Search Results (187)

The insulin-like growth factor binding protein, acid-labile subunit (IGFALS), plays a crucial role in glucose metabolism and immune regulation, key processes in recovery from surgery. Here, we studied the perioperative serum IGFALS dynamics and explored potential clinical implications. A total of 79 patients undergoing elective cardiac surgery with implementation of cardiopulmonary bypass had their serum isolated at baseline, 24 h, seven days, and three months postoperatively to assess serum concentrations of IGFALS and insulin growth factor 1 (IGF-1). Markers of perioperative injury included troponin I (TnI), high-mobility group box 1 (HMGB-1), and heat shock protein 60 (Hsp-60). Inflammatory status was assessed via interleukin-6 (IL-6) and interleukin-8 (IL-8). Additionally, we measured in vitro cytokine production to viral stimulation of whole blood and monocytes. Surrogates of neuronal distress included neurofilament light chain (NF-L), total tau (τ), phosphorylated tau at threonine 181 (τp181), and amyloid β40 and β42. Renal impairment was defined by RIFLE criteria. Cardiac dysfunction was denoted by serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Serum IGFALS levels declined significantly after surgery and remained depressed even at 3 months. Administration of acetaminophen and acetylsalicylic acid differentiated IGFALS levels at the 24 h postoperatively. Serum IGFALS 24 h post-operatively correlated with production of cytokines by leukocytes after in vitro viral stimulation. Serum amyloid-β1-42 was significantly associated with IGFALS at baseline and 24 h post-surgery Patients discharged home had higher IGFALS levels at 28 days and 3 months than those discharged to healthcare facilities or who died. These findings suggest that IGFALS may serve as a prognostic biomarker for recovery trajectory and postoperative outcomes in cardiac surgery patients. Full article

Background: PP-007 (SANGUINATE^®, PEGylated carboxyhemoglobin, bovine) is under development to treat conditions of ischemia/hypoxia. Hemorrhagic/hypovolemic shock (H/HVS) becomes a life-threatening comorbidity due in part to hypotension and hypoxia. Blood transfusions are indicated, but supply and compatibility issues may limit subject access or when blood is not an option due to religious restriction or concern for clinical complications. PP-007 is universally compatible with an effective hydrodynamic radius and colloidal osmotic pressure facilitating perfusion without promoting extravasation. Methods: A review of previous clinical trials was performed and revealed an Open-Label Phase 1 safety study of acute severe anemia (hemoglobin ≤ 5 g/dL) in adult (≥18 y) patients unable to receive red blood cell transfusion (NCT02754999). Primary outcomes included safety events with secondary efficacy measures of organ function and survival at 1, 14, and 28 days. Additionally, a retrospective review of published, peer-reviewed case reports was performed, evaluating the administration of Sanguinate for Expanded Access in those patient populations where blood was not an option over the past 12 years. Results: A total of 103 subjects were enrolled in the Phase I safety study with significant co-morbidities that most commonly included hypertension (n = 43), acute and chronic kidney disease (n = 38), diabetes mellitus (n = 29), gastrointestinal bleeds (n = 18), and sickle cell disease (n = 13). Enrollment characteristics included decreased hemoglobin and severe anemia (mean baseline hemoglobin of 4.2 g/dL). Treatments included an average of three infusions [range 1–17]. Secondary efficacy measures were mean Hb levels, respiratory support, and vasopressor requirements, all demonstrating clinically relevant improvements. Fourteen additional cases were identified in the literature. Though one patient died due to pre-treatment conditions, all patients but one were discharged home in stable condition. Conclusion: Collectively, these observations are encouraging and provide support for the continued evaluation of PP-007 in advanced clinical trials in severe anemia including H/HVS. The review of published case reports underscored the potential of Sanguinate to reduce early mortality. Adverse effects included transient hypertension, lethargy, dizziness, and troponin elevation. These findings highlight the need for continued research and funding of blood alternatives to improve outcomes when standard blood transfusions are unavailable or contraindicated. Full article

