BACKGROUND AND AIMS:For pregnant women with perianal Crohn's disease (CD), major guidelines recommend delivery by caesarean section (c-section) for active disease, and that delivery mode be governed by obstetric indications for women with inactive disease. However, a significant gray zone exists between active versus inactive disease, such as for women who had a history of prior perianal surgery. We examined adverse maternal outcomes of vaginal delivery versus c-section in women with perianal CD and prior perianal surgeries. METHODS:We used the Danish national registries to collect information on singleton live births from 1997 through 2022 by mothers with CD and previous perianal surgery. Adverse postpartum maternal outcomes included new perianal or intestinal surgery within 12 months, hospital diagnosed infection or outpatient antibiotic prescription within 6 months, and major haemorrhage within 3 days. Adjusted odds ratios (aOR) were estimated in logistic regression models. RESULTS:There were 704 deliveries by women with CD and prior perianal surgery, including 245 vaginal deliveries (34.8%) and 459 c-sections (65.2%). Women who delivered vaginally versus by c-section had less new perianal surgery (aOR 0.47, 95% CI, 0.24-0.93) and no significant differences in intestinal CD surgery (aOR 0.87, 95% CI, 0.43-1.75), hospital diagnosed infection (aOR 0.50, 95% CI, 0.18-1.38), outpatient antibiotic prescription (aOR 0.92, 95% CI, 0.65-1.28), or major hemorrhage (aOR 0.79, 95% CI, 0.39-1.59). CONCLUSIONS:Vaginal delivery was not associated with increased important adverse maternal outcomes in mothers with CD and prior perianal surgery.

INTRODUCTION:Mothers with inflammatory bowel disease (IBD) are at increased risk of delivering their infants preterm. In the general population, chronic diseases in adulthood as well as increased morbidity and mortality are associated with being born preterm. We aimed to examine whether this was true for preterm versus full-term infants born to mothers with IBD. METHODS:This is an observational cohort study based on the Danish Health Registries. The study population comprised all live-born singleton children, born to mothers with IBD, during the study period of 1995 through 2016. We estimated the risk of selected chronic diseases in offspring born preterm to mothers with IBD. These included epilepsy, chronic lung disease and asthma, depression and bipolar affective disorder, autism spectrum disorders, schizophrenia/psychosis, attention-deficit hyperactivity disorder, and mental retardation/intellectual disabilities. We adjusted for relevant confounders. RESULTS:In all, 736 children were born preterm, and 9655 were born full-term to mothers with IBD. The median, 25th, and 75th percentiles of the follow-up time of the children were 11.1 (6.4, 16.3) years and 11.4 (7.3, 16.3) years for the full-term and preterm cohorts, respectively. There was a statistically significant increased risk of mental retardation/intellectual disabilities in preterm versus full-term children (aHR 2.15; 95% CI 1.07-4.36). We also found a non-significantly increased risk of epilepsy (1.11; 0.51-2.42), chronic lung disease and asthma (1.10; 0.76-1.60), schizophrenia/psychosis (1.17; 0.50-2.73), and attention-deficit/hyperactivity disorder 1.15 (0.83-1.60). CONCLUSION:Our study indicates the possibility of chronic health consequences in children born preterm to mothers with IBD.

