Towards understanding post-COVID-19 condition: A systematic meta-analysis of transcriptomic alterations with sex-specific insights.

BACKGROUND: Post COVID-19 Condition (PCC), characterized by lingering symptoms post-acute COVID-19, poses clinical challenges, highlighting the need to understand its underlying molecular mechanisms. This meta-analysis aims to shed light on the transcriptomic landscapes and sex-specific molecular dynamics intrinsic to PCC. METHODS: A systematic review identified three studies suitable for comprehensive meta-analysis, encompassing 135 samples (57 PCC subjects and 78 recovered subjects). We performed meta-analysis on differential gene expression, a gene set enrichment analysis of Reactome pathways, and weighted gene co-expression network analysis (WGCNA). We performed a drug and disease enrichment analysis and also assessed sex-specific differences in expression patterns. KEY FINDINGS: A clear difference was observed in the transcriptomic profiles of PCC subjects, with 530 differentially expressed genes (DEGs) identified. Enrichment analysis revealed that the altered pathways were predominantly implicated in cell cycle processes, immune dysregulation and histone modifications. Antioxidant compounds such as hesperitin were predominantly linked to the hub genes of the DEGs. Sex-specific analyses highlighted disparities in DEGs and altered pathways in male and female PCC patients, revealing a difference in the expression of ribosomal proteins. PCC in men was mostly linked to neuro-cardiovascular disorders, while women exhibited more diverse disorders, with a high index of respiratory conditions. CONCLUSION: Our study reveals the intricate molecular processes underlying PCC, highlighting that the differences in molecular dynamics between males and females could be key to understanding and effectively managing the varied symptomatology of this condition.

Platelet-associated biomarkers in nonalcoholic steatohepatitis: Insights from a female cohort with obesity.

BACKGROUND: There is a lack of noninvasive diagnostic methods for nonalcoholic steatohepatitis (NASH), the severe condition of metabolic dysfunction-associated steatotic liver disease (MASLD). Platelet activation, evaluated through certain related parameters, is associated with liver disease and inflammation, but previous results are inconclusive. AIM: To investigate the potential utility of platelet-related indices as noninvasive diagnostic markers for the detection and prediction of MASLD, focusing on NASH. RESULTS: We found that mean platelet volume (MPV), plateletcrit (PCT) and platelet distribution width (PDW) were increased in the severe and morbidly obese (SMO) group compared to the normal weight (NW) group. We found decreased levels of MPV in steatosis and NASH patients. MPV and PCT values were decreased in the presence of mild liver inflammation. Platelet count (PLA) and PCT values were lower in the presence of ballooning. We obtained an area under the ROC curve of 0.84 using MPV and three other variables to predict MASLD. CONCLUSIONS: Some platelet-related indices vary depending on liver condition. Here, we reported decreased MPV in MASLD presence. Moreover, we presented for the first time a predictive model using MPV, ALT levels and the presence of diabetes mellitus and metabolic syndrome to predict MASLD in obese women. Also, MPV is closely related to early liver inflammation in NASH, and PLA and PCT are related to hepatic ballooning. These indices could be widely used for the early detection of NASH since they are usually determined in routine laboratory tests.

A Surprising Case of Triple Acute Hepatitis Infection.

Viral hepatitis continues to be the leading cause of morbidity and mortality worldwide, but the burden has significantly diminished thanks to the large-scale use of vaccines and antivirals. However, there are still challenges regarding viral hepatitis management, especially when more than one pathogenic agent is involved. We present the case of a 45-year-old woman who had a simultaneous infection involving three hepatitis viruses: HAV, HBV, and HEV.

Systems analyses of the Fabry kidney transcriptome and its response to enzyme replacement therapy identified and cross-validated enzyme replacement therapy-resistant targets amenable to drug repurposing.

