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Pancreatic exocrine insufficiency (PEI) results in maldigestion of fat, leading to steatorrhea, malabsorption and weight loss. Sjögren's syndrome (SS) is a chronic autoimmune rheumatic disease with unknown etiology. The exocrine pancreas and the salivary glands are functionally and histologically comparable, and pancreatic dysfunction in SS has been hypothesized.Patients were recruited from the Department for Rheumatology at the Karolinska University Hospital in Stockholm, Sweden, between June and December 2019. PEI was assessed by fecal elastase-1 (FE-1) andFifty-seven patients with primary SS were included in the study, comprising 92% females with a median age of 63 years. In total, 87% of SS patients were tested for FE-1 and all had normal results. All patients who underwent aIn our study, most SS patients suffered from irritable bowel syndrome (IBS)-like GI symptoms that could not be attributed to PEI.

Background and purpose: A femoral neck fracture (FNF) may have long-term effects on the patient's func-tion, also in patients younger than 70 years. These long-term effects are not well described, since most studies have short follow-ups. The aim of this study was to investigate clinical outcome by performance -based functional tests, hand grip strength, and hip function in different subgroups. The secondary aim was to study surgical complications, bone mineral density (BMD) and occurrence of sarcopenia 10 years after a FNF. Patients and methods: A prospective multicenter study with a 10-year follow-up of patients aged 20- 69 years with a FNF treated with internal fixation (IF). Five-times sit-to-stand test (5TSST), 4-m walking speed test, hand grip strength (HGS) and Harris Hip Score (HHS) were performed.A radiographic examination of the hip was performed and re-operations were registered. Bone min-eral density (BMD) at the hip, spine and total body composition were assessed with dual energy x-ray absorptiometry (DXA). Present sarcopenia was determined by the combination of reduced functional per-formance and low fat-free mass index (FFMI).Results: A total of 58 patients were included. 5TSTS was normal in 45% of the patients and old age was associated with poorer performance ( p < 0.001). 76% of the study population had a normal speed gait and likewise, old age ( p = 0.005) and walking aids ( p = 0.001) were associated with poor performance. HGS was normal in 82% of the men and 64% of the women. HHS showed that 85% had a good/excellent function. A major re-operation was performed in 34% of the patients with displaced FNF and in 20% of patients with non-displaced FNF. 74% displayed osteopenia and 12% osteoporosis. 17% of the men and 38% of the women had sarcopenia.Interpretation: The majority of patients less than 70 years of age with a FNF treated with IF, had normal functional tests, muscle strength and a good hip function ten years post-operatively. However, one in ten had osteoporosis, and one third was sarcopenic which indicate the importance of encouraging regular muscle preserving resistance training after hip fracture.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

BACKGROUND Fetal cardiac magnetic resonance imaging (MRI) improves the diagnosis of congenital heart defects, but is sensitive to fetal motion due to long image acquisition time. This may be overcome with faster image acquisition with low resolution, followed by image enhancement to provide clinically useful images. PURPOSE To combine phase-encoding undersampling with super-resolution neural networks to achieve high-resolution fetal cine cardiac MR images with short acquisition time. STUDY TYPE Prospective. SUBJECTS Twenty-eight fetuses (gestational week 36 [interquartile range 33-38 weeks]). FIELD STRENGTH/SEQUENCE 1.5 T, balanced steady-state free precession (bSSFP) cine sequence. ASSESSMENT Images were acquired using fully sampled Doppler ultrasound-gated clinical bSSFP cine as reference, with equivalent cine sequences with decreased phase-encoding resolution (25%, 33%, and 50% of clinical standard). Two super-resolution methods based on convolutional neural networks were proposed and evaluated (phasrGAN and phasrresnet). Data were partitioned into training (36 cine slices), validation (3 cine slices), and test sets (67 cine slices) without overlap. Conventional reconstruction methods using bicubic interpolation and k-space zeropadding were used for comparison. Three blinded observers scored image quality between 1 and 10. STATISTICAL TESTS Image scores are reported as median [interquartile range] and were compared using Mann-Whitney's nonparametric test with P

Summary This study examines the association between the ASA physical status classification score at hip fracture surgery and severe postoperative complications in patients aged 60 and older. Among both men and women, ASA scores consistently predict a wide range of complications including infections, cardiovascular complications, hospital readmissions, and death. Introduction Hip fractures are common in aging populations and associated with poor prognosis. This study examines how the American Society of Anaesthesiologists (ASA) physical status classification is related to severe complications among hip fracture patients including infections, cardiovascular diseases, hospital readmissions, and death. Methods Based on a linkage of the Swedish National Inpatient Register with the Swedish National Registry for Hip Fractures (RIKSHÖFT), this study includes patients aged 60+ with first hip fracture between 1998 and 2017. We estimated associations between ASA score and complications during the hospital stay and during 1 year after hip fracture using multivariable-adjusted logistic regression and Cox proportional hazard regression. Results The study population included 170,193 hip fracture patients of which 24% died and 39% were readmitted to hospital within 1 year. The most common complications were urinary tract infections, pneumonia, second hip fractures, and heart failure. Among both men and women, higher ASA scores were consistently associated with higher risks for all complications included in this study. The strongest associations were observed for heart failure, myocardial infarction, pneumonia, and death. Conclusion ASA scores are routinely assessed in clinical practice and predict a wide range of postoperative complications among hip fracture patients. Since many complications may be preventable through adequate drug treatment, rehabilitation, and risk awareness, future studies should examine the mechanisms linking ASA scores to complication risk in order to improve preventive strategies. Particularly, the high risk of cardiovascular complications among patients with high ASA scores deserves clinical and scientific attention. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-021-05956-w.

ObjectiveIt has been debated whether the different clinical disease courses in multiple sclerosis (MS) are the consequence of different pathogenic mechanisms, with distinct risk factors, or if all MS clinical phenotypes are variations of similar underlying disease mechanisms. We aimed to study environmental risk factors and their interactions with human leucocyte antigen DRB1*15:01 with regards to relapsing-onset and progressive-onset MS.MethodsWe used two Swedish population-based case–control studies, including 7520 relapsing-onset cases, 540 progressive-onset cases and 11 386 controls matched by age, sex and residential area. Logistic regression was used to estimate ORs with 95% CIs for associations between the different MS phenotypes and a number of environmental and lifestyle factors. Interaction between the DRB1*15:01 allele and environmental risk factors was evaluated on the additive scale.ResultsAll environmental and lifestyle factors associated with risk of developing MS apply to both relapsing-onset and progressive-onset disease. Smoking, obesity and Epstein-Barr virus nuclear antigen-1 (EBNA-1) antibody levels were associated with increased risk of both MS phenotypes, whereas snuff use, alcohol consumption and sun exposure were associated with reduced risk. Additive interactions between DRB1*15:01 and smoking, obesity, EBNA-1 antibody levels and sun exposure, respectively, occurred to increase MS risk regardless of the clinical phenotype.InterpretationOur finding that the same environmental and lifestyle factors affect both relapsing-onset and progressive-onset MS supports the notion that the different clinical phenotypes share common underlying disease mechanisms.

Background and purpose — Studies regarding hip fractures in young patients are rare since the patient population is small. We assessed clinical outcomes 4 months after hip fracture in patients < 50 years of age and whether there were differences between sexes and different age groups. Patients and methods — We included adult patients < 50 years with a hip fracture between January 1, 2014 and December 31, 2018. Baseline data were extracted from the Swedish Registry for Hip Fracture Patients and Treatment (RIKSHÖFT) and mortality data was obtained from Statistics Sweden. The outcome variables were change of walking ability, pain in fractured hip, use of analgesics, living conditions, and mortality rate at 4 months. Results — Of the 905 patients included, 72% were men and femoral neck fractures were most common (58%). 4 months after surgery, 23% used a walking aid and 7% reported severe pain. Women reported slightly more pain and higher usage of analgesics. Patients aged 40–49 reported higher usage of analgesics than patients aged 15–39, although the latter group reported more pain. Nearly all of those who lived independently before fracture did so at 4 months. The mortality rate was < 1%. Interpretation — Most patients did not use any walking aid and few had severe pain at 4 months. Furthermore, a hip fracture is not a life-threatening event in a patient < 50 years. The living conditions did not change for those who lived independently before the fracture.

