Clinical implications of diabetes in chronic liver disease:Diagnosis,outcomes and management,current and future perspectives

Diabetes mellitus(DM)is common in liver cirrhosis(LC).The pathophysiological association is bidirectional.DM is a risk factor of LC and LC is a diabetogenic condition.In the recent years,research on different aspects of the association DM and LC has been intensified.Nevertheless,it has been insufficient and still exist many gaps.The aims of this review are:(1)To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis;(2)To evaluate the impact of DM on outcomes of LC patients;and(3)To select the most adequate management benefiting the two conditions.Literature searches were conducted using Pub Med,Ovid and Scopus engines for DM and LC,diagnosis,outcomes and management.The authors also provided insight from their own published experience.Based on the published studies,two types of DM associated with LC have emerged:Type 2 DM(T2 DM)and hepatogenous diabetes(HD).High-quality evidences have determined that T2 DM or HD significantly increase complications and death pre and post-liver transplantation.HD has been poorly studied and has not been recognized as a complication of LC.The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure.In conclusion,the clinical impact of DM in outcomes of LC patients has been the most studied item recently.Nevertheless many gaps still exist particularly in the management.These most important gaps were highlighted in order to propose future lines for research.

Aortic stenosis： insights on pathogenesis and clinical implications

Aortic stenosis （AS） is a common valvular heart disease in the Western populations, with an estimated overall prevalence of 3% in adults over 75 years. To understand its patho-biological processes represents a priority. In elderly patients, AS usually involves trileaflet valves and is referred to as degenerative calcific processes. Scientific evidence suggests the involvement of an active ＂atherosclerosis-like＂ pathogenesis in the initiation phase of degenerative AS. To the contrary, the progression could be driven by different forces （such as mechanical stress, genetic factors and interaction between inflammation and calcification）. The improved understanding presents potentially new therapeutic targets for preventing and inhibiting the development and progression of the disease. Furthermore, in clinical practice the management of AS patients implies the evaluation of generalized atherosclerotic manifestations （i.e., in the coronary and carotid arteries） even for prognostic reasons. In counselling elderly patients, the risk stratification should address individual frailty beyond the generic risk scores. In these regard, the co-morbidities, and in particular those linked to the global atherosclerotic burden, should be carefully investigated in order to define the risk/benefit ratio for invasive treatment strategies. We present a detailed overview of insights in pathogenesis of AS with possible practical implications.

Detection of circulating tumour cells in colorectal cancer:Emerging techniques and clinical implications

Despite several advances in oncological management of colorectal cancer,morbidity and mortality are still high and devastating.The diagnostic evaluation by endoscopy is cumbersome,which is uncomfortable to many.Because of the intra-and inter-tumour heterogeneity and changing tumour dynamics,which is continuous in nature,the diagnostic biopsy and assessment of the pathological sample are difficult and also not adequate.Late manifestation of the disease and delayed diagnosis may lead to relapse or metastases.One of the keys to improving the outcome is early detection of cancer,ease of technology to detect with uniformity,and its therapeutic implications,which are yet to come."Liquid biopsy"is currently the most recent area of interest in oncology,which may provide important tools regarding the characterization of the primary tumour and its metastasis as cancer cells shed into the bloodstream even at the early stages of the disease.By using this approach,clinicians may be able to find out information about the tumour at a given time.Any of the following three types of sampling of biological material can be used in the"liquid biopsy".These are circulating tumour cells(CTCs),circulating tumour DNA,and exosomes.The most commonly studied amongst the three is CTCs.CTCs with their different applications and prognostic value has been found useful in colorectal cancer detection and therapeutics.In this review,we will discuss various markers for CTCs,the core tools/techniques for detection,and also important findings of clinical studies in colorectal cancer and its clinical implications.

