Search Results (32)

Background/Objectives: In the context of acute heart failure, proenkephalin A (penKid) has emerged as a prognostic marker for acute kidney injury (AKI), whereas bioactive adrenomedullin (bio-ADM) has been identified as a significant biomarker linked to shock and organ dysfunction. This raises the question of whether they can serve as predictors of postoperative complications in patients receiving left ventricular assist devices (LVADs). Methods: This observational study prospectively enrolled patients who had received LVAD implantation. Routine laboratory values as well as plasma levels of penKid and bio-ADM were assessed at four time intervals, spanning from preinduction of anesthesia to 48 h post surgery. Clinical data, the HeartMate 3-risk-score (HM3RS), HeartMateII-risk-score (HMRS), Michigan-right-heart-failure risk score (MRHFS), Euromacs-RHFS (EURORHFS), and kidney failure risk score (KFR) were calculated. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were performed. We entered the biomarkers with the established risk scores into the models. Results: In 20 patients who had undergone LVAD implantation, preoperative penKid level was a predictor of postoperative AKI (OR: 1.05, 95%-CI: 1.0–1.09; p = 0.049) and 30-day mortality (OR: 1.01, 95%-CI: 1.0–1.02; p = 0.033). Bio-ADM was the only predictor of postoperative right heart failure (RHF) (OR: 1.11, 95%-CI: 1.01–1.23; p = 0.034) and rehospitalization (OR: 1.06, 95%-CI: 1.0–1.13; p = 0.047). In the ROC analysis, bio-ADM, as a predictor of post-LVAD RHF, had an area under the curve (AUC) of 0.88. When bio-ADM was added to the accepted clinical scores for post-LVAD RHF prediction (CRITT-score, MRHFS, and EURORHFS), the AUC reached 0.98. The AUC for preoperative penKid, as a predictor of postoperative AKI, was 0.95, and after adding its predictive value to the KFR score, the AUC reached 0.97. Conclusions: In the present study, the biomarkers penKid and bio-ADM predicted clinically significant patient outcomes after LVAD implantation such as AKI, RHF, and 30-day mortality. Adding biomarkers to well-established risk scores improved the AUC for prediction of postoperative complications. Full article

Heart failure (HF) is a challenging clinical syndrome with high morbidity and mortality rates. Along the spectrum of cardiovascular diseases, HF constitutes an ever-expanding area of research aiming at combating the associated mortality and improving the prognosis of patients with HF. Although natriuretic peptides have an established role among biomarkers in HF diagnosis and prognosis, several novel biomarkers reflecting the complex pathophysiology of HF are under investigation for their ability to predict adverse clinical outcomes in HF. Proenkephalin 119–159 (PENK_119–159) is a non-functional peptide belonging to the enkephalin family of the endogenous opioid system and is considered a surrogate biomarker of the biologically active enkephalin peptides. PENK_119–159 has demonstrated promising results in predicting short- and long-term mortality, readmission rates, and worsening renal function in patients with HF. Indeed, in the setting of HF, the levels of both active enkephalins and their surrogate PENK_119–159 are elevated and are associated with a dismal prognosis. However, the biological effects of PENK_119–159 remain largely unknown. Thus, it is crucial to gain a deeper insight into both the physiology of the enkephalin peptide family and the enkephalin-mediated cardiovascular regulation. In order to elucidate the complex pathophysiological mechanisms that lead to the upregulation of enkephalins in patients with HF, as well as the potential clinical implications of elevated enkephalins and PENK_119–159 levels in this patient population, the present review will describe the physiology and distribution of the endogenous opioid peptides and their corresponding opioid receptors, with a particular focus on the action of enkephalins. The effects of the enkephalin peptides will be analyzed in both healthy subjects and patients with HF, especially with regard to their role in the regulation of cardiovascular and renal function. The review will also discuss the findings of recent studies that have explored the prognostic value of PENK_119–159 in patients with HF. Full article