ObjectiveWe aimed to investigate the influence of environmental risk factors for multiple sclerosis (MS) in different genetic contexts, and study if interactions between environmental factors and human leucocyte antigen (HLA) genes differ in magnitude according to heterozygocity and homozygocity for HLA-DRB1*15:01.MethodsUsing population-based case–control studies (6985 cases, 6569 controls), subjects with different genotypes and smoking, EBNA-1 status and adolescent Body Mass status, were compared regarding MS risk, by calculating OR with 95% CI employing logistic regression. The interaction between different genotypes and each environmental factor was evaluated on the additive scale.ResultsThe effect of each DRB1*15:01 allele on MS risk was additive on the log-odds scale for each additional allele. Interaction between DRB1*15:01 and each assessed environmental factor was of similar magnitude regardless of the number of DRB1*15:01 alleles, although ORs were affected. When any of the environmental factors were present in DRB1*15:01 carriers without the protective A*02:01 allele, a three-way interaction occurred and rendered high ORs, especially among DRB1*15:01 homozygotes (OR 20.0, 95% CI 13.1 to 30.5 among smokers, OR 21.9, 95% CI 15.0 to 31.8 among those with elevated EBNA-1 antibody levels, and OR 44.3, 95% CI 13.5 to 145 among those who reported adolescent overweight/obesity).ConclusionsThe strikingly increased MS risk among DRB*15:01 homozygotes exposed to any of the environmental factors is a further argument in favour of these factors acting on immune-related mechanisms. The data further reinforce the importance of preventive measures, in particular for those with a genetic susceptibility to MS.

Background The aim of this study was to adapt the instrument and evaluate the psychometric properties of the Swedish version of the Swallowing Quality of Care questionnaire (S-SWAL-CARE) in patients with oropharyngeal dysphagia. Methods Translation and adaptation of the original SWAL-CARE into Swedish was performed according to established international guidelines. Field testing was performed using 100 patients with oropharyngeal dysphagia due to multiple reasons such as head and neck cancer and neurologic/neuromuscular disease, who had undergone swallowing evaluation within 6 months prior to the study. The patients answered the S-SWAL-CARE, the Quality from the Patient’s Perspective (QPP) and the Swallowing Quality of Life (SWAL-QOL). Test–retest was performed in 20% of the participants. The reliability and validity of the S-SWAL-CARE were assessed by Pearson correlation coefficient and Cronbach’s alpha as well as convergent and discriminative validity, respectively. Results The field testing of the S-SWAL-CARE resulted in sufficient reliability, with Cronbach’s alpha values exceeding 0.90 for all domains. All items correlated strongly to their own domain, with weaker correlations to the other domains, indicating proper scale structure. Results also indicate sufficient convergent and discriminant validity when tested for association to the QPP domains and the SWAL-QOL Total score. The test–retest reliability of the S-SWAL-CARE demonstrated sufficient intraclass correlation coefficient (ICC) for the General advice domain (0.73) and Clinical advice domain (0.82). The ICC for the Patient satisfaction domain was lower (0.44). Conclusion The S-SWAL-CARE can be considered a reliable and valid tool to assess the dysphagia-related quality of care in a mixed Swedish dysphagia patient population.

Timing and indication for pulmonary valve replacement (PVR) in patients with repaired Tetralogy of Fallot (rToF) and pulmonary regurgitation (PR) are uncertain. To improve understanding of pumping mechanics, we investigated atrioventricular coupling before and after surgical PVR. Cardiovascular magnetic resonance was performed in patients ( n = 12) with rToF and PR > 35% before and after PVR and in healthy controls ( n = 15). Atrioventricular plane displacement (AVPD), global longitudinal peak systolic strain (GLS), atrial and ventricular volumes, and caval blood flows were analyzed. Right ventricular (RV) AVPD and RV free wall GLS were lower in patients before PVR compared with controls ( P < 0.0001; P < 0.01) and decreased after PVR ( P < 0.0001 for both). Left ventricular AVPD was lower in patients before PVR compared with controls ( P < 0.05) and decreased after PVR ( P < 0.01). Left ventricular GLS did not differ between patients and controls ( P > 0.05). Right atrial reservoir volume and RV stroke volume generated by AVPD correlated in controls ( r = 0.93; P < 0.0001) and patients before PVR ( r = 0.88; P < 0.001) but not after PVR. In conclusion, there is a clear atrioventricular coupling in patients before PVR that is lost after PVR, possibly because of loss of pericardial integrity. Impaired atrioventricular coupling complicates assessment of ventricular function after surgery using measurements of longitudinal function. Changes in atrioventricular coupling seen in patients with rToF may be energetically unfavorable, and long-term effects of surgery on atrioventricular coupling is therefore of interest. Also, AVPD and GLS cannot be used interchangeably to assess longitudinal function in rToF. NEW & NOTEWORTHY There is a clear atrioventricular coupling in patients with Tetralogy of Fallot (ToF) and pulmonary regurgitation before surgical pulmonary valve replacement (PVR) that is lost after operation, possibly because of loss of pericardial integrity. The impaired atrioventricular coupling complicates assessment of ventricular function after surgery when using measurements of longitudinal function. Left ventricular atrioventricular plane displacement (AVPD) found differences between patients and controls and changes after PVR that longitudinal strain could not detect. This indicates that AVPD and strain cannot be used interchangeably to assess longitudinal function in repaired ToF.

Background: Nonalcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide. It is subdivided into nonalcoholic fatty liver (NAFL) and the more aggressive form, nonalcoholic steatohepatitis (NASH), which carries a higher risk of developing fibrosis and cirrhosis. There is currently no reliable non-invasive method for differentiating NASH from NAFL. Purpose: To investigate the ability of magnetic resonance imaging (MRI)-based imaging biomarkers to diagnose NASH and moderate fibrosis as well as assess their repeatability. Study Type: Prospective. Subjects: Sixty-eight participants (41% women) with biopsy-proven NAFLD (53 NASH and 15 NAFL). Thirty participants underwent a second MRI in order to assess repeatability. Field Strength/Sequence: 3.0 T; MR elastography (MRE) (a spin-echo echo-planar imaging [SE-EPI] sequence with motion-encoding gradients), MR proton density fat fraction (PDFF) and R2* mapping (a multi-echo three-dimensional gradient-echo sequence), T1 mapping (a single-point saturation-recovery technique), and diffusion-weighted imaging (SE-EPI sequence). Assessment: Quantitative MRI measurements were obtained and assessed alone and in combination with biochemical markers (cytokeratin-18 [CK18] M30, alanine transaminase [ALT], and aspartate transaminase [AST]) using logistic regression models. Models that could differentiate between NASH and NAFL and between moderate to advanced fibrosis (F2–4) and no or mild fibrosis (F0–1), based on the histopathological results, were identified. Statistical Tests: Independent samples t-test, Pearson's chi-squared test, area under the receiver operating characteristic curve (AUROC), Spearman's correlation, intra-individual coefficient of variation, and intraclass correlation coefficient (ICC). Statistical significance was set at P < 0.05. Results: There was a significant difference between the NASH and NAFL groups with liver stiffness assessed with MRE, CK18 M30, and ALT, with an AUROC of 0.74, 0.76, and 0.70, respectively. Both MRE and PDFF contributed significantly to a bivariate model for diagnosing NASH (AUROC = 0.84). MRE could significantly differentiate between F2–4 and F0–1 (AUROC = 0.74). A model combining MRE with AST improved the diagnosis of F2–4 (AUROC = 0.83). The ICC for repeatability was 0.94 and 0.99 for MRE and PDFF, respectively. Data Conclusion: MRE can potentially diagnose NASH and differentiate between fibrosis stages. Combining MRE with PDFF improves the diagnosis of NASH. Level of Evidence: 2. Technical Efficacy: Stage 2.

Yearly 16 000 osteoporosis related hip fractures occur in Sweden. They cause suffering for patients and high costs for society. Subsequent fractures can be reduced with osteoporosis diagnostics and treatment. 4 322 patients from two hospitals using Fracture Liaisson Services in Sweden were included to identify the rate of osteoporosis diagnostics and treatment during the first year after a hip fracture. Data between 2010-01-01 and 2018-12-31 were included from the Swedish National Hip Fracture Registry (Rikshöft). 99.2 % of all patients underwent FRAX risk assessment and DEXA was conducted on 17.3 % of patients. Women were more frequently examined with DEXA than men (21% vs 10.2 %). 6% received medical osteoporosis treatment after the fracture, women were treated more often than men (7% vs 4%). Conclusions: less than 10% received drug therapy after the first year after the hip fracture. Men underwent diagnostics and received treatment at a lower rate than women.