Atypical variants of takotsubo cardiomyopathy: mechanistic and clinical implications

Over past decades,takotsubo cardiomyopathy(TTC)has drawn a substantial interest as a unique form of acute and reversible cardiomyopathy that usually emerges in response to adrenergic hyperactivation associated with a variety of emotional and physical triggers.[1,2]Even though,this phenomenon is generally characterized by an apical balloning pattern(classical variant),it might occasionally present with atypical morphological variants including mid-ventricular,inverted and focal forms of myocardial involvement.

DETERMINATION OF SERUM HARRINGTONINE IN PATIENTS WITH ANLL AND ITS CLINICAL IMPLICATION

Harringtonine(H) level in serum was quantified by high-performance liquid chromatographic (HPLC) technique and its pharmacokinetic parameters were determined in 11 patients with ANLL after 4 hours continuous infusion of 4 mg of H. 74 serum samples over the range of H administered 1-6 mg/d were also determined, the dose of H administered paralleled the mean serum H concentration, but the highest concentration were 1.6-7 folds higher than the lowest under the same doses. It seems that the dosage of harringtonine must be individualized in order to achieve better antileukemia effect. It was found that under the similar serum H concentration the marrow blast decrease index (MBDI) in types M4 and M5 of ANLL is much more greater than in M2 after the first course of chemotherapy and in 3 patients of M2, the serum H level and the MBDI show positive correlation.

Clinical implications of forkhead box M1, cyclooxygenase-2, and glucose-regulated protein 78 in breast invasive ductal carcinoma

BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expression profiles and clinical implications of forkhead box M1(FOXM1),cyclooxygenase-2(COX-2),and glucose-regulated protein 78(GRP78)in BIDC.METHODS A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis.The peripheral blood FOXM1,COX-2,and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined.Additionally,we investigated the diagnostic value of FOXM1,COX-2,and GRP78 in patients with BIDC and their correlations with clinicopathological features.Furthermore,BIDC patients were followed for 1 year to identify factors influencing patient prognosis.RESULTS The levels of FOXM1,COX-2,and GRP78 were significantly higher in BIDC patients compared to healthy controls(P<0.05),and a positive correlation was observed among them(P<0.05).Receiver operating characteristic analysis demonstrated that FOXM1,COX-2,and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC(P<0.05).Subsequently,we found significant differences in FOXM1,COX-2,and GRP78 levels among patients with different histological grades and metastasis statuses(with vs without)(P<0.05).Cox analysis revealed that FOXM1,COX-2,GRP78,increased histological grade,and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC(P<0.001).CONCLUSION FOXM1,COX-2,and GRP78 exhibit abnormally high expression in BIDC,promoting malignant tumor development and closely correlating with prognosis.These findings hold significant research implications for the future diagnosis and treatment of BIDC.

The possible role and clinical implication of myeloid-derived suppressor cells in the peripheral blood of patients with hepatitis B virus-related acute-on-chronic liver failure

Objective To explore the possible role and clinical implications of myeloid-derived suppressor cells(MDSC)in the peripheral blood of patients with hepatitis B virus(HBV)-related acute-on-chronic liver failure(HBVACLF).Methods A total of 25 HBV-ACLF patients

Evaluating the scope of human leukocyte antigen polymorphisms influencing hepatitis B virus-related liver cancer and cirrhosis through multi-clustering analysis

Hepatitis B virus remains a major cause of cirrhosis and hepatocellular carcinoma,with genetic polymorphisms and mutations influencing immune responses and disease progression.Nguyen et al present novel findings on specific human leukocyte antigen(HLA)alleles,including rs2856718 of HLA-DQ and rs3077 and rs9277535 of HLA-DP,which may predispose individuals to cirrhosis and liver cancer,based on multi-clustering analysis.Here,we discuss the feasibility of this approach and identify key areas for further investigation,aiming to offer insights for advancing clinical practice and research in liver disease and related cancers.

