Transcutaneous vagal nerve stimulation for treating gastrointestinal symptoms in individuals with diabetes: a randomised, double-blind, sham-controlled, multicentre trial.

AIMS/HYPOTHESIS: Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study. METHODS: This study included adults (aged 20-86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function. RESULTS: Sixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: -0.26 ± 0.64 vs -0.17 ± 0.62, p=0.44; GSRS: -0.35 ± 0.62 vs -0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: -0.47 ± 0.78 vs -0.33 ± 0.75, p=0.34; GSRS: -0.46 ± 0.90 vs -0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs -19 min, p=0.04). Segmental intestinal transit times and cardiovascular autonomic measurements did not differ between treatment groups (all p>0.05). The tVNS was well-tolerated. CONCLUSIONS/INTERPRETATION: Cervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04143269 FUNDING: The study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045).

Monocyte recruitment in venous pulmonary embolism at time of cancer diagnosis in upper gastrointestinal cancer patients.

Upper gastrointestinal cancer is frequently complicated by venous thromboembolisms (VTE), especially pulmonary embolisms (PE) increase the mortality rate. Monocytes are a part of the innate immune system and up-regulation may indicate an ongoing inflammatory response or infectious disease and has lately been associated with a moderate risk of suffering from VTE. This prospectively study aims to compare the incidence of pulmonary embolism with markers of coagulation and compare it to the absolute monocyte count. A consecutive cohort of 250 patients with biopsy proven upper gastrointestinal cancer (i.e. pancreas, biliary tract, esophagus and gastric cancer) where included at the time of cancer diagnosis and before treatment. All patients underwent bilateral compression ultrasonography for detection of deep vein thrombosis (DVT). Of these 143 had an additionally pulmonary angiografi (CTPA) with the staging computer tomography. 13 of 250 patients (5.2%) had a DVT and 11 of 143 (7.7%) had CTPA proven PE. PE was significantly more common among patients with elevated D-dimer (OR 11.62, 95%CI: 1.13-119, P = 0.039) and elevated absolute monocyte count (OR 7.59, 95%CI: 1.37-41.98, P = 0.020). Only patients with pancreatic cancer had a significantly higher risk of DVT (OR 11.03, 95%CI: 1.25-97.43, P = 0.031). The sensitivity of absolute monocyte count was 63.6 (95%CI: 30.8-89.1) and specificity 80.3 (95%CI: 72.5-86.7), with a negative predictive value of 96.4 (95%CI: 91-99) in PE. An increased absolute monocyte count was detected in patients suffering from PE but not DVT, suggesting a possible interaction with the innate immune system.

Vitamin K supplementation and bone mineral density in dialysis: results of the double-blind, randomized, placebo-controlled RenaKvit trial.

BACKGROUND: Vitamin K deficiency is highly prevalent in patients on dialysis and may contribute to their low bone mineral density (BMD) and increased risk of fracture. This study investigated the effect of menaquinone-7 (MK-7) supplementation on BMD in patients on chronic dialysis. METHODS: In a multicentre, double-blind, placebo-controlled intervention trial, 123 patients on chronic dialysis were randomised to a daily oral supplement of either MK-7 360 µg or placebo for 2 years. BMD of the distal radius (1/3, mid, ultradistal and total), femoral neck, lumbar spine (L1-L4) and whole body was assessed by dual-energy X-ray absorptiometry. Serum levels of vitamin K1 and MK-7 and plasma levels of total osteocalcin, dephosphorylated-uncarboxylated matrix Gla protein and protein induced by vitamin K absence II were measured to assess vitamin K status. RESULTS: After 2 years, an accelerated BMD loss of the 1/3 distal radius was found with MK-7 supplementation {mean difference of changes relative to placebo -0.023 g/cm2 [95% confidence interval (CI) -0.039 to -0.008]}, whereas the decrease in lumbar spine BMD seen in the placebo group was prevented [mean difference of changes between groups 0.050 g/cm2 (95% CI 0.015-0.085)]. No significant effects were observed at the remaining skeletal sites. Vitamin K status strongly improved in MK-7-supplemented participants. CONCLUSION: Compared with placebo, an accelerated BMD loss of the 1/3 distal radius was found after 2 years of MK-7 supplementation, whereas a decline in lumbar spine BMD was prevented. As such, MK-7 supplementation might modify BMD site-specifically in patients on dialysis. In aggregate, our findings do not support MK-7 supplementation to preserve bone in patients on dialysis.

