Data integration for prediction of weight loss in randomized controlled dietary trials.

Diet is an important component in weight management strategies, but heterogeneous responses to the same diet make it difficult to foresee individual weight-loss outcomes. Omics-based technologies now allow for analysis of multiple factors for weight loss prediction at the individual level. Here, we classify weight loss responders (N = 106) and non-responders (N = 97) of overweight non-diabetic middle-aged Danes to two earlier reported dietary trials over 8 weeks. Random forest models integrated gut microbiome, host genetics, urine metabolome, measures of physiology and anthropometrics measured prior to any dietary intervention to identify individual predisposing features of weight loss in combination with diet. The most predictive models for weight loss included features of diet, gut bacterial species and urine metabolites (ROC-AUC: 0.84-0.88) compared to a diet-only model (ROC-AUC: 0.62). A model ensemble integrating multi-omics identified 64% of the non-responders with 80% confidence. Such models will be useful to assist in selecting appropriate weight management strategies, as individual predisposition to diet response varies.

Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial.

OBJECTIVE: To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. DESIGN: 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. RESULTS: 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. CONCLUSION: Compared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation. TRIAL REGISTRATION NUMBER: NCT01731366; Results.

A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults.

Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.

Arterial spin labeling: a technical overview.

Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging perfusion method based on changes in net-magnetization of blood water. The absence of contrast use and ionizing radiation, renders ASL valuable in hyper-acute settings as a monitoring tool for repeated dynamical measurements during and after intervention, and for patients with known co-morbidities. This text provides a short methodological introduction to ASL and contrasts it with traditional contrast-enhanced perfusion imaging. The review focused on sequence usefulness in the clinical setting of acute cerebral ischemia investigation.

Reliability of standing weight-bearing (0.25T) MR imaging findings and positional changes in the lumbar spine.

OBJECTIVE: To test the reliability and absolute agreement of common degenerative findings in standing positional magnetic resonance imaging (pMRI). METHODS AND MATERIALS: Low back pain patients with and without sciatica were consecutively enrolled to undergo a supine and standing pMRI. Three readers independently evaluated the standing pMRI for herniation, spinal stenosis, spondylolisthesis, HIZ lesions and facet joint effusion. The evaluation included a semi-quantitative grading of spinal stenosis, foraminal stenosis and spinal nerve root compression. The standing pMRI images were evaluated with full access to supine MRI. In case lower grades or the degenerative findings were not present in the supine images, this was reported separately as position-dependent changes. A subsample of 20 pMRI examinations was reevaluated after two months. The reproducibility was assessed by inter- and intra-reader reliability (kappa statistic) and absolute agreement between readers. RESULTS: Fifty-six patients were included in this study. There was fair-to-substantial inter-reader reliability (κ 0.47 to 0.82) and high absolute agreement (72.3% to 99.1%) for the pMRI findings. The intra-reader assessment showed similar reliability and agreement (κ 0.36 to 0.85; absolute agreement: 62.5% to 98.8%). Positional changes between the supine and standing position showed a fair-to-moderate inter- and intra-reader reliability (κ 0.25 to 0.52; absolute agreement: 97.0% to 99.1). CONCLUSION: Evaluation of the lumbar spine for degenerative findings by standing pMRI has acceptable reproducibility; however, positional changes from the supine to the standing position as an independent outcome should be interpreted with caution because of lower reliability, which calls for further standardisation.

A computer-based method for precise detection and calculation of affected skin areas.

BACKGROUND: The aim of this study was to describe and validate a method to obtain reproducible and comparable results concerning extension of a specific skin area, unaffected by individual differences in body surface area. METHODS: A phantom simulating the human torso was equipped with three irregular areas representing the increasing extension of an affected skin area over time. A large sheet of flexible calques paper was placed at the phantom, and five clinicians copied the three irregular shapes two times, resulting in 60 copies. Subsequently, a digital photograph was taken of the calques papers with a clinical ruler placed at the margin. The images were postprocessed and measured in the program 'ImageJ' by two observers. An exact area measurement of the three irregular shapes was performed for comparison. RESULTS: We found an interobserver variation of 0·36% when comparing the measurements of all three areas. Comparing observer measurements with the exact areas size, we found an underestimate of 2·52%. We observed a tendency that the discrepancy in measurement increases when the measured area decreases. CONCLUSION: We find this method accurate, reproducible and easy to use. The presented method can be of help when documenting psoriasis and other dermatologic conditions as well as when exploring the effects of new types and variations of ultrasound-guided peripheral nerve blocks - especially in study volunteers.