BackgroundThe use of selective serotonin reuptake inhibitors (SSRIs) has increased over time. Several studies indicate that paternal use of medication may adversely affect the developing fetus. Only a few studies have investigated the association between preconceptional paternal exposure to SSRIs and the risks of adverse health outcomes in children.ObjectivesThis study aimed to assess adverse birth outcomes and adverse early life events in children fathered by men using SSRIs prior to conception.Materials and methodsAll live-born singleton children born in Denmark from 1997 until 2019 and their parents were included. The exposed cohort comprised all children fathered by men using SSRIs 3 months prior to conception and the unexposed cohort comprised all other children. We estimated the odds ratios for adverse birth outcomes: small for gestational age (SGA), preterm birth, low Apgar score, and major congenital malformations. Furthermore, we estimated the hazard ratios for adverse early life events of infections and hospitalizations within 1 year from birth. We also examined adverse birth outcomes and the adverse early life events according to SSRI subgroups.ResultsThere was a statistically significantly increased odds ratio 1.15 (confidence interval, CI: 1.06-1.23) for preterm birth. No significant results were found for SGA, low Apgar score, and major congenital malformations. The adjusted hazard ratios for hospitalizations and infections were 1.06 (CI: 1.02-1.11) and 1.02 (CI: 0.97-1.07), respectively. There was a statistically significantly increased odds ratio for preterm birth with respect to the SSRI subgroups citalopram and escitalopram, and for hospitalizations with respect to citalopram.Discussion and conclusionAlthough the risks of certain adverse birth and adverse early life outcomes were statistically significantly increased, the ratios were small and may have limited clinical importance. Paternal use of SSRI was in general safe in the preconceptual period.

Background Elderly patients with inflammatory bowel disease [IBD] are fragile in many respects. Therefore, in these patients, we studied postoperative complications [new abdominal surgery and serious infections after the first IBD surgery].Methods This is a nationwide cohort study based on Danish health registries and included patients with IBD undergoing surgery. The study population was split into ulcerative colitis [UC] and Crohn's disease [CD]. The exposed cohort [elderly] constituted those at an age of >= 60 years at first IBD surgery, and the unexposed [adults] those with surgery at the age of 18-59 years. We estimated adjusted hazard ratios [aHRs] of: a] new abdominal surgery within 2 years; and b] serious [hospital-diagnosed] infections within 6 and 12 months. We adjusted for several confounders including type of index surgery [laparoscopic or open].Results The aHR for a new surgery among elderly with UC and CD were 0.69 [95% CI 0.58-0.83] and 0.98 [95% CI 0.83-1.15], respectively. In elderly with UC, the aHRs of infections within 6 and 12 months after surgery were 1.07 [95% CI 0.81-1.40] and 0.85 [95% CI 0.67-1.08], respectively. In the elderly with CD, the aHRs of infections within 6 and 12 months were 1.45 [95% CI 1.12-1.88] and 1.26 [95% CI 1.00-1.59], respectively.Conclusion The elderly with IBD did not have an increased risk of new abdominal surgery within 2 years of the first surgery. Elderly with CD, but not UC, had an increased risk of serious infections within 6 months of surgery. Graphical Abstract

Introduction: Venom immunotherapy (VIT) and adrenaline autoinjector (AAI) are important therapies in venom anaphylaxis. Adherence to VIT and AAI in patients with venom allergy has been evaluated in a few studies; however, solid data are lacking. This study aimed to evaluate VIT and AAI retrieval rates in patients with venom allergy with a special focus on adherence to treatment. Adherence was compared to subcutaneous immunotherapy (SCIT) with inhalant allergens. Methods: This was a retrospective study among patients registered for allergen immunotherapy at the Allergy Center, Odense University Hospital, Denmark, from January 1, 2010, to December 31, 2014. Data on purchased immunotherapy and AAI were obtained from the Danish National Health Service Prescription Database. Multivariable logistic regression was used to analyze if allergen, age, sex, mastocytosis, and treatment site affected adherence. Results: The 3-year adherence to VIT was 92.4% (244/264) compared to 87.4% (215/246) in SCIT with inhalant allergens, and the 5-year adherence to VIT was 84.1% (222/264) compared to 74.8% (184/246) in SCIT with inhalant allergens (p = 0.045). Females treated with VIT were more adherent than males (p = 0.45 [3-year], p = 0.008 [5-year]), whereas allergen, age, mastocytosis, or treatment site did not significantly affect adherence. Only 28.6% of patients (12/42) purchased an AAI after premature termination of VIT. Conclusion: In this register-based study, we found that the 3- and 5-year adherences to VIT and SCIT with inhalant allergens are at the upper end of the spectrum hitherto reported. Patients’ 5-year adherence to VIT was higher than patients’ 5-year adherence to SCIT with inhalant allergens. If VIT was prematurely terminated, less than 1/3 would have purchased an AAI.

