Search Results (1,149)

Background/Objectives: The gut–liver axis is central to sepsis, but assessing mesenteric perfusion remains challenging. Indocyanine green (ICG) clearance reflects hepatic blood flow. Since portal flow is derived from mesenteric circulation and supplies most of the liver, reduced ICG clearance may indicate mesenteric hypoperfusion, which can lead to enteral feeding intolerance (EFI). This study examines whether reduced ICG clearance in septic patients without overt liver injury is associated with EFI. Methods: This study is a secondary analysis of a prospective cohort study (March–May 2024, 20-bed ICU). Septic patients without sepsis-related liver injury or recent abdominal surgery were included. ICG plasma disappearance rate (ICG-PDR) was measured at admission; patients were grouped by ICG-PDR (≤18%/min vs. >18%/min). The primary outcome was EFI within 7 days. Multivariate logistic regression and correlation analyses were performed. Results: Among 77 patients (44 with ICG-PDR > 18%/min, 33 with ≤18%/min), the decreased ICG-PDR group had higher SOFA scores (8.4 ± 4.2 vs. 5.4 ± 3.5, p = 0.001) and higher EFI rates (66.7% vs. 43.1%, p = 0.041). Univariate analysis showed ICG-PDR ≤ 18%/min associated with EFI (OR = 2.632, p = 0.043), but this was attenuated after SOFA adjustment (OR = 2.247, p = 0.171). Reduced ICG-PDR correlated with central venous pressure (CVP) (r = 0.626, p < 0.001) but not with mean arterial pressure (r = −0.175, p = 0.129). Conclusions: In septic patients with preserved hepatocyte function, reduced ICG clearance is associated with EFI, but this relationship is largely explained by disease severity (SOFA). Reduced ICG clearance correlates with CVP; however, ICG-PDR cannot distinguish between portal venous and arterial inflow components. The exact mechanism remains speculative. Full article

Background: The main “peptic” cells of the gastric glands provide the body’s only source of pepsinogen synthesis and incretion. Small amounts of endogenously supplied pepsinogen in biological fluids play an important role in anabolic processes in the mother and newborn. The aim: This work aimed to analyze the dynamics of pepsinogen activity in the blood serum, saliva, urine, and coprofiltrate in pregnant women in each trimester of pregnancy and in the postpartum period, taking into account the body weight of the newborn—normal weight, underweight, and overweight. Methods: Data from studies involving non-pregnant (n = 45) and pregnant (n = 152) women with newborns with different weights were analyzed. There were 86 women with a normal-weight newborn, 34 women with an underweight newborn, and 32 women with an overweight newborn. Total proteolytic activity in biological fluids was determined using the spectrophotometric tyrosine (tyr) Kunitz–Northrop method modified by Korot’ko. A 2% solution of dry plasma was used as a substrate. Outcomes: In non-pregnant women, the blood proteolytic activity was 58.1 ± 1.4 tyr U/mL, and saliva at 1520.9 ± 112.2 tyr U/mL, urine at 4520.3 ± 154.3 tyr U/mL, and coprofiltrate at 442.2 ± 20.5 tyr U/mL. We established that the pepsinogen activity during pregnancy is distributed unevenly, taking into account the body weight of the newborn, and changes significantly in women with an underweight or overweight newborn. Conclusions: Pepsinogen homeostasis in pregnant women is maintained by renal and extrarenal pathways, and an important role is played by the salivary glands, with the most significant changes occurring in women with overweight and underweight newborns. Full article

The COVID-19 pandemic exposed vulnerabilities in global blood supply systems and accelerated the adoption of patient blood management (PBM) strategies aimed at optimizing transfusion practices in surgical care. Perioperative anemia is a key contributor to adverse outcomes and is frequently treated with allogeneic blood transfusion (ABT), which carries infectious and immunologic risks. Iron deficiency remains the most common and potentially correctable cause of perioperative anemia. This narrative review examines various approaches to perioperative anemia, strategies to minimize reliance on ABT, and alternatives within the PBM paradigm. Evidence supports the use of iron therapy, erythropoiesis-stimulating agents, antifibrinolytic strategies, and blood conservation techniques to reduce transfusion requirements and improve clinical outcomes. Lessons from the COVID-19 pandemic highlight PBM as a framework to enhance transfusion safety and sustainability. Broader implementation of PBM may improve patient outcomes, reduce unnecessary transfusions, and preserve scarce blood resources. Full article

