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Aims: To investigate the co-existence of diabetic peripheral neuropathy (DPN), painful diabetic peripheral neuropathy (PDPN), and cardiac autonomic neuropathy (CAN) and to establish a model to predict CAN based on peripheral measurements.Methods: Eighty participants (20 type 1 diabetes (T1DM) + PDPN, 20 T1DM + DPN, 20 T1DM-DPN (without DPN), and 20 healthy controls (HC)) underwent quantitative sensory testing, cardiac autonomic reflex tests (CARTs), and conventional nerve conduction. CAN was defined as ≥ 2 abnormal CARTs. After the initial analysis, the participants with diabetes were re-grouped based on the presence or absence of small (SFN) and large fibre neuropathy (LFN), respectively. A prediction model for CAN was made using logistic regression with backward elimination.Results: CAN was most prevalent in T1DM + PDPN (50%), followed by T1DM + DPN (25%) and T1DM-DPN and HC (0%). The differences in prevalence of CAN between T1DM + PDPN and T1DM-DPN/HC were significant (p < 0.001). When re-grouping, 58% had CAN in the SFN group and 55% in the LFN group, while no participants without either SFN or LFN had CAN. The prediction model had a sensitivity of 64%, a specificity of 67%, a positive predictive value of 30%, and a negative predictive value of 90%.Conclusion: This study suggests that CAN predominantly co-exists with concomitant DPN. Aims: To investigate the co-existence of diabetic peripheral neuropathy (DPN), painful diabetic peripheral neuropathy (PDPN), and cardiac autonomic neuropathy (CAN) and to establish a model to predict CAN based on peripheral measurements. Methods: Eighty participants (20 type 1 diabetes (T1DM) + PDPN, 20 T1DM + DPN, 20 T1DM-DPN (without DPN), and 20 healthy controls (HC)) underwent quantitative sensory testing, cardiac autonomic reflex tests (CARTs), and conventional nerve conduction. CAN was defined as ≥ 2 abnormal CARTs. After the initial analysis, the participants with diabetes were re-grouped based on the presence or absence of small (SFN) and large fibre neuropathy (LFN), respectively. A prediction model for CAN was made using logistic regression with backward elimination. Results: CAN was most prevalent in T1DM + PDPN (50%), followed by T1DM + DPN (25%) and T1DM-DPN and HC (0%). The differences in prevalence of CAN between T1DM + PDPN and T1DM-DPN/HC were significant (p < 0.001). When re-grouping, 58% had CAN in the SFN group and 55% in the LFN group, while no participants without either SFN or LFN had CAN. The prediction model had a sensitivity of 64%, a specificity of 67%, a positive predictive value of 30%, and a negative predictive value of 90%. Conclusion: This study suggests that CAN predominantly co-exists with concomitant DPN.

Background: Acute on chronic pancreatitis (ACP) is a relatively common condition, but there are significant gaps in our knowledge on the definition, incidence, diagnosis, treatment and prognosis. Methods: A systematic review that followed PICO (Population; Intervention; Comparator; Outcome) recommendation for quantitative questions and PICo (Population, Phenomenon of Interest, Context) for qualitative research was done to answer 10 of the most relevant questions about ACP. Quality of evidence was judged by the GRADE criteria (Grades of Recommendation, Assessment, Development and Evaluation). The manuscript was sent for review to 12 international experts from various disciplines and continents using a Delphi process. Results: The quality of evidence, for most statements, was low to very low, which means that the recommendations in general are only conditional. Despite that, it was possible to reach strong levels of agreement by the expert panel for all 10 questions. A new consensus definition of ACP was reached. Although common, the real incidence of ACP is not known, with alcohol as a major risk factor. Although pain dominates, other non-specific symptoms and signs can be present. Serum levels of pancreatic enzymes may be less than 3 times the upper limit of normal and cross-sectional imaging is considered more accurate for the diagnosis in many cases. It appears that it is less severe and with a lower mortality risk than acute pancreatitis.Conclusions: Although the evidence base is poor, this position statement provides a foundation from which to advance management of ACP.(c) 2023 The Authors. Published by Elsevier B.V. on behalf of IAP and EPC. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Small nerve fibres are important when studying diabetic peripheral neuropathy (DPN) as they could be first affected. However, assessing their integrity and function adequately remains a major challenge. The aim of this study was to investigate the association between different degrees of DPN, the presence of neuropathic pain, and the intensity of the axon-reflex flare response provoked by epidermal histamine. Eighty adults were included and divided into 4 groups of 20 with type 1 diabetes and: painful DPN (T1DM+PDPN), non-painful DPN (T1DM+DPN), no DPN and no pain (T1DM-DPN), and 20 persons without diabetes or pain (HC). The vasomotor responses were captured by a Full-field Laser Speckle Perfusion Imager. The response was lowest in T1DM+DPN, followed by T1DM+PDPN, T1DM-DPN and HC. The response was significantly reduced in DPN (T1DM+DPN, T1DM+PDPN) compared with people without (T1DM-DPN, HC) (P < .001). The response was also attenuated in diabetes irrespective of the degree of DPN (T1DM+PDPN, T1DM+DPN, T1DM-DPN) (P < .001). There were no differences in the response between painful neuropathy (T1DM+PDPN) and painless DPN (T1DM+DPN) (P = .189). The method can distinguish between groups with and without diabetes and with and without DPN but cannot distinguish between groups with and without painful DPN. Perspective: This study describes how diabetes attenuates the axon-reflex response, and how it is affected by neuropathy and pain clarifying previous findings. Furthermore, the study is the first to utilize histamine when evoking the response, thus providing a new and fast alternative for future studies into the pathophysiology of neuropathic pain.

