Endoscopic retrograde cholangiopancreatography(ERCP)in patients with surgically altered anatomy remains a challenging field in therapeutic endoscopy due to the complex anatomical reconstructions that limit access to t...Endoscopic retrograde cholangiopancreatography(ERCP)in patients with surgically altered anatomy remains a challenging field in therapeutic endoscopy due to the complex anatomical reconstructions that limit access to the biliary tree.Over the past two decades,device-assisted enteroscopy(DAE),including singleballoon,double-balloon,and motorized spiral enteroscopy,has expanded the feasibility of ERCP in this population,with overall technical success rates generally reported between 70%and 90%.Nevertheless,these techniques are technically demanding,time-consuming,and frequently affected by limited reach and unstable positioning.More recently,interventional endoscopic ultrasound(EUS)-guided procedures have emerged as highly effective alternatives,significantly improving clinical outcomes in selected patients,particularly in those with long-limb Roux-en-Y reconstructions where conventional methods are less effective.Percutaneous transhepatic biliary drainage continues to represent a valuable salvage option when endoscopic approaches fail,though it is associated with a greater burden of reinterventions and adverse events.This minireview provides a comprehensive overview of the main endoscopic strategies for biliary drainage in altered anatomy,focusing on technical considerations,efficacy,and safety profiles of DAE-assisted ERCP,EUS-guided interventions,and motorized systems.The evolving landscape of biliary drainage in this setting highlights the need for tailored treatment strategies,multidisciplinary collaboration,referral to high-volume centers,and further prospective studies to refine patient selection and optimize clinical outcomes.展开更多
Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to i...Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.展开更多
Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves ...Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.展开更多
Prognostication of compensated advanced chronic liver disease(cACLD)is of paramount importance for the physician-and-patient communication and for rational clinical decisions.The paper published by Dallio et al report...Prognostication of compensated advanced chronic liver disease(cACLD)is of paramount importance for the physician-and-patient communication and for rational clinical decisions.The paper published by Dallio et al reports on red cell distribution width(RDW)/platelet ratio(RPR)as a non-invasive biomarker in predicting decompensation of metabolic dysfunction-associated steatotic liver disease(MASLD)-related cACLD.Differently from other biomarkers and algorithms,RPR is inexpensive and widely available,based on parameters which are included in a complete blood count.RPR is computed on the grounds of two different items,one of which,RDW,mirrors the host’s response to a variety of disease stimuli and is non-specific.The second parameter involved in RPR,platelet count,is more specific and has been used in the hepatological clinic to discriminate cirrhotic from non-cirrhotic chronic liver disease for decades.Cardiovascular disease is the primary cause of mortality among MASLD subjects,followed by extra-hepatic cancers and liver-related mortality.Therefore,MASLD biomarkers should be validated not only in terms of liver-related events but also in the prediction of major adverse cardiovascular events and cardiovascular mortality and extra-hepatic cancers.Adequately sized multi-ethnic confirmatory investigation is required to define the role and significance of RPR in the stratification of MASLD-cACLD.展开更多
This editorial is a commentary on the case report by Furuya et al focusing on the challenging diagnosis of early pancreatic adenocarcinoma and new tools for an earlier diagnosis.Currently,pancreatic cancer still has a...This editorial is a commentary on the case report by Furuya et al focusing on the challenging diagnosis of early pancreatic adenocarcinoma and new tools for an earlier diagnosis.Currently,pancreatic cancer still has a poor prognosis,mainly due to late diagnosis in an advanced stage.Two main precancerous routes have been identified as pathways to pancreatic adenocarcinoma:The first encompasses a large group of mucinous cystic lesions:intraductal papillary mucinous neoplasm and mucinous cystic neoplasm,and the second is pancreatic intraepithelial neoplasia.In the last decade the focus of research has been to identify high-risk patients,using advanced imaging techniques(magnetic resonance cholangiopancreatography or endoscopic ultrasonography)which could be helpful in finding“indirect signs”of early stage pancreatic lesions.Nevertheless,the survival rate still remains poor,and alternative screening methods are under investigation.Endoscopic retrograde cholangiopancreatography followed by serial pancreatic juice aspiration cytology could be a promising tool for identifying precursor lesions such as intraductal papillary mucinous neoplasm,but confirming data are still needed to validate its role.Probably a combination of cross-sectional imaging,endoscopic techniques(old and new ones)and genetic and biological biomarkers also in pancreatic juice)could be the best solution to reach an early diagnosis.Biomarkers could help to predict and follow the progression of early pancreatic lesions.However,further studies are needed to validate their diagnostic reliability and to establish diagnostic algorithms to improve prognosis and survival in patients with pancreatic cancer.展开更多
Caffeine is a widely consumed stimulant known for its cardiovascular and metabolic effects.However,its impact on cardiovascular risk,including arrhythmias,in older adults remains underexplored.Emerging evidence highli...Caffeine is a widely consumed stimulant known for its cardiovascular and metabolic effects.However,its impact on cardiovascular risk,including arrhythmias,in older adults remains underexplored.Emerging evidence highlights sex-specific differences in caffeine metabolism,which may influence its role in cardiovascular health.This perspective examines the interaction between caffeine,hormonal changes,metabolic processes,and lifestyle factors,focusing on older women compared to men.Understanding these differences is essential for tailoring dietary and clinical recommendations to mitigate cardiovascular risks and promote healthy aging.展开更多
