Long-term outcomes and renal responses following autologous hematopoietic stem cell transplantation for light chain deposition disease: a retrospective study on behalf of the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation.

There is little long-term outcome data on the efficacy of autologous hematopoietic stem cell transplantation (ASCT) in light chain deposition disease (LCDD). We identified 51 LCDD patients in the EBMT registry who had undergone upfront ASCT between 1995 and 2021. The median serum creatinine was 280 µmol/L and 45% required renal replacement therapy (RRT) at time of transplant. The melphalan dose was 100mg/m2 in 23%, 140mg/m2 in 55% and 200 mg/m2 in 21%. The rate of very good partial response or better improved from 41% pre-transplant to 66% at Day +100 post-ASCT. In RRT-independent patients, there was a modest improvement in renal function within the first 3 months; the median eGFR increased from 44 to 51 ml/min/1.73 m2. There was no further change between 3 and 12 months post- ASCT. No patient who was RRT-independent at ASCT became RRT dependent by Day + 100 post-ASCT. Median follow-up post-ASCT was 84 months (IQR: 46-122). At 6-years post ASCT, overall survival (OS) was 88% (95% CI: 78-98%) and PFS was 44% (95% CI: 28-60%). The 2-year cumulative incidence of relapse and non-relapse mortality (NRM) was 17% (95% CI: 6-27%) and 2% (95% CI: 0-6%), respectively. The cumulative incidence of renal transplantation at 4 years after ASCT was 27% (95% CI 13-41) with renal transplantation performed between 6.3 and 52.9 months post-ASCT (median 24.7 months). ASCT represents a feasible option for LCDD patients even if RRT dependent at time of transplant. Outcomes are favourable with low NRM and good long-term OS.

Rescreening on RBANS Delayed Memory Index? Forget About It!

OBJECTIVE: To assess the value of rescreening patients with Alzheimer's disease who do not meet the inclusion criteria for the Repeatable Battery for the Assessment of Neuropsychological Status Delayed Memory Index (RBANS DMI) at the initial assessment. PATIENTS AND METHODS: Participants (aged 50-85 years, without dementia, Mini-Mental State Examination score ≥22, valid Clinical Dementia Rating [CDR] global score, and amyloid status at baseline) were identified in the European Prevention of Alzheimer's Dementia database. Changes from baseline in RBANS DMI were estimated using a mixed model for repeated measurements. Logistic regressions were used to estimate the probability of participants with baseline RBANS DMI 86-95 having RBANS DMI ≤85, CDR global score ≥0.5, and amyloid positivity at 6 and 12 months. RESULTS: There was significant variability in the change in RBANS DMI scores over time (median change at 6 months: 2.0). An estimated 15% of participants with RBANS DMI 86-95 at baseline progressed to ≤85 at 6 months; 8% also achieved CDR global score ≥0.5 and 5% were also amyloid positive. CONCLUSIONS: The results from our analysis indicate that there is limited value in rescreening patients based on their initial RBANS DMI score.

Neonatal mortality and video assessment of resuscitation in four district hospitals in Pemba, Tanzania.

BACKGROUND: We aimed to assess risk factors for neonatal mortality, quality of neonatal resuscitation (NR) on videos and identify potential areas for improvement. METHODS: This prospective cohort study included women in childbirth and their newborns at four district hospitals in Pemba, Tanzania. Videos were analysed for quality-of-care. Questionnaires on quality-of-care indicators were answered by health workers (HW) and women. Risk factors for neonatal mortality were analysed in a binomial logistic regression model. RESULTS: 1440 newborns were enrolled. 34 newborns died within the neonatal period (23.6 per 1000 live births). Ninety neonatal resuscitations were performed, 20 cases on video. Positive pressure ventilation (PPV) was inadequate in 15 cases (75%). Half (10/20) did not have PPV initiated within the first minute, and in one case (5.0%), no PPV was performed. PPV was not sustained in 16/20 (80%) newborns. Of the 20 videos analysed, death occurred in 10 newborns: 8 after resuscitation attempts and two within the first 24 h. Most of HW 49/56 (87.5%) had received training in NR. CONCLUSIONS: Video analysis of NR revealed significant deviations from guidelines despite 87.5% of HW being trained in NR. Videos provided direct evidence of gaps in the quality of care and areas for future education, particularly effective PPV. IMPACT: Neonatal mortality in Pemba is 23.6 per 1000 livebirths, with more than 90% occurring in the first 24 h of life. Video assessment of neonatal resuscitation revealed deviations from guidelines and can add to understanding challenges and aid intervention design. The present study using video assessment of neonatal resuscitation is the first one performed at secondary-level hospitals where many of the world's births are conducted. Almost 90% of the health workers had received training in neonatal resuscitation, and the paper can aid intervention design by understanding the actual challenges in neonatal resuscitation.