Background Computed tomography (CT) is increasingly used in the clinical workup, and existing scan contains unused body composition data, potentially useful in a clinical setting. However, there is no healthy reference for contrast-enhanced thoracic CT-derived muscle measures. Therefore, we aimed at investigating whether there is a correlation between each of the thoracic and third lumbar vertebra level (L3) skeletal muscle area (SMA), skeletal muscle index (SMI), and skeletal muscle density (SMD) at contrast-enhanced CT in patients without chronic disease. Methods A proof-of-concept retrospective observational study was based on Caucasian patients without chronic disease, who received CT for trauma between 2012 and 2014. Muscle measures were assessed using a semiautomated threshold-based software by two raters independently. Pearson’s correlation between each thoracic level and third lumbar and intraclass correlation between two raters and test–retest with SMA as proxy parameters were used. Results Twenty-one patients (11 males, 10 females; median age 29 years) were included. The second thoracic vertebra (T2) had the highest median of cumulated SMA (males 314.7 cm2, females 118.5 cm2) and SMI (97.8 cm2/m2 and 70.4 cm2/m2, respectively). The strongest SMA correlation was observed between T5 and L3 (r = 0.970), the SMI between T11 and L3 (r = 0.938), and the SMD between the T10 and L3 (r = 0.890). Conclusions This study suggests that any of the thoracic levels can be valid to assess skeletal muscle mass. However, the T5 may be most favourable for measuring SMA, the T11 for SMI, and T10 for SMD when using contrast-enhanced thoracic CT. Relevance statement In COPD patients, a CT-derived thoracic muscle mass assessment may help identify who would benefit from focused pulmonary rehabilitation: thoracic contrast-enhanced CT conducted as part of the standard clinical workup can be used for this evaluation. Key points • Any thoracic level can be used to assess thoracic muscle mass. • Thoracic level 5 is strongly associated with the 3rd lumbar muscle area. • A strong correlation between the thoracic level 11 and the 3rd lumbar muscle index. • Thoracic level 10 is strongly associated with the 3rd lumbar muscle density. Graphical Abstract

It remains unknown why some people with diabetes develop painful neuropathies while others experience no pain. This study aimed to validate a novel method for assessing the function of small sensory nerves in diabetes to further elucidate this phenomenon. The function of large and small nerves was assessed using a novel perception threshold tracking technique in 3 well-characterized groups (n = 60) with type 1 diabetes, namely, (1) painful diabetic peripheral neuropathy (T1DM + PDPN), (2) painless diabetic peripheral neuropathy (T1DM + DPN), and (3) no neuropathy (T1DM - DPN), and healthy controls (n = 20). Electrical currents with different shapes, duration, and intensities were applied by 2 different skin electrodes activating large and small fibers, respectively. The minimal current needed to activate the fibers were analyzed as the rheobase of the stimulus-response function. Nerve fiber selectivity was measured by accommodation properties of stimulated nerves. The rheobase of both fiber types were highest for T1DM + PDPN, followed by T1DM + DPN, T1DM - DPN, and healthy controls, indicating that the nerve properties are specific in individuals with diabetes and pain. There was an overall significant difference between the groups ( P < 0.01). The accommodation properties of stimulated fibers were different between the 2 electrodes ( P < 0.05) apart from in the group with T1DM + PDPN, where both electrodes stimulated nerves displaying properties similar to large fibers. Perception threshold tracking reveals differences in large and small nerve fiber function between the groups with and without diabetes, DPN, and pain. This indicates that the methods have potential applications in screening DPN and explore further the features differentiating painful from nonpainful DPN. It remains unknown why some people with diabetes develop painful neuropathies while others experience no pain. This study aimed to validate a novel method for assessing the function of small sensory nerves in diabetes to further elucidate this phenomenon. The function of large and small nerves was assessed using a novel perception threshold tracking technique in 3 well-characterized groups (n = 60) with type 1 diabetes, namely, (1) painful diabetic peripheral neuropathy (T1DM + PDPN), (2) painless diabetic peripheral neuropathy (T1DM + DPN), and (3) no neuropathy (T1DM - DPN), and healthy controls (n = 20). Electrical currents with different shapes, duration, and intensities were applied by 2 different skin electrodes activating large and small fibers, respectively. The minimal current needed to activate the fibers were analyzed as the rheobase of the stimulus-response function. Nerve fiber selectivity was measured by accommodation properties of stimulated nerves. The rheobase of both fiber types were highest for T1DM + PDPN, followed by T1DM + DPN, T1DM - DPN, and healthy controls, indicating that the nerve properties are specific in individuals with diabetes and pain. There was an overall significant difference between the groups ( P < 0.01). The accommodation properties of stimulated fibers were different between the 2 electrodes ( P < 0.05) apart from in the group with T1DM + PDPN, where both electrodes stimulated nerves displaying properties similar to large fibers. Perception threshold tracking reveals differences in large and small nerve fiber function between the groups with and without diabetes, DPN, and pain. This indicates that the methods have potential applications in screening DPN and explore further the features differentiating painful from nonpainful DPN.

Background Non-invasive modalities for assessing chronic pancreatitis (CP) are needed in clinical practice. Purpose To investigate the correlation between magnetic resonance elastography (MRE)-derived stiffness and T1 relaxation times (as proxies of fibrosis) and explore their relationships to gland volume and pancreatic functions in patients with CP and healthy controls (HCs). Material and Methods In 49 patients with CP and 35 HCs, pancreatic stiffness, T1 relaxation times, and gland volume were assessed. Fecal elastase and the presence of diabetes were used to evaluate pancreatic exocrine and endocrine functions. Uni- and multivariable linear regression models were used to analyze correlations between imaging parameters. Results There was a positive correlation between MRE-derived stiffness and T1 relaxation times in patients with CP (R2 = 0.42; P 2 = 0.14; P = 0.028). There was no correlation between MRE-derived stiffness and gland volume in patients (R2 = 0.007; P = 0.065) or HCs (R2 = 0.010; P = 0.57). T1 relaxation time was correlated to gland volume (R2 = 0.19; P = 0.002) in patients with CP but not in the HCs ( P = 0.056). Severity of pancreatic functional impairment was reflected by increased fibrosis-related parameters in patients without functional impairment, followed by a further increase in fibrosis-related parameters and reduction in gland volume in patients with pancreatic functional impairments. Conclusion Pancreatic MRE-derived stiffness and T1 relaxation times might reflect early pathophysiological changes in CP. The dynamic correlation with pancreatic function suggests that these parameters may be useful for the non-invasive and early identification of CP.

Aim: An objective assessment of small nerve fibers is key to the early detection of diabetic peripheral neuropathy (DPN). This study investigates the diagnostic accuracy of a novel perception threshold tracking technique in detecting small nerve fiber damage. Methods: Participants with type 1 diabetes (T1DM) without DPN (n = 20), with DPN (n = 20), with painful DPN (n = 20) and 20 healthy controls (HCs) underwent perception threshold tracking on the foot and corneal confocal microscopy. Diagnostic accuracy of perception threshold tracking compared to corneal confocal microscopy was analyzed using logistic regression. Results: The rheobase, corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) (all P < .001) differed between groups. The diagnostic accuracy of perception threshold tracking (rheobase) was excellent for identifying small nerve fiber damage, especially for CNFL with a sensitivity of 94%, specificity 94%, positive predictive value 97%, and negative predictive value 89%. There was a significant correlation between rheobase with CNFD, CNBD, CNFL, and Michigan Neuropathy Screening Instrument (all P < .001). Conclusion: Perception threshold tracking had a very high diagnostic agreement with corneal confocal microscopy for detecting small nerve fiber loss and may have clinical utility for assessing small nerve fiber damage and hence early DPN. Clinical Trials: NCT04078516

