Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,im...Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.展开更多
Introduction Human papillomavirus(HPV)vaccination is a cornerstone of cervical cancer prevention,particularly in low-and middle-income countries(LMICs),where the burden of disease remains high~1.The World Health Organ...Introduction Human papillomavirus(HPV)vaccination is a cornerstone of cervical cancer prevention,particularly in low-and middle-income countries(LMICs),where the burden of disease remains high~1.The World Health Organization(WHO)HPV Vaccine Introduction Clearing House reported that 147 countries(of 194 reporting)had fully introduced the HPV vaccine into their national schedules as of 20242.After COVID-19 pandemic disruptions,global coverage is again increasing.展开更多
The field of biometric identification has seen significant advancements over the years,with research focusing on enhancing the accuracy and security of these systems.One of the key developments is the integration of d...The field of biometric identification has seen significant advancements over the years,with research focusing on enhancing the accuracy and security of these systems.One of the key developments is the integration of deep learning techniques in biometric systems.However,despite these advancements,certain challenges persist.One of the most significant challenges is scalability over growing complexity.Traditional methods either require maintaining and securing a growing database,introducing serious security challenges,or relying on retraining the entiremodelwhen new data is introduced-a process that can be computationally expensive and complex.This challenge underscores the need for more efficient methods to scale securely.To this end,we introduce a novel approach that addresses these challenges by integrating multimodal biometrics,cancelable biometrics,and incremental learning techniques.This work is among the first attempts to seamlessly incorporate deep cancelable biometrics with dynamic architectural updates,applied incrementally to the deep learning model as new users are enrolled,achieving high performance with minimal catastrophic forgetting.By leveraging a One-Dimensional Convolutional Neural Network(1D-CNN)architecture combined with a hybrid incremental learning approach,our system achieves high recognition accuracy,averaging 98.98% over incrementing datasets,while ensuring user privacy through cancelable templates generated via a pre-trained CNN model and random projection.The approach demonstrates remarkable adaptability,utilizing the least intrusive biometric traits like facial features and fingerprints,ensuring not only robust performance but also long-term serviceability.展开更多
BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM)are independent risk factors for the development of cardiovascular disease(CVD)and an exaggerated CVD risk is exp...BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM)are independent risk factors for the development of cardiovascular disease(CVD)and an exaggerated CVD risk is expected when both diseases co-exist.Therefore,thorough risk stratification is important to inform better clinical practice decisions based on good quality evidence for patient with MAFLD and T2DM.AIM To identify the CVD and cardiovascular event(CVE)risk in a systematic review when MAFLD and T2DM co-exist to inform better clinical practice decisions.METHODS A systematic review was performed by compiling data by searching PubMed,EMBASE and Cochrane Library databases.Quality appraisal of retrieved studies and the meta-analysis were performed using Joanna Briggs Institute(JBI)tool and RevMan 5.4 software respectively.The effect indicators for CVE and CVD risk were expressed as odds ratios(OR)and 95%CI with P-values<0.05 as significant.RESULTS Fourteen(5 cohort and 9 cross-sectional)studies with 370013 participants were included in this review.The metaanalysis of CVE showed that the risk of CVE in T2DM was higher in the MAFLD group when compared to the non-MAFLD group[OR 1.28(95%CI,1.04-1.56)P=0.02]with follow up duration ranging between 5-6 years.The prevalence of CVD in the metanalysis of cross-sectional studies was found to be higher[OR 1.47(95%CI,1.21-1.78)P=0.0001]in T2DM with MAFLD when compared to T2DM without MAFLD.Significant heterogeneity exists due to variations in study design,methodologies,and MAFLD diagnostic criteria,which may have influenced the study's findings.CONCLUSION The presence of MAFLD in T2DM increased the risk of CVE.The prevalence of CVD is higher in T2DM with MAFLD as compared to T2DM without MAFLD.Large well-designed multicentric long-term prospective studies are necessary to appropriately risk stratify the cardiovascular effect of the MAFLD in T2DM patients.展开更多