Vasculogenic mimicry (VM) refers to the capacity of cancer cells from aggressive tumors to form a set of sinuses and channels that mimic normal blood vessels and lack endothelial cells. The rapid growth of a tumor leads to a deficiency in normal vessels, followed by poor oxygen and nutrient supply to tumor cells and VM induction. Understanding the mechanisms behind the development of the VM phenotype is important for the development of new anti-cancer therapies. Previous reports indicate that, during VM formation by melanoma Mel Z cells, about 2000 developmental genes undergo dramatic changes in expression. To identify genes more tightly linked to VM development, we compared the transcriptomes of Mel Z and MDA-MB-231 cells (triple-negative breast cancer cells), which also form VM. Most of the genes that change expression differ substantially between these two cell types. However, we identified 51 up- and 98 downregulated genes common to both cell lines. The non-overlapping groups of these genes are involved in regulating cell adhesion and proliferation. The group of common upregulated genes includes nine genes controlling blood vessel development and tube morphogenesis. Two genes in this group (BAK1 and SERPINE1) rapidly form numerous contacts with nucleoli during VM phenotype formation. We observed that knockdown of the SERPINE1 gene prevents the development of VM in Mel Z cells. Our data indicate that the formation of VM by aggressive cancer cells might be controlled by a special set of genes. Full article

Background: The growing demand for versatile laboratory automation is exemplified in the context of liquid biopsy, where multi-analyte approaches are increasingly recognised for their potential to enhance diagnostic sensitivity in oncology. However, current practice often necessitates the use of dedicated instruments and workflows for the extraction of each analyte, posing financial and logistical barriers for automated multi-analyte liquid biopsy. Methods: Here, we present Robotic Centrifugal Microfluidics (RoCM), an all-in-one platform that combines the versatility of centrifugal microfluidics and operational flexibility of robotic liquid handling. This combination enables the automation of complex micro- and macrofluidic protocols, realised through the use of (1). exchangeable microfluidic cartridges and (2). programmable robotic operations such as in-rotation liquid supply, magnetic bead manipulation, or microfluidic valving. In-rotation robotic liquid manipulation maintains fluid control under centrifugal forces and reduces the cartridge footprint associated with pre-loaded liquid reservoirs. Platform applicability was demonstrated using two exemplary liquid biopsy workflows: the extraction of cell-free DNA (cfDNA) from blood plasma using RoCM-cfDNA slices and the extraction of extracellular vesicles (EVs) from blood plasma using RoCM-EV slices. Results: In a pilot study with patient samples from different cancer entities, the RoCM-cfDNA slices yielded comparable variant allele frequencies to a commercial bead-based instrument, while the RoCM-EV slices achieved a recovery of a greater diversity of EV subpopulations than semi-automated size-exclusion chromatography. Conclusions: By simply exchanging cartridges, RoCM enables the extraction of diverse analytes within a single automated system. Its application can be extended to further analytes, such as circulating tumour cells (CTCs), or to applications beyond liquid biopsies, where versatile micro- and macrofluidic protocols benefit from implementation in a single automation instrument. Full article