Aim: Our goal was to describe a precision medicine program in a regional academic hospital, characterize features of included patients and present early data on clinical impact. Materials and methods: We prospectively included 163 eligible patients with late-stage cancer of any diagnosis from June 2020 to May 2022 in the Proseq Cancer trial. Molecular profiling of new or fresh frozen tumor biopsies was done by WES and RNAseq with parallel sequencing of non-tumoral DNA as individual reference. Cases were presented at a National Molecular Tumor Board (NMTB) for discussion of targeted treatment. Subsequently, patients were followed for at least 7 months. Results: 80% (N = 131) of patients had a successful analysis done, disclosing at least one pathogenic or likely pathogenic variant in 96%. A strongly or potentially druggable variant was found in 19% and 73% of patients, respectively. A germline variant was identified in 2.5%. Median time from trial inclusion to NMTB decision was one month. One third (N = 44) of patients who underwent molecularly profiling were matched with a targeted treatment, however, only 16% were either treated (N = 16) or are waiting for treatment (N = 5), deteriorating performance status being the primary cause of failure. A history of cancer among 1st degree relatives, and a diagnosis of lung or prostate cancer correlated with greater chance of targeted treatment being available. The response rate of targeted treatments was 40%, the clinical benefit rate 53%, and the median time on treatment was 3.8 months. 23% of patients presented at NMTB were recommended clinical trial participation, not dependent on biomarkers. Conclusions: Precision medicine in end-stage cancer patients is feasible in a regional academic hospital but should continue within the frame of clinical protocols as few patients benefit. Close collaboration with comprehensive cancer centers ensures expert evaluations and equality in access to early clinical trials and modern treatment.

Prospective studies applying fluoroscopy for assessment of right ventricular (RV) lead position have failed to show clear benefits from RV septal pacing. We investigated the impact of different RV lead positions verified by computed tomography (CT) on the risk of pacing-induced cardiomyopathy (PICM). We retrospectively included 153 patients who underwent routine fluoroscopy-guided pacemaker implantation between March 2012 and May 2020. All patients had normal pre-implant left ventricular ejection fraction (LVEF). Patients attended a follow-up visit including contrast-enhanced cardiac CT and transthoracic echocardiography. Patients were classified as septal or non-septal based on CT analysis. The primary endpoint was PICM (LVEF < 50% with ≥10% decrease after implantation). Based on CT, 48 (31.4%) leads were septal and 105 (68.6%) were non-septal. Over a median follow-up of 3.1 years, 16 patients (33.3%) in the septal group developed PICM compared to 31 (29.5%) in the non-septal group (p = 0.6). Overall, 13.1% deteriorated to LVEF ≤ 40%, 5.9% were upgraded to cardiac resynchronization therapy device, and 14.4% developed new-onset atrial fibrillation, with no significant differences between the groups. This study demonstrated a high risk of PICM despite normal pre-implant left ventricular systolic function with no significant difference between CT-verified RV septal or non-septal lead position.

BACKGROUND: Several magnetic resonance imaging (MRI) protocols have been used to assess gastric emptying (GE) with MRI. This systematic review summarizes the current literature on the topic. The aim was to provide an overview of the available imaging protocols and underline the items that appear most agreed upon and those that deserve further investigation.METHODS: According to PRISMA guidelines, two independent reviewers conducted a systematic literature search with a pre-specified strategy in different databases. Peer-reviewed articles that utilized MRI techniques to assess GE in healthy volunteers (HVs) were included. The quality and the outcomes of the studies were reported and analyzed.KEY RESULTS: The literature search yielded 30 studies (531 HVs, weighted mean age 27.4, weighted mean body mass index 23.0 kg/m2 ), T2-weighted sequences, balanced turbo field echo, and balanced gradient echo were evenly utilized, with volunteers in the supine position (74% of the studies). After overnight fasting, both liquid (56%) and mixed (44%) meals were equally utilized. Segmentation of the volumes was predominantly performed manually (63%) with a reported mean T50 ranging from 7 to 330 min.CONCLUSIONS & INFERENCES: As observed in this systematic review, MRI is a flexible tool for assessing GE. Different protocols were analyzed, showing an equal capacity to assess the GE. However, many items in these protocols still require further investigation to obtain a common standard and increase this assessment quality.

ObjectiveSeveral 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).DesignWe 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.ResultsClinical 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 (pConclusionPain-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 numberThe study was registered with ClinicalTrials.gov (NCT03434392).

Purpose: The study aimed to determine the performance of advanced magnetic resonance imaging (MRI), including a multiparametric MRI-index, for diagnosing and severity grading of chronic pancreatitis (CP) at various functional stages with focus on detection of CP with preserved pancreatic function. Methods: Fifty-four CP patients and 35 healthy controls underwent MRI including assessment of pancreatic volume, main pancreatic duct (MPD) diameter, T1 relaxation time, magnetic resonance elastography (MRE) derived stiffness, and intravoxel incoherent motion (IVIM) diffusion-weighted imaging. Patients were categorized into three subgroups: Preserved pancreatic function (n = 14), partial pancreatic insufficiency (exocrine insufficiency or diabetes, n = 25), and complete pancreatic insufficiency (exocrine insufficiency and diabetes, n = 15). A multiparametric MRI-index was based on ordinal logistic regression analysis. Diagnostic performances of MRI parameters for diagnosing CP at different functional stages were determined using receiver operating characteristic (ROC) analysis. Results: All MRI parameters differed across CP subgroups and healthy controls (all P < 0.001), except for IVIM. T1 relaxation time (ROC area under the curve (ROC-AUC) 0.82), MRE (ROC-AUC 0.88), and MRI-index (ROC-AUC 0.86) showed the highest performance for detecting patients with preserved pancreatic function (early CP) vs. healthy controls. For detecting preserved pancreatic function vs. partial insufficiency, pancreatic volume, MRI-index, and T1 relaxation time performed best (all ROC-AUC > 0.75), with the MRI-index tending to outperform MRE (ROC-AUC 0.77 vs. 0.63; P = 0.10). Conclusion: Quantitative assessments of T1 relaxation time and MRE-derived stiffness seem promising for diagnosing CP at different functional stages and may together with multiparametric MRI-index be used for early identification, staging and monitoring of CP. Graphical abstract: [Figure not available: see fulltext.].