Fabry disease is a rare disorder caused by variations in the alpha-galactosidase gene. To a degree, Fabry disease is manageable via enzyme replacement therapy (ERT). By understanding the molecular basis of Fabry nephropathy (FN) and ERT's long-term impact, here we aimed to provide a framework for selection of potential disease biomarkers and drug targets. We obtained biopsies from eight control individuals and two independent FN cohorts comprising 16 individuals taken prior to and after up to ten years of ERT, and performed RNAseq analysis. Combining pathway-centered analyses with network-science allowed computation of transcriptional landscapes from four nephron compartments and their integration with existing proteome and drug-target interactome data. Comparing these transcriptional landscapes revealed high inter-cohort heterogeneity. Kidney compartment transcriptional landscapes comprehensively reflected differences in FN cohort characteristics. With exception of a few aspects, in particular arteries, early ERT in patients with classical Fabry could lastingly revert FN gene expression patterns to closely match that of control individuals. Pathways nonetheless consistently altered in both FN cohorts pre-ERT were mostly in glomeruli and arteries and related to the same biological themes. While keratinization-related processes in glomeruli were sensitive to ERT, a majority of alterations, such as transporter activity and responses to stimuli, remained dysregulated or reemerged despite ERT. Inferring an ERT-resistant genetic module of expressed genes identified 69 drugs for potential repurposing matching the proteins encoded by 12 genes. Thus, we identified and cross-validated ERT-resistant gene product modules that, when leveraged with external data, allowed estimating their suitability as biomarkers to potentially track disease course or treatment efficacy and potential targets for adjunct pharmaceutical treatment.

The Role of Fascial Tissue Layer in Electric Signal Transmission from the Forearm Musculature to the Cutaneous Layer as a Possibility for Increased Signal Strength in Myoelectric Forearm Exoprosthesis Development.

Myoelectric exoprostheses serve to aid in the everyday activities of patients with forearm or hand amputations. While electrical signals are known key factors controlling exoprosthesis, little is known about how we can improve their transmission strength from the forearm muscles as to obtain better sEMG. The purpose of this study is to evaluate the role of the forearm fascial layer in transmitting myoelectrical current. We examined the sEMG signals in three individual muscles, each from six healthy forearms (Group 1) and six amputation stumps (Group 2), along with their complete biometric characteristics. Following the tests, one patient underwent a circumferential osteoneuromuscular stump revision surgery (CONM) that also involved partial removal of fascia and subcutaneous fat in the amputation stump, with re-testing after complete healing. In group 1, we obtained a stronger sEMG signal than in Group 2. In the CONM case, after surgery, the patient's data suggest that the removal of fascia, alongside the fibrotic and subcutaneous fat tissue, generates a stronger sEMG signal. Therefore, a reduction in the fascial layer, especially if accompanied by a reduction of the subcutaneous fat layer may prove significant for improving the strength of sEMG signals used in the control of modern exoprosthetics.

Patellar Resurfacing in Total Knee Arthroplasty, a Never-Ending Controversy; Case Report and Literature Review.

Total knee arthroplasty (TKA) remains a lifesaving procedure for advanced gonarthrosis. However, patella resurfacing (PR) in TKA remains a controversial procedure, leading to extensive discussions amongst orthopedic surgeons, regarding its indications and results. Based on these premises, we present a clinical case of a 70-year-old Caucasian woman admitted for pain, swelling and limitation of left knee joint mobility. Her medical history records an Ahlback stage IV gonarthrosis with simultaneous bilateral TKA surgery performed in different hospital, when two NexGen cemented total prostheses were implanted with patellar resurfacing being performed only on the right side. Our clinical (American Knee Society Score, Lonner and Feller scales) and radiological evaluations (CT scan and Xray) revealed left patellar arthrosis and a slight lateral subluxation of the patella. The chosen treatment plan was revision surgery for PR and patellar prosthesis with a cemented patellar component, cross-linked polyethylene, no 32 NexGen model with 8.5 mm thickness. The immediate and distant postoperative evolution was favorable. Extensive literature review shows that, at present, PR remains at surgeon's discretion mainly based on his previous results. Therefore, we believe there is an imperative need to develop high quality studies based on accurate scientific evidence to universally establish valid guidelines for PR in TKA.

Ten-year multicentric retrospective analysis regarding postoperative complications and impact of comorbidities in hemorrhoidal surgery with literature review.