Kidney injury encompasses a broad spectrum of structural and functional abnormalities, directly associated with stem cell transplantation. Acute kidney injury and chronic kidney disease represent perilous complications of hematopoietic stem cell transplantation (HSCT), with an elevated risk of mortality and progression to end-stage renal disease. The early detection of these complications is, therefore, paramount, and research is increasingly focused on the identification of novel biomarkers of kidney damage. Recently, proenkephalin (PENK), a monomeric peptide that is freely filtered by the glomerulus and thus reflects glomerular filtration very well, has been shown to be an additional useful predictor of the occurrence of acute kidney injury and heart failure. Dickkopf-3 (DKK3) is a glycoprotein secreted by the renal tubular epithelium in response to stress and has been implicated in the development of interstitial fibrosis. It has therefore been evaluated primarily as a marker of fibrosis in chronic kidney disease (CKD), but may also help predict the development of acute kiney injury. Uromodulin is regarded as a renal marker. Previous studies have examined the potential of PENK, DKK-3 and uromodulin as a biomarker in individuals with preserved renal function. However, the urinary levels of PENK, DKK-3 and uromodulin in patients following HSCT have not yet been established. The objective of the present study was to assess urinary PENK, DKK-3, and uromodulin concentrations in patients who had been under ambulatory care of the Hematology, Transplantation and Internal Medicine Department for a minimum of three months following HSCT, and to investigate their correlations with kidney function, as reflected by serum creatinine and eGFR. The study population comprised 80 patients who had undergone allogeneic HSCT for various reasons, primarily hematological malignancies such as acute leukemias and lymphomas. In addition, 32 healthy volunteers were included in order to establish normal ranges for the biomarkers of interest. Urine concentrations of proenkephalin, DKK-3, and uromodulin were evaluated using a commercially available sandwich ELISA immunoassay. Demographic and clinical data were retrieved from the patients’ records. Statistical analyses were conducted using XLSLAT 2022 (Lumivero, Denver, CO, USA) and STATISTICAv13.0 (StatSoft, Tulsa, OH, USA). The results showed that PENK and DKK-3 levels were significantly higher in patients after HSCT compared to healthy volunteers. Furthermore, when patients were divided according to kidney function (below and over 60 mL/min/1.72 m²), it was found that the concentration of PENK and DKK-3 were significantly higher in 23 patients with CKD stage 3 relative to patients with eGFR over 60 mL min 1.72 m². In univariate correlations, PENK demonstrated an inverse relationship with eGFR (r: −0.21, p < 0.05), while DKK-3 exhibited no significant correlation with creatinine or eGFR.Patients following allogeneic HSCT, despite having normal or near-normal kidney function, exhibited evidence of kidney injury. However, further research is necessary to ascertain the clinical utility of the novel biomarker. Full article

Proenkephalin A 119–159 (PENK) is a promising functional kidney biomarker, evaluated in various clinical settings. In critical care medicine, early diagnosis of acute kidney injury (AKI) is crucial; however, to date, the diagnosis and the assessment of kidney function is still based on serum creatinine (sCr) and urine output, both associated with several limitations. Between November 2020 and March 2022, we implemented PENK in our daily practice on our intensive care units (ICU). PENK, sCr, AKI stage, and the start and duration of renal replacement therapy (RRT) were documented. Almost 18,000 PENK measurements from 4169 patients were analyzed, and the glomerular filtration rate (GFR) was estimated with the new PENK-GFR formula. PENK outperformed sCR in the kidney function assessment and sCR trajectory over time. Moreover, PENK predicted the use of RRT and thus showed its usefulness in critical care daily practice. Full article

Sepsis-associated acute kidney injury (SA-AKI) is defined as the development of AKI in the context of a potentially life-threatening organ dysfunction attributed to an abnormal immune response to infection. SA-AKI has been associated with increased mortality when compared to sepsis or AKI alone. Therefore, its early recognition is of the utmost importance in terms of its morbidity and mortality rates. The aim of this review is to shed light on the pathophysiological pathways implicated in SA-AKI as well as its diagnostics and therapeutics. In this review, we will elucidate upon serum and urinary biomarkers, such as creatinine, cystatin, neutrophil gelatinase-associated lipocalin (NGAL), proenkephalin A 119–159, interleukin-6, interleukin-8 and interleukin-18, soluble toll-like receptor 2 (sTLR2), chemokine ligand 2 (CCL2) and chemokine C-C-motif 14 (CCL14). In addition, the role of RNA omics as well as machine learning programs for the timely diagnosis of SA-AKI will be further discussed. Moreover, regarding SA-AKI treatment, we will elaborate upon potential therapeutic agents that are being studied, based on the pathophysiology of SA-AKI, in humans and in animal models. Full article

Acute kidney injury (AKI) is a severe and prevalent syndrome, primarily observed in intensive care units (ICUs) and perioperative settings. The discovery of a new biomarker for kidney function and injury, capable of overcoming the limitations of traditional markers, has the potential to improve the diagnosis and management of AKI. Proenkephalin A 119–159 (PENK) has emerged as a novel biomarker for AKI and has been validated in various clinical settings. It has demonstrated a faster response to AKI compared to creatinine and has been shown to predict successful weaning from renal replacement therapy in the ICU. PENK has also shown promise as an AKI biomarker in perioperative patients. Additionally, PENK has been proven to be effective in estimating mortality and morbidity in patients undergoing cardiac surgery, and those with traumatic brain injury or ischemic stroke. Incorporating PENK into a novel estimation of the glomerular filtration rate, referred to as the PENK-Crea equation, has yielded promising results. Full article

Introduction: Sepsis remains a major contributor to critical care mortality and morbidity worldwide. Despite advances in understanding its complex immunopathology, the compartmentalized nature of immune responses across different organs has yet to be fully translated into targeted therapies. This review explores the burden of sepsis on organ-specific immune dysregulation, immune resilience, and epigenetic reprogramming, emphasizing translational challenges and opportunities. Methods: We implemented a systematic literature search strategy, incorporating data from studies published between 2010 and 2024, to evaluate the role of molecular profiling techniques, including transcriptomics and epigenetic markers, in assessing the feasibility of targeted therapies. Results: Sepsis-induced immune dysregulation manifests differently in various organs, with lung, heart, liver, and kidney responses driven by unique local immune environments. Organ-specific biomarkers, such as the Spns2/S1P axis in lung macrophages, mitochondrial dysfunction in the heart, proenkephalin for early acute kidney injury (AKI), and adrenomedullin for predicting multi-organ failure, offer promising avenues for timely intervention. Furthermore, immune resilience, particularly through regulatory T-cell modulation and cytokine targeting (e.g., IL-18), is crucial for long-term recovery. Epigenetic mechanisms, including histone modification and trained immunity, present opportunities for reprogramming immune responses but require more precision to avoid unintended inflammatory sequelae. Conclusions: A deeper understanding of compartmentalized immune responses and the dynamic immune landscape in sepsis is critical for developing precision therapies. Real-time immune monitoring and organ-targeted interventions could revolutionize sepsis management, although significant barriers remain in clinical translation. Further research is required to establish biomarkers and treatment timing that optimize therapeutic efficacy while minimizing systemic risks. Full article

An acute kidney injury (AKI) is the most common complication following cardiac surgery, and can lead to the initiation of continuous renal replacement therapy (CRRT). However, there is still insufficient evidence for when patients should be liberated from CRRT. Proenkephalin A 119–159 (PENK) is a novel biomarker that reflects kidney function independently of other factors. This study investigated whether PENK could guide successful liberation from CRRT. Therefore, we performed a prospective, observational, single-center study at the Medical University of Vienna between July 2022 and May 2023, which included adult patients who underwent cardiac surgery for a cardiopulmonary bypass; patients on preoperative RRT were excluded. The PENK levels were measured at the time of AKI diagnosis and at the initiation of and liberation from CRRT, and were subsequently compared to determine whether the patients were successfully liberated from CRRT. We screened 61 patients with postoperative AKI; 20 patients experienced a progression of AKI requiring CRRT. The patients who were successfully liberated from CRRT had mean PENK levels of 113 ± 95.4 pmol/L, while the patients who were unsuccessfully liberated from CRRT had mean PENK levels of 290 ± 175 pmol/L (p = 0.018). For the prediction of the successful liberation from CRRT, we found an area under the curve of 0.798 (95% CI, 0.599–0.997) with an optimal threshold value of 126.7 pmol/L for PENK (Youden Index = 0.53, 95% CI, 0.10–0.76) at the time of CRRT liberation (sensitivity = 0.64, specificity = 0.89). In conclusion, PENK is a novel biomarker that has the potential to predict the successful liberation from CRRT for patients with AKI after cardiac surgery. Full article

Introduction: Acute brain injury is one of the most important causes of morbidity, mortality and disability worldwide. Time is the most important aspect of acute brain injury management. In this context, biomarkers could mitigate the limitations of neuroimaging. Neuro-biomarkers could be used both to diagnose intracranial pathology and to predict the effectiveness of treatment applications. Aim: The aim of this review is to describe the role of various and specific markers of brain damage with particular emphasis on acute brain injury and stroke. Results/discussion: The diagnostic and prognostic value of modern biomarkers remains relatively questionable, although grouping biomarkers into panels is improving their usefulness. The groups of biomarkers that will be analyzed include astrocytic, axonal, neuronal as well as extracellular biomarkers. Conclusion: Future studies will demonstrate the utility of neuro-biomarkers in the diagnosis, prognosis and therapeutic monitoring of patients with acute brain injury in the intensive care unit. Full article