Approximately 5%of patients with renal cancer present with synchronous bilateral renal masses(SBRM).1,2 Bilateral renal tumors associated with hereditary syndromes often exhibit more aggressive biological behaviors co...Approximately 5%of patients with renal cancer present with synchronous bilateral renal masses(SBRM).1,2 Bilateral renal tumors associated with hereditary syndromes often exhibit more aggressive biological behaviors compared to sporadic SBRM cases.3,4 Notably,the prognosis for sporadic cases,in terms of cancerspecific and distant metastasis-free survival,is comparable to that of unilateral renal masses.展开更多
Background:immune checkpoint inhibitors(ICIs)have revolutionized the treatment of metastatic urothelial carcinoma(mUC),significantly improving survival outcomes.However,a subset of patients do not respond to ICIs,prom...Background:immune checkpoint inhibitors(ICIs)have revolutionized the treatment of metastatic urothelial carcinoma(mUC),significantly improving survival outcomes.However,a subset of patients do not respond to ICIs,prompting research into potential predictive factors.Commonly prescribed medications such as corticosteroids,proton-pump inhibitors(PPIs),antibiotics(Abs),antihypertensives,and analgesics may influence ICI effectiveness.Methods:we conducted a literature search on PubMed to investigate the impact of concomitant medications on the outcomes of patients with mUC,treated with ICIs.We selected the most relevant studies and performed a narrative review.Results:corticosteroids,PPIs and Abs have been associated with reduced survival in ICI-treated patients,including those with mUC.In contrast,antihypertensive agents like renin-angiotensin system inhibitors and betablockers may enhance ICI efficacy,though evidence remains inconclusive.The impact of other medications,such as statins,metformin,and analgesics,on ICI outcomes is less clear,with some data suggesting a detrimental impact on immune response.Conclusions:this narrative review synthesizes current evidence on how concomitant medications affect outcomes in mUC patients treated with ICIs.展开更多
Grain size and formation of the Peripheral Coarse Grain(PCG)defect influence the mechanical and crash properties of extruded profiles.Controlling microstructural evolution during the extrusion of 6XXX series aluminum ...Grain size and formation of the Peripheral Coarse Grain(PCG)defect influence the mechanical and crash properties of extruded profiles.Controlling microstructural evolution during the extrusion of 6XXX series aluminum alloys is therefore essential to ensure the performance of structural components.In this work,three profiles with the same nominal geometry were extruded with a die comprising three different bearing geometries to create different extrusion conditions.Each profile was analyzed experimentally to gather data on the microstructure and mechanical properties.Bulge testing revealed that Profile 2,with the thickest PCG layer(490-1150µm),exhibited worse mechanical performance,with a hoop strain at fracture of 0.08 and a peak load of 51.5 kN,compared to Profiles 1 and 3,which had higher hoop strains(0.13 and 0.14)and peak loads(56.1 and 57.6 kN,respectively).Finite Element Method(FEM)simulations of the extrusion process were carried out using Qform Extrusion UK with a post-processing subroutine developed and implemented to calculate additional parameters such as the stored energy,percentage dynamic recrystallization,grain size,and PCG formation based on standard output parameters from the simulation including strain,temperature and strain rate.The simulation demonstrated that the highest strain rate(40-220 s^(-1))and stored energy(150,000-440,000 J m^(-3))in Profile 2 led to the thickest PCG layer.Based on these results,the proposed predictive model was validated against experimental data,demonstrating high accuracy in predicting PCG thickness and grain size while effectively capturing the influence of process parameters on microstructural evolution.展开更多
BACKGROUND Chronic liver disease(CLD)causes approximately two million deaths each year,and its clinical diagnosis and management remain challenging.Ultrasound is currently the most widely used technique for disease de...BACKGROUND Chronic liver disease(CLD)causes approximately two million deaths each year,and its clinical diagnosis and management remain challenging.Ultrasound is currently the most widely used technique for disease detection.AIM To propose a practical cut-off value for identifying patients with hepatocellular carcinoma(HCC)among those with compensated advanced CLD or healthy individuals using the GALAD score,an algorithm based on a formula that incorporates gender,age,serum alpha-fetoprotein(AFP),AFP-L3,and des-gamma-carboxy prothrombin values.METHODS This cross-sectional analysis was conducted using prospectively collected data from five cohorts(n=1431)comprising healthy individuals,cirrhosis,and HCC patients.These subjects were enrolled from an Italian retrospective cohort,including patients from the IRCCS“Saverio de Bellis”,Department of Gastroenterology,the University of Modena and Reggio Emilia Gastroenterology Department,and the Padua University Hospital and the Department of Gastroenterology,Hepatology,Infectious diseases and Endocrinology,Hannover Medical School.RESULTS Using healthy subjects as reference,a GALAD score cut-off of-1.67 identified HCC with a sensitivity of 89.77%and specificity of 97.59%.Individuals with GALAD values>-1.67 exhibited a moderate to very high probability(over 90%)of having HCC.When cirrhotic patients were used as the reference category,a cut-off of-0.77 yielded a sensitivity of 78.17%and a specificity of 89.55%.CONCLUSION We strongly recommend incorporating this GALAD cut-off into clinical guidelines for the screening of patients with a compensated advanced CLD who are at high risk of developing HCC.Given the rapid global rise in metabolic-associated steatotic liver disease(MASLD)-related CLD,future research should prioritize larger MASLD cohorts to establish the most appropriate GALAD cut-off for diagnostic use,compared to healthy controls and to patients with other forms of CLD.展开更多
