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Dennis Lund Hansen,1,2 Sören Möller,1,3 Kjeld Andersen,1,4 David Gaist,1,5 Henrik Frederiksen1,2 1Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 2Department of Hematology, Odense University Hospital, Odense, Denmark; 3OPEN, Odense University Hospital, Odense, Denmark; 4Department of Psychiatry, Odense, Region of Southern Denmark, Odense, Denmark; 5Neurology Research Unit, Department of Neurology, Odense University Hospital, Odense, DenmarkCorrespondence: Dennis Lund Hansen Email dlh@dadlnet.dkBackground: Acquired hemolytic disorders—autoimmune hemolytic anemia (AIHA), cold agglutinin disease (CAD), paroxysmal nocturnal hemoglobinuria (PNH), drug-induced hemolysis (DIHA), and acquired hemolysis not otherwise specified (AHNOS)—are considered rare. Despite their potentially major health implications, data regarding their incidence and prevalence are scarce.Methods: To fill this gap we collected data regarding all patients with acquired hemolytic disorder diagnoses in 1977– 2016 from the Danish National Patient Register. These data were linked with vital and migration status information from the Danish Civil Registration System. From these data combined with annual demographic data for the background population, we calculated age- and sex-specific incidence rates and prevalence proportions of acquired hemolytic disorders for specified time periods.Results: Our analysis included 5868 patients with acquired hemolytic disorders (2715 with AIHA, 112 CAD, 397 DIHA, 116 PNH, and 2154 AHNOS). The incidence rates per 100 000 person-years in 1980– 1993 and 2008– 2016 were 0.81 and 1.77 for AIHA, 0.31 and 0.12 for DIHA, and 0.04 and 0.08 for PNH, respectively. The 2008– 2016 CAD incidence rate was 0.18/100 000 person-years, CAD diagnosis code was not defined before 1994. All incidence rates increased with age. The prevalence proportion per 100 000 persons in 1980 and 2015 was 2.52 and 17.01 for AIHA, 0.80 and 1.50 for DIHA, and 0.18 and 1.04 for PNH. CAD prevalence in 2015 was 1.04/100 000 persons.Conclusion: Acquired hemolytic anemia incidence rates and prevalence proportions with the exception of DIHA are markedly increasing.Keywords: autoimmune hemolytic anemia, cold agglutinin disease, paroxysmal nocturnal hemoglobinuria, drug-induced hemolytic anemia, incidence, prevalence

Dennis Lund Hansen,1,2 Andreas Glenthøj,3 Sören Möller,1,4 Bart J Biemond,5 Kjeld Andersen,1,6 David Gaist,1,7 Jesper Petersen,3 Henrik Frederiksen1,2 1Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 2Department of Hematology, Odense University Hospital, Odense, Denmark; 3Department of Hematology, Center for Hemoglobinopathies, Herlev and Gentofte Hospital, Herlev, Denmark; 4OPEN, Odense University Hospital, Odense, Denmark; 5Department of Hematology, Amsterdam University Medical Centre’s, Amsterdam, Netherlands; 6Department of Mental Health - Odense, Region of Southern Denmark, Odense, Denmark; 7Neurology Research Unit, Department of Neurology, Odense University Hospital, Odense, DenmarkCorrespondence: Dennis Lund Hansen Email dlh@dadlnet.dkBackground: Congenital red blood cell (RBC) disorders, such as hemoglobinopathies, are frequent worldwide but with large geographical variation. Growing migration has increased the number of patients with RBC disorders in formerly low prevalence countries, eg, Denmark. However, accurate prevalences are unknown.Methods: Patients with a registered diagnosis of congenital hemolysis in the Danish National Patient Register between 1977 and 2016 were linked to a national laboratory database of RBC disorders and the Danish civil registration system. We calculate annual age- and sex-specific prevalences of the congenital hemolytic disorders from 2000 to 2016.Results: Prevalences of all subtypes of congenital hemolytic disorders increased during the study period. The prevalence of hereditary spherocytosis increased 1.73 times between 2000 and 2015, from 10.2/105 persons to 17.7/105 persons. Alpha thalassemia trait had a prevalence of 0.5/105 persons in 2000, but increased 41 times to 19.2/105 persons in 2015. Beta thalassemia minor increased eightfold from 4.5/105 persons in 2000 to 34.9/105 persons in 2015. Likewise, sickle cell trait increased 11 times from 0.7/105 persons in 2000 to 8.1/105 persons in 2015, whereas sickle cell disease increased from 0.5/105 persons to 2.7/105 persons in 2015, a fivefold increase.Conclusion: The prevalence of congenital RBC disorders in Denmark is increasing. The hemoglobinopathy traits now have prevalences as high as hereditary spherocytosis. These estimates of congenital hemolytic disorders in Denmark emphasize that inborn hemoglobin disorders are a public health concern, even in some formerly low prevalence countries.Keywords: hemolytic anemia, thalassemia, sickle cell disease, hereditary spherocytosis, hemoglobinopathies, sickle cell anemia

Dennis Lund Hansen,1 Ulrik Malthe Overgaard,2 Lars Pedersen,3 Henrik Frederiksen1,3 1Department of Haematology, Odense University Hospital, Odense, 2Department of Haematology, Herlev Hospital, Herlev, 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Purpose: The nationwide public health registers in Denmark provide a unique opportunity for evaluation of disease-associated morbidity if the positive predictive values (PPVs) of the primary diagnosis are known. The aim of this study was to evaluate the predictive values of hemolytic anemias registered in the Danish National Patient Register. Patients and methods: All patients with a first-ever diagnosis of hemolytic anemia from either specialist outpatient clinic contact or inpatient admission at Odense University Hospital from January 1994 through December 2011 were considered for inclusion. Patients with mechanical reason for hemolysis such as an artificial heart valve, and patients with vitamin-B12 or folic acid deficiency were excluded. Results: We identified 412 eligible patients: 249 with a congenital hemolytic anemia diagnosis and 163 with acquired hemolytic anemia diagnosis. In all, hemolysis was confirmed in 359 patients, yielding an overall PPV of 87.1% (95% confidence interval [CI]: 83.5%–90.2%). A diagnosis could be established in 392 patients of whom 355 patients had a hemolytic diagnosis. Diagnosis was confirmed in 197 of the 249 patients with congenital hemolytic anemia, yielding a PPV of 79.1% (95% CI: 73.5%–84.0%). Diagnosis of acquired hemolytic anemia could be confirmed in 136 of the 163 patients, resulting in a PPV of 83.4% (95% CI: 76.8%–88.8%). For hemoglobinopathy PPV was 84.1% (95% CI: 77.4%–89.4%), for hereditary spherocytosis PPV was 80.6% (95% CI: 69.5%–88.9%), and for autoimmune hemolytic anemia PPV was 78.4% (95% CI: 70.4%–85.0%). Conclusion: The PPV of hemolytic anemias was moderately high. The PPVs were comparable in the three main categories of overall hemolysis, and congenital and acquired hemolytic anemia. Keywords: ICD-10 coding, diagnosis validation, hemoglobinopathy, spherocytosis, epidemiology, congenital hemolytic anemia, acquired hemolytic anemia

Overweight and obesity is a health threat of increasing concern and understanding the neurobiology behind obesity is instrumental to the development of effective treatment regimes. Serotonergic neurotransmission is critically involved in eating behaviour; cerebral level of serotonin (5-HT) in animal models is inversely related to food intake and body weight and some effective anti-obesity agents involve blockade of the serotonin transporter (SERT). We investigated in 60 healthy volunteers body mass index (BMI) and regional cerebral SERT binding as measured with [(11)C]DASB PET. In a linear regression model with adjustment for relevant covariates, we found that cortical and subcortical SERT binding was negatively correlated to BMI (-0.003 to -0.012 BP(ND) unit per kg/m(2)). Tobacco smoking and alcohol consumption did not affect cerebral SERT binding. Several effective anti-obesity drugs encompass blockade of the SERT; yet, our study is the first to demonstrate an abnormally decreased cerebral SERT binding in obese individuals. Whether the SERT has a direct role in the regulation of appetite and eating behaviour or whether the finding is due to a compensatory downregulation of SERT secondary to other dysfunction(s) in the serotonergic transmitter system, such as low baseline serotonin levels, remains to be established.

