution depends on local vessel curvature in the majority of vessels. The second study analyzes the correlation between plaque distribution and wall shear stress in a set of 48 in vivo vessel segments. The results were conclusive for both studies, with a stronger correlation of circumferential plaque thickness with local curvature than with wall shear stress. The inverse relationship between local wall shear stress and plaque thickness was significantly more pronounced (p<0.025) in vessel cross sections exhibiting compensatory enlargement (positive remodeling) without luminal narrowing than when the full spectrum of disease severity was considered. The inverse relationship was no longer observed in vessels where less than 35% of vessel cross sections remained without luminal narrowing. The findings of this study confirm, in vivo, the hypothesis that relatively lower wall shear stress is associated with early plaque development.