The effects of stressors were examined on Met-enkephalin-related parameters and plasma concentrations of corticosterone in 14-week-old female chickens. Water deprivation for 24 h was accompanied by a tendency for increased plasma concentration of Met-enkephalin while plasma concentrations of corticosterone were elevated in water-deprived birds. Concentrations of Met-enkephalin were reduced in the anterior pituitary gland and adrenal gland in water-deprived pullets while proenkephalin (PENK) expression was increased in both tissues. There were changes in the plasma concentrations of Met-enkephalin and corticosterone in pullets subjected to either feed withholding or crowding. Concentrations of Met-enkephalin were increased in the anterior pituitary gland but decreased in adrenal glands in pullets subjected to crowding stress. The increase in the plasma concentrations of Met-enkephalin was ablated when the chickens were pretreated with naltrexone. However, naltrexone did not influence either basal or crowding on plasma concentrations of corticosterone. In vitro release of Met-enkephalin from the anterior pituitary or adrenal tissues was depressed in the presence of naltrexone. It was concluded that Met-enkephalin was part of the neuroendocrine response to stress in female chickens. It was concluded that stress influenced the release of both Met-enkephalin and corticosterone, but there was not complete parallelism. Full article

The skin of bony fish is the first physical barrier and is responsible for maintaining the integrity of the fish. Lesions make the skin vulnerable to potential infection by pathogens present in the aquatic environment. In this way, wound repair has barely been studied in gilthead sea bream. Thus, this study investigated the modulation of peripheral neuro-endocrine and tissue repair markers at the transcriptional level in the skin of teleost fish subjected to mechanical damage above or below the lateral line (dorsal and ventral lesions, respectively). Samples were evaluated using RT-qPCR at 2-, 4-, and 20-days post-injury. Fish with a ventral lesion presented a trend of progressive increase in the expressions of corticotropin-releasing hormone (crh), pro-opiomelanocortin-A (pomca), proenkephalin-B (penkb), cholecystokinin (cck), oxytocin (oxt), angiotensinogen (agt), and (less pronounced) somatostatin-1B (sst1b). By contrast, fish with a dorsal lesion registered no significant increase or biological trend for the genes evaluated at the different sampling times. Collectively, the results show a rapid and more robust response of neuro-endocrine and tissue repair markers in the injuries below than above the lateral line, which could be attributable to their proximity to vital organs. Full article

Background: The aim of the present study is to investigate the prognostic utility of point-of-care (POC)-measured proenkephalin (PENK), a novel biomarker, in terms of predicting in-hospital mortality in patients presenting to the emergency department (ED) with septic shock. Methods: Bedside PENK was measured in consecutive patients presenting to the ED with septic shock according to the Sepsis-3 clinical criteria. The association of PENK with inflammatory and routine biomarkers, and its role as a predictor of in-hospital mortality, was examined. Results: Sixty-one patients with septic shock [53% females, median age 83 years (IQR 71–88)] were evaluated. Median (IQR) values of creatinine, plasma lactate, soluble urokinase plasminogen activator receptor (SuPAR), procalcitonin and PENK were 1.7 (1.0–2.9) mg/dL, 3.6 (2.1–6.8) mmol/L, 13.1 (10.0–21.4) ng/mL, 2.06 (0.84–3.49) ng/mL, and 205 (129–425) pmol/L, respectively. LogPENK significantly correlated with LogLactate (rho = 0.369, p = 0.004), LogCreatinine (rho = 0.537, p < 0.001), LogProcalcitonin (rho = 0.557, p < 0.001), and LogSuPAR (rho = 0.327, p = 0.011). During hospitalization, 39/61 (64%) patients died. In a multivariable logistic regression model, logPENK was an independent predictor of in-hospital mortality (OR 11.9, 95% CI: 1.7–84.6, p = 0.013). Conclusion: POC PENK levels measured upon presentation to the ED strongly correlated with metabolic, renal and inflammatory biomarkers, and may serve as a predictor of in-hospital mortality in patients with septic shock. Full article