Large-scale deep-seated landslides pose a significant threat to human life and infrastructure.Therefore,closely monitoring these landslides is crucial for assessing and mitigating their associated risks.In this paper,...Large-scale deep-seated landslides pose a significant threat to human life and infrastructure.Therefore,closely monitoring these landslides is crucial for assessing and mitigating their associated risks.In this paper,the authors introduce the So Lo Mon framework,a comprehensive monitoring system developed for three large-scale landslides in the Autonomous Province of Bolzano,Italy.A web-based platform integrates various monitoring data(GNSS,topographic data,in-place inclinometer),providing a user-friendly interface for visualizing and analyzing the collected data.This facilitates the identification of trends and patterns in landslide behaviour,enabling the triggering of warnings and the implementation of appropriate mitigation measures.The So Lo Mon platform has proven to be an invaluable tool for managing the risks associated with large-scale landslides through non-structural measures and driving countermeasure works design.It serves as a centralized data repository,offering visualization and analysis tools.This information empowers decisionmakers to make informed choices regarding risk mitigation,ultimately ensuring the safety of communities and infrastructures.展开更多
Climate change can affect rainfall and temperature worldwide,and the ability of birds to react to these changes can be mirrored by studying population phenology and their breeding success.Some European species have ad...Climate change can affect rainfall and temperature worldwide,and the ability of birds to react to these changes can be mirrored by studying population phenology and their breeding success.Some European species have advanced arrival and breeding dates in response to local spring advancement,but conditions experienced during winter seasons may also affect arrival dates and subsequent breeding success.We utilized data collected from 1983 to 2020 in four colonies of Common Swift(Apus apus)in Northern Italy(5486 breeding attempts)to examine the variations of laying date and breeding success in relation to non-breeding conditions(previous winter in Africa)and local conditions in breeding period(spring).Climatic conditions were monitored using the North Atlantic Oscillation(NAO)and El Nino Southern Oscillation(ENSO)indices to describe conditions experienced in winter quarters and the local temperature and rainfall conditions of the breeding area.Common Swifts laid their eggs earlier in warmer springs,and this in turn had a positive effect on breeding success.We did not find evidence for any effects of African winter conditions on laying date nor on breeding success.However,because studies made in the same area have demonstrated a relationship of winter conditions(NAO)on individual survival,our data highlight the importance of considering environmental variables across the annual life cycle to understand variation in Common Swift populations.展开更多
Background:Undifferentiated shock is recognized as a criticality state that is transitional in immune-mediated topology for casual risk of lethal microcirculatory dysfunction.This was a sensitivity analysis of a drug(...Background:Undifferentiated shock is recognized as a criticality state that is transitional in immune-mediated topology for casual risk of lethal microcirculatory dysfunction.This was a sensitivity analysis of a drug(tetracosactide;TCS10)targeting melanocortin receptors(MCRs)in a phase 3 randomized controlled trial to improve cardiovascular surgical rescue outcome by reversing mortality and hemostatic disorders.Methods:Sensitivity analysis was based on a randomized,two-arm,multicenter,double-blind,controlled trial.The Naïve Bayes classifier was performed by density-based sensitivity index for principal strata as proportional hazard model of 30-day surgical risk mortality according to European System for Cardiac Operative Risk Evaluation inputs outputs in 100 consecutive cases(from August to September 2013 from Emilia Romagna region,Italy).Patients included an agent-based TCS10 group(10 mg,single intravenous bolus before surgery;n=56)and control group(n=44)and the association with cytokines,lactate,and bleeding-blood transfusion episodes with the prior-risk log odds for mortality rate in time-to-event was analyzed.Results:Thirty-day mortality was significantly improved in the TCS10 group vs.control group(0 vs.8 deaths,P<0.0001).Baseline levels of interleukin(IL)-6,IL-10,and lactate were associated with bleeding episodes,independent of TCS10 treatment[odds ratio(OR)=1.90,95%confidence interval(CI)1.39-2.79;OR=1.53,95%CI 1.17-2.12;and OR=2.92,95%CI 1.40-6.66,respectively],while baseline level of Fms-like tyrosine kinase 3 ligand(Flt3L)was associated with lower bleeding rates in TCS10-treated patients(OR=0.31,95%CI 0.11-0.90,P=0.03).For every 8 TCS10-treated patients,1 bleeding case was avoided.Blood transfusion episodes were significantly reduced in the TCS10 group compared to the control group(OR=0.32,95%CI 0.14-0.73,P=0.01).For every 4 TCS10-treated patients,1 transfusion case was avoided.Conclusions:Sensitivity index underlines the quality target product profile of TCS10 in the runway of emergency casualty care.To introduce the technology readiness level in real-life critically ill patients,further large-scale studies are required.Trial registration:European Union Drug Regulating Authorities Clinical Trials Database(EudraCT Number:2007-006445-41).展开更多