Background/Objectives: The place where a person dies serves as an indicator of end-of-life care quality. This study aims to identify the congruence of place of death (POD) and the reasons behind decision-making among terminally ill cancer patients in East Asia. Methods: We conducted a prospective multicenter cohort study in palliative care units in Japan, Korea, and Taiwan. Data were collected by the responsible physicians during routine clinical practice. Sankey diagrams were applied to present changes in reasons for POD incongruence. Results: A total of 2638 participants from 37 palliative care units in the three countries were enrolled, and most of them died at PCUs (Japan: 95.7%, Korea: 94%, Taiwan: 82%, p < 0.05). The congruence rate of the preferred and actual POD among PCU inpatients ranged from 70% to 80%. Availability of end-of-life care is the most common reason for preferred and eventual PCU death (78.6%, 72.2%, and 52.1%, respectively, p < 0.05). However, 13–22% of patients admitted to PCUs still preferred to die at home, for which traditional culture (20.2%, 40.8%, and 82%, respectively, p < 0.05) or family influence (44.4%, 38.8%, and 51.7%, respectively, p > 0.05) are the main reasons. Cultural and environmental factors, such as influences from family members’ preferences in the three countries or the ownership of housing/housing settings in Japan, are the main challenges in achieving POD congruence. Conclusions: Culturally inclusive strategies in clinical practice and policy implementation for identifying the preferred POD, enhancing communication among stakeholders, and facilitating transitional support may improve the quality of goal-concordant care. Full article

In this article, we present a case of a 49-year-old woman presenting with a recurrent metastatic neuroendocrine tumor. Background: Insulinomas are neuroendocrine tumors derived from beta cells of the pancreas that secrete insulin. Usually, they are benign tumors; however, metastatic insulinomas are an extremely rare malignant form of these tumors, carrying a significantly worse prognosis. Case Presentation: A 49-year-old woman, a patient in the University Hospital in Wroclaw in the Department of Endocrinology, Diabetes and Isotope Therapy, first presented with abdominal pain in 2009, when ultrasound and further examination led to the diagnosis of a tumor in the pancreas (a solid pseudopapillary tumor of the pancreas—meta NET G2), and the patient underwent distal pancreatectomy with splenectomy. For ten years, she was under observation, and her symptoms, such as abdominal pain, nausea, weight loss, and general weakness, reappeared in 2019. Then, magnetic resonance imaging (MRI) showed a lesion in the liver, and further histopathology revealed neuroendocrine tumor (NET) metastasis to the liver. In 2022, the patient presented with loss of consciousness and convulsion, loss of weight, and hypoglycemia after meals. In April 2022, the daily glycemic profile was recorded and a 72 h fasting test was performed; however, their results excluded insulinoma. Positron emission tomography–computed tomography (PET-CT) with 18F-fluorodeoxyglucose (18F-FDG) and PET with gallium-68-DOTA-(Tyr3)-octreotate (68Ga-DOTA-TATE) showed a metastatic proliferative process in the liver. Persistent hypoglycemia led to another hospitalization in May 2022, and repeated tests allowed for the diagnosis of insulinoma. Treatment with somatostatin analogs and diazoxide was started. A CT scan in November 2022 and a PET scan in January 2023 showed new metastases to the liver, bones, and cervical lymph nodes, and it was decided to intensify the treatment. In May 2023, the patient was qualified for Lutathera treatment for insulinoma at the University Clinical Hospital in Poznań. In June 2023, another disturbing symptom was reported by the patient, a painful lump in the breast. During diagnostics, metastases with high proliferation markers were found in both breasts. Two months later, in August 2023, the patient received another dose of Lutathera. In October 2023, significant progression of liver lesions, metastases to bones of the spine, ribs, and pelvis, and periaortic and pelvic lymphadenopathy were found as well as elevated values of neuron-specific enolase and calcitonin. The patient was also referred to the Palliative Medicine Home Hospice. In consultation with the Lower Silesian Cancer Center, the decision was made to forgo further treatment with PRRT and initiate systemic chemotherapy. Despite the chosen treatment, the patient died on 27/DEC/2023. Conclusions: This case report can serve clinicians, as it presents a case of an extremely rare and insidious tumor, metastatic insulinoma. Full article