Little is known about healthy young women's everyday experiences with medicine use and their general perceptions of medicines. In this article, we describe a user-perspective study involving in-depth qualitative interviews with 20 young women between the ages of 16 and 20 in Copenhagen, Denmark. Inspired by Schutz's phenomenology, informants' medicine-taking experiences were considered within the context of their life-worlds. Analysis revealed that the young women possessed predominantly negative perceptions of medicines, which were linked to a preference for complete avoidance of medicines and a desire to maintain a natural body ideal. The essence of participants' experiences was characterized by conflict, as most used medicines at least occasionally, despite the negative perceptions they held. Participants strove to make sense of their medicine-taking practices and provided rationales for their use of medicine, often based on perceptions of need and reduced personal risk. [ABSTRACT FROM AUTHOR]

Abstract   Objective To explore adolescents’ struggles with taking oral medications. Setting Copenhagen, Denmark. Method Semi-structured qualitative interviews were conducted with 89 adolescents (33 boys, 56 girls) between the ages of 11 and 20. Adolescents were recruited through four public schools. To identify struggles with taking oral medication, interview transcripts were systematically searched for statements including the terms swallow, chew, crush and eat. Thematic analysis of the identified statements was carried out to reveal dominant themes in the adolescents’ accounts. Results Over one-third of the adolescents spontaneously provided accounts of the difficulties they experienced with taking oral medications, especially with swallowing tablets. Three themes were dominant in their narratives: barriers, strategies and learning. Barriers experienced by the adolescents involved the medications’ properties, e.g. taste. Adolescents developed strategies to overcome these barriers, e.g. crushing tablets. Via a process of learning-by-doing and the acquisition of increased experience and autonomy, many adolescents mastered the skill of swallowing tablets. Conclusion Many adolescents experienced barriers in their attempts to swallow tablets. They developed various strategies to overcome these barriers and gradually mastered taking medicines in a learning-by-doing process. [ABSTRACT FROM AUTHOR]

The authors explored parents' perceptions of and everyday experiences with the stimulant medication used to treat their child's attention deficit hyperactivity disorder (ADHD) in this phenomenological study. They elicited experiences through semistructured interviews with 10 Canadian parents of children with ADHD. In the interviews, parents revealed the meaning the stimulant medication had taken on in the context of their everyday lives. Through the interview analysis, dilemma emerged as the dominant theme. Parents were caught in a dynamic balancing act, as they considered the medication's desirable and undesirable effects in various settings. In addition, parents shared their expectations regarding the medication's role in their child's future. The study's findings reinforce the necessity of further qualitative research in this area, given the growing number of families around the globe whose children have been diagnosed with ADHD. [ABSTRACT FROM AUTHOR]

Objective: To examine after gastric bypass the effect of peroral versus gastroduodenal feeding on glucose metabolism.Research Design and Methods: A type 2 diabetic patient was examined on 2 consecutive days 5 weeks after gastric bypass. A standard liquid meal was given on the first day into the bypassed gastric remnant and on the second day perorally. Plasma glucose, insulin, C-peptide, glucagon, incretin hormones, peptide YY, and free fatty acids were measured.Results: Peroral feeding reduced 2-h postprandial plasma glucose (7.8 vs. 11.1 mmol/l) and incremental area under the glucose curve (iAUC) (0.33 vs. 0.49 mmol . l(-1) . min(-1)) compared with gastroduodenal feeding. beta-Cell function (iAUC(Cpeptide/Glu)) was more than twofold improved during peroral feeding, and the glucagon-like peptide (GLP)-1 response increased nearly fivefold.Conclusions: Improvement in postprandial glucose metabolism after gastric bypass is an immediate and direct consequence of the gastrointestinal rearrangement, associated with exaggerated GLP-1 release and independent of changes in insulin sensitivity, weight loss, and caloric restriction. [ABSTRACT FROM AUTHOR]

Background: Individuals with diabetes and co-existing psychiatric disorders have more diabetes complications and lower life expectancy than those with diabetes but no co-existing psychiatric disorders. Psychiatric health professionals may have a role in improving these outcomes but often lack diabetes knowledge and skills. This study aims to examine the effectiveness of a diabetes training course for psychiatric health professionals on their diabetes knowledge and skills and clinical outcomes, diabetes support and diabetes distress among individuals with diabetes and psychiatric disorders treated in psychiatric outpatient clinics., Methods: A pragmatic non-randomized controlled cluster trial was conducted in eight psychiatric outpatient clinics in Denmark. All psychiatric health professionals from four clinics participated in the diabetes training course (the intervention) and completed a questionnaire on experience of the training course and a 20-item pre- and post-test to measure diabetes knowledge and skills. Difference in pre- and post-tests were analyzed using t-tests. From August 2018 - June 2019, individuals with diabetes were recruited from the intervention clinics (n = 49) and from four control clinics continuing usual clinical practice (n = 57). Differences in clinical outcomes, diabetes support and diabetes distress between the intervention and control groups at six and 12 months after the training course, were analyzed using logistic and linear regression models adjusted for baseline levels., Results: Psychiatric health professionals (n = 64) had more correct answers after completing the course, with a mean increase of 6.3 [95% CI 5.6 to 7.0] correct answers. A total of 49 and 57 individuals were recruited for the intervention and control group, respectively. At follow-up, individuals treated in the intervention group had lower levels (clinical improvement) of systolic blood pressure, but had lower receipt of annual assessment of blood pressure, and body mass index (BMI) (worsening of process measures). While there were observed differences in odds and means for several other outcomes, none of these received statistical significance (see Table 2 and Fig. 2)., Conclusions: Training psychiatric health professionals in diabetes care improved their diabetes knowledge and skills and improved clinical levels of systolic blood pressure in individuals treated in the intervention group. However, this training intervention was associated with a lower likelihood of receiving annual assessment of blood pressure and BMI., Trial Registration: ISRCTN registry registration number ISRCTN15523920, registration date: 02/10/2019., Competing Interests: Declarations Ethics approval and consent to participate This study was conducted according to the guidelines in the Declaration of Helsinki. The study was approved by the Danish Data Protection Agency P-2019–338. The Danish Committee on Health Research Ethics assessed that ethical approval was not required for this study according to the Danish Act on Research Ethics Review of Health Research Projects (H-18009189). Interested and eligible individuals with diabetes and psychiatric disorder were given written and verbal information about the study before giving oral and written informed consent to participate. Consent for publication Not applicable. Competing interests LEJ, LLN, AJ, MAN, KL, and DLH have no conflicts of interest to declare. LK, GSA and KKBC owns shares in Novo Nordisk A/S. LJD, KKBC and GSA are currently employed by Novo Nordisk A/S. During contribution to the manuscript, LJD, KKBC, and GSA were employed by Steno Diabetes Center Copenhagen. MEJ holds shares in Novo Nordisk, and has received research grants from AMGEN, Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, and Sanofi Aventis., (© 2024. The Author(s).)

