Atypical presentation of acute pancreatitis in a man with pancreatic insufficiency and cystic fibrosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Whether acute pancreatitis can occur in pancreatically insufficient individuals with cystic fibrosis remains a matter of debate.</p> <p>Case presentation</p> <p>We describe a case of acute pancreatitis occurring in a 52-year-old Caucasian Australian man with moderately severe cystic fibrosis lung disease and pancreatic insufficiency. An inflammatory mass within the head of his pancreas was confirmed using computed tomography, magnetic resonance imaging and pancreatic biopsy, but serum amylase and lipase remained normal throughout the acute phase of his illness. His symptoms and the pancreatic mass resolved following the insertion of a biliary stent and the introduction of ursodeoxycholic acid.</p> <p>Conclusion</p> <p>Our case report highlights the potential for acute pancreatitis to occur in patients with pancreatic insufficiency and cystic fibrosis. We further demonstrate that conventional biochemical markers that are normally assessed to confirm the diagnosis may not be of particular use. As patients with cystic fibrosis survive into their fourth and fifth decades of life, atypical presentations of acute pancreatitis may become more common.</p

Tracking development assistance for health and for COVID-19: a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050

Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached$8. 8 trillion (95% uncertainty interval UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total,$40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this,$13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and$1.4 billion was repurposed from existing health projects. $3.1 billion (22.4$2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7$1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

Mobilisation of the splenic monocyte reservoir and peripheral CX(3)CR1 deficiency adversely affects recovery from spinal cord injury

Macrophages in the injured spinal cord originate from resident microglia and blood monocytes. Whether this diversity in origins contributes to their seemingly dual role in immunopathology and repair processes has remained poorly understood. Here we took advantage of Cx(3)cr1(gfp) mice to visualise monocyte-derived macrophages in the injured spinal cord via adoptive cell transfer and bone marrow (BM) chimera approaches. We show that the majority of infiltrating monocytes at 7 days post-injury originate from the spleen and only to a lesser extent from the BM. Prevention of early monocyte infiltration via splenectomy was associated with improved recovery at 42 days post-SCI. In addition, an increased early presence of infiltrating monocytes/macrophages, as a result of CX(3)CR1 deficiency within the peripheral immune compartment, correlated with worsened injury outcomes. Adoptive transfer of identified Cx(3)cr1(gfp/+) monocytes confirmed peak infiltration at 7 days post-injury, with inflammatory (Ly6C(high)) monocytes being most efficiently recruited: Focal SCI also changed the composition of the two major monocyte subsets in the blood, with more Ly6C(high) cells present during peak recruitment. Adoptive transfer experiments further suggested high turnover of inflammatory monocytes in the spinal cord at 7 days post-injury. Consistent with this, only a small proportion of infiltrating cells unequivocally expressed polarisation markers for pro-inflammatory (M1) or alternatively activated (M2) macrophages at this time point. Our findings offer new insights into the origins of monocyte-derived macrophages after SCI and their contribution to functional recovery, providing a basis for further scrutiny and selective targeting of Ly6C(high) monocytes to improve outcomes from neurotraumatic events. (C) 2013 Elsevier Inc. All rights reserved

Genetic determinants of micronucleus formation in vivo

Genomic instability arising from defective responses to DNA damage or mitotic chromosomal imbalances can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology