Estimation of heart weight by post-mortem cardiac magnetic resonance imaging

Introduction The aim of this study was to determine which single measurement on post-mortem cardiac MR reflects actual heart weight as measured at autopsy, assess the intra- and inter-observer reliability of MR measurements, derive a formula to predict heart weight from MR measurements and test the accuracy of the formula to prospectively predict heart weight. Materials and methods 53 human cadavers underwent post-mortem cardiac MR and forensic autopsy. In Phase 1, left ventricular area and wall thickness were measured on short axis and four chamber view images of 29 cases. All measurements were correlated to heart weight at autopsy using linear regression analysis. In Phase 2, single left ventricular area measurements on four chamber view images (LVA_4C) from 24 cases were used to predict heart weight at autopsy based on equations derived during Phase 1. Intra-class correlation coefficient (ICC) was used to determine inter- and intra-reader agreement. Results Heart weight strongly correlates with LVA_4C (r=0.78 M; p<0.001). Intra-reader and inter-reader reliability was excellent for LVA_4C (ICC=0.81–0.91; p<0.001 and ICC=0.90; p<0.001 respectively). A simplified formula for heart weight ([g]≈LVA_4C [mm2]×0.11) was derived based on linear regression analysis. Conclusions This study shows that single circumferential area measurements of the left ventricle in the four chamber view on post-mortem cardiac MR reflect actual heart weight as measured at autopsy. These measurements yield an excellent intra- and inter-reader reliability and can be used to predict heart weight prior to autopsy or to give a reasonable estimate of heart weight in cases where autopsy is not performed.

Age dependency of safety and outcome of endovascular therapy for acute stroke

Elderly patients generally experience less favorable outcomes and higher mortality after acute stroke than younger patients. The aim of this study was to analyze the influence of age on outcome and safety after endovascular therapy in a large cohort of patients aged between 20 and 90 years. We prospectively acquired data of 1,000 stroke patients treated with endovascular therapy at a single center. Logistic regression analysis was performed to determine predictors of outcome and linear regression analysis to evaluate the association of age and outcome after 3 months. Younger age was an independent predictor of favorable outcome (OR 0.954, p < 0.001) and survival (OR 0.947, p < 0.001) in multivariate regression analysis. There was a linear relationship between age and outcome. Ever increase in 26 years of age was associated with an increase in the modified Rankin Scale of 1 point (p < 0.001). However, increasing age was not a risk factor for symptomatic (p = 0.086) or asymptomatic (p = 0.674) intracerebral hemorrhage and did not influence recanalization success (p = 0.674). Advancing age was associated with a decline of favorable outcomes and survival after endovascular therapy. This decline was linear from age 20 to 90 years, but was not related to lower recanalization rates or higher bleeding risk in the elderly. The efficacy of endovascular stroke therapy seems to be preserved also in the elderly and other factors than efficacy of endovascular therapy such as decreased plasticity are likely to explain the worse outcome with advancing age.

Respiratory-related leg movements and their relationship with periodic leg movements during sleep

STUDY OBJECTIVES: To describe the time structure of leg movements (LM) in obstructive sleep apnea (OSA) syndrome, in order to advance understanding of their clinical significance. LOCATION: Sleep Research Centre, Oasi Institute (IRCCS), Troina, Italy. SETTING: Sleep laboratory. PATIENTS: Eighty-four patients (16 females, 68 males, mean age 55.1 y, range 29-74 y). METHODS: Respiratory-related leg movements (RRLM) and those unrelated to respiratory events (NRLM) were examined within diagnostic polysomnograms alone and together for their distributions within the sleep period and for their periodicity. MEASUREMENTS AND RESULTS: Patients with OSA and RRLM exhibited more periodic leg movements in sleep (PLMS), particularly in NREM sleep. A gradual decrease in number of NRLM across the sleep period was observed in patients with RRLM. This pattern was less clear for RRLM. Frequency histograms of intermovement intervals of all LMs in patients with RRLM showed a prominent first peak at 4 sec, and a second peak at approximately 24 sec coincident with that of PLMS occurring in the absence of OSA. A third peak of lowest amplitude was the broadest with a maximum at approximately 42 sec. In patients lacking RRLM, NRLM were evident with a single peak at 2-4 sec. A stepwise linear regression analysis showed that, after controlling for a diagnosis of restless legs syndrome and apnea-hypopnea index, PLMS remained significantly associated with RRLM. CONCLUSION: The time structure of leg movements occurring in conjunction with respiratory events exhibit features of periodic leg movements in sleep occurring alone, only with a different and longer period. This brings into question the validity, both biologic and clinical, of scoring conventions with their a priori exclusion from consideration as periodic leg movements in sleep.