Haemophagocytic lymphohistiocytosis (HLH) is a syndrome with an abnormal activation of the immune system and is associated with a high mortality even with treatment. We present a case of a woman in her mid-50s who developed HLH triggered by miliary tuberculosis (TB) while receiving a tumour necrosis factor alpha inhibitor.The patient was admitted with a high fever and respiratory pain. Her condition deteriorated despite empirical treatment. Diagnosis of HLH was established based on clinical presentation, H-score and HLH-04 criteria. Concurrently, miliary TB was identified as the trigger. She was treated with anti-tuberculous therapy and HLH-directed treatment with dexamethasone, etoposide and anakinra. Initial improvement was observed, leading to the withholding of HLH-orientated treatment. However, several relapses occurred, necessitating prolonged HLH treatment.A literature review corroborated the importance of combined anti-tuberculous and immunosuppressive therapy for managing HLH. This case underscores the necessity of timely and comprehensive management of HLH-oriented treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To construct and test patient-reported outcome measures (PROMs) for identifying diabetes support needs of adults with co-existing diabetes and severe mental illness (SMI) provided by mental health professionals at psychiatric outpatient clinics., Methods: Design thinking was used to identify, select, and modify PROMs in collaboration with 18 adults with type 1 or type 2 diabetes and SMI and 10 healthcare experts. The PROMs were then tested with 86 adults with diabetes and SMI recruited from eight psychiatric outpatient clinics in Denmark. Data were analysed using systematic text condensation (questionnaire construction) and descriptive statistics (testing)., Results: Four principles for PROMs were identified: (a) be modified to be relevant for the target group, (b) be concise and simple to complete, (c) have a clear and unambiguous wording, and (d) be designed to measure topics that are perceived as meaningful. Test of the questionnaire contained 49 items in four domains. Missing response rates in the test were 1.2-4.7% in three domains and 4.7-11.6% in a domain addressing potential sources of diabetes support., Discussion: PROMs can successfully be constructed in collaboration with this vulnerable population that yield low rates of missing responses., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Patients with primary immune thrombocytopenia (ITP) suffer from reduced survival and quality of life, but the underlying reasons for this are largely undescribed. Mental health and the use of psychotropic drugs in ITP is unknown. We investigated the risk of hospital-registered mental health events including fatigue and the use of psychotropic drugs in adult patients with ITP compared with the general population, using nationwide registry-data. We identified 3,749 patients with ITP and 149,849 age- and sex-matched general population comparators in the Danish Health Registries in the period 1997-2016. The median age was 60 years (interquartile range [IQR], 40-73) and 53% were women. We followed the individuals for incident mental health events and estimated the use of psychotropic drugs over calendar-years and in temporal relation to diagnosis of ITP. The first year cumulative incidence of any mental health event was 2.3% (95% confidence interval [CI]: 1.9-2.9) in patients and 0.7% (95% CI: 0.6-0.7) in comparators, yielding an adjusted cause-specific hazard ratio (csHR) of 3.57 (95% CI: 2.84-4.50). The corresponding estimates for depression were 1.2% (95% CI: 0.9-1.6) and 0.3% (0.3-0.4) respectively, with an adjusted csHR of 3.53 (95% CI: 2.56-4.85). We found similar findings for anxiety and fatigue, but risks generally diminished after 1-5 years. The use of opioids, antidepressants, and benzodiazepines increased in temporal relation to diagnosis of ITP. The risk of mental health events and the use of psychotropic drugs is higher in adult patients with ITP compared with the general population, and has a temporal relation to diagnosis of ITP emphasizing that mental health in ITP is a concern.

Background: Hereditary anemias are a group of genetic diseases prevalent worldwide and pose a significant health burden on patients and societies. The clinical phenotype of hereditary anemias varies from compensated hemolysis to life-threatening anemia. They can be roughly categorized into three broad categories: hemoglobinopathies, membranopathies, and enzymopathies. Traditional therapeutic approaches like blood transfusions, iron chelation, and splenectomy are witnessing a paradigm shift with the advent of targeted treatments. However, access to these treatments remains limited due to lacking or imprecise diagnoses. The primary objective of the study is to establish accurate diagnoses for patients with hereditary anemias, enabling optimal management. As a secondary objective, the study aims to enhance our diagnostic capabilities., Results: The DAHEAN study is a nationwide cohort study that collects advanced phenotypic and genotypic data from patients suspected of having hereditary anemias from all pediatric and hematological departments in Denmark. The study deliberates monthly by a multidisciplinary anemia board involving experts from across Denmark. So far, fifty-seven patients have been thoroughly evaluated, and several have been given diagnoses not before seen in Denmark., Conclusions: The DAHEAN study and infrastructure harness recent advancements in diagnostic tools to offer precise diagnoses and improved management strategies for patients with hereditary anemias., (© 2024. The Author(s).)

Aims: To explore the feasibility and potential benefits of a peer support programme for adults with insulin-treated type 2 diabetes (T2D) starting continuous glucose monitoring (CGM)., Methods: This part of the Steno2tech study is an exploratory, single-centre, open-labelled, prospective, randomised controlled trial (RCT). A total of 60 participants were randomised 2:1 to 12 months of CGM with or without peer support. All participants received a 3-h diabetes self-management education course including a CGM part on how to use the CGM and interpret the CGM-derived data. Peer support consisted of three 3-h peer support meetings over the first 6 months of the study period with groups of three to six people. The exploratory outcomes included the acceptability and feasibility of the peer support intervention, and the between-group difference in change in several glycaemic, metabolic and participant-reported outcomes measured at baseline, 6 and 12 months., Results: The peer support intervention was found acceptable and feasible. Participants shared their experiences of using and interpreting CGM data and its association with health behaviour. While both groups had improvements in glycaemic, metabolic and participant-reported outcomes, there were no significant between-group differences., Conclusions: Although feasible, we found no measured additional benefits when adding a peer support programme after starting CGM in this exploratory RCT including adults with insulin-treated T2D. Understanding the perceived effect of and preferences for a peer support intervention from the participants' points of view, including why individuals declined to participate, would be of value for future research., (© 2024 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Aim: Postmortem Computed Tomography (PMCT) is gradually introduced at forensic institutes. Image reconstruction software can increase diagnostic potential in CT by increasing distinction between structures and reduction of artifacts. The aim of this study was to develop and evaluate novel image reconstruction parameters for postmortem conditions, to increase image quality and diagnostic potential of CT scans., Method: Twenty PMCT scans of deceased hereof two in severe decay were subjected to four reconstruction techniques: a standard reconstruction algorithm, the detail reconstruction algorithm and two novel algorithms based on the standard algorithm, but with different Hounsfield settings. Image quality was evaluated by visual grading analysis (VGA) by four forensic radiologist observers., Results: The VGA did not prove that any of the reconstruction techniques were superior to the others. For standard and detail, the two pre-defined reconstruction algorithms, VGA scores were indiscernible and were superior to the equally indiscernible Hounsfield reconstructions on parameters translated into Sharpness and Low Contrast Resolution. The two alternative Hounsfield settings were superior with respect to Noise and Artifacts/Beam Hardening., Conclusion: The study elucidates the possiblity for multiple reconstructions specialized for PMCT conditions, to accommodate the special conditions when working with the deceased. Despite the lack of clear improvements in the tested reconstructions, this study provides an insight into some of the possibilities of improving PMCT quality using reconstruction techniques., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: To compare the 12-month effects of continuous glucose monitoring (CGM) versus blood glucose monitoring (BGM) in adults with insulin-treated type 2 diabetes., Research Design and Methods: This is a single-center, parallel, open-label, randomized controlled trial including adults with inadequately controlled, insulin-treated type 2 diabetes from the outpatient clinic at Steno Diabetes Center Copenhagen, Denmark. Inclusion criteria were ≥18 years of age, insulin-treated type 2 diabetes, and HbA1c ≥7.5% (58 mmol/mol). Participants were randomly assigned (1:1) to 12 months of either CGM or BGM. All participants received a diabetes self-management education course and were followed by their usual health care providers. Primary outcome was between-group differences in change in time in range (TIR) 3.9-10.0 mmol/L, assessed at baseline, after 6 and 12 months by blinded CGM. The prespecified secondary outcomes were differences in change in several other glycemic, metabolic, and participant-reported outcomes., Results: The 76 participants had a median baseline HbA1c of 8.3 (7.8, 9.1)% (67 [62-76] mmol/mol), and 61.8% were male. Compared with BGM, CGM usage was associated with significantly greater improvements in TIR (between-group difference 15.2%, 95% CI 4.6; 25.9), HbA1c (-0.9%, -1.4; -0.3 [-9.4 mmol/mol, -15.2; -3.5]), total daily insulin dose (-10.6 units/day, -19.9; -1.3), weight (-3.3 kg, -5.5; -1.1), and BMI (-1.1 kg/m2, -1.8; -0.3) and greater self-rated diabetes-related health, well-being, satisfaction, and health behavior., Conclusions: In adults with inadequately controlled insulin-treated type 2 diabetes, the 12-month impact of CGM was superior to BGM in improving glucose control and other crucial health parameters. The findings support the use of CGM in the insulin-treated subgroup of type 2 diabetes., (© 2024 by the American Diabetes Association.)

