Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic ...Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.展开更多
BACKGROUND Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase(DPD),encoded by the DPYD gene.About 7%of the European population is a carrier of DPYD gene polymorphisms associat...BACKGROUND Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase(DPD),encoded by the DPYD gene.About 7%of the European population is a carrier of DPYD gene polymorphisms associated with reduced DPD enzyme activity.AIM To assess the prevalence of DPYD polymorphisms and their impact on fluoropyrimidine tolerability in Italian patients with gastrointestinal malignancies.METHODS A total of 300 consecutive patients with a diagnosis of gastrointestinal malignancy and treated with a fluoropyrimidine-based regimen were included in the analysis and divided into two cohorts:(1)149 patients who started fluoropyrimidines after DPYD testing;and(2)151 patients treated without DPYD testing.Among the patients in cohort A,15%tested only the DPYD2A polymorphism,19%tested four polymorphisms(DPYD2A,HapB3,c.2846A>T,and DPYD13),and 66%tested five polymorphisms including DPYD6.RESULTS Overall,14.8%of patients were found to be carriers of a DPYD variant,the most common being DPYD6(12.1%).Patients in cohort A reported≥G3 toxicities(P=0.00098),particularly fewer nonhematological toxicities(P=0.0028)compared with cohort B,whereas there was no statistically significant difference between the two cohorts in hematological toxicities(P=0.6944).Significantly fewer chemotherapy dose reductions(P=0.00002)were observed in cohort A compared to cohort B,whereas there was no statistically significant differences in chemotherapy delay.CONCLUSION Although this study had a limited sample size,it provides additional information on the prevalence of DPYD polymorphisms in the Italian population and highlights the role of pharmacogenetic testing to prevent severe toxicity.展开更多
Treatments for low degree hemorrhoids(I-III degree)are numerous and so are their counterparts for higher degrees.These treatments present nebulous diffe-rences in terms of indications and outcomes among techniques.Met...Treatments for low degree hemorrhoids(I-III degree)are numerous and so are their counterparts for higher degrees.These treatments present nebulous diffe-rences in terms of indications and outcomes among techniques.Methods previously abandoned due to side effects and long-term results have recently rejoined the mainstream due to recent peculiar modifications:Hemorrhoidal sclerotherapy is enjoying a new age of interest due to the use of the foam form of polidocanol,which is more effective than the liquid one.Various articles have already shown promising results and the logical next step is the combination of polidocanol foam with rubber-band ligation(the historical counterpart of sclero-therapy)in a technique called“sclerobanding”.In this article,we comment on the publication by Qu et al further modifying the use of sclerobanding through an endoscopic delivery for patients with grade II-III internal hemorrhoids,and present results compared with endoscopic rubber band ligation.The results achieved are promising.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
Celiac disease(CD)is a systemic autoimmune disorder triggered by gluten ingestion ingenetically predisposed individuals.It is characterized by intestinal histological damage and the production of specific autoantibodi...Celiac disease(CD)is a systemic autoimmune disorder triggered by gluten ingestion ingenetically predisposed individuals.It is characterized by intestinal histological damage and the production of specific autoantibodies.The latest European Society for Paediatric Gastroenterology,Hepatology,and Nutrition(ESPGHAN)2020 guidelines have excluded human leukocyte antigen(HLA)genotyping from the no-biopsy diagnostic approach due to its weak positive predictive value,limited availability,and high cost in some countries.However,HLA genetic testing remains valuable in certain clinical contexts.This study provided practical indications for when to request and how to interpret HLA genotyping,emphasizing its continued relevance for CD diagnosis in specific cases.We also proposed a strategy for monitoring the risk of developing type 1 diabetes(T1D)in patients with CD,based on the risk stratification carried by different HLA genotypes.A retrospective analysis of 746 patients with CD and 627 controls was conducted at our hospital starting in2012,when HLA genotyping became mandatory for the diagnosis of CD.We identified key clinical scenarios where HLA testing remains useful.Several high risk HLA-DQ genotypes strongly associated with CD were highlighted,including HLA-DQ2.5/HLA-DQ2.2and HLA-DQ2.5/HLA-DQ2.5.Notably,while the HLA-DQ2.5/HLA-DQ2.2 genotype is linked to CD,it appears to confer protection against T1D.To support clinical practice,we presented a table clarifying commonly used HLA terminology,and another summarized the main clinical situations in which HLAgenotyping should still be considered.These findings underscore the dual role of HLA testing:Not only can it help rule out CD in selected cases,but it also identifies patients with CD at risk for T1D,guiding personalized monitoring strategies.展开更多