BACKGROUND Hepatitis delta virus(HDV)infection is the most severe form of chronic viral hepatitis,yet sex-based clinical differences remain poorly defined.Understanding these differences may inform disease management ...BACKGROUND Hepatitis delta virus(HDV)infection is the most severe form of chronic viral hepatitis,yet sex-based clinical differences remain poorly defined.Understanding these differences may inform disease management and guide research.AIM To investigate sex-related differences in demographic and clinical characteristics of patients with chronic HDV infection in a nationwide,real-world Italian setting.METHODS We analyzed demographic,clinical,and virological data from 513 hepatitis B surface antigen/anti-HDV-positive patients,consecutively enrolled between 2019 and 2024,across 58 liver clinics in the Italian PITER HDV cohort.A propensity score-weighted logistic regression model evaluated the association between sex and cirrhosis and/or hepatocellular carcinoma.RESULTS Among 513 patients(61.6%male),median age(56.0 years)and age distribution were similar by sex(P=0.41).Cirrhosis was frequent:73.4%vs 66.0%(anti-HDV-positive)and 77.8%vs 74.2%(HDV RNA-positive)in males and females,respectively.HDV RNA levels were comparable(P=0.93).The highest proportion of females with cirrhosis(33.8%)was in the 56-60-year group,similar to males(34.9%).Among patients with cirrhosis aged≤40 years,females,(80.9%of whom of non-Italian origin),were more represented than males(16.1%vs 6.5%respectively,P<0.05).Male sex was associated with cirrhosis(odds ratio=1.85;95%confidence interval:1.004-3.40).Among HDV RNA-positive patients,males more often had hepatocellular carcinoma,elevated gammaglutamyl transpeptidase,alcohol use,diabetes,hypertension,steatotic liver disease,and hepatitis C virus/human immunodeficiency virus coinfection.Interferon eligibility was similar.CONCLUSION HDV-infected females develop cirrhosis earlier,without liver disease cofactors,while males show advanced liver disease with multiple cofactors.Tailored care for young migrant women and cofactor-guided management for men may improve HDV outcomes,promoting equity.展开更多
Objective:As prostate cancer(Pr C)shows a BRCA mutation rate as high as 30%,it becomes crucial to find the optimal selection criteria for genetic testing.The primary objective of this study was to evaluate the BRCA mu...Objective:As prostate cancer(Pr C)shows a BRCA mutation rate as high as 30%,it becomes crucial to find the optimal selection criteria for genetic testing.The primary objective of this study was to evaluate the BRCA mutation rate in families with Pr C associated with breast and/or ovarian cancers;secondary aims were to compare the characteristics of families and BRCA-related Pr C outcome among BRCA1 and BRCA2 carriers.Methods:Following the Modena criteria for the BRCA test,we evaluated the mutation rate in families with breast and/or ovarian cancer with a Gleason score≥7 Pr Cs,by testing breast or ovarian cases and inferring the mutation in the prostate cases.The characteristics of families and BRCA-related Pr C outcomes were measured using the chi-square(χ^(2))test and Kaplan–Meier methods,respectively.Results:Among 6,591 families,580(8.8%)with a Gleason score≥7 Pr Cs were identified,of which 332(57.2%)met the Modena selection criteria for BRCA testing.Overall,215 breast or ovarian cancer probands(64.8%)were tested,of which 41 resulted positive for BRCA and one for CHEK2 genes(19.5%).No statistically significant differences were found in BRCA-related Pr C prognosis and in the characteristics of families among BRCA1,BRCA2 and non-tested patients.Ten of 23(44%)mutations in the BRCA2 gene fell in the prostate cancer cluster region(PCCR)at the 3′terminal of the 7914 codon.Conclusions:It appears the Modena criteria are very useful for BRCA testing selection in families with breast and/or ovarian cancer and Pr C.A trend toward a worse prognosis has been found in BRCA2 carriers.展开更多
Nonalcoholic fatty liver disease(NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic(nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifes...Nonalcoholic fatty liver disease(NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic(nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications(cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment(diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients.展开更多
In the last years new evidence has accumulated on nonalcoholic fatty liver disease(NAFLD)challenging the paradigms that had been holding the scene over the previous 30 years.NAFLD has such an epidemic prevalence as to...In the last years new evidence has accumulated on nonalcoholic fatty liver disease(NAFLD)challenging the paradigms that had been holding the scene over the previous 30 years.NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases.Conversely,focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach.NAFLD,which can be diagnosed with either non-invasive strategies or through liver biopsy,is a pathogenically complex and clinically heterogeneous disease.The existence of metabolic as opposed to genetic-associated disease,notably including"lean NAFLD"has recently been recognized.Moreover,NAFLD is a systemic condition,featuring metabolic,cardiovascular and(hepatic/extrahepatic)cancer risk.Among the clinico-laboratory features of NAFLD we discuss hyperuricemia,insulin resistance,atherosclerosis,gallstones,psoriasis and selected endocrine derangements.NAFLD is a precursor of type 2 diabetes(T2D)and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD.Finally,lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed.In conclusion,this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD,a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations.It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies,intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible.展开更多