Psychometric and biohormonal indices of dental anxiety in children. A prospective cohort study.

The stress of dental treatment often elicits negative emotions in children, expressed as dental fear or anxiety. Highly anxious children obstruct treatment and avoid therapy, further amplifying oral health problems. The aim of this study was to examine the neuroendocrine and autonomic nervous system responses to dental treatment and their possible interactions and associations with psychometric indices of anxiety, caries, previous dental experience, anesthesia, age and gender in school children. Upon informed consent, saliva was obtained from 97 children (59% males, mean age ±  SD: 89.73 ± 15 months) in the Clinic of pediatric dentistry before treatment, immediately post-treatment and at the recall visit to determine cortisol and salivary alpha-amylase (sAA) levels. Dental and general anxiety was assessed through specific questionnaires completed by the children. Compared to pre-treatment, cortisol levels were increased following treatment, while sAA levels were higher at the recall. Pre- and post-treatment cortisol and sAA responses were positively correlated. Dental and general anxiety questionnaire scores were also significantly correlated with each other. The integrated autonomic and neuroendocrine responses prior to treatment were correlated with state anxiety and those following treatment with dental anxiety. However, univariable and multivariable linear regression analysis associated post-treatment cortisol, but not sAA, levels with dental anxiety. No associations of cortisol or sAA responses with caries, age, gender, previous dental experience or anesthesia were detected. These data provide some evidence that both sAA and cortisol levels are altered in children in anticipation or during dental treatment, but only cortisol levels are associated to dental anxiety.

Contrasting interannual and multidecadal NAO variability

Decadal and longer timescale variability in the winter North Atlantic Oscillation (NAO) has considerable impact on regional climate, yet it remains unclear what fraction of this variability is potentially predictable. This study takes a new approach to this question by demonstrating clear physical differences between NAO variability on interannual-decadal (<30 year) and multidecadal (>30 year) timescales. It is shown that on the shorter timescale the NAO is dominated by variations in the latitude of the North Atlantic jet and storm track, whereas on the longer timescale it represents changes in their strength instead. NAO variability on the two timescales is associated with different dynamical behaviour in terms of eddy-mean flow interaction, Rossby wave breaking and blocking. The two timescales also exhibit different regional impacts on temperature and precipitation and different relationships to sea surface temperatures. These results are derived from linear regression analysis of the Twentieth Century and NCEP-NCAR reanalyses and of a high-resolution HiGEM General Circulation Model control simulation, with additional analysis of a long sea level pressure reconstruction. Evidence is presented for an influence of the ocean circulation on the longer timescale variability of the NAO, which is particularly clear in the model data. As well as providing new evidence of potential predictability, these findings are shown to have implications for the reconstruction and interpretation of long climate records.

Prevalence and predictors of fatigue in glioblastoma: a prospective study.