Previous studies have observed an inverse association between alcohol consumption and multiple sclerosis (MS) risk. We aimed to investigate possible interactions between alcohol consumption, MS-associated human leukocyte antigen (HLA) genes and smoking regarding MS risk. We used a Swedish population-based case–control study (2059 incident cases, 2887 controls) matched by age, sex, and residential area. Subjects with different genotypes and alcohol consumption habits were compared regarding MS risk, by calculating odds ratios with 95% confidence intervals using logistic regression models. Interaction on the additive scale between non-drinking and both genotype and smoking were assessed by calculating the attributable proportion due to interaction (AP). There was a dose-dependent inverse association between alcohol consumption and MS risk (p for trend

Objective To study white-coat hypertension (WCHT, blood pressure ≥140/90 mmHg in a clinic and normal blood pressure

Background and purpose — Having patients self-evaluate the outcome is an important part of the follow-up after knee arthroplasty. The Forgotten Joint Score-12 (FJS-12) introduced joint awareness as a new approach, suggested to be sensitive enough to differentiate well-functioning patients. This study evaluated the Swedish translation of the FJS-12 and investigated the validity, reliability, and interpretability in patients undergoing knee arthroplasty Patients and methods — We included 109 consecutive patients 1 year after primary knee arthroplasty to assess construct validity (Pearson’s correlation coefficient, r), internal consistency (Cronbach’s alpha [CA]), floor and ceiling effects, and score distribution. The Knee injury and Osteoarthritis Outcome Score (KOOS) was the comparator instrument for the analyses. Further, 31 patients preoperatively and 22 patients postoperatively were included to assess test–retest reliability (intraclass correlation coefficient [ICC]). Results — Construct validity was moderate to excellent (r = 0.62–0.84). The FJS-12 showed a high degree of internal consistency (CA = 0.96). The ICC was good preoperatively (0.76) and postoperatively (0.87). Ceiling effects were 2.8% in the FJS-12 and ranging between 0.9% and 10% in the KOOS. Interpretation — The Swedish translation of the FJS-12 showed good validity and reliability and can be used to assess outcome after knee arthroplasty. Moreover, the FJS-12 shows promising results in its ability to differentiate well-functioning patients. Future studies on unidimensionality, scale validity, interpretability, and responsiveness are needed for a more explicit analysis of the psychometric properties.

Background Biliary complications during pregnancy is an important issue. The aim of this study was to examine if there is an increased risk to perform cholecystectomy during pregnancy in patients with previous bariatric surgery in comparison to other females subjected to cholecystectomy. Methods The Nationwide Swedish Registry for Gallstone Surgery (GallRiks) and the Scandinavian Obesity Surgery Registry (SOReg) were combined. Female patients 18–45 years old were included. The study group was patients with a history of bariatric surgery whom were pregnant at the time of cholecystectomy. This group was compared with pregnant patients without previous bariatric surgery and non-pregnant with and without previous bariatric surgery. Results In total, 21,314 patients were included and 292 underwent surgery during pregnancy. From 1282 patients identified in both registers, 16 patients were pregnant at the time of cholecystectomy. Acute cholecystectomy was performed in 5922 (28%) non-pregnant and 199 (68%) pregnant (p p = 0.031) and length of stay (p = 0.043), but no differences were seen when only comparing patients with an acute indication for surgery. There was no difference in complications comparing pregnant patients with previous bariatric surgery with non-pregnant, both with and without previous bariatric surgery. Conclusions Cholecystectomy during pregnancy in patients with previous bariatric surgery seems to be safe. The increased risk seen in the non-pregnant group after previous bariatric surgery is not seen in pregnancy, possibly due to an optimization of the circumstances at surgery.

Background and purpose — The incidence of manipulation under anesthesia (MUA) after knee arthroplasty surgery has been reported to vary between 0.5% and 10%. We evaluated the incidence of MUA after primary knee arthroplasty in Sweden, the demographics of the patients and the risk of revision. Patients and methods — Between 2009 and 2013, 64,840 primary total and unicompartmental knee arthroplasties (TKA and UKA) were registered in the Swedish Knee Arthroplasty Register (SKAR). MUAs performed between 2009 and 2014 were identified through the in- and outpatient registers of the Swedish National Board of Health and Welfare. Pertinent data were verified through medical records and patient demographics and revisions were obtained from the SKAR. Results — 1,258 MUAs were identified. Of these, 1,078 were 1st-time MUAs, performed within 1 year after the primary knee arthroplasty. The incidence of MUA was 1.7% and the incidence varied between hospitals from 0% to 5%. The majority were performed after TKA (98%), in younger patients (65% < 65 years), women (64%), and relatively healthy persons (88% had ASA ≤ 2). The cumulative risk of revision at 10 years was 10% (95% CI 8.6–12), similar for men and women. Interpretation — In Sweden, MUA is a rather uncommon measure after knee arthroplasty, especially after UKA. The CRR at 10 years was doubled compared to the general knee arthroplasty population. The frequency of the procedure varies between hospitals but in general it is performed more frequently in healthier and younger patients.

Background: Patients with certain autoimmune diseases (AID) have an increased risk of developing diffuse large B-cell lymphoma (DLBCL). However, the occurrence of AID in patients with DLBCL as well ...

In a scientific effort to understand the reasons for low physical-activity levels among children, there is a need to consider how children perceive and interact with their complex environments holistically. This study outlines an image of the perceived landscape within which children in two lower-socioeconomic contexts engage in daily physical activity. By applying bioecological perspectives (Bronfenbrenner, U. 2005. Making human Beings human: Bioecological perspectives on human development. SAGE), the aim included an analysis of how the perceived landscape and its interrelated factors influence children’s physical activity. We used 15 focus-group interviews with children (n = 63, ages 8–13) from four different rural and suburban areas of southern and central Sweden. Through analyzing the children’s stories about their experiences of everyday physical activity from a bioecological perspective, an image of a complex landscape was revealed. Structural (schools’ institutional frameworks), cultural (local sports cultures), and environmental factors (e.g. schoolyard design) were evident in interpersonal relations within the microsystem and interacted with personal characteristics, primarily gender and level of physical competence and, thereby, affected the possibilities of the children engaging in proximal processes related to physical activity. This study contributes new qualitative understanding based on children’s voices about how the performance of daily physical activity among younger children (ages 7–13) in lower-socioeconomic areas may be considered an interactional process between individuals and their perceived environment, which can be thought of as a multidimensional landscape. Implications include actions which contribute to more diverse environments enabling proximal processes among a broader group of children.

Key Points Question Does fetal cardiovascular magnetic resonance improve prenatal diagnosis of complex congenital heart defects when fetal echocardiography is insufficient? Findings In this cohort study of 31 fetuses referred for fetal cardiovascular magnetic resonance imaging, additional clinically useful information regarding cardiovascular anatomy and function was obtained in 84% of referred cases, covering a wide spectrum of congenital heart defects. This information affected choice of mode of delivery, planning of early postnatal care, and parental counseling. Meaning These findings suggest that fetal cardiovascular magnetic resonance imaging can add important diagnostic information and affect clinical decision-making and parental counseling., This cohort study assesses the clinical utility of fetal cardiovascular magnetic resonance imaging when fetal echocardiography could not visualize all relevant anatomy., Importance Prenatal diagnosis of complex congenital heart defects reduces mortality and morbidity in affected infants. However, fetal echocardiography can be limited by poor acoustic windows, and there is a need for improved diagnostic methods. Objective To assess the clinical utility of fetal cardiovascular magnetic resonance imaging in cases in which fetal echocardiography could not visualize all relevant anatomy. Design, Setting, and Participants This cohort study was conducted between January 20, 2017, and June 29, 2020, at Skåne University Hospital (Lund, Sweden), a tertiary center for pediatric cardiology and thoracic surgery. Participants were fetuses referred for fetal cardiovascular magnetic resonance examination by a pediatric cardiologist after an inconclusive echocardiograph. Exposures Fetal cardiovascular magnetic resonance examination requested by the patient’s pediatric cardiologist. Main Outcomes and Measures Any change in patient management because of diagnostic information gained from fetal cardiovascular magnetic resonance imaging. Results A total of 31 fetuses underwent cardiovascular magnetic resonance examination at a median gestational age of 36 weeks (range, 31-39 weeks). Overall, fetal cardiovascular magnetic resonance imaging had clinical utility, affecting patient management and/or parental counseling in 26 cases (84%). For aortic arch anatomy including signs of coarctation (20 fetuses), fetal cardiovascular magnetic resonance imaging added diagnostic information in 16 cases (80%). For assessment of univentricular vs biventricular outcome in borderline left ventricle, unbalanced atrioventricular septal defect, and pulmonary atresia with intact ventricular septum (15 fetuses), fetal cardiovascular magnetic resonance imaging visualized intracardiac anatomy and ventricular function, allowing assessment of outcome in 13 cases (87%). In 4 fetuses with hypoplastic left heart syndrome, fetal cardiovascular magnetic resonance imaging helped delivery planning in 3 cases (75%). Finally, fetal cardiovascular magnetic resonance imaging provided valuable information for parental counseling in 21 cases (68%). Conclusions and Relevance In this cohort study, fetal cardiovascular magnetic resonance imaging added clinically useful information to what was available from echocardiography. These findings suggest that fetal CMR has the potential to affect clinical decision-making in challenging cases of congenital heart defects with inconclusive data from echocardiography. Fetal cardiovascular magnetic resonance imaging showed an association with clinical decision-making, including mode of delivery and early postnatal care, as well as with parental counseling.