Pan-alimentary assessment of motility, luminal content, and structures: an MRI-based framework.

BACKGROUND: Gastrointestinal symptoms originating from different segments overlap and complicate diagnosis and treatment. In this study, we aimed to develop and test a pan-alimentary framework for the evaluation of gastrointestinal (GI) motility and different static endpoints based on magnetic resonance imaging (MRI) without contrast agents or bowel preparation. METHODS: Twenty healthy volunteers (55.6 ± 10.9 years, BMI 30.8 ± 9.2 kg/m2) underwent baseline and post-meal MRI scans at multiple time points. From the scans, the following were obtained: Gastric segmental volumes and motility, emptying half time (T50), small bowel volume and motility, colonic segmental volumes, and fecal water content. Questionnaires to assess GI symptoms were collected between and after MRI scans. KEY RESULTS: We observed an increase in stomach and small bowel volume immediately after meal intake from baseline values (p<.001 for the stomach and p=.05 for the small bowel). The volume increase of the stomach primarily involved the fundus (p<.001) in the earliest phase of digestion with a T50 of 92.1 ± 35.3 min. The intake of the meal immediately elicited a motility increase in the small bowel (p<.001). No differences in colonic fecal water content between baseline and 105 min were observed. CONCLUSION & INFERENCES: We developed a framework for a pan-alimentary assessment of GI endpoints and observed how different dynamic and static physiological endpoints responded to meal intake. All endpoints aligned with the current literature for individual gut segments, showing that a comprehensive model may unravel complex and incoherent gastrointestinal symptoms in patients.

Overlap and cumulative effects of pancreatic duct obstruction, abnormal pain processing and psychological distress on patient-reported outcomes in chronic pancreatitis.

OBJECTIVE: Several factors have been suggested to mediate pain in patients with chronic pancreatitis. However, it is unknown whether these factors are overlapping and if they have cumulative effects on patient-reported outcomes (PROs). DESIGN: We performed a multicentre cross-sectional study of 201 prospectively enrolled subjects with definitive chronic pancreatitis. All subjects underwent evaluation for pancreatic duct obstruction, abnormalities in pain processing using quantitative sensory testing, and screening for psychological distress (anxiety, depression and pain catastrophising) based on validated questionnaires. Abnormality was defined by normal reference values. PROs included pain symptom severity (Brief Pain Inventory short form) and quality of life (EORTC-QLQ-C30 questionnaire). Associations between pain-related factors and PROs were investigated by linear trend analyses, multiple regression models and mediation analyses. RESULTS: Clinical evaluation suggestive of pancreatic duct obstruction was observed in 29%, abnormal pain processing in 23%, anxiety in 47%, depression in 39% and pain catastrophising in 28%; each of these factors was associated with severity of at least one PRO. Two or more factors were present in 51% of subjects. With an increasing number of factors, there was an increase in pain severity scores (p<0.001) and pain interference scores (p<0.001), and a reduction in quality of life (p<0.001). All factors had independent and direct effects on PROs, with the strongest effect size observed for psychological distress. CONCLUSION: Pain-related factors in chronic pancreatitis are often present in an overlapping manner and have a cumulative detrimental effect on PROs. These findings support a multidisciplinary strategy for pain management. TRIAL REGISTRATION NUMBER: The study was registered with ClinicalTrials.gov (NCT03434392).

Arteria lusoria: a trick of nature.

Dysphagia has several typical causes. In this case report a young adult with difficulties in swallowing since childhood is diagnosed with a rare anatomical variation of the aortal branches.

Placental transverse relaxation time (T2) estimated by MRI: Normal values and the correlation with birthweight.