BACKGROUND The main goal of this study was to assess frequency, clinical correlates, and independent predictors of fatigue in a homogeneous cohort of well-defined glioblastoma patients at baseline prior to combined radio-chemotherapy. METHODS We prospectively included 65 glioblastoma patients at postsurgical baseline and assessed fatigue, sleepiness, mean bedtimes, mood disturbances, and clinical characteristics such as clinical performance status, presenting symptomatology, details on neurosurgical procedure, and tumor location and diameter as well as pharmacological treatment including antiepileptic drugs, antidepressants, and use of corticosteroids. Data on fatigue and sleepiness were measured with the Fatigue Severity Scale and the Epworth Sleepiness Scale, respectively, and compared with 130 age- and sex-matched healthy controls. RESULTS We observed a significant correlation between fatigue and sleepiness scores in both patients (r = 0.26; P = .04) and controls (r = 0.36; P < .001). Only fatigue appeared to be more common in glioblastoma patients than in healthy controls (48% vs 11%; P < .001) but not the frequency of sleepiness (22% vs 19%; P = .43). Female sex was associated with increased fatigue frequency among glioblastoma patients but not among control participants. Multiple linear regression analyses identified depression, left-sided tumor location, and female sex as strongest associates of baseline fatigue severity. CONCLUSIONS Our findings indicate that glioblastoma patients are frequently affected by fatigue at baseline, suggesting that factors other than those related to radio- or chemotherapy have significant impact, particularly depression and tumor localization.

Determination of respiratory gas flow by electrical impedance tomography in an animal model of mechanical ventilation

Background A recent method determines regional gas flow of the lung by electrical impedance tomography (EIT). The aim of this study is to show the applicability of this method in a porcine model of mechanical ventilation in healthy and diseased lungs. Our primary hypothesis is that global gas flow measured by EIT can be correlated with spirometry. Our secondary hypothesis is that regional analysis of respiratory gas flow delivers physiologically meaningful results. Methods In two sets of experiments n = 7 healthy pigs and n = 6 pigs before and after induction of lavage lung injury were investigated. EIT of the lung and spirometry were registered synchronously during ongoing mechanical ventilation. In-vivo aeration of the lung was analysed in four regions-of-interest (ROI) by EIT: 1) global, 2) ventral (non-dependent), 3) middle and 4) dorsal (dependent) ROI. Respiratory gas flow was calculated by the first derivative of the regional aeration curve. Four phases of the respiratory cycle were discriminated. They delivered peak and late inspiratory and expiratory gas flow (PIF, LIF, PEF, LEF) characterizing early or late inspiration or expiration. Results Linear regression analysis of EIT and spirometry in healthy pigs revealed a very good correlation measuring peak flow and a good correlation detecting late flow. PIFEIT = 0.702 · PIFspiro + 117.4, r2 = 0.809; PEFEIT = 0.690 · PEFspiro-124.2, r2 = 0.760; LIFEIT = 0.909 · LIFspiro + 27.32, r2 = 0.572 and LEFEIT = 0.858 · LEFspiro-10.94, r2 = 0.647. EIT derived absolute gas flow was generally smaller than data from spirometry. Regional gas flow was distributed heterogeneously during different phases of the respiratory cycle. But, the regional distribution of gas flow stayed stable during different ventilator settings. Moderate lung injury changed the regional pattern of gas flow. Conclusions We conclude that the presented method is able to determine global respiratory gas flow of the lung in different phases of the respiratory cycle. Additionally, it delivers meaningful insight into regional pulmonary characteristics, i.e. the regional ability of the lung to take up and to release air.

Prediction of Post-Weaning Fibrinogen Status during Cardiopulmonary Bypass: An Observational Study in 110 Patients.