Purpose This study based exclusively on register-data provides a scientific basis for further research on the use of opioids in patients with degenerative back disorder. The main objective of this study is to investigate whether surgically treated back pain patients have the same risk of being long-term opioid users as back pain patients who did not have surgery. Methods We performed a retrospective register-based cohort study based on all patients diagnosed with a degenerative back disorder at the Spine Center of Southern Denmark from 2011 to 2017. The primary outcome of the study was the use of opioids two years after the patient's first hospital contact with a degenerative back condition. Fisher exact tests were used for descriptive analyses. The effect of the surgery was estimated using adjusted logistic regression analyses. Results For patients who used opioids before the first hospital contact, the ratio for long-term opioid use for surgically treated patients is significantly lower than for non-surgically treated patients (OR = 0.75, 95%CI (0.66; 0.86)). For patients who did not use opioids before, the ratio for long-term opioid use for surgically treated patients does not differ from that of non-surgically treated patients (OR = 1.01, 95%CI (0.84; 1.22)). Conclusions Patients with a degenerative back disorder who used opioids before their first visit to a specialized spine center have a lower risk of becoming long-term opioid users if they were surgically treated. Whereas for patients who did not use opioids before the first visit, surgical treatment does not influence the risk of becoming long-term opioid users.

Aims: The aim of this study was to evaluate whether patients with a non-specific back pain disorder are more likely to be diagnosed with a psychiatric disorder than patients with a specific back pain disorder (such as a herniated disc or inflammatory back disorder). Methods: This was a retrospective cohort study using Danish registries. Results: Our study population included 24,518 patients younger than 61 years and 12,274 patients older than 61 years. In both subpopulations, 60% had a non-specific back pain diagnosis (BPD). In the younger subpopulation, 2.1% of the patients with a non-specific BPD and 1.3% of the patients with a specific BPD had a psychiatric diagnosis within one year of their BPD. In the older subpopulation, 0.6% of patients had a psychiatric diagnosis in both BPD groups. The most frequent psychiatric diagnoses were stress-related disorders. In the younger subpopulation, patients with non-specific back pain had a higher risk of being diagnosed with a psychiatric disorder than patients with specific back pain (adjusted odds ratio 1.56, 95% confidence interval 1.25-1.94). The type of BPD had no effect on the risk of having a psychiatric diagnosis among older patients. Conclusions: Patients with a non-specific back pain disorder younger than 61 years were more likely to be diagnosed with a psychiatric disorder than patients with a specific back pain disorder. We recommend that spine specialists pay special attention to patients younger than 61 years with a back pain disorder to prevent them from developing a psychiatric disorder.

We developed four algorithms for the automatic capture of C-reactive protein (CRP) peaks in 296 adult patients with acute myeloid leukemia who had bloodstream infection (BSI) episodes, negative blood cultures (BCs) or possible infections where no BCs were performed. The algorithms detected CRP peaks for 418-446 of the 586 documented BSI episodes (71.3-76.1%) and 2714-3118 of the 4382 negative BCs (61.9-71.2%). The four algorithms captured 382-789 CRP peaks in which there were neither BSI episodes nor negative BCs. We conclude that automatic capture of CRP peaks is a tool for the monitoring of BSI episodes and possibly other infections in patients with acute myeloid leukemia.