Immature testicular tissue transplantation is a promising strategy for restoring fertility in prepubertal boys undergoing gonadotoxic treatments, yet it faces challenges such as significant germ cell loss and poor graft survival due to the initial period without a blood supply. This study utilized an in vivo tissue-engineering platform involving decellularized testicular extracellular matrix to enhance graft stability and maturation. Immature testicular tissue from three-week-old transgenic mice was transplanted into age-matched recipient mice across four experimental groups: tissue co-transplanted with young decellularized matrix into a cleared testicular cavity, tissue with adult matrix in a cleared cavity, tissue transplanted alone in a cleared cavity, and tissue injected directly into an intact recipient testis. Graft growth was monitored longitudinally using bioluminescence imaging, and spermatogenesis was evaluated via histology and immunohistochemistry sixty-five days post-transplantation. The decellularization protocol successfully removed more than 98 percent of host deoxyribonucleic acid while preserving key matrix components. Grafts injected into intact testes showed the earliest bioluminescence peak but subsequently declined. Conversely, tissue co-transplanted with young decellularized matrix in a cleared cavity exhibited a delayed but significantly higher and more sustained peak compared to the group without a scaffold. The young matrix group appeared to provide more sustained support for spermatogenic progression, as reflected by a more stable increase and a prolonged spermatogenic peak over time. Evidence of advanced spermatogenic stages, including spermatids and sperm-like cells, was observed in all groups by day sixty-five. In conclusion, decellularized testicular matrix serves as a supportive bioactive scaffold that improves long-term graft stability, with outcomes significantly influenced by the age of the scaffold’s donor and the transplantation microenvironment. Full article

Impairment in blood supply to the brain deprives its cells of the much-needed nutrients and molecules such as oxygen and glucose necessary for its development, growth and survival. This will set up a host of pathological processes such as impaired homeostasis, energy failure, excitotoxicity, oxidative stress, impaired protein synthesis, inflammation, cytokine-mediated toxicity and impairment of blood–brain barrier. These pathological processes will result in the damage or death of the cells depending on the extent of the deprivation. Similarly, they will impair synthesis of acetylcholine (Ach) and norepinephrine (NE), which are important neurotransmitters in the cholinergic and adrenergic systems responsible for cellular communication and functions. Thus, interventions to help arrest and/or modulate the initial and subsequent pathological states and help recover the functions of the brain are needed. One of such interventions is vagus nerve stimulation, which helps activate the cholinergic and the adrenergic systems via projections of the afferent fibers of the vagus nerve to the nucleus of the solitary tract (NTS). Activation of the cholinergic and the adrenergic systems results in reduction in pro-inflammatory factors such as tumor necrosis α, increase in pro-angiogenic factors and increase in firing of adrenergic neurons in the central nervous system (CNS). Full article

Hemato-oncological patients with chemotherapy-induced thrombocytopenia are a major recipient group of frequent platelet (PLT) transfusion. Prophylactic platelet transfusions are administered when platelet counts fall below 10 × 10⁹ PLT/L, to prevent severe or fatal bleeding. However, these prophylactic platelet transfusions do not always result in the prevention of bleeding. Pre- or post-transfusion acquired dysfunction of donor platelets in this respect could play a role. We previously reported intrinsic and transfusion-dependent platelet alterations in hemato-oncological patients. In particular, the expression of relevant platelet receptors was affected in donor platelets after incubation with patient’s plasma, which could explain, at least in part, the variable efficacy of platelet transfusions in these patients. In the present manuscript we show that plasma from acute myeloid leukemia (AML) patients undergoing chemotherapy inhibits functionality of allogenic platelets. Further proteomic analysis allowed us to observe alterations in the composition of plasma samples, and to identify key plasma components which could be responsible for platelet function inhibition and explain bleeding in patients notwithstanding platelet transfusions. We anticipate that with the obtained results, platelet transfusion support can be further personalized in patients receiving chemotherapy and applications might expand to maximize the clinical efficacy of procedures such as bone marrow transplantation. Full article

Background: Spleen-preserving (SP) distal pancreatectomy (DP) with splenic vessels resection (SVR) (Warsaw procedure, WP) is an option for the treatment of tumors with low malignant potential. The reverse blood flow through the short gastric arteries (SGA) explains the preservation of the spleen after SVR, but leaves the source of the blood supply to the SGAs hidden. The types of blood supply to the spleen after WP and their incidence have not been previously described, nor has the significance of these types for locally advanced pancreatic head cancer (LAPHC) surgery been determined. Aim: To determine the main types of spleen blood supply after WP, and to assess the feasibility and safety of splenic artery (SA) rotation for the organ-preserving surgery of LAPHC. Methods: Retrospective analyses of demographic and perioperative data, including CT scans, overall (OS) and progression-free (PFS) survival after 71 SP DP SVR and 41 SP SVR pancreaticoduodenectomies (PD) and total pancreatectomies (TP) for LAPHC (2007–2025). Results: In 134 SP procedures, SA was resected in 115 cases (71DP, 9 TP, 3 central, and 32 PD). Indications for surgery were MCN (41), IPMN (14), CSA (3), NEN (25), SPPN (8), PHDAC (40), sarcoma (1), autoimmune (1), and calculous chronic pancreatitis (1). There were no deaths or ischemia-related splenectomies. Morbidity—31% (n23); Dindo–Clavien (D-C) > 3b-2.8%; POPF-grade B-n7 (10.6%); splenic infarctions on CT after SVR-n18 (23%), one symptomatic. CT revealed three types of arterial blood supply to the spleen after SPDP SVR: left gastric artery (LGA) type (n50, 70, 5%), gastro-epyploic arcade (GEA) type (n9, 12, 5%), and an intermediate type (n12, 17%). Spleen- and pancreas tail-preserving SVR pancreatectomies for LAPHC (n41) were accompanied by rotation of the SA to substitute resected SMA (n19) and CHA (n15) for 26 Whipples and 8TPs. There were no ischemic complications. D-C > 3–19.5%. Median OS and PFS for PDAC were 35 and 21 months for 29.5 months median follow-up. Conclusions: Despite the preservation of blood flow through all potential sources of splenic blood supply following resection of the splenic artery, the main collaterals supplying the spleen after WP are LGA branches (~90%). This knowledge, with strict adherence to the developed criteria, allows for the safe preservation of the spleen, pancreatic tail, and stomach during pancreatectomies with SA resection, including its rotation for the substitution of the SMA and CHA in LAPHC. Full article

Diabetes Mellitus is a chronic metabolic disorder characterized by elevated blood glucose due to defects in insulin secretion or action, or both, leading to serious short- and long-term complications if not effectively managed. However, there is limited qualitative evidence exploring how youths diagnosed with Type 1 Diabetes Mellitus (T1DM) experience disease onset, management, complications, emotional adaptation, and education within the South African public healthcare system. The study aims to investigate the lived experiences of youths living with T1DM in a selected public hospital in Limpopo province, South Africa. The objectives were to explore and describe the lived experiences of youths living with T1DM. A qualitative, explorative, descriptive, and contextual design was used to gain a thorough understanding of the experiences of youths living with T1DM. A non-probability sampling technique was used to select 12 participants using a pre-determined criterion. Data were collected through individual semi-structured interviews using an interview guide. The data were analyzed using Colaizzi’s method, where themes and sub-themes were developed with the inclusion of an independent coder. Measures to ensure trustworthiness and ethical considerations were adhered to throughout the study. The findings revealed that, despite the participants sharing the same diagnosis, they experience multiple interrelated barriers that significantly hindered effective self-care management, such as limited access to diabetic diet, glucometers and supplies, treatment and informational-related barriers, school-related challenges, transportation constraints and inadequate social support. Furthermore, the findings highlighted gaps in early recognition of symptoms, standardized diabetes education, psychosocial support, and continuity of care. The study recommends the need for holistic, patient-centred, and contextualized interventions that do not only address medical management but the socioeconomic, educational, and psychological needs of youths. Full article