BACKGROUND After cardiac surgery with cardiopulmonary bypass (CPB), acquired coagulopathy often leads to post-CPB bleeding. Though multifactorial in origin, this coagulopathy is often aggravated by deficient fibrinogen levels. OBJECTIVE To assess whether laboratory and thrombelastometric testing on CPB can predict plasma fibrinogen immediately after CPB weaning. PATIENTS / METHODS This prospective study in 110 patients undergoing major cardiovascular surgery at risk of post-CPB bleeding compares fibrinogen level (Clauss method) and function (fibrin-specific thrombelastometry) in order to study the predictability of their course early after termination of CPB. Linear regression analysis and receiver operating characteristics were used to determine correlations and predictive accuracy. RESULTS Quantitative estimation of post-CPB Clauss fibrinogen from on-CPB fibrinogen was feasible with small bias (+0.19 g/l), but with poor precision and a percentage of error >30%. A clinically useful alternative approach was developed by using on-CPB A10 to predict a Clauss fibrinogen range of interest instead of a discrete level. An on-CPB A10 ≤10 mm identified patients with a post-CPB Clauss fibrinogen of ≤1.5 g/l with a sensitivity of 0.99 and a positive predictive value of 0.60; it also identified those without a post-CPB Clauss fibrinogen <2.0 g/l with a specificity of 0.83. CONCLUSIONS When measured on CPB prior to weaning, a FIBTEM A10 ≤10 mm is an early alert for post-CPB fibrinogen levels below or within the substitution range (1.5-2.0 g/l) recommended in case of post-CPB coagulopathic bleeding. This helps to minimize the delay to data-based hemostatic management after weaning from CPB.

Migration and population expansion of Abies, Fagus, Picea, and Quercus since 15000 years in and across the Alps, based on pollen-percentage threshold values

Aims: The aim of this study is to explore the migration (colonization of new areas) and subsequent population expansion (within an area) since 15 ka cal BP of Abies, Fagus, Picea, and Quercus into and through the Alps solely on the basis of high-quality pollen data. Methods: Chronologies of 101 pollen sequences are improved or created. Data from the area delimited by 45.5–48.1°N and 6–14°E are summarized in three ways: (1) in a selection of pollen-percentage threshold maps (thresholds 0.5%, 1%, 2%, 4%, 8%, 16%, and 32% of land pollen); (2) in graphic summaries of 250-year time slices and geographic segments (lengthwise and transverse in relation to the main axis of the Alps) as pollen-percentage curves, pollen-percentage difference curves, and pollen-percentage threshold ages cal BP graphed against both the length and the transverse Alpine axes; and (3) in tables showing statistical relationships of either pollen-percentage threshold ages cal BP or pollen expansion durations (=time lapse between different pollen-percentage threshold ages cal BP) with latitude, longitude, and elevation; to establish these relationships we used both simple linear regression and multiple linear regression after stepwise-forward selection. Results: The statistical results indicate that (a) the use of pollen-percentage thresholds between 0.5% and 8% yield mostly similar directions of tree migration, so the method is fairly robust, (b) Abies migrated northward, Fagus southward, Picea westward, and Quercus northward; more detail does not emerge due to an extreme scarcity of high-quality data especially along the southern foothills of the Alps and in the eastern Alps. This scarcity allows the reconstruction of one immigration route only of Abies into the southern Alps. The speed of population expansion (following arrival) of Abies increased and of Picea decreased during the Holocene, of Fagus it decreased especially during the later Holocene, and of Quercus it increased especially at the start of the Holocene.

Interlaboratory variability of MIB1 staining in well-differentiated pancreatic neuroendocrine tumors

Neuroendocrine tumors (NET) are routinely graded and staged to judge prognosis. Proliferation index using MIB1 staining has been introduced to assess grading. There are vivid discussions on cutoff definitions, automated counting, and interobserver variability. However, no data exist regarding interlaboratory reproducibility for low proliferation indices which are of importance to discriminate between G1 and G2 NET. We performed MIB1 staining in three different university hospital-based pathology laboratories on a tissue micro array (TMA) of a well-characterized patient cohort, containing pancreatic NET of 61 patients. To calculate the proliferation index, number of positive tumor nuclei was divided by the total number of tumor nuclei. Labeling index was compared to mitotic counts in whole tissue sections and to clinical outcome. Linear regression analysis, intraclass comparison, and log-rank analysis were performed. Intraclass correlation showed moderate-to-fair agreement. Especially low proliferating tumors were affected by interlaboratory differences. Log-rank analysis was performed for each lab and resulted in three different cutoffs (5.0, 3.0, and 0.5 %). Every calculated cutoff stratified the patient cohort to a significant extent for the underlying stain (p < 0.001, <0.001, and <0.001) but showed no or lesser significance when applied to the other stains. Significant and relevant interlab differences for MIB1 exist. Since the MIB1 proliferation index influences grading, local cutoffs or external standardization should urgently be introduced to achieve reliability and reproducibility.