The surge in electric vehicles (EVs) in Denmark challenges the country’s residential low-voltage (LV) distribution system. In particular, it increases the demand for home EV charging significantly and possibly overloads the LV grid. This study analyzes the impact of EV charging integration on Denmark’s residential distribution networks. A residential grid comprising 67 households powered by a 630 kVA transformer is studied using DiGSILENT PowerFactory. With the assumption of simultaneous charging of all EVs, the transformer can be heavily loaded up to 147.2%. Thus, a voltage-droop based autonomous control approach is adopted, where the EV charging power is dynamically adjusted based on the point-of-connection voltage of each charger instead of the fixed rated power. This strategy eliminates overloading of the transformers and cables, ensuring they operate within a pre-set limit of 80%. Voltage drops are mitigated within the acceptable safety range of ±10% from normal voltage. These results highlight the effectiveness of the droop control strategy in managing EV charging power. Finally, it exemplifies the benefits of intelligent EV charging systems in Horizon 2020 EU Projects like SERENE and SUSTENANCE. The findings underscore the necessity to integrate smart control mechanisms, consider reinforcing grids, and promote active consumer participation to meet the rising demand for a low-carbon future. Full article

Background: Kyphoscoliosis is a restrictive thoracic disorder frequently associated with chronic respiratory failure. While home non-invasive ventilation (NIV) improves short-term outcomes, long-term mortality predictors remain underexplored in this context. Methods: This retrospective cohort study evaluated 88 kyphoscoliosis patients with chronic respiratory failure who were initiated on home-based NIV between 2008 and 2018 at a tertiary ICU outpatient clinic. The demographic, clinical, and laboratory data were analyzed. Survival was assessed using Kaplan–Meier analysis, and independent predictors of mortality were identified via Cox regression. Results: Among the 88 patients (52% male), 28 (32%) died during long-term follow-up. Age, BMI, pulmonary function, and arterial blood gas values were similar between survivors and non-survivors. Non-survivors had significantly higher mMRC dyspnea scores, were more likely to be active smokers, and had a higher prevalence of coronary artery disease (CAD) (p = 0.015). The Kaplan–Meier survival analysis revealed significantly lower survival in patients with CAD (p = 0.021) and active smokers (p = 0.034). Cox regression analysis indicated that the presence of CAD (HR: 5.69, 95% CI: 1.34–24.08, p = 0.018) and hospital admission after the initiation of home-based NIV therapy (HR: 1.97, 95% CI: 1.01–3.85, p = 0.040) increased the risk of mortality. Conversely, a higher pH at the last outpatient visit was associated with improved survival (HR: 0.50, 95% CI: 0.00–0.692, p = 0.003). Conclusions: CAD, pH value, and increased ICU admissions after the initiation of home-based NIV are predictors of mortality in kyphoscoliosis patients. The study results highlight reduced survival associated with the presence of coronary artery disease and smoking, emphasizing the importance of routine cardiovascular assessment and close clinical follow-up in this high-risk population. Full article

Increasing consumer awareness on significant environmental challenges, in addition to forthcoming regulations, is driving domestic appliance manufacturers to adopt an Ecodesign approach to more effectively and significantly reduce the environmental impacts along all of the life cycle phases of their products, minimising energy and material consumption, optimising the life of the product, facilitating recycling, facilitating disassembly, optimising material conservation/renewability, and minimising toxicity. This paper emphasises and discusses the significance of supporting this process by creating a company-specific handbook of guidelines and checklists to design low-environmental-impact products across an entire company’s appliance range. Checklists are design support tools intended to qualitatively assess whether, and to what extent, an Ecodesign guideline has been applied, enabling the evaluation of existing products or newly developed concepts, while also serving to guide and inspire sustainable design decisions. It is argued that these are effective tools in translating eco-efficient design into practice and guiding the whole of product development organisation through a knowledge-based approach. The Handbook of Guidelines to Design Low Environmental Impact Products is the result of a project commissioned by a home appliance company to the LeNSlab (research group on Design and System Innovation for Sustainability) of the Design Department of Politecnico di Milano, elaborated, after preliminary desk research, through a series of activities, interactions, knowledge exchanges, and operative workshops in cooperation with the company team of experts. The handbook contains 7 Ecodesign strategies, 27 sub-strategies, 157 guidelines, and related checklists, to be specific to such a level that they can effectively be applied to all types of company appliances. Full article