Pancreatic neuroendocrine tumors(pNETs)are rare,presenting significant challenges in timely diagnosis and subsequent treatment.The clinical and pathobiological behavior of these tumors varies significantly,making foll...Pancreatic neuroendocrine tumors(pNETs)are rare,presenting significant challenges in timely diagnosis and subsequent treatment.The clinical and pathobiological behavior of these tumors varies significantly,making follow-up and therapeutic approaches challenging for clinicians.Although the majority of these neoplasms are hormonally inactive,some can be associated with endocrine dysfunction.Very rarely,a nonfunctional tumor can later become hormonally active,further complicating prognostication and management.Depending on the character of the disease,clinical picture and prognosis,different treatment modalities are instituted with varying effectivities.We recently came across a unique case of nonfunctioning malignant pNET at an advanced stage,metastatic disease upon diagnosis,managed medically with somatostatin analog therapy(Octreotide)and targeted therapy(Everolimus)with stable disease for 40 months that subsequently turned out to become functional(insulinoma).With the aid of this unique case,we update the current clinical,diagnostic and therapeutic approach to pNETs in this evidence-based review.展开更多
BACKGROUND Type 2 diabetes(T2D),as well as obesity,are risk factors for chronic kidney disease(CKD)and end-stage renal disease.The renal impacts of glucose-lowering and weight-lowering drugs and their potential benefi...BACKGROUND Type 2 diabetes(T2D),as well as obesity,are risk factors for chronic kidney disease(CKD)and end-stage renal disease.The renal impacts of glucose-lowering and weight-lowering drugs and their potential benefits in preventing CKD often guide clinicians in choosing them appropriately.Only limited data based on randomized controlled trials(RCTs)is currently available on the renal effects and safety profile of tirzepatide.AIM To explore the renal benefits and safety of tirzepatide vs controls.METHODS RCTs involving patients receiving tirzepatide for any indication in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases.The co-primary outcomes were percent change from baseline(CFB)in urine albumin-to-creatinine ratio(UACR)and absolute CFB in estimated glomerular filtration rate(eGFR;in mL/min/1.73 m^(2));the secondary outcome was tirzepatide’s renal safety profile.RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as mean differences(MD)or risk ratios with 95%confidence intervals.RESULTS Fifteen RCTs(n=14471)with mostly low risk of bias(RoB)were included.Over 26-72 weeks,tirzepatide 10 mg[MD-26.95%(-40.13,-13.76),P<0.0001]and 15 mg[MD-18.03%(-28.58,-7.47),P=0.0008]were superior to placebo in percent reductions of UACR.Tirzepatide,at all doses,outperformed insulin in percent reductions of UACR.Compared to the placebo,the percent UACR reduction was greater in subjects with T2D than those with obesity but without T2D(MD-33.25%vs-7.93%;P=0.001).The CFB in eGFR with all doses of tirzepatide was comparable[5 mg:MD 0.36(-1.41,2.14);10 mg:MD 1.17(-0.22,2.56);15 mg:MD 1.42(-0.04,2.88)];P>0.05 for all vs insulin.Tirzepatide(pooled and separate doses)did not increase the risks of adverse renal events,urinary tract infection,nephrolithiasis,acute kidney injury,and renal cancer compared to the placebo,insulin,and glucagon-like peptide-1 receptor agonists.CONCLUSION Short-term data from RCTs with low RoB suggests that tirzepatide positively impacts UACR without detrimental effects on eGFR in subjects with T2D and obesity without T2D,with a reassuring renal safety profile.Larger RCTs are warranted to prove the longer-term renal benefits of tirzepatide,which might also prevent eGFR decline and worsening of CKD.展开更多
BACKGROUND Diabesity(diabetes as a consequence of obesity)has emerged as a huge healthcare challenge across the globe due to the obesity pandemic.Judicious use of antidiabetic medications including semaglutide is impo...BACKGROUND Diabesity(diabetes as a consequence of obesity)has emerged as a huge healthcare challenge across the globe due to the obesity pandemic.Judicious use of antidiabetic medications including semaglutide is important for optimal management of diabesity as proven by multiple randomized controlled trials.However,more real-world data is needed to further improve the clinical practice.AIM To study the real-world benefits and side effects of using semaglutide to manage patients with diabesity.METHODS We evaluated the efficacy and safety of semaglutide use in managing patients with diabesity in a large academic hospital in the United States.Several parameters were analyzed including demographic information,the data on improvement of glycated hemoglobin(HbA1c),body weight reduction and insulin dose adjustments at 6 and 12 months,as well as at the latest follow up period.The data was obtained from