BACKGROUND: Hemorrhoidal disease (HD) is considered a low-severity pathology by both general population and physicians, but the lengthy conservative therapy and postoperative complications suggest otherwise. AIM: To assess the effectiveness of different treatment options, both conservative and surgical, in contrast with some preexisting comorbidities. METHODS: We conducted a retrospective, 10-yearlong study between January 2011 and December 2021 in two surgical centers, a private and a state-owned hospital. We compared the efficacy and safety of several treatment options, such as open hemorrhoidectomy, stapled hemorrhoidopexy, rubber band ligation and infrared coagulation in terms of complication rates and types and their correlation with different preexisting comorbidities such as inflammatory bowel disease (IBD), use of anticoagulant medication (AM) and liver cirrhosis. We also conducted a 20-years long PubMed research (1.263 articles) for relevant comparisons. RESULTS: Our study recorded 10940 patients with HD, 10241 with conservative and 699 with surgical treatment. Out of these, the male-to-female ratio of 1.3, and a peak in age distribution between 59 and 68 years old (32% of patients). For the entire study, we recorded a 90% incidence of immediate pain, immediate bleeding in 1.5% (11 cases), delayed bleeding in 1.0% (7 cases), and 0.6% surgical site infections. Urinary retention was also present, with 0.2% of patients, anal stricture in 1% and fecal incontinence for 0.5% of patients (4 cases). We recorded no severe complications such as Fournier`s gangrene or rectovaginal perforations. IBD accounted for 6% of the patients, with ulcerative colitis in 12% and Chron`s disease in 10.5%. 6.6% of the patients had AM, determining 4% immediate and 2% delayed bleeding, in surgically treated patients. CONCLUSION: Our study determined that most common complications (pain, urinary retention, bleeding, and stricture) are correlated with each surgical technique and pre-existing comorbidities.

Looking Under the Lamppost: The Search for New Cancer Targets in the Human Kinome.

The number of cancer drugs is increasing as new chemical entities are developed to target molecules, often protein kinases, driving cancer progression. In 2009, Fedorov et al. identified that of the protein kinases in the human kinome, most of the focus has been on a small subset. They highlighted that many poorly investigated protein kinases were cancer drivers, but there was no relationship between publications and involvement in cancer development or progression. Since 2009, there has been a doubling in the number of publications, patents, and drugs targeting the kinome. To determine whether this was an expansion in knowledge of well-studied targets-searching in the light under the lamppost-or an explosion of investigations into previously poorly investigated targets, we searched the literature for publications on each kinase, updating Federov et al.'s assessment of the druggable kinome. The proportion of papers focusing on the 50 most-studied kinases had not changed, and the makeup of those 50 had barely changed. The majority of new drugs (80%) were against the same group of 50 kinases identified as targets 10 years ago, and the proportion of studies investigating previously poorly investigated kinases (<1%) was unchanged. With three exceptions [p38 mitogenactivated protein kinase (p38a), AMP-activated protein kinase catalytic α-subunit 1,2, and B-Raf proto-oncogene (BRAF) serine/threonine kinase], >95% of publications addressing kinases still focused on a relatively small proportion (<50%) of the human kinome independently of their involvement as cancer drivers. There is, therefore, still extensive scope for discovery of therapeutics targeting different protein kinases in cancer and still a bias toward well-characterized targets over the innovative searchlight into the unknown. SIGNIFICANCE STATEMENT: This study presents evidence that drug discovery efforts in cancer are still to some extent focused on a narrow group of well-studied kinases 10 years after the identification of multiple novel cancer targets in the human kinome. This suggests that there is still room for researchers in academia, industry, and the not-for-profit sector to develop new and diverse therapies targeting kinases for cancer.

In Vivo Study of Local and Systemic Responses to Clinical Use of Mg-1Ca Bioresorbable Orthopedic Implants.