Computed Tomography as a Method for Age Determination of Carnivora and Odontocetes with Validation from Individuals with Known Age.

Traditional methods for age determination of wildlife include either slicing thin sections off or grinding a tooth, both of which are laborious and invasive. Especially when it comes to ancient and valuable museum samples of rare or extinct species, non-invasive methods are preferable. In this study, X-ray micro-computed tomography (µ-CT) was verified as an alternative non-invasive method for age determination of three species within the order of Carnivora and suborders Odontoceti. Teeth from 13 red foxes (Vulpes vulpes), 2 American mink (Neogale vison), and 2 harbor porpoises (Phocoena phocoena) of known age were studied using µ-CT. The number of visible dental growth layers in the µ-CT were highly correlated with true age for all three species (R2 = 96%, p < 0.001). In addition, the Bland-Altman plot showed high agreement between the age of individuals and visible dental layers represented in 2D slices of the 3D µ-CT images. The true age of individuals was on average 0.3 (±0.6 SD) years higher than the age interpreted by the µ-CT image, and there was a 95% agreement between the true age and the age interpreted from visible dental layers in the µ-CT.

Sex Difference in Amebiasis.

Infection with the protozoan parasite Entamoeba histolytica is much more likely to cause severe, focal liver damage in males than females, although the infection rate is the same in both sexes. The differences in disease susceptibility may be due to modulation of key mechanisms of the innate immune response by sex hormones. Complement-mediated mechanisms and estrogen-dependent activated natural killer T cells lead to early elimination of the parasite in females, whereas a pathological immune axis is triggered in males. Testosterone, which is generally thought to have more immunosuppressive properties on cells of the immune response, leads to overwhelming activation of monocytes and host-dependent destruction of liver tissue in males resulting in worse outcomes.

Sirtuin1, not NAMPT, possesses anti-inflammatory effects in epicardial, pericardial and subcutaneous adipose tissue in patients with CHD.

