The diagnostic accuracy of 18F-FDG PET/CT in diagnosing fracture-related infections.

PURPOSE: 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) is frequently used to diagnose fracture-related infections (FRIs), but its diagnostic performance in this field is still unknown. The aims of this study were: (1) to assess the diagnostic performance of qualitative assessment of 18F-FDG PET/CT scans in diagnosing FRI, (2) to establish the diagnostic performance of standardized uptake values (SUVs) extracted from 18F-FDG PET/CT scans and to determine their associated optimal cut-off values, and (3) to identify variables that predict a false-positive (FP) or false-negative (FN) 18F-FDG PET/CT result. METHODS: This retrospective cohort study included all patients with suspected FRI undergoing 18F-FDG PET/CT between 2011 and 2017 in two level-1 trauma centres. Two nuclear medicine physicians independently reassessed all 18F-FDG PET/CT scans. The reference standard consisted of the result of at least two deep, representative microbiological cultures or the presence/absence of clinical confirmatory signs of FRI (AO/EBJIS consensus definition) during a follow-up of at least 6 months. Diagnostic performance in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was calculated. Additionally, SUVs were measured on 18F-FDG PET/CT scans. Volumes of interest were drawn around the suspected and corresponding contralateral areas to obtain absolute values and ratios between suspected and contralateral areas. A multivariable logistic regression analysis was also performed to identify the most important predictor(s) of FP or FN 18F-FDG PET/CT results. RESULTS: The study included 156 18F-FDG PET/CT scans in 135 patients. Qualitative assessment of 18F-FDG PET/CT scans showed a sensitivity of 0.89, specificity of 0.80, PPV of 0.74, NPV of 0.91 and diagnostic accuracy of 0.83. SUVs on their own resulted in lower diagnostic performance, but combining them with qualitative assessments yielded an AUC of 0.89 compared to an AUC of 0.84 when considering only the qualitative assessment results (p = 0.007). 18F-FDG PET/CT performed <1 month after surgery was found to be the independent variable with the highest predictive value for a false test result, with an absolute risk of 46% (95% CI 27-66%), compared with 7% (95% CI 4-12%) in patients with 18F-FDG PET/CT performed 1-6 months after surgery. CONCLUSION: Qualitative assessment of 18F-FDG PET/CT scans had a diagnostic accuracy of 0.83 and an excellent NPV of 0.91 in diagnosing FRI. Adding SUV measurements to qualitative assessment provided additional accuracy in comparison to qualitative assessment alone. An interval between surgery and 18F-FDG PET/CT of <1 month was associated with a sharp increase in false test results.

On the variable inverse sum deg index.

Several important topological indices studied in mathematical chemistry are expressed in the following way $ \sum_{uv \in E(G)} F(d_u, d_v) $, where $ F $ is a two variable function that satisfies the condition $ F(x, y) = F(y, x) $, $ uv $ denotes an edge of the graph $ G $ and $ d_u $ is the degree of the vertex $ u $. Among them, the variable inverse sum deg index $ IS\!D_a $, with $ F(d_u, d_v) = 1/(d_u^a+d_v^a) $, was found to have several applications. In this paper, we solve some problems posed by Vukicevic [1], and we characterize graphs with maximum and minimum values of the $ IS\!D_a $ index, for $ a < 0 $, in the following sets of graphs with $ n $ vertices: graphs with fixed minimum degree, connected graphs with fixed minimum degree, graphs with fixed maximum degree, and connected graphs with fixed maximum degree. Also, we performed a QSPR analysis to test the predictive power of this index for some physicochemical properties of polyaromatic hydrocarbons.

Bilingual nurse education program: applicant characteristics that predict success.

Nurses are in great demand across the United States, but those fluent in both Spanish and English are in particularly short supply. This study examined three cohorts of students that entered a Spanish-English nursing education program to determine characteristics of applicants that produced student success. Unlike many nursing programs, entrance requirements for this bilingual program did not include a minimal grade point average (GPA) or previous course completions. Logistic regression was used to analyze the relationship between five different characteristics of entering students and their later success in the program. Success was measured in terms of program persistence and performance on the NCLEX-PN and NCLEX-RN exams. Incoming students with relatively high GPAs (M = 3.2) were significantly more likely to persist through the entire nursing 0ronram and oass the NCLEX-RN exam (t < .05) than those with lower GPAs (M = 2.5).