the electronic patient records between January 2019 to May 2023.RESULTS 106 patients(56 males)with type 2 diabetes mellitus(T2DM),mean age 60.8±11.2 years,mean durations of T2DM 12.4±7.2 years and mean semaglutide treatment for 2.6±1.1 years were included.Semaglutide treatment was associated with significant improvement in diabesity outcomes such as mean weight reductions from baseline 110.4±24.6 kg to 99.9±24.9 kg at 12 months and 96.8±22.9 kg at latest follow up and HbA1c improvement from baseline of 82±21 mmol/mol to 67±20 at 12 months and 71±23 mmol/mol at the latest follow up.An insulin dose reduction from mean baseline of 95±74 units to 76.5±56.2 units was also observed at the latest follow up.Side effects were mild and mainly gastrointestinal like bloating and nausea improving with prolonged use of semaglutide.CONCLUSION Semaglutide treatment is associated with significant improvement in diabesity outcomes such as reduction in body weight,HbA1c and insulin doses without major adverse effects.Reviews of largescale real-world data are expected to inform better clinical practice decision making to improve the care of patients with diabesity.展开更多
BACKGROUND Sodium glucose cotransporter-2 inhibitors(SGLT-2i)are a class of drugs with modest antidiabetic efficacy,weight loss effect,and cardiovascular benefits as proven by multiple randomised controlled trials(RCT...BACKGROUND Sodium glucose cotransporter-2 inhibitors(SGLT-2i)are a class of drugs with modest antidiabetic efficacy,weight loss effect,and cardiovascular benefits as proven by multiple randomised controlled trials(RCTs).However,real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse.AIM To study the comparative efficacy and safety of SGLT-2i using real-world clinical data.METHODS We evaluated the comparative efficacy data of 3 SGLT-2i drugs(dapagliflozin,canagliflozin,and empagliflozin)used for treating patients with type 2 diabetes mellitus.Data on the reduction of glycated hemoglobin(HbA1c),body weight,blood pressure(BP),urine albumin creatinine ratio(ACR),and adverse effects were recorded retrospectively.RESULTS Data from 467 patients with a median age of 64(14.8)years,294(62.96%)males and 375(80.5%)Caucasians were analysed.Median diabetes duration was 16.0(9.0)years,and the duration of SGLT-2i use was 3.6(2.1)years.SGLT-2i molecules used were dapagliflozin 10 mg(n=227;48.6%),canagliflozin 300 mg(n=160;34.3%),and empagliflozin 25 mg(n=80;17.1).Baseline median(interquartile range)HbA1c in mmol/mol were:dapagliflozin-78.0(25.3),canagliflozin-80.0(25.5),and empagliflozin-75.0(23.5)respectively.The respective median HbA1c reduction at 12 months and the latest review(just prior to the study)were:66.5(22.8)&69.0(24.0),67.0(16.3)&66.0(28.0),and 67.0(22.5)&66.5(25.8)respectively(P<0.001 for all comparisons from baseline).Significant improvements in body weight(in kilograms)from baseline to study end were noticed with dapagliflozin-101(29.5)to 92.2(25.6),and canagliflozin 100(28.3)to 95.3(27.5)only.Significant reductions in median systolic and diastolic BP,from 144(21)mmHg to 139(23)mmHg;(P=0.015),and from 82(16)mmHg to 78(19)mmHg;(P<0.001)respectively were also observed.A significant reduction of microalbuminuria was observed with canagliflozin only[ACR 14.6(42.6)at baseline to 8.9(23.7)at the study end;P=0.043].Adverse effects of SGLT-2i were as follows:genital thrush and urinary infection-20(8.8%)&17(7.5%)with dapagliflozin;9(5.6%)&5(3.13%)with canagliflozin;and 4(5%)&4(5%)with empagliflozin.Diabetic ketoacidosis was observed in 4(1.8%)with dapagliflozin and 1(0.63%)with canagliflozin.CONCLUSION Treatment of patients with SGLT-2i is associated with statistically significant reductions in HbA1c,body weight,and better than those reported in RCTs,with low side effect profiles.A review of large-scale real-world data is needed to inform better clinical practice decision making.展开更多
Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome(HRS),outside of conventional understanding that liver cirrhosis is traditionally considered the sole ...Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome(HRS),outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context.In the absence of established heart disease,cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease.It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities.Despite the clinical description of these potential cardiac-related complications of the liver,the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS.Yet from a physiological sense,temporality(prior onset)of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients.In this review,we discuss current concepts surrounding how the heart may influence the development and progression of HRS,and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting.The temporality of heart and kidney dysfunction in HRS will be discussed.For a subgroup of patients who receive portosystemic shunting,the dynamics of cardiorenal interactions following treatment is reviewed.Continued research to determine the unknowns in this topic is anticipated,hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.展开更多