(1) Background: Resorbable Mg-based implants represent a new direction in orthopedic surgery but have some drawbacks, such as their rapid biodegradation and increased rate of corrosion. Some in vitro studies hypothesized that tissue necrosis, incision dehiscence, risk of gas embolization in vital organs, interference with coagulation processes, and trophocyte viability impairment can occur. (2) Methods: We conducted an in vivo study on ten rabbit cases, in two groups; group one, consisting of six cases, received cylindrical implants of Mg-1Ca alloy in tibial intramedullary bone tissue. Group two, consisting of four cases, received Mg-1Ca parallelepiped implants, in the thigh muscular tissue. We recorded and compared weight (preoperatively and at 2, 4, and 6 weeks postoperatively), complete blood count, serum electrolytes, liver and kidney functional markers, and coagulation parameters, prior to and at 6 weeks after surgery. Local evolution was assessed radiologically and with tissue biopsies with complete pathology analysis. (3) Results: All biological markers and clinical evolution were favorable, showing good integration of the implants with none of the local or systemic signs of degradation. (4) Conclusions: Our study shows that the clinical use of Mg-1Ca bioresorbable alloys can be safe as none of the cited local or systemic complications have been identified.

The Impact of Kidney Biopsy for Fabry Nephropathy Evaluation on Patients' Management and Long-Term Outcomes: Experience of a Single Center.

BACKGROUND: Fabry disease (FD) is a rare lysosomal storage disease causing progressive loss of target organ function. All renal cell types are involved from the early stages, even before clinical signs can be detected. FD-specific therapies can stop/mitigate disease progression. Thus, it is important to validate early markers of renal lesions so that they can be adopted as criteria for timely treatment initiation. MATERIALS AND METHODS: We retrospectively analyzed and extensively evaluated 21 FD case patients; this evaluation included a kidney biopsy. We looked for the influence of pathological findings on the management of FD patients. In addition, we investigated the association between general and FD-specific features and long-term patients' outcomes. We defined a combined endpoint as being at least one of the following: 50% decrease of estimated glomerular filtration rate (eGFR) from baseline, kidney failure (KF), end-stage kidney disease (ESKD), or death and mortality. RESULTS: Our cohort of 21 FD patients (11 males and 10 females) was stratified according to the presence of the combined endpoint: group 1 (n = 15) included patients without the combined endpoint, while group 2 (n = 6) patients reached the combined endpoint outcome. Patients from group 2 presented lower mean baseline eGFR (72.2 ± 38.7 mL/min/1.73 m2 vs. 82.5 ± 26.4 mL/min/1.73 m2) without statistical significance (p = 0.44), but significantly (p = 0.22) higher median baseline proteinuria (2.7 g/24 h vs. 0.4 g/24 h). Specific lysosomal deposits were identified in all patients. Segmental sclerosis was present in all patients with the combined endpoint and in only 33% of patients without the combined endpoint (p = 0.009). Global sclerosis and interstitial fibrosis were present in both groups, with no significant differences. A total of 15 out of the 16 treatment-naïve patients (7 males and 9 females) started FD-specific therapy after kidney biopsy. Treatment was initiated in all male FD patients and in 8 female patients. In 2 females, pathological findings in kidney biopsy offered important reasons to start FD treatment, although specific criteria of the Romanian protocol for prescription of FD-specific therapy were still not fulfilled. Cox univariate analysis showed that every increase in 24 h proteinuria with 1 g is associated with a 65% risk of developing the combined endpoint (HR = 1.65; 95%CI: 1.05-2.58; p = 0.02), and that the presence of segmental sclerosis increased the risk of developing the combined endpoint by 51.3 times (HR = 51.3; 95% CI: 95% CI: 1.67-103.5; p = 0.01). Kaplan-Meier analysis showed that the cumulative risk of developing the combined endpoint was higher in patients in whom segmental sclerosis (100% vs. 0%, log-rank test, p = 0.03) was present. CONCLUSIONS: Histological evaluation is an important tool for the detection of early kidney involvement and provides additional support to the early initiation of FD-specific therapy. Presence of segmental sclerosis can predict the long-term outcomes of kidney disease deterioration and mortality and may be used as an early indicator of disease progression. Additionally, in the absence of other criteria according to current guidelines, specific FD renal lesions as revealed by kidney biopsy might become a distinct criterion to initiate FD therapy.