BACKGROUND: Inflammation in cardiac adipose tissue (AT) is associated with atherosclerosis. We investigated whether the epicardial-, pericardial and pre-sternal subcutaneous AT (EAT, PAT and SAT) expression of Sirtuin1 (SIRT1) and nicotinamide phosphoribosyl transferase (NAMPT) are involved in the inflammatory process in coronary heart disease (CHD), and potentially associated to nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-related markers, macrophage polarization markers, cell markers and the cardiometabolic profile. METHODS: In this cohort study performed between 2016 and 2018, EAT, PAT and SAT biopsies were retrieved from 52 CHD patients (77% men, median age 67) undergoing open-chest coronary artery bypass grafting (CABG), and 22 patients (50% men, median age 69) undergoing aortic valve replacement serving as controls. AT samples were snap-frozen at - 80 °C until RNA extraction and AT expression of actual markers, relatively quantified by PCR. Circulating SIRT1 and NAMPT were measured with Enzyme-linked immunosorbent assays (ELISAs). Non-parametric statistical tests were mainly used, including Friedman's test coupled to Wilcoxon signed-rank test and Spearman Correlation. RESULTS: SIRT1 and NAMPT levels were similar in CHD and controls. In CHD, SIRT1 and NAMPT were inter-correlated in all AT compartments (r = 0.37-0.56, p < 0.01, all), and differently expressed between compartments, with the highest expression in SAT, significantly different from EAT (p < 0.01, both). Circulating SIRT1 and NAMPT levels were inversely associated (r = - 0.32, p = 0.024). In EAT and SAT, SIRT1 expression was inversely associated with IL-18 (r = - 0.43 and r = - 0.38, p < 0.01, both), whereas NAMPT expression was positively associated with the NLRP3 inflammasome-related markers in all compartments (r = 0.37-0.55, p < 0.01, all). While SIRT1 and NAMPT correlated to nitric oxide synthase 2 (NOS2), especially in SAT (r = 0.50-0.52, p ≤ 0.01, both), SIRT1 expression was related to endothelial cells, and NAMPT to macrophages. SIRT1 levels were correlated to weight and waist (r = 0.32 and r = 0.38, p < 0.03, both) and inversely to triglycerides and glycated haemoglobin (HbA1c) (r = - 0.33-- 0.37, p < 0.03, all), the latter positively correlated to NAMPT concentration (r = 0.39, p = 0.010). CONCLUSION: The study indicates that targeting SIRT1, with its anti-inflammatory properties, may be a novel anti-inflammatory strategy in preventing atherosclerosis and CHD progression. NAMPT may be an early player in AT inflammation, mediating/reflecting a pro-inflammatory state. TRIAL REGISTRATION: Registration: Clinicaltrials.gov ID: NCT02760914, registered the 5th of February 2016, http://clinicaltrials.gov/NCT02760914.

Risk factors of stillbirths in four district hospitals on Pemba Island, Tanzania: a prospective cohort study.

BACKGROUND: More than 2 million third-trimester stillbirths occur yearly, most of them in low- and middle-income countries. Data on stillbirths in these countries are rarely collected systematically. This study investigated the stillbirth rate and risk factors associated with stillbirth in four district hospitals in Pemba Island, Tanzania. METHODS: A prospective cohort study was completed between the 13th of September and the 29th of November 2019. All singleton births were eligible for inclusion. Events and history during pregnancy and indicators for adherence to guidelines were analysed in a logistic regression model that identified odds ratios [OR] with a 95% confidence interval [95% CI]. RESULTS: A stillbirth rate of 22 per 1000 total births in the cohort was identified; 35.5% were intrapartum stillbirths (total number of stillbirths in the cohort, n = 31). Risk factors for stillbirth were breech or cephalic malpresentation (OR 17.67, CI 7.5-41.64), decreased or no foetal movements (OR 2.6, CI 1.13-5.98), caesarean section [CS] (OR 5.19, CI 2.32-11.62), previous CS (OR 2.63, CI 1.05-6.59), preeclampsia (OR 21.54, CI 5.28-87.8), premature rupture of membranes or rupture of membranes 18 h before birth (OR 2.5, CI 1.06-5.94) and meconium stained amniotic fluid (OR 12.03, CI 5.23-27.67). Blood pressure was not routinely measured, and 25% of women with stillbirths with no registered foetal heart rate [FHR] at admission underwent CS. CONCLUSIONS: The stillbirth rate in this cohort was 22 per 1000 total births and did not fulfil the Every Newborn Action Plan's goal of 12 stillbirths per 1000 total births in 2030. Awareness of risk factors associated with stillbirth, preventive interventions and improved adherence to clinical guidelines during labour, and hence improved quality of care, are needed to decrease the stillbirth rate in resource-limited settings.

Macrophage polarization markers in subcutaneous, pericardial, and epicardial adipose tissue are altered in patients with coronary heart disease.

