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Cavitron ultrasonic surgical aspirator (CUSA) compared with conventional pancreatic transection in distal pancreatectomy: study protocol for the randomised controlled CUSA-1 pilot trial

Por: Holze · M. · Loos · M. · Hüttner · F. · Tenckhoff · S. · Feisst · M. · Knebel · P. · Klotz · R. · Mehrabi · A. · Michalski · C. · Pianka · F.
Background

Postoperative pancreatic fistula (POPF) remains the most common and serious complication after distal pancreatectomy. Many attempts at lowering fistula rates have led to unrewarding insignificant results as still up to 30% of the patients suffer from clinically relevant POPF. Therefore, the development of new innovative methods and procedures is still a cornerstone of current surgical research.

The cavitron ultrasonic surgical aspirator (CUSA) device is a well-known ultrasound-based parenchyma transection method, often used in liver and neurosurgery which has not yet been thoroughly investigated in pancreatic surgery, but the first results seem very promising.

Methods

The CUSA-1 trial is a randomised controlled pilot trial with two parallel study groups. This single-centre trial is assessor and patient blinded. A total of 60 patients with an indication for open distal pancreatectomy will be intraoperatively randomised after informed consent. The patients will be randomly assigned to either the control group with conventional pancreas transection (scalpel or stapler) or the experimental group, with transection using the CUSA device. The primary safety endpoint of this trial will be postoperative complications ≥grade 3 according to the Clavien-Dindo classification. The primary endpoint to investigate the effect will be the rate of POPF within 30 days postoperatively according to the ISGPS definition. Further perioperative outcomes, including postpancreatectomy haemorrhage, length of hospital stay and mortality will be analysed as secondary endpoints.

Discussion

Based on the available literature, CUSA may have a beneficial effect on POPF occurrence after distal pancreatectomy. The rationale of the CUSA-1 pilot trial is to investigate the safety and feasibility of the CUSA device in elective open distal pancreatectomy compared with conventional dissection methods and gather the first data on the effect on POPF occurrence. This data will lay the groundwork for a future confirmatory multicentre randomised controlled trial.

Ethics and dissemination

The CUSA-1 trial protocol was approved by the ethics committee of the University of Heidelberg (No. S-098/2022). Results will be published in an international peer-reviewed journal and summaries will be provided in lay language to study participants and their relatives.

Trial registration number

DRKS00027474.

Inequities and trends of polio immunisation among children aged 12-23 months in Ethiopia: a multilevel analysis of Ethiopian demographic and health survey

Por: Fekadu · H. · Mekonnen · W. · Adugna · A. · Kloos · H. · HaileMariam · D.
Introduction

Despite Ethiopia’s policy intention to provide recommended vaccination services to underprivileged populations, inequity in polio immunisation persists.

Objective

This study examined inequity and trends in polio immunisation and determinant factors among children aged 12–23 months in Ethiopia between 2000 and 2019.

Methods

Cross-sectional data from 2000, 2005, 2011, 2016 and 2019 Ethiopian demographic and health surveys were analysed with the updated version of the WHO’s Health Equity Assessment Toolkit software. Six standard equity measures: equity gaps, equity ratios, population attributable risk, population attributable fraction, slope index of inequality and relative index of inequality were used. Datasets were analysed and disaggregated by the five equality stratifiers: economic status, education, place of residence, sex of the child and regions. Multilevel logistic regression analysis was used to identify determinant factors.

Results

Polio immunisation coverage was increased from 34.5% (2000) to 60.0% (2019). The wealth index-related inequity, in coverage of polio immunisation between quintiles 5 and 1, was 20 percentage points for most surveys. The population attributable risk and population attributable fraction measure in 2011 indicate that the national polio immunisation coverage in that year could have been improved by nearly 36 and 81 percentage points, respectively, if absolute and relative wealth-driven inequity, respectively, had been avoided. The absolute difference between Addis Ababa and Afar Region was 74 percentage points in 2000 and 60 percentage points in 2019. In multilevel analysis result, individual-level factors like wealth index, maternal education antenatal care and place of delivery showed statistical significance.

Conclusion

Although polio immunisation coverage gradually increased over time, in the 20-year survey periods, still 40% of children remained unvaccinated. Inequities in coverage by wealth, educational status, urban–rural residence and administrative regions persisted. Increasing service coverage and improving equitable access to immunisations services may narrow the existing inequity gaps.

Trends of inequality in DPT3 immunization services utilization in Ethiopia and its determinant factors: Evidence from Ethiopian demographic and health surveys, 2000–2019

by Hailu Fekadu, Wubegzier Mekonnen, Aynalem Adugna, Helmut Kloos, Damen Hailemariam

Background

Low levels of diphtheria, tetanus toxoid, pertussis (DPT3) immunization services utilization and high deaths among under five children are concentrated in economically and socially disadvantaged groups, especially in low and middle-income countries, including Ethiopia. Hence, the aim of this study is to assess levels and trends in DPT3 immunization services utilization in Ethiopia and identify inequalities.

