Real-life experiences of switching from intravenous to subcutaneous vedolizumab maintenance therapy in patients with inflammatory bowel disease.

BACKGROUND: A few prospective cohort studies support the safety of switching from intravenous to subcutaneous administration of vedolizumab during maintenance therapy in patients with inflammatory bowel disease. Real-life data on switching after intravenous induction therapy are lacking. OBJECTIVE: The aim was to obtain real-world data on subcutaneous vedolizumab treatment in patients with inflammatory bowel disease after switching from intravenous vedolizumab induction or maintenance therapy, and to evaluate treatment persistence, safety, and changes in disease activity and serum vedolizumab concentrations. METHODS: We performed a retrospective registry-based study of inflammatory bowel disease patients who received subcutaneous vedolizumab therapy in two tertiary centres. RESULTS: Altogether, 103 patients (26 Crohn's disease and 77 ulcerative colitis) switching from intravenous maintenance therapy (group 1) and 44 patients (14 and 30, respectively) switching from intravenous induction therapy (group 2) were included. At 6 months from baseline, 90.3% of the patients in group 1 and 90.9% of the patients in group 2 continued on subcutaneous vedolizumab. After the switch in group 1, disease activity remained stable. In group 2, clinical disease activity decreased significantly in ulcerative colitis patients (P = 0.002). The median serum vedolizumab concentration was 34.00 µg/ml during subcutaneous maintenance therapy in group 1, which was significantly higher than the median concentration during intravenous therapy (17.00 µg/ml, P < 0.001), but remained unchanged in group 2 after the switch (31.50 µg/ml). CONCLUSION: Based on these data, subcutaneous vedolizumab treatment is well-tolerated and the treatment persistence remains high after switching from intravenous to subcutaneous vedolizumab therapy.

Daily standing time, dietary fiber, and intake of unsaturated fatty acids are beneficially associated with hepatic insulin sensitivity in adults with metabolic syndrome.

Background: Obesity is associated with impaired glucose metabolism and hepatic insulin resistance. The aim was to investigate the associations of hepatic glucose uptake (HGU) and endogenous glucose production (EGP) to sedentary behavior (SB), physical activity (PA), cardiorespiratory fitness, dietary factors, and metabolic risk markers. Methods: Forty-four adults with metabolic syndrome (mean age 58 [SD 7] years, BMI ranging from 25-40kg/; 25 females) were included. HGU was measured by positron emission tomography during the hyperinsulinemic-euglycemic clamp. EGP was calculated by subtracting the glucose infusion rate during clamp from the glucose rate of disappearance. SB and PA were measured with hip-worn accelerometers (26 [SD3] days). Fitness was assessed by maximal bicycle ergometry with respiratory gas measurements and dietary intake of nutrients by 4-day food diaries. Results: HGU was not associated with fitness or any of the SB or PA measures. When adjusted for sex, age, and body fat-%, HGU was associated with whole-body insulin sensitivity (ß=0.58), water-insoluble dietary fiber (ß=0.29), energy percent (E%) of carbohydrates (ß=-0.32), saccharose (ß=-0.32), mono- and polyunsaturated fatty acids (ß=0.35, ß=0.41, respectively). EGP was associated with whole-body insulin sensitivity (ß=-0.53), and low-density lipoprotein cholesterol [ß=-0.31], and when further adjusted for accelerometry wear time, EGP was associated with standing [ß=-0.43]. (p-value for all< 0.05). Conclusions: Standing more, consuming a diet rich in fiber and unsaturated fatty acids, and a lower intake of carbohydrates, especially sugar, associate beneficially with hepatic insulin sensitivity. Habitual SB, PA, or fitness may not be the primary modulators of HGU and EGP. However, these associations need to be confirmed with intervention studies.

Germline-specific RNA helicase DDX4 forms cytoplasmic granules in cancer cells and promotes tumor growth.

Cancer cells undergo major epigenetic alterations and transcriptomic changes, including ectopic expression of tissue- and cell-type-specific genes. Here, we show that the germline-specific RNA helicase DDX4 forms germ-granule-like cytoplasmic ribonucleoprotein granules in various human tumors, but not in cultured cancer cells. These cancerous DDX4 complexes contain RNA-binding proteins and splicing regulators, including many known germ granule components. The deletion of DDX4 in cancer cells induces transcriptomic changes and affects the alternative splicing landscape of a number of genes involved in cancer growth and invasiveness, leading to compromised capability of DDX4-null cancer cells to form xenograft tumors in immunocompromised mice. Importantly, the occurrence of DDX4 granules is associated with poor survival in patients with head and neck squamous cell carcinoma and higher histological grade of prostate cancer. Taken together, these results show that the germ-granule-resembling cancerous DDX4 granules control gene expression and promote malignant and invasive properties of cancer cells.

Evaluation of bone marrow glucose uptake and adiposity in male rats after diet and exercise interventions.

Objectives: Obesity impairs bone marrow (BM) glucose metabolism. Adult BM constitutes mostly of adipocytes that respond to changes in energy metabolism by modulating their morphology and number. Here we evaluated whether diet or exercise intervention could improve the high-fat diet (HFD) associated impairment in BM glucose uptake (BMGU) and whether this associates with the morphology of BM adipocytes (BMAds) in rats. Methods: Eight-week-old male Sprague-Dawley rats were fed ad libitum either HFD or chow diet for 24 weeks. Additionally after 12 weeks, HFD-fed rats switched either to chow diet, voluntary intermittent running exercise, or both for another 12 weeks. BMAd morphology was assessed by perilipin-1 immunofluorescence staining in formalin-fixed paraffin-embedded tibial sections. Insulin-stimulated sternal and humeral BMGU were measured using [18F]FDG-PET/CT. Tibial microarchitecture and mineral density were measured with microCT. Results: HFD rats had significantly higher whole-body fat percentage compared to the chow group (17% vs 13%, respectively; p = 0.004) and larger median size of BMAds in the proximal tibia (815 µm2 vs 592 µm2, respectively; p = 0.03) but not in the distal tibia. Switch to chow diet combined with running exercise normalized whole-body fat percentage (p < 0.001) but not the BMAd size. At 32 weeks of age, there was no significant difference in insulin-stimulated BMGU between the study groups. However, BMGU was significantly higher in sternum compared to humerus (p < 0.001) and higher in 8-week-old compared to 32-week-old rats (p < 0.001). BMAd size in proximal tibia correlated positively with whole-body fat percentage (r = 0.48, p = 0.005) and negatively with humeral BMGU (r = -0.63, p = 0.02). HFD significantly reduced trabecular number (p < 0.001) compared to the chow group. Switch to chow diet reversed this as the trabecular number was significantly higher (p = 0.008) than in the HFD group. Conclusion: In this study we showed that insulin-stimulated BMGU is age- and site-dependent. BMGU was not affected by the study interventions. HFD increased whole-body fat percentage and the size of BMAds in proximal tibia. Switching from HFD to a chow diet and running exercise improved glucose homeostasis and normalized the HFD-induced increase in body fat but not the hypertrophy of BMAds.

Maternal risk factors for congenital vertebral formation and mixed defects: A population-based case-control study.

Background: The etiology and risk factors of congenital vertebral anomalies are mainly unclear in isolated cases. Also, there are no reports on the risk factors for different subgroups of vertebral anomalies. Therefore, we assessed and identified potential maternal risk factors for these anomalies and hypothesized that diabetes, other chronic diseases, smoking, obesity, and medication in early pregnancy would increase the risk of congenital vertebral anomalies. Methods: All cases with congenital vertebral anomalies were identified in the Finnish Register of Congenital Malformations from 1997 to 2016 for this nationwide register-based case-control study. Five matched controls without vertebral malformations were randomly selected. Analyzed maternal risk factors included maternal age, body mass index, parity, smoking, history of miscarriages, chronic diseases, and prescription drug purchases in early pregnancy. Results: The register search identified 256 cases with congenital vertebral malformations. After excluding 66 syndromic cases, 190 non-syndromic malformations (74 formation defects, 4 segmentation defects, and 112 mixed anomalies) were included in the study. Maternal smoking was a significant risk factor for formation defects (adjusted odds ratio 2.33, 95% confidence interval 1.21-4.47). Also, pregestational diabetes (adjusted odds ratio 8.53, 95% confidence interval 2.33-31.20) and rheumatoid arthritis (adjusted odds ratio 13.19, 95% confidence interval 1.31-132.95) were associated with mixed vertebral anomalies. Conclusion: Maternal pregestational diabetes and rheumatoid arthritis were associated with an increased risk of mixed vertebral anomalies. Maternal smoking increases the risk of formation defects and represents an avoidable risk factor for congenital scoliosis. Level of evidence: III.