INTRODUCTION: Placental transverse relaxation time (T2) assessed by MRI may have the potential to improve the antenatal identification of small for gestational age. The aims of this study were to provide normal values of placental T2 in relation to gestational age at the time of MRI and to explore the correlation between placental T2 and birthweight. MATERIAL AND METHODS: A mixed cohort of 112 singleton pregnancies was retrieved from our placental MRI research database. MRI was performed at 23.6-41.3 weeks of gestation in a 1.5T system (TE (8): 50-440 ms, TR: 4000 ms). Normal pregnancies were defined by uncomplicated pregnancies with normal obstetric outcome and birthweight deviation within ±1 SD of the expected for gestational age. The correlation between placental T2 and birthweight was investigated using the following outcomes; small for gestational age (birthweight ≤-2 SD of the expected for gestational age) and birthweight deviation (birthweight Z-scores). RESULTS: In normal pregnancies (n = 27), placenta T2 showed a significant negative linear correlation with gestational age (r = -.91, P = .0001) being 184 ms ± 15.94 ms (mean ± SD) at 20 weeks of gestation and 89 ms ± 15.94 ms at 40 weeks of gestation. Placental T2 was significantly reduced among small-for-gestational-age pregnancies (mean Z-score -1.95, P < .001). Moreover, we found a significant positive correlation between placenta T2 deviation (Z-score) and birthweight deviation (Z-score) (R2  = .26, P = .0001). CONCLUSIONS: This study provides normal values of placental T2 to be used in future studies on placental MRI. Placental T2 is closely related to birthweight and may improve the antenatal identification of small-for-gestational-age pregnancies.

MRI analysis of fecal volume and dryness: Validation study using an experimental oxycodone-induced constipation model.

BACKGROUND: Opioids are known to affect gastrointestinal motility, but their effect on fluid absorption and secretion is poorly understood in humans. PURPOSE: To investigate the effect of oxycodone on colonic fecal volume and stool dryness by using a novel MRI-based technique. STUDY TYPE: Prospective, randomized, double-blinded, crossover study. SUBJECTS: Twenty-five healthy male volunteers (median age: 24 years [range: 21-56]; mean body mass index [BMI]: 23.9 kg/m2 [range: 22.9-25.0]) without known gastrointestinal disease. FIELD STRENGTH/SEQUENCE: T2 -weighted and two-point Dixon MRI scans of the abdomen at 1.5 T. ASSESSMENT: Subjects were treated for 5 days with prolonged-release oxycodone or a placebo. Imaging was performed on the first and last study day in each period. Images of the colon were analyzed with semiautomatic k-means-based segmentation software. Regional colonic fecal volumes were quantified excluding gas volume and colon wall. Two-point Dixon and T2 -weighted MRI signal intensity were assessed as a proxy of colonic stool dryness. Data were obtained in a previously reported study. STATISTICAL TESTS: Intraclass correlation coefficients were used to test the reliability of measurements between days, while repeated measures mixed models were applied to test treatment effects. RESULTS: After oxycodone treatment, total colonic fecal volume was significantly increased compared with placebo (mean change 100 mL vs. -13 mL; P = 0.001), with the largest increase (24%) observed in the ascending colon/cecum (P = 0.001). Dixon signal increased (less water in colon content) after oxycodone treatment compared with placebo (mean 0.09 vs. -0.02; P < 0.001). T2 -weighted signal decreased (less water in colon content) after oxycodone treatment compared with placebo (mean -0.03 vs. 0.03; P = 0.002). DATA CONCLUSION: The 5-day oxycodone treatment increased colonic fecal volume and increased stool dryness compared with placebo. This imaging-based method for noninvasive analysis of colon content has the potential to characterize gastrointestinal symptoms in general, such as in constipation. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:733-745.

Pancreatic calcifications associate with diverse aetiological risk factors in patients with chronic pancreatitis: A multicentre study of 1500 cases.