Phytoestrogens are plant-derived phenolic compounds that structurally resemble endogenous estrogens and can exert both estrogenic and anti-estrogenic effects in animals. In ruminant nutrition, the main classes of phytoestrogens (isoflavones, lignans, stilbenes, coumestans and selected flavonoids) are supplied predominantly by legume forages and soybean-based feeds, in which concentrations can reach several mg/g of dry matter. After ingestion, these compounds are extensively metabolized by the rumen microbiota to derivatives with altered biological potency, such as equol and p-ethyl-phenol, which influence endocrine, immune and metabolic pathways. Experimental and field studies in cattle, sheep and goats indicate that dietary phytoestrogens may improve nitrogen utilization, immune competence, growth performance, antioxidant status and milk yield. However, they can also impair fertility, modify hormone profiles and compromise embryo survival in a compound-, dose-, and species-dependent manner. In this review, we summarize current knowledge on the botanical and nutritional sources, ruminal metabolism and transfer of phytoestrogens in ruminants, and critically examine their effects on blood metabolites, immune responses, growth and carcass traits and lactational performance and reproductive function. A structured literature search based on PRISMA principles was used to identify and appraise experimental and observational studies in both grazing and intensive production systems up to 2025. Remaining knowledge gaps and practical implications for the safe use of phytoestrogen-rich feeds in livestock production are highlighted. Full article

Although echocardiography remains the primary imaging modality for assessing Fontan palliation, a standardized systematic approach for evaluating the univentricular heart throughout the different stages of palliation has yet to be established. This document aims to provide a narrative review and practical guide for the echocardiographic assessment of the univentricular heart at various phases of Fontan palliation. Additional objectives include highlighting the potential of advanced three-dimensional (3D) and four-dimensional (4D) imaging modalities, as well as outlining a systematic strategy for detecting thromboembolic complications. We propose a sequential framework for echocardiographic evaluation, encompassing key anatomical and functional components of the univentricular heart. This includes the atrial septum and pulmonary veins, ventricular function, atrioventricular valve, aorta and neo-aorta, sub-aortic region, aortic arch, and pulmonary arteries. Furthermore, we detail the assessment of pulmonary blood supply at different stages of palliation, including the modified Blalock–Taussig–Thomas (mBTT) shunt, Sano conduit, Glenn procedure, and total cavo-pulmonary connection (TCPC). A comprehensive analysis of potential thrombus formation sites is provided, along with diagnostic pitfalls. Additionally, we outline methods for screening for extracardiac clots following Glenn and TCPC procedures. This document serves as a practical guide for the systematic echocardiographic evaluation of the univentricular heart across all stages of Fontan palliation, offering guidance for clinical practice. It also explores the capabilities of emerging 3D and 4D echocardiographic techniques in univentricular heart assessment and provides an in-depth review of thromboembolic complications, emphasizing key diagnostic challenges. Full article

Chondroblastoma is a generally benign tumor occurring at a young age; however, its location near a joint and its tendency to recur make the treatment particularly challenging. This is especially true in the case of its occurrence in the hip joint. Surgical removal—curettage—is the primary method, but the remaining defect can be filled with several methods depending on the size of the tumor. The approach to the lesion is another difficulty. There are several available options, but due to the characteristics of the blood supply to the joint, this is a significant risk. In our case, we used an open autologous osteochondral graft transplantation (mosaicplasty) to treat juvenile hip chondroblastoma in a young female patient, for which the ipsilateral knee joint served as the donor area. The patient was followed up for 3 years after surgery, and, in addition to physical examinations, numerous imaging studies were performed to exclude local recurrence or avascular necrosis in the femoral head and to ensure that the congruence of the implanted osteochondral grafts was maintained. Full article

