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Bisalbuminemia is a rare, typically benign condition marked by the presence of a bifid albumin band on serum protein electrophoresis. It can either be inherited due to a point mutation or acquired in association with various medical conditions, most commonly diabetes mellitus. Bisalbuminuria, the presence of bifid albumin in urine, may or may not accompany bisalbuminemia. Both conditions are often discovered incidentally during screening for monoclonal gammopathy. Bisalbuminemia and related variants provide insights into albumin's genetic diversity and functional roles, influencing clinical diagnostics and research in human genetics. Understanding these variants aids in distinguishing benign conditions from potential disease states, guiding appropriate clinical management. In this case-based review, we present a case of hereditary bisalbuminemia identified unexpectedly during an investigation of a positive Direct Antiglobulin Test Coombs in an adult female patient. This review aims to highlight the key features of bisalbuminemia, a rare condition that should be recognized by clinicians.

Paraneoplastic hypoglycemia, also known as non-islet cell tumor hypoglycemia (NICTH), is a rare but critical condition occurring in patients with different types of malignancy. This condition is commonly linked to tumors producing insulin-like growth (IGF) factors, particularly IGF-2 and its precursors, which disrupt glucose homeostasis and lead to excessive glucose consumption. The diagnosis typically involves documenting symptomatic hypoglycemia and ruling out other potential causes. Essential diagnostic tools include imaging studies and laboratory tests, specifically measuring IGF-2 levels and the IGF-2:IGF-1 ratio. Treatment strategies for NICTH are multifaceted and may include surgical resection of the tumor if feasible, pharmacological interventions such as corticosteroids to suppress IGF-2 production, or supportive measures to manage acute hypoglycemic episodes. Novel therapeutic approaches targeting IGF-2, such as monoclonal antibodies or siRNA, are also being explored and hold promise for future treatment options. This review aims to enhance understanding of paraneoplastic hypoglycemia, focusing on its pathogenesis and diagnosis, to guide optimal medical treatment.

Background: Diabetes mellitus (DM) is tightly associated with the increased prevalence of diabetic kidney disease (DKD). Nonetheless, severe renal function impairment and/or nephrotic range-proteinuria could also result from non-diabetic renal disease (non-DRD) among patients with DM. The ‘Gold standard’ for the differential diagnosis between DKD and non-DRD is kidney biopsy, although no real consensus exists. Thus, this study intends to associate the clinical and biochemical profile of patients with DM and renal disease with the histopathological data of kidney biopsy.In addition, we aimed to evaluate the role of kidney biopsy, especially when other causes, other than DM, are highly suspected among patients with DM and kidney disease. Methods: Thirty two patients with T2DM and nephrotic range levels of proteinuria or with co-existing factors pointing towards a non-diabetic origin of kidney disease were studied, retrospectively. All 32 patients underwent kidney biopsy and were classified according to histopathological findings into 3 groups: a) isolated diabetic kidney disease (DKD), b) non-diabetic kidney disease (NDKD) and c) mixed kidney disease (MKD). Results: Fifteen out of the 32 patients had findings of an isolated DKD, while 17 out of 32 patients suffered from NDKD (13 patients) or MKD (4 patients). DKD patients were younger (p = 0.016) and had a higher HbA1c value (p = 0.069, borderline statistical significance), while the NDKD patients had significantly shorter disease duration (p = 0.04). Furthermore, the incidence of diabetic retinopathy (DR) was lower among the NDKD patients (p

Hypovitaminosis D is highly prevalent in critically ill patients, and it has been suggested to be a risk factor for infections, sepsis and higher mortality. We sought to investigate whether serum 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) in critically ill patients with new onset sepsis are associated with severity and outcome. We prospectively included 50 consecutive critically ill adult cases with new onset sepsis and 50 healthy controls matched for age and sex. PTH and 25(OH)D were determined in serum via electrochemiluminescence immunoassays at inclusion in the study in all cases and controls, and one week after sepsis onset in cases. Patients had reduced 25(OH)D compared to controls at sepsis onset (7.9 ± 3 vs 24.6 ± 6.7 ng/mL, p 0.05). 25(OH)D was positively correlated with ionized calcium (r = 0.46, p

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.