Circulating oxidized LDL is associated with the occurrence of echolucent plaques in the carotid artery in 61-year-old men.

OBJECTIVE The aim of this study was to elucidate the relationship between the echogenicity of carotid artery plaques and the following risk factors: circulating oxLDL, hsCRP, the metabolic syndrome (MetS), and several of the traditional cardiovascular (CV) risk factors. MATERIAL AND METHODS A cross-sectional population-based study of 513 sixty-one-year-old men. The levels of circulating oxLDL were determined in plasma samples by sandwich ELISA utilizing a specific murine monoclonal antibody (mAb-4E6). High-sensitivity CRP was measured in plasma by ELISA. Plaque occurrence, size and echogenicity were evaluated from B-mode ultrasound registrations in the carotid arteries. Plaque echogenicity was assessed based on a four-graded classification scale. RESULTS A higher frequency of echolucent carotid plaques was observed with increasing levels of oxLDL and systolic blood pressure (p = 0.008 and p = 0.041, respectively). Subjects with the MetS had a significantly higher frequency of echogenic plaques than subjects without the MetS (p = 0.009). In a multiple logistic regression analysis, oxLDL turned out to be independently associated with echolucent carotid plaques. CONCLUSIONS The occurrence of echolucent carotid plaques was associated with oxLDL and systolic blood pressure, and oxLDL was associated with echolucent carotid plaques independently of systolic blood pressure.

Circulating oxidized low-density lipoprotein is associated with echolucent plaques in the femoral artery independently of hsCRP in 61-year-old men.

OBJECTIVES The aim of the study was to test the hypothesis that circulating markers of inflammation (high-sensitive C-reactive protein, hsCRP) and oxidative modification of lipids (oxidized low-density lipoprotein, oxLDL) were associated with the occurrence of echolucent rather than echogenic femoral artery plaques in a cross-sectional population based cohort of 513, 61-year-old men. BACKGROUND The relationships between circulating oxLDL, hsCRP and the occurrence of echolucent plaques in the femoral artery have not previously been investigated. METHODS The levels of circulating oxLDL and hsCRP were determined in plasma by ELISA. Plaque occurrence, size and echogenicity were measured by B-mode ultrasound in the right femoral artery. Assessment of plaque echogenicity was based on the classification (grades 1-4) proposed by Gray-Weale et al. RESULTS A higher frequency of echolucent femoral plaques was observed in subjects with the metabolic syndrome and current smokers (p=0.01 and p<0.001, respectively) as well as with increasing levels of oxLDL and hsCRP (p=0.002 and p=0.005, respectively). In a multiple logistic regression analysis oxLDL and current smokers turned out to be independent associated with the presence of echolucent femoral artery plaques. CONCLUSIONS The results of the present study support our hypothesis that circulating oxLDL is a marker of an unstable echolucent plaque phenotype in the femoral artery in man.

Medical, psychological and socio-economic implications of chronic hand eczema: a cross-sectional study.

BACKGROUND Hand eczema (HE) is a common skin disease with major medical psychological and socio-economic implications. Onset and prognosis of HE are determined by individual as well as environmental factors. So far, most epidemiological data on HE have been reported from Scandinavian and recently German studies. OBJECTIVE To investigate the characteristics and medical care of patients with chronic HE (CHE) in Switzerland, and identify risk factors. METHODS In this cross-sectional study, data from patients with chronic HE were obtained by means of medical history, dermatological examination and patient questionnaires. Multiple logistic regression analysis was applied to identify risk factors for high severity and dermatology life quality index (DLQI). RESULTS In seven dermatology departments, 199 patients (mean age 40.4 years, 50.8% female) with CHE (mean duration 6.6 years) were enrolled. Moderate to severe HE was reported by 70.9% of patients, and was associated with age <30 or >50 years, localization of lesions and pruritus. Because of the CHE, 37.3% of patients were on sick leave over the past 12 months, 14.8% had changed or lost their job. Practically all patients applied topical therapy, 21% were treated with alitretinoin, and 21% with psoralen plus UVA light (PUVA). The effects on the health-related quality of life was moderate to large in 33.7% and 39.4% of CHE patients, respectively. Factors associated with a high impact on DLQI (mean 9.7 ± 5.8) were female sex, lesions on back of the hands and pruritus as well as mechanical skin irritation and wearing gloves. CONCLUSION In agreement with recent studies, the Swiss data demonstrate the high impact of CHE on medical well-being, patient quality of life and work ability. As it is associated with an intense use of health care services, high rate of sick leave, job loss and change, CHE may cause a high socio-economic burden.