Computed Tomography--Verified Leukoaraiosis Is a Risk Factor for Post-thrombolytic Hemorrhage.

BACKGROUND: Is computed tomography (CT)-verified leukoaraiosis (LA) a risk factor for post-thrombolytic hemorrhagic transformation and symptomatic hemorrhage? METHODS: (1) Retrospective analysis based on a prospectively planned single-center registry of consecutive tissue plasminogen activator (tPA)-treated patients within 4.5 hours from symptom onset. Standard work-up included baseline noncontrast CT and CT angiography and next day follow-up noncontrast CT. Baseline noncontrast CT LA was graded using Fazekas' score and dichotomized as the absence (Fazekas, 0) or the presence (Fazekas, 1-3). Hemorrhagic transformation was rated using European Cooperative Acute Stroke Study (ECASS) criteria. Symptomatic intracerebral hemorrhage was defined as hemorrhage and deterioration of National Institutes of Health Stroke Scale (NIHSS) of 4 or greater within 36 hours from symptom onset. Endovascularly treated patients were excluded. (2) Pooled analysis with 1312 tPA-treated patients from literature. RESULTS: In all, 311 tPA-treated patients were included between April 2009 and July 2012. LA was present in 113 (36%). Twenty-three (7%) showed hemorrhagic transformation. LA positive patients had significantly higher hemorrhagic transformation frequency (11.5%, P = .04). LA doubled hemorrhagic transformation risk (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.4-5.8). Only 4 patients developed symptomatic intracerebral hemorrhage, 3 with LA. LA was not an independent risk factor for hemorrhagic transformation (P = .2). Pooled analysis of 1623 patients in total, hereof 479 LA positive patients, showed significantly higher symptomatic intracerebral hemorrhage frequency in 35 (7.3%) LA positive than that in 44 (3.8%) LA negative patients, (P = .005) and doubled symptomatic intracerebral hemorrhage risk in LA positives (OR, 1.97; 95% CI 1.22-3.19). CONCLUSIONS: LA doubles the risk of post-thrombolytic hemorrhagic transformation and symptomatic hemorrhage; this finding does not support withholding thrombolysis from patients with LA.

Showing no spot sign is a strong predictor of independent living after intracerebral haemorrhage.

BACKGROUND: A spot sign on computed tomography angiography (CTA) is a potentially strong predictor of poor outcome on ultra-early radiological imaging. The aim of this study was to assess the spot sign as a predictor of functional outcome at 3 months as well as long-term mortality, with a focus on the ability to identify patients with a spontaneous, acceptable outcome. METHODS: In a prospective, consecutive single-centre registry of acute stroke patients, we investigated patients with spontaneous intracerebral haemorrhage (ICH) admitted within 4.5 h after symptom onset from April 2009 to January 2013. The standard work-up in our centre included CTA for spot sign status, unless a contraindication was present. Modified Rankin Scale (mRS) scores were assessed at 3 months in the outpatient clinic or by telephone interviews. Long-term mortality was assessed by electronic chart follow-up for up to 1,500 days. RESULTS: Of the 128 patients, 37 (28.9%) had a spot sign on admission CTA. The presence of a spot sign was associated with larger median admission haematoma volume [38.0 ml (IQR 18.0-78.0) vs. 12.0 ml (5.0-24.0); p<0.0001] and higher median National Institutes of Health Stroke Scale score [19 (IQR 12-23) vs. 12 (6-16); p<0.0001]. Three months after stroke, the median functional outcome was considerably better in patients without spot sign [mRS score 3 (IQR 2-4) vs. 6 (4-6); p<0.0001]. The absence of a spot sign showed a sensitivity and specificity for good outcome (mRS scores 0-2) of 0.91 and 0.36, respectively. The presence of a spot sign was, in multivariate models, an independent inverse predictor of good 3-month outcome (OR 0.17; 95% CI: 0.03-0.88) as well as a prominent independent predictor of poor 3-month outcome (mRS scores 5-6; OR 3.40; 95% CI: 1.10-10.5) and death during follow-up (HR 3.04; 95% CI: 1.45-6.34). Patients with a spot sign surviving the acute phase had long-term survival comparable to patients with no spot sign. CONCLUSION: The absence or presence of a spot sign is a reliable ultra-early predictor of long-term mortality and functional outcome in patients with spontaneous ICH.