BACKGROUND: Pancreatic calcifications is a common finding in patients with chronic pancreatitis (CP), but the underlying pathophysiology is incompletely understood. Past studies for risk factors of calcifications have generally been focused on single parameters or limited by small sample sizes. The aim of this study was to explore several patient and disease characteristics and their associations with pancreatic calcifications in a large cohort of CP patients with diverse aetiological risk factors. METHODS: This was a multicentre, cross-sectional study including 1509 patients with CP. Patient and disease characteristics were compared for patients with calcifications (n = 912) vs. without calcifications (n = 597). Multivariable logistic regression was performed to assess the parameters independently associated with calcifications. RESULTS: The mean age of patients was 53.9 ±â€¯14.5 years and 1006 (67%) were men. The prevalence of calcifications was 60.4% in the overall patient cohort, but highly variable between patients with different aetiological risk factors (range: 2-69%). On multivariate analysis, alcoholic aetiology (OR 1.76 [95% CI, 1.39-2.24]; p < 0.001) and smoking aetiology (OR 1.77 [95% CI, 1.39-2.26], p < 0.001) were positively associated with the presence of calcifications, while an autoimmune aetiology was negatively associated with calcifications (OR 0.15 [95% CI, 0.08-0.27], p < 0.001). Patients with pancreatic calcifications were more likely to have undergone pancreatic duct stenting (OR 1.59 [95%CI, 1.16-2.19], p = 0.004). CONCLUSION: The presence of pancreatic calcifications is associated with diverse aetiological risk factors in patients with CP. This observation attest to the understanding of CP as a complex disease and may have implications for disease classification.

Superior Reproducibility of the Leading to Leading Edge and Inner to Inner Edge Methods in the Ultrasound Assessment of Maximum Abdominal Aortic Diameter.

OBJECTIVES: Controversy exists regarding optimal caliper placement in ultrasound assessment of maximum abdominal aortic diameter. This study aimed primarily to determine reproducibility of caliper placement in relation to the aortic wall with the three principal methods: leading to leading edge (LTL), inner to inner edge (ITI), and outer to outer edge (OTO). The secondary aim was to assess the mean difference between the OTO, ITI, and LTL diameters and estimate the impact of using either of these methods on abdominal aortic aneurysm (AAA) prevalence in a screening program. METHODS: Radiologists (n=18) assessed the maximum antero-posterior abdominal aortic diameter by completing repeated caliper placements with the OTO, LTL, and ITI methods on 50 still abdominal aortic images obtained from an AAA screening program. Inter-observer reproducibility was calculated as the limit of agreement with the mean (LoA), which represents expected deviation of a single observer from the mean of all observers. Intra-observer reproducibility was assessed averaging the LoA for each observer with their repeated measurements. Based on data from an AAA screening trial and the estimated mean differences between the three principal methods, AAA prevalence was estimated using each of the methods. RESULTS: The inter-observer LoA of the OTO, ITI, and LTL was 2.6, 1.9, and 1.9 mm, whereas the intra-observer LoA was 2.0, 1.6, and 1.5 mm, respectively. Mean differences of 5.0 mm were found between OTO and ITI measurements, 2.6 mm between OTO and LTL measurements, and 2.4 mm between LTL and ITI measurements. The prevalence of AAA almost doubled using OTO instead of ITI, while the difference between ITI and LTL was minor (3.3% vs. 4.0% AAA). CONCLUSIONS: The study shows superior reproducibility of LTL and ITI compared with the OTO method of caliper placement in ultrasound determination of maximum abdominal aortic diameter, and the choice of caliper placement method significantly affects the prevalence of AAAs in screening programs.

Postpartum computed tomography angiography of the fetoplacental macrovasculature in normal pregnancies and in those complicated by fetal growth restriction.