Duodenal Atresia in Finland from 2004 to 2017: Prevalence, Mortality, and Associated Anomalies-A Population-Based Study.

INTRODUCTION: Duodenal atresia (DA) is the most common atresia of the small bowel. This study aims to assess the prevalence, mortality, and associated anomalies related to DA in Finland from 2004 to 2017. MATERIAL AND METHODS: A nationwide study based on registers maintained by the Finnish Institute for Health and Welfare and Statistics Finland containing data on all live births and stillbirths and terminations of pregnancy. The cases were identified based on the ICD-9 and 10 (International Classification of Diseases revisions 9 and 10) codes. Associated anomalies were classified based on the EUROCAT criteria; minor anomalies were excluded. RESULTS: There were 249 DA cases including 222 (89.2%) live births, 16 (6.4%) stillbirths, and 11 (4.4%) terminations. There was no significant change in the prevalence rates between 2004 and 2017. Live birth prevalence was 2.75/10,000 and total prevalence was 3.08/10,000 births. A total of 100 (40.2%) cases were isolated, 67 (26.9%) had other multiple congenital anomalies, and 83 (33.3%) were syndromic. There were no terminations in isolated DA. Most associated anomalies were cardiac (36.1%), followed by other gastrointestinal tract anomalies (23.7%) and limb deformities/defects (7.2%). Trisomy 21 was observed in 63 cases (25.3%). Neonatal mortality was 3.6% (n = 8) and at 1 year 95.0% were alive. Both neonatal and infant mortalities were associated with cardiac anomalies (p < 0.001 and p = 0.001, respectively). All neonatal deaths had associated cardiac defect(s). CONCLUSIONS: The prevalence of DA in Finland remains stable and among the highest reported. DA is often associated with cardiac anomalies, which portend a high risk for mortality. Despite the burden of associated anomalies, overall survival is high.

Sensorimotor tests in patients with neck pain and its associated disorders: a systematic review and meta-analysis.

This systematic review aimed to synthesize the current evidence regarding neck sensorimotor testing in individuals with neck pain, assess the differences between neck pain groups and healthy controls, and recognize factors that might affect test results. We performed the data search using PubMed, Embase, PsycINFO, CINAHL, and Scopus databases. We used a two-step screening process to identify studies. Furthermore, we screened the reference lists for additional studies. Hedges g was used to present the difference between neck pain groups and asymptomatic individuals. We assessed the quality of the studies using the QUADAS tool. The final review included 34 studies, of which 25 were related to the joint position error test, four to the smooth pursuit neck torsion test and six to the balance test. Our meta-analysis showed poorer joint-position sense, oculomotor function, and wider postural sway in individuals with neck pain than healthy controls. The size of the difference between the groups seemed to be influenced by the intensity of the pain and the presence of dizziness. Therefore, it might be helpful in future studies to differentiate patients with neck pain into subgroups based on their symptom and demographic profiles to assess other factors that significantly affect cervical sensorimotor control.

Tiredness after work associates with less leisure-time physical activity.

Physical activities and sedentary behaviors take place in different contexts. This study aimed to determine if the context, total score, and leisure-time MET-index assessed by the Baecke questionnaire associate with each other or with sedentary behavior and physical activity outcomes from a 4-week accelerometer measurement in physically inactive adults with overweight. The item "After working I am tired" correlated negatively with items related to leisure-time physical activity and sports participation. The total Baecke Score showed weak but significant correlations with accelerometer-measured sedentary behavior, physical activity, daily steps, and mean activity intensity of the day (r = - 0.33, 0.41, 0.35, and 0.41, respectively). The associations strengthened when the Sport Index was omitted from the Score. The leisure-time MET-Index did not correlate with accelerometer-measured sedentary behavior or physical activity. Tiredness after working associated with less self-reported physical activity during leisure time. This suggests that better recovery from work-related stress could increase leisure-time physical activity, or increasing leisure-time physical activity could reduce tiredness after working. Moreover, among self-reportedly inactive adults with overweight, focusing the questionnaire on work and non-sport leisure time instead of total time might give more accurate estimates of sedentary behavior and physical activity when compared to accelerometry.The study is registered at ClinicalTrials.gov (NCT03101228, 05/04/2017).