The peripheral nerve injuries,representing some of the most common types of traumatic lesions affecting the nervous system,are highly invalidating for the patients besides being a huge social burden.Although periphera...The peripheral nerve injuries,representing some of the most common types of traumatic lesions affecting the nervous system,are highly invalidating for the patients besides being a huge social burden.Although peripheral nervous system owns a higher regenerative capacity than does central nervous system,mostly depending on Schwann cells intervention in injury repair,several factors determine the extent of functional outcome after healing.Based on the injury type,different therapeutic approaches have been investigated so far.Nerve grafting and Schwann cell transplantation have represented the gold standard treatment for peripheral nerve injuries,however these approaches own limitations,such as scarce donor nerve availability and donor site morbidity.Cell based therapies might provide a suitable tool for peripheral nerve regeneration,in fact,the ability of different stem cell types to differentiate towards Schwann cells in combination with the use of different scaffolds have been widely investigated in animal models of peripheral nerve injuries in the last decade.Dental pulp is a promising cell source for regenerative medicine,because of the ease of isolation procedures,stem cell proliferation and multipotency abilities,which are due to the embryological origin from neural crest.In this article we review the literature concerning the application of tooth derived stem cell populations combined with different conduits to peripheral nerve injuries animal models,highlighting their regenerative contribution exerted through either glial differentiation and neuroprotective/neurotrophic effects on the host tissue.展开更多
文摘Endoscopic retrograde cholangiopancreatography(ERCP)in patients with surgically altered anatomy remains a challenging field in therapeutic endoscopy due to the complex anatomical reconstructions that limit access to the biliary tree.Over the past two decades,device-assisted enteroscopy(DAE),including singleballoon,double-balloon,and motorized spiral enteroscopy,has expanded the feasibility of ERCP in this population,with overall technical success rates generally reported between 70%and 90%.Nevertheless,these techniques are technically demanding,time-consuming,and frequently affected by limited reach and unstable positioning.More recently,interventional endoscopic ultrasound(EUS)-guided procedures have emerged as highly effective alternatives,significantly improving clinical outcomes in selected patients,particularly in those with long-limb Roux-en-Y reconstructions where conventional methods are less effective.Percutaneous transhepatic biliary drainage continues to represent a valuable salvage option when endoscopic approaches fail,though it is associated with a greater burden of reinterventions and adverse events.This minireview provides a comprehensive overview of the main endoscopic strategies for biliary drainage in altered anatomy,focusing on technical considerations,efficacy,and safety profiles of DAE-assisted ERCP,EUS-guided interventions,and motorized systems.The evolving landscape of biliary drainage in this setting highlights the need for tailored treatment strategies,multidisciplinary collaboration,referral to high-volume centers,and further prospective studies to refine patient selection and optimize clinical outcomes.
文摘Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.
文摘Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.
文摘Prognostication of compensated advanced chronic liver disease(cACLD)is of paramount importance for the physician-and-patient communication and for rational clinical decisions.The paper published by Dallio et al reports on red cell distribution width(RDW)/platelet ratio(RPR)as a non-invasive biomarker in predicting decompensation of metabolic dysfunction-associated steatotic liver disease(MASLD)-related cACLD.Differently from other biomarkers and algorithms,RPR is inexpensive and widely available,based on parameters which are included in a complete blood count.RPR is computed on the grounds of two different items,one of which,RDW,mirrors the host’s response to a variety of disease stimuli and is non-specific.The second parameter involved in RPR,platelet count,is more specific and has been used in the hepatological clinic to discriminate cirrhotic from non-cirrhotic chronic liver disease for decades.Cardiovascular disease is the primary cause of mortality among MASLD subjects,followed by extra-hepatic cancers and liver-related mortality.Therefore,MASLD biomarkers should be validated not only in terms of liver-related events but also in the prediction of major adverse cardiovascular events and cardiovascular mortality and extra-hepatic cancers.Adequately sized multi-ethnic confirmatory investigation is required to define the role and significance of RPR in the stratification of MASLD-cACLD.
文摘This editorial is a commentary on the case report by Furuya et al focusing on the challenging diagnosis of early pancreatic adenocarcinoma and new tools for an earlier diagnosis.Currently,pancreatic cancer still has a poor prognosis,mainly due to late diagnosis in an advanced stage.Two main precancerous routes have been identified as pathways to pancreatic adenocarcinoma:The first encompasses a large group of mucinous cystic lesions:intraductal papillary mucinous neoplasm and mucinous cystic neoplasm,and the second is pancreatic intraepithelial neoplasia.In the last decade the focus of research has been to identify high-risk patients,using advanced imaging techniques(magnetic resonance cholangiopancreatography or endoscopic ultrasonography)which could be helpful in finding“indirect signs”of early stage pancreatic lesions.Nevertheless,the survival rate still remains poor,and alternative screening methods are under investigation.Endoscopic retrograde cholangiopancreatography followed by serial pancreatic juice aspiration cytology could be a promising tool for identifying precursor lesions such as intraductal papillary mucinous neoplasm,but confirming data are still needed to validate its role.Probably a combination of cross-sectional imaging,endoscopic techniques(old and new ones)and genetic and biological biomarkers also in pancreatic juice)could be the best solution to reach an early diagnosis.Biomarkers could help to predict and follow the progression of early pancreatic lesions.However,further studies are needed to validate their diagnostic reliability and to establish diagnostic algorithms to improve prognosis and survival in patients with pancreatic cancer.