BACKGROUND:It is mandatory to label food products with the 14 main allergens in the EU. Reasonable allergen labeling requires knowledge of population-based thresholds derived from food challenges. The aim of this study was to evaluate the threshold-distribution in clinically verified food allergic patients for allergens mandatory for labeling. METHODS:All positive open oral food challenges and double-blind placebo-controlled food challenges (DBPCFC) performed at the Allergy Center, Odense University Hospital, Denmark (2000-2022) were included. For each included challenge, the cumulative threshold (LOAEL) was obtained and NOAEL estimated. Data were modelled as an interval censored log-normal distribution. RESULTS:Overall, 38 of all 2612 challenges (1.5%) in 1229 patients (717 male, 986 children) reacted to <5 mg protein. The majority of the most sensitive patients reacted with a Sampson severity score of 2-3. Using interval censored log-normal models only five groups (hens´ egg, fish, peanut, milk, tree-nuts) elicited reactions after ingestion of 0.5 mg protein and in low frequencies of the population. Hen's egg was the most potent allergen, with reactivity to <0.5 mg protein in 0.24% [0.13-0.44%] of egg allergic patients while the estimated fraction of allergic patients reacting to a eliciting dose on 0.5 mg protein for most other allergens were below 0.04%. CONCLUSION:Our data demonstrates that the majority of food allergic patients as expected tolerating traces of allergenic foods without developing severe allergic symptoms and signs. Hen's egg appears to be the food most likely to elicit reactions in the most sensitive individuals at very low doses.

Background and aimPaternal use of analgesics during the time of conception and adverse birth outcomes are poorly studied. We investigated the association between paternal exposure to non-steroid anti-inflammatory drugs and opioids within 3 months before the date of conception and the risk of adverse birth outcomes (preterm birth, small for gestational age, low Apgar score, and major congenital malformations).MethodsWe used nationwide data from the Danish health registers. We included information on all singleton live births, and their fathers and mothers from 1997 to 2018. We created two exposed cohorts, children with preconception paternal exposure to (1) non-steroid anti-inflammatory drugs and (2) opioids. The unexposed cohort was children without preconception paternal exposure to non-steroid anti-inflammatory drugs or opioids, and we performed a sub-analysis against paternal use of acetaminophen (paracetamol). We used logistic regression models to estimate the odds ratios of adverse birth outcomes including 95% confidence intervals.ResultsWe identified 1,260,934 children, 45,667 children with paternal exposure to non-steroid anti-inflammatory drugs, 10,086 children with paternal exposure to opioids, and 1,205,181 unexposed children. The adjusted odds ratio for preterm birth was 1.08 (95% confidence interval, 1.03-1.13) after paternal exposure to non-steroid anti-inflammatory drugs and 1.21 (95% confidence interval, 1.08-1.35) after paternal exposure to opioids. The adjusted odds ratio for small for gestational age was 1.09 (95% confidence interval, 1.03-1.17) after paternal exposure to non-steroid anti-inflammatory drugs, and 1.03 (95% confidence interval, 0.88-1.21) after paternal exposure to opioids. We found null-associations for a low Apgar score and major congenital malformations. Estimates were attenuated when compared against paternal paracetamol exposure.ConclusionsOverall, we found null-associations across the comparisons made. Weak associations were found for paternal exposure to non-steroid anti-inflammatory drugs or opioids and preterm birth and small for gestational age, but not with low Apgar score or major congenital malformation. All associations were attenuated when compared against an active comparator of paternal paracetamol exposure. The effect sizes were small and less likely to be of clinical relevance.

Information regarding the impact of paternal inflammatory bowel disease (IBD) medications on child outcomes is scarce.

Background Patients with back pain are often in contact with 2–4 hospital departments when receiving a back pain diagnosis and treatment. This complicates the entire clinical course description. There is, currently, no model that describes the course across departments for patients with back pain. This study aims to construct an interdisciplinary clinical course using the central register’s information. Methods All patients with back pain referred for diagnosis and treatment at the Spine Center of Southern Denmark from 1 January 2011 until 31 December 2017 were included. By means of information available in central registers, we described the interdisciplinary clinical course for the individual patient, including information on all contacts at different departments, and proposed three different models to define the index and final date. The index date was defined as the first visit without a previous contact to the Spine Center for 6 months for model I, 1 year for model II, and 2 years for model III. The final date was defined as the last visit without following contacts for 6 months, 1 year, and 2 years, respectively, for models I, II, and III. Results A total of 69,564 patients (male: n = 30,976) with back pain diagnosis were identified. The three models all leave the information on the entire course at the hospital. In model I (64,757 clinical back pain courses), the time span to a possible previous clinical course is too short to secure the start of a new course (14% had two or more). With at least 1 year between a possible previous contact, model II (60,914 courses) fits the everyday clinical practice (9% had two or more clinical back pain courses). In model III (60,173 courses) it seems that two independent courses might be connected in the same course as only 5% had two or more clinical back pain courses. Conclusions Despite contact with different departments, the clinical course for back pain patients can be described by information from the central registers. A one-year time interval fits best the clinicians’ everyday observations.