High levels of social stress are known to negatively impact pig welfare. The aim of this study was to evaluate the impact of social stress in growing–finishing pigs by measuring serum metabolome changes and saliva biomarkers. Seventy-two undocked pigs (thirty-six males and thirty-six females) were housed in single-sex pens of four, with the second dominant pig in each pen selected as the focal pig. A social challenge was conducted by mixing the focal pig with three new pigs in its home pen on two consecutive days on trial days 62–64. Saliva and blood samples were collected, and the pigs’ behaviour and body lesions were evaluated pre- and post-challenge. A total of 630 serum metabolites were analysed, 292 of which could be statistically compared using Biocrates WebIDQ v5 software. Salivary haptoglobin concentrations and the number of body lesions significantly increased after the challenge (p < 0.001), whereas the average daily weight gain decreased (p < 0.05). The serum showed decreases in essential amino acids (Thr, Met, and Phe), non-essential amino acids (Glu, Asn, Asp, Pro, and Tyr), betaine, ornithine, indoxyl sulphate, taurine, and some blood di- and triacylglycerols (q < 0.05), and increases in oleic, eicosanoic, eicosadienoic, and dihomo-gamma-linolenic acids; EPA; and DHA post-challenge (q < 0.05). Overall, the results suggest the potential of metabolomics as a tool providing a more holistic view of the impact of social stress. Full article

Background: Post-production storage plays a pivotal role in developing the characteristic flavor profile of Baijiu, a traditional alcoholic beverage in China. While aging markers remain crucial for quality authentication, the identification of reliable metabolic indicators for chronological determination requires further exploration. Methods: This study establishes a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology for quantifying five linoleic acid-derived oxidative metabolites in Baijiu: 9,12,13-trihydroxy-10(E)-octadecenoic acid (9,12,13-TriHOME), 9,10-Dihydroxy-12-octadecenoic acid (9,10-DiHOME), 9-oxo-(10E,12Z)-octadecadienoic acid (9-OxoODE), 9-hydroxy-(10E,12Z)-octadecadienoic acid (9-HODE) and 13-hydroxyoctadeca-(9Z,11E)-octadecadienoic acid (13-HODE). Results: The optimized protocol demonstrated exceptional sensitivity with limits of detection at 0.4 ppb through membrane-filtered direct dilution. Calibration curves exhibited excellent linearity (R² > 0.9990) across 1.0–100.0 ppb ranges. Method validation revealed satisfactory recovery rates (87.25–119.44%) at three spiking levels (10/20/50 ppb) with precision below 6.96% RSD. Application to authentic samples showed distinct temporal accumulation patterns. Light-aroma Baijiu exhibited storage duration-dependent increases in all five oxides. Strong aroma variants demonstrated significant positive correlations for 9,12,13-TriHOME, 9,10-DiHOME, and 9-OxoODE with aging time. Conclusions: These findings systematically characterize linoleic acid oxidation products as potential aging markers, providing both methodological advancements and new insights into Baijiu aging mechanisms. Full article