Platelet rich plasma(PRP)is an autologous blood product rich in platelets,showing promise in reducing inflammation and accelerating healing.While extensively utilized in plastic surgery,dermatology,and osteoarthritis ...Platelet rich plasma(PRP)is an autologous blood product rich in platelets,showing promise in reducing inflammation and accelerating healing.While extensively utilized in plastic surgery,dermatology,and osteoarthritis treatment,its application in anterior cruciate ligament(ACL)injuries is limited.This article examines PRP's potential in ACL reconstruction(ACLR),exploring its history,current usage,controversies and future directions.PRP has demonstrated significant early benefits in ligamentisation and vascularisation post-ACLR,though its long-term efficacy is inconsistent.Studies suggest that PRP may serve as both an adjunct therapy in ACLR to enhance initial healing and reduce postoperative complications,and as a non-surgical alternative for small ACL tears.Despite these promising findings,outcome variability necessitates further high-quality research to optimize PRP formulations and determine its most effective applications.The exploration of PRP as a treatment modality in ACLR offers promising but varied outcomes.PRP holds considerable promise as both an adjunct and alternative to traditional ACLR.This article underscores the need for targeted research to fully realize PRP's therapeutic potential in ACL treatment,aiming to inform future studies and clinical practices.By understanding PRP's mechanisms of efficacy and identifying the most beneficial patient populations,PRP could significantly impact orthopaedics and sports medicine,improving recovery pathways and patient outcomes.展开更多
AIM: To investigate the correlation between autoimmune thyroid diseases (ATDs) and the prevalence of Cag-A positive strains of Helicobacter pylori (H. pylori) in stool samples. METHODS: We investigated 112 consecutive...AIM: To investigate the correlation between autoimmune thyroid diseases (ATDs) and the prevalence of Cag-A positive strains of Helicobacter pylori (H. pylori) in stool samples. METHODS: We investigated 112 consecutive Caucasian patients (48 females and 4 males with Graves' disease and 54 females and 6 males with Hashimoto' s thyroiditis HT), at their first diagnosis of ATDs. We tested for H. pylori in stool samples using an amplified enzyme immunoassay and Cag-A in serum samples using an enzyme-linked immunoassay method (ELISA). The results were analyzed using the two-sided Fisher' s exact test and the respective odds ratio (OR) was calculated. RESULTS: A marked correlation was found between the presence of H. pylori (P ≤ 0.0001, OR 6.3) and, in particular, Cag-A positive strains (P ≤ 0.005, OR 5.3)in Graves' disease, but not in Hashimoto's thyroiditis, where we found only a correlation with Cag-A strains (P ≤ 0.005, OR 8.73) but not when H. pylori was present. CONCLUSION: The marked correlation between H. pylori and Cag-A, found in ATDs, could be dependent on the different expression of adhesion molecules in the gastric mucosa.展开更多
Radical gastrectomy with an adequate lymphadenectomy is the main procedure which makes it possible to cure patients with resectable gastric cancer (GC). A number of randomized controlled trials and meta-analysis provi...Radical gastrectomy with an adequate lymphadenectomy is the main procedure which makes it possible to cure patients with resectable gastric cancer (GC). A number of randomized controlled trials and meta-analysis provide phase III evidence that laparoscopic gastrectomy is technically safe and that it yields better short-term outcomes than conventional open gastrectomy for early-stage GC. While laparoscopic gastrectomy has become standard therapy for early-stage GC, especially in Asian countries such as Japan and South Korea, the use of minimally invasive techniques is still controversial for the treatment of more advanced tumours, principally due to existing concerns about its oncological adequacy and capacity to carry out an adequately extended lymphadenectomy. Some intrinsic drawbacks of the conventional laparoscopic technique have prevented the worldwide spread of laparoscopic gastrectomy for cancer and, despite technological advances in recent year, it remains a technically challenging procedure. The introduction of robotic surgery over the last ten years has implied a notable mutation of certain minimally invasive procedures, making it possible to overcome some limitations of the traditional laparoscopic technique. Robot-assisted gastric resection with D2 lymph node dissection has been shown to be safe and feasible in prospective and retrospective studies. However, to date there are no high quality comparative studies investigating the advantages of a robotic approach to GC over traditional laparoscopic and open gastrectomy. On the basis of the literature review here presented, robot-assisted surgery seems to fulfill oncologic criteria for D2 dissection and has a comparable oncologic outcome to traditional laparoscopic and open procedure. Robot-assisted gastrectomy was associated with the trend toward a shorter hospital stay with a comparable morbidity of conventional laparoscopic and open gastrectomy, but randomized clinical trials and longer follow-ups are needed to evaluate the possible influence of robot gastrectomy on GC patient survival.展开更多