We investigate the importance of adult children and/or cohabitation with a partner for older hip fracture patients' probability of independent living, public home care use and hospital readmission. Data from 35,066 Swedish hip fracture patients between 2012 and 2017, aged 65 years, and living at home at the time of the fracture in the Swedish Registry for Hip Fracture Patients and Treatment were linked with national registers. We applied adjusted logistic regression models and Cox proportional hazard models. In total, 959 (4.0%) women and 817 (7.3%) men had no adult children, 13,384 (56.0%) women and 3,623 (32.5%) men had no cohabiting partner and 2,780 (11.6%) women and 1,389 (12.5%) men neither had a cohabiting partner nor adult children. In comparison with women and men who had both a cohabiting partner and adult children, those without a cohabiting partner (i.e. only adult children) and those who neither had a cohabiting partner nor adult children had significantly lower probabilities of returning home (at discharge and after 4 months). They also had a greater probability of both receiving home care and having an increase in the amount of home care they receive. Having a close next of kin and hospital readmission were not associated. In conclusion, absence of a close next of kin, specifically a cohabiting partner, reduces the chance of return to independent living and increases the use of home care after a hip fracture hospitalisation. The findings highlight the importance of family support for older adults living situation after a hip fracture.

Background Charlson Comorbidity Index (CCI) has been suggested to be associated with mortality in hip fracture patients, to the same extent as more expensive and time-consuming tools. However, even CCI might be too time-consuming in a clinical setting. Aim To investigate whether the American Society of Anaesthesiologists score (ASA score), a simple grading from the anaesthesiologist’s examination, is comparable with CCI in the association with 1-year mortality after a hip fracture. Methods The study population was patients 60 + years registered in the Swedish Hip Fracture Registry with a first-time hip fracture between 1997 and 2017 (N = 165,596). The outcome was 1-year mortality, and the exposures were ASA score and CCI. The association between comorbidity and mortality was described with Kaplan–Meier curves and analyzed with Cox proportional hazards models. Results The Kaplan–Meier curves showed a stepwise increase in mortality for increasing values of both ASA and CCI. The Hazard Ratios (HRs) for the highest ASA (4–5) were 3.8 (95% Confidence Interval 3.5–4.2) for women and 3.2 (2.8–3.6) for men in the fully adjusted models. Adjusted HRs for the highest CCI (4 +) were 3.6 (3.3–3.9) for women and 2.5 (2.3–2.7) for men. Reference was the lowest score value for both tools. The correlation between the tools was moderate. Conclusions Both ASA and CCI show a similar stepwise association with 1-year mortality in hip fracture patients, despite measuring different factors and capturing different individuals at risk. Since the ASA score is already accessible for health care staff, it might be preferable to aid in prioritizing vulnerable hip fracture patients at risk of adverse outcomes.

Supplemental Digital Content is available in the text., Background: Hip fractures are common and severe conditions among older individuals, associated with high mortality, and the Nordic countries have the highest incidence rates globally. With this study, we aim to present a comprehensive picture of trends in hip fracture incidence and survival in the older Swedish population stratified by education, birth country, and comorbidity level. Methods: This study is based on a linkage of several population registers and included the entire population over the age of 60 living in Sweden. We calculated age-standardized incidence rates for first and recurrent hip fractures as well as age-standardized proportions of patients surviving 30 and 365 days through the time period 1998 to 2017. We calculated all outcomes for men and women in the total population and in each population stratum. Results: Altogether, we observed 289,603 first hip fractures during the study period. Age-standardized incidence rates of first and recurrent fractures declined among men and women in the total population and in each educational-, birth country-, and comorbidity group. Declines in incidence were more pronounced for recurrent than for first fractures. Approximately 20% of women and 30% of men died within 1 year of their first hip fracture. Overall, survival proportions remained constant throughout the study period but improved when taking into account comorbidity level. Conclusions: Hip fracture incidence has declined across the Swedish population, but mortality after hip fracture remained high, especially among men. Hip fracture patients constitute a vulnerable population group with increasing comorbidity burden and high mortality risk.

Summary Pathologies of the micro- and macrovascular systems are a hallmark of the metabolic syndrome, which can lead to chronically elevated blood pressure. However, the underlying pathomechanisms involved still need to be clarified. Here, we report that an obesity-associated increase in serum leptin triggers the select expansion of the micro-angioarchitecture in pre-autonomic brain centers that regulate hemodynamic homeostasis. By using a series of cell- and region-specific loss- and gain-of-function models, we show that this pathophysiological process depends on hypothalamic astroglial hypoxia-inducible factor 1α-vascular endothelial growth factor (HIF1α-VEGF) signaling downstream of leptin signaling. Importantly, several distinct models of HIF1α-VEGF pathway disruption in astrocytes are protected not only from obesity-induced hypothalamic angiopathy but also from sympathetic hyperactivity or arterial hypertension. These results suggest that hyperleptinemia promotes obesity-induced hypertension via a HIF1α-VEGF signaling cascade in hypothalamic astrocytes while establishing a novel mechanistic link that connects hypothalamic micro-angioarchitecture with control over systemic blood pressure., Graphical abstract, Highlights • The hypothalamic gliovascular interface is dynamically remodeled during obesity • Circulating leptin couples hypercaloric states with hypothalamic microangiopathy • Leptin-induced astroglial HIF1α-VEGF drives angiogenesis in the hypothalamus • VEGF in astrocytes promotes the development of arterial hypertension during obesity, Here, Gruber et al. show that during diet-induced obesity in mice there is a profound remodeling of the gliovascular interface in the hypothalamus, resulting in arterial hypertension. This process is driven by elevated leptin levels and upregulation of a HIF1α-VEGF signaling axis in local astrocytes.

Routine follow-up for diffuse large B-cell lymphoma have been shortened to 2 years when event-free survival at 24 months (EFS24) emerged as a new milestone. In the present study, we aimed to determine whether the achievement of this milestone affected overall survival (OS). We compared OS to that of an age- and sex-matched population, analysed other factors governing OS, and reviewed the causes of death. Data were collected from the Swedish Cancer Registry and from individual patient's records. We included 1169 adult patients from five counties between the years 2001 and 2014. The median (range) age was 64·6 (18-91) years, 56·6% were men and the median follow-up was 82·3 months. For early stages, the achievement of EFS12 did not improve OS. More than two-thirds of the patients (n = 837, 71·6%) achieved EFS24, of which 190 (22·7%) died during follow-up. Lymphoma (20%), cardiovascular disease (22·4%) and malignancies (16%) contributed to causes of death. Patients aged 60 years significantly affected OS after EFS24 compared with the standard population. We concluded that follow-up beyond EFS24 should be considered for patients aged >60 years. Amal Abu Sabaa and Charlott Mörth share first authorship

Potential long-term consequences of hypnotics remain controversial. We used the prospective Swedish National March Cohort, a study based on 41,695 participants with a mean follow-up duration of 18.9 years. Logistic regression models and Cox proportional hazards models with attained age as timescale were used to assess associations of hypnotic use with short- and long-term mortality. The proportion of subjects who initiated or discontinued hypnotic use during follow-up was substantial. All groups of hypnotics were associated with increased mortality within 2 years after a first prescription, with an overall OR of 2.38 (95% CI, 2.13-2.66). The association was more pronounced among subjects younger than 60 years (OR, 6.16; 95% CI, 3.98-9.52). There was no association between hypnotic use and long-term mortality. The association between hypnotic use and increased mortality was thus restricted to a relatively short period after treatment initiation, and may be explained in terms of confounding by indication.