BACKGROUND: Gastric motility and accommodation have a critical role in maintaining normal gastrointestinal homeostasis. Different modalities can be adopted to quantify those processes, that is, scintigraphy to measure emptying time and intragastric Barostat for accommodation assessment. However, magnetic resonance imaging (MRI) can assess the same parameters noninvasively without ionizing radiation. Our study aimed to develop a detailed three-dimensional (3D) MRI model of the stomach to describe gastric volumes, surface areas, wall tension distribution, and interobserver agreement.METHODS: Twelve healthy volunteers underwent an MRI protocol of six axial T2-weighted acquisitions. Each dataset was used to construct a 3D model of the stomach: First, the volumes of the whole stomach, gastric liquid, and air were segmented. After landmark placing, a raw 3D model was generated from segmentation data. Subsequently, irregularities were removed, and the model was divided into compartments. Finally, surface area and 3D geometry parameters (inverse curvatures) were extracted. The inverse curvatures were used as a proxy for wall tension distribution without measuring the intragastric pressure.KEY RESULTS: The model was able to describe changes in volume and surface geometry for each compartment with a distinct pattern in response to filling and emptying. The surface tension was distributed nonhomogeneously between compartments and showed dynamical changes at various time points.CONCLUSION & INFERENCES: The presented model offers a detailed tool for evaluating gastric volumes, surface geometry, and wall tension in response to filling and emptying and will provide insights into gastric emptying and accommodation in diseases such as diabetic gastroparesis.

Aims: We aimed to quantify microstructural white matter abnormalities using magnetic resonance imaging and examine their associations with 1) brain metabolite and volumes and 2) clinical diabetes-specific characteristics and complications in adults with type 1 diabetes mellitus (T1DM) and distal symmetric peripheral neuropathy (DSPN). Methods: Diffusion tensor images (DTI) obtained from 46 adults with T1DM and DSPN and 28 healthy controls were analyzed using tract-based spatial statistics and were then associated with 1) brain metabolites and volumes and 2) diabetes-specific clinical characteristics (incl. HbA 1c, diabetes duration, level of retinopathy, nerve conduction assessment). Results: Adults with T1DM and DSPN had reduced whole-brain FA skeleton (P = 0.018), most prominently in the inferior longitudinal fasciculus and retrolenticular internal capsule (P < 0.001). Reduced fractional anisotropy (FA) was associated with lower parietal N-acetylaspartate/creatine metabolite ratio (r = 0.399, P = 0.006), brain volumes (P ≤ 0.002), diabetes duration (r = −0.495, P < 0.001) and sural nerve amplitude (r = 0.296, P = 0.046). Additionally, FA was reduced in the subgroup with concomitant proliferative retinopathy compared to non-proliferative retinopathy (P = 0.03). No association was observed between FA and HbA 1c. Conclusions: This hypothesis-generating study provided that altered white matter microstructural abnormalities in T1DM with DSPN were associated with reduced metabolites central for neuronal communications and diabetes complications, indicating that peripheral neuropathic complications are often accompanied by central neuropathy.

OBJECTIVE: With hepatic steatosis (HS) being an established risk factor for CVD in the general population, it may also be a predictor of CVD in patients with schizophrenia. The aim of the present study was to investigate if time since schizophrenia diagnosis, body mass index (BMI), sex, metabolic syndrome, alcohol use, smoking, alanine transaminase (ALT), and body fat percentage (as measured by bioelectrical impedance) were associated with HS, determined by computed tomography (CT), in a population of patients diagnosed with schizophrenia.METHODS: Moderate to severe HS (40 CT Hounsfield units as threshold) was determined utilizing non-contrast enhanced CT. The association between the explanatory variables and outcome of HS was assessed using multivariable logistic regression.RESULTS: In the present study, 145 patients diagnosed with schizophrenia (mean age 42.2 years (SD ± 13.8)) were included, with 88 (60.7%) being male. On average, patients had been diagnosed for 14.8 (SD ± 10.7) years. A total of 31 (21.4%) patients had HS as determined by CT. The presence of HS was associated with ALT (OR 1.06, 95% CI (1.02-1.10) per 1 U/L increase), and the presence of metabolic syndrome (OR 62.89, 95% CI (2.03-1949.55)). The presence of HS was not associated with BMI, body fat percentage or time since diagnosis in the multivariable analysis.CONCLUSION: Higher ALT and the presence of metabolic syndrome were associated with HS in patients with schizophrenia utilizing multivariable analysis. The findings suggest that risk factors for HS are similar in both the general population and in patients with schizophrenia.

Objective: Alterations of the central nervous system are increasingly being recognized as a part of diabetes, especially in the thalamus and the default mode network (DMN). However, the functional involvement in diabetic peripheral neuropathy (DPN) is poorly understood. This study aimed to investigate functional connectivity of thalamus and DMN in individuals with DPN and the associations to clinical characteristics. Methods: Forty-seven type 1 diabetes mellitus (T1DM) individuals with DPN and 28 healthy controls underwent resting-state functional magnetic resonance imaging. Seed-to-voxel and ROI-to-ROI analyses were performed for thalamus and DMN. The connectivity for both thalamus and DMN were correlated to clinical parameters. Results: Alterations in the functional connectivity of the thalamus and DMN were observed in individuals with T1DM and DPN. Thalamus showed decreased connectivity to the middle frontal, superior frontal, and precentral cortex (all p FWE-correcteduncorrected

Purpose: Constipation is among the most common gastrointestinal disorders, although, there is no generally accepted objective diagnostic criteria thereof. It has been proposed that colorectal dimensions assessed with Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) may support the diagnosis, but normative data are lacking. The aim of this study was to describe colorectal dimensions in a sample of the general population and to investigate whether the dimensions were under influence by age and gender. Methods: The maximum diameters and cross-sectional areas of the ascending colon, descending colon and rectum were determined from 119 CT scans of trauma patients (age groups from 15 to 70 years, 84 men and 35 women). A regression model was applied to explore the impact of age and gender on colorectal dimensions. Results: Overall, great variations were found for all colorectal diameters and cross-sectional areas (median diameter (5% percentiles; 95% percentiles): ascending 46 (26; 63) mm; descending 29 (16; 48) mm; rectum 39 (22; 67) mm. Women had larger rectal cross-sectional areas, reflecting more rectal content, compared to men (p = 0.003). Age did not affect colorectal diameters or cross-sectional areas (all p > 0.10). Conclusion: Great variations of colorectal dimensions were found. Larger rectal cross-sectional areas in women could likely reflect the fact that women have increased prevalence of constipation. Future studies should take gender into consideration when evaluating colorectal dimensions.

