Dystocia in cattle and horses: a compilation of historical artworks dedicated to Professor Gerhard Sand (1861-1921).

Professor Gerhard Sand (1861-1921) was the first professor of veterinary obstetrics at the Royal Veterinary and Agricultural University, Copenhagen, Denmark. He began teaching the theory and practice of obstetrics to veterinary students in 1887 and spent the following years until his death in 1921 developing the veterinary obstetrics teaching program. During this period, veterinary obstetrics was established as an independent discipline at the Royal Veterinary and Agricultural University. Professor Sand's teaching had a major impact on the field of veterinary obstetrics in Scandinavia. He was devoted to teaching veterinary obstetrics and produced a number of obstetrical illustrations, some of which showed different causes of dystocia, mainly fetal malpresentation in cattle and horses. Professor Sand created the illustrations with the intention of publishing a handbook of obstetrics, but due to illness and an early death, this work was never completed. This compilation of historical artworks of dystocia in cattle and horses includes some of these illustrations and is published to honour Professor Sand, with the intention of making his illustrations widely available for the teaching of veterinary obstetrics.

PROphylactic closed incision Negative-PRESSure treatment in open incisional hernia repair: Protocol for a multicenter randomized trial (PROPRESS study).

Background: Negative Pressure Therapy in closed incisions (ciNPT) after surgery has shown positive effects including reduction of Surgical Site Infection (SSI) incidence. In patients undergoing elective open incisional hernia repair, however, ciNPT is not standard care, perhaps due to high-quality evidence still not provided. This study hypothesizes that this patient group would benefit from ciNPT by reducing wound complications and improving postoperative quality of life. Method: This is a multicenter Randomized Controlled Trial (RCT) including a total of 110 patients allocated in a 1:1 ratio with one intervention arm and one active control arm receiving ciNPT (i.e., Prevena™) and standard wound dressing, respectively. The primary outcome is the incidence of SSI at 30 days postoperatively and secondary outcomes are 1) pooled incidence of Surgical Site Occurrence (SSO), 2) patient-reported pain and satisfaction with the scar, and 3) hernia-related quality of life. Conclusion: Patients undergoing elective open incisional hernia repair are fragile with a high risk of wound complication development. This multicenter RCT seeks to deliver the high-quality evidence needed to establish the role ciNPT must play for exactly this group with the aim of reducing SSI incidence and health economic costs, and finally improving quality of life. There are no theoretical or clinical experience of unwanted consequences of this treatment.

Real-world outcomes following third or subsequent lines of therapy: A Danish population-based study on 189 patients with relapsed/refractory large B-cell lymphomas.

Outcome data of patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) beyond the second line are scarce outside of clinical trials. Novel therapies in the R/R setting have been approved based on single-arm trials, but results need to be contextualized by real-world outcomes. Medical records from 3753 Danish adults diagnosed with DLBCL were reviewed. Patients previously treated with rituximab and anthracycline-based chemotherapy who received the third or later line (3 L+) of treatment after 1 January 2015, were included. Only 189 patients with a median age of 71 years were eligible. The median time since the last line of therapy was 6 months. Patients were treated with either best supportive care (22%), platinum-based salvage therapy (13%), low-intensity chemotherapy (22%), in clinical trial (14%) or various combination treatments (32%). The 2-year OS-/PFS estimates were 25% and 12% for all patients and 49% and 17% for those treated with platinum-based salvage therapy. Age ≥70, CNS involvement, elevated LDH and ECOG ≥2 predicted poor outcomes, and patients with 0-1 of these risk factors had a 2-year OS estimate of 65%. Only a very small fraction of DLBCL patients received third-line treatment and were eligible for inclusion. Outcomes were generally poor, but better in intensively treated, fit young patients with limited disease.

The multidisciplinary approach to eosinophilia.