Corticosteroids remain the first-line treatment of immune thrombocytopenia (ITP), but increase the risk of osteoporosis and fractures. Bisphosphonates are used for the treatment of osteoporosis, but their usage among patients with ITP has not been systemically described. We investigated the risk of fractures and the use of bisphosphonates in adult patients with primary (pITP) and secondary ITP (sITP) compared with matched comparators in a nationwide registry-based cohort study. We identified 4030 patients with pITP (median age 60 years [IQR, 40-74]), 550 with sITP (median age 59 years [IQR, 43-74]) and 182 939 age-sex-matched general population comparators. All individuals were followed for incident fractures. Bisphosphonate use was estimated for calendar-years and in temporal relation to the ITP diagnosis. Adjusted cause-specific hazard ratio (csHR) for any fracture was 1.37 (95% confidence interval [CI] 1.23; 1.54) for pITP and 1.54 (1.17; 2.03) for sITP. The first-year csHR was 1.82 (1.39; 2.40) for pITP and 2.78 (1.58; 4.91) for sITP. Bisphosphonate use over calendar-years and in the early years following ITP diagnosis was higher among patients with ITP diagnosis compared with the general population. In conclusion, the risk of fractures and the use of bisphosphonates are higher in patients with ITP compared with the general population., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Primary autoimmune haemolytic anaemia (AIHA) causes the destruction of red blood cells and a subsequent pro-thrombotic state, potentially increasing the risk of ischaemic stroke. We investigated the risk of ischaemic stroke in patients with AIHA in a binational study. We used prospectively collected data from nationwide registers in Denmark and France to identify cohorts of patients with primary AIHA and age- and sex-matched general population comparators. We followed the patient and comparison cohorts for up to 5 years, with the first hospitalization of a stroke during follow-up as the main outcome. We estimated cumulative incidence, cause-specific hazard ratios (csHR) and adjusted for comorbidity and exposure to selected medications. The combined AIHA cohorts from both countries comprised 5994 patients and the 81 525 comparators. There were 130 ischaemic strokes in the AIHA cohort and 1821 among the comparators. Country-specific estimates were comparable, and the overall adjusted csHR was 1.36 [95% CI: 1.13-1.65], p = 0.001; the higher rate was limited to the first year after AIHA diagnosis (csHR 2.29 [95% CI: 1.77-2.97], p < 10 -9 ) and decreased thereafter (csHR 0.89 [95% CI: 0.66-1.20], p = 0.45) (p-interaction < 10 -5 ). The findings indicate that patients diagnosed with primary AIHA are at higher risk of ischaemic stroke in the first year after diagnosis., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Cancer in pregnancy is rare, and most physicians lack knowledge in handling pregnant cancer patients. This review summarises the present knowledge on this condition. In the Netherlands, an Advisory Board on Cancer in Pregnancy was established in 2012. The board supports Dutch physicians' decisions in the management of pregnant patients with cancer. In 2021 the International Advisory Board on Cancer in Pregnancy was established, and in continuation, the Danish Advisory Board on Cancer in Pregnancy (DABCIP) has now been founded. DABCIP consists of 22 members from 13 different medical disciplines., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Currently, bone marrow (BM) biopsy (BMB) is recommended in the initial staging of patients with the presumed primary central nervous system (CNS) lymphoma (PCNSL). However, the added value of BMB in the era of positron emission tomography (PET-CT) has been challenged in other lymphoma subtypes. We analyzed BM findings in patients with biopsy-proven CNS lymphoma and a negative PET-CT scan for disease outside CNS. A comprehensive Danish population-based registry search was performed to identify all patients with CNS lymphoma of diffuse large B cell lymphoma (DLBCL) histology with available BMB results and staging PET-CT without systemic lymphoma. A total of 300 patients fulfilled the inclusion criteria. Of them, 16% had a previous history of lymphoma, while 84% were diagnosed with PCNSL. None of the patients had DLBCL in the BM. A minority (8.3%) had discordant BMB findings, mainly low-grade histologies that did not influence treatment choice in any case. In conclusion, the risk of overlooking concordant BM infiltration in patients with CNS lymphoma of DLBCL histology and negative PET-CT scan is negligible. As we did not find any patient with DLBCL in the BMB, our results suggest that BMB can be safely omitted in the diagnostic workup in patients with CNS lymphoma and a negative PET-CT., (© 2023. The Author(s).)