文摘Caffeine is a widely consumed stimulant known for its cardiovascular and metabolic effects.However,its impact on cardiovascular risk,including arrhythmias,in older adults remains underexplored.Emerging evidence highlights sex-specific differences in caffeine metabolism,which may influence its role in cardiovascular health.This perspective examines the interaction between caffeine,hormonal changes,metabolic processes,and lifestyle factors,focusing on older women compared to men.Understanding these differences is essential for tailoring dietary and clinical recommendations to mitigate cardiovascular risks and promote healthy aging.
文摘Approximately 5%of patients with renal cancer present with synchronous bilateral renal masses(SBRM).1,2 Bilateral renal tumors associated with hereditary syndromes often exhibit more aggressive biological behaviors compared to sporadic SBRM cases.3,4 Notably,the prognosis for sporadic cases,in terms of cancerspecific and distant metastasis-free survival,is comparable to that of unilateral renal masses.
文摘Background:immune checkpoint inhibitors(ICIs)have revolutionized the treatment of metastatic urothelial carcinoma(mUC),significantly improving survival outcomes.However,a subset of patients do not respond to ICIs,prompting research into potential predictive factors.Commonly prescribed medications such as corticosteroids,proton-pump inhibitors(PPIs),antibiotics(Abs),antihypertensives,and analgesics may influence ICI effectiveness.Methods:we conducted a literature search on PubMed to investigate the impact of concomitant medications on the outcomes of patients with mUC,treated with ICIs.We selected the most relevant studies and performed a narrative review.Results:corticosteroids,PPIs and Abs have been associated with reduced survival in ICI-treated patients,including those with mUC.In contrast,antihypertensive agents like renin-angiotensin system inhibitors and betablockers may enhance ICI efficacy,though evidence remains inconclusive.The impact of other medications,such as statins,metformin,and analgesics,on ICI outcomes is less clear,with some data suggesting a detrimental impact on immune response.Conclusions:this narrative review synthesizes current evidence on how concomitant medications affect outcomes in mUC patients treated with ICIs.
基金supported by the European Union’s Horizon Europe research and innovation programme,Zero Emission electric Vehicles enabled by haRmonised circularity,under No.101138034.
文摘Grain size and formation of the Peripheral Coarse Grain(PCG)defect influence the mechanical and crash properties of extruded profiles.Controlling microstructural evolution during the extrusion of 6XXX series aluminum alloys is therefore essential to ensure the performance of structural components.In this work,three profiles with the same nominal geometry were extruded with a die comprising three different bearing geometries to create different extrusion conditions.Each profile was analyzed experimentally to gather data on the microstructure and mechanical properties.Bulge testing revealed that Profile 2,with the thickest PCG layer(490-1150µm),exhibited worse mechanical performance,with a hoop strain at fracture of 0.08 and a peak load of 51.5 kN,compared to Profiles 1 and 3,which had higher hoop strains(0.13 and 0.14)and peak loads(56.1 and 57.6 kN,respectively).Finite Element Method(FEM)simulations of the extrusion process were carried out using Qform Extrusion UK with a post-processing subroutine developed and implemented to calculate additional parameters such as the stored energy,percentage dynamic recrystallization,grain size,and PCG formation based on standard output parameters from the simulation including strain,temperature and strain rate.The simulation demonstrated that the highest strain rate(40-220 s^(-1))and stored energy(150,000-440,000 J m^(-3))in Profile 2 led to the thickest PCG layer.Based on these results,the proposed predictive model was validated against experimental data,demonstrating high accuracy in predicting PCG thickness and grain size while effectively capturing the influence of process parameters on microstructural evolution.
文摘BACKGROUND Chronic liver disease(CLD)causes approximately two million deaths each year,and its clinical diagnosis and management remain challenging.Ultrasound is currently the most widely used technique for disease detection.AIM To propose a practical cut-off value for identifying patients with hepatocellular carcinoma(HCC)among those with compensated advanced CLD or healthy individuals using the GALAD score,an algorithm based on a formula that incorporates gender,age,serum alpha-fetoprotein(AFP),AFP-L3,and des-gamma-carboxy prothrombin values.METHODS This cross-sectional analysis was conducted using prospectively collected data from five cohorts(n=1431)comprising healthy individuals,cirrhosis,and HCC patients.These subjects were enrolled from an Italian retrospective cohort,including patients from the IRCCS“Saverio de Bellis”,Department of Gastroenterology,the University of Modena and Reggio Emilia Gastroenterology Department,and the Padua University Hospital and the Department of Gastroenterology,Hepatology,Infectious diseases and Endocrinology,Hannover Medical School.RESULTS Using healthy subjects as reference,a GALAD score cut-off of-1.67 identified HCC with a sensitivity of 89.77%and specificity of 97.59%.Individuals with GALAD values>-1.67 exhibited a moderate to very high probability(over 90%)of having HCC.When cirrhotic patients were used as the reference category,a cut-off of-0.77 yielded a sensitivity of 78.17%and a specificity of 89.55%.CONCLUSION We strongly recommend incorporating this GALAD cut-off into clinical guidelines for the screening of patients with a compensated advanced CLD who are at high risk of developing HCC.Given the rapid global rise in metabolic-associated steatotic liver disease(MASLD)-related CLD,future research should prioritize larger MASLD cohorts to establish the most appropriate GALAD cut-off for diagnostic use,compared to healthy controls and to patients with other forms of CLD.