Atherosclerotic cardiovascular disease poses a significant global health issue, with dyslipidemia standing out as a major risk factor. In recent decades, lipid-lowering therapies have evolved significantly, with statins emerging as the cornerstone treatment. These interventions play a crucial role in both primary and secondary prevention by effectively reducing cardiovascular risk through lipid profile enhancements. Beyond their primary lipid-lowering effects, extensive research indicates that these therapies exhibit pleiotropic actions, offering additional health benefits. These include anti-inflammatory properties, improvements in vascular health and glucose metabolism, and potential implications in cancer management. While statins and ezetimibe have been extensively studied, newer lipid-lowering agents also demonstrate similar pleiotropic effects, even in the absence of direct cardiovascular benefits. This narrative review explores the diverse pleiotropic properties of lipid-modifying therapies, emphasizing their non-lipid effects that contribute to reducing cardiovascular burden and exploring emerging benefits for non-cardiovascular conditions. Mechanistic insights into these actions are discussed alongside their potential therapeutic implications

Nonalcoholic fatty liver disease (NAFLD) poses an emerging threat topublic health. Nonalcoholic steatohepatitis (NASH) is reported to be the most rapidly rising cause of hepatocellular carcinoma in the western world. Recently, a new term has been proposed: metabolic dysfunction-associated steatotic liver disease (MASLD). The introduction of this new terminology has sparked a debate about the interchangeability of these terms. The pathogenesis of NAFLD/MASLD is thought to be multifactorial, involving both genetic and environmental factors. Among these factors, alterations in gut microbiota and gut dysbiosis have recently garnered significant attention. In this context, this review will further discuss the gut–liver axis, which refers to the bidirectional interaction between the human gut microbiota and the liver. Additionally, the therapeutic potential of probiotics, particularly next-generation probiotics and genetically engineered bacteria, will be explored. Moreover, the role of prebiotics, synbiotics, postbiotics, and phages as well as fecal microbiota transplantation will be analyzed. Particularly for lean patients with NAFLD/MASLD, who have limited treatment options, approaches that modify the diversity and composition of the gut microbiota may hold promise. However, due to ongoing safety concerns with approaches that modulate gut microbiota, further large-scale studies are necessary to better assess their efficacy and safety in treating NAFLD/MASLD.

Tetracyclines constitute a unique class of antibiotic agents, widely prescribed for both community and hospital infections due to their broad spectrum of activity. Acting by disrupting protein synthesis through tight binding to the 30S ribosomal subunit, their interference is typically reversible, rendering them bacteriostatic in action. Resistance to tetracyclines has primarily been associated with changes in pump efflux or ribosomal protection mechanisms. To address this challenge, tetracycline molecules have been chemically modified, resulting in the development of third-generation tetracyclines. These novel tetracyclines offer significant advantages in treating infections, whether used alone or in combination therapies, especially in hospital settings. Beyond their conventional antimicrobial properties, research has highlighted their potential non-antibiotic properties, including their impact on immunomodulation and malignancy. This review will focus on third-generation tetracyclines, namely tigecycline, eravacycline, and omadacycline. We will delve into their mechanisms of action and resistance, while also evaluating their pros and cons over time. Additionally, we will explore their therapeutic potential, analyzing their primary indications of prescription, potential future uses, and non-antibiotic features. This review aims to provide valuable insights into the clinical applications of third-generation tetracyclines, thereby enhancing understanding and guiding optimal clinical use.

Non-alcoholic fatty liver disease (NAFLD) is a major public health issue worldwide. It is the most common liver disease in Western countries, andits global prevalence is estimated to be up to 35%. However, its diagnosis may be elusive, because liver biopsy is relatively rarely performed and usually only in advanced stages of the disease. Therefore, several non-invasive scores may be applied to more easily diagnose and monitor NAFLD. In this review, we discuss the various biomarkers and imaging scores that could be useful in diagnosing and managing NAFLD. Despite the fact that general measures, such as abstinence from alcohol and modulation of other cardiovascular disease risk factors, should be applied, the mainstay of prevention and management is weight loss. Bariatric surgery may be suggested as a means to confront NAFLD. In addition, pharmacological treatment with GLP-1 analogues or the GIP agonist tirzepatide may be advisable. In this review, we focus on the utility of GLP-1 analogues and GIP agonists in lowering body weight, their pharmaceutical potential, and their safety profile, as already evidenced inanimal and human studies. We also elaborate on other options, such as the use of vitamin E, probiotics, especially next-generation probiotics, and prebiotics in this context. Finally, we explore future perspectives regarding the administration of GLP-1 analogues, GIP agonists, and probiotics/prebiotics as a means to prevent and combat NAFLD. The newest drugs pegozafermin and resmetiron, which seem to be very promising, arealso discussed.