INTRODUCTION: Current knowledge of the fetoplacental vasculature in fetal growth restriction (FGR) due to placental dysfunction focuses on the microvasculature rather than the macrovasculature. The aim of this study was to investigate the feasibility of computed tomography angiography to analyze the fetoplacental macrovasculature in normal and FGR pregnancies. MATERIAL AND METHODS: We included 29 placentas (22-42 weeks of gestation) from normal birthweight pregnancies and eight placentas (26-37 weeks of gestation) from FGR pregnancies (birthweight < -15% and abnormal umbilical Doppler flow). We performed postpartum placental computed tomography angiography followed by semi-automatic three-dimensional image segmentation. RESULTS: A median of nine (range seven to eleven) vessel generations was identified. In normal birthweight placentas, gestational age was positively linearly correlated with macrovascular volume (p = 0.002), vascular surface area (p < 0.0005) and number of vessel junctions (p = 0.012), but not with vessel diameter and inter-branch length. The FGR placentas had a lower weight (p = 0.004) and smaller convex volume (p = 0.022) (smallest convex volume containing the macrovasculature); however, macrovascular volume was not significantly reduced. Hence, macrovascular density given as macrovascular outcomes per placental volume was increased in FGR placentas: macrovascular volume per convex volume (p = 0.004), vascular surface area per convex volume (p = 0.004) and number of vessel junctions per convex volume (p = 0.037). CONCLUSIONS: Evaluation of the fetoplacental macrovasculature is feasible with computed tomography angiography. In normal birthweight placentas, macrovascular volume and surface area increase as pregnancy advances by vessel branching rather than increased vessel diameter and elongation. The FGR placenta was smaller; however, the macrovascular volume was within normal range because of an increased macrovascular density.

The Scandinavian baltic pancreatic club (SBPC) database: design, rationale and characterisation of the study cohort.

OBJECTIVES: Chronic pancreatitis (CP) is a multifaceted disease associated with several risk factors and a complex clinical presentation. We established the Scandinavian Baltic Pancreatic Club (SBPC) Database to characterise and study the natural history of CP in a Northern European cohort. Here, we describe the design of the database and characteristics of the study cohort. METHODS: Nine centres from six different countries in the Scandinavian-Baltic region joined the database. Patients with definitive or probable CP (M-ANNHEIM diagnostic criteria) were included. Standardised case report forms were used to collect several assessment variables including disease aetiology, duration of CP, preceding acute pancreatitis, as well as symptoms, complications, and treatments. The clinical stage of CP was characterised according to M-ANNNHEIM. Yearly follow-up is planned for all patients. RESULTS: The study cohort comprised of 910 patients (608 men: 302 women; median age 58 (IQR: 48-67) years with definite 848 (93%) or probable CP 62 (7%). Nicotine (70%) and alcohol (59%) were the most frequent aetiologies and seen in combination in 44% of patients. A history of recurrent acute pancreatitis was seen in 49% prior to the development of CP. Pain (69%) and exocrine pancreatic insufficiency (68%) were the most common complications followed by diabetes (43%). Most patients (30%) were classified as clinical stage II (symptomatic CP with exocrine or endocrine insufficiency). Less than 10% of the patients had undergone pancreatic surgery. CONCLUSION: The SBPC database provides a mean for future prospective, observational studies of CP in the Northern European continent.

Presurgical functional magnetic resonance imaging in patients with brain tumors.

BACKGROUND: Clinical functional magnetic resonance imaging (fMRI) is still an upcoming diagnostic tool because it is time-consuming to perform the post-scan calculations and interpretations. A standardized and easily used method for the clinical assessment of fMRI scans could decrease the workload and make fMRI more attractive for clinical use. PURPOSE: To evaluate a standardized clinical approach for distance measurement between benign brain tumors and eloquent cortex in terms of the ability to predict pre- and postoperative neurological deficits after intraoperative neuronavigation-assisted surgery. MATERIAL AND METHODS: A retrospective study of 34 patients. The fMRI data were reanalyzed using a standardized distance measurement procedure combining data from both fMRI and three-dimensional T1 MRI scans. The pre- and postoperative neurological status of each patient was obtained from hospital records. Data analysis was performed using logistic regression analysis to determine whether the distance measured between the tumor margin and fMRI activity could serve as a predictor for neurological deficits. RESULTS: An odds ratio of 0.89 mm(-1) (P = 0.03) was found between the risk of preoperative neurological motor deficits and the tumor-fMRI distance. An odds ratio of 0.82 mm(-1) (P = 0.04) was found between the risk of additional postoperative neurological motor deficits and the tumor-fMRI distance. The tumor was radically removed in 10 cases; five patients experienced additional postoperative motor deficits (tumor-fMRI distance <18 mm) and five did not (tumor-fMRI distance >18 mm) (P = 0.008). CONCLUSION: This study indicates that the distance measured between the tumor margin and fMRI activation could serve as a valuable predictor of neurological motor deficits.