Bariatric interventions have shown the best therapeutic benefits in individuals with obesity.They can be classified into surgical procedures(bariatric/metabolic surgery)and endoscopic procedures.Common surgical proced...Bariatric interventions have shown the best therapeutic benefits in individuals with obesity.They can be classified into surgical procedures(bariatric/metabolic surgery)and endoscopic procedures.Common surgical procedures include sleeve gastrectomy,Roux-en-Y gastric bypass,bilio-pancreatic diversion with or without duodenal switch and Stomach Intestinal Pylorus Sparing Surgery.Endoscopic procedures include intragastric balloons,transpyloric shuttle,endoscopic gastroplasties,aspiration therapy,duodenal mucosal resurfacing,duodeno-jejunal bypass liner,gastro-duodeno-jejunal bypass and incisionless magnetic anastomosis system among others.However,these procedures are limited by lack of wide availability,high costs,immediate and long-term complications and poor acceptability in some regions.Weight re-gain is a common concern and revisional metabolic surgery is often required.Appropriate pre-operative evaluation and correction of nutritional deficiencies post-surgery are very important.The most appropriate procedure for a person would depend on multiple factors like the intended magnitude of weight-loss,comorbidities and surgical fitness,as well as choice of the patient.Recently,glucagon-like insulinotropic peptide-1 receptor agonists(GLP)and the GLP-1/gastric inhibitory polypeptide co-agonist-Tirzepatide have shown remarkable weight loss potential,which is at par with bariatric interventions in some patients.How far these can help in avoiding invasive bariatric procedures in near future remains to be explored.An updated and comprehensive clinical review by He et al in the recent issue of World Journal of Diabetes address has addressed the avenues and challenges of currently available bariatric surgeries which will enable clinicians to make better decisions in their practice,including their applicability in special populations like the elderly and pediatric age groups,type 1 diabetes mellitus,and non-diabetics.展开更多
While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a p...While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin.Although,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also encountered.The World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et al.It is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical problem.This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.展开更多
The bidirectional association between type 2 diabetes mellitus(T2DM)and periodontitis is now well established,resulting in periodontal disease being considered as the 6th major complication of diabetes mellitus(DM)aft...The bidirectional association between type 2 diabetes mellitus(T2DM)and periodontitis is now well established,resulting in periodontal disease being considered as the 6th major complication of diabetes mellitus(DM)after cardiovascular disease,eye disease,neuropathy,nephropathy,and peripheral vascular disease.DM can worsen the virulence and invasiveness of pathogenic oral microbial flora aggravating the local inflammation and infection in those with periodontal disease.On the other hand,the chemical and immunological mediators released into the circulation as part of periodontal inflammation worsen the systemic insulin resistance with worsening of T2DM.Periodontitis if undiagnosed or left untreated can also result in eventual tooth loss.A study by Xu et al in the World Journal of Diabetes examined the predictive factors associated with periodontitis in Chinese patients with T2DM.The prevalence of periodontitis was found to be 75.7%in this study.Based on logistic regression analysis,the predictive factors for higher risk were low tooth brushing frequency[odds ratio(OR)=4.3],high triglycerides(TG;OR=3.31),high total cholesterol(TC;OR=2.87),higher glycated hemoglobin(HbA1c;OR=2.55),and higher age(OR=1.05)while higher education level was protective(OR=0.53).However,the most influential variables were HbA1c followed by age,TC,TG,low education level,brushing frequency,and sex on the random forest model(this model showed higher sensitivity for predicting the risk).A good understanding of the predictors for periodontitis in T2DM patients is important in prevention,early detection of susceptible patients,and intervention to improve periodontal health and enable long-term glycaemic control as observed by Xu et al.展开更多
文摘Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.