Lipoprotein(a) [Lp(a)] consists of a low-density lipoprotein-like molecule and an apolipoprotein(a) [apo(a)] particle. Lp(a) has been suggested to be an independent risk factor of atherosclerotic cardiovascular disease (ASCVD). Lp(a) plasma levels are considered to be 70–90% genetically determined through the codominant expression of the LPA gene. Therefore, Lp(a) levels are almost stable during an individual’s lifetime. This lifelong stability, together with the difficulties in measuring Lp(a) levels in a standardized manner, may account for the scarcity of available drugs targeting Lp(a). In this review, we synopsize the latest data regarding the structure, metabolism, and factors affecting circulating levels of Lp(a), as well as the laboratory determination measurement of Lp(a), its role in the pathogenesis of ASCVD and thrombosis, and the potential use of various therapeutic agents targeting Lp(a). In particular, we discuss novel agents, such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) that are currently being developed and target Lp(a). The promising role of muvalaplin, an oral inhibitor of Lp(a) formation, is then further analyzed.

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.

Irisin, a novel adipo-myokine with metabolic regulatory functions, exerts anti-inflammatory, antioxidant, and anti-apoptotic actions that may confer protection against sepsis-induced organ injury in experimental studies. Until now, only one human study has explored circulating irisin at sepsis onset. We aimed to examine serum irisin and its kinetics in critically ill patients with sepsis and septic shock with regard to sepsis severity and outcome. We enrolled 102 critically ill patients with sepsis or septic shock within 48 h of diagnosis and 102 age- and gender-matched healthy controls. Irisin was determined in serum upon enrollment in all participants and one week later in patients using an immunoenzymatic method. The outcome of sepsis was recorded 28 days after enrollment. At enrollment, circulating irisin was significantly lower in patients than controls (22.3 ± 6.8 μg/L vs. 28.1 ± 6.7 μg/L, p < 0.001), and increased significantly one week later (22.3 ± 6.8 μg/L vs. 26.6 ± 9.5 μg/L, p < 0.001). Irisin was significantly lower in patients who presented with septic shock than those with sepsis, and in non-survivors than survivors both at enrollment and one week later. However, kinetics of irisin did not differ between the groups (p > 0.05). Patients with higher circulating irisin during the first week of sepsis had a better outcome (p < 0.001). Lower irisin was independently associated with 28-day mortality (sepsis onset: HR 0.44, 95% C.I. 0.26–0.77, p = 0.004 and one week after: HR 0.37, 95% C.I. 0.23–0.58, p < 0.001). Irisin was negatively correlated with severity scores, metabolic, and inflammatory biomarkers. Circulating irisin decreases early in sepsis and is an independent predictor of 28-day mortality. Irisin may be a promising diagnostic and prognostic sepsis biomarker; nevertheless, larger studies are needed to explore its role in sepsis.

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.

Excess body weight constitutes one of the major health challenges for societies and healthcare systems worldwide. Besides the type of diet, calorie intake and the lack of physical exercise, recent data have highlighted a possible association between endocrine-disrupting chemicals (EDCs), such as bisphenol A, phthalates and their analogs, and obesity. EDCs represent a heterogeneous group of chemicals that may influence the hormonal regulation of body mass and adipose tissue morphology. Based on the available data from mechanistic, animal and epidemiological studies including meta-analyses, the weight of evidence points towards the contribution of EDCs to the development of obesity, associated disorders and obesity-related adipose tissue dysfunction by (1) impacting adipogenesis; (2) modulating epigenetic pathways during development, enhancing susceptibility to obesity; (3) influencing neuroendocrine signals responsible for appetite and satiety; (4) promoting a proinflammatory milieu in adipose tissue and inducing a state of chronic subclinical inflammation; (5) dysregulating gut microbiome and immune homeostasis; and (6) inducing dysfunction in thermogenic adipose tissue. Critical periods of exposure to obesogenic EDCs are the prenatal, neonatal, pubertal and reproductive periods. Interestingly, EDCs even at low doses may promote epigenetic transgenerational inheritance of adult obesity in subsequent generations. The aim of this review is to summarize the available evidence on the role of obesogenic EDCs, specifically BPA and phthalate plasticizers, in the development of obesity, taking into account in vitro, animal and epidemiologic studies; discuss mechanisms linking EDCs to obesity; analyze the effects of EDCs on obesity in critical chronic periods of exposure; and present interesting perspectives, challenges and preventive measures in this research area.

Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far it has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; a chronic, low-grade inflammatory response; immune dysregulation and a defective immune response; the reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal and metabolic dysregulation; mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response, although this effort may be hampered by challenges pertaining to the non-specific nature of the majority of clinical manifestations in the LC spectrum, small sample sizes of relevant studies and other methodological issues. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation, including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, the reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; and cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers, their link to etiopathogenetic mechanisms or the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on pathogenetic mechanisms and the main LC symptomatology in the frame of the epidemiological and clinical aspects of the syndrome and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions.

Background and Objectives: Omentin-1, also known as intelectin-1, is a novel adipokine with anti-inflammatory activities implicated in inflammatory diseases and sepsis. We aimed to explore serum omentin-1 and its kinetics in critically ill patients early in sepsis and its association with severity and prognosis. Materials and Methods: Serum omentin-1 was determined in 102 critically ill patients with sepsis during the first 48 h from sepsis onset and 1 week later, and in 102 age- and gender-matched healthy controls. The outcome of sepsis at 28 days after enrollment was recorded. Results: Serum omentin-1 at enrollment was significantly higher in patients compared to controls (763.3 ± 249.3 vs. 451.7 ± 122.3 μg/L, p < 0.001) and it further increased 1 week after (950.6 ± 215.5 vs. 763.3 ± 249.3 μg/L, p < 0.001). Patients with septic shock (n = 42) had higher omentin-1 compared to those with sepsis (n = 60) at enrollment (877.9 ± 241.2 vs. 683.1 ± 223.7 μg/L, p < 0.001) and 1 week after (1020.4 ± 224.7 vs. 901.7 ± 196.3 μg/L, p = 0.007). Furthermore, nonsurvivors (n = 30) had higher omentin-1 at sepsis onset (952.1 ± 248.2 vs. 684.6 ± 204.7 μg/L, p < 0.001) and 1 week after (1051.8 ± 242 vs. 908.4 ± 189.8 μg/L, p < 0.01). Patients with sepsis and survivors presented higher kinetics than those with septic shock and nonsurvivors (Δ(omentin-1)% 39.8 ± 35.9% vs. 20.2 ± 23.3%, p = 0.01, and 39.4 ± 34.3% vs. 13.3 ± 18.1%, p < 0.001, respectively). Higher omentin-1 at sepsis onset and 1 week after was an independent predictor of 28-day mortality (HR 2.26, 95% C.I. 1.21–4.19, p = 0.01 and HR: 2.15, 95% C.I. 1.43–3.22, p < 0.001, respectively). Finally, omentin-1 was significantly correlated with the severity scores, the white blood cells, coagulation biomarkers, and CRP, but not procalcitonin and other inflammatory biomarkers. Conclusions: Serum omentin-1 is increased in sepsis, while higher levels and lower kinetics during the first week of sepsis are associated with the severity and 28-day mortality of sepsis. Omentin-1 may be a promising biomarker of sepsis. However, more studies are needed to explore its role in sepsis.

Obesity and obesity-associated disorders pose a major public health issue worldwide. Apart from conventional weight loss drugs, next-generation probiotics (NGPs) seem to be very promising as potential preventive and therapeutic agents against obesity. Candidate NGPs such as Akkermansia muciniphila, Faecalibacterium prausnitzii, Anaerobutyricum hallii, Bacteroides uniformis, Bacteroides coprocola, Parabacteroides distasonis, Parabacteroides goldsteinii, Hafnia alvei, Odoribacter laneus and Christensenella minuta have shown promise in preclinical models of obesity and obesity-associated disorders. Proposed mechanisms include the modulation of gut flora and amelioration of intestinal dysbiosis, improvement of intestinal barrier function, reduction in chronic low-grade inflammation and modulation of gut peptide secretion. Akkermansia muciniphila and Hafnia alvei have already been administered in overweight/obese patients with encouraging results. However, safety issues and strict regulations should be constantly implemented and updated. In this review, we aim to explore (1) current knowledge regarding NGPs; (2) their utility in obesity and obesity-associated disorders; (3) their safety profile; and (4) their therapeutic potential in individuals with overweight/obesity. More large-scale, multicentric and longitudinal studies are mandatory to explore their preventive and therapeutic potential against obesity and its related disorders.