Ultrasound-guided single-penetration dual-injection block for leg and foot surgery: a prospective, randomized, double-blind study.

BACKGROUND AND OBJECTIVES: We describe a new approach to blocking the sciatic and saphenous nerves in the proximal thigh (level of the lesser trochanter or immediately below) using a single-penetration dual-injection (SPEDI) technique. The popliteal-sciatic approach necessitates repositioning of the leg exposing the popliteal fossa and an extra injection for the saphenous nerve (SAN) block at the midthigh level. We introduce an alternative, effective, and possibly faster method. METHODS: Sixty patients undergoing leg and foot surgery under general anesthesia were included. We deposited 15 mL of ropivacaine 0.75% around the sciatic nerve (SCN) and 5 mL of ropivacaine 0.75% at the SAN. Patients were randomized to the popliteal-sciatic/saphenous technique or the SPEDI technique. The primary outcome measure was performance time. Positioning time, pain assessment, nausea in the postanesthesia care unit, sufentanil demand, dermatomal anesthesia, and degree of motor blockade were also recorded. RESULTS: Performance time was significantly faster with the SPEDI technique (median time, 110 seconds [range, 57-315 seconds] vs 246 seconds [range, 163-472 seconds]; P < 0.0001). Positioning time was significantly shorter with the SPEDI technique (P < 0.0001). No other statistically significant differences were recorded. CONCLUSIONS: The SPEDI block resulted in significantly faster performance time and reduced positioning time with statistically equal efficacy in relation to pain assessment, nausea, sufentanil demand, dermatomal anesthesia, and motor blockade. The SPEDI block is statistically an equally effective alternative to the traditional popliteal-sciatic/saphenous block combination for leg and foot surgery, but it is faster, requires only 1 skin penetration, and does not require repositioning of the leg.

Distribution patterns, dermatomal anesthesia, and ropivacaine serum concentrations after bilateral dual transversus abdominis plane block.

BACKGROUND AND OBJECTIVES: The ability of transversus abdominis plane (TAP) blocks to anesthetize the upper abdomen remains debatable. We aimed to describe the local anesthetic distribution following ultrasound-guided TAP blocks with repeated magnetic resonance imaging investigations and to relate this to the resulting dermatomal anesthesia. METHODS: Eight volunteers were included in a randomized, observer-blinded study. Sixty milliliters of ropivacaine 0.375% was administered: 1 injection of 30 mL as a lateral classic TAP block, followed by a sham upper intercostal TAP block, and on the contralateral side, 2 separate 15-mL injections at the upper intercostal and lateral classic TAP plexuses, respectively. The primary outcome measure was magnetic resonance imaging-assessed area expansion of all injectates over a 6-hr period. Dermatomal anesthesia and sequential serum ropivacaine levels were recorded at the same time intervals. RESULTS: All injectate areas expanded in a statistically significant manner in the anterior abdominal wall. Lateral classic TAP blocks with 30-mL injectates did not extend into the upper intercostal TAP plexus. The dual 15-mL injectates on the other hemiabdomen remained within the upper intercostal and lateral classic TAP compartments and resulted in significantly (P < 0.018) more widespread dermatomal anesthesia. Measured serum ropivacaine concentrations were below the potential level of toxicity. CONCLUSIONS: Magnetic resonance imaging analysis revealed a significant time-dependent expansion of injectates. Magnetic resonance imaging and the degree of dermatomal anesthesia confirmed that the upper and lateral TAP compartments do not appear to communicate. Separate injections at the upper intercostal and lateral classic TAP plexuses are necessary to block the entire abdominal wall.

Interobserver and intraobserver variation of two-dimensional and three-dimensional anal endosonography in the evaluation of recurrent anal cancer.