Eosinophilic granulocytes are normally present in low numbers in the bloodstream. Patients with an increased number of eosinophilic granulocytes in the differential count (eosinophilia) are common and can pose a clinical challenge because conditions with eosinophilia occur in all medical specialties. The diagnostic approach must be guided by a thorough medical history, supported by specific tests to guide individualized treatment. Neoplastic (primary) eosinophilia is identified by one of several unique acquired genetic causes. In contrast, reactive (secondary) eosinophilia is associated with a cytokine stimulus in a specific disease, while idiopathic eosinophilia is a diagnosis by exclusion. Rational treatment is disease-directed in secondary cases and has paved the way for targeted treatment against the driver in primary eosinophilia, whereas idiopathic cases are treated as needed by principles in eosinophilia originating from clonal drivers. The vast majority of patients are diagnosed with secondary eosinophilia and are managed by the relevant specialty-e.g., rheumatology, allergy, dermatology, gastroenterology, pulmonary medicine, hematology, or infectious disease. The overlap in symptoms and the risk of irreversible organ involvement in eosinophilia, irrespective of the cause, warrants that patients without a diagnostic clarification or who do not respond to adequate treatment should be referred to a multidisciplinary function anchored in a hematology department for evaluation. This review presents the pathophysiology, manifestations, differential diagnosis, diagnostic workup, and management of (adult) patients with eosinophilia. The purpose is to place eosinophilia in a clinical context, and therefore justify and inspire the establishment of a multidisciplinary team of experts from diagnostic and clinical specialties at the regional level to support the second opinion. The target patient population requires highly specialized laboratory analysis and therapy and occasionally has severe eosinophil-induced organ dysfunction. An added value of a centralized, clinical function is to serve as a platform for education and research to further improve the management of patients with eosinophilia. Primary and idiopathic eosinophilia are key topics in the review, which also address current research and discusses outstanding issues in the field.

Genetic variants in the adenosine triphosphate-binding cassette transporter A1 and risk of age-related macular degeneration.

Genetic variants in ABCA1 are associated with higher concentrations of high-density lipoprotein (HDL) cholesterol. Higher HDL cholesterol concentrations are observationally and genetically associated with higher risk of age-related macular degeneration (AMD). However, whether amino acid-changing genetic variants in ABCA1 associated with high HDL cholesterol concentrations confer a higher risk of AMD in the general population is currently unknown. We tested this hypothesis. The study included 80,972 individuals (1,370 AMD cases) from the Copenhagen General Population Study (CGPS) and 9,584 individuals (142 AMD cases) from the Copenhagen City Heart Study (CCHS) with 10 to 18 years of follow-up. We created an HDL cholesterol weighted allele score based on amino acid-changing ABCA1 variants with a minor allele frequency above 0.001 and divided it into tertiles. The study included 55% women. Mean age was 58 years. The ABCA1 allele score for the third versus the first tertile was associated with HRs (95% confidence intervals (CIs)) of 1.30 (1.14-1.49) for all-cause AMD, 1.26 (1.06-1.50) for nonneovascular AMD, and 1.31 (1.12-1.53) for neovascular AMD in a multivariable adjusted model. On a continuous scale, higher concentrations of genetically determined HDL cholesterol were associated with higher risk of all-cause AMD, nonneovascular AMD, and neovascular AMD in an age- and sex adjusted model and in a multivariable adjusted model. In conclusion, amino acid-changing genetic variants in ABCA1 associated with higher HDL cholesterol concentrations were also associated with higher risk of AMD, suggesting a role for ABCA1 in AMD pathogenesis.

Umbilical Hernia Repair in Patients with Cirrhosis and in Patients with Severe Comorbidities-A Nationwide Cohort Study.

INTRODUCTION: Umbilical hernia is a frequent condition in patients with cirrhosis. The aim of the study was to evaluate the risks associated with umbilical hernia repair in patients with cirrhosis in the elective and emergency setting. Secondly, to compare patients with cirrhosis with a population of patients with equally severe comorbidities but without cirrhosis. METHODS: Patients with cirrhosis who underwent umbilical hernia repair from January 1, 2007, to December 31, 2018, were included from the Danish Hernia Database. A control group of patients with a similar Charlson score (≥ 3) without cirrhosis was generated using propensity score matching. The primary outcome was postoperative re-intervention within 30 days following hernia repair. Secondary outcomes were mortality within 90 days and readmission within 30 days following hernia repair. RESULTS: A total of 252 patients with cirrhosis and 504 controls were included. Emergency repair in patients with cirrhosis was associated with a significantly increased rate of re-intervention (54/108 (50%) vs. 24/144 (16.7%), P < 0.001), 30-day readmission rate (50/108 (46.3%) compared with elective repair vs. 36/144 (25%) (P < 0.0001)), and 90-day mortality (18/108 (16.7%) vs. 5/144 (3.5%), P < 0.001). Patients with cirrhosis were more likely to undergo a postoperative re-intervention compared with comorbid patients without cirrhosis (OR = 2.10; 95% CI [1.45-3.03]). CONCLUSION: Patients with cirrhosis and other severe comorbidity undergo emergency umbilical hernia repair frequently. Emergency repair is associated with increased risk of poor outcome. Patients with cirrhosis undergo a postoperative reintervention more frequently than patients with other severe comorbidity undergoing umbilical hernia repair.