Neutrophil extracellular traps (NETs) may play a pathogenic role in the thrombosis associated with myeloproliferative neoplasms (MPNs). We measured serum NET levels in 128 pretreatment samples from patients with MPNs and in 85 samples taken after 12 months of treatment with interferon alpha-2 (PEG-IFNα-2) formulations or hydroxyurea (HU). No differences in NET levels were observed across subdiagnoses or phenotypic driver mutations. In PV, a JAK2V617F + allele burden ≥50% associated with increased NET levels (p = 0.006). Baseline NET levels correlated with neutrophil count (r = 0.29, p = 0.001), neutrophil-to-lymphocyte ratio (r = 0.26, p = 0.004) and JAK2V617F allele burden (r = 0.22, p = 0.03), particularly in patients with PV and with allele burden ≥50% (r = 0.50, p = 0.01, r = 0.56, p = 0.002 and r = 0.45, p = 0.03 respectively). In PV, after 12 months of treatment, NET levels decreased on average by 60% in patients with allele burden ≥50%, compared to only 36% in patients with an allele burden <50%. Overall, treatment with PEG-IFNα-2a or PEG-IFNα-2b reduced NETs levels in 77% and 73% of patients, respectively, versus only 53% of HU-treated patients (average decrease across treatments: 48%). Normalization of blood counts did not per se account for these reductions. In conclusion, baseline NET levels correlated with neutrophil count, NLR and JAK2V617F allele burden, and IFNα was more effective at reducing prothrombotic NET levels than HU., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Surgical residents routinely participate in open and laparoscopic groin hernia repairs. The increasing popularity of robot-assisted groin hernia repair could lead to an educational loss for residents. We aimed to explore the involvement of surgical specialists and surgical residents, i.e., non-specialists, in robot-assisted groin hernia repair. The scoping review was reported according to PRISMA-ScR guideline. A protocol was uploaded at Open Science Framework, and a systematic search was conducted in four databases: PubMed, EMBASE, Cochrane CENTRAL, and Web of Science. Included studies had to report on robot-assisted groin hernia repairs. Data charting was conducted in duplicate. Of the 67 included studies, 85% of the studies described that the robot-assisted groin hernia repair was performed by a surgical specialist. The rest of the studies had no description of the primary operating surgeon. Only 13% of the included studies reported that a resident attended the robot-assisted groin hernia repair. Thus, robot-assisted groin hernia repair was mainly performed by surgical specialists, and robot-assisted groin hernia repair therefore seems to be underutilized to educate surgical residents., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Objectives: In vivo hemolysis is associated with thromboembolism. Although an increased Hemolysis Index (HI) can be due to in vitro as well as in vivo hemolysis, both reflects a more fragile erythrocyte population. We therefore hypothesized that HI above upper reference limit would be associated with an increased risk of cardiovascular disease (CVD)., Methods: We identified persons with two elevated HI (HI + ) from blood samples analyzed at a university hospital laboratory from 2012 to 2017. We compared their risk of CVD with the risk in matched comparators with normal HI and from the general population. HI + persons and comparators were followed from start date (date of the second elevated HI) until the first of the main outcome: CVD, emigration, death, or end of observation time on December 31, 2018., Results: In 43,102 unique HI + persons, the risk of developing CVD was 40% higher compared with the general population and 13% higher compared with the matched blood sample cohort. HI + was associated with a significantly increased cumulative incidence of both arterial and venous CVD compared with the matched blood sample cohort and the general population (respectively 47 and 14% for arterial CVD; 78 and 24% for venous CVD). Moreover, overall mortality risk was significantly higher in patients with HI + than in the two comparator groups., Conclusions: Elevated HI is associated with increased risk of arterial and venous CVD and with increased mortality. Our findings imply that HI may contribute as a CVD risk biomarker., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Background: Few studies have investigated long-term survival in patients with primary immune thrombocytopenia (pITP). Further, changes in prognosis over the past decades and prognosis of secondary immune thrombocytopenia (sITP) are largely unstudied. Our objectives were to study comorbidity-adjusted prognostic changes and causes of death in chronic pITP and sITP patients., Study Design/methods: Using nationwide Danish health registries 1980-2016, we identified 1762 patients with chronic pITP (median age 58 (IQR, 37-73) years) and 128 with chronic sITP (median age 59 (IQR, 40-73) years). Patients were age-sex-matched to 74,781 general population comparators. Comorbidity was assessed using Charlson Comorbidity Index (CCI)., Results: Overall median survival was reduced by 5.1 years (95% CI, 0.7-9.4) (p < .001) for pITP and 11.1 years (95% CI, 5.8-16.4) (p < .001) for sITP. 5-year survival increased from 69% (95% CI, 59-78) in 1980-89 to 80% (95% CI, 75-83) in 2010-16 for pITP, and decreased from 100% (95% CI, 89-98) to 64% (95% CI, 87-91) for sITP. However, numbers were small for sITP. 5-year survival for pITP with high CCI was 41% (95% CI, 32-49), and 85% (95% CI, 83-87) for low CCI. Bleeding, infection and hematological cancer were relatively frequent causes of death with adjusted subhazard ratios of 3.25 (95% CI, 2.33-4.52), 1.53 (95% CI, 1.08-2.16) and 2.16 (95% CI, 1.12-4.16) in pITP respectively, and 10.52 (95% CI, 1.43-77.36) for hematological cancer in sITP., Conclusions: Long-term survival is reduced in chronic ITP but seems to be improving. Comorbidity and sITP are associated with a poor prognosis., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: This study aims to examine quality of diabetes care in persons with type 2 diabetes with and without severe mental illness (SMI)., Methods: In a nationwide prospective register-based study, we followed persons with type 2 diabetes in Denmark with and without SMI including schizophrenia, bipolar disorder, or major depression. Quality of care was measured as receipt of care (hemoglobin A1c, low-density lipoprotein-cholesterol and urine albumin creatinine ratio assessment and eye and foot screening) and achievement of treatment targets between 2015 and 2019. Quality of care was compared in persons with and without SMI using generalized linear mixed models adjusted for key confounders., Findings: We included 216,537 persons with type 2 diabetes. At entry 16,874 (8%) had SMI. SMI was associated with lower odds of receiving care, with the most pronounced difference in urine albumin creatinine ratio assessment and eye screening (OR: 0.55, 95% CI: 0.53-0.58 and OR: 0.37 95% CI: 0.32-0.42, respectively). Among those with an assessment, we found that SMI was associated with higher achievement of recommended hemoglobin A1c levels and lower achievement of recommended low-density lipoprotein-cholesterol levels. Achievement of recommended low-density lipoprotein-cholesterol levels was similar in persons with versus without schizophrenia., Interpretation: Compared to persons without SMI, persons with SMI were less likely to receive process of care, with the most pronounced differences in urine albumin creatinine ratio assessment and eye screening., Funding: This study was funded by Steno Diabetes Center Copenhagen through an unrestricted grant from Novo Nordisk Foundation., Competing Interests: LK: holds shares in Novo Nordisk A/S, SHS: none, LJD: none, CAJ: none, SHW: none, MEB: none, DLH: None, MEJ: holds shares in Novo Nordisk, has received research grants from AMGEN, Astra Zeneca, 10.13039/100001003Boehringer Ingelheim, Novo Nordisk and Sanofi Aventis, GSA: holds shares in Novo Nordisk A/S., (© 2022 The Authors.)

Purpose: Robot-assisted groin hernia repair is becoming more popular in recent years but may remove operations from surgical trainees. We aimed to investigate the educational level of the surgeons who performed robot-assisted groin hernia repair and the rate of supervision and compare this to open and laparoscopic groin hernia repair., Methods: This register-based study was reported according to the RECORD statement and used linked data from the Danish Hernia Database and the Danish Patient Safety Authority's Online Register. We included surgeons that performed robot-assisted, laparoscopic, and/or open groin hernia repairs performed between January 1, 2015, and June 15, 2021 in Denmark., Results: A total of 916 surgeons performing 43,856 groin hernia repairs were included in this study. Surgical specialists performed 98% of the robot-assisted groin hernia repairs, 89% of the laparoscopic repairs (p < 0.0001), and 54% of the Lichtenstein repairs (p < 0.0001). Only 5% of the robot-assisted groin hernia repairs were supervised compared with 11% of the laparoscopic repairs (p < 0.0001) and 28% of the open repairs (p < 0.0001)., Conclusion: Almost all groin hernia repairs performed with the robot-assisted technique were performed by surgeons specialized in general surgery. The proportions of surgeons specialized in surgery were higher for robot-assisted operations compared with laparoscopic or open groin hernia surgery. Thus, our data suggest a lack of involvement of surgeons in training, and this diminishes the educational potential in the pool of groin hernia operations by the use of robot-assisted repairs., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Despite significant improvements in the prognosis of thrombotic thrombocytopenic purpura (TTP), long-term neuropsychological deficits are frequent but probably under-recognised. Regular assessment of cognitive impairment using screening tools is therefore recommended. In this case report we describe two patients with neuropsychological late effects severely affecting their work capacity and quality of life. These late effects were not diagnosed until neuropsychological testing. We conclude that screening tools may not be sufficient to capture neuropsychological late effects in TTP.