Background: Epicardial and pericardial adipose tissue (EAT and PAT) surround and protect the heart, with EAT directly sharing the microcirculation with the myocardium, possibly presenting a distinct macrophage phenotype that might affect the inflammatory environment in coronary heart disease (CHD). This study aims to investigate the expression of genes in different AT compartments driving the polarization of AT macrophages toward an anti-inflammatory (L-Galectin 9; CD206) or pro-inflammatory (NOS2) phenotype. Methods: EAT, PAT, and subcutaneous (SAT) biopsies were collected from 52 CHD patients undergoing coronary artery bypass grafting, and from 22 CTRLs undergoing aortic valve replacement. L-Galectin9 (L-Gal9), CD206, and NOS2 AT gene expression and circulating levels were analyzed through RT-PCR and ELISA, respectively. Results: L-Gal9, CD206, and NOS2 gene expression was similar in all AT compartments in CHD and CTRLs, as were also L-Gal9 and CD206 circulating levels, while NOS2 serum levels were higher in CHD (p = 0.012 vs. CTRLs). In CTRLs, NOS2 expression was lower in EAT vs. SAT (p = 0.007), while in CHD patients CD206 expression was lower in both SAT and EAT as compared to PAT (p = 0.003, p = 0.006, respectively), suggestive of a possible macrophage reprogramming toward a pro-inflammatory phenotype in EAT. In CHD patients, NOS2 expression in SAT correlated to that in PAT and EAT (p = 0.007, both), CD206 expression correlated positively to L-Gal9 (p < 0.001) only in EAT, and CD206 expression associated with that of macrophage identifying markers in all AT compartments (p < 0.001, all). In CHD patients, subjects with LDL-C above 1.8 mmol/L showed significantly higher NOS2 expression in PAT and EAT as compared to subjects with LDL-C levels below (p < 0.05), possibly reflecting increased cardiac AT pro-inflammatory activation. In SAT and PAT, CD206 expression associated with BMI in both CHD and CTRLs (p < 0.05, all), and with L-Gal9 in EAT, however only in CTRLs (p = 0.002). Conclusion: CHD seems to be accompanied by an altered cardiac, and especially epicardial AT macrophage polarization. This may represent an important pathophysiological mechanism and a promising field of therapy targeting the excessive AT inflammation, in need of further investigation.

Amyloidosis is a disease with many faces.

Amyloidosis is a severe disease caused by protein misfolding and deposition in tissues and organs. Thirty-eight different proteins are known to be amyloidogenic. Amyloidosis is categorized into inherited or acquired, and systemic or localized. Light-chain (AL)- and transthyretin (ATTR) amyloidosis are the two most common subtypes. Awareness, early diagnosis, accurate subtyping and relevant treatment are crucial for the management. Novel therapies of systemic AL and ATTR amyloidosis have considerably improved outcome and survival. The aim of this review is to increase awareness and knowledge on diagnosing amyloidosis.

Testosterone affects type I/type II interferon response of neutrophils during hepatic amebiasis.

Differences in immune response between men and women may influence the outcome of infectious diseases. Intestinal infection with Entamoeba histolytica leads to hepatic amebiasis, which is more common in males. Previously, we reported that innate immune cells contribute to liver damage in males in the murine model for hepatic amebiasis. Here, we focused on the influences of sex and androgens on neutrophils in particular. Infection associated with neutrophil accumulation in the liver was higher in male than in female mice and further increased after testosterone treatment in both sexes. Compared with female neutrophils, male neutrophils exhibit a more immature and less activated status, as evidenced by a lower proinflammatory N1-like phenotype and deconvolution, decreased gene expression of type I and type II interferon stimulated genes (ISGs) as well as downregulation of signaling pathways related to neutrophil activation. Neutrophils from females showed higher protein expression of the type I ISG viperin/RSAD2 during infection, which decreased by testosterone substitution. Moreover, ex vivo stimulation of human neutrophils revealed lower production of RSAD2 in neutrophils from men compared with women. These findings indicate that sex-specific effects on neutrophil physiology associated with maturation and type I IFN responsiveness might be important in the outcome of hepatic amebiasis.

Risk factors for neonatal sepsis in Sub-Saharan Africa: a systematic review with meta-analysis.