Mechanisms Leading to Increased Insulin-Stimulated Cerebral Glucose Uptake in Obesity and Insulin Resistance: A High-Fat Diet and Exercise Training Intervention PET Study with Rats (CROSRAT).

Recent studies have shown that obesity and insulin resistance are associated with increased insulin-stimulated glucose uptake (GU) in the brain. Thus, insulin sensitivity seems to work differently in the brain compared to the peripheral tissues like skeletal muscles, but the underlying mechanisms remain unknown. Regular exercise training improves skeletal muscle and whole-body insulin sensitivity. However, the effect of exercise on glucose metabolism in the brain and internal organs is less well understood. The CROSRAT study aims to investigate the effects of exercise training on brain glucose metabolism and inflammation in a high-fat diet-induced rat model of obesity and insulin resistance. Male Sprague Dawley rats (n = 144) are divided into nine study groups that undergo different dietary and/or exercise training interventions lasting 12 to 24 weeks. Insulin-stimulated GU from various tissues and brain inflammation are investigated using [18F]FDG-PET/CT and [11C]PK11195-PET/CT, respectively. In addition, peripheral tissue, brain, and fecal samples are collected to study the underlying mechanisms. The strength of this study design is that it allows examining the effects of both diet and exercise training on obesity-induced insulin resistance and inflammation. As the pathophysiological changes are studied simultaneously in many tissues and organs at several time points, the study provides insight into when and where these pathophysiological changes occur.

Survival, cumulative hospital days and infectious complications in urgent-start PD compared with urgent-start HD.

BACKGROUND: Urgent-start peritoneal dialysis (PD) carries a similar efficacy and safety profile compared to urgent-start haemodialysis (HD) but is only sparsely applied due to resource issues and concerns of complication risks. Furthermore, few data exist on adverse outcomes associated with central venous catheter (CVC) insertions in urgent-start HD patients. Thus, we sought to compare patient and dialysis-related outcomes in patients undergoing urgent-start PD or HD. METHODS: All patients initiating urgent-start PD in a tertiary research hospital in 2005-2018 were included in this retrospective, single-centre, comparative study and matched with urgent-start HD patients of similar age and chronic kidney disease aetiology. All urgent-start PDs were initiated within 72 h after catheter insertion, and urgent-start HDs were performed via a CVC. All analyses were performed at 3 months and at 1 year of follow-up, respectively. RESULTS: Thirty-three patients who commenced urgent-start PD and 58 matched urgent-start HD control patients were included. Altogether, 26 patients (29%; PD: 36%, HD 24%) died within the 1-year follow-up, and patient survival was similar at 3 months (hazard ratio (HR): 1.15, 95% confidence interval (CI): 0.35-3.81, p = 0.82) and at 1 year of follow-up (HR: 0.64, 95% CI: 0.30-1.39, p = 0.26) between the study groups. There were no differences in the total kidney replacement therapy (KRT)-related infection rate (p = 0.66) or cumulative first-year hospital care days (p = 0.43) between the treatment groups. Altogether, 139 CVCs were inserted during the 1-year follow-up. The number of CVCs per patient was associated with the emergence of blood culture-positive bacteraemia and increased cumulative first-year hospital care days. CONCLUSIONS: Patient survival, cumulative first-year hospital care days and total KRT-related infection rate at 3 months and 1-year follow-up are similar between urgent-start PD and urgent-start HD patients. Furthermore, CVC insertion rate is associated with incident blood culture-positive bacteraemia and increased cumulative first-year hospital care days.