Efficacy and Safety of Deep Sedation and Anaesthesia for Complex Endoscopic Procedures-A Narrative Review.

Propofol sedation for advanced endoscopic procedures is a widespread technique at present, which generates controversy worldwide when anaesthetic or non-anaesthetic personnel administer this form of sedation. There is some evidence for safe administered propofol sedation by non-anaesthetic personnel in patients undergoing endoscopy procedures, but there are only few randomised trials addressing the safety and efficacy of propofol in patients undergoing advanced procedures. A serious possible consequence of propofol sedation is the rapid and unpredictable progression from deep sedation to general anaesthesia mostly when elderly and frail patients are involved in the diagnosis or treatment of various neoplasia. This situation requires rescue measures with skilled airway management. The aim of this paper is to review the safety and efficacy aspects of sedation techniques, with special reference to propofol administration covering the whole patient journey, including preassessment, sedation options and discharge when advanced endoscopic procedures are performed.

Magnesium Orotate and the Microbiome-Gut-Brain Axis Modulation: New Approaches in Psychological Comorbidities of Gastrointestinal Functional Disorders.

Magnesium orotate has been cited in the medical literature for the past three years as a possible adjuvant in some pediatric and adult gastroenterological disorders associated with dysbiosis. Studies also focus on the possibility of adding magnesium orotate in psychiatric disorders' treatment, such as major depression and anxiety. The most relevant element in these studies is the efficiency of magnesium orotate therapy in cases with both gastroenterological and psychiatric symptoms. This article proposes a literature review, focused on the studies published in the last three years, targeting magnesium orotate treatment and probiotic supplementation in patients with both digestive and psychiatric symptoms. Moreover, this review will compare the efficiency of magnesium orotate and probiotics within both the pediatric and adult communities, focusing on the possibility of gut-brain axis modulation and its involvement in the clinical evolution of these patients.

Glial Fibrillary Acidic Protein Autoimmunity: A French Cohort Study.

BACKGROUND AND OBJECTIVES: To report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies. METHODS: We retrospectively included all patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα since 2017 from 2 French referral centers. RESULTS: We identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other autoimmune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T-cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%), with cerebellar dysfunction in 57% of cases. Other clinical presentations included myelitis (30%) and visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. A total of 33 of 40 patients had a monophasic course, associated with a good outcome at last follow-up (Rankin Score ≤2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. A total of 11/22 patients showed negative conversion of GFAP antibodies. DISCUSSION: GFAP autoimmunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T-cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome.

The Role of Thromboprophylaxis in Patients with Portal Vein Thrombosis: A Life-Threatening Complication after Laparoscopic Sleeve Gastrectomy Following 8 Years of Experience in a Bariatric Center of Excellence.

Porto-mesenteric vein thrombosis (PVMT) is a rare but life-threatening complication after laparoscopic sleeve gastrectomy (LSG). Laparoscopic sleeve gastrectomy (LSG) is considered the most common procedure for efficiently realizing weight loss and treating obesity-related co-morbidities. This study aimed to shed light on this relatively rare complication by presenting a series of patients who developed PMVT after LSG in light of the need to change the specific protocol of thromboprophylaxis in bariatric patients. We proposed to answer two questions: whether we should perform a thrombophilia workup as a standard practice and whether we should extend chemoprophylaxis to more than 3 weeks among all bariatric patients. This study also aimed to investigate the possible risk factors and eventually present our updated protocol for PMVT management and prophylaxis.

Clinical and surgical algorithm for managing iatrogenic bile duct injuries during laparoscopic cholecystectomy: A multicenter study.

The present study was a multicenter, analytical, nonrandomized research on 108 cases of intraoperative vascular and bile duct lesions during laparoscopic cholecystectomies. We selected these cases from 16,559 cholecystectomies performed entirely laparoscopically or debuted laparoscopically and converted to an open approach. The study included two surgical centers labeled as primary, with extensive experience in hepato-biliary reconstructive surgery, and four other centers labeled as secondary that referred cases to the previous two. Our study analyzed several key parameters such as the percentage of iatrogenic lesions recorded, the variability of the main biliary pathway and conformation as well as its relationship to the adjacent critical anatomical landmarks, the anatomical and physiopathological characteristics of pathology requiring surgical intervention, factors related to laparoscopic surgical technique, the surgical technique used to repair the recorded lesions, the duration of survivability and the rate of the occurring complications. Based on the analysis of these parameters, we developed a descriptive algorithm with visual representation relying on several decisional points to guide the surgeons in choosing the optimal treatment method so that patients will benefit from a favorable clinical path.