OBJECTIVES: To identify the risk factors for neonatal sepsis in Sub-Saharan Africa. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Web of Science, African Index Medicus and ClinicalTrials.gov were searched for observational studies from January 2010 to August 2020. SETTING: Sub-Saharan Africa, at all levels of healthcare facilities. PARTICIPANTS: 'Neonates' (<28 days of age) at risk of developing either clinical and/or laboratory-dependent diagnosis of sepsis. OUTCOME MEASURES: Identification of any risk factors for neonatal sepsis. RESULTS: A total of 36 studies with 23 605 patients from secondary or tertiary level of care facilities in 10 countries were included. Six studies were rated as good quality, 8 as fair and 22 as poor. Four studies were omitted in the meta-analysis due to insufficient data. The significant risk factors were resuscitation (OR 2.70, 95% CI 1.36 to 5.35), low birth weight <1.5 kg (OR 3.37, 95% CI 1.59 to 7.13) and 1.5-2.5 kg (OR 1.36, 95% CI 1.01 to 1.83), low Apgar score at the first minute (OR 3.69, 95% CI 2.34 to 5.81) and fifth minute (OR 2.55, 95% CI 1.46 to 4.45), prematurity <37 weeks (OR 1.91, 95% CI 1.27 to 2.86), no crying at birth (OR 3.49, 95% CI 1.42 to 8.55), male sex (OR 1.30, 95% CI 1.01 to 1.67), prolonged labour (OR 1.57, 95% CI 1.08 to 2.27), premature rupture of membranes (OR 2.15, 95% CI 1.34 to 3.47), multiple digital vaginal examinations (OR 2.22, 95% CI 1.27 to 3.89), meconium-stained amniotic fluid (OR 2.72, 95% CI 1.58 to 4.69), intrapartum maternal fever (OR 2.28, 95% CI 1.18 to 4.39), foul-smelling vaginal discharge (OR 3.31, 95% CI 2.16 to 5.09) and low socioeconomic status (OR 1.93, 95% CI 1.11 to 3.35). We found considerable heterogeneity in the meta-analysis of 11 out of 15 identified risk factors. CONCLUSION: Multiple risk factors for neonatal sepsis in Sub-Saharan Africa were identified. We revealed risk factors not listed by the WHO guidelines. The included studies overall had high risk of bias and high heterogeneity and thus, additional research of high quality is needed. PROSPERO REGISTRATION NUMBER: CRD42020191067.

The Properties of Proinflammatory Ly6Chi Monocytes Are Differentially Shaped by Parasitic and Bacterial Liver Infections.

In the past, proinflammatory CD11b+Ly6Chi monocytes were predominantly considered as a uniform population. However, recent investigations suggests that this population is far more diverse than previously thought. For example, in mouse models of Entamoeba (E.) histolytica and Listeria (L.) monocytogenes liver infections, it was shown that their absence had opposite effects. In the former model, it ameliorated parasite-dependent liver injury, whereas in the listeria model it exacerbated liver pathology. Here, we analyzed Ly6Chi monocytes from the liver of both infection models at transcriptome, protein, and functional levels. Paralleled by E. histolytica- and L. monocytogenes-specific differences in recruitment-relevant chemokines, both infections induced accumulation of Ly6C+ monocytes at infection sites. Transcriptomic analysis revealed a high similarity between monocytes from naïve and parasite-infected mice and a clear proinflammatory phenotype of listeria-induced monocytes. This was further reflected by the upregulation of M2-related transcription factors (e.g., Mafb, Nr4a1, Fos) and higher CD14 expression by Ly6Chi monocytes in the E. histolytica infection model. In contrast, monocytes from the listeria infection model expressed M1-related transcription factors (e.g., Irf2, Mndal, Ifi204) and showed higher expression of CD38, CD74, and CD86, as well as higher ROS production. Taken together, proinflammatory Ly6Chi monocytes vary considerably depending on the causative pathogen. By using markers identified in the study, Ly6Chi monocytes can be further subdivided into different populations.

Essential newborn care practices for healthy newborns at a district hospital in Pemba, Tanzania: a cross-sectional observational study utilizing video recordings.