Sedentary time associates detrimentally and physical activity beneficially with metabolic flexibility in adults with metabolic syndrome.

Metabolic flexibility (MetFlex) describes the ability to respond and adapt to changes in metabolic demand and substrate availability. The relationship between physical (in)activity and MetFlex is unclear. This study aimed to determine whether sedentary time, physical activity (PA), and cardiorespiratory fitness associate with MetFlex. Sedentary time, standing, and PA were measured with accelerometers for 4 weeks in 64 sedentary adults with metabolic syndrome [37 women, 27 men; 58.3 (SD 6.8) years]. Fitness (V̇o2max; mL·kg-1·min-1) was measured with graded maximal cycle ergometry. MetFlex was assessed with indirect calorimetry as the change in respiratory exchange ratio (ΔRER) from fasting to insulin stimulation with hyperinsulinemic-euglycemic clamp and from low-intensity to maximal exercise. Carbohydrate (CHOox) and fat oxidation (FATox) were calculated from respiratory gases. High sedentary time associated with higher fasting RER [ß = 0.35 (95% confidence interval: 0.04, 0.67)], impaired insulin-stimulated MetFlex (ΔRER) [ß=-0.41 (-0.72, -0.09)], and lower fasting FATox [ß=-0.36 (-0.67, -0.04)]. Standing associated with lower fasting RER [ß=-0.32 (-0.62, -0.02)]. Higher standing time and steps/day associated with higher fasting FATox [ß = 0.31 (0.01, 0.61), and ß = 0.26 (0.00, 0.53)]. Light-intensity and total PA associated with better insulin-stimulated MetFlex [ß = 0.33 (0.05, 0.61)], and ß = 0.33 (0.05, 0.60)]. Higher V̇o2max associated with higher CHOox during maximal exercise [ß = 0.81 (0.62, 1.00)], as well as during insulin stimulation [ß = 0.43 (0.13, 0.73)]. P values are less than 0.05 for all associations. Sedentary time and PA associate with MetFlex. Reducing sitting and increasing PA of even light intensity might aid in the prevention of metabolic diseases in risk populations through their potential effects on energy metabolism.NEW & NOTEWORTHY High accelerometer-assessed sedentary time associates with metabolic inflexibility measured during hyperinsulinemic-euglycemic clamp in adults with metabolic syndrome, and more light-intensity and total physical activity associate with more metabolic flexibility. Physical activity behaviors may thus play an important role in the regulation of fuel metabolism. This highlights the potential of reduced sedentary time and increased physical activity of any intensity to induce metabolic health benefits and help in disease prevention in risk populations.

The changing incidence of childhood epilepsy in Finland.

INTRODUCTION: to investigate the childhood epilepsy incidence, population trends, associated factors, and validate the national population registers. METHODS: a comprehensive comparative analysis of childhood epilepsy in the population during two distinct time intervals using medical records, appropriate national medical and population registers, and two random samples for control. RESULTS: In 1961-1964, the average incidence of epilepsy was 38/100,000 and during 1991-2000 65.9 (95 % CI 59.6 to 72.2) and 65.6/100,000 person-years after adjustment for the European Standard Population. This increase was significant (p<0.0001) as was a decline (p<0.003) from 1991 to 1995 to 1996-2000. The decline in incidence for girls occurred at a younger age compared to boys. Epilepsy cases associated with prenatal and perinatal factors were 50 % lower in 1991-2000 than in 1961-1964, especially related to asphyxia, infections, pre-eclampsia, and imminent abortion. The national Register for Healthcare independently identified 94.5 % of relevant cases (University Hospital alone 81.2 %, and Drug Register alone 74.3 %). DISCUSSION: Over the past five decades, the incidence rate of childhood epilepsy has exhibited a dynamic pattern, with a notable increase until the 1990's, followed by a stabilization at an incidence rate of approximately 60-70 per 100,000 person-years. Our findings, in line with other recent Finnish research, support a significant decrease in incidence since the mid-1990's. The underlying reasons for the increase and decrease remain unclear. Finnish national registers for epilepsy have established themselves as highly dependable resources for conducting epidemiological research. CONCLUSION: Childhood epilepsy incidence in Finland is similar to other industrialized countries, but there are signs of a declining trend emerging.