Introduction: Autoimmune hemolytic anemia (AIHA) is considered a chronic disease, with an overall good prognosis. However, recent reports indicate pre-mature mortality. Causes of death have not been evaluated previously., Methods: In a nationwide setting, we identified all patients with warm type AIHA or cold agglutinin disease (CAD), and age-sex-matched comparators from Denmark, 1980-2016. We estimated overall survival and cause-specific mortality from anemia, infection, cardiovascular causes, hematological or solid cancer, bleeding, or other causes, using cumulative incidence proportions., Results: We identified 1460 patients with primary AIHA, 1078 with secondary AIHA, 112 with CAD, and 130 801 comparators. One-year survival and median survival were, 82.7% and 9.8 years for primary AIHA, 69.1% and 3.3 years for secondary AIHA, and 85.5% and 8.8 years for CAD. Prognosis was comparable to the general population only in patients with primary AIHA below 30 years. In all other age and subgroups, the difference was considerable. Cumulated cause-specific mortality at 1 year was increased among patients versus comparators., Discussion: All groups of autoimmune hemolytic anemia are associated with increased overall and cause-specific mortality compared to the general population. This probably reflects unmet needs in both treatment and follow-up programs., (© 2022 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

The majority of JAK2 V617F -negative myeloproliferative neoplasms (MPNs) have disease-initiating frameshift mutations in calreticulin ( CALR ), resulting in a common carboxyl-terminal mutant fragment (CALR MUT ), representing an attractive source of neoantigens for cancer vaccines. However, studies have shown that CALR MUT -specific T cells are rare in patients with CALR MUT MPN for unknown reasons. We examined class I major histocompatibility complex (MHC-I) allele frequencies in patients with CALR MUT MPN from two independent cohorts. We observed that MHC-I alleles that present CALR MUT neoepitopes with high affinity are underrepresented in patients with CALR MUT MPN. We speculated that this was due to an increased chance of immune-mediated tumor rejection by individuals expressing one of these MHC-I alleles such that the disease never clinically manifested. As a consequence of this MHC-I allele restriction, we reasoned that patients with CALR MUT MPN would not efficiently respond to a CALR MUT fragment cancer vaccine but would when immunized with a modified CALR MUT heteroclitic peptide vaccine approach. We found that heteroclitic CALR MUT peptides specifically designed for the MHC-I alleles of patients with CALR MUT MPN efficiently elicited a CALR MUT cross-reactive CD8 + T cell response in human peripheral blood samples but not to the matched weakly immunogenic CALR MUT native peptides. We corroborated this effect in vivo in mice and observed that C57BL/6J mice can mount a CD8 + T cell response to the CALR MUT fragment upon immunization with a CALR MUT heteroclitic, but not native, peptide. Together, our data emphasize the therapeutic potential of heteroclitic peptide-based cancer vaccines in patients with CALR MUT MPN.

Objective: To investigate the efficacy and safety of dasiglucagon, a novel stable glucagon analog in a liquid formulation, in Roux-en-Y gastric bypass (RYGB)-operated individuals suffering from postbariatric hypoglycemia (PBH)., Research Design and Methods: In a randomized, double-blind, placebo-controlled, crossover trial, 10 RYGB-operated participants with continuous glucose monitoring-verified PBH were randomly assigned to 3 trial days, each consisting of a 240-min standardized liquid mixed-meal test with the subcutaneous injection of placebo or 80 μg or 200 μg dasiglucagon., Results: Compared with placebo, treatment with both 80 and 200 μg dasiglucagon raised nadir plasma glucose (PG) (placebo: 3.0 ± 0.2 mmol/L [mean ± SEM]; 80 μg dasiglucagon: 3.9 ± 0.3 mmol/L, P = 0.002; 200 μg dasiglucagon: 4.5 ± 0.2 mmol/L, P = 0.0002) and reduced time in hypoglycemia (PG <3.9 mmol/L) by 70.0 min (P = 0.030 and P = 0.008)., Conclusions: Single-dose administration of dasiglucagon effectively mitigated postprandial hypoglycemia., (© 2022 by the American Diabetes Association.)

Although somatic mutations influence the pathogenesis, phenotype, and outcome of myeloproliferative neoplasms (MPNs), little is known about their impact on molecular response to cytoreductive treatment. We performed targeted next-generation sequencing (NGS) on 202 pretreatment samples obtained from patients with MPN enrolled in the DALIAH trial (A Study of Low Dose Interferon Alpha Versus Hydroxyurea in Treatment of Chronic Myeloid Neoplasms; #NCT01387763), a randomized controlled phase 3 clinical trial, and 135 samples obtained after 24 months of therapy with recombinant interferon-alpha (IFNα) or hydroxyurea. The primary aim was to evaluate the association between complete clinicohematologic response (CHR) at 24 months and molecular response through sequential assessment of 120 genes using NGS. Among JAK2-mutated patients treated with IFNα, those with CHR had a greater reduction in the JAK2 variant allele frequency (median, 0.29 to 0.07; P < .0001) compared with those not achieving CHR (median, 0.27 to 0.14; P < .0001). In contrast, the CALR variant allele frequency did not significantly decline in those achieving CHR or in those not achieving CHR. Treatment-emergent mutations in DNMT3A were observed more commonly in patients treated with IFNα compared with hydroxyurea (P = .04). Furthermore, treatment-emergent DNMT3A mutations were significantly enriched in IFNα-treated patients not attaining CHR (P = .02). A mutation in TET2, DNMT3A, or ASXL1 was significantly associated with prior stroke (age-adjusted odds ratio, 5.29; 95% confidence interval, 1.59-17.54; P = .007), as was a mutation in TET2 alone (age-adjusted odds ratio, 3.03; 95% confidence interval, 1.03-9.01; P = .044). At 24 months, we found mutation-specific response patterns to IFNα: (1) JAK2- and CALR-mutated MPN exhibited distinct molecular responses; and (2) DNMT3A-mutated clones/subclones emerged on treatment., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: The number of scientific articles published each year is increasing, resulting in greater competition to get work published. Spin is defined as specific reporting strategies used to distort the readers' interpretation of results so that they are viewed more favorable. However, prevalence of spin in studies comparing robot-assisted groin hernia repair with traditional methods is unknown., Objectives/aim: To determine the frequency and extent of spin in studies assessing robot-assisted groin hernia repair., Methods: This systematic review was reported according to PRISMA guidelines, and a protocol was registered at PROSPERO before data extraction. Database search included PubMed, EMBASE, and Cochrane Central., Results: Of 35 included studies, spin was present in 57%. Within these, 95% had spin present in the abstract and 80% in the conclusion of the article. There was no association between study size and spin (p > 0.05). However, presence of spin in studies positively minded towards robot-assisted hernia repair was higher (p < 0.001) compared with those against or being neutral in their view of the procedure. Furthermore, being funded by or receiving grants from Intuitive Surgical were associated with a higher prevalence of spin (p < 0.05) compared with those who were not., Conclusion: Spin was found to be common in articles reporting on robot-assisted groin hernia repair, and presence of spin was higher in studies funded by or receiving grants from the robot company. This suggests that readers should be cautious when reading similar literature., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: People with psychiatric disorders have increased risk of premature death partly due to diabetes. This study aims to explore the quality of diabetes care, diabetes management, diabetes support and well-being of people with psychiatric disorders and diabetes., Research Design and Methods: A total of 107 participants aged ≥18 years with diabetes and psychiatric disorders treated at psychiatric outpatient clinics in Denmark were recruited from August 2018 to June 2019. This descriptive cross-sectional study includes data from medical records on quality of diabetes care (eg, level and annual examination of hemoglobin A1c (HbA 1c )) and questionnaires on diabetes management (measured on items from the Summary of Diabetes Self-Care Activities Scale and diabetes distress based on Problem Areas in Diabetes Scale (PAID-5)), diabetes support (no, some or high support from eight potential support persons and experience of care actions measured on items from Patient Assessment of Chronic Illness Care) and well-being (WHO 5-Item Scale and self-rated general health)., Results: The mean age was 52 years, 56% were men, the mean body mass index was 31.9 kg/m 2 , the median HbA 1c was 53 mmol/mol (7.0%) and the mean blood pressure was 131/83 mm Hg. The proportion with annual measurements of HbA 1c was 93%, blood pressure 80%, cholesterol 93%, foot examination 77% and eye examination 75%. Fifty-one per cent had high diabetes distress (PAID-5 score ≥8). Diabetologists and general practitioners (39% and 37%) were the health professionals most frequently reported to provide high diabetes support., Conclusions: This study highlights a need for improved diabetes support in people with psychiatric disorders and diabetes. Although a high proportion received appropriate diabetes care, we found high levels of diabetes distress, moderate levels of optimal self-management behaviors, low well-being and low diabetes support from psychiatric health professionals, while one-third of the population found it relevant to receive diabetes support from psychiatric health professionals., Competing Interests: Competing interests: LK owns shares in Novo Nordisk A/S. RW owns shares in Novo Nordisk A/S. MEJ has received research grants from Amgen, AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Sanofi-Aventis. MEJ holds shares in Novo Nordisk. GSA owns shares in Novo Nordisk A/S., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Evans syndrome (ES) is a rare condition, defined as the presence of 2 autoimmune cytopenias, most frequently autoimmune hemolytic anemia and immune thrombocytopenia (ITP) and rarely autoimmune neutropenia. ES can be classified as primary or secondary to various conditions, including lymphoproliferative disorders, other systemic autoimmune diseases, and primary immunodeficiencies, particularly in children. In adult ES, little is known about clinical features, disease associations, and outcomes. In this retrospective international study, we analyzed 116 adult patients followed at 13 European tertiary centers, focusing on treatment requirements, occurrence of complications, and death. ES was secondary to or associated with underlying conditions in 24 cases (21%), mainly other autoimmune diseases and hematologic neoplasms. Bleeding occurred in 42% of patients, mainly low grade and at ITP onset. Almost all patients received first-line treatment (steroids with or without intravenous immunoglobulin), and 23% needed early additional therapy for primary refractoriness. Additional therapy lines included rituximab, splenectomy, immunosuppressants, thrombopoietin receptor agonists, and others, with response rates >80%. However, a remarkable number of relapses occurred, requiring ≥3 therapy lines in 54% of cases. Infections and thrombotic complications occurred in 33% and 21% of patients, respectively, mainly grade ≥3, and correlated with the number of therapy lines. In addition to age, other factors negatively affecting survival were severe anemia at onset and occurrence of relapse, infection, and thrombosis. These data show that adult ES is often severe and marked by a relapsing clinical course and potentially fatal complications, pinpointing the need for high clinical awareness, prompt therapy, and anti-infectious/anti-thrombotic prophylaxis., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Distinguishing thrombotic thrombocytopenic purpura (TTP) from other thrombotic microangiopathies requires measurement of ADAMTS13 enzyme activity, but treatment must often be commenced before results from the ADAMTS13 analysis is available. Scoring systems to facilitate prediction of severe ADAMTS13 deficiency and therefore immediate clinical management have been developed. This combined with advances in treatment and monitoring holds optimism for improvements in late effects and survival in future patients. In this review, we discuss status in diagnosing, managing, and follow-up of patients with TTP.