Implantation of an inflatable penile prosthesis （IPP） is a well-established definitive solution for erectile dysfunction when conservative treatments fail. Penile implants may shorten the penis. The AMS 700 LGX IPP ...Implantation of an inflatable penile prosthesis （IPP） is a well-established definitive solution for erectile dysfunction when conservative treatments fail. Penile implants may shorten the penis. The AMS 700 LGX IPP is in common use but reports on its mechanical reliability, medium-term postsurgical patient satisfaction, and mean penile length preservation are lacking. We investigate the mean penile length, mechanical reliability, and patient satisfaction at 6 and 12 months after implantation of the AMS 700 LGX. This prospective study consecutively enrolled men undergoing first-time IPP implant surgery from February 2009 to April 2012. Stretched flaccid penile length, penile length at 50% and 100% of stiffness （PSO and P100） and International Index of Erectile Function （IIEF） and Erectile Dysfunction Inventory of Treatment Satisfaction （EDITS） scores, were measured at 6 and 12 months postsurgery. Of 45 patients who underwent AMS 700 LGX implantation （median age 61 years） and completed 6 months＇ follow-up, 36 （80%） completed the study. A significant difference in stretched flaccid penile length was seen between 6 and 12 months （P= 0.033）. P100 was also significantly increased at 6 and 12 months, with a mean 10% increase （1.3 ±0.4 cm） from baseline to 12 months. Differences in mean IIEF scores at 6 and 12 months were significant for the desired domain （P = 0.0001） and for overall satisfaction （P = 0.002）; however, mean EDITS scores at 6 and 12 months were not significantly improved. AMS 700 LGX is a powerful tool for preserving penile length in men undergoing penile prosthesis implantation.展开更多
Myocarditis is a bacterial or viral inflammatory disease,often unnoticed or misdiagnosed.Athletes with myocarditis must stop practicing their activity since International medical Literature described some cases of sud...Myocarditis is a bacterial or viral inflammatory disease,often unnoticed or misdiagnosed.Athletes with myocarditis must stop practicing their activity since International medical Literature described some cases of sudden death.In the present report,we describe a case of an asymptomatic,apparently healthy,competitive athletes,who was diagnosed a myocarditis and as incidental finding a myocardial bridging.We focused the attention on the importance of anamnesis,electrocardiogram and athletes' entourage for the diagnosis of such insidious pathologies and we evaluated the follow up,focusing the attention on electrocardiogram changes as well as on restitution ad integrum and prognosis,especially for the athletes.展开更多
One out of three hospitalizations for acute coronary syndrome(ACS)involve nowadays elderly patients,carrying together a significant burden of comorbidities and a higher risk of complications.In particular,both ischemi...One out of three hospitalizations for acute coronary syndrome(ACS)involve nowadays elderly patients,carrying together a significant burden of comorbidities and a higher risk of complications.In particular,both ischemic and haemorrhagic risk are markedly enhanced in advanced age,and strictly interconnected,challenging the management of dual antiplatelet therapy(DAPT)in these patients.The recent development of several therapeutic options in terms of duration and combination of antiplatelet agents have offered a wider spectrum of opportunities for a more individualized approach in the management of DAPT after an ACS,although the criteria for the selection of the most appropriate strategy in each patient still lack validation.In particular,dose-adjustment,early aspirin discontinuation,laboratory-driven tailoring and shorter or extended DAPT have been addressed with promising safety and efficacy results.The present review provides an updated overview on the emerging evidencefrom randomized clinical trials and subanalyses dedicated to the management of DAPT in elderly patients presenting with ACS.展开更多
Emergence from anesthesia(AE) is the ending stage of anesthesia featuring the transition from unconsciousness to complete wakefulness and recovery of consciousness(RoC). A wide range of undesirable complications, incl...Emergence from anesthesia(AE) is the ending stage of anesthesia featuring the transition from unconsciousness to complete wakefulness and recovery of consciousness(RoC). A wide range of undesirable complications, including coughing, respiratory/cardiovascular events, and mental status changes such as emergence delirium, and delayed RoC, may occur during this critical phase. In general anesthesia processes, induction and AE represent a neurobiological example of "hysteresis". Indeed, AE mechanisms should not be simply considered as reverse events of those occurring in the induction phase. Anesthesia-induced loss of consciousness(LoC) and AE until RoC are quite distinct phenomena with, in part, a distinct neurobiology. Althoughanaesthetics produce LoC mostly by affecting cortical connectivity, arousal processes at the end of anesthesia are triggered by structures deep in the brain, rather than being induced within the neocortex. This work aimed to provide an overview on AE processes research, in terms of mechanisms, and EEG findings. Because most of the research in this field concerns preclinical investigations, translational suggestions and research perspectives are proposed. However, little is known about the relationship between AE neurobiology, and potential complications occurring during the emergence, and after the RoC. Thus, another scope of this review is to underline why a better understanding of AE mechanisms could have significant clinical implications, such as improving the patients' quality of recovery, and avoiding early and late postoperative complications.展开更多
AIM:To clarify which method has accuracy:2nd gen-eration contrast-enhanced ultrasound or biopsy of portal vein thrombus in the differential diagnosis of portal vein thrombosis.METHODS:One hundred and eighty-six patien...AIM:To clarify which method has accuracy:2nd gen-eration contrast-enhanced ultrasound or biopsy of portal vein thrombus in the differential diagnosis of portal vein thrombosis.METHODS:One hundred and eighty-six patients with hepatocellular carcinoma and portal vein thrombosis underwent in blinded fashion a 2nd generation contrast-enhanced ultrasound and biopsy of portal vein thrombus;both results were examined on the basis of the follow-up of patients compared to reference-standard.RESULTS:One hundred and eight patients completed the study.Benign thrombosis on 2nd generation contrast-enhanced ultrasound was characterised by progressive hypoenhancing of the thrombus;in malignant portal vein thrombosis there was a precocious homo-geneous enhancement of the thrombus.On follow-up there were 50 of 108 patients with benign thrombosis:all were correctly diagnosed by both methods.There were 58 of 108 patients with malignant thrombosis:amongst these,52 were correctly diagnosed by both methods,the remainder did not present malignant cells on portal vein thrombus biopsy and showed on 2nd generation contrast-enhanced ultrasound an inho-mogeneous enhancement pattern.A new biopsy during the follow-up,guided to the area of thrombus that showed up on 2nd generation contrast-enhanced ultra-sound,demonstrated an enhancing pattern indicating malignant cells.CONCLUSION:In patients with hepatocellular carcinoma complicated by portal vein thrombosis,2nd generation contrast-enhanced ultrasound of portal vein thrombus is very useful in assessing the benign or malignant nature of the thrombus.Puncture biopsy of thrombus is usually accurate but presents some sampling errors,so,when pathological results are required,2nd generation contrast-enhanced ultrasound could guide the sampling needle to the correct area of the thrombus.展开更多
Emergency physicians are required to care for unstable patients with life-threatening conditions,and thus must make decisions that are both quick and precise about unclear clinical situations.There is increasing conse...Emergency physicians are required to care for unstable patients with life-threatening conditions,and thus must make decisions that are both quick and precise about unclear clinical situations.There is increasing consensus in favor of using ultrasound as a real-time bedside clinical tool for clinicians in emergency settings alongside the irreplaceable use of historical and physical examinations.B-mode sonography is an old technology that was first proposed for medical applications more than 50 years ago.Its application in the diagnosis of thoracic diseases has always been considered limited,due to the presence of air in the lung and the presence of the bones of the thoracic cage,which prevent the progression of the ultrasound beam.However,the close relationship between air and water in the lungs causes a variety of artifacts on ultrasounds.At the bedside,thoracic ultrasound is based primarily on the analysis of these artifacts,with the aim of improving accuracy and safety in the diagnosis and therapy of the various varieties of pulmonary pathologic diseases which are predominantly"water-rich"or"air-rich".The indications,contraindications,advantages,disadvantages,and techniques of thoracic ultrasound and its related procedures are analyzed in the present review.展开更多
Objectives:Intensive health services'utilization is common in older individuals affected by chronic diseases.This study assessed whether a structured family nurse-led educational intervention would be effective in...Objectives:Intensive health services'utilization is common in older individuals affected by chronic diseases.This study assessed whether a structured family nurse-led educational intervention would be effective in reducing health services'use(readmissions and/or emergency service access)among older people affected by chronic conditions.Methods:This is a non-randomized before-after pilot study.A sample of 78 patients was recruited from two general practices in Italy and 70 among them were followed for 8 months.Standard home care was provided during the first four months'period(months 1-4),followed by the educational intervention until the end of the study(months 5-8).The intervention,based on the teach-back method,consisted of by-weekly 60-min home sessions targeting aspects of the disease and its treatment,potential complications,medication adherence,and health behaviours.Rates of health services'use were collected immediately before(T0),and after the interventions(T1).Differences in utilization rates were examined by the McNemar's test.Potential factors associated with the risk of health services'use were explored with a Cox proportional hazard regression model.Results:The sample(n=78)was predominantly female(n=50,64.1%),and had a mean age of 76.2(SD=4.8)years.Diabetes mellitus was the most frequent disease(n=27,34.6%).McNemar's test indicated a significant reduction in health services'use at T1(McNemar χ^(2)==28.03,P<0.001).Cox regressions indicated that time and patient education,as well as their interaction,were the only variables positively associated with the probability of health services'use.Conclusion:A teach-back intervention led by a family nurse practitioner has the potential to reduce health services'use in older patients with chronic diseases.展开更多
文摘Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.
文摘BACKGROUND Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase(DPD),encoded by the DPYD gene.About 7%of the European population is a