Single-sweep spectral analysis of contact heat evoked potentials: a novel approach to identify altered cortical processing after morphine treatment.

AIMS: The cortical response to nociceptive thermal stimuli recorded as contact heat evoked potentials (CHEPs) may be altered by morphine. However, previous studies have averaged CHEPs over multiple stimuli, which are confounded by jitter between sweeps. Thus, the aim was to assess single-sweep characteristics to identify alterations induced by morphine. METHODS: In a crossover study 15 single-sweep CHEPs were analyzed from 62 electroencephalography electrodes in 26 healthy volunteers before and after administration of morphine or placebo. Each sweep was decomposed by a continuous wavelet transform to obtain normalized spectral indices in the delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-32 Hz) and gamma (32-80 Hz) bands. The average distribution over all sweeps and channels was calculated for the four recordings for each volunteer, and the two recordings before treatments were assessed for reproducibility. Baseline corrected spectral indices after morphine and placebo treatments were compared to identify alterations induced by morphine. RESULTS: Reproducibility between baseline CHEPs was demonstrated. As compared with placebo, morphine decreased the spectral indices in the delta and theta bands by 13% (P = 0.04) and 9% (P = 0.007), while the beta and gamma bands were increased by 10% (P = 0.006) and 24% (P = 0.04). CONCLUSION: The decreases in the delta and theta band are suggested to represent a decrease in the pain specific morphology of the CHEPs, which indicates a diminished pain response after morphine administration. Hence, assessment of spectral indices in single-sweep CHEPs can be used to study cortical mechanisms induced by morphine treatment.

An image-based method to quantify biomechanical properties of the rectum in radiotherapy of prostate cancer.

BACKGROUND: Gastrointestinal morbidity after radiotherapy (RT) for prostate cancer may be related to the biomechanical properties of the rectum. In this study we present a magnetic resonance imaging (MRI)-based method to quantitate the thickness and elasticity of the rectal wall in prostate cancer patients treated with RT. MATERIAL AND METHODS: Four patients previously treated with RT for prostate cancer underwent an MRI session with stepwise rectal bag deflation (from a maximum tolerable volume to 0 ml, in 50 ml steps), with a probe inserted inside the bag to monitor the internal rectal pressure. MRIs were acquired using Dixon sequences (4 mm axial slice thickness) at each deflation step. Rectal walls were defined from the recto-sigmoid junction to 3 cm above the anal canal as the space between the inner and outer wall surfaces. The wall thickness was determined and biomechanical properties (strain and stress) were calculated from the pressure measurements and the MRI-segmented rectal walls. RESULTS: The integral rectal pressure varied for the maximum tolerable volume (range 150-250 ml) across patients and ranged from 1.3 to 4.0 kPa (SD = 1.2 kPa). Wall thickness was found to vary between patients and also across different rectum segments, with a mean (SD) thickness for the different segments at the 50 ml distension volume of 1.8-4.0 (0.6) mm. Stress showed larger variation than strain, with mean (SD) values for the different segments ranging between 1.5 and 7.0 (1.5) kPa. CONCLUSION: We have developed a method to quantify biomechanical properties of the rectal wall. The resulting rectal wall thickness, strain and stress differed between patients, as well as across different rectal wall sections. These findings could provide guidance in future predictive outcome modelling in order to better understand the rectal dose-volume response relationship.

Decreased patency rates following endoscopic vein harvest in coronary artery bypass surgery.

OBJECTIVES: Endoscopic vein harvest has gained widespread use in coronary artery bypass surgery. However, potential negative mid- and long-term effects following endoscopic vein harvest have been described. We aimed to compare long-term clinical outcomes following endoscopic and open vein graft harvesting. DESIGN: This study was a clinical follow-up with additional computed tomographic coronary angiography among 126 first-time bypass patients originally included in a randomized study comparing early leg wound complications and cosmetic results. Deceased patients were retrospectively followed up. RESULTS: Follow-up was complete, but information on clinical endpoints was not available in all patients. A total of 111 patients were alive at follow-up. Median observation time was 6.3 (range: 0.2­9.1) years including three in-hospital deaths. Vein graft failure was significantly higher in the endoscopic vein harvest (EVH) group (13 of 31; 42%) compared with the open vein harvest (OVH) group (2 of 32, 6%) (P = 0.001). However, this difference was not reflected by differences in recurrence of angina (P = 0.44), myocardial infarction (P = 0.11), and all-cause mortality (P = 0.15). CONCLUSIONS: Using a median follow-up time of 6.3 years significantly more vein graft failures were identified following EVH compared with OVH without any differences in long-term clinical outcomes.

Bisphosphonate Use and Risk of Atypical Femoral Fractures: A Danish Case Cohort Study with Blinded Radiographic Review.

CONTEXT: Prolonged bisphosphonate (BP) treatment for osteoporosis prevents hip and other fractures but causes atypical femoral fractures (AFF). OBJECTIVE: To establish the relationship between patterns of BP use and the risk of AFF and hip fractures. Other potential risk factors for AFF were also examined. DESIGN: Population-based case-cohort study. SETTING: The Danish National Healthcare system maintains longitudinal records of medication use, healthcare utilization, and x-ray images. PARTICIPANTS: Among all 1.9 million Danish adults ≥50, those with subtrochanteric or femoral shaft fractures between 2010-2015 (n = 4,973) were identified and compared to a random sample (n = 37,021). PREDICTORS: Bisphosphonate use was collected from 1995-2015. MAIN OUTCOME MEASURES: Fracture radiographs (n = 4,769) were reviewed by blinded study radiologists to identify AFFs (n = 181) using established criteria. Traditional hip fractures in the random sample (n = 691) were identified by ICD-10. RESULTS: Compared to <1 year of BP use, 5-7 years of use was associated with a 7-fold increase in AFF [adjusted HR = 7.29 (CI: 3.07,17.30)]; the risk of AFF fell quickly after discontinuation. The 5-year number-needed-to-harm for one AFF was 1,424, while the 5-year number-needed-to-treat to prevent one hip fracture was 56. Glucocorticoid and proton pump inhibitor use were independently associated with increased AFF risk. Thirty-one percent of those with AFF had no BP exposure. CONCLUSIONS: The risk of AFF increases with duration of BP use but the beneficial effects of BP therapy in adults ≥50 dramatically exceed this increased risk. Nearly one-third of those with AFF have no BP exposure.

Alterations in Functional Connectivity of Thalamus and Primary Somatosensory Cortex in Painful and Painless Diabetic Peripheral Neuropathy.

OBJECTIVE: In this study we aimed to investigate the functional connectivity of brain regions involved in sensory processing in diabetes with and without painful and painless diabetic peripheral neuropathy (DPN) and the association with peripheral nerve function and pain intensity. RESEARCH DESIGN AND METHODS: In this cross-sectional study we used resting-state functional MRI (fMRI) to investigate functional brain connectivity of 19 individuals with type 1 diabetes and painful DPN, 19 with type 1 diabetes and painless DPN, 18 with type 1 diabetes without DPN, and 20 healthy control subjects. Seed-based connectivity analyses were performed for thalamus, postcentral gyrus, and insula, and the connectivity z scores were correlated with peripheral nerve function measurements and pain scores. RESULTS: Overall, compared with those with painful DPN and healthy control subjects, subjects with type 1 diabetes without DPN showed hyperconnectivity between thalamus and motor areas and between postcentral gyrus and motor areas (all P ≤ 0.029). Poorer peripheral nerve functions and higher pain scores were associated with lower connectivity of the thalamus and postcentral gyrus (all P ≤ 0.043). No connectivity differences were found in insula (all P ≥ 0.071). CONCLUSIONS: Higher functional connectivity of thalamus and postcentral gyrus appeared only in diabetes without neuropathic complications. Thalamic/postcentral gyral connectivity measures demonstrated an association with peripheral nerve functions. Based on thalamic connectivity, it was possible to group the phenotypes of type 1 diabetes with painful/painless DPN and type 1 diabetes without DPN. The results of the current study support that fMRI can be used for phenotyping, and with validation, it may contribute to early detection and prevention of neuropathic complications.