文摘Introduction Human papillomavirus(HPV)vaccination is a cornerstone of cervical cancer prevention,particularly in low-and middle-income countries(LMICs),where the burden of disease remains high~1.The World Health Organization(WHO)HPV Vaccine Introduction Clearing House reported that 147 countries(of 194 reporting)had fully introduced the HPV vaccine into their national schedules as of 20242.After COVID-19 pandemic disruptions,global coverage is again increasing.
基金the Deputyship for Research&Innovation,Ministry of Education in Saudi Arabia for funding this research work through project number RI-44-0833.
文摘The field of biometric identification has seen significant advancements over the years,with research focusing on enhancing the accuracy and security of these systems.One of the key developments is the integration of deep learning techniques in biometric systems.However,despite these advancements,certain challenges persist.One of the most significant challenges is scalability over growing complexity.Traditional methods either require maintaining and securing a growing database,introducing serious security challenges,or relying on retraining the entiremodelwhen new data is introduced-a process that can be computationally expensive and complex.This challenge underscores the need for more efficient methods to scale securely.To this end,we introduce a novel approach that addresses these challenges by integrating multimodal biometrics,cancelable biometrics,and incremental learning techniques.This work is among the first attempts to seamlessly incorporate deep cancelable biometrics with dynamic architectural updates,applied incrementally to the deep learning model as new users are enrolled,achieving high performance with minimal catastrophic forgetting.By leveraging a One-Dimensional Convolutional Neural Network(1D-CNN)architecture combined with a hybrid incremental learning approach,our system achieves high recognition accuracy,averaging 98.98% over incrementing datasets,while ensuring user privacy through cancelable templates generated via a pre-trained CNN model and random projection.The approach demonstrates remarkable adaptability,utilizing the least intrusive biometric traits like facial features and fingerprints,ensuring not only robust performance but also long-term serviceability.
文摘BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM)are independent risk factors for the development of cardiovascular disease(CVD)and an exaggerated CVD risk is expected when both diseases co-exist.Therefore,thorough risk stratification is important to inform better clinical practice decisions based on good quality evidence for patient with MAFLD and T2DM.AIM To identify the CVD and cardiovascular event(CVE)risk in a systematic review when MAFLD and T2DM co-exist to inform better clinical practice decisions.METHODS A systematic review was performed by compiling data by searching PubMed,EMBASE and Cochrane Library databases.Quality appraisal of retrieved studies and the meta-analysis were performed using Joanna Briggs Institute(JBI)tool and RevMan 5.4 software respectively.The effect indicators for CVE and CVD risk were expressed as odds ratios(OR)and 95%CI with P-values<0.05 as significant.RESULTS Fourteen(5 cohort and 9 cross-sectional)studies with 370013 participants were included in this review.The metaanalysis of CVE showed that the risk of CVE in T2DM was higher in the MAFLD group when compared to the non-MAFLD group[OR 1.28(95%CI,1.04-1.56)P=0.02]with follow up duration ranging between 5-6 years.The prevalence of CVD in the metanalysis of cross-sectional studies was found to be higher[OR 1.47(95%CI,1.21-1.78)P=0.0001]in T2DM with MAFLD when compared to T2DM without MAFLD.Significant heterogeneity exists due to variations in study design,methodologies,and MAFLD diagnostic criteria,which may have influenced the study's findings.CONCLUSION The presence of MAFLD in T2DM increased the risk of CVE.The prevalence of CVD is higher in T2DM with MAFLD as compared to T2DM without MAFLD.Large well-designed multicentric long-term prospective studies are necessary to appropriately risk stratify the cardiovascular effect of the MAFLD in T2DM patients.