Background and purpose — Waiting time to surgery for patients with hip fractures and its potential association with mortality has been frequently studied with the hypothesis that longer waiting time is associated with adverse outcomes. However, despite numerous studies, there is no consensus regarding which time frames are appropriate, and whether some patients are more vulnerable to waiting than others. We explored the association between waiting time to surgery and short-term mortality and whether sex, age, surgical method, and comorbidity (ASA) modified this association. Patients and methods — This is a nationwide cohort study of 59,675 patients undergoing hip fracture surgery between January 1, 2013 and December 31, 2017 with a 4-month follow-up of mortality. Data were extracted from the Swedish Registry for Hip Fracture Patients and Treatment (RIKSHÖFT) and mortality was obtained from Statistics Sweden. Results — Unadjusted analyses revealed an association between waiting more than 24 hours for surgery and increased mortality, primarily for women. However, when stratifying for ASA grade, an association persisted only among patients with ASA 3 and 4. Furthermore, the absolute differences in mortality risk between those waiting less or longer than 24 hours were small. Age, fracture type, and surgical method did not modify the association between waiting time and mortality. Interpretation — This study suggests that there may be a need for new guidelines, which take into account the heterogeneity of the patient population.

Objective Because obesity affects the cellular immune response to infections, we aimed to investigate whether high body mass index (BMI) in young adulthood and high Epstein-Barr nuclear antigen 1 (EBNA-1) antibody levels interact with regard to MS risk. We also aimed at exploring potential 3-way interactions between BMI at age 20 years, aspects of Epstein-Barr virus (EBV) infection (high EBNA-1 antibody levels and infectious mononucleosis [IM] history, respectively) and the human leukocyte antigen (HLA)-DRB1*15:01 allele. Methods Using Swedish population-based case-control studies (5,460 cases and 7,275 controls), we assessed MS risk in relation to interactions between overweight/obesity at age 20 years, IM history, EBNA-1 levels, and HLA-DRB1*15:01 status by calculating ORs with 95% CIs using logistic regression. Potential interactions were evaluated on the additive scale. Results Overweight/obesity, compared with normal weight, interacted significantly with high (>50th percentile) EBNA-1 antibody levels (attributable proportion due to interaction 0.2, 95% CI 0.1–0.4). The strength of the interaction increased with higher category of EBNA-1 antibody levels. Furthermore, 3-way interactions were present between HLA-DRB1*15:01, overweight/obesity at age 20 years, and each aspect of EBV infection. Conclusions With regard to MS risk, overweight/obesity in young adulthood acts synergistically with both aspects of EBV infection, predominantly among those with a genetic susceptibility to the disease. The obese state both induces a chronic immune-mediated inflammation and affects the cellular immune response to infections, which may contribute to explain our findings.

Background According to the European evidence-based consensus, published by European Crohn's and Colitis Organization (ECCO), diseases of the pancreas are included as extra-intestinal manifestations in IBD in the forms of acute pancreatitis (AP), chronic pancreatitis (CP), autoimmune pancreatitis (AIP), pancreatic duct abnormalities and pancreatic exocrine insufficiency (PEI). Presence of pancreatic autoantibodies directed against the exocrine of the pancreas has been reported in about one-third of CD. However, association between CD and PEI is not fully elucidated. Methods Patients with a diagnosis of CD were recruited at the Department for Digestive Diseases at Karolinska University Hospital in Stockholm, Sweden. Demographic, clinical and laboratory data were analyzed. Fecal elastase-1 (FE-1) measurements were performed using the enzyme-linked immunosorbent assay (ELISA) method. Results There were 20 patients included in the study, 13 (65%) males and 7 (35%) females, mean age 48.3±1.4 years (range 29-67 years). Mean duration of CD was 15.7±2.1 years (range 1-40 years). There were 11 (55%) patients without history of bowel surgery and 9 (45%) patients after ileocecal resection. FE-1 test was normal in all patients, among them 15 (75%) patients with the values of FE-1>500. Conclusions Fecal elastase-1 level was normal in all patients with CD strongly indicated absence of PEI in this group of patients.

Objective We aimed to investigate the influence of lean and fatty fish consumption on MS risk and to what extent a potential effect may be mediated by vitamin D. We also studied the interplay between fish consumption, sun exposure, DRB1*15:01, and A*02:01. Methods We used 2 population-based case-control studies (6,914 cases and 6,590 controls). Subjects with different fish consumption habits were compared regarding MS risk by calculating ORs with 95% CIs using logistic regression models. The mediation effect of vitamin D on the relationship between fish consumption and MS risk was assessed. Potential interactions between fish consumption, sun exposure, and MS-associated HLA genes were assessed on the additive scale. Results Irrespective of sun exposure habits, low fish consumption, including both lean and fatty fish, was associated with increased MS risk (OR 1.2, 95% CI 1.1–1.4) and interacted with the DRB1*15:01 allele (AP 0.3, p < 0.0001). The mediation analysis did not support vitamin D as a mediator of the association between fish consumption and MS risk. There was no interaction between fish consumption and sun exposure habits with regard to MS risk. Conclusions Low fish consumption and low sun exposure seem to be separate risk factors for MS. Our findings suggest that fish consumption predominantly influences MS risk by other means than by effecting vitamin D status, which is of relevance for prevention, in particular for those with a genetic susceptibility to MS.

The cause of obesity in narcolepsy type 1 (NT1) patients is not fully understood. The present study investigated if a reduced physical activity could explain weight gain in NT1. Seventy-nine patients were included in this retrospective study and divided into an NT1 group (n = 56) and a non-NT1 group (n = 23), including NT2 and idiopathic hypersomnia (IH). Accelerometry-derived measures of physical activity, total energy expenditure and skin temperature were collected from patients during seven consecutive days without medication. In addition, results from multiple sleep latency tests and the Epworth Sleepiness Scale questionnaire, body weight, height and CSF orexin/hypocretin were acquired. Three measurements of physical activity, including metabolic equivalent of task (MET), the average time of physical activity and step count, were compared without differences between groups. Neither could we find a significant difference in total energy expenditure or skin temperature. Thus, by analysing accelerometric data, we could not find any differences in the amount of physical activity or total energy expenditure explaining overweight in NT1.

Intracardiac hemodynamic forces have been proposed to influence remodeling and be a marker of ventricular dysfunction. We aimed to quantify the hemodynamic forces in patients with repaired tetralogy of Fallot (rToF) to further understand the pathophysiological mechanisms as this could be a potential marker for pulmonary valve replacement (PVR) in these patients. Patients with rToF and pulmonary regurgitation (PR) > 20% ( n = 18) and healthy control subjects ( n = 15) underwent MRI, including four-dimensional flow. A subset of patients ( n = 8) underwent PVR and MRI after surgery. Time-resolved hemodynamic forces were quantified using 4D-flow data and indexed to ventricular volume. Patients had higher systolic and diastolic left ventricular (LV) hemodynamic forces compared with control subjects in the lateral-septal/LV outflow tract ( P = 0.011 and P = 0.0031) and inferior-anterior ( P < 0.0001 and P < 0.0001) directions, which are forces not aligned with blood flow. Forces did not change after PVR. Patients had higher RV diastolic forces compared with control subjects in the diaphragm-right ventricular (RV) outflow tract (RVOT; P < 0.001) and apical-basal ( P = 0.0017) directions. After PVR, RV systolic forces in the diaphragm-RVOT direction decreased ( P = 0.039) to lower levels than in control subjects ( P = 0.0064). RV diastolic forces decreased in all directions ( P = 0.0078, P = 0.0078, and P = 0.039) but were still higher than in control subjects in the diaphragm-RVOT direction ( P = 0.046). In conclusion, patients with rToF and PR had LV hemodynamic forces less aligned with intraventricular blood flow compared with control subjects and higher diastolic RV forces along the regurgitant flow direction in the RVOT and that of tricuspid inflow. Remaining force differences in the LV and RV after PVR suggest that biventricular pumping does not normalize after surgery. NEW & NOTEWORTHY Biventricular hemodynamic forces in patients with repaired tetralogy of Fallot and pulmonary regurgitation were quantified for the first time. Left ventricular hemodynamic forces were less aligned to the main blood flow direction in patients compared with control subjects. Higher right ventricular forces were seen along the pulmonary regurgitant and tricuspid inflow directions. Differences in forces versus control subjects remain after pulmonary valve replacement, suggesting that altered biventricular pumping does not normalize after surgery.