BACKGROUND: High-quality essential newborn care (ENC) can improve newborn health and reduce preventable newborn mortality. The World Health Organization recommends specific ENC interventions. Video recordings have potential as a tool for assessment of clinical care also in low and middle-income countries. OBJECTIVE: To use video observations of healthy newborns to describe ENC practices in a low-income setting and compare actual clinical practice with WHO recommendations. METHOD: This is a cross-sectional observational study. Video records of neonatal interventions to 324 healthy newborns were assessed. They were obtained at baseline of a pre-post intervention study during a 10-week study period in Pemba, Tanzania. Data also included postnatal structured questionnaires. Eight ENC interventions and quality indicators were defined as per the WHO recommendations. Descriptive statistics were used to summarize ENC practices and maternal and neonatal characteristics. RESULTS: None of the newborns received all eight recommended ENC interventions. The median duration of separation from the mother was 25 minutes and 15 seconds (ranging from 22 seconds to 3 hours and 36 minutes), 51% of the newborns received proper thermal care during the separation. Twenty-one percent had sufficient umbilical cord care, 8% were stimulated for breathing, 69% were observed at least once by healthcare staff and 9% did undergo suctioning. None of the newborns received antibiotic ointments or vitamin K. CONCLUSION: Video recording of healthy newborns was feasible. The study identified omission of key ENC practices including proper thermal care, skin-to-skin contact and establishment of breastfeeding within the first hour of life, vitamin K administration as well as application of unnecessary practices such as excessive suctioning of breathing newborns.

Video recording as an objective assessment tool of health worker performance in neonatal resuscitation at a district hospital in Pemba, Tanzania: a feasibility study.

OBJECTIVES: To assess the feasibility of using video recordings of neonatal resuscitation (NR) to evaluate the quality of care in a low-resource district hospital. DESIGN: Prospective observational feasibility study. SETTING: Chake-Chake Hospital, a district hospital in Pemba, Tanzania, in April and May 2019. PARTICIPANTS: All delivering women and their newborns were eligible for participation. MAIN OUTCOME MEASURES: Motion-triggered cameras were mounted on resuscitation tables and provided recordings that were analysed for quality of care indicators based on the national NR algorithm. Assessment of feasibility was conducted using Bowen's 8-point framework for feasibility studies. RESULTS: 91% (126 of 139) of women and 96% (24 of 26) of health workers were comfortable or very comfortable with the video recordings. Of 139 newborns, 8 underwent resuscitation with bag and mask ventilation. In resuscitations, heat loss prevention measures were not performed in half of the cases (four of eight), clearing the airway was not performed correctly in five of eight cases, and all newborns were suctioned vigorously and repeatedly, even when not indicated. In a quarter (two of eight) of cases, the newborn's head was not positioned correctly. Additionally, two of the eight newborns needing ventilation were not ventilated within the first minute of life. In none of the eight cases did ventilation appear to be performed effectively. CONCLUSIONS: It proved feasible to use video recordings to assess quality of care during NR in a low-resource setting, and the method was considered acceptable for the delivering women and health workers. Recordings of eight resuscitations all demonstrated deviations from NR guidelines.

Outcome measures in rheumatology applied in self-management interventions targeting people with inflammatory Arthritis A systematic review of outcome domains and measurement instruments.

OBJECTIVE: Evaluating the effect of self-management interventions targeting people with inflammatory arthritis (IA) is a challenge because self-management interventions are complex and consensus on important outcomes is lacking. The aim is to identify, and map applied outcome domains and outcome measurement instruments from previous trials measuring the effect of self-management interventions targeting people with IA. METHOD: We performed an informative systematic literature review following guidance from the 'Outcome Measures in Rheumatology' (OMERACT) and 'Core Outcome Measures in Effectiveness Trials' (COMET) initiatives. Trials describing their experimental intervention as "self-management" applied in people diagnosed with any IA were included. Information on outcome domains and the corresponding measurement instruments were extracted, sorted, and categorized in domains and sub-domains. RESULTS: From a total of 2,502 records, we included 38 trials published between 1988 and 2021. We identified 12 different outcome domains, covering 39 subdomains, collected with 119 different measurement instruments. The most frequently applied outcome domains were self-efficacy, pain, physical functioning/disability, anxiety and depression, quality of life, fatigue, global assessment/disease activity and coping. The applied measurement instruments varied within each outcome domain and were predominantly patient-reported outcomes. CONCLUSION: The outcome domains and measurement instruments used in self-management trials were widely diverse and differ from the current general OMERACT Core Outcome Sets (COS) for IA conditions. Further steps towards the establishment of a COS to be reported in all self-management intervention trials will enhance the relevance and the subsequent impact on the body of evidence from these trials.