Although mRNA-based vaccines BNT162b2 and mRNA-1273 exhibit a remarkable efficacy and effectiveness in preventing particularly severe Covid-19 with an overall favorable adverse event profile, their use has been associated with rare cases of acute myocarditis. These occur most commonly after the second dose, with the highest incidence among young male recipients. This complication has not been frequently observed among adenoviral vector vaccine receivers, and its clinical, laboratory and imaging features resemble those of other common causes of acute myocarditis. The pathogenesis of mRNA-vaccine associated myocarditis has not yet been elucidated, although a number of mechanisms have been proposed, typically implicating the administered S-protein mRNA and likely mediated through an autoimmune mechanism. Nonetheless, other mechanisms may be implicated given the fact that myocarditis cases are very rarely observed among recipients of non mRNA vaccines. The recent observation of a similar adverse event in a recipient of the non-mRNA, peptide-based NVX-CoV2373 in the frame of a phase III clinical trial with 7020 participants in the active treatment arm raises the question whether the lipid nanoparticle sheath, which is a common structural component of these platforms could be implicated in the pathogenesis of vaccine-induced myocarditis.

Reactivation of varicella-zoster virus (VZV) has been reported after the administration of different vaccine platforms against SARS-CoV-2, also among individuals without known immunosuppressive states. Herein, we describe for the first time a case of herpes zoster after mRNA vaccination against SARS-CoV-2 in a 53-year-old immunocompetent adult without any known comorbidities, who was previously vaccinated with a live attenuated zoster vaccine. The fact that the patient had no history of varicella and had been tested seronegative for VZV prior to immunization with the live attenuated zoster vaccine further contribute to the challenge of this unusual case. This advocates for a high level of vigilance on the part of clinicians regarding this rare complication among receivers of COVID-19 vaccines.

Liver dysfunction during sepsis is associated with increased bilirubin and decreased fetuin-A, a major hepatokine. We aimed to explore the association of bilirubin to fetuin-A (B/F) ratio early in sepsis with severity and outcome in critically ill patients. Based on a previous prospective study, we analyzed data of 90 critically ill patients (52 males, age: 65 ± 15 years, APACHE II: 24 ± 7 and SOFA: 10 ± 3) with sepsis. Bilirubin and fetuin-A increased during the first week of sepsis, (median (IQR) 0.45 (0.32–1) vs 0.55 (0.29–0.78) mg/dL, p = 0.03 and 302 (248–336) vs 358 (307–399) μg/mL, p

Abstract Endothelial cell involvement with COVID-19 has been shown in the lung, heart, kidney, intestine and brain with histopathological evidence of endotheliitis and vasculitis. Viral RNA of COVID-19 has been detected in the retina of affected patients and recent publications highlight the possibility of retinal microangiopathy in patients with confirmed COVID-19 infection. Given the magnitude of the current pandemic, emphasis should be given to better reporting of clinically significant ocular symptoms, e.g. new scotoma, which could indicate the need for a retinal examination as well as follow-up testing after recovery from COVID-19.

Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, represents the primary cause of death due to infection [...]

The coronavirus disease 2019 (COVID-19) pandemic is still ongoing, while no treatment has been proven effective. COVID-19 pathophysiology involves the activation of three main pathways: the inflammatory, the coagulation and the bradykinin cascades. Here, we highlight for the first time the joint potential therapeutic role of bromelain and curcumin, two well-known nutraceuticals, in the prevention of severe COVID-19. Bromelain (a cysteine protease isolated from the pineapple stem) and curcumin (a natural phenol found in turmeric) exert important immunomodulatory actions interfering in the crucial steps of COVID-19 pathophysiology. Their anti-inflammatory properties include inhibition of transcription factors and subsequent downregulation of proinflammatory mediators. They also present fibrinolytic and anticoagulant properties. Additionally, bromelain inhibits cyclooxygenase and modulates prostaglandins and thromboxane, affecting both inflammation and coagulation, and also hydrolyzes bradykinin. Interestingly, curcumin has been shown in silico studies to prevent entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into cells as well as viral replication, while a recent experimental study has demonstrated that bromelain may also inhibit viral entry into cells. Notably, bromelain substantially increases the absorption of curcumin after oral administration. To the best of our knowledge, this is the first report highlighting the significance of bromelain and, most importantly, the potential preventive value of the synergistic effects of bromelain and curcumin against severe COVID-19.

