Publications

An unacceptably large number of newborn infants die in developing countries. For a considerable number of cases (particularly in preterm infants), morbidity and mortality can be reduced by simply maintaining newborn thermal homeostasis during the first weeks of life. Unfortunately, deaths caused by prematurity remain inordinately common in low- and middle-income countries (LMICs) due to reduced access to incubators in light of the high cost of commercially available devices. We herein describe and test a low-cost and easy-to-assemble neonatal incubator created with inexpensive materials readily available in LMICs. The incubator is based on an Arduino microcontroller. It maintains controlled temperature and relative humidity inside the main chamber while continuously measuring newborn weight progress. Moreover, the incubator has a tilting bed system and an additional independent safety temperature alarm. The performance of the novel low-cost neonatal incubator was evaluated and successfully passed the IEC 60601-2-19 standards. In the present work, we provide all the necessary technical information, which is distributed as open source. This will enable assembly of very low-cost (<250 €) and fully functional incubators in LMICs that should help reduce neonatal mortality.© 2023 The Authors. Published by Elsevier Ltd.

JTD Keywords: arduino, control systems, developing countries, low-cost, low-resource regions, noise, preterm infant, Arduino, Control systems, Developing countries, Low-cost, Low-resource regions, Mortality, Neonatal incubator, Preterm infant

Liver cirrhosis is the end stage of all chronic liver diseases and contributes significantly to overall mortality of 2% globally. The age-standardized mortality from liver cirrhosis in Europe is between 10 and 20% and can be explained by not only the development of liver cancer but also the acute deterioration in the patient's overall condition. The development of complications including accumulation of fluid in the abdomen (ascites), bleeding in the gastrointestinal tract (variceal bleeding), bacterial infections, or a decrease in brain function (hepatic encephalopathy) define an acute decompensation that requires therapy and often leads to acute-on-chronic liver failure (ACLF) by different precipitating events. However, due to its complexity and organ-spanning nature, the pathogenesis of ACLF is poorly understood, and the common underlying mechanisms leading to the development of organ dysfunction or failure in ACLF are still elusive. Apart from general intensive care interventions, there are no specific therapy options for ACLF. Liver transplantation is often not possible in these patients due to contraindications and a lack of prioritization. In this review, we describe the framework of the ACLF-I project consortium funded by the Hessian Ministry of Higher Education, Research and the Arts (HMWK) based on existing findings and will provide answers to these open questions.

JTD Keywords: 12/15-lipoxygenase, combination, inflammation, interleukin-22, metabolism, mortality, organ failure, portal-hypertension, receptor, regeneration, systemic inflammation, systems medicine, translational hepatology, Decompensated cirrhosis, Organ failure, Systemic inflammation, Systems medicine, Translational hepatology

The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, by sex, underlying liver disease etiology, and severity of hepatic dysfunction.PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with additional manual search of bibliographies of relevant articles. Cohort studies of ?100 patients with cirrhosis and ?12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included.22 studies with 6965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), higher in male patients, patients with alcohol associated liver disease (ALD), patients with CTP grade C, and when sarcopenia was defined in patients by lumbar 3- skeletal muscle index (L3-SMI). Sarcopenia was associated with the increased risk of mortality in patients with cirrhosis (adjusted-hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in sensitivity analysis of cirrhosis patients without HCC (aHR 2.35, 95% CI 1.95-2.83) and in subgroup analysis by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the poor prognosis for patients with sarcopenia (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in all analyses.Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis.The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% in patients with ALD or Child's class C cirrhosis. Sarcopenia was independently associated with about 2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer period of having sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.Copyright © 2021. Published by Elsevier B.V.