Treatment of incisional and parastomal hernias in Denmark.

Incisional and parastomal hernias are frequent complications after abdominal surgery. Patients with relevant symptoms should be referred to the local surgical department for diagnosis and indication for surgery. Patients with giant and parastomal hernias are referred to one of the five Danish regional hernia centres. Patients with parastomal hernias often benefit from being referred to a stoma nurse. The most frequent complications after hernia repair are wound complications and recurrence. In case of severe wound infection, incarceration, or strangulation the patient must always be referred acutely, as argued in this review.

Less postoperative pain and shorter length of stay after robot-assisted retrorectus hernia repair (rRetrorectus) compared with laparoscopic intraperitoneal onlay mesh repair (IPOM) for small or medium-sized ventral hernias.

BACKGROUND: The optimal repair of ventral hernia remains unknown. We aimed to evaluate the results after robotic-assisted laparoscopic transabdominal repair with retrorectus mesh placement (rRetrorectus) compared with laparoscopic intraperitoneal onlay mesh repair (IPOM) for patients with small- or medium-sized ventral hernia. METHODS: This was a retrospective cohort study of consecutive patients undergoing elective rRetrorectus or IPOM repair for small or medium-sized primary ventral or incisional hernias. The primary outcome was the postoperative need for transverse abdominis plane (TAP) block or epidural analgesia, secondary outcomes were length of stay and postoperative complications. All patients were followed for 30 days postoperatively. RESULTS: A total of 59 patients were included undergoing rRetrorectus (n = 27) and IPOM (n = 32). Patients in the two groups were comparable in terms of age, sex, comorbidities, smoking status, body mass index (BMI), and type of hernia. The median fascial defect area was slightly larger in the rRetrorectus group (9 cm2 vs. 6.2 cm2, P = 0.031). The duration of surgery was longer for rRetrorectus (median 117.2 min. vs. 84.4, P = 0.003), whereas the postoperative need for TAP block or epidural analgesia was less after rRetrorectus compared with IPOM (3.7% versus 43.7%, P = 0.002). There were no severe complications or reoperations after either procedure. The length of stay was shorter after rRetrorectus (median 0 vs. 1 day, P < 0.001). CONCLUSIONS: rRetrorectus was associated with reduced postoperative analgesic requirement and shorter length of stay compared with laparoscopic IPOM. Registration Clinicaltrial.gov: NCT05320055.

Clinical Presentation and Outcome of Sinonasal Extraosseous Plasmacytoma in Denmark: A Nationwide Cohort From 1980 to 2017.

OBJECTIVES: Extraosseous plasmacytoma (EOP) is a rare plasma cell neoplasm that tends to convert to plasma cell myeloma (PCM) in about 11% to 35% of cases. It has a predilection for the upper respiratory tract, prototypically affecting the nasal cavity and paranasal sinuses. Contemporary first-line treatment is radiotherapy, with more recent studies showing an added benefit of combining radiation with surgery. In this cohort study, we aimed to examine clinical presentation, treatment, and prognosis for all patients nationwide from 1980 through 2017. Furthermore, we determined the size and extension of tumors, investigating the rate at which minimally invasive surgery would have been possible. METHODS: Patients were found in the national pathology registry, and all biopsies were collected for pathology review by a hematopathologist. We performed survival statistics for overall survival (OS), progression-free survival (PFS), and the cumulative incidence of conversion to PCM. RESULTS: Twenty-three patients were included. The median age was 65, and patients were primarily men (78%). Tumors were located in either the nasal cavity (57%), maxillary sinus (39%), or sphenoid sinus (4%). In most cases, the tumor was <5 cm (65%) without extension to adjacent structures (60%). The national incidence was 0.02/100,000 person-years, the median symptom duration until diagnosis was 5 months, and none of the patients presented with contiguous spread to regional lymph nodes. Stand-alone radiotherapy was the predominant treatment (61%). In the entire cohort, one patient died from the initial disease, and six patients died from either relapse of EOP or PCM. The 5-year OS, PFS, and conversion rate to PCM were 78%, 56%, and 23%, respectively. CONCLUSION: SN-EOP responds well to radiotherapy, but relapse and conversion to PCM were not uncommon and entailed a poor prognosis. Most tumors were endoscopically resectable and non-invasive, making the majority of tumors suitable for surgery as an addition to radiation.

Shared Risk Factors between Dementia and Atherosclerotic Cardiovascular Disease.