EFNA1 in gastrointestinal cancer:Expression,regulation and clinical significance

Ephrin-A1 is a protein that in humans is encoded by the EFNA1 gene.The ephrins and EPH-related receptors comprise the largest subfamily of receptor proteintyrosine kinases which play an indispensable role in normal growth and development or in the pathophysiology of various tumors.The role of EFNA1 in tumorigenesis and development is complex and depends on the cell type and microenvironment which in turn affect the expression of EFNA1.This article reviews the expression,prognostic value,regulation and clinical significance of EFNA1 in gastrointestinal tumors.

Exploring the connection between BRCA2 and thyroid cancer

Background:This study investigated the multifaceted role of BRCA2(breast cancer 2)in various cancer types,with a specific focus on thyroid carcinoma(THCA).Methods:Data sets were obtained from the University of California Santa Cruz database to analyze BRCA2 expression,genetic alterations,and clinical implications.Sample filtering criteria were applied,and immunohistochemistry from the Human Protein Atlas was used to validate protein expression.Correlation analyses were used to explore associations between immune-related genes,and immunological signatures were assessed using various tools.Genetic alterations in BRCA2 were analyzed using cBioPortal,and prognostic analysis involved evaluating gene expression differences at different clinical stages of THCA.Results:In patients with THCA,differences in BRCA2 expression were observed at both the mRNA and protein levels when comparing tumor and normal tissues.Correlation studies revealed associations between BRCA2 and immune-related genes,emphasizing its potential role in modulating the tumor microenvironment.Immunological signature analyses indicated distinct frequencies of tumor-infiltrating immune cell subsets in BRCA2 high versus low tumors.Moreover,genetic alterations in BRCA2,particularly the A2738S mutation in exon 18,have been identified in patients with THCA.The prognostic analysis demonstrated a significant correlation between altered BRCA2 levels and improved overall survival in patients with THCA.Additionally,BRCA2 expression was associated with prognostic factors such as stage and N.Conclusions:This study provides a holistic exploration of BRCA2 in cancer and highlights its diverse roles in expression,immune modulation,genetic alterations,and clinical prognosis.These findings underscore the potential significance of BRCA2 as a diagnostic and prognostic marker and offer valuable insights for future research and potential clinical applications in cancer management.

Colorectal cancer:Artificial intelligence and its role in surgical decision making

Despite several advances in the oncological management of colorectal cancer(CRC),there still remains a lacuna in the treatment strategy,which differs from center to center and on the philosophy of the treating clinician that is not without bias.Personalized treatment is essential for the treatment of CRC to achieve better long-term outcomes and to reduce morbidity.Surgery has an important role to play in the treatment.Surgical treatment of CRC is decided based on clinical parameters and investigations and hence likely to have judgmental errors.Artificial intelligence has been reported to be useful in the surveillance,diagnosis,treatment,and follow-up with accuracy in several malignancies.However,it is still evolving and yet to be established in surgical decision making in CRC.It is not only useful preoperatively but also intraoperatively.Artificial intelligence helps to rectify the human surgical decision when clinical data and radiological and laboratory parameters are fed into the computer and may guide correct surgical treatment.

Advancements in diabetic retinopathy:Insights and future directions

This editorial discusses recent advancements and ongoing challenges in diabetic retinopathy,as reviewed by Morya et al in their comprehensive analysis.In their review,Morya et al discussed the pathophysiology of diabetic retinopathy and explored novel treatment modalities.This editorial highlights the importance of these advancements and emphasizes the need for continued research and innovation for the enhanced management of diabetic retinopathy.It also reflects upon the implications of the authors’review findings for clinical practice and future research directions,underscoring the potential of emerging therapies for improving patient outcomes and providing a deeper understanding of disease mechanisms.

Enhancing the outcomes of diabetic vitrectomy with pharmacological adjuvants

This editorial offers insights from a minireview by Venkatesh et al,who explored pharmacological adjuvants for diabetic vitrectomy.Specifically,they synthesized current knowledge and evaluated the efficacy of various adjunctive therapies in improving the outcomes of diabetic retinopathy and managing associated complications.Herein,we highlight the key roles of pharmacological adjuvants in optimizing surgical techniques,minimizing intraoperative challenges,and enhancing postoperative recovery.We further discuss the potential implications of this approach for clinical practice and future research directions in this evolving field.Overall,this editorial underscores the importance of incorporating pharmacological adjuvants into standard diabetic vitrectomy care to improve surgical outcomes and thus patients’quality of life.