文摘Pancreatic neuroendocrine tumors(pNETs)are rare,presenting significant challenges in timely diagnosis and subsequent treatment.The clinical and pathobiological behavior of these tumors varies significantly,making follow-up and therapeutic approaches challenging for clinicians.Although the majority of these neoplasms are hormonally inactive,some can be associated with endocrine dysfunction.Very rarely,a nonfunctional tumor can later become hormonally active,further complicating prognostication and management.Depending on the character of the disease,clinical picture and prognosis,different treatment modalities are instituted with varying effectivities.We recently came across a unique case of nonfunctioning malignant pNET at an advanced stage,metastatic disease upon diagnosis,managed medically with somatostatin analog therapy(Octreotide)and targeted therapy(Everolimus)with stable disease for 40 months that subsequently turned out to become functional(insulinoma).With the aid of this unique case,we update the current clinical,diagnostic and therapeutic approach to pNETs in this evidence-based review.
文摘BACKGROUND Type 2 diabetes(T2D),as well as obesity,are risk factors for chronic kidney disease(CKD)and end-stage renal disease.The renal impacts of glucose-lowering and weight-lowering drugs and their potential benefits in preventing CKD often guide clinicians in choosing them appropriately.Only limited data based on randomized controlled trials(RCTs)is currently available on the renal effects and safety profile of tirzepatide.AIM To explore the renal benefits and safety of tirzepatide vs controls.METHODS RCTs involving patients receiving tirzepatide for any indication in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases.The co-primary outcomes were percent change from baseline(CFB)in urine albumin-to-creatinine ratio(UACR)and absolute CFB in estimated glomerular filtration rate(eGFR;in mL/min/1.73 m^(2));the secondary outcome was tirzepatide’s renal safety profile.RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as mean differences(MD)or risk ratios with 95%confidence intervals.RESULTS Fifteen RCTs(n=14471)with mostly low risk of bias(RoB)were included.Over 26-72 weeks,tirzepatide 10 mg[MD-26.95%(-40.13,-13.76),P<0.0001]and 15 mg[MD-18.03%(-28.58,-7.47),P=0.0008]were superior to placebo in percent reductions of UACR.Tirzepatide,at all doses,outperformed insulin in percent reductions of UACR.Compared to the placebo,the percent UACR reduction was greater in subjects with T2D than those with obesity but without T2D(MD-33.25%vs-7.93%;P=0.001).The CFB in eGFR with all doses of tirzepatide was comparable[5 mg:MD 0.36(-1.41,2.14);10 mg:MD 1.17(-0.22,2.56);15 mg:MD 1.42(-0.04,2.88)];P>0.05 for all vs insulin.Tirzepatide(pooled and separate doses)did not increase the risks of adverse renal events,urinary tract infection,nephrolithiasis,acute kidney injury,and renal cancer compared to the placebo,insulin,and glucagon-like peptide-1 receptor agonists.CONCLUSION Short-term data from RCTs with low RoB suggests that tirzepatide positively impacts UACR without detrimental effects on eGFR in subjects with T2D and obesity without T2D,with a reassuring renal safety profile.Larger RCTs are warranted to prove the longer-term renal benefits of tirzepatide,which might also prevent eGFR decline and worsening of CKD.