A clinical classification system for rheumatoid forefoot deformity.

BACKGROUND AND PURPOSE: In the present study a classification system for the rheumatoid forefoot is reported with its intra- and interobserver reliability and clinical relevance. The classification is based on the sequence of anatomical changes resulting from the loss of integrity of the MTP joints, loss of motion and changes regarding the quality and position of the plantar soft tissues. It is hypothesized that with progression of the amount of deformity of the MTP joint(s), patients have more pain and functional loss. PATIENTS AND METHODS: In total 94 patients were included in the study following precise inclusion criteria. The forefeet of the patients were classified according to the introduced classification system by two observers in order to determine the intra- and interobserver reliability. The relation of the suggested classification between pain, function scores, and plantar foot pressure measurements was examined. RESULTS AND CONCLUSION: According to the Cohen's kappa and the ICC, the intra- and inter-observer reliability were high. Despite the large variation between subjects in a certain grade, a clear trend was found between increase in classification and VAS for pain, FFI difficulty with activities, and plantar peak pressure under the metatarsals. The suggested classification is of clinical relevance and can be used to develop therapeutical algorithms and to test interventions.

White Blood Cell Scintigraphy for Fracture-Related Infection: Is Semiquantitative Analysis of Equivocal Scans Accurate?

PURPOSE: White blood cell (WBC) scintigraphy is considered the gold-standard nuclear imaging technique for diagnosing fracture-related infection (FRI). Correct interpretation of WBC scans in FRI is important since a false positive or false negative diagnosis has major consequences for the patient in terms of clinical decision-making. The European Association of Nuclear Medicine (EANM) guideline for correct analysis and interpretation of WBC scans recommends semiquantitative analysis of visually equivocal scans. Therefore, this study aims to assess the diagnostic accuracy of semiquantitative analysis of visually equivocal WBC scans for diagnosing FRI. METHODS: A retrospective single-center study was performed in consecutive patients who received WBC scintigraphy in the diagnostic work-up for FRI between February 2012 and January 2017. All the visually equivocal scans were analysed using semiquantitative analysis by comparing leukocyte uptake in the manually selected suspected infection focus with the contralateral bone marrow (L/R ratio). Cut-off points for a 'positive' scan result of >0%, >10% and >20% leukocyte increase between the early and late scans were used in separate analyses. The discriminative ability was quantified by calculating the sensitivity, specificity and diagnostic accuracy. RESULTS: In total, 153 WBC scans were eligible for inclusion. After visual assessment of all the scans, 28 visually equivocal scans were included. Dichotomization of the ratios using the cut-off of >0% resulted in a sensitivity of 30%, a specificity of 45% and a diagnostic accuracy of 40%. The >10% cut-off point resulted in a sensitivity of 18%, a specificity of 82% and a diagnostic accuracy of 66%. The >20% cut-off point resulted in a sensitivity of 0%, a specificity of 89% and a diagnostic accuracy of 67%. CONCLUSION: Semiquantitative analysis of visually equivocal WBC scans is insufficient for correctly diagnosing FRI.

Mining EEG with SVM for Understanding Cognitive Underpinnings of Math Problem Solving Strategies.

We have developed a new methodology for examining and extracting patterns from brain electric activity by using data mining and machine learning techniques. Data was collected from experiments focused on the study of cognitive processes that might evoke different specific strategies in the resolution of math problems. A binary classification problem was constructed using correlations and phase synchronization between different electroencephalographic channels as characteristics and, as labels or classes, the math performances of individuals participating in specially designed experiments. The proposed methodology is based on using well-established procedures of feature selection, which were used to determine a suitable brain functional network size related to math problem solving strategies and also to discover the most relevant links in this network without including noisy connections or excluding significant connections.