Molecular mechanisms in septic shock (Review).

Sepsis is a clinical syndrome defined by the presence of infection and systemic inflammatory response to infection and results from a complex interaction between the host and infectious agents. It is characterized by the activation of multiple inflammatory pathways, with an increased risk of mortality. The incidence of sepsis has been on an ever-increasing pathway in recent years. Sepsis can be induced by several clinical situations that predispose to its occurrence: malignant tumors, organ transplantation, AIDS, radiation therapy, burns, sores, polytrauma, diabetes mellitus, hepatic failure, renal failure, malnutrition, catheters or different invasive devices, and urinary catheters. The microorganisms involved in the pathogenesis of sepsis are Gram-positive cocci (Staphylococci, Streptococci) and Gram-negative bacilli (Klebsiella, Pseudomonas aeruginosa, E. coli), fungi (Candida), parasites, and viruses. Among mechanisms involved in septic shock production, two pathological phenomena appear: the profound decompensation of circulation and metabolic disturbances that evolve towards an irreversible state. The intimate mechanism of shock involves the activation of monocytes, macrophages and neutrophils by lipopolysaccharides of Gram-negative bacteria. The microvascular bed is directly involved in the etiopathogenesis of disorders of acute inflammatory states associated with or without sepsis. A better comprehension of sepsis pathophysiology, especially the molecular mechanisms of septic shock, allows for new therapeutic perspectives.

Surface Enhanced Raman Spectroscopy for Quantitative Analysis: Results of a Large-Scale European Multi-Instrument Interlaboratory Study.

Surface-enhanced Raman scattering (SERS) is a powerful and sensitive technique for the detection of fingerprint signals of molecules and for the investigation of a series of surface chemical reactions. Many studies introduced quantitative applications of SERS in various fields, and several SERS methods have been implemented for each specific application, ranging in performance characteristics, analytes used, instruments, and analytical matrices. In general, very few methods have been validated according to international guidelines. As a consequence, the application of SERS in highly regulated environments is still considered risky, and the perception of a poorly reproducible and insufficiently robust analytical technique has persistently retarded its routine implementation. Collaborative trials are a type of interlaboratory study (ILS) frequently performed to ascertain the quality of a single analytical method. The idea of an ILS of quantification with SERS arose within the framework of Working Group 1 (WG1) of the EU COST Action BM1401 Raman4Clinics in an effort to overcome the problematic perception of quantitative SERS methods. Here, we report the first interlaboratory SERS study ever conducted, involving 15 laboratories and 44 researchers. In this study, we tried to define a methodology to assess the reproducibility and trueness of a quantitative SERS method and to compare different methods. In our opinion, this is a first important step toward a "standardization" process of SERS protocols, not proposed by a single laboratory but by a larger community.

Inflammation-Related Patterns in the Clinical Staging and Severity Assessment of Chronic Kidney Disease.