文摘BACKGROUND Diabesity(diabetes as a consequence of obesity)has emerged as a huge healthcare challenge across the globe due to the obesity pandemic.Judicious use of antidiabetic medications including semaglutide is important for optimal management of diabesity as proven by multiple randomized controlled trials.However,more real-world data is needed to further improve the clinical practice.AIM To study the real-world benefits and side effects of using semaglutide to manage patients with diabesity.METHODS We evaluated the efficacy and safety of semaglutide use in managing patients with diabesity in a large academic hospital in the United States.Several parameters were analyzed including demographic information,the data on improvement of glycated hemoglobin(HbA1c),body weight reduction and insulin dose adjustments at 6 and 12 months,as well as at the latest follow up period.The data was obtained from the electronic patient records between January 2019 to May 2023.RESULTS 106 patients(56 males)with type 2 diabetes mellitus(T2DM),mean age 60.8±11.2 years,mean durations of T2DM 12.4±7.2 years and mean semaglutide treatment for 2.6±1.1 years were included.Semaglutide treatment was associated with significant improvement in diabesity outcomes such as mean weight reductions from baseline 110.4±24.6 kg to 99.9±24.9 kg at 12 months and 96.8±22.9 kg at latest follow up and HbA1c improvement from baseline of 82±21 mmol/mol to 67±20 at 12 months and 71±23 mmol/mol at the latest follow up.An insulin dose reduction from mean baseline of 95±74 units to 76.5±56.2 units was also observed at the latest follow up.Side effects were mild and mainly gastrointestinal like bloating and nausea improving with prolonged use of semaglutide.CONCLUSION Semaglutide treatment is associated with significant improvement in diabesity outcomes such as reduction in body weight,HbA1c and insulin doses without major adverse effects.Reviews of largescale real-world data are expected to inform better clinical practice decision making to improve the care of patients with diabesity.
文摘BACKGROUND Sodium glucose cotransporter-2 inhibitors(SGLT-2i)are a class of drugs with modest antidiabetic efficacy,weight loss effect,and cardiovascular benefits as proven by multiple randomised controlled trials(RCTs).However,real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse.AIM To study the comparative efficacy and safety of SGLT-2i using real-world clinical data.METHODS We evaluated the comparative efficacy data of 3 SGLT-2i drugs(dapagliflozin,canagliflozin,and empagliflozin)used for treating patients with type 2 diabetes mellitus.Data on the reduction of glycated hemoglobin(HbA1c),body weight,blood pressure(BP),urine albumin creatinine ratio(ACR),and adverse effects were recorded retrospectively.RESULTS Data from 467 patients with a median age of 64(14.8)years,294(62.96%)males and 375(80.5%)Caucasians were analysed.Median diabetes duration was 16.0(9.0)years,and the duration of SGLT-2i use was 3.6(2.1)years.SGLT-2i molecules used were dapagliflozin 10 mg(n=227;48.6%),canagliflozin 300 mg(n=160;34.3%),and empagliflozin 25 mg(n=80;17.1).Baseline median(interquartile range)HbA1c in mmol/mol were:dapagliflozin-78.0(25.3),canagliflozin-80.0(25.5),and empagliflozin-75.0(23.5)respectively.The respective median HbA1c reduction at 12 months and the latest review(just prior to the study)were:66.5(22.8)&69.0(24.0),67.0(16.3)&66.0(28.0),and 67.0(22.5)&66.5(25.8)respectively(P<0.001 for all comparisons from baseline).Significant improvements in body weight(in kilograms)from baseline to study end were noticed with dapagliflozin-101(29.5)to 92.2(25.6),and canagliflozin 100(28.3)to 95.3(27.5)only.Significant reductions in median systolic and diastolic BP,from 144(21)mmHg to 139(23)mmHg;(P=0.015),and from 82(16)mmHg to 78(19)mmHg;(P<0.001)respectively were also observed.A significant reduction of microalbuminuria was observed with canagliflozin only[ACR 14.6(42.6)at baseline to 8.9(23.7)at the study end;P=0.043].Adverse effects of SGLT-2i were as follows:genital thrush and urinary infection-20(8.8%)&17(7.5%)with dapagliflozin;9(5.6%)&5(3.13%)with canagliflozin;and 4(5%)&4(5%)with empagliflozin.Diabetic ketoacidosis was observed in 4(1.8%)with dapagliflozin and 1(0.63%)with canagliflozin.CONCLUSION Treatment of patients with SGLT-2i is associated with statistically significant reductions in HbA1c,body weight,and better than those reported in RCTs,with low side effect profiles.A review of large-scale real-world data is needed to inform better clinical practice decision making.
