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.

ApoB is the main protein of triglyceride-rich lipoproteins and is further divided into ApoB48 in the intestine and ApoB100 in the liver. Very low-density lipoprotein (VLDL) is produced by the liver, contains ApoB100, and is metabolized into its remnants, intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL). ApoB100 has been suggested to play a crucial role in the formation of the atherogenic plaque. Apart from being a biomarker of atherosclerosis, ApoB100 seems to be implicated in the inflammatory process of atherosclerosis per se. In this review, we will focus on the structure, the metabolism, and the function of ApoB100, as well as its role as a predictor biomarker of cardiovascular risk. Moreover, we will elaborate upon the molecular mechanisms regarding the pathophysiology of atherosclerosis, and we will discuss the disorders associated with the APOB gene mutations, and the potential role of various drugs as therapeutic targets.

The lactate to albumin ratio (LAR) has been associated with the severity and outcome of critical illness and sepsis. However, there are no studies on the kinetics of the LAR during the early phase of sepsis. Therefore, we aimed to investigate the LAR and its kinetics in critically ill patients with new onset sepsis regarding the severity and outcome of sepsis. We prospectively enrolled 102 patients with sepsis or septic shock within 48 h from diagnosis. LARs were recorded at inclusion in the study and one week later. Patients were followed for 28 days. LAR was significantly lower one week after enrollment compared to baseline in all patients (p < 0.001). LARs were significantly higher in patients with septic shock and in nonsurvivors compared to patients with sepsis and survivors, respectively, both at inclusion (p < 0.001, p < 0.001) and at one week later (p < 0.001, p < 0.001). LARs at baseline were positively associated with the severity of sepsis (APACHE II: r = 0.29, p = 0.003; SOFA: r = 0.33, p < 0.001) and inflammatory biomarkers, such as C-reactive protein (r = 0.29, p < 0.1), procalcitonin (r = 0.47, p < 0.001), interleukin 6 (r = 0.28, p = 0.005) interleukin 10 (r = 0.3, p = 0.002) and suPAR (r = 0.28, p = 0.004). In addition, a higher LAR, but not its kinetics, was an independent predictor of 28-day mortality (at inclusion: HR 2.27, 95% C.I. 1.01–5.09, p = 0.04; one week later: HR: 4.29, 95% C.I. 1.71–10.78, p = 0.002). In conclusion, the LAR may be a valuable prognostic indicator in critically ill patients with sepsis at admission and one week later.

Kidney disease is linked to the development of cardiovascular disorders, further increasing morbidity and mortality in this high-risk population. Thus, early detection of myocardial damage is imperative in order to prevent devastating cardiovascular complications within this patient group. Over the years, cardiac biomarkers have been identified and are now widely used in everyday clinical practice. More specifically, available data suggest that cardiac troponin and its regulatory subunits (TnT, TnI, and TnC) reflect the injury and necrosis of myocardial tissue. While cTnC is identical in cardiac and skeletal muscle, TnT and TnI constitute cardiac-specific forms of troponin, and, as such, they have been established by international societies as biomarkers of cardiac damage and diagnostic indicators for acute myocardial infarction. Elevations in the levels of both cardiac troponins (cTnT and cTnI) have been also reported in asymptomatic patients suffering from chronic kidney disease. Therefore, if abnormal, they often generate confusion among clinicians regarding the interpretation and clinical significance of their numerical values in emergency settings. The aim of this review is to explore the reasons behind elevated troponin levels in patients with chronic kidney disease and identify when these elevated levels of biomarkers indicate the need for urgent intervention, considering the high cardiovascular risk in this patient group.

Macrophage migration inhibitory factor (MIF) is a highly conserved cytokine with pleiotropic properties, mainly pro-inflammatory. MIF seems to exert its pro-inflammatory features by binding to its transmembrane cellular receptor CD74. MIF also has CXCR4, which acts as a co-receptor in this inflammatory process. Apart from MIF, D-dopachrome tautomerase (DDT) or MIF2, which belongs to the MIF superfamily, also binds to receptor CD74. Therefore, these molecules, MIF, CD74, DDT and CXCR4 are suggested to work together orchestrating an inflammatory process. Diabetes mellitus is characterised by chronic low-grade inflammation. Therefore, the aim of the present study was to evaluate serum and urinary levels of the aforementioned molecules among patients with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and among healthy controls. We enrolled 13 patients with T1DM, 74 patients with T2DM and 25 healthy individuals as controls. Levels of CD74, CXCR4, DDT, and MIF were measured using ELISA Kits according to the manufacturer's instructions. We documented increased serum MIF levels together with higher urinary CD74 levels among patients with T1DM, when compared to patients with T2DM and healthy adults. In particular, patients with T1DM showed significantly increased levels of MIF compared to T2DM (p = 0.011) and healthy controls (p = 0.0093). CD74 in urine were significantly higher in patients with T1DM compared to those affected with T2DM (p = 0.0302) and healthy group (p = 0.0099). On the contrary, serum CD74 were similar among the three groups. No statistical differences were identified in CXCR4 levels both in serum and in urine of all groups. Patients with T2DM and overweight/obesity had increased urinary levels of CD74, when compared to lean patients with T2DM. The increased serum MIF levels and urinary CD74 levels among patients with T1DM may be attributed to the autoimmune milieu, which characterises patients with T1DM, when compared to patients with T2DM. These two findings merit further attention as they could pave the way for further research regarding the potential beneficial effects of inhibitors of MIF among patients with T1DM, especially in the early stages of T1DM. Finally, the role of inhibitors of MIF could be further explored in the context of obesity among patients with T2DM.

Background and Objectives: Clostridioides difficile infection (CDI) poses a major public health problem worldwide. Materials and Methods: In this retrospective study, we included 274 patients with CDI, who were hospitalized in Internal Medicine Departments in Evangelismos General Hospital in Athens, Greece, during the past decade. Demographic, clinical and laboratory parameters of the patients were recorded. Statistical analysis revealed an association between older age and mortality as well as heart failure and mortality among patients with CDI. Results: Notably, WBC (white blood count), neutrophils, NLR (neutrophil-to-lymphocyte ratio), dNLR (derived NLR), SII (systemic immune–inflammation index) and hs-CRP (high-sensitivity C-reactive protein) demonstrated a positive association with mortality, whereas serum albumin levels and PNR (platelet-to-neutrophil ratio) exhibited an inverse relationship with mortality. We propose that the aforementioned biomarkers may be used as prognostic parameters regarding mortality from CDI. Conclusions: Large scale studies among patients with CDI with the advent of AI (artificial intelligence) may incorporate demographic, clinical and laboratory features into prognostic scores to further characterize the global CDI threat.