Clinical outcome and component-specific antibody levels in egg allergic children after lightened oral immunotherapy

Objective: To evaluate the clinical outcome of lightened version of egg oral immunotherapy (OIT) and to analyze egg allergen component-specific antibody levels during short up-dosing with egg white powder and maintenance by egg in daily diet. Patients and methods: Eighteen egg-allergic children received egg powder with short up--dosing and they maintained tolerance using egg in daily diet. Seventeen egg-allergic children served as a control group. Component-resolved analysis of serum immunoglobulin E (IgE), IgA1, IgA2, and IgG4 levels were determined at inclusion, after up-dosing and after 1 year of immunotherapy. Skin-prick tests were performed at inclusion and after 1 year of therapy. Results: All 18 patients in the egg OIT group were successfully desensitized. Desensitization was achieved on average in 4.5 months. In the control group, only two children tolerated egg in oral food challenge after 1 year. Of the measured immune markers, smaller wheal diameters in skin-prick testing, reduction in component-specific IgE levels, and increase in component-specific IgA1, IgA2, and IgG4 levels were associated with desensitization. Conclusion: A lightened egg OIT is effective and safe in children with egg allergy. Increase in all egg component-specific IgA1, IgA2 and IgG4 levels and decrease in all egg component--specific IgE levels were observed after 12 months of OIT (AU)

Effects of reduced sedentary time on resting, exercise and post-exercise blood pressure in inactive adults with metabolic syndrome - a six-month exploratory RCT.

Evidence on the long-term effects of reducing sedentary behaviour (SB) on blood pressure (BP) is scarce. Therefore, we performed a sub-analysis of the BP effects of a six-month intervention that aimed at reducing SB by 1 h/day and replacing it with non-exercise activities. Sixty-four physically inactive and sedentary adults with metabolic syndrome (58% female, 58 [SD 7] years, BP 143/88 [16/9] mmHg, SB 10 [1] h/day) were randomised into intervention (INT, n = 33) and control (CON, n = 31) groups. Resting BP and BP at each stage during and after a graded maximal bicycle ergometer test were measured before and after the intervention. SB, standing, moderate-to-vigorous physical activity (MVPA), and light physical activity (LPA) were measured in six-second intervals at baseline and during the whole six-month intervention using hip-worn accelerometers. The analyses were adjusted for BP medication status. The intervention resulted in a 40 min/day reduction in SB and concomitant 20 min/day increase in MVPA. Resting systolic BP was lower in the CON group before and after the intervention. No group x time interactions were observed in resting BP or BP during exercise at submaximal or maximal intensities, or during recovery. The changes in LPA and MVPA were inversely correlated with the changes in BP during light-to-moderate intensity exercise. An intervention that resulted in a 40 min/day reduction in SB for six months was not sufficient at influencing BP at rest, during or after exercise in adults with metabolic syndrome. However, successfully increasing LPA or MVPA might lower BP during light-to-moderate-intensity activities.

Clinical outcome and component-specific antibody levels in egg allergic children after lightened oral immunotherapy.

OBJECTIVE: To evaluate the clinical outcome of lightened version of egg oral immunotherapy (OIT) and to analyze egg allergen component-specific antibody levels during short up-dosing with egg white powder and maintenance by egg in daily diet. PATIENTS AND METHODS: Eighteen egg-allergic children received egg powder with short up--dosing and they maintained tolerance using egg in daily diet. Seventeen egg-allergic children served as a control group. Component-resolved analysis of serum immunoglobulin E (IgE), IgA1, IgA2, and IgG4 levels were determined at inclusion, after up-dosing and after 1 year of immunotherapy. Skin-prick tests were performed at inclusion and after 1 year of therapy. RESULTS: All 18 patients in the egg OIT group were successfully desensitized. Desensitization was achieved on average in 4.5 months. In the control group, only two children tolerated egg in oral food challenge after 1 year. Of the measured immune markers, smaller wheal diameters in skin-prick testing, reduction in component-specific IgE levels, and increase in component-specific IgA1, IgA2, and IgG4 levels were associated with desensitization. CONCLUSION: A lightened egg OIT is effective and safe in children with egg allergy. Increase in all egg component-specific IgA1, IgA2 and IgG4 levels and decrease in all egg component--specific IgE levels were observed after 12 months of OIT.