Priapism is a persistent, painful erection, which can lead to permanent penile damage and reduced quality of life. Patients with sickle cell disease have an increased risk of priapism which has been related to chronic hemolysis. This study investigates the prevalence of priapism in all major hereditary and acquired forms of hemolytic disorders. Patients with hemolytic disorders were identified in the nationwide Danish Hemolysis Cohort. Each patient was age-sex-matched with 50 comparisons from the general population without hemolysis. We identified the episodes of hospital-registered priapism events for both patients with hemolysis disorders and comparisons in the Danish National Patient Register between 1977 and 2016. We identified 4181 male patients with hemolytic disorders and 205,994 male comparisons, with 2,294,027 person-years of total observation time. Totally, 101 episodes of priapism occurred during follow-up period. Six episodes of priapism were recorded in three patients with a hemolytic disorder, all affected by sickle cell disease. Two of these patients had verified genotype HbSS. The incidence rate for first priapism in sickle cell disease was 432.8 per 100,000 person-years [95% CI: 139.6; 1341.8] versus 0.84 per 100,000 person-years [95% CI 0.54; 1.32] in comparisons. Using a large nationwide cohort, we found that only sickle cell disease is associated with priapism among patients with hemolytic disorders. The incidence rate of priapism in patients with sickle cell disease was lower than previously reported., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Warm autoimmune haemolytic anaemia (wAIHA) is a haemolytic disorder, most commonly seen among adults and is classified as either primary or secondary to an underlying disease. We describe the age and sex distribution and the proportion of secondary wAIHA., Method: We retrieved 2635 published articles, screened abstracts and titles, and identified 27 articles eligible for full-text review. From these studies, we extracted data regarding number of patients, sex distribution, age at diagnosis, number of patients with secondary wAIHA, and whether the patients were diagnosed through local or referral centres. All data were weighted according to the number of included patients in each study., Results: 27 studies including a total of 4311 patients with wAIHA, of which 66% were females, were included. The median age at diagnosis was 68.7 years, however, wAIHA affected all ages. The mean proportion of secondary wAIHA was 49%, most frequently secondary to systemic lupus erythematosus. The proportions of secondary wAIHA reported from primary vs. referral centres were 35% vs. 59%, respectively., Conclusion: This review consolidates previously reported gender distribution. The higher proportion of secondary wAIHA in referral centres suggests that the most severely affected patients are disproportionally more frequent in such facilities.

Background: Postbariatric hypoglycemia (PBH) is a potentially serious complication after Roux-en-Y gastric bypass (RYGB), and impaired counterregulatory hormone responses have been suggested to contribute to the condition., Objectives: We evaluated counterregulatory responses during postprandial hypoglycemia in individuals with PBH who underwent RYGB., Setting: University hospital., Methods: Eleven women with documented PBH who had RYGB underwent a baseline liquid mixed meal test (MMT) followed by 5 MMTs preceded by treatment with (1) acarbose 50 mg, (2) sitagliptin 100 mg, (3) verapamil 120 mg, (4) liraglutide 1.2 mg, and (5) pasireotide 300 μg. Blood was collected at fixed time intervals. Plasma and serum were analyzed for glucose, insulin, glucagon, epinephrine, norepinephrine, pancreatic polypeptide (PP), and cortisol., Results: During the baseline MMT, participants had nadir blood glucose concentrations of 3.3 ± .2 mmol/L. At the time of nadir glucose, there was a small but significant increase in plasma glucagon. Plasma epinephrine concentrations were not increased at nadir glucose but were significantly elevated by the end of the MMT. There were no changes in norepinephrine, PP, and cortisol concentrations in response to hypoglycemia. After treatment with sitagliptin, 8 individuals had glucose nadirs <3.2 mmol/L (versus 4 individuals at baseline), and significant increases in glucagon, PP, and cortisol responses were observed., Conclusions: In response to postprandial hypoglycemia, individuals with PBH who underwent RYGB only had minor increases in counterregulatory hormones, while larger hormone responses occurred when glucose levels were lowered during treatment with sitagliptin. The glycemic threshold for counterregulatory activation could be altered in individuals with PBH, possibly explained by recurrent hypoglycemia., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Increased oxidative stress in obesity and diabetes is associated with morbidity and mortality risks. Levels of oxidative damage to DNA and RNA can be estimated through measurement of 8-oxo-7,8-dihydro-2´-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) in urine. Both markers have been associated with type 2 diabetes, where especially 8-oxoGuo is prognostic for mortality risk. We hypothesized that Roux-en-Y gastric bypass (RYGB) surgery that has considerable effects on bodyweight, hyperglycemia and mortality, might be working through mechanisms that reduce oxidative stress, thereby reducing levels of the urinary markers. We used liquid chromatography coupled with tandem mass spectrometry to analyze the content of 8-oxodG and 8-oxoGuo in urinary samples from 356 obese patients treated with the RYGB-procedure. Mean age (SD) was 44.2 (9.6) years, BMI was 42.1 (5.6) kg/m2. Ninety-six (27%) of the patients had type 2 diabetes. Excretion levels of each marker before and after surgery were compared as estimates of the total 24-hour excretion, using a model based on glomerular filtration rate (calculated from cystatin C, age, height and weight), plasma- and urinary creatinine. The excretion of 8-oxodG increased in the first months after RYGB. For 8-oxoGuo, a gradual decrease was seen. Two years after RYGB and a mean weight loss of 35 kg, decreased hyperglycemia and insulin resistance, excretion levels of both markers were reduced by approximately 12% (P < 0.001). For both markers, mean excretion levels were about 30% lower in the female subgroup (P < 0.0001). Also, in this subgroup, excretion of 8-oxodG was significantly lower in patients with than without diabetes. We conclude, that oxidative damage to nucleic acids, reflected in the excretion of 8-oxodG and 8-oxoGuo, had decreased significantly two years after RYGB-indicating that reduced oxidative stress could be contributing to the many long-term benefits of RYGB-surgery in obesity and type 2 diabetes., Competing Interests: The authors have declared that no competing interests exist.