Chronic kidney disease (CKD) is an irreversible loss of kidney function, and it represents a major global public health burden due to both its prevalence and its continuously increasing incidence. Mineral bone disorders (MBDs) constitute a hallmark of CKD, and alongside cardiovascular complications, they underlie a poor prognosis for these patients. Thus, our study focused on novel CKD biomarker patterns and their impact on the clinical staging of the disease. As a first testing approach, the relative expression levels of 105 proteins were assessed by the Proteome Profiler Cytokine Array Kit for pooled CKD stage 2-4 serum samples to establish an overall view regarding the proteins involved in CKD pathogenesis. Among the molecules that displayed significant dysregulation in the CKD stages, we further explored the involvement of Dickkopf-related protein 1 (Dkk-1), a recognised inhibitor of the Wnt signalling pathway, and its crosstalk with 1,25OH2D3 (calcitriol) as new players in renal bone and vascular disease. The serum levels of these two molecules were quantified by an ELISA (76 samples), and the results reveal decreasing circulating levels of Dkk-1 and calcitriol in advanced CKD stages, with their circulating expression showing a downward trend as the CKD develops. In the next step, we analysed the inflammation and MBD biomarkers' expression in CKD (by xMAP array). Our results show that the molecules involved in orchestrating the inflammatory response, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα), as well as the mineral biomarkers osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN), and fibroblast growth factor 23 (FGF-23), correlate with Dkk-1 and calcitriol, raising the possibility of them being potential useful CKD biomarkers. These results reveal the impact of different biomarker patterns in CKD staging and severity, thus opening up novel approaches to be explored in CKD clinical management.

Proteomic Biomarkers Panel: New Insights in Chronic Kidney Disease.

Chronic kidney disease, despite being a "silent epidemic" disease, represents one of the main causes of mortality in general population, along with cardiovascular disease, which is the leading cause of poor prognosis for these patients. The specific objective of our study was to characterize the relationship between the inflammatory status, the bone disorders markers, and kidney failure in chronic kidney disease patient stages 2-4, in order to design a novel biomarker panel that improves early disease diagnosis and therapeutic response, thus being further integrated into clinical applications. A panel of proteomic biomarkers, assessed by xMAP array, which includes mediators of inflammation (IL-6, TNF-α) and mineral and bone disorder biomarkers (OPG, OPN, OCN, FGF-23, and Fetuin-A), was found to be more relevant than a single biomarker to detect early CKD stages. The association between inflammatory cytokines and bone disorders markers, IL-6, TNF-α, OPN, OPG, and FGF-23, reflects the severity of vascular changes in CKD and predicts disease progression. Proteomic xMAP analyses shed light on a new approach to clinical evaluation for CKD staging and prognosis.

Prevalence of steatosis and insulin resistance in patients with chronic hepatitis B compared with chronic hepatitis C and non-alcoholic fatty liver disease.

UNLABELLED: The association of NAFLD with chronic hepatitis C (CHC) has been extensively studied but little is known about its coexistence with chronic hepatitis B (CHB). AIMS: To investigate the prevalence and determinants of steatosis and insulin resistance (IR) in CHB and its consequences on liver injury compared with CHC and NAFLD. METHODS: Patients with CHB (N=110), CHC (N=111) and NAFLD (N=136) were evaluated by biomarkers of steatosis (SteatoTest>0.38 as a surrogate for steatosis >5%), IR (HOMA-IR>2.7 as a surrogate for IR) and fibrosis (FibroTest>0.48 as a surrogate for significant fibrosis, ≥F2). RESULTS: HOMA-IR gradually increased in CHB, CHC and NAFLD: 2.3±1.8; 3±2.6 and 3.8±2.7 (p<0.001). The prevalence of steatosis >5% was 21% (CHB), 43% (CHC) and 82% (NAFLD), (p<0.001). The prevalence of fibrosis≥F2 was 10% (CHB), 42% (CHC) and 21% (NAFLD), p<0.001. In CHB, IR was related to host and not viral factors. CHB patients with steatosis had higher BMI (29±5.7kg/m(2) vs. 24±4kg/m(2), p<0.001), waist circumference (96±14cm vs. 84±11cm, p=0.001) and HOMA-IR (3.9±2.6 vs. 1.8±1.2, p<0.001) than those without steatosis. HOMA-IR independently predicted steatosis in CHB (OR=1.9, 95% CI, 1.09-3.27, p<0.05) and CHC (OR=1.38; 95% CI, 1.07-1.78, p<0.02). In CHB, metabolic risk factors and HOMA-IR were not associated with significant fibrosis. HOMA-IR was an independent predictor of fibrosis in CHC. CONCLUSIONS: Steatosis may co-exist in CHB patients but with a lower prevalence than in CHC and NAFLD. In CHB steatosis is related to host and not viral factors, and is not associated with the severity of fibrosis.