Endothelial progenitor cells as a biological marker of peripheral artery disease.

The role of endothelial progenitor cells (EPCs) in peripheral artery disease (PAD) remains unclear. We hypothesized that EPC mobilization and function play a central role in the development of endothelial dysfunction and directly influence the degree of atherosclerotic burden in peripheral artery vessels. The number of circulating EPCs, defined as CD34(+)/KDR(+) cells, were assessed by flow cytometry in 91 subjects classified according to a predefined sample size of 31 non-diabetic PAD patients, 30 diabetic PAD patients, and 30 healthy volunteers. Both PAD groups had undergone endovascular treatment in the past. As a functional parameter, EPC colony-forming units were determined ex vivo. Apart from a broad laboratory analysis, a series of clinical measures using the ankle-brachial index (ABI), flow-mediated dilatation (FMD) and carotid intima-media thickness (cIMT) were investigated. A significant reduction of EPC counts and proliferation indices in both PAD groups compared to healthy subjects were observed. Low EPC number and pathological findings in the clinical assessment were strongly correlated to the group allocation. Multivariate statistical analysis revealed these findings to be independent predictors of disease appearance. Linear regression analysis showed the ABI to be a predictor of circulating EPC number (p=0.02). Moreover, the functionality of EPCs was correlated by linear regression (p=0.017) to cIMT. The influence of diabetes mellitus on EPCs in our study has to be considered marginal in already disease-affected patients. This study demonstrated that EPCs could predict the prevalence and severity of symptomatic PAD, with ABI as the determinant of the state of EPC populations in disease-affected groups.

Influence of previous surgery on patient-rated outcome after surgery for degenerative disorders of the lumbar spine.

PURPOSE Few studies have used multivariate models to quantify the effect of multiple previous spine surgeries on patient-oriented outcome after spine surgery. This study sought to quantify the effect of prior spine surgery on 12-month postoperative outcomes in patients undergoing surgery for different degenerative disorders of the lumbar spine. METHODS The study included 4940 patients with lumbar degenerative disease documented in the Spine Tango Registry of EUROSPINE, the Spine Society of Europe, from 2004 to 2015. Preoperatively and 12 months postoperatively, patients completed the multidimensional Core Outcome Measures Index (COMI; 0-10 scale). Patients' medical history and surgical details were recorded using the Spine Tango Surgery 2006 and 2011 forms. Multiple linear regression models were used to investigate the relationship between the number of previous surgeries and the 12-month postoperative COMI score, controlling for the baseline COMI score and other potential confounders. RESULTS In the adjusted model including all cases, the 12-month COMI score showed a 0.37-point worse value [95 % confidence intervals (95 % CI) 0.29-0.45; p < 0.001] for each additional prior spine surgery. In the subgroup of patients with lumbar disc herniation, the corresponding effect was 0.52 points (95 % CI 0.27-0.77; p < 0.001) and in lumbar degenerative spondylolisthesis, 0.40 points (95 % CI 0.17-0.64; p = 0.001). CONCLUSIONS We were able to demonstrate a clear "dose-response" effect for previous surgery: the greater the number of prior spine surgeries, the systematically worse the outcome at 12 months' follow-up. The results of this study can be used when considering or consenting a patient for further surgery, to better inform the patient of the likely outcome and to set realistic expectations.