Chemerin, a novel adipokine, is a potent chemoattractant molecule with antimicrobial properties, implicated in immune responses. Our aim was to investigate circulating chemerin and its kinetics, early in sepsis in critically ill patients and its association with severity and prognosis. Serum chemerin was determined in a cohort of 102 critically ill patients with sepsis during the first 48 h from sepsis onset and one week later, and in 102 age- and gender-matched healthy controls. Patients were followed for 28 days and their outcomes were recorded. Circulating chemerin was significantly higher in septic patients at onset compared to controls (342.3 ± 108.1 vs. 200.8 ± 40.1 μg/L, p < 0.001). Chemerin decreased significantly from sepsis onset to one week later (342.3 ± 108.1 vs. 308.2 ± 108.5 μg/L, p < 0.001), but remained higher than in controls. Chemerin was higher in patients presenting with septic shock than those with sepsis (sepsis onset: 403.2 ± 89.9 vs. 299.7 ± 99.5 μg/L, p < 0.001; one week after: 374.9 ± 95.3 vs. 261.6 ± 91.9 μg/L, p < 0.001), and in nonsurvivors than survivors (sepsis onset: 427.2 ± 96.7 vs. 306.9 ± 92.1 μg/L, p < 0.001; one week after: 414.1 ± 94.5 vs. 264.2 ± 79.9 μg/L, p < 0.001). Moreover, patients with septic shock and nonsurvivors, presented a significantly lower absolute and relative decrease in chemerin one week after sepsis onset compared to baseline (p < 0.001). Based on ROC curve analyses, the diagnostic performance of chemerin (AUC 0.78, 95% CI 0.69–0.87) was similar to C-reactive protein (CRP) (AUC 0.78, 95% CI 0.68–0.87) in discriminating sepsis severity. However, increased chemerin at sepsis onset and one week later was an independent predictor of 28-day mortality (sepsis onset: HR 3.58, 95% CI 1.48–8.65, p = 0.005; one week after: HR 10.01, 95% CI 4.32–23.20, p < 0.001). Finally, serum chemerin exhibited significant correlations with the severity scores, white blood cells, lactate, CRP and procalcitonin, as well as with biomarkers of glucose homeostasis, but not with cytokines and soluble urokinase-type plasminogen activator receptor (suPAR). Circulating chemerin is increased early in sepsis and its kinetics may have diagnostic and prognostic value in critically ill patients. Further studies are needed to shed light on the role of chemerin in sepsis.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. NAFLD begins as a relatively benign hepatic steatosis which can evolve to non-alcoholic steatohepatitis (NASH); the risk of cirrhosis and hepatocellular carcinoma (HCC) increases when fibrosis is present. NAFLD represents a complex process implicating numerous factors—genetic, metabolic, and dietary—intertwined in a multi-hit etiopathogenetic model. Recent data have highlighted the role of gut dysbiosis, which may render the bowel more permeable, leading to increased free fatty acid absorption, bacterial migration, and a parallel release of toxic bacterial products, lipopolysaccharide (LPS), and proinflammatory cytokines that initiate and sustain inflammation. Although gut dysbiosis is present in each disease stage, there is currently no single microbial signature to distinguish or predict which patients will evolve from NAFLD to NASH and HCC. Using 16S rRNA sequencing, the majority of patients with NAFLD/NASH exhibit increased numbers of Bacteroidetes and differences in the presence of Firmicutes, resulting in a decreased F/B ratio in most studies. They also present an increased proportion of species belonging to Clostridium, Anaerobacter, Streptococcus, Escherichia, and Lactobacillus, whereas Oscillibacter, Flavonifaractor, Odoribacter, and Alistipes spp. are less prominent. In comparison to healthy controls, patients with NASH show a higher abundance of Proteobacteria, Enterobacteriaceae, and Escherichia spp., while Faecalibacterium prausnitzii and Akkermansia muciniphila are diminished. Children with NAFLD/NASH have a decreased proportion of Oscillospira spp. accompanied by an elevated proportion of Dorea, Blautia, Prevotella copri, and Ruminococcus spp. Gut microbiota composition may vary between population groups and different stages of NAFLD, making any conclusive or causative claims about gut microbiota profiles in NAFLD patients challenging. Moreover, various metabolites may be involved in the pathogenesis of NAFLD, such as short-chain fatty acids, lipopolysaccharide, bile acids, choline and trimethylamine-N-oxide, and ammonia. In this review, we summarize the role of the gut microbiome and metabolites in NAFLD pathogenesis, and we discuss potential preventive and therapeutic interventions related to the gut microbiome, such as the administration of probiotics, prebiotics, synbiotics, antibiotics, and bacteriophages, as well as the contribution of bariatric surgery and fecal microbiota transplantation in the therapeutic armamentarium against NAFLD. Larger and longer-term prospective studies, including well-defined cohorts as well as a multi-omics approach, are required to better identify the associations between the gut microbiome, microbial metabolites, and NAFLD occurrence and progression.