Background: A considerable amount of research has been put into the explanation of the origin of the vampire myth by focussing on possible symptoms of the vampire; however, very little attention has been given to the victims., Aims: To elucidate whether the myth of vampire victims follows the course of disease of acute leukaemia., Method: We studied three classical vampire novels published 1819-1897, focusing on 8 victims and their symptoms. The novels were chosen based on their iconic status in classic vampire literature, which defined the vampire genre and the symptoms of the victims for many years. The symptoms and course of disease following vampire attacks described in these novels were then compared with symptoms commonly seen in untreated acute leukaemia and other contemporary disorders., Results: The earliest novel (1819) did not provide a sufficient description of any symptoms in detail; however, the later novels (1872 and 1897) both provided elaborate portrayals of symptoms and course of the disease. The patients studied were all factitious-explaining the variation in symptoms; however, they share common features. One case, a young woman named Lucy Westenra, described by Bram Stoker, 1897, mirrors a textbook example of an acute leukaemia patient-despite being described before the time of common acknowledgment of the diagnosis., Conclusion: Victims in the gothic vampire novels from the nineteenth century could very likely be inspired by real-life acute leukaemia patients.

Introduction: A hospital environment can be a significant burden and a health risk especially for dementia patients. Mobile x-ray equipment (ME) is used to enable imaging of these patients at home. The aim was to compare image quality (IQ) of chest, hip and pelvis images from ME to the stationary equipment (SE) used in a hospital department., Methods: We analysed examinations of the chest (n = 20), hip (n = 64) and pelvis (n = 32). Images were equally obtained from each setting of ME and SE. All images were graded using Visual Grading Analysis (VGA) by three radiographers (hip and pelvis) and three radiologists (chest). Technical IQ assessment was done by 80 additional images of a Contrast-Detail Radiography phantom (CDRAD)., Results: All chest images were approved for diagnostic use, as well as the hip AP and pelvis images from SE. 'Approved proportion of ME images was for HIP antero-posterior (AP) and pelvis, 78% [95% CI: 52-94%] and 81% [95% CI: 54-96%] respectively. Hip axial had an overall low, but not significant different approval rate. Ordered logistic regression indicated higher IQ of HIP AP and pelvic images from SE. This contrasts that the CDRAD substudy indicated better IQ, expressed as IQF inv , from ME., Conclusion: The VGA showed higher IQ for the SE system, while the CDRAD showed higher IQ for the ME system., Implications for Practice: Dementia patients can be examined at their home if the acquisition is optimised according to image quality in conjunct to radiation dose. Performing imaging out of the hospital and coordinating the patients' further treatment are new work areas for radiographers and requires excellent communication skills., (Copyright © 2019 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.)

Evans syndrome is defined by autoimmune haemolytic anaemia and immune thrombocytopenia occurring in the same patient. Although known to be rare the frequency and prognosis of Evans syndrome in children is unknown, and only few registry-based studies are available. The epidemiology and prognosis of Evans syndrome in patients above 13 years of age has recently been investigated. In this age group both incidence and prevalence of Evans syndrome increased during the study period and median survival was just 7.2 years. Using Danish health registries and the same approach, we identified 21 children below 13 years of age with Evans syndrome during 1981-2015. Patients with Evans syndrome were age-and sex matched with children both from the general population, and with patients with either autoimmune haemolytic anaemia or immune thrombocytopenia. The incidence of Evans syndrome ranged between 0.5 and 1.2/1,000,000 person-years. Prevalence was 6.7 and 19.3/1,000,000 in 1990 and 2015 respectively. Hazard ratio for death was 22 fold higher for children with ES compared to matched children from general population, and was also elevated compared to children with autoimmune haemolytic anaemia or immune thrombocytopenia. We conclude that pediatric ES is very rare and associated with elevated mortality. However, despite the nationwide study and a long and complete follow-up, results are imprecise due to the rarity of this disorder., Competing Interests: The project was funded by Alexion Pharma Nordic AB and Novartis Healthcare. None of the authors have any financial interests of any kind in any of the companies, employment in e.g. Advisory Boards or consultancy work. None of the authors are currently participating in any kind of drug development related to any of the companies. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Post-bariatric hypoglycemia (PBH) can be a serious complication after Roux-en-Y gastric bypass (RYGB), and treatment with somatostatin analogs has been suggested. We investigated the acute effects of three different doses of pasireotide (75 μg, 150 μg, and 300 μg) on the postprandial glucose metabolism in five RYGB-operated individuals with PBH using a mixed meal test. All three doses prevented hypoglycemia but were associated with a notable increase in postprandial hyperglycemia. Moreover, all doses greatly diminished insulin, C-peptide, and glucagon-like peptide-1 responses. Considering its strong hyperglycemic potential, we suggest that pasireotide should be administered carefully in RYGB-operated individuals with PBH, and if necessary, a 75 μg dose seems sufficient to prevent hypoglycemia.

Background: Early dumping and post-bariatric hypoglycemia (PBH) are often addressed as two separate postprandial complications after Roux-en-Y gastric bypass (RYGB). The aim of the study was to evaluate the occurrence of early dumping in RYGB-operated individuals with PBH with and without treatment intervention., Methods: Eleven RYGB-operated women with documented PBH each underwent a baseline liquid mixed meal test (MMT) followed by five MMTs preceded by treatment with: acarbose 50 mg for 1 week, sitagliptin 100 mg for 1 week, verapamil 120 mg for 1 week, liraglutide 1.2 mg for 3 weeks, and pasireotide 300 μg as a single dose. Repetitive venous blood sampling and continuous electrocardiogram recordings were performed at fasting and during a 3-h postprandial period., Results: During the baseline MMT, there was a significant increase in HR (from 65 ± 2 to 90 ± 4 bpm, p < 0.0001) within 30 min after meal intake, while hypoglycemia occurred in the later postprandial period. The HR increase was accompanied by significant increases in serum albumin, plasma norepinephrine, blood glucose, serum insulin, and plasma GLP-1 concentrations. The postprandial HR changes were positively correlated with the changes in insulin and GLP-1 concentrations. Treatment with acarbose and pasireotide both reduced HR, plasma norepinephrine, and serum insulin, and pasireotide also decreased plasma GLP-1., Conclusions: RYGB-operated individuals with PBH also have large early postprandial HR increases, hemoconcentration, and sympathetic activation, consistent with early dumping. Moreover, hormone excursions associated with PBH appear to be related to measures of early dumping, suggesting a causal relationship between early dumping and PBH., Trial Registration: NCT02527993.