The Economic Cost of Burnout in Veterinary Medicine.

The purpose of this study is to estimate the economic cost of burnout in the veterinary profession and highlight the financial reasons why the industry should address the burnout crisis from an organizational perspective. Using data from 5,786 associate veterinarians in private practice, information was obtained using employment information related to compensation, work hours, hour preferences, and job turnover. Burnout was measured using the Professional Quality of Life Scale and used to calculate conditional probabilities on turnover and reduced working hours due to burnout. Lost revenue from each outcome (turnover and reduced working hours) was then used to calculate the economic costs to the veterinary services industry. The attributable cost of burnout of veterinarians to the US industry is between $1 and 2 billion annually in lost revenue, though there is a large amount of uncertainty. The cost is dependent on whether veterinary technicians are included in the analysis. The highest economic cost per veterinarian is among food animal practitioners, while the lowest is among equine. This study demonstrates that there are significant economic costs due to burnout among veterinarians and veterinary technicians. We suggest pursuing organizational interventions as these have shown the most impact in decreasing burnout and increasing satisfaction among human health physicians.

Treatment with glucagon-like peptide-1 receptor agonists and incidence of dementia: Data from pooled double-blind randomized controlled trials and nationwide disease and prescription registers.

INTRODUCTION: People with type 2 diabetes have increased risk of dementia. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are among the promising therapies for repurposing as a treatment for Alzheimer's disease; a key unanswered question is whether they reduce dementia incidence in people with type 2 diabetes. METHODS: We assessed exposure to GLP-1 RAs in patients with type 2 diabetes and subsequent diagnosis of dementia in two large data sources with long-term follow-up: pooled data from three randomized double-blind placebo-controlled cardiovascular outcome trials (15,820 patients) and a nationwide Danish registry-based cohort (120,054 patients). RESULTS: Dementia rate was lower both in patients randomized to GLP-1 RAs versus placebo (hazard ratio [HR]: 0.47 (95% confidence interval [CI]: 0.25-0.86) and in the nationwide cohort (HR: 0.89; 95% CI: 0.86-0.93 with yearly increased exposure to GLP-1 RAs). DISCUSSION: Treatment with GLP-1 RAs may provide a new opportunity to reduce the incidence of dementia in patients with type 2 diabetes.

HIF-1α modulates sex-specific Th17/Treg responses during hepatic amoebiasis.

BACKGROUND & AIMS: An invasive form of intestinal Entamoeba (E.) histolytica infection, which causes amoebic liver abscess, is more common in men than in women. Immunopathological mechanisms are responsible for the more severe outcome in males. Here, we used a mouse model of hepatic amoebiasis to investigate the contribution of hepatic hypoxia-inducible factor (HIF)-1α to T helper 17 (Th17)/regulatory T cell (Treg) responses in the context of the sex-specific outcome of liver damage. METHODS: C57BL/6J mice were infected intrahepatically with E. histolytica trophozoites. HIF-1α expression was determined by qPCR, flow cytometry and immunohistochemistry. Tregs and Th17 cells were analysed by immunohistochemistry and flow cytometry. Finally, male and female hepatocyte-specific Hif1α knockout mice were generated, and the effect of HIF-1α on abscess development, the cytokine milieu, and Th17/Treg differentiation was examined. RESULTS: E. histolytica infection increased hepatic HIF-1α levels, along with the elevated frequencies of hepatic Th17 and Treg cells. While the Th17 cell population was larger in male mice, Tregs characterised by increased expression of Foxp3 in female mice. Male mice displayed increased IL-6 expression, contributing to immunopathology; this increase in IL-6 expression declined upon deletion of hepatic HIF-1α. In both sexes, hepatic deletion of HIF-1α reduced the Th17 cell frequency; however, the percentage of Tregs was reduced in female mice only. CONCLUSIONS: Hepatic HIF-1α modulates the sex-specific outcome of murine E. histolytica infection. Our results suggest that in male mice, Th17 cells can be modulated by hepatic HIF-1α via IL-6, indicating marked involvement in the immunopathology underlying abscess development. Strong expression of Foxp3 by hepatic Tregs from female mice suggests a potent immunosuppressive function, leading to initiation of liver regeneration. LAY SUMMARY: Infection with the parasite Entamoeba histolytica activates immunopathological mechanisms in male mice, which lead to liver abscesses that are larger than those in female mice. In the absence of the protein HIF-1α in hepatocytes, abscess formation is reduced; moreover, the sex difference in abscess size is abolished. These results suggest that HIF-1α modulates the immune response involved in the induction of immunopathology, resulting in differential disease susceptibility in males and females.