Aberrant circulating omentin-1, which is an anti-inflammatory and pro-apoptotic adipokine, has been reported in various solid tumors. Therefore, we investigated whether or not circulating omentin-1 could be associated with postmenopausal BC (PBC) and could be used as a potential diagnostic and clinical tool taking into consideration clinicopathologic features, tumor markers, as well as anthropometric, metabolic, and inflammatory parameters. Serum omentin-1, tumor markers (CA15-3 and CEA); metabolic (insulin, glucose, HOMA index, and serum lipids), anthropometric (BMI, waist circumference, and fat mass), and inflammatory (TNF-α, IL-6, hsCRP) parameters; classic adipokines (leptin and adiponectin); the Mediterranean diet (MedDiet) score; and cardiovascular (CVD) risk were determined in 103 postmenopausal women with pathologically confirmed incident invasive BC, 103 controls matched on age, 51 patients with benign breast lesions (BBL), and 50 obese postmenopausal women of similar age. The mean serum omentin-1 was significantly lower in cases than in controls and patients with BBL (p < 0.001). In the patients, omentin-1 was inversely associated with tumor, metabolic and inflammatory biomarkers, cancer stage, and the number of infiltrated lymph nodes (p < 0.05). In all study participants, omentin-1 was negatively correlated with CVD risk and positively correlated with MedDiet score. Lower circulating omentin-1 was independently associated with PBC occurrence above and beyond known risk factors. According to the ROC curve analysis, the overall diagnostic performance of omentin-1 (0.84, 95% CI 0.79–0.89) is similar to CA15-3. Circulating omentin-1 may be a biomarker at the intersection of PBC and cardiometabolic risk in postmenopausal women, and could be modulated by the adoption of a MedDiet. Further mechanistic and large multicentric prospective and longitudinal studies are required to elucidate the ontological role of omentin-1 in BC and CVD risks, as well as its diagnostic and prognostic ability and its therapeutic potential.

Background: To date, most researchhas focused on the bacterial composition of the human microbiota. In this review, we synopsize recent data on the human mycobiome and cancer, highlighting specific cancer types based on current available evidence, presenting interesting perspectives and limitations of studies and laboratory methodologies. Recent findings: Head and neck cancer carcinoma (HNCC), colorectal carcinoma (CRC) and pancreatic ductal adenocarcinoma (PDA) have been associated with dissimilarities in the composition of mycobiota between cancer cases and non-cancer participants. Overall, fungal dysbiosis with decreased fungal richness and diversity was common in cancer patients; however, a specific mycobiotic signature in HNSCC or CRC has not emerged. Different strains of Candida albicans have been identified among cases with HNCC, whilst Lichtheimia corymbifera, a member of the Mucoraceae family, has been shown to predominate among patients with oral tongue cancer. Virulence factors of Candida spp. include the formation of biofilm and filamentation, and the secretion of toxins and metabolites. CRC patients present a dysregulated ratio of Basidiomycota/Ascomycota. Abundance of Malassezia has been linked to the occurrence and progression of CRC and PDA, particularly in animal models of PDA. Interestingly, Schizophyllum, a component of the oral mycobiome, may exhibit anti-cancer potential. Conclusion: The human mycobiome, per se, along with its interactions with the human bacteriome and the host, may be implicated in the promotion and progression of carcinogenesis. Fungi may be used as diagnostic and prognostic/predictive tools or treatment targets for cancer in the coming years. More large-scale, prospective, multicentric and longitudinal studies with an integrative multi-omics methodology are required to examine the precise contribution of the mycobiome in the etiopathogenesis of cancer, and to delineate whether changes that occur in the mycobiome are causal or consequent of cancer.