文摘Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome(HRS),outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context.In the absence of established heart disease,cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease.It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities.Despite the clinical description of these potential cardiac-related complications of the liver,the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS.Yet from a physiological sense,temporality(prior onset)of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients.In this review,we discuss current concepts surrounding how the heart may influence the development and progression of HRS,and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting.The temporality of heart and kidney dysfunction in HRS will be discussed.For a subgroup of patients who receive portosystemic shunting,the dynamics of cardiorenal interactions following treatment is reviewed.Continued research to determine the unknowns in this topic is anticipated,hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.
文摘Bariatric interventions have shown the best therapeutic benefits in individuals with obesity.They can be classified into surgical procedures(bariatric/metabolic surgery)and endoscopic procedures.Common surgical procedures include sleeve gastrectomy,Roux-en-Y gastric bypass,bilio-pancreatic diversion with or without duodenal switch and Stomach Intestinal Pylorus Sparing Surgery.Endoscopic procedures include intragastric balloons,transpyloric shuttle,endoscopic gastroplasties,aspiration therapy,duodenal mucosal resurfacing,duodeno-jejunal bypass liner,gastro-duodeno-jejunal bypass and incisionless magnetic anastomosis system among others.However,these procedures are limited by lack of wide availability,high costs,immediate and long-term complications and poor acceptability in some regions.Weight re-gain is a common concern and revisional metabolic surgery is often required.Appropriate pre-operative evaluation and correction of nutritional deficiencies post-surgery are very important.The most appropriate procedure for a person would depend on multiple factors like the intended magnitude of weight-loss,comorbidities and surgical fitness,as well as choice of the patient.Recently,glucagon-like insulinotropic peptide-1 receptor agonists(GLP)and the GLP-1/gastric inhibitory polypeptide co-agonist-Tirzepatide have shown remarkable weight loss potential,which is at par with bariatric interventions in some patients.How far these can help in avoiding invasive bariatric procedures in near future remains to be explored.An updated and comprehensive clinical review by He et al in the recent issue of World Journal of Diabetes address has addressed the avenues and challenges of currently available bariatric surgeries which will enable clinicians to make better decisions in their practice,including their applicability in special populations like the elderly and pediatric age groups,type 1 diabetes mellitus,and non-diabetics.
文摘While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin.Although,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also encountered.The World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et al.It is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical problem.This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.
文摘The bidirectional association between type 2 diabetes mellitus(T2DM)and periodontitis is now well established,resulting in periodontal disease being considered as the 6th major complication of diabetes mellitus(DM)after cardiovascular disease,eye disease,neuropathy,nephropathy,and peripheral vascular disease.DM can worsen the virulence and invasiveness of pathogenic oral microbial flora aggravating the local inflammation and infection in those with periodontal disease.On the other hand,the chemical and immunological mediators released into the circulation as part of periodontal inflammation worsen the systemic insulin resistance with worsening of T2DM.Periodontitis if undiagnosed or left untreated can also result in eventual tooth loss.A study by Xu et al in the World Journal of Diabetes examined the predictive factors associated with periodontitis in Chinese patients with T2DM.The prevalence of periodontitis was found to be 75.7%in this study.Based on logistic regression analysis,the predictive factors for higher risk were low tooth brushing frequency[odds ratio(OR)=4.3],high triglycerides(TG;OR=3.31),high total cholesterol(TC;OR=2.87),higher glycated hemoglobin(HbA1c;OR=2.55),and higher age(OR=1.05)while higher education level was protective(OR=0.53).However,the most influential variables were HbA1c followed by age,TC,TG,low education level,brushing frequency,and sex on the random forest model(this model showed higher sensitivity for predicting the risk).A good understanding of the predictors for periodontitis in T2DM patients is important in prevention,early detection of susceptible patients,and intervention to improve periodontal health and enable long-term glycaemic control as observed by Xu et al.