PURPOSE: To validate metric optimized gating phase-contrast MR (MOG PC-MR) flow measurements for a range of fetal flow velocities in phantom experiments. 2) To investigate intra- and interobserver variability for fetal flow measurements at an imaging center other than the original site.METHODS: MOG PC-MR was compared to timer/beaker measurements in a pulsatile flow phantom using a heart rate (∼145 bpm), nozzle diameter (∼6 mm), and flow range (∼130-700 mL/min) similar to fetal imaging. Fifteen healthy fetuses were included for intra- and interobserver variability in the fetal descending aorta and umbilical vein.RESULTS: Phantom MOG PC-MR flow bias and variability was 2% ± 23%. Accuracy of MOG PC-MR was degraded for flow profiles with low velocity-to-noise ratio. Intra- and interobserver coefficients of variation were 6% and 19%, respectively, for fetal descending aorta; and 10% and 17%, respectively, for the umbilical vein.CONCLUSION: Phantom validation showed good agreement between MOG and conventionally gated PC-MR, except for cases with low velocity-to-noise ratio, which resulted in MOG misgating and underestimated peak velocities and warranted optimization of sequence parameters to individual fetal vessels. Inter- and intraobserver variability for fetal MOG PC-MR imaging were comparable to previously reported values.

ObjectiveWe hypothesize that different sources of lung irritation may contribute to elicit an immune reaction in the lungs and subsequently lead to multiple sclerosis (MS) in people with a genetic susceptibility to the disease. We aimed to investigate the influence of exposure to organic solvents on MS risk, and a potential interaction between organic solvents and MS risk human leukocyte antigen (HLA) genes.MethodsUsing a Swedish population-based case-control study (2,042 incident cases of MS and 2,947 controls), participants with different genotypes, smoking habits, and exposures to organic solvents were compared regarding occurrence of MS, by calculating odds ratios with 95% confidence intervals using logistic regression. A potential interaction between exposure to organic solvents and MS risk HLA genes was evaluated by calculating the attributable proportion due to interaction.ResultsOverall, exposure to organic solvents increased the risk of MS (odds ratio 1.5, 95% confidence interval 1.2–1.8, p = 0.0004). Among both ever and never smokers, an interaction between organic solvents, carriage of HLA-DRB1*15, and absence of HLA-A*02 was observed with regard to MS risk, similar to the previously reported gene-environment interaction involving the same MS risk HLA genes and smoke exposure.ConclusionThe mechanism linking both smoking and exposure to organic solvents to MS risk may involve lung inflammation with a proinflammatory profile. Their interaction with MS risk HLA genes argues for an action of these environmental factors on adaptive immunity, perhaps through activation of autoaggressive cells resident in the lungs subsequently attacking the CNS.

BACKGROUND Platelet microparticles (PMPs) are subcellular procoagulant vesicles released upon platelet activation. In people with clinical diseases, alterations in PMP concentrations have been extensively investigated, but few canine studies exist. OBJECTIVES This study aims to validate a canine flow cytometric protocol for PMP quantification and to assess the influence of calcium on PMP concentrations. METHODS Microparticles (MP) were quantified in citrated whole blood (WB) and platelet-poor plasma (PPP) using flow cytometry. Anti-CD61 antibody and Annexin V (AnV) were used to detect platelets and phosphatidylserine, respectively. In 13 healthy dogs, CD61+ /AnV- concentrations were analyzed with/without a calcium buffer. CD61+ /AnV- , CD61+ /AnV+ , and CD61- /AnV+ MP quantification were validated in 10 healthy dogs. The coefficient of variation (CV) for duplicate (intra-assay) and parallel (inter-assay) analyses and detection limits (DLs) were calculated. RESULTS CD61+ /AnV- concentrations were higher in calcium buffer; 841,800 MP/μL (526,000-1,666,200) vs without; 474,200 MP/μL (278,800-997,500), P

[Background] High reproducibility and low intra- and interobserver variability are important strengths of cardiac magnetic resonance (CMR). In clinical practice a significant learning curve may however be observed. Basic CMR courses offer an average of 1.4 h dedicated to lecturing and demonstrating left ventricular (LV) function analysis. The purpose of this study was to evaluate the effect of initial teaching on complete and intermediate beginners’ quantitative measurements of LV volumes and function by CMR., [Methods] Standard clinical cine CMR sequences were acquired in 15 patients. Five observers (two complete beginners, one intermediate, two experienced) measured LV volumes. Before initial evaluation beginners read the SCMR guidelines on CMR analysis. After initial evaluation, beginners participated in a two-hour teaching session including cases and hands-on training, representative for most basic CMR courses, after which it is uncertain to what extent different centres provide continued teaching and feedback in-house. Dice Similarity Coefficient (DSC) assessed delineations. Agreement, accuracy, precision, repeatability and reliability were assessed by Bland-Altman, coefficient of variation, and intraclass correlation coefficient methods., [Results] Endocardial DSC improved after teaching (+0.14 ± 0.17;p, [Conclusions] Initial teaching to complete beginners increases accuracy for assessment of LV volumes, however with high bias and low precision even after standardised teaching as offered in most basic CMR courses. Even though the intermediate beginner showed quite high accuracy already before teaching, precision did generally not improve after standardised teaching. To maintain CMR as a technique known for high accuracy and reproducibility and low intra- and inter-observer variability for quantitative measurements, internationally standardised training should be encouraged including high-quality feedback mechanisms. Objective measurements of training methods, training duration and, above all, quality of assessments are required., This work was supported by a European Union Grant (224495); the British Heart Foundation (Research Excellence Award RE/08/003 and FS/10/029/ 28253); the Biomedical Research Centre (BRC-CTF 196); the Wellcome Trust and EPSRC (WT 088641/Z/09/Z); Lund University Medical Faculty and Lund University Hospital, Sweden; the Foundation BLANCEFLOR BoncompagniLudovisi, née Bildt, Sweden; and the Swedish societies of Medicine, Cardiology, and Radiology; the Erasmus Mundus + Programme of the European Union (Framework Agreement number: 2013–0040); and the German Centre for Cardiovascular Research (DZHK).

Background and purpose - The number of revision total knee arthroplasties (TKA) is continuously increasing, leading to a growing need for reliable management of metaphyseal bone loss. We evaluated patients operated with a TKA using metal metaphyseal sleeves for bone defects with a minimum 5-year follow-up. Patients and methods - 37 patients had been operated on. 3 patients died and 3 patients were lost during follow-up. Of the 31 remainders (20 women), 9 had been operated on with a primary TKA and 22 with a revision TKA at the index surgery. The mean age at surgery was 69 (54-89) years and the mean follow-up time was 7.4 (5-12) years. Bone defects were classified according to the Anderson Orthopaedic Research Institute classification (tibia: type I n = 9, type II n = 5 and type III n = 17; femur: type I n = 12, type II n = 3 and type III n = 16). Results - At final follow-up one-third experienced an improvement concerning walking aids and walking distance. Except for 1 patient, all had full extension and a mean knee flexion of 110 (90-140) degrees. VAS pain at rest was 13 (SD 25) and on movement 30 (SD 31). 7 patients were reoperated due to: infection (n = 4), periprosthetic fracture (n = 1), skin necrosis (n = 1), and wound rupture (n = 1). The cumulative 5-year survival rate for reoperation was 77% (CI 63-92) and for revision 97% (CI 91-100). At the time of final follow-up, the sleeves showed good osseointegration with no signs of progressive radiolucency or migration. Interpretation - Titanium sleeves are a promising option in managing difficult cases with metaphyseal bone defects in TKA, providing a stable construct with good medium-term radiographic outcome.

Background: Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology. Objective: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS. Methods: Cases with onset Results: HLA–DRB1*15:01 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p −16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated ( p avg = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (ORmeta = 2.77, 95% confidence interval: 2.33, 3.32, p −16) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA–DRB1*15:01 and HLA–A*02. Conclusion: Pediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA–DRB1*15:01 and HLA–A*02 are also associated with POMS.