Arterial calcification is associated with cardiovascular mortality in dialysis patients. Active matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of arterial calcification. Elevated plasma concentrations of inactive MGP, i.e. dephosphorylated-uncarboxylated MGP (dp-ucMGP), are prevalent in dialysis patients. MGP inactivity might contribute to arterial calcification. We investigated whether vitamin K supplementation had an effect on arterial calcification in chronic dialysis patients.In a 2-year, double-blind, placebo-controlled intervention trial, 48 dialysis patients were randomized to vitamin K [menaquinone-7 (MK-7), 360 µg daily] or placebo. MK-7 in serum and dp-ucMGP in plasma were used to assess vitamin K status. Carotid-femoral pulse wave velocity (cfPWV) and scores of coronary arterial calcification (CAC) and abdominal aortic calcification (AAC) were used to assess arterial calcification.Thirty-seven participants completed Year 1, and 21 completed Year 2. At Year 2, serum MK-7 was 40-fold higher, and plasma dp-ucMGP 40\% lower after vitamin K supplementation compared with placebo \mean dp-ucMGP difference: −1380 pmol/L [95\CI) −2029 to −730]\. There was no significant effect of vitamin K supplementation on cfPWV [mean difference at Year 2: 1.2 m/s (95\0.1 to 2.4)]. CAC Agatston score increased significantly in vitamin K supplemented participants, but was not significantly different from placebo [mean difference at Year 2: 664 (95\554 to 1881)]. AAC scores increased in both groups, significantly so within the placebo group at Year 1, but with no significant between-group differences.Vitamin K supplementation improved vitamin K status, but did not hinder or modify the progression of arterial calcification in dialysis patients. BackgroundArterial calcification is associated with cardiovascular mortality in dialysis patients. Active matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of arterial calcification. Elevated plasma concentrations of inactive MGP, i.e. dephosphorylated-uncarboxylated MGP (dp-ucMGP), are prevalent in dialysis patients. MGP inactivity might contribute to arterial calcification. We investigated whether vitamin K supplementation had an effect on arterial calcification in chronic dialysis patients.MethodsIn a 2-year, double-blind, placebo-controlled intervention trial, 48 dialysis patients were randomized to vitamin K [menaquinone-7 (MK-7), 360 µg daily] or placebo. MK-7 in serum and dp-ucMGP in plasma were used to assess vitamin K status. Carotid-femoral pulse wave velocity (cfPWV) and scores of coronary arterial calcification (CAC) and abdominal aortic calcification (AAC) were used to assess arterial calcification.ResultsThirty-seven participants completed Year 1, and 21 completed Year 2. At Year 2, serum MK-7 was 40-fold higher, and plasma dp-ucMGP 40% lower after vitamin K supplementation compared with placebo {mean dp-ucMGP difference: −1380 pmol/L [95% confidence interval (CI) −2029 to −730]}. There was no significant effect of vitamin K supplementation on cfPWV [mean difference at Year 2: 1.2 m/s (95% CI −0.1 to 2.4)]. CAC Agatston score increased significantly in vitamin K supplemented participants, but was not significantly different from placebo [mean difference at Year 2: 664 (95% CI −554 to 1881)]. AAC scores increased in both groups, significantly so within the placebo group at Year 1, but with no significant between-group differences.ConclusionsVitamin K supplementation improved vitamin K status, but did not hinder or modify the progression of arterial calcification in dialysis patients.

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 2 =.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.

Objective Thalamus is essential in processing of sensory information. This study explored the associations between thalamic volume and intra-thalamic metabolites and associations to clinical and experimental characteristics of sensory function in adults with diabetic polyneuropathy. Methods 48 adults with type 1 diabetes and confirmed distal symmetric peripheral neuropathy (DPSN) and 28 healthy controls participated in a cross-sectional study and underwent a brain magnetic resonance imaging scan. Estimates for thalamic volume were extracted using voxel-based morphometry and intra-thalamic N-acetylaspartate/creatine (NAA/cre) levels were assessed by magnetic resonance spectroscopy. Associations between thalamic volume and clinical measures, quantitative sensory testing and neuropathic phenotype were explored. Results In diabetes, reduced gray matter volume was identified including bilateral thalamus (all p≤0.001) in comparison to healthy participants. Thalamic volume estimates were positively associated to intra-thalamic NAA/cre (r=0.4; p=0.006), however not to diabetes duration (p=0.5), severity of DSPN (p=0.7), or presence of pain (p=0.3). Individuals with the lowest thalamic volume had greatest loss of protective sensation (light touch using von Frey-like filaments, p=0.037) and highest pain tolerance to electric stimulation (tetanic stimulation, p=0.008) compared to individuals with the highest thalamic volume. Conclusions In this cohort with type 1 diabetes and severe DSPN, thalamic atrophy was present and associated with reduced NAA/cre, indicating thalamic structural loss and dysfunction. Thalamic atrophy was associated to reduced sensory function involving large fiber neuropathy and sensation to tetanic stimulation that may reflect synaptic transmission. This may ultimately contribute to the current understanding of the pathophysiology behind the perception changes evident in DSPN.

Purpose: The purpose of this study was to evaluate different renal proton density fat fraction (PDFF) analysis approaches. Additionally, we assessed renal fat in obese individuals and lean individuals. Methods: This was a retrospective observational case–control study. Twenty-eight obese individuals and 14 lean controls underwent MRI with multi-point Dixon technique for PDFF maps. The following renal PDFF image analysis approaches were performed and compared: (1) five circular regions of interest (ROIs) in six slices, (2) three circular ROIs in one slice, (3) freehand segmentation of renal parenchyma in one slice, and (4) freehand segmentation of renal parenchyma avoiding the renal border in one slice. Furthermore, renal PDFF was compared between obese and lean individuals. Results: Methods 1, 2, and 4 were positively correlated (r ≥ 0.498, p ≤ 0.001). Renal PDFF values varied more with regards to ROI placement within slices than mean PDFF between slices. Using all methods, the obese individuals had significantly higher renal PDFF values compared with the lean controls. Conclusion: Renal PDFF should be measured covering large areas of the kidney while excluding artifacts. This can be achieved using multiple circular ROIs. Increased lipid accumulation in the kidneys was related to obesity. Graphical abstract: [Figure not available: see fulltext.]