Objectives: We assessed C-reactive protein (CRP) and plasma albumin (PA) kinetics to evaluate community-acquired bloodstream infection (CA-BSI) patients’ 1-year outcomes. Methods: Population-based study, with CRP and PA measurements on day 1 (D1) and D4. Relative CRP variations in relation to D1 CRP value were evaluated (CRP-ratio). Patients were classified as fast response, slow response, non-response, and biphasic response. Results: A total of 935 patients were included. At D4, the CRP-ratio was lower in survivors on D365 in comparison with D4–D30 non-survivors and D30–D365 non-survivors (p < 0.001). In comparison with fast response patients, non-response and biphasic response patients had 2.74 and 5.29 increased risk, respectively, of death in D4–D30 and 2.77 and 3.16 increased risk, respectively, of death in D31–D365. PA levels remained roughly unchanged from D1–D4, but lower D1 PA predicted higher short and long-term mortality (p < 0.001). The discriminative performance of the CRP-ratio and D1 PA to identify patients with poor short and long-term mortality after adjustments was acceptable (AUROC = 0.79). Conclusions: Serial CRP measurements at D1 and D4 after CA-BSI is clinically useful to identify patients with poor outcome. Individual patterns of CRP-ratio response with PA at D1 further refine our ability of predicting short or long-term mortality.

Early changes in biomarker levels probably occur before bloodstream infection (BSI) is diagnosed. However, this issue has not been fully addressed. We aimed at evaluating the kinetics of C-reactive protein (CRP) and plasma albumin (PA) in the 30 days before community-acquired (CA) BSI diagnosis. From a population-based BSI database we identified 658 patients with at least one measurement of CRP or PA from day -30 (D-30) through day -1 (D-1) before the day of CA-BSI (D0) and a measurement of the same biomarker at D0 or D1. Amongst these, 502 had both CRP and PA measurements which fitted these criteria. CRP and PA concentrations began to change inversely some days before CA-BSI diagnosis, CRP increasing by day -3.1 and PA decreasing by day -1.3. From D-30 to D-4, CRP kinetics (expressed as slopes - rate of concentration change per day) was -1.5 mg/l/day. From D-3 to D1, the CRP slope increased to 36.3 mg/l/day. For albumin, the slope between D-30 to D-2 was 0.1 g/l/day and changed to -1.8 g/l/day between D-1 and D1. We showed that biomarker levels begin to change some days before the CA-BSI diagnosis, CRP 3.1 days and PA 1.3 days before.

Many factors contribute to the plasma albumin (PA) level. We aimed to quantify different factors’ relative contribution to the PA level when diagnosing hematological malignancy (HM). The study was a population-based registry study including patients with HM in a Danish region. We applied multivariate linear regression analyses with C-reactive protein (CRP), WHO performance score (WHO-PS), age, sex, comorbidity, and HM type as exposures and the PA level on the day of the HM diagnosis (DX) as the outcome. The relative contribution of each exposure was determined as a percentage of the models’ coefficient of determination (R2). In total, 2528 patients with HM had PA measured on DX. In the model comprising all exposures, CRP contributed with 65.8% to the R2 of 0.389 whereas 3 variables (CRP, WHO-PS, HM type) together contributed with 96.1%. When CRP was excluded from the model, R2 declined to 0.215 and the WHO-PS contributed with 96%. Other models, including separate analyses for each HM type, corroborated these results, except in myeloma patients where WHO-PS contributed with 61.1% to the R2 of 0.234. The inflammation biomarker CRP was the main predictor of the PA level on DX. The WHO-PS also contributed to the PA level on DX whereas the remaining factors (HM type, age, sex, and comorbidity) were of much less importance.