Evaluation of PET imaging as a tool for detecting neonatal hypoxic-ischemic encephalopathy in a preclinical animal model.

Hypoxic-ischemic encephalopathy due to insufficient oxygen delivery to brain tissue is a leading cause of death or severe morbidity in neonates. The early recognition of the most severely affected individuals remains a clinical challenge. We hypothesized that hypoxic-ischemic injury can be detected using PET radiotracers for hypoxia ([18F]EF5), glucose metabolism ([18F]FDG), and inflammation ([18F]F-DPA). METHODS: A preclinical model of neonatal hypoxic-ischemic brain injury was made in 9-d-old rat pups by permanent ligation of the left common carotid artery followed by hypoxia (8% oxygen and 92% nitrogen) for 120 min. In vivo PET imaging was performed immediately after injury induction or at different timepoints up to 21 d later. After imaging, ex vivo brain autoradiography was performed. Brain sections were stained with cresyl violet to evaluate the extent of the brain injury and to correlate it with [18F]FDG uptake. RESULTS: PET imaging revealed that all three of the radiotracers tested had significant uptake in the injured brain hemisphere. Ex vivo autoradiography revealed high [18F]EF5 uptake in the hypoxic hemisphere immediately after the injury (P < 0.0001), decreasing to baseline even 1 d postinjury. [18F]FDG uptake was highest in the injured hemisphere on the day of injury (P < 0.0001), whereas [18F]F-DPA uptake was evident after 4 d (P = 0.029), peaking 7 d postinjury (P < 0.0001), and remained significant 21 d after the injury. Targeted evaluation demonstrated that [18F]FDG uptake measured by in vivo imaging 1 d postinjury correlated positively with the brain volume loss detected 21 d later (r = 0.72, P = 0.028). CONCLUSION: Neonatal hypoxic-ischemic brain injury can be detected using PET imaging. Different types of radiotracers illustrate distinct phases of hypoxic brain damage. PET may be a new useful technique, worthy of being explored for clinical use, to predict and evaluate the course of the injury.

Finnish paediatric study found a low incidence of bacterial meningitis from 2011 to 2018 but a substantial proportion of nosocomial meningitis.

AIM: This study examined the predisposing factors, clinical picture, bacterial aetiology and clinical outcomes of infants and children with bacterial meningitis (BM). METHODS: The medical records of patients under 16 years of age, treated by Turku University Hospital, Finland, from 2011 to 2018, were screened for meningitis using the International Classification of Diseases, Tenth Revision codes. Patients were included if bacteria were detected in cerebrospinal fluid (CSF) or other predefined laboratory variables indicated BM, despite CSF testing negative for bacteria. The Glasgow Outcome Scale (GOS) was used to determine outcomes. RESULTS: We identified 37 children with BM: 22 infants aged 0-89 days and 15 children aged 90 days to 15 years. The overall incidence was approximately 5.7/100 000/year. Nosocomial meningitis was documented in 51%. Bacterial growth was detected in the CSF or blood cultures of the majority of patients (57%). Escherichia coli (14%), group B streptococcus (11%) and Streptococcus pneumoniae (8%) were the most common pathogens. There were 14% of patients with unfavourable outcomes, namely GOS scores of 1-4, but no deaths. CONCLUSION: The incidence of paediatric BM was low during the study period, but the proportion of nosocomial meningitis was substantial. The frequency of unfavourable long-term outcomes was relatively low.

Bone marrow metabolism is affected by body weight and response to exercise training varies according to anatomical location.