Background: Research indicates that hepatic gluconeogenesis mediates metabolic coupling between the liver and muscles via the Cori cycle and participates in liver–brain axis communication through its metabolic products and regulatory networks, thereby linking it to the pathogenesis of depression. Together, these mechanisms form the molecular basis for the antidepressant effects of exercise-regulated hepatic gluconeogenesis. Regular exercise promotes skeletal muscle contraction, causing the muscles to release more lactate into the circulatory system. Lactate acts as a substrate for gluconeogenesis and activates downstream signaling pathways, thereby enhancing the gluconeogenic response. During exercise, glycogenolysis directly provides energy, while lactate produced by glycolysis enters the liver via the Cori cycle to serve as a substrate for gluconeogenesis. By maintaining blood glucose homeostasis, this process ensures a stable energy supply to the brain, thereby improving cognitive and emotional functions. This study aims to elucidate how key substrates, regulatory factors, and rate-limiting enzymes involved in hepatic gluconeogenesis and exercise influence brain energy supply, cognitive function, and emotional regulation during depression. It seeks to identify the potential targets and mechanisms through which exercise exerts its antidepressant effects via hepatic gluconeogenesis, with the goal of providing a theoretical foundation for research into the mechanisms of depression and for clinical exercise interventions. Methods: This review conducted a comprehensive search of the recent literature on exercise, hepatic gluconeogenesis, and depression in major domestic and international databases. Adopting an interdisciplinary approach that integrates hepatic gluconeogenesis and exercise, it synthesizes existing evidence to explore the metabolic mechanisms by which exercise improves depression through the regulation of hepatic gluconeogenesis pathways. Results: Research has found that exercise may modulate hepatic gluconeogenic substrates and regulate the expression of cAMP-responsive element-binding protein in states of depression, regulatory factors such as liver kinase B1, forkhead box protein 01, hepatocyte nuclear factor 4 alpha, and peroxisome proliferator activated receptor gamma co activator factor 1 alpha are used to affect key rate limiting enzymes of hepatic gluconeogenesis, such as phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, enhance hepatic gluconeogenesis processes, maintain blood glucose homeostasis, ensure brain energy supply, and improve depression. Conclusions: Exercise intervention targeting hepatic gluconeogenesis may be a potential therapeutic strategy for depression. Full article

Background: Anterior cruciate ligament (ACL) injuries are increasing in young athletes and many are related to non-contact, spontaneous mechanical fatigue-related ruptures. The objective of this narrative review is to identify and synthesize the anatomical, histological, physiological, and biomechanical basis of extracellular matrix (ECM) factors that contribute to ACL injuries and suggest ways to decrease their occurrence. Methods: The primary investigator searched PubMed, Web of Science, and Google Scholar database titles and abstracts using search phrases with Boolean operators: “anterior cruciate ligament” OR “ACL”, OR “cranial cruciate ligament” AND “disease”; “anterior cruciate ligament” OR “ACL”, OR “cranial cruciate ligament” AND “spontaneous rupture” OR “non-contact injury”; and “anterior cruciate ligament” OR ACL, OR cranial cruciate ligament” AND “crosslink”, “collagen” OR “extracellular matrix”; and “anterior cruciate ligament” OR “ACL”, OR “cranial cruciate ligament” AND “microtrauma”, OR “sudden” OR “fatigue failure”. The primary investigator and a sports orthopedic surgeon reviewed titles and abstracts of diverse evidence sources. From these identified sources, the study team performed full text reviews, selected contributing articles, performed Strength of Recommendation Taxonomy (SORT) grading, and synthesized the following themes: A Hostile Environment, ACL Strain, and Poor Nutrient Delivery; Accumulative ACL Microtrauma and Mechanical Failure; The ACL Differs From Other Ligaments; Collagen, the ECM, and ACL Mechanobiology; Crimps and ACL ECM Stretch; Crosslinks Improve ECM Mechanical Properties; The Delicate Collagen Synthesis and Degradation Balance; Exercise Training and the ACL; Can Nutraceuticals Help Restore the Balance?; Training Induced ACL Hypoxia; Estrogen and the Female Athlete; Counting Pitches or Counting Collagen Fiber Ruptures; and Restoring A Positive Anabolic–Catabolic Collagen Balance. Results: Regular exercise training within a physiologically safe loading range is vital to ACL ECM health. However, low or moderate evidence suggested that poor blood supply, slow metabolism, and a hypoxic environment may unbalance anabolic and catabolic homeostasis. Active rest and recovery concepts that prevent youth baseball shoulder and elbow injuries may help prevent non-contact ACL injuries. Conclusions: More prescriptive active rest and recovery intervals and neuromuscular control training may restore the anabolic–catabolic balance that increases mature crosslink density and improves ACL ECM strength. Confirmatory studies are needed to better establish therapeutic intervention mode(s), timing, dosage, and frequency optimization. Full article