JTD Keywords: alcohol associated liver disease, alcohol-associated liver disease, cirrhosis, failure, frailty, impact, list, mass, model, mortality, prognosis, prognostic value, sarcopenia, severe muscle depletion, skeletal muscle index, Alcohol-associated liver disease, Cirrhosis, Liver-transplant candidates, Prognosis, Sarcopenia, Skeletal muscle index

High ambient temperature and humidity greatly increase the risk of hyperthermia and mortality, particularly in infants, who are especially prone to dehydration. World areas at high risk of heat stress include many of the low-and middle-income countries (LMICs) where most of their inhabitants have no access to air conditioning. This study aimed to design, evaluate, and test a novel low-cost and easy-to-assemble device aimed at preventing the risk of infant hyperthermia in LMICs. The device is based on optimizing negative heat transfer from a small amount of ice and transferring it directly to the infant by airflow of refrigerated air. As a proof of concept, a device was assembled mainly using recycled materials, and its performance was assessed under laboratory-controlled conditions in a climatic chamber mimicking realistic stress conditions of high temperature and humidity. The device, which can be assembled by any layperson using easily available materials, provided sufficient refrigerating capacity for several hours from just 1–2 kg of ice obtained from a domestic freezer. Thus, application of this novel device may serve to attenuate the adverse effects of heat stress in infants, particularly in the context of the evolving climatic change trends. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

JTD Keywords: air conditioning, ambient-temperature, death, heat, heat index, heat shock, heatwave, high ambient temperature, hyperthermia, low-cost refrigeration, low-middle income countries, mortality, negative heat transfer, Air conditioning, Algorithm, Article, Climate change, Cost benefit analysis, Environmental temperature, Heat index, Heat shock, Heat stress, Heat transfer, Heating, Heatwave, High ambient temperature, High temperature, Humidity, Hyperthermia, Low income country, Low-cost refrigeration, Low-middle income countries, Middle income country, Middle-income countries, Negative heat transfer, Prevention study, Refrigeration, Temperature stress, Thawing

Background: Alcohol is a main cause of preventable deaths and frequently leads to the development of alcohol-related liver disease. Due to the lack of diagnostics, patients are commonly diagnosed after developing clinical manifestations. Recently, the biomarker PRO-C3 was shown to accurately identify fibrosis due to non-alcoholic fatty liver disease. Aim: To assess the diagnostic accuracy of PRO-C3, the ADAPT score and best-performing non-patented serological test to detect advanced alcohol-related liver fibrosis. Methods: We enrolled 426 patients with alcohol overuse in a prospective biopsy-controlled study. We evaluated the accuracy of PRO-C3 and the PRO-C3-based algorithm ADAPT to detect advanced liver fibrosis. Results: The accuracy of PRO-C3 was good with an AUROC of 0.85 (95% CI 0.79-0.90). The best-performing non-patented test was the Forns index with an AUROC of 0.83 (95% CI 0.78-0.89). The ADAPT algorithm performed better as compared to both the Forns index and PRO-C3 alone with an AUROC = 0.88 (95% CI 0.83-0.93). Conclusion: PRO-C3 is a new marker with high accuracy to detect advanced alcohol-related liver fibrosis. The diagnostic accuracy of PRO-C3 can be further improved by using the ADAPT algorithm in which the test outperforms currently available non-patented serological fibrosis markers. The study is registered in the Odense Patient Data Exploratory Network (OPEN) under study identification numbers OP_040 (https://open.rsyd.dk/OpenProjects/da/openProject.jsp?openNo=40) and OP_239 (https://open.rsyd.dk/OpenProjects/openProject.jsp?openNo=239&lang=da).