AIM: High body weight is a protective factor against osteoporosis, but obesity also suppresses bone metabolism and whole-body insulin sensitivity. However, the impact of body weight and regular training on bone marrow (BM) glucose metabolism is unclear. We studied the effects of regular exercise training on bone and BM metabolism in monozygotic twin pairs discordant for body weight. METHODS: We recruited 12 monozygotic twin pairs (mean ± SD age 40.4 ± 4.5 years; body mass index 32.9 ± 7.6, mean difference between co-twins 7.6 kg/m2 ; eight female pairs). Ten pairs completed the 6-month long training intervention. We measured lumbar vertebral and femoral BM insulin-stimulated glucose uptake (GU) using 18 F-FDG positron emission tomography, lumbar spine bone mineral density and bone turnover markers. RESULTS: At baseline, heavier co-twins had higher lumbar vertebral BM GU (p < .001) and lower bone turnover markers (all p < .01) compared with leaner co-twins but there was no significant difference in femoral BM GU, or bone mineral density. Training improved whole-body insulin sensitivity, aerobic capacity (both p < .05) and femoral BM GU (p = .008). The training response in lumbar vertebral BM GU was different between the groups (time × group, p = .02), as GU tended to decrease in heavier co-twins (p = .06) while there was no change in leaner co-twins. CONCLUSIONS: In this study, regular exercise training increases femoral BM GU regardless of weight and genetics. Interestingly, lumbar vertebral BM GU is higher in participants with higher body weight, and training counteracts this effect in heavier co-twins even without reduction in weight. These data suggest that BM metabolism is altered by physical activity.

Discrepancies between Radiology Specialists and Residents in Fracture Detection from Musculoskeletal Radiographs.

(1) Background: The aim of this study was to compare the competence in appendicular trauma radiograph image interpretation between radiology specialists and residents. (2) Methods: In this multicenter retrospective cohort study, we collected radiology reports from radiology specialists (N = 506) and residents (N = 500) during 2018-2021. As a reference standard, we used the consensus of two subspecialty-level musculoskeletal (MSK) radiologists, who reviewed all original reports. (3) Results: A total of 1006 radiograph reports were reviewed by the two subspecialty-level MSK radiologists. Out of the 1006 radiographs, 41% were abnormal. In total, 67 radiographic findings were missed (6.7%) and 31 findings were overcalled (3.1%) in the original reports. Sensitivity, specificity, positive predictive value, and negative predictive value were 0.86, 0.92, 0.91 and 0.88 respectively. There were no statistically significant differences between radiology specialists' and residents' competence in interpretation (p = 0.44). However, radiology specialists reported more subtle cases than residents did (p = 0.04). There were no statistically significant differences between errors made in the morning, evening, or night shifts (p = 0.57). (4) Conclusions: This study found a lack of major discrepancies between radiology specialists and residents in radiograph interpretation, although there were differences between MSK regions and in subtle or obvious radiographic findings. In addition, missed findings found in this study often affected patient treatment. Finally, there are MSK regions where the sensitivity or specificity is below 90%, and these should raise concerns and highlight the need for double reading and should be taken into consideration in radiology education.

Online training to improve evidence-based leadership competencies among nurse leaders in Finland and China: study protocols for two randomised feasibility trials.

INTRODUCTION: This study protocol describes two randomised feasibility trials that will evaluate the feasibility and preliminary effectiveness of an online training course to improve evidence-based leadership competences among nurse leaders working in hospitals in Finland and China. METHODS AND ANALYSIS: Two randomised, parallel-group studies will be conducted separately: one in Finland (n=140) and one in China (n=160). Nurse leaders who fulfil the eligibility criteria will be randomly allocated (1:1) to participate in either the online evidence-based leadership training or conventional online training (reading material only). The primary outcomes will be acceptance of the online course (logging into the platform) and adherence in the online course (returned course tasks and drop-out rate of the participants). The secondary outcomes will be acceptance of the study regarding recruitment, feasibility of the eligibility criteria and outcome measures and potential effectiveness of the online course on leadership skills, evidence-based knowledge, attitudes, practice, self-efficacy, self-esteem and intention to leave. In addition, the feedback will be asked after the course. ETHICS AND DISSEMINATION: Two separate trials have received ethical clearance from local ethics committees (12/2022 in Finland, E2021167 in China). Permission to conduct the study will be granted by hospital authorities. All participants will provide electronic informed consent before baseline data are collected. The trial results will be published locally, nationally and internationally in professional and peer-reviewed journals, and shared at national and international meetings and conferences. TRIAL REGISTRATION NUMBERS: NCT05244512; NCT05244499.