BACKGROUND: Functional constipation (FC) and irritable bowel syndrome constipation type (IBS-C) share many similarities, and it remains unknown whether they are distinct entities or part of the same spectrum of disease. Magnetic resonance imaging (MRI) allows quantification of intraluminal fecal volume. We hypothesized that colonic volumes of patients with FC would be larger than those of patients with IBS-C, and that both patient groups would have larger colonic volumes than healthy controls (HC).METHODS: Based on validated questionnaires, three groups of participants were classified into FC (n = 13), IBS-C (n = 10), and HC (n = 19). The colonic volume of each subject was determined by MRI. Stool consistency was described by the Bristol stool scale and colonic transit times were assessed with radiopaque makers.KEY RESULTS: Overall, total colonic volumes were different in the three groups, HC (median 629 ml, interquartile range (IQR)(562-868)), FC (864 ml, IQR(742-940)), and IBS-C (520 ml IQR(489-593)) (p = 0.001). Patients with IBS-C had lower colonic volumes than patients with FC (p = 0.001) and HC (p = 0.019), but there was no difference between FC and HC (p = 0.10). Stool consistency was similar in the two patient groups, but patients with FC had longer colonic transit time than those with IBS-C (117.6 h versus 43.2 h, p = 0.019).CONCLUSION: Patients with IBS-C have lower total colonic volumes and shorter colonic transit times than patients with FC. Future studies are needed to confirm that colonic volume allows objective distinction between the two conditions.

In this study we investigated brain morphology in adults with diabetic neuropathy. We aimed to characterize gray matter volume (GMV) and cortical thickness, and to explore associations between whole brain morphology and clinical characteristics. 46 adults with type 1 diabetes and distal symmetric peripheral neuropathy (DSPN) and 28 healthy controls underwent magnetic resonance imaging scans. GMV and cortical thickness were estimated using voxel-/surface-based morphometry. Associations between total GMV and clinical characteristics were explored. Adults with DSPN had reduced total GMV compared with controls (627.4 ± 4.1 mL vs. 642.5 ± 5.2 mL, P = 0.026). GMV loss was more pronounced for participants with painful neuropathy compared with controls (619.1±8.9 mL vs. 642.4±5.2 mL, P = 0.026) and for those with proliferative vs. non-proliferative retinopathy (609.9 ± 6.8 mL vs. 636.0 ± 4.7 mL, P = 0.003). Characteristics such as severity of neuropathy and decreased parietal N-acetylaspartate/creatine metabolite concentration seem to be related to GMV loss in this cohort. Regional GMV loss was confined to bilateral thalamus/putamen/caudate, occipital and precentral regions, and decreased cortical thickness was identified in frontal areas. Since the observed total GMV loss influenced with clinical characteristics, brain imaging could be useful for supplementary characterization of diabetic neuropathy. The regional brain changes could suggest that some areas are more vulnerable in this cohort.

PURPOSE: This feasibility and validation study addresses the potential use of magnetic resonance imaging (MRI) texture analysis of the pancreas in patients with chronic pancreatitis (CP).METHODS: Extraction of 851 MRI texture features from diffusion weighted imaging (DWI) of the pancreas was performed in 77 CP patients and 22 healthy controls. Features were reduced to classify patients into subgroups, and a Bayes classifier was trained using a tenfold cross-validation forward selection procedure. The classifier was optimized to obtain the best average m-fold accuracy, sensitivity, specificity, and positive predictive value. Classifiers were: presence of disease (CP vs. healthy controls), etiological risk factors (alcoholic vs. nonalcoholic etiology of CP and tobacco use vs. no tobacco use), and complications to CP (presumed pancreatogenic diabetes vs. no diabetes and pancreatic exocrine insufficiency vs. normal pancreatic function).RESULTS: The best classification performance was obtained for the disease classifier selecting only five of the original features with 98% accuracy, 97% sensitivity, 100% specificity, and 100% positive predictive value. The risk factor classifiers obtained good performance using 9 (alcohol: 88% accuracy) and 10 features (tobacco: 86% accuracy). The two complication classifiers obtained similar accuracies with only 4 (diabetes: 83% accuracy) and 3 features (exocrine pancreatic function: 82% accuracy).CONCLUSION: Pancreatic texture analysis demonstrated to be feasible in patients with CP and discriminate clinically relevant subgroups based on etiological risk factors and complications. In future studies, the method may provide useful information on disease progression (monitoring) and detection of biomarkers characterizing early-stage CP.

Studies have reported sex-based differences in conduit artery function, however little is known about possible sex-based differences in microvascular function, and possible influence of muscle group. Blood-oxygen-level-dependent (BOLD) MR images acquired during ischemia-reperfusion assess the reactive hyperemic response in the microvasculature of skeletal muscle. We tested the hypothesis that women have greater microvascular reactivity, reflected by faster time-to-peak (TTP) and time-to-half-peak (TTHP) of the BOLD response, across all lower leg muscles. In healthy, young men (n = 18) and women (n = 12), BOLD images of both lower legs were acquired continuously during 30 s of rest, 5 min of cuff occlusion and 2 min of reperfusion, in a 3 T MR scanner. Segmentation of tibialis anterior (TA), soleus (SO), gastrocnemius medial (GM), and the peroneal group (PG) were performed using image registration, and TTP and TTHP of the BOLD response were determined for each muscle. Overall, women had faster TTP (p = 0.001) and TTHP (p = 0.01) than men. Specifically, women had shorter TTP and TTHP in TA (27.5–28.4%), PG (33.9–41.6%), SO (14.7–19.7%) and GM (15.4–18.8%). Overall, TTP and TTHP were shorter in TA compared with PG (25.1–31.1%; p ≤ 0.007), SO (14.3–16%; p ≤ 0.03) and GM (15.6–26%; p ≤ 0.01). Intra class correlations analyses showed large variation in absolute agreement (range: 0.10–0.81) of BOLD parameters between legs (within distinct muscles). Faster TTP and TTHP across all lower leg muscles, in women, provide novel evidence of sex-based differences in microvascular function of young adults matched for age, body mass index, and physical activity level.

Background Moderate to severe acute pancreatitis (AP) is associated with a high rate of complications and increased mortality, yet no targeted pharmacologic treatment currently exists. As pain is a dominant symptom in AP, patients are exposed to excess levels of both endo- and exogenous opioids, which may have harmful effects on the course of AP. This trial investigates the effects of the peripherally acting μ-opioid receptor antagonist (PAMORA) methylnaltrexone on disease severity and clinical outcomes in patients with moderate to severe AP. Methods PAMORA-AP is a multicentre, investigator-initiated, double-blind, randomised, placebo-controlled, interventional trial, which will be conducted at four referral centres for acute pancreatitis in Denmark. Ninety patients with early-onset AP (pain onset within 48 h) as well as predicted moderate to severe disease (two or more systemic inflammatory response syndrome criteria upon admission) will be prospectively included. Subsequently, participants will be randomised (1:1) to intravenous treatment with either methylnaltrexone or matching placebo (Ringer’s lactate) during 5 days of admission. The primary endpoint will be the group difference in disease severity as defined and measured by the Pancreatitis Activity Scoring System (PASS) score 48 h after randomisation. Secondary endpoints include daily PASS scores; disease severity according to the Atlanta classification; quantification of need for analgesics, nutritional support, intravenous fluid resuscitation and antibiotics; duration of hospital admissions, readmission rates and mortality. Pain intensity and gut function will be self-reported using validated questionnaires. Exploratory endpoints include circulating levels of pro-and anti-inflammatory markers, polyethylene glycol recovery from the urine, circulating levels of blood markers of intestinal permeability, the prevalence of pancreatic complications on computed tomography (CT) scans, and colon transit time assessed using a CT-based radiopaque marker method. Discussion This trial aims to evaluate the PAMORA methylnaltrexone as a novel targeted pharmacotherapy in patients with moderate to severe AP with the potential benefit of improved patient outcomes. Trial registration ClinicalTrials.govNCT04743570. Registered on 28 January 2021. EudraCT 2020-002313-18.