Dysphagia is a common and severe toxicity after oncological treatment of head and neck cancer (HNC). The study aim was to investigate relationships between patient-reported dysphagia and clinically measured swallowing function in HNC after modern curative radiotherapy with or without chemotherapy to identify possible alarm symptoms for clinically manifest dysphagia. Patients with tumors of the tonsil, base of tongue, hypopharynx, and larynx treated in 2007–2015 were assessed for dysphagia post-treatment by telephone interview and videofluoroscopy (VFS). A study-specific categorized symptom score was used to determine patient-reported dysphagia (DESdC = presence of Drinking, Eating, Swallowing difficulties, and Coughing when eating/drinking (any combination); scores between 0 and 4 with 0 = no symptom); the penetration–aspiration scale (PAS) to determine swallowing function by VFS. Swallowing difficulties were defined as DESdC ≥ 1 and PAS ≥ 2. Relationships between clinically relevant cut-offs for DESdC and PAS were determined by Pearson’s correlation coefficient (Pr). Swallowing difficulties according to DESdC were reported by 89% of the patients and according to PAS by 60% at a median of 7 months post-treatment. Averaged correlations between DESdC score 1/2/3/4 and PAS were 0.16/0.10/0.27/0.18. Almost one in two patients with DESdC score ≥3 had severe swallowing difficulties according to PAS. Correlations between individual DESdC:s were highest for swallowing and eating (Pr = 0.53) and lowest for swallowing and coughing (Pr = 0.11). Our data suggest that if a patient reports having swallowing difficulties, it is likely that he or she also has eating difficulties but not necessarily coughing problems when eating/drinking. However, if all these three symptoms are reported, it is likely that the patient will present with moderate or severe impaired swallowing function according to PAS and thus should be referred for further evaluation and treatment.

Interactions between environment and genetics may contribute to multiple sclerosis (MS) development. We investigated whether the previously observed interaction between smoking and HLA genotype in the Swedish population could be replicated, refined and extended to include other populations. We used six independent case–control studies from five different countries (Sweden, Denmark, Norway, Serbia, United States). A pooled analysis was performed for replication of previous observations (7190 cases, 8876 controls). Refined detailed analyses were carried out by combining the genetically similar populations from the Nordic studies (6265 cases, 8401 controls). In both the pooled analyses and in the combined Nordic material, interactions were observed between HLA-DRB*15 and absence of HLA-A*02 and between smoking and each of the genetic risk factors. Two way interactions were observed between each combination of the three variables, invariant over categories of the third. Further, there was also a three way interaction between the risk factors. The difference in MS risk between the extremes was considerable; smokers carrying HLA-DRB1*15 and lacking HLA-A*02 had a 13-fold increased risk compared with never smokers without these genetic risk factors (OR 12.7, 95% CI 10.8–14.9). The risk of MS associated with HLA genotypes is strongly influenced by smoking status and vice versa. Since the function of HLA molecules is to present peptide antigens to T cells, the demonstrated interactions strongly suggest that smoking alters MS risk through actions on adaptive immunity. Electronic supplementary material The online version of this article (doi:10.1007/s10654-017-0250-2) contains supplementary material, which is available to authorized users.

To compare two consecutive swallowing attempts to study if there is a difference in Rosenbek's penetration-aspiration scale (PAS) scores between the first and second swallowing attempt of the same bolus type in videofluoroscopic examination of swallowing (VFS). Additional aims include reflecting on which bolus sizes and consistencies are the most relevant to include in further studies for head and neck cancer (HNC) patients. The VFS for 38 patients curatively treated for HNC was studied. All included patients showed swallowing difficulties (PAS ≥ 2). The examination protocol included two swallows each of six different boluses: 3, 5, 10, 20 ml thin, 5 ml mildly thick, and 3 ml of extremely thick liquid. All boluses were compared between the first and second swallowing attempt with regard to PAS scores. No statistically significant differences in PAS were found between the first and second swallow for any of the boluses in this study on group level. For 20 ml thin and 3 ml extremely thick liquid, there were low Intra-Class Correlations, indicating a low within-bolus agreement. The greatest within-bolus differences were found for 20 ml thin, 5 ml mildly thick and 3 ml extremely thick liquid, which demonstrated high intra-individual coefficient of variation (0.458-0.759). The data of this study show a high within-bolus variability of the PAS score between two subsequent swallows for all different consistencies. In order to assess swallowing safety, the highest PAS score for each bolus type is suggested for use in studies of HNC patients.

Limited knowledge exists regarding the impact of symptomatic knee osteoarthritis (OA) on the overall gait pattern; and whether gait deviations are associated with performance-based measures (PBMs) and patient-reported outcomes (PROs). This cross-sectional study evaluated overall gait patterns in patients with knee OA using the Gait Deviation Index for kinematics (GDI) and kinetics (GDI-kinetic), and explored associations between gait deviations, PBMs, and PROs.Forty patients with knee OA and 25 age and gender-matched controls underwent three-dimensional gait analysis. Participants performed the Timed Up and Go (TUG), Five Times Sit-to-Stand (5STS), and Single Limb Mini Squat (SLMS) tests and completed a disease-specific PRO. Associations between gait deviations, PBMs, and PROs were assessed by Pearson's correlation and multiple linear regression.Patients with OA demonstrated significantly lower GDI and GDI-kinetic scores of the OA and contralateral limbs compared to controls; with GDI-kinetic scores on the contralateral limb more impacted than the OA limb. On the contralateral limb, GDI-kinetic score significantly correlated with TUG (r=-0.42) and 5STS (r=-0.33), while on the OA limb with TUG (r=-0.68), 5STS (r=-0.38), SLMS (r=-0.38), activities of daily living (r=0.35) and Knee-related Quality of Life (r=0.35). No significant associations existed between kinematic GDI scores, PBMs and PROs.The overall gait pattern, as represented by GDI and GDI-kinetic scores, in patients with symptomatic knee OA is affected both on the painful OA limb and the contralateral limb. The GDI and GDI-kinetic scores provide different information regarding function that is not revealed by PBMs or PROs.

Objectives To identify temporal patterns of patient-reported trismus during the first year post-radiotherapy, and to study their associations with maximal interincisal opening distances (MIOs). Design Single institution case series. Setting University hospital ENT clinic. Participants One hundred ninety six subjects who received radiotherapy (RT) for head and neck cancer (HNC) with or without chemotherapy in 2007-2012 to total dose of 64.6/68 Gy in 38/34 fractions, respectively. All subjects were prospectively assessed for mouth-opening ability (Gothenburg Trismus Questionnaire (GTQ), and MIO) pre-RT and at 3, 6, and 12 months after RT. Main outcome measures Correlations between temporally robust GTQ-symptoms and MIO as given by Pearson's correlation coefficients (Pr); temporally robust GTQ-symptom domains as given by factor analysis; rates of trismus with respect to baseline by risk ratios (RRs). Results Four temporally robust domains were identified: Eating (3-7 symptoms), Jaw (3-7), Pain (2-5), and Quality of Life (QoL, 2-5), and included 2-3 persistent symptoms across all post- RT assessments. The median RR for a moderate/severe (>2/>3) cut-off was the highest for Jaw (3.7/3.6) and QoL (3.2/2.9). The median Pr between temporally robust symptoms and MIO post-radiotherapy was 0.25-0.35/0.34-0.43/0.24-0.31/0.34-0.50 for Eating/Jaw/Pain/QoL, respectively. Conclusions Mouth-opening distances in HNC patients post-RT can be understood in terms of associated patient-reported outcomes on trismus-related difficulties. Our data suggest that a reduction in MIO can be expected as patients communicate their mouth-opening status to interfere with private/social life, a clinical warning signal for emerging or worsening trismus as patients are being followed after RT. This article is protected by copyright. All rights reserved.

Childhood obesity is associated with metabolic and cardiovascular comorbidities. The development of these alterations may have its origin in early life stages such as the lactation period through metabolic programming. Insulin resistance is a common complication in obese patients and may be responsible for the cardiovascular alterations associated with this condition. This study analyzed the development of cardiovascular insulin resistance in a rat model of childhood overweight induced by overfeeding during the lactation period. On birth day, litters were divided into twelve (L12) or three pups per mother (L3). Overfed rats showed a lower increase in myocardial contractility in response to insulin perfusion and a reduced insulin‐induced vasodilation, suggesting a state of cardiovascular insulin resistance. Vascular insulin resistance was due to decreased activation of phosphoinositide 3-kinase (PI3K)/Akt pathway, whereas cardiac insulin resistance was associated with mitogen-activated protein kinase (MAPK) hyperactivity. Early overfeeding was also associated with a proinflammatory and pro-oxidant state, endothelial dysfunction, decreased release of nitrites and nitrates, and decreased gene expression of insulin receptor (IR), glucose transporter-4 (GLUT-4), and endothelial nitric oxide synthase (eNOS) in response to insulin. In conclusion, overweight induced by lactational overnutrition in rat pups is associated with cardiovascular insulin resistance that could be related to the cardiovascular alterations associated with this condition.