The NLRP3 inflammasome activation in subcutaneous, epicardial and pericardial adipose tissue in patients with coronary heart disease undergoing coronary by-pass surgery.

Background and aims: Epicardial and pericardial adipose tissue (EAT and PAT) associate with atherosclerosis, however, discussed to have different inflammatory properties. We examined the NLRP3 inflammasome related pathway, playing a pivotal role in atherosclerosis, in EAT, PAT and subcutaneous AT (SAT), their relationship to cell types and anthropometric measures in patients undergoing coronary artery bypass grafting. Methods: Biopsies from EAT, PAT and SAT were collected from 52 patients with coronary heart disease (CHD) (median body weight 85.0 kg) and 22 controls. RNA was extracted and expression of interleukin (IL)-1ß, IL-18, NLRP3, Caspase-1, toll-like receptor 4 (TLR4), IL-6, IL-6 receptor and gp130 were analyzed by RT-PCR. Results: Limited differences in any genes between CHD patients and controls. IL-18 and IL-6 were 4-fold higher expressed in EAT versus PAT (p < 0.01, both) and SAT (p < 0.001, both), whereas caspase-1, IL-6R and gp130 were higher expressed in SAT compared to the other compartments (all p = 0.06-<0.001). Significant correlations between SAT and PAT gene expressions (r = 0.358-0.579, all p ≤ 0.01). Especially NLRP3 and TLR4 associated with the expression of macrophages in all compartments (all p < 0.001). In EAT IL-18 correlated inversely with the expression of macrophages and T-cells. In SAT and PAT most of the mediators associated with body weight. Conclusions: Higher expression of IL-18 and IL-6 was observed in EAT in our non-obese CHD patients, not related to inflammatory cells. The NLRP3 inflammasome activation in SAT that mirrored PAT, both related to anthropometrics, suggest that SAT samples, being easily available, to a certain degree, represent adipose tissue inflammation in general.

Combined Subcutaneous Fat Aspirate and Skin Tru-Cut Biopsy for Amyloid Screening in Patients with Suspected Systemic Amyloidosis.

Screening for systemic amyloidosis is typically carried out with abdominal fat aspirates with varying reported sensitivities. Fat aspirates are preferred for use in primary screening instead of organ biopsies as they are less invasive and thereby minimize the potential risk of complications. At Odense Amyloidosis Center, we performed a prospective study on whether the combined use of fat aspirate and tru-cut skin biopsy could increase the diagnostic sensitivity. Both fat aspirates and skin biopsies were screened with Congo Red staining, and positive biopsies were subsequently subtyped using immunoelectron microscopy and mass spectrometry. Seventy-six patients were included. In total, 24 patients had systemic amyloidosis (11 AL, 12 wtATTR, 1 AA), and 6 patients had localized amyloidosis. Combined fat aspirate and skin biopsy were Congo Red-positive in 15 patients (overall sensitivity (OS) 62.5%). Fat aspirates were positive in 14 patients (OS 58.3%), and the skin biopsy was positive in 5 patients (OS 20.8%). In only one patient did the skin biopsy add extra diagnostic information. The sensitivity differed between AL and ATTR amyloidosis-81.8% and 41.7%, respectively. Using skin biopsy as the only screening method is not recommended.