基金funded by the So Lo Mon project“Monitoraggio a Lungo Termine di Grandi Frane basato su Sistemi Integrati di Sensori e Reti”(Longterm monitoring of large-scale landslides based on integrated systems of sensors and networks),Program EFRE-FESR 2014–2020,Project EFRE-FESR4008 South Tyrol–Person in charge:V.Mair。
文摘Large-scale deep-seated landslides pose a significant threat to human life and infrastructure.Therefore,closely monitoring these landslides is crucial for assessing and mitigating their associated risks.In this paper,the authors introduce the So Lo Mon framework,a comprehensive monitoring system developed for three large-scale landslides in the Autonomous Province of Bolzano,Italy.A web-based platform integrates various monitoring data(GNSS,topographic data,in-place inclinometer),providing a user-friendly interface for visualizing and analyzing the collected data.This facilitates the identification of trends and patterns in landslide behaviour,enabling the triggering of warnings and the implementation of appropriate mitigation measures.The So Lo Mon platform has proven to be an invaluable tool for managing the risks associated with large-scale landslides through non-structural measures and driving countermeasure works design.It serves as a centralized data repository,offering visualization and analysis tools.This information empowers decisionmakers to make informed choices regarding risk mitigation,ultimately ensuring the safety of communities and infrastructures.
文摘Climate change can affect rainfall and temperature worldwide,and the ability of birds to react to these changes can be mirrored by studying population phenology and their breeding success.Some European species have advanced arrival and breeding dates in response to local spring advancement,but conditions experienced during winter seasons may also affect arrival dates and subsequent breeding success.We utilized data collected from 1983 to 2020 in four colonies of Common Swift(Apus apus)in Northern Italy(5486 breeding attempts)to examine the variations of laying date and breeding success in relation to non-breeding conditions(previous winter in Africa)and local conditions in breeding period(spring).Climatic conditions were monitored using the North Atlantic Oscillation(NAO)and El Nino Southern Oscillation(ENSO)indices to describe conditions experienced in winter quarters and the local temperature and rainfall conditions of the breeding area.Common Swifts laid their eggs earlier in warmer springs,and this in turn had a positive effect on breeding success.We did not find evidence for any effects of African winter conditions on laying date nor on breeding success.However,because studies made in the same area have demonstrated a relationship of winter conditions(NAO)on individual survival,our data highlight the importance of considering environmental variables across the annual life cycle to understand variation in Common Swift populations.
基金funded by the National Plan Military Research (EF a2011.188)
文摘Background:Undifferentiated shock is recognized as a criticality state that is transitional in immune-mediated topology for casual risk of lethal microcirculatory dysfunction.This was a sensitivity analysis of a drug(tetracosactide;TCS10)targeting melanocortin receptors(MCRs)in a phase 3 randomized controlled trial to improve cardiovascular surgical rescue outcome by reversing mortality and hemostatic disorders.Methods:Sensitivity analysis was based on a randomized,two-arm,multicenter,double-blind,controlled trial.The Naïve Bayes classifier was performed by density-based sensitivity index for principal strata as proportional hazard model of 30-day surgical risk mortality according to European System for Cardiac Operative Risk Evaluation inputs outputs in 100 consecutive cases(from August to September 2013 from Emilia Romagna region,Italy).Patients included an agent-based TCS10 group(10 mg,single intravenous bolus before surgery;n=56)and control group(n=44)and the association with cytokines,lactate,and bleeding-blood transfusion episodes with the prior-risk log odds for mortality rate in time-to-event was analyzed.Results:Thirty-day mortality was significantly improved in the TCS10 group vs.control group(0 vs.8 deaths,P<0.0001).Baseline levels of interleukin(IL)-6,IL-10,and lactate were associated with bleeding episodes,independent of TCS10 treatment[odds ratio(OR)=1.90,95%confidence interval(CI)1.39-2.79;OR=1.53,95%CI 1.17-2.12;and OR=2.92,95%CI 1.40-6.66,respectively],while baseline level of Fms-like tyrosine kinase 3 ligand(Flt3L)was associated with lower bleeding rates in TCS10-treated patients(OR=0.31,95%CI 0.11-0.90,P=0.03).For every 8 TCS10-treated patients,1 bleeding case was avoided.Blood transfusion episodes were significantly reduced in the TCS10 group compared to the control group(OR=0.32,95%CI 0.14-0.73,P=0.01).For every 4 TCS10-treated patients,1 transfusion case was avoided.Conclusions:Sensitivity index underlines the quality target product profile of TCS10 in the runway of emergency casualty care.To introduce the technology readiness level in real-life critically ill patients,further large-scale studies are required.Trial registration:European Union Drug Regulating Authorities Clinical Trials Database(EudraCT Number:2007-006445-41).
基金Supported by the Investigator Sponsored Research Grant from Gilead Sciences,No.IN-IT-980-6816the Fondazione Italiana per la Ricerca sul Cancro(AIRC),No.IG 2020 ID 24858.