Cardiovascular disease is the leading cause of death throughout most of the industrialized world. Metabolic syndrome (MetS) and its associated pathologies are underlying factors in the etiology of cardiovascular disease, as well as a plethora of other maladies which cause excess morbidity and mortality. Adipose tissue (AT) has come to be regarded as a bona fide endocrine organ which secretes specific molecular entities constituting part of a complex web of inter-organ crosstalk that functions as a key determinant of whole-body metabolic phenotype. Brown adipose tissue (BAT) has classically been regarded as a thermogenic tissue exerting its metabolic effects primarily through its capacity to oxidize substrates decoupled from ATP resynthesis, thereby resulting in increased energy expenditure (EE) and heat production. However, in recent years, BAT has begun to receive attention as a secretory organ in its own right. The molecules secreted specifically by BAT have been termed “batokines”, and currently available evidence supports the notion that batokines exert favorable metabolic effects on multiple organ systems. While maintenance of healthy body composition by conferring resistance to excessive adiposity is a rather obvious mechanism by which BAT operates via increased EE, effects on critical organs such as the heart remain unclear. This narrative review focuses on four types of batokines (FGF21, neuregulin 4, 12,13-diHOME, and BAT-derived microRNAs) for which evidence of modulation of cardiovascular function exists in the context of pathological states such as hypertension, atherosclerosis, and ischemia/reperfusion injury. Given the overwhelming burden of cardiometabolic disease, further study of the functions of BAT and its secretome is warranted and will intensify in the future. Full article

This comprehensive review reports on concentrations, sources, emissions, and potential health effects from Semi-Volatile Organic Compounds (SVOCs) identified in the internal home environment in European residences. A total of 84 studies were identified, and concentrations were collated for inhalation exposure from dust, air and aerosol. A total of 298 individual SVOCs were identified and 67 compounds belonging to eight chemical classes: phthalates, flame retardants, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), per- and polyfluorinated alkyl substances (PFAS), biocides, bisphenols and musks were prioritised. Phthalates are the most abundant SVOCs with DEHP being the most abundant in both the dust and aerosol phases (WAGMs 426.4 μg g⁻¹ and 52.2 ng m⁻³, respectively) followed by DBP for dust (WAGMs are 95.9 μg g⁻¹). In the air, the most abundant SVOCs are DiBP (284.1 ng m⁻³), DBP (179.5 ng m⁻³), DEHP (106.2 ng m⁻³) and DMP (27.79 ng m⁻³). Chemicals from all SVOC categories are emitted from building and construction materials, furnishings and consumer products, especially phthalates. Both legacy chemicals and their alternatives were detected. Complexities of reporting on SVOCs included differing sampling methodologies, multiple standards in their definition, lack of industry data, and toxicological data focused primarily on ingestion not inhalation exposures. Further research is recommended to develop the evidence base for potential health effects including via inhalation, reporting of emission rates and undertaking future monitoring studies. Full article

Cats are popular companions for humans, and their health is of importance to a growing number of pet owners. The juvenile period is a critical stage of cat growth; in particular, the metabolic activity of the intestinal microbiome of kittens is critical for processing nutrients and supporting overall health. In this study, the effect of complex probiotics on the intestinal health of kittens was explored through a metabolomics analysis. Twenty-four healthy kittens were randomly assigned to two groups (n = 12): the control group was provided a basal diet and the probiotics group was provided the basal diet supplemented with complex probiotics (given at the same time daily). The kittens were acclimatized for 5 days, and the experiment was conducted for 14 days. We collected feces from each kitten on days 1 and 14 for metabolomic analyses. Compared to the control, the probiotics group had significantly higher (p < 0.05) methylmalonylcarnitine, lysyl-hydroxyproline, phenylpropionylglycine, and vitamin K3 levels, and significantly lower (p < 0.05) gamma-glutamyl-L-putrescine, cis-gondoic acid, myristic acid, 12,13-DiHOME, and glycodeoxycholic acid levels. The results of this study suggest that complex probiotics promote intestinal health in kittens by regulating changes in various metabolites in the intestine and may have a mitigating effect on intestinal inflammation. Full article