Abstract Background No study has evaluated C-reactive protein (CRP) and plasma albumin (PA) levels longitudinally in patients with acute myeloid leukaemia (AML). Methods We studied defined events in 818 adult patients with AML in relation to 60,209 CRP and PA measures. We investigated correlations between CRP and PA levels and daily CRP and PA levels in relation to AML diagnosis, AML relapse, or bacteraemia (all ±30 days), and death (─30–0 days). Results On the AML diagnosis date (D0), CRP levels increased with higher WHO performance score (PS), e.g. patients with PS 3/4 had 68.1 mg/L higher CRP compared to patients with PS 0, adjusted for relevant covariates. On D0, the PA level declined with increasing PS, e.g. PS 3/4 had 7.54 g/L lower adjusted PA compared to PS 0. CRP and PA levels were inversely correlated for the PA interval 25–55 g/L (R = − 0.51, p < 10–5), but not for ≤24 g/L (R = 0.01, p = 0.57). CRP increases and PA decreases were seen prior to bacteraemia and death, whereas no changes occurred up to AML diagnosis or relapse. CRP increases and PA decreases were also found frequently in individuals, unrelated to a pre-specified event. Conclusions PA decrease is an important biomarker for imminent bacteraemia in adult patients with AML.

Higher sterols are universally present in large amounts (20–30%) in the plasma membranes of all eukaryotes whereas they are universally absent in prokaryotes. It is remarkable that each kingdom of the eukaryotes has chosen, during the course of evolution, its preferred sterol: cholesterol in animals, ergosterol in fungi and yeast, phytosterols in higher plants, and e.g., fucosterol and desmosterol in algae. The question arises as to which specific properties do sterols impart to membranes and to which extent do these properties differ among the different sterols. Using a range of biophysical techniques, including calorimetry, fluorescence microscopy, vesicle-fluctuation analysis, and atomic force microscopy, we have found that fucosterol and desmosterol, found in red and brown macroalgae (seaweeds), similar to cholesterol support liquid-ordered membrane phases and induce coexistence between liquid-ordered and liquid-disordered domains in lipid bilayers. Fucosterol and desmosterol induce acyl-chain order in liquid membranes, but less effectively than cholesterol and ergosterol in the order: cholesterol>ergosterol>desmosterol>fucosterol, possibly reflecting the different molecular structure of the sterols at the hydrocarbon tail.

Cholesterol with BODIPY at carbon-24 of the side chain (BCh2) has recently been introduced as new cholesterol probe with superior fluorescence properties. We compare BCh2 with the intrinsically fluorescent dehydroergosterol (DHE), a well-established marker for cholesterol, by introducing simultaneous imaging of both sterols in model membranes and living cells. BCh2 had a lower affinity than DHE for the biologically relevant liquid-ordered phase in model membranes. Still, DHE and BCh2 trafficked from the plasma membrane to the endocytic recycling compartment (ERC) of BHK cells with identical kinetics. This transport pathway was strongly reduced after energy depletion of cells or expression of the dominant-negative clathrin heavy chain. The partitioning into lipid droplets of BHK and HeLa cells was higher for BCh2 than for DHE. Within droplets, the photodegradation of BCh2 was enhanced and followed a stretched exponential decay, while the fluorescence lifetime of BCh2 was comparable in various cellular regions. Our results indicate that BCh2 is suitable for analyzing sterol uptake pathways and inter-organelle sterol flux in living cells. The BODIPY-moiety affects lipid phase preference of the sterol probe and causes some differential targeting of BCh2 and DHE in cells with high fat content.