JTD Keywords: mortality, Collagen

Background & Aims: Prognostic models of cirrhosis underestimate disease severity for patients with cirrhosis and ascites. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein linked to hepatic neoangiogenesis and fibrogenesis. We investigated ascites MFAP4 as a predictor of transplant-free survival in patients with cirrhosis and ascites. Methods: A dual-centre observational study of patients with cirrhosis and ascites recruited consecutively in relation to a paracentesis was carried out. Patients were followed up for 1 year, until death or liver transplantation (LTx). Ascites MFAP4 was tested with the model for end-stage liver disease (MELD-Na), CLIF Consortium Acute Decompensation (CLIF-C AD), and Child-Pugh score in Cox regression models. Results: Ninety-three patients requiring paracentesis were included. Median ascites MFAP4 was 29.7 U/L [22.3–41.3], and MELD-Na was 19 [16–23]. A low MELD-Na score (<20) was observed in 49 patients (53%). During follow-up, 20 patients died (22%), and 6 received LTx (6%). High ascites MFAP4 (>29.7 U/L) was associated with 1-year transplant-free survival (p = 0.002). In Cox regression, ascites MFAP4 and MELD-Na independently predicted 1-year transplant-free survival (hazard ratio [HR] = 0.97, p = 0.03, and HR = 1.08, p = 0.01, respectively). Ascites MFAP4 and CLIF-C AD also predicted survival independently (HR = 0.96, p = 0.02, and HR = 1.05, p = 0.03, respectively), whereas only ascites MFAP4 did, controlling for the Child-Pugh score (HR = 0.97, p = 0.03, and HR = 1.18, p = 0.16, respectively). For patients with MELD-Na <20, ascites MFAP4 but not ascites protein predicted 1-year transplant-free survival (HR 0.91, p = 0.02, and HR = 0.94, p = 0.17, respectively). Conclusions: Ascites MFAP4 predicts 1-year transplant-free survival in patients with cirrhosis and ascites. In patients with low MELD-Na scores, ascites MFAP4, but not total ascites protein, significantly predicted 1-year transplant-free survival. Lay summary: Patients with cirrhosis who have fluid in the abdomen, ascites, are at an increased risk of death and in need for liver transplantation. Our study identified patients with ascites and a poor prognosis by measuring microfibrillar associated protein 4 (MFAP4), a protein present in the abdominal fluid. Patients with low levels of the MFAP4 protein are at particularly increased risk of death or liver transplantation, suggesting that clinical care should be intensified in this group of patients. © 2021 The Authors

JTD Keywords: biomarker, clif-c ad, clif consortium acute decompensation, cps, child-pugh score, crp, c-reactive protein, ct, computed tomography, decompensated, ecm, extracellular matrix, fibrosis, fluid protein, gfr, glomerular filtration rate, hr, hazard ratio, inr, internationalised normal ratio, liver disease, liver-cirrhosis, ltx, liver transplantation, markers, meld-na, model for end-stage liver disease, mfap4, microfibrillar associated protein 4, mortality, nash, non-alcoholic steatohepatitis, natural-history, prognosis, risk-factors, sbp, spontaneous bacterial peritonitis, scores, stage, Biomarker, Decompensated, Egfr, estimated gfr, Fibrosis, Liver disease, Mortality, Prognosis, Spontaneous bacterial peritonitis

Background: Home hospitalization is widely accepted as a cost-effective alternative to conventional hospitalization for selected patients. A recent analysis of the home hospitalization and early discharge (HH/ED) program at Hospital Clínic de Barcelona over a 10-year period demonstrated high levels of acceptance by patients and professionals, as well as health value-based generation at the provider and health-system levels. However, health risk assessment was identified as an unmet need with the potential to enhance clinical decision making. Objective: The objective of this study is to generate and assess predictive models of mortality and in-hospital admission at entry and at HH/ED discharge. Methods: Predictive modeling of mortality and in-hospital admission was done in 2 different scenarios: at entry into the HH/ED program and at discharge, from January 2009 to December 2015. Multisource predictive variables, including standard clinical data, patients’ functional features, and population health risk assessment, were considered. Results: We studied 1925 HH/ED patients by applying a random forest classifier, as it showed the best performance. Average results of the area under the receiver operating characteristic curve (AUROC; sensitivity/specificity) for the prediction of mortality were 0.88 (0.81/0.76) and 0.89 (0.81/0.81) at entry and at home hospitalization discharge, respectively; the AUROC (sensitivity/specificity) values for in-hospital admission were 0.71 (0.67/0.64) and 0.70 (0.71/0.61) at entry and at home hospitalization discharge, respectively. Conclusions: The results showed potential for feeding clinical decision support systems aimed at supporting health professionals for inclusion of candidates into the HH/ED program, and have the capacity to guide transitions toward community-based care at HH discharge.

JTD Keywords: Home hospitalization, Health risk assessment, Predictive modeling, Chronic care, Integrated care, Modeling, Hospitalization, Health risk, Prediction, Mortality, Clinical decision support