T2* weighted fetal MRI and the correlation with placental dysfunction.

INTRODUCTION: Transverse relaxation time (T2*) is related to tissue oxygenation and morphology. We aimed to describe T2* weighted MRI in selected fetal organs in normal pregnancies, and to investigate the correlation between fetal organ T2* and placental T2*, birthweight (BW) deviation, and redistribution of fetal blood flow. METHODS: T2*-weighted MRI was performed in 126 singleton pregnancies between 23+6- and 41+3-weeks' gestation. The T2* value was obtained from the placenta and fetal organs (brain, lungs, heart, liver, kidneys, and spleen). In normal BW pregnancies (BW > 10th centile), the correlation between the T2* value and gestational age (GA) at MRI was estimated by linear regression. The correlation between fetal organ Z-score and BW group was demonstrated by boxplots and investigated by analysis of variance (ANOVA) for each organ. RESULTS: In normal BW pregnancies fetal organ T2* was negatively correlated with GA. We found a significant correlation between BW group and fetal organ T2* z-score in the fetal heart, kidney, lung and spleen. A positive linear correlation was demonstrated between fetal organ T2* and outcomes related to placental function such as BW deviation and placenta T2* in all investigated fetal organs except for the fetal liver. In the fetal heart, kidneys, and spleen the T2* value showed a significant correlation with fetal redistribution of blood flow (Middle cerebral artery Pulsatility Index) before delivery. DISCUSSION: Fetal T2* is correlated with BW, placental function, and redistribution of fetal blood flow, suggesting that fetal organ T2* reflects fetal oxygenation and morphological changes related to placental dysfunction.

Clinical Course of Medically Managed Patients With Large and Small Duct Chronic Pancreatitis.

INTRODUCTION: Pancreatic duct obstruction is the primary indication for endoscopic and/or surgical therapy in patients with chronic pancreatitis (CP). However, the clinical course of medically managed patients in relation to pancreatic duct obstruction is largely unknown. METHODS: This was a retrospective cohort study of medically managed patients with CP. We classified patients based on pancreatic duct obstruction from a stricture or stone using cross-sectional imaging (i.e., large vs small duct CP). We compared prevalence of diabetes and exocrine insufficiency (EPI) between subgroups at inclusion and investigated risk of new-onset diabetes, EPI, and all-cause mortality over a follow-up period of 5 years. Changes in pancreatic morphology were studied in patients who underwent follow-up imaging. RESULTS: A total of 198 patients (mean age 58 ± 12 years, 70% male, 60% alcoholic etiology, 38% large duct CP) were evaluated. At inclusion, patients with large vs small duct CP had a higher prevalence of both diabetes (43% vs 24%, P = 0.004) and EPI (47% vs 28%, P = 0.007). There was an increased risk of new-onset EPI in patients with large duct CP (hazard ratio 1.72; 95% confidence interval [1.05-2.80], P = 0.031) and higher rates of pancreatic atrophy ( P < 0.001). No differences between groups were observed for new-onset diabetes and all-cause mortality. Conversion from small to large duct CP or vice versa during follow-up was observed in 14% of patients. DISCUSSION: In a medically managed cohort of patients, large duct CP was associated with increased risk of EPI and pancreatic atrophy compared with small duct CP.