Purpose: Non-invasive imaging methods to detect morphological changes of the pancreas in patients with mild chronic pancreatitis (CP) are needed. This study aimed to compare magnetic resonance imaging-based parameters, pancreatic volume, T1 mapping, magnetic resonance elastography (MRE), and proton density fat fraction between CP patients and controls, and determine the diagnostic performance for diagnosing different stages of CP. Methods: Nineteen patients with mild CP (Cambridge grade 2 or less or recurring acute pancreatitis; n = 19), 30 with moderate/severe CP (Cambridge grade 3 and 4), and 35 healthy controls underwent pancreatic magnetic resonance imaging to assess the above mentioned magnetic resonance imaging-based parameters. The diagnostic performance of each parameter for detecting any mild and moderate/severe CP was determined using receiver operating characteristic analysis. Results: Pancreatic volume, T1 relaxation times, MRE-derived stiffness, and proton density fat fraction differed significantly between patients with mild CP, moderate/severe CP, and healthy controls (all p < 0.05). T1 mapping and MRE showed a very high diagnostic performance for distinguishing the mild CP group from the control group (T1 mapping: receiver operating characteristic area under the curve (ROC-AUC): 0.94; sensitivity: 84%; specificity: 91%, MRE: ROC-AUC: 0.93; sensitivity: 89%; specificity: 94%). T1 mapping and MRE also had the highest performance for diagnosing the presence of any CP from the control group (ROC-AUCs of 0.98 and 0.97, respectively). Conclusion: Quantitative assessments of T1 relaxation time and MRE-derived stiffness had high performance in detecting mild CP and could probably reflect the early fibrotic changes in CP.

Background: Tapentadol is a combined opioid agonist and norepinephrine reuptake inhibitor with fewer gastrointestinal side effects at equianalgesic doses compared with classical strong opioids. Previous studies on tapentadol have included multi-morbid patients in whom confounders exclude detailed assessment of the mechanistic effects and strict comparison with other opioids or placebo. This study aimed at investigating the effects of tapentadol and oxycodone on gastrointestinal motility and gastrointestinal side effects. Methods: 21 healthy males participated in a randomized, double-blind, placebo-controlled, crossover study. Tapentadol (50 mg twice daily), oxycodone (10 mg twice daily), or placebo tablets were administered for 14 days. Segmental gastrointestinal transit times and colonic motility parameters were measured with electromagnetic capsules. Gastrointestinal side effects were assessed using questionnaires. Key Results: During dosing with tapentadol, gastrointestinal side effects and motility parameters were on placebo level. Compared with tapentadol, oxycodone increased whole gut transit time by 17.9 hours (p =.015) and rectosigmoid transit time by 6.5 hours (p =.005). Compared with tapentadol, oxycodone also reduced long, fast antegrade colonic movements (p =.001). In comparison with placebo, oxycodone prolonged whole gut transit time by 31.6 hours, (p

Introduction Placental dysfunction may be found among normal birth weight (BW) pregnancies, as indicated by abnormal histological findings in postnatal placental examination in some of these pregnancies. T2* weighted placental MRI provides non-invasive information on placental oxygenation and thereby placental function. The aim of this study was to investigate the correlation between placental T2*, BW and placental histology. Methods A total of 63 pregnant women underwent T2* weighted placental MRI at 15–40 week's gestation and a standardized placental histological examination (PHE). Abnormal PHE was defined by vascular malperfusion according to the Amsterdam workshop consensus. The correlation between PHE, BW z-score and T2* z-score was analyzed by logistic regression. Results Abnormal PHE was revealed in 28 pregnancies. Multiple logistic regression revealed a significant correlation between abnormal PHE and T2* z-score (OR = 0.34, p = 0.008), whereas BW z-score did not add significantly to the correlation of placental histology (OR = 0.52, p = 0.115). In BW z-score≥0, PHE was normal in 100% of pregnancies. In BW z-score ≤ −2, PHE was abnormal in 89% of pregnancies. In intermediate BW (z-score between −2 and 0), PPE was abnormal in 35% of pregnancies. In this intermediate group, placental T2* z-score was reduced (−1.52 ± 1.22 (mean SD)) when compared to normal PHE pregnancies (−0.28 ± 1.17), p = 0.006. Discussion This study demonstrates a correlation between abnormal placental histology and low placental T2* value regardless of fetal size. This indicates that T2* provides information of placental function in vivo even when fetal size is normal. This finding highlights that fetal size alone is not a valid marker of placental dysfunction.

Objective The antenatal detection of small for gestational age (SGA) pregnancies is a challenge, which may be improved by placental MRI. The longitudinal relaxation time (T1) is a tissue constant related to tissue morphology and tissue oxygenation, thereby placental T1 may be related to placental function. The aim of this study is to investigate placental T1 in appropriate for gestational age (AGA) and SGA pregnancies. Methods A total of 132 singleton pregnancies were retrieved from our MRI research database. MRI and ultrasound estimated fetal weight (EFW) was performed at gestational week 20.6–41.7 in a 1.5 T system. SGA was defined as BW ≤ −15% of the expected for gestational age (≤10th centile). A subgroup of SGA pregnancies underwent postnatal placental histological examination (PHE) and abnormal PHE was defined as vascular malperfusion. The placental T1 values were converted into Z-scores adjusted for gestational age at MRI. The predictive performance of placental T1 and EFW was compared by receiver operating curves (ROC). Results In AGA pregnancies, placental T1 showed a negative linear correlation with gestational age (r = −0.36, p = 0.004) Placental T1 was significantly reduced in SGA pregnancies (mean Z-score = −0.34) when compared to AGA pregnancies, p = 0.03. Among SGA pregnancies placental T1 was not reduced in cases with abnormal PHE, p = 0.84. The predictive performance of EFW (AUC = 0.84, 95% CI, 0.77–0.91) was significantly stronger than placental T1 (AUC = 0.62, 95% CI, 0.52–0.72) (p = 0.002). Discussion A low placental T1 relaxation time is associated with SGA at birth. However, the predictive performance of placental T1 is not as strong as EFW.