Prevalence of non-communicable diseases and access to care among non-camp Syrian refugees in northern Jordan.

BACKGROUND: Tackling the high non-communicable disease (NCD) burden among Syrian refugees poses a challenge to humanitarian actors and host countries. Current response priorities are the identification and integration of key interventions for NCD care into humanitarian programs as well as sustainable financing. To provide evidence for effective NCD intervention planning, we conducted a cross-sectional survey among non-camp Syrian refugees in northern Jordan to investigate the burden and determinants for high NCDs prevalence and NCD multi-morbidities and assess the access to NCD care. METHODS: We used a two-stage cluster design with 329 randomly selected clusters and eight households identified through snowball sampling. Consenting households were interviewed about self-reported NCDs, NCD service utilization, and barriers to care.We estimated the adult prevalence of hypertension, diabetes type I/II, cardiovascular- and chronic respiratory conditions, thyroid disease and cancer and analysed the pattern of NCD multi-morbidities. We used the Cox proportional hazard model to calculate the prevalence ratios (PR) to analyse determinants for NCD prevalence and logistic regression to determine risk factors for NCD multi-morbidities by calculating odds ratios (ORs). RESULTS: Among 8041 adults, 21.8%, (95% CI: 20.9-22.8) suffered from at least one NCD; hypertension (14.0, 95% CI: 13.2-14.8) and diabetes (9.2, 95% CI: 8.5-9.9) were the most prevalent NCDs. NCD multi-morbidities were reported by 44.7% (95% CI: 42.4-47.0) of patients. Higher age was associated with higher NCD prevalence and the risk for NCD-multi-morbidities; education was inversely associated.Of those patients who needed NCD care, 23.0% (95% CI: 20.5-25.6) did not seek it; 61.5% (95% CI: 54.7-67.9) cited provider cost as the main barrier. An NCD medication interruption was reported by 23.1% (95% CI: 20-4-26.1) of patients with regular medication needs; predominant reason was unaffordability (63.4, 95% CI: 56.7-69.6). CONCLUSION: The burden of NCDs and multi-morbidities is high among Syrian refugees in northern Jordan. Elderly and those with a lower education are key target groups for NCD prevention and care, which informs NCD service planning and developing patient-centred approaches.Important unmet needs for NCD care exist; removing the main barriers to care could include cost-reduction for medications through humanitarian pricing models. Nevertheless, it is still essential that international donors agencies and countries fulfill their commitment to support the Syrian-crisis response.

Limited Predictive Value of Serum Inflammatory Markers for Diagnosing Fracture-Related Infections: results of a large retrospective multicenter cohort study.

Introduction: Diagnosing Fracture-Related Infections (FRI) based on clinical symptoms alone can be challenging and additional diagnostic tools such as serum inflammatory markers are often utilized. The aims of this study were 1) to determine the individual diagnostic performance of three commonly used serum inflammatory markers: C-Reactive Protein (CRP), Leukocyte Count (LC) and Erythrocyte Sedimentation Rate (ESR), and 2) to determine the diagnostic performance of a combination of these markers, and the additional value of including clinical parameters predictive of FRI. Methods: This cohort study included patients who presented with a suspected FRI at two participating level I academic trauma centers between February 1st 2009 and December 31st 2017. The parameters CRP, LC and ESR, determined at diagnostic work-up of the suspected FRI, were retrieved from hospital records. The gold standard for diagnosing or ruling out FRI was defined as: positive microbiology results of surgically obtained tissue samples, or absence of FRI at a clinical follow-up of at least six months. The diagnostic accuracy of the individual serum inflammatory markers was assessed. Analyses were done with both dichotomized values using hospital thresholds as well as with continuous values. Multivariable logistic regression analyses were performed to obtain the discriminative performance (Area Under the Receiver Operating Characteristic, AUROC) of (1) the combined inflammatory markers, and (2) the added value of these markers to clinical parameters. Results: A total of 168 patients met the inclusion criteria and were included for analysis. CRP had a 38% sensitivity, 34% specificity, 42% positive predictive value (PPV) and 78% negative predictive value (NPV). For LC this was 39%, 74%, 46% and 67% and for ESR 62%, 64%, 45% and 76% respectively. The diagnostic accuracy was 52%, 61% and 80% respectively. The AUROC was 0.64 for CRP, 0.60 for LC and 0.58 for ESR. The AUROC of the combined inflammatory markers was 0.63. Serum inflammatory markers combined with clinical parameters resulted in AUROC of 0.66 as opposed to 0.62 for clinical parameters alone. Conclusion: The added value of CRP, LC and ESR for diagnosing FRI is limited. Clinicians should be cautious when interpreting the results of these tests in patients with suspected FRI.

Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy.

Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150µM or 400µM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when evaluated in an in vitro model of DN. Altogether, our findings suggest that DFX preconditioning of AD-MSCs improves their therapeutic potential and should be considered as a potential strategy for the generation of new alternatives for DN treatment.

Mathematical modeling confirms the length-dependency of telomere shortening.

Telomeres, the ends of chromosomes, shorten with each cell division in human somatic cells, because of the end-replication problem, C-strand processing and oxidative damage. On the other hand, the reverse transcriptase telomerase can add back telomeric repeats at the telomere ends. It has been suggested that once telomeres have reached a critical length, cells cease proliferation, also known as senescence. Evidence is accumulating that telomere shortening and subsequent senescence might play a crucial role in life-threatening diseases. So far, mathematical models described telomere shortening as an autonomous process, where the loss per cell division does not depend on the telomere length itself. In this study, published measurements of telomere distributions in human fibroblasts and human endothelial cells were used to show that telomeres shorten in a length-dependent fashion. Thereafter, a mathematical model of telomere attrition was composed, in which a shortening factor and an autonomous loss were incorporated. It was assumed that the percentage of senescence was related to the percentage of telomeres below a critical length. The model was compared with published data of telomere length and senescence of human endothelial cells using the maximum likelihood method. This enabled the estimation of physiologically important parameters and confirmed the length-dependency of telomere shortening.

Modeling the spread of tuberculosis in semiclosed communities.

We address the problem of long-term dynamics of tuberculosis (TB) and latent tuberculosis (LTB) in semiclosed communities. These communities are congregate settings with the potential for sustained daily contact for weeks, months, and even years between their members. Basic examples of these communities are prisons, but certain urban/rural communities, some schools, among others could possibly fit well into this definition. These communities present a sort of ideal conditions for TB spread. In order to describe key relevant dynamics of the disease in these communities, we consider a five compartments SEIR model with five possible routes toward TB infection: primary infection after a contact with infected and infectious individuals (fast TB), endogenous reactivation after a period of latency (slow TB), relapse by natural causes after a cure, exogenous reinfection of latently infected, and exogenous reinfection of recovered individuals. We discuss the possible existence of multiple endemic equilibrium states and the role that the two types of exogenous reinfections in the long-term dynamics of the disease could play.

On the identifiability of pharmacokinetic parameters in dynamic contrast-enhanced imaging.

The so-called "Kety model" is a two-compartment pharmacokinetic model describing tumor perfusion kinetics. Its parameters, the transendothelial transfer constant (K(trans)), extravascular extracellular volume fraction (upsilon(e)), and microvascular plasma volume fraction (upsilon(p)), can be estimated with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). However, the results obtained by current methods show large variation in predictability and reliability. Here, the aim was to examine which experimental conditions have to be fulfilled to avoid large uncertainties and mutual dependencies of the parameters. Using frequency response analysis and simulation, the identifiability of the model was examined. The requirements and influence of contrast enhancement measurements, such as temporal resolution, signal to noise ratio, and contrast injection rate, on the accuracy of the parameters were analyzed. Tissue response characteristics revealed a low-frequency system with a cutoff frequency equal to K(trans)/upsilon(e), which confines the required temporal resolution. For malignant tissue with hyperpermeable vasculature (high K(trans)) a higher sampling frequency is required to accurately estimate K(trans) than for normal tissue. Too low sampling rates or too low injection rates resulted in inaccurate K(trans) values and hereby unreliable classification of malignant tissue.