文摘BACKGROUND Hepatitis delta virus(HDV)infection is the most severe form of chronic viral hepatitis,yet sex-based clinical differences remain poorly defined.Understanding these differences may inform disease management and guide research.AIM To investigate sex-related differences in demographic and clinical characteristics of patients with chronic HDV infection in a nationwide,real-world Italian setting.METHODS We analyzed demographic,clinical,and virological data from 513 hepatitis B surface antigen/anti-HDV-positive patients,consecutively enrolled between 2019 and 2024,across 58 liver clinics in the Italian PITER HDV cohort.A propensity score-weighted logistic regression model evaluated the association between sex and cirrhosis and/or hepatocellular carcinoma.RESULTS Among 513 patients(61.6%male),median age(56.0 years)and age distribution were similar by sex(P=0.41).Cirrhosis was frequent:73.4%vs 66.0%(anti-HDV-positive)and 77.8%vs 74.2%(HDV RNA-positive)in males and females,respectively.HDV RNA levels were comparable(P=0.93).The highest proportion of females with cirrhosis(33.8%)was in the 56-60-year group,similar to males(34.9%).Among patients with cirrhosis aged≤40 years,females,(80.9%of whom of non-Italian origin),were more represented than males(16.1%vs 6.5%respectively,P<0.05).Male sex was associated with cirrhosis(odds ratio=1.85;95%confidence interval:1.004-3.40).Among HDV RNA-positive patients,males more often had hepatocellular carcinoma,elevated gammaglutamyl transpeptidase,alcohol use,diabetes,hypertension,steatotic liver disease,and hepatitis C virus/human immunodeficiency virus coinfection.Interferon eligibility was similar.CONCLUSION HDV-infected females develop cirrhosis earlier,without liver disease cofactors,while males show advanced liver disease with multiple cofactors.Tailored care for young migrant women and cofactor-guided management for men may improve HDV outcomes,promoting equity.
文摘Objective:As prostate cancer(Pr C)shows a BRCA mutation rate as high as 30%,it becomes crucial to find the optimal selection criteria for genetic testing.The primary objective of this study was to evaluate the BRCA mutation rate in families with Pr C associated with breast and/or ovarian cancers;secondary aims were to compare the characteristics of families and BRCA-related Pr C outcome among BRCA1 and BRCA2 carriers.Methods:Following the Modena criteria for the BRCA test,we evaluated the mutation rate in families with breast and/or ovarian cancer with a Gleason score≥7 Pr Cs,by testing breast or ovarian cases and inferring the mutation in the prostate cases.The characteristics of families and BRCA-related Pr C outcomes were measured using the chi-square(χ^(2))test and Kaplan–Meier methods,respectively.Results:Among 6,591 families,580(8.8%)with a Gleason score≥7 Pr Cs were identified,of which 332(57.2%)met the Modena selection criteria for BRCA testing.Overall,215 breast or ovarian cancer probands(64.8%)were tested,of which 41 resulted positive for BRCA and one for CHEK2 genes(19.5%).No statistically significant differences were found in BRCA-related Pr C prognosis and in the characteristics of families among BRCA1,BRCA2 and non-tested patients.Ten of 23(44%)mutations in the BRCA2 gene fell in the prostate cancer cluster region(PCCR)at the 3′terminal of the 7914 codon.Conclusions:It appears the Modena criteria are very useful for BRCA testing selection in families with breast and/or ovarian cancer and Pr C.A trend toward a worse prognosis has been found in BRCA2 carriers.
文摘Nonalcoholic fatty liver disease(NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic(nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications(cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment(diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients.
文摘In the last years new evidence has accumulated on nonalcoholic fatty liver disease(NAFLD)challenging the paradigms that had been holding the scene over the previous 30 years.NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases.Conversely,focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach.NAFLD,which can be diagnosed with either non-invasive strategies or through liver biopsy,is a pathogenically complex and clinically heterogeneous disease.The existence of metabolic as opposed to genetic-associated disease,notably including"lean NAFLD"has recently been recognized.Moreover,NAFLD is a systemic condition,featuring metabolic,cardiovascular and(hepatic/extrahepatic)cancer risk.Among the clinico-laboratory features of NAFLD we discuss hyperuricemia,insulin resistance,atherosclerosis,gallstones,psoriasis and selected endocrine derangements.NAFLD is a precursor of type 2 diabetes(T2D)and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD.Finally,lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed.In conclusion,this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD,a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations.It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies,intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible.
文摘The peripheral nerve injuries,representing some of the most common types of traumatic lesions affecting the nervous system,are highly invalidating for the patients besides being a huge social burden.Although peripheral nervous system owns a higher regenerative capacity than does central nervous system,mostly depending on Schwann cells intervention in injury repair,several factors determine the extent of functional outcome after healing.Based on the injury type,different therapeutic approaches have been investigated so far.Nerve grafting and Schwann cell transplantation have represented the gold standard treatment for peripheral nerve injuries,however these approaches own limitations,such as scarce donor nerve availability and donor site morbidity.Cell based therapies might provide a suitable tool for peripheral nerve regeneration,in fact,the ability of different stem cell types to differentiate towards Schwann cells in combination with the use of different scaffolds have been widely investigated in animal models of peripheral nerve injuries in the last decade.Dental pulp is a promising cell source for regenerative medicine,because of the ease of isolation procedures,stem cell proliferation and multipotency abilities,which are due to the embryological origin from neural crest.In this article we review the literature concerning the application of tooth derived stem cell populations combined with different conduits to peripheral nerve injuries animal models,highlighting their regenerative contribution exerted through either glial differentiation and neuroprotective/neurotrophic effects on the host tissue.