Application of anterior scleral thickness measurement in different ocular conditions using anterior segment optical coherence tomography:a systemic review

Purpose:To conduct a review to systematically evaluate the use of anterior segment optical coherence tomography(AS-OCT)in measuring anterior scleral thickness across diverse ocular conditions and its clinical implications.Methods:Literature search was conducted across electronic databases,including PubMed,Scopus,and Embase,to identify relevant studies.The risk of bias was assessed,and the main characteristics of each studies were analyzed.We calculated the overall mean anterior scleral thickness using the data which have measurement at the same locations.Results:A total of 32 studies were included that utilized AS-OCT to measure anterior scleral thickness in both healthy subjects and individuals with ocular disorders such as myopia,keratoconus,scleritis,and others.The review found that anterior scleral thickness is significantly influenced by age,diurnal variation,and specific ocular conditions.For example,myopic eyes may exhibit thinner sclera,particularly along certain meridians,while conditions like scleritis showed increased scleral thickness due to inflammation.However,some studies have inconsistent results.Additionally,AS-OCT proved effective in detecting subtle variations in anterior scleral thickness,which could be linked to the progression of ocular diseases.Conclusions:Anterior scleral thickness varies considerably depending on age,time of day,and ocular health,making it a valuable parameter in the assessment of eye conditions.AS-OCT's ability to measure these variations non-invasively broadens its application in both clinical practice and research,offering new insights into the biomechanical properties of the sclera and their implications for ocular diseases.

The role and clinical applications of exosomes in cancer drug resistance

Tumor-secreted exosomes are heterogeneous multi-signal messengers that support cancer growth and dissemination by mediating intercellular crosstalk and activating signaling pathways.Distinct from previous reviews,we focus intently on exosome-therapeutic resistance dynamics and summarize the new findings about the regulation of cancer treatment resistance by exosomes,shedding light on the complex processes via which these nanovesicles facilitate therapeutic refractoriness across various malignancies.Future research in exosome biology can potentially transform diagnostic paradigms and therapeutic interventions for cancer management.This review synthesizes recent insights into the exosome-driven regulation of cancer drug resistance,illuminates the sophisticated mechanisms by which these nanovesicles facilitate therapeutic refractoriness across various malignancies,and summarizes some strategies to overcome drug resistance.

Navigating the complex role of senescence in liver disease

Cellular senescence,an irreversible state of cell cycle arrest characterized by phenotypic changes and a specific secretory profile,plays a dual role in liver health and disease.Under physiological conditions,senescence aids organ repair and regeneration,but its accumulation due to aging or pathological stress significantly contributes to chronic liver diseases,including alcoholic liver disease,metabolic dysfunction-associated steatohepatitis,liver fibrosis,and hepatocellular carcinoma.Senescence is identified by a range of cellular and molecular changes,such as morphological alterations,expression of cell cycle inhibitors,senescence-associated β-galactosidase activity,and nuclear membrane changes.The onset of senescence in organ cells can affect the entire organism,primarily through the senescence-associated secretory phenotype,which has autocrine,paracrine,and endocrine effects on tissue microenvironments.The objective of this review is to offer a contemporary overview of the pathophysiological events involving hepatic senescent cells and to elucidate their role in the onset and progression of liver diseases,particularly through mechanisms like telomere shortening,genomic and mitochondrial DNA damage,and inflammation.Additionally,this review discusses the emerging senolytic therapies aimed at targeting senescent cells to delay or mitigate liver disease progression.The therapeutic potential of these interventions,alongside their safety and effectiveness,highlights the need for further research to refine these approaches and address unresolved problems in the field of hepatic cellular senescence.