Methods

This study used data from 2000, 2005, 2011, 2016, and 2019 Ethiopian Demographic Health Surveys (EDHSs). The 2019 updated version of the world health organization (WHO’s) Health Equity Assessment Toolkit (HEAT) software was used to analyze the data. Six measure of inequality was calculated: ratio (R), differences (D), relative index of inequality (RII), slope index of inequality (SII), population attributable fraction (PAF) and population attributable risk (PAR). The findings were disaggregated by the five equity stratifiers: economic status, education, place of residence, regions and sex of the child.

Results

This study showed an erratic distribution of DPT3 immunization services utilization in Ethiopia. The trends in national DPT3 immunization coverage increased from 21% in (2000) to 62% in (2019) (by 41 percentage points). Regarding economic inequality, DPT3 immunization coverages for the poorest quintiles over 20 years were 15.3% (2000), and 47.7% (2019), for the richest quintiles coverage were 43.1 (2000), and 83.4% (2019). However, the service utilization among the poorest groups were increased three fold compared to the richest groups. Regarding educational status, inequality (RII) show decreasing pattern from 7.2% (2000) to 1.5% in(2019). Concerning DPT3 immunization inequality related to sex, (PAR) show that, sex related inequality is zero in 2000, 2005 and in 2019. However, based on the subnational region level, significance difference (PAR) was found in all surveys: 59.7 (2000), 51.1 (2005), 52.2 (2011), 42.5 (2016) and 30.7 (2019). The interesting point of this finding was that, the value of absolute inequality measures (PAR) and (PAF), are shown a decreasing trends from 2000 to 2019, and the gap among the better of regions and poor regions becoming narrowed over the last 20 years. Concerning individual and community level factors, household wealth index, education of the mother, age of respondent, antenatal care, and place of delivery show statically significant with outcome variable. Keeping the other variables constant the odds of an average child in Amhara Region getting DPT3 immunization was 54% less than for a child who lived in Addis Ababa (OR: 0.46, 95% CI: 0.34 – 0.63). Respondents from households with the richest and richer wealth status had 1.21, and 1.26 times higher odds of DPT3 immunization services utilization compared to their counterpart (OR: 1.21, 95% CI: 1.04 -1.41) and (OR: 1.26, 95% CI: 1.13 – 1.40) respectively.

Conclusion

We conclude that DPT3 immunization coverage shows a growing trend over 20 years in Ethiopia. But inequalities in utilization of DPT3 immunization services among five equality stratifies studied persisted. Reasons for this could be complex and multifactorial and depending on economic, social, maternal education, place of residence, and healthcare context. Therefore, policy has to be structured and be implemented in a ways that address context specific barriers to achieving equality among population sub-groups and regions.

Proteomic and transcriptomic characterisation of FIA10, a novel murine leukemic cell line that metastasizes into the brain

by Ursula Just, Helmut Burtscher, Sylvia Jeratsch, Meike Fischer, Carol Stocking, Jens Preussner, Mario Looso, Ralf Schwanbeck, Stefan Günther, Ralf Huss, Lynne Mullen, Thomas Braun

Brain metastasis leads to increased mortality and is a major site of relapse for several cancers, yet the molecular mechanisms of brain metastasis are not well understood. In this study, we established and characterized a new leukemic cell line, FIA10, that metastasizes into the central nervous system (CNS) following injection into the tail vein of syngeneic mice. Mice injected with FIA10 cells developed neurological symptoms such as loss of balance, tremor, ataxic gait and seizures, leading to death within 3 months. Histopathology coupled with PCR analysis clearly showed infiltration of leukemic FIA10 cells into the brain parenchyma of diseased mice, with little involvement of bone marrow, peripheral blood and other organs. To define pathways that contribute to CNS metastasis, global transcriptome and proteome analysis was performed on FIA10 cells and compared with that of the parental stem cell line FDCP-Mix and the related FIA18 cells, which give rise to myeloid leukemia without CNS involvement. 188 expressed genes (RNA level) and 189 proteins were upregulated (log2 ratio FIA10/FIA18 ≥ 1) and 120 mRNAs and 177 proteins were downregulated (log2 ratio FIA10/FIA18 ≤ 1) in FIA10 cells compared with FIA18 cells. Major upregulated pathways in FIA10 cells revealed by biofunctional analyses involved immune response components, adhesion molecules and enzymes implicated in extracellular matrix remodeling, opening and crossing the blood-brain barrier (BBB), molecules supporting migration within the brain parenchyma, alterations in metabolism necessary for growth within the brain microenvironment, and regulators for these functions. Downregulated RNA and protein included several tumor suppressors and DNA repair enzymes. In line with the function of FIA10 cells to specifically infiltrate the brain, FIA10 cells have acquired a phenotype that permits crossing the BBB and adapting to the brain microenvironment thereby escaping immune surveillance. These data and our model system FIA10 will be valuable resources to study the occurrence of brain metastases and may help in the development of potential therapies against brain invasion.
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