Alzheimer's disease is the most common form of dementia, and the prodromal phases of Alzheimer's disease can last for decades. Vascular dementia is the second most common form of dementia and is distinguished from Alzheimer's disease by evidence of previous stroke or hemorrhage and current cerebrovascular disease. A compiled group of vascular-related dementias (vascular dementia and unspecified dementia) is often referred to as non-Alzheimer dementia. Recent evidence indicates that preventing dementia by lifestyle interventions early in life with a focus on reducing cardiovascular risk factors is a promising strategy for reducing future risk. Approximately 40% of dementia cases is estimated to be preventable by targeting modifiable, primarily cardiovascular risk factors. The aim of this review is to describe the association between risk factors for atherosclerotic cardiovascular disease and the risk of Alzheimer's disease and non-Alzheimer dementia by providing an overview of the current evidence and to shed light on possible shared pathogenic pathways between dementia and cardiovascular disease. The included risk factors are body mass index (BMI); plasma triglyceride-, high-density lipoprotein (HDL) cholesterol-, low-density lipoprotein (LDL) cholesterol-, and total cholesterol concentrations; hypertension; diabetes; non-alcoholic fatty liver disease (NAFLD); physical inactivity; smoking; diet; the gut microbiome; and genetics. Furthermore, we aim to disentangle the difference between associations of risk factors in midlife as compared with in late life.

NK- and T-cell lymphoma of the nasal cavity and paranasal sinuses in Denmark 1980-2017: a nationwide cohort study.

Compared to Asian and Latin American populations, sinonasal NK- or T-cell lymphoma is rare in Europe. All patients with sinonasal NK- or T-cell lymphoma in Denmark from 1980 to 2017 were validated histologically, and the disease behavior and demographics were extracted from medical records and national registries. Prognostic factors associated with mortality were determined using survival statistics. We included 56 patients: 40 extranodal NK/T-cell lymphoma (nasal type) (ENKTCL) and 16 peripheral T-cell lymphoma (not otherwise specified) (PTCL). The median age was 66, and most patients were male (72%). The ENKTCL and PTCL 5-year overall survival was 48% and 50%, respectively; progression-free survival was 38% for both. With ENKTCL, stage and performance status increased mortality significantly (HR = 8.6; p < 0.001 and HR = 4.23; p = 0.04). In conclusion, disseminated disease had a dismal outcome and the onset of ENKTCL in this ethnically homogeneous European cohort was about a decade later than reported in Asian populations.

Sinonasal B-cell lymphomas: A nationwide cohort study, with an emphasis on the prognosis and the recurrence pattern of primary diffuse large B-cell lymphoma.

Lymphomas of the nasal cavity and paranasal sinuses (NPS) are rare. Knowledge on sinonasal B-cell lymphoma (SNBCL) primarily comes from case series or single-center studies on small cohorts. We sought to determine the subtype distribution, clinical characteristics, disease behavior, and prognosis on a nationwide scale, with an emphasis on prognostic factors for the most common sinonasal lymphoma, primary sinonasal diffuse large B-cell lymphoma (PSDLBCL). We collated all data from medical records and national databases on patients registered with SNBCL from 1980 through 2018 in the national pathology registry and collected all tissue samples for validation of diagnosis. We included 205 patients and found 10 different subtypes of lymphoma. Diffuse large B-cell lymphoma (DLBCL) was the predominant subtype (80%). The incidence of SNBCL was 0.14/100,000 person-years. The five-year progression-free survival (PFS) and overall survival rates for PSDLBCL were 50% and 56%, respectively. For PSDLBCL, Rituximab showed a statistically significant effect (Hazard Ratio 0.22, p < 0.001), whereas consolidative radiotherapy combined with immunochemotherapy was of limited value (PFS, p = 0.93). When treatment failure occurred, DLBCL showed a distinct pattern of recurrence/dissemination to the NPS, skin, breast, central nervous system (CNS), and/or testis. Collectively, DLBCL comprised a clear majority of SNBCLs, although nine other subtypes were represented. Data showed that immunochemotherapy increased survival for PSDLBCL and that the addition of radiotherapy did not benefit patients. Furthermore, treatment failure for sinonasal DLBCL showed a possible common pathogenesis with primary extranodal lymphomas of specific locations (e.g., CNS, skin, breast, and testis).

Long-term Benefits and Harms Associated With Genetic Cholesteryl Ester Transfer Protein Deficiency in the General Population.

Importance: The balance between the potential long-term clinical benefits and harms associated with genetic cholesteryl ester transfer protein (CETP) deficiency, mimicking pharmacologic CETP inhibition, is unknown. Objective: To assess the relative benefits and harms associated with genetic CETP deficiency. Design, Setting, and Participants: This study examined 2 similar prospective cohorts of the Danish general population, with data on a total of 102 607 participants collected from October 10, 1991, through December 7, 2018. Exposures: Weighted CETP allele scores. Main Outcomes and Measures: Incident cardiovascular mortality, ischemic heart disease, myocardial infarction, ischemic stroke, peripheral arterial disease, vascular dementia, Alzheimer disease, all-cause mortality, and age-related macular degeneration (AMD). The study first tested whether a CETP allele score was associated with morbidity and mortality, when scaled to genetically lower levels of non-high-density lipoprotein (HDL) cholesterol (ie, 17 mg/dL), corresponding to the reduction observed for anacetrapib vs placebo in the Randomized Evaluation of the Effects of Anacetrapib Through Lipid-Modification (REVEAL) trial. Second, the study assessed how much of the change in morbidity and mortality was associated with genetically lower levels of non-HDL cholesterol. Finally, the balance between the potential long-term clinical benefits and harms associated with genetic CETP deficiency was quantified. For AMD, the analyses also included higher levels of HDL cholesterol associated with genetic CETP deficiency. Results: Of 102 607 individuals in the study, 56 559 (55%) were women (median age, 58 years [IQR, 47-67 years]). Multivariable adjusted hazard ratios showed that a genetically lower level of non-HDL cholesterol (ie, 17 mg/dL) was associated with a lower risk of cardiovascular mortality (hazard ratio [HR], 0.77 [95% CI, 0.62-0.95]), ischemic heart disease (HR, 0.80 [95% CI, 0.68-0.95]), myocardial infarction (HR, 0.72 [95% CI, 0.55-0.93]), peripheral arterial disease (HR, 0.80 [95% CI, 0.63-1.02]), and vascular dementia (HR, 0.38 [95% CI, 0.18-0.80]) and an increased risk of AMD (HR, 2.33 [95% CI, 1.63-3.30]) but was not associated with all-cause mortality (HR, 0.91 [95% CI, 0.81-1.02]), ischemic stroke (HR, 1.05 [95% CI, 0.81-1.36]), or Alzheimer disease (HR, 1.25 [95% CI, 0.89-1.76]). When scaled to a higher level of HDL cholesterol, the increased risk of AMD was even larger. A considerable fraction of the lower risk of cardiovascular end points was associated with genetically lower levels of non-HDL cholesterol, while the higher risk of AMD was associated with genetically higher levels of HDL cholesterol. Per 1 million person-years, the projected 1916 more AMD events associated with genetically higher levels of HDL cholesterol was similar to the 1962 fewer events of cardiovascular mortality and myocardial infarction combined associated with genetically lower levels of non-HDL cholesterol. Conclusions and Relevance: This study suggests that genetic CETP deficiency, mimicking pharmacologic CETP inhibition, was associated with a lower risk of cardiovascular morbidity and mortality, but with a markedly higher risk of AMD.

A Diagnostic Survey of Aborted Equine Fetuses and Stillborn Premature Foals in Denmark.

Background: Loss of pregnancy in mares can have many different causes, including both infectious and non-infectious conditions. Extrapolation of findings from other studies is often uncertain as the significance of each cause varies across regions. Causes of pregnancy loss in mares have never been thoroughly studied in Denmark, so a prospective cross-sectional cohort study targeting the entire Danish population of pregnant mares was performed over a period of 13 months to obtain knowledge of the significance of individual causes. Fifty aborted or prematurely delivered stillborn fetuses were submitted for necropsy and examined by a panel of diagnostic laboratory methods. Results: Overall, a cause of fetal loss was established for 72% of the examined cases. Most cases (62%) were lost due to a non-infectious cause, of which obstruction of the feto-placental blood circulation due to severe torsion of the umbilical cord was most prevalent. Pregnancy loss due to a variety of opportunistic bacteria, including bacteria not previously associated with abortion in mares, accounted for 12%, while equid alphaherpesvirus (EHV) type 1 was the cause of pregnancy loss in 8% of the cases. EHV type 4 and Chlamydiaceae species were identified in some cases, but not regarded as the cause of fetal loss. Conclusion: Umbilical cord torsion was found to be the most prevalent cause of fetal loss in Danish mares, while infectious causes such as EHV type 1 and streptococci only accounted for a minor proportion of the losses. The study highlights the need for defined criteria for establishing an abortion diagnosis in mares, particularly in relation to EHV types 1 and 4.