IntroductionSmoking has consistently been associated with increased risk of developing rheumatoid arthritis (RA). The aim of this study was to estimate the influence of passive smoking on the risk of developing anti-cyclic citrullinated peptide antibodies (ACPA)-positive and ACPA-negative RA.MethodsA population-based case–control study using incident cases of RA was performed in Sweden, and the study population in this report was restricted to include never-smokers (589 cases, 1764 controls). The incidence of RA among never-smokers who had been exposed to passive smoking was compared with that of never-smokers who had never been exposed, by calculating the OR with a 95% CI employing logistic regression.ResultsNo association was observed between exposure to passive smoking and RA risk (OR 1.0, 95% CI 0.8 to 1.2 for ACPA-positive RA, and OR 0.9, 95% CI 0.7 to 1.2, for ACPA-negative RA). No suggestion of a trend between duration of passive smoking and RA risk was observed.DiscussionsNo association was observed between exposure to passive smoking and RA risk, which may be explained by a threshold below which no association between smoke exposure and RA occurs.

The objective of the study was to compare patients with hip fracture in the Swedish Hip Fracture Register (SHR) and the National Patient Register (NPR) between 2008 and 2017 regarding coverage, agreement, and representativeness.The NPR and SHR were linked through the personal identity number assigned to all residents of Sweden. The proportion of matching records in both registers was calculated in total, for different fracture types, and for the first and recurrent fractures separately. Representativeness was estimated using logistic regression and survival analysis.The agreement between fracture types in both registers was excellent, but our comparison with the SHR indicated that the NPR may overestimate the number of recurrent fractures in Sweden. The SHR covers more than 80% of all hip fractures in the NPR. Patients in the SHR were similar to those in the NPR with regard to many, but not all, characteristics and long-term survival. However, patients who die shortly after hip fracture were underreported to the SHR.Both registers are valuable data sources for epidemiological research. Although neither register constitutes a gold standard, their excellent agreement suggests high-data quality. Nevertheless, both registers have some limitations that may be relevant depending on the research question under study.

Aim Critical illness myopathy (CIM) represents a common consequence of modern intensive care, negatively impacting patient health and significantly increasing health care costs; however, there is no treatment available apart from symptomatic and supportive interventions. The chaperone co-inducer BGP-15 has previously been shown to have a positive effect on the diaphragm in rats exposed to the intensive care unit (ICU) condition. In this study, we aim to explore the effects of BGP-15 on a limb muscle (soleus muscle) in response to the ICU condition. Methods Sprague-Dawley rats were subjected to the ICU condition for 5, 8 and 10 days and compared with untreated sham-operated controls. Results BGP-15 significantly improved soleus muscle fibre force after 5 days exposure to the ICU condition. This improvement was associated with the protection of myosin from post-translational myosin modifications, improved mitochondrial structure/biogenesis and reduced the expression of MuRF1 and Fbxo31 E3 ligases. At longer durations (8 and 10 days), BGP-15 had no protective effect when the hallmark of CIM had become manifest, that is, preferential loss of myosin. Unrelated to the effects on skeletal muscle, BGP-15 had a strong positive effect on survival compared with untreated animals. Conclusions BGP-15 treatment improved soleus muscle fibre and motor protein function after 5 days exposure to the ICU condition, but not at longer durations (8 and 10 days) when the preferential loss of myosin was manifest. Thus, long-term CIM interventions targeting limb muscle fibre/myosin force generation capacity need to consider both the post-translational modifications and the loss of myosin.

Preeclampsia (PE) is a common pregnancy-related disorder associated with cardiovascular long-term disease. Eighty percent are late-onset PE, occurring after 34 gestational weeks, and can present with severe symptoms. Magnitude and reversibility rate of maternal cardiovascular changes after severe late-onset PE have not been characterized. This study therefore evaluated longitudinal dynamics of maternal cardiovascular changes after severe late-onset PE.Six previously normotensive women with severe late-onset PE and eight pregnant controls were included. Severe PE was defined as systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 110 mmHg and proteinuria with/without evidence of end-organ dysfunction, or SBP ≥ 140 mmHg or DBP ≥ 90 mmHg with/without proteinuria and with evidence of end-organ dysfunction. Cardiovascular function was assessed by magnetic resonance imaging at 1-3 days, one week and six months postpartum.Left ventricular mass at 1-3 days postpartum was higher after severe late-onset PE (57 g/mCardiac effects after severe late-onset PE were small and transient. This indicates that left ventricular hypertrophy after severe late-onset PE may be a secondary physiologic response to increased peripheral resistance in PE. Vascular mechanisms rather than persistent cardiac hypertrophy postpartum may be the culprit for increased long-term cardiovascular risk after PE.

Preeclampsia is a human placental disorder affecting 2–8% of pregnancies worldwide annually, with hypertension and proteinuria appearing after 20 weeks of gestation. The underlying cause is believed to be incomplete trophoblast invasion of the maternal spiral arteries during placentation in the first trimester, resulting in oxidative and nitrative stress as well as maternal inflammation and organ alterations. In the Storkhead box 1 (STOX1) preeclampsia mouse model, pregnant females develop severe and early onset manifestations as seen in human preeclampsia e.g. gestational hypertension, proteinuria, and organ alterations. Here we aimed to evaluate the therapeutic potential of human recombinant alpha-1 microglobulin (rA1M) to alleviate the manifestations observed. Human rA1M significantly reduced the hypertension during gestation and significantly reduced the level of hypoxia and nitrative stress in the placenta. In addition, rA1M treatment reduced cellular damage in both placenta and kidneys, thereby protecting the tissue and improving their function. This study confirms that rA1M has the potential as a therapeutic drug in preeclampsia, and likely also in other pathological conditions associated with oxidative stress, by preserving normal organ function.

Introduction Fetal cardiovascular magnetic resonance (CMR) imaging is used clinically and for research, but has been previously limited due to lack of direct gating methods. A CMR-compatible Doppler ultrasound (DUS) gating device has resolved this. However, the DUS-gating method is not validated against the current reference method for fetal phase-contrast blood flow measurements, metric optimized gating (MOG). Further, we investigated how different methods for vessel delineation affect flow volumes and observer variability in fetal flow acquisitions. Aims To 1) validate DUS gating versus MOG for quantifying fetal blood flow; 2) assess repeatability of DUS gating; 3) assess impact of region of interest (ROI) size on flow volume; and 4) compare time-resolved and static delineations for flow volume and observer variability. Methods Phase-contrast CMR was acquired in the fetal descending aorta (DAo) and umbilical vein by DUS gating and MOG in 22 women with singleton pregnancy in gestational week 360 (265–400) with repeated scans in six fetuses. Impact of ROI size on measured flow was assessed for ROI:s 50–150% of the vessel diameter. Four observers from two centers provided time-resolved and static delineations. Bland-Altman analysis was used to determine agreement between both observers and methods. Results DAo flow was 726 (348–1130) ml/min and umbilical vein flow 366 (150–782) ml/min by DUS gating. Bias±SD for DUS-gating versus MOG were − 45 ± 122 ml/min (−6 ± 15%) for DAo and 19 ± 136 ml/min (2 ± 24%) for umbilical vein flow. Repeated flow measurements in the same fetus showed similar volumes (median CoV = 11% (DAo) and 23% (umbilical vein)). Region of interest 50–150% of vessel diameter yielded flow 35–120%. Bias±SD for time-resolved versus static DUS-gated flow was 33 ± 39 ml/min (4 ± 6%) for DAo and 11 ± 84 ml/min (2 ± 15%) for umbilical vein flow. Conclusions Quantification of blood flow in the fetal DAo and umbilical vein using DUS-gated phase-contrast CMR is feasible and agrees with the current reference method. Repeatability was generally high for CMR fetal blood flow assessment. An ROI similar to the vessel area or slightly larger is recommended. A static ROI is sufficient for fetal flow quantification using currently available CMR sequences.