Sepsis and acute kidney injury (AKI) are two major public health concerns that contribute significantly to illness and death worldwide. Early diagnosis and prompt treatment are essential for achieving the best possible outcomes. To date, there are no specific clinical, imaging, or biochemical indicators available to diagnose sepsis, and diagnosis of AKI based on the KDIGO criterion has limitations. To improve the diagnostic process for sepsis and AKI, it is essential to continually evolve our understanding of these conditions. Delays in diagnosis and appropriate treatment can have serious consequences. Sepsis and AKI often occur together, and patients with kidney dysfunction are more prone to developing sepsis. Therefore, identifying potential biomarkers for both conditions is crucial. In this review, we talk about the main biomarkers that evolve the diagnostic of sepsis and AKI, namely neutrophil gelatinase-associated lipocalin (NGAL), proenkephalin (PENK), and cell-free DNA. Full article

Worldwide, sepsis is a well-recognized cause of death. Acute kidney injury (AKI) may be related to sepsis in up to 70% of AKI cases. Sepsis-associated AKI (SA-AKI) is defined as the presence of AKI according to the Kidney Disease: Improving Global Outcomes criteria in the context of sepsis. SA-AKI is categorized into early, which presents during the first 48 h of sepsis, and late, presenting between 48 h and 7 days of sepsis. SA-AKI is associated with a worse prognosis among patients with sepsis. However, there are different SA-AKI phenotypes as well as different pathophysiological pathways of SA-AKI. The aim of this review is to provide an updated synopsis of the pathogenetic mechanisms underlying the development of SA-AKI as well as to analyze its different phenotypes and prognosis. In addition, potential novel diagnostic and prognostic biomarkers as well as therapeutic approaches are discussed. A plethora of mechanisms are implicated in the pathogenesis of SA-AKI, including inflammation and metabolic reprogramming during sepsis; various types of cell death such as apoptosis, necroptosis, pyroptosis and ferroptosis; autophagy and efferocytosis; and hemodynamic changes (macrovascular and microvascular dysfunction). Apart from urine output and serum creatinine levels, which have been incorporated in the definition of AKI, several serum and urinary diagnostic and prognostic biomarkers have also been developed, comprising, among others, interleukins 6, 8 and 18, osteoprotegerin, galectin-3, presepsin, cystatin C, NGAL, proenkephalin A, CCL-14, TIMP-2 and L-FABP as well as biomarkers stemming from multi-omics technologies and machine learning algorithms. Interestingly, the presence of long non-coding RNAs (lncRNAs) as well as microRNAs (miRNAs), such as PlncRNA-1, miR-22-3p, miR-526b, LncRNA NKILA, miR-140-5p and miR-214, which are implicated in the pathogenesis of SA-AKI, may also serve as potential therapeutic targets. The combination of omics technologies represents an innovative holistic approach toward providing a more integrated view of the molecular and physiological events underlying SA-AKI as well as for deciphering unique and specific phenotypes. Although more evidence is still necessary, it is expected that the incorporation of integrative omics may be useful not only for the early diagnosis and risk prognosis of SA-AKI, but also for the development of potential therapeutic targets that could revolutionize the management of SA-AKI in a personalized manner. Full article

(1) Background: Dry eye disease (DED) is a multifactorial ocular surface disease characterized by an imbalance in ocular surface homeostasis, and tear substitutes constitute the first line of treatment. The present study aimed to evaluate the changes in the signs and symptoms of patients with DED treated with a novel tear substitute containing the GlicoPro^® complex. (2) Methods: Patients with DED not successfully responding to other tear substitutes were enrolled and treated with a novel ophthalmic solution (two drops four times daily). Patients were examined before starting the study treatment (T0) and after 30 (T1) and 60 (T2) days of treatment by means of Keratograph for the evaluation of the following: (i) tear meniscus height (TMH); (ii) noninvasive Keratograph break-up time (NIKBUT); (iii) bulbar redness; and (iv) infrared meibography. The SANDE questionnaire was administered to assess ocular discomfort symptoms. Analysis of the tear content of proenkephalin and Met/Leu-enkephalin was also performed. (3) Results: At T2, a significant improvement in NIKBUT first, average, and class, TMH, and SANDE score was found. The tear content of proenkephalins was significantly higher at T1, whereas processed active Met/Leu-enkephalins increased at both T1 and T2. (4) Conclusions: Our novel tear substitute based on GlicoPro^® resulted in a significant improvement in ocular discomfort symptoms, tear volume, and stability in the patients treated. The increase in active peptides processed in tears may represent the pathophysiological substrate underlying this finding. Full article