PURPOSE: This study was designed to evaluate the interobserver and intraobserver agreement of two-dimensional (2-D) and three-dimensional (3-D) anal endosonography for the detection of local recurrence anal carcinoma. METHODS: Thirty-six patients were treated for anal carcinoma, and seven had recurrent disease. They were investigated by using 3-D endosonography at Rigshospitalet from July 2001 to January 2005 because of suspected local recurrence. The 3-D endosonographic examinations were reviewed from the hard disc by two observers who twice reviewed all 2-D examinations (the axial projection) as well as all 3-D examinations (the axial, as well as the reconstructed coronal and sagittal projections). The observers scored each examination according to the following scale regarding presence of local recurrence: 1 = no finding/benign findings; 2 = properly benign findings; 3 = suspicious findings/malignant findings. Kappa statistic-statistic was used to evaluate interobserver and intraobserver variation. RESULTS: Three-dimensional endosonography achieved better interobserver agreement than 2-D endosonography: kappa 3-D 0.34-047 vs. kappa 2-D 0.15-0.28 and better intraobserver agreement: kappa 3-D 0.34-0.62 vs. kappa 2-D 0.22-0.28. These differences showed P < 0.05. CONCLUSIONS: Three-dimensional endosonography proved to have significantly better interobserver and intraobserver agreement than 2-D endosonography concerning detection of recurrent anal cancer. Three-dimensional endosonography seems to be less dependent of the individual examiner than 2-D endosonography.

Three-dimensional anal endosonography may improve detection of recurrent anal cancer.

PURPOSE: In our center since 2001, follow-up examination has included three-dimensional endosonography in all patients with suspicion of local recurrence of anal cancer. This study was designed to investigate whether three-dimensional endosonography surpassed two-dimensional endosonography as a diagnostic tool for patients with suspected local recurrence. METHODS: This prospective study included 38 consecutive patients who have had anal carcinoma and were investigated using three-dimensional endosonography in combination with anoscopy and digital rectal examination at Rigshospitalet from July 2001 to January 2005 under suspicion of local recurrence. All endosonographic examinations-two-dimensional, three-dimensional, and three-dimensional in combination with anoscopy and digital rectal examination-were evaluated by blinded observers. The observers scored each examination according to a five-point scale in which a score from 1 to 3 was regarded as benign endosonographic findings and a score from 4 to 5 was regarded as malignant endosonographic findings. The endosonographic diagnosis for each examination was compared with histologic evaluation or when no biopsy had been taken with a follow-up period of at least six months. If a patient showed no signs of local recurrence in the follow-up period, no local recurrence was considered to be present at the time of the investigation. RESULTS: The sensitivity was 1.0 for three-dimensional endosonography in combination with palpation, 0.86 for three-dimensional endosonography alone, and 0.57 for two-dimensional endosonography. The differences between two-dimensional endosonography and three-dimensional endosonography alone as well as two-dimensional endosonography and three-dimensional endosonography + anoscopy and digital rectal examination both reached significance with P values <0.05. CONCLUSIONS: This study indicates that three-dimensional endosonography surpasses two-dimensional endosonography in the evaluation of patients with suspicion of local recurrence of anal cancer especially in combination with anoscopy and digital rectal examination.

Three-dimensional anal endosonography may improve staging of anal cancer compared with two-dimensional endosonography.

PURPOSE: Three-dimensional (3-D) endosonography is a new method of staging anal carcinoma that has not yet been validated in comparison with two-dimensional (2-D) endosonography, the latter using only a single scan plane. The aim of this study was to investigate the differences between the two endosonographic techniques. METHODS: Thirty patients with an endosonographically detectable anal tumor were examined with a 10 MHz rotating endoprobe. Cross-sectional images of the anal sphincters were stored on a 3-D system during retraction of the endoprobe through the anal canal. Afterwards, any projection could be reconstructed. Cross-sectional images (2-D) were compared with reconstructed projections (3-D) according to five parameters concerning tumor spread and presence of regional lymph nodes. In this study, a scale of 0 to 5 points on critical issues was used; ideally, the results should be identical in 2-D and 3-D endosonography. RESULTS: The 3-D method detected a median of 5 diagnostic findings, compared with a median of 4 findings with the 2-D method ( P = 0.001). In eight patients the lateral tumor margin was visualized only by 3-D endosonography. The median number of lymph nodes visualized in 3-D was 1 (range, 0-13), in 2-D the median number was 0 (range, 0-6), P = 0.002. CONCLUSIONS: Use of 3-D endosonography in patients with anal carcinoma improves detection of perirectal lymph nodes and may improve that of tumor invasion, compared with 2-D endosonography. This may affect local tumor staging and thus planning of treatment. A study with histopathologic correlation is needed to verify this endosonographic study.