Background and aims: Evaluation of gastric wall stiffness and intragastric pressure is essential for detailed assessments of gastric accommodation. However, non-invasive assessments are needed for large scale clinical studies and none of the existing methods takes abdominal wall effect into the calculation. This study aimed to assess gastric wall stiffness and gastric content stiffness as a proxy for intragastric pressure using novel mechanical modeling and non-invasive indentation tests on a silicon stomach model. Methods: A silicon stomach model (scaling 1:1 with the human stomach) was indented using a pressure algometer at intragastric pressures from 0 to 0.8 kPa. Wall thicknesses and luminal cross-sectional areas along the stomach were measured with ultrasound images. The gastric wall stiffness was compared between measurements from tensile tests on strips cut from the silicon stomach and estimations from a shell indentation model. The pressurized gastric content stiffness was predicted from a bonded two-layer axisymmetric half-space indentation model. Results: The gastric wall stiffness estimated from the shell indentation model showed no difference to measurements from the mechanical tests on the cutting strips (p = 0.14). The predicted gastric content stiffness was strongly associated with the intragastric pressure (r > 0.83, p < 0.001). Conclusions: The mechanical model developed in this study can simultaneously predict the gastric wall stiffness and the pressurized gastric content stiffness. In future studies, the method can be applied to reveal intragastric pressure conditions non-invasively via the pressurized gastric content stiffness during gastric accommodation and emptying such as with magnetic resonance imaging.

Background Coronary heart disease (CHD) is a major cause of increased mortality rates in patients with schizophrenia. Moreover, coronary artery calcium (CAC) score is associated with CHD. We hypothesized that patients with schizophrenia have more CAC than the general population and aimed to investigate the CAC score in patients with schizophrenia compared to norms based on the general population. Additionally, this study investigated if age, sex, diabetes, dyslipidemia and smoking were associated with the CAC score. Methods In a cross-sectional study, 163 patients with schizophrenia underwent cardiac computed tomography, and the CAC score was measured and compared to norms by classifying the CAC scores in relation to the age- and gender matched norm 50th, 75th and 90th percentiles. Logistic and linear regression were carried out to investigate explanatory variables for the presence and extent of CAC, respectively. Results A total of 127 (77.9%) patients had a CAC score below or equal to the matched 50th, 20 (12.3%) above the 75th and nine (5.5%) above the 90th percentile. Male sex (P < 0.05), age (P < 0.001) and smoking (P < 0.05) were associated with the presence of CAC while age (P < 0.001) and diabetes (P < 0.01) were associated with the extent of CAC. Conclusions The amount of CAC in patients with schizophrenia follows norm percentiles, and variables associated with the CAC score are similar in patients with schizophrenia and the general population. These findings indicate that the CAC score may not be sufficient to detect the risk of CHD in patients with schizophrenia. Future studies should explore other measures of subclinical CHD, including measures of peripheral atherosclerosis or cardiac autonomic neuropathy to improve early detection and intervention. Trial registration ClinicalTrials.gov Identifier: NCT02885792, September 1, 2016.

Background Symptomatic radiation pneumonitis (RP) may be a serious complication after thoracic radiation therapy (RT) for non-small cell lung cancer (NSCLC). This prospective observational study sought to evaluate the utility of a novel radiation-induced lung injury (RILI) grading scale (RGS) for the prediction of RP. Materials and methods Data of 41 patients with NSCLC treated with thoracic RT of 60–66 Gy were analysed. CT scans were scheduled before RT, one month post-RT, and every three months thereafter for one year. Symptomatic RP was defined as Common Terminology Criteria for Adverse Events grade ≥ 2. RGS grading ranged from 0 to 3. The inter-observer variability of the RGS was assessed by four senior radiologists. CT scans performed 28 ± 10 days after RT were used to analyse the predictive value of the RGS. The change in the RGS severity was correlated to dosimetric parameters. Results The CT obtained one month post-RT showed RILI in 36 (88%) of patients (RGS grade 0 [5 patients], 1 [25 patients], 2 [6 patients], and 3 [5 patients]). The inter-observer agreement of the RGS grading was high (Kendall’s W coefficient of concordance = 0.80, p p p Conclusions The RGS is a simple radiologic tool associated with symptomatic RP. A validation study is warranted.

Tapentadol and oxycodone are commonly used analgesics. Preclinical studies have shown that oxycodone modulates brain metabolites related to opioid pathways, whereas tapentadol also affects noradrenergic activity. However, knowledge about the function of the medications in the human brain is limited. The aim was to investigate effects of tapentadol and oxycodone on brain glutamate, the most important neurotransmitter in pain processing. Magnetic resonance spectroscopy was obtained in 21 healthy subjects from the anterior cingulate cortex, prefrontal cortex, and insula at baseline and after 14 days of treatment with either 50 mg tapentadol, 10 mg oxycodone (equipotent dose, both extended release) or placebo twice daily in a randomized double-blind cross-over study. Compared to baseline, decreased glutamate/creatine levels were identified in anterior cingulate cortex after tapentadol (1.26 ± 0.14 vs. 1.35 ± 0.18, P =.04) and oxycodone (1.26 ± 0.10 vs. 1.35 ± 0.12, P =.05) treatments, both with 7% reduction. This indicates that both analgesics modulate the glutamatergic system at the supraspinal level in humans.

OBJECTIVES: Sarcopenia is a serious but often overlooked complication of chronic pancreatitis (CP). We investigated the prevalence and risk factors for sarcopenia in patients with CP and determined the utility of a computed tomography (CT)-based method, based on psoas muscle measurements, for easy and clinical feasible diagnosis of sarcopenia.METHODS: This was a retrospective multicenter study of 265 patients with CP. We used segmentation of CT images to quantify skeletal muscle mass and diagnose sarcopenia. On the same CT image as used for muscle segmentation, psoas muscle thickness and cross-sectional area were measured and receiver operating characteristic analyses defined age and sex-specific cutoffs for diagnosing sarcopenia.RESULTS: The prevalence of sarcopenia was 20.4%. The optimal height-adjusted psoas muscle cross-sectional area cutoff for diagnosing sarcopenia was 3.3 cm/m in males and 2.5 cm/m in females. The corresponding area under the receiver operating characteristic curves were 0.8 and 0.9, with sensitivities of 84% and 81% and specificities of 62% and 81%, respectively. Comparable diagnostic performance characteristics were observed for psoas muscle thickness.CONCLUSIONS: Sarcopenia is present in 1 of 5 patients with CP. Assessment of psoas muscle parameters provides a clinical feasible method to diagnose sarcopenia.