Background: The impact of home parenteral nutrition (HPN) on the quality of life (QoL) of cancer patients has been previously investigated. However, scarce data are available regarding near-death QoL in patients with cancer receiving HPN. This study aims to investigate the changes of QoL in these patients in the last two months before death. Methods: This is a secondary analysis of a previous, prospective, longitudinal, observational study. QoL was assessed using the EORTC QLQ-C30 questionnaire. Results: Eighty-four adult cancer patients who died on HPN and had filled out the questionnaire between 31 and 60 days (M2) and within 30 days prior (M1) to death were included in this analysis. The questionnaires filled out at M2 and M1 were compared with those filled out by the same patients at HPN start (T0). At M2, there was a significant improvement in both the global QoL and symptoms scales (p < 0.001 and p < 0.033, respectively), while at M1, a significant improvement in the global QoL scale persisted (p < 0.035) compared with T0. Conclusions: Our study first reports that HPN, if started early and according to European guidelines, is associated with an improvement in the QoL of patients with cancer even in the last two months before death. Full article

Introduction: Children born small or sick are at risk of death and poor development, but many lack access to preventative follow-up services. We assessed the impact of Pediatric Development Clinics (PDC), which provide structured follow-up after discharge from hospital neonatal care units, on children’s survival, nutrition and development in rural Rwanda. Methods: This quasi-experimental study compared a historic control group to children receiving PDC in Kayonza and Kirehe districts. Study populations in both districts included children born preterm or with birthweight < 2000 g and discharged alive. Kirehe additionally included children with hypoxic ischemic encephalopathy (HIE). Home-based cross-sectional surveys were conducted in Kayonza among children with expected chronological age 11–36 months in 2014 (controls) and 2018 (PDC group) and in Kirehe among children with expected chronological age 17–39 months in 2018 (controls) and 2019 (PDC group). Outcomes were measured using anthropometrics and the Ages and Stages Questionnaires. We used weighted logistic regression to control for confounding and differential non-participation. Results: PDC children (n = 464/812, 57.1%) were significantly more likely to participate in surveys (83.0% vs. 65.5%), have very low birthweight (27.6% vs. 19.0%), and be younger at the survey (26.2 vs. 31.1 months). 6.9% (n = 56) died before the survey. PDC was associated with reduced odds of death (aOR = 0.49, 95% CI: 0.26–0.92) and reduced odds of developmental delay (aOR = 0.48, 95% CI: 0.30–0.77). In Kayonza, PDC was associated with reduced stunting (aOR = 0.52, 95% CI: 0.28–0.98). PDC was not associated with reduced underweight or wasting. Conclusions: PDC was associated with improved survival and development among children born preterm, with low birthweight, or with HIE. Increased access to PDC, scale-up across Rwanda, and implementation of similar services and early intervention in other low-resource settings could support children born small or sick. Full article

Background/Objectives: Home parenteral support (HPS) is the core of chronic intestinal failure (IF) treatment. For legal reasons, HPS in Portugal lags behind other European countries, and only a few patients were taken care of at home by nurses. Now, the legislation has changed, allowing patient self-care. The authors report their pioneer experience as the largest Portuguese IF center, evaluating the underlying conditions leading to IF, HPS nutritional impact, HPS-related complications and survival. Methods: This is a retrospective study including IF patients who underwent HPS in a Portuguese IF center. The data included demographics, underlying conditions, IF types, HPS duration, BMI at the beginning and end of HPS/follow-up, complications, microbiological agents of infectious complications and current status (deceased or alive with/without HPS). Survival was calculated until death or September 2024. Results: A total of 23 patients (52.2% female, mean age 57.3 years), all with type III IF, were included. Short bowel syndrome (SBS) was the most common cause of IF (69.6%). Of the included patients, 78.3% received home parenteral nutrition; the others received home parenteral hydration. The mean BMI increased significantly, from 19.1 kg/m² to 22.5 kg/m² (p < 0.001). Two patients received Teduglutide. The most common complication was catheter-related bloodstream infection (2.5/1000 catheter days). The complications did not increase with patient self-care. At the end of follow-up, 21.7% of patients remained on HPS, 34.8% were alive without HPS, and 43.5% died. The average survival was 43.4 months. One death (4.35%) was attributable to HPS-related complications. Conclusions: The conditions underlying IF varied, with SBS being the most frequent condition. HPS improved the BMI, allowing considerable survival. Despite the complications and one attributable death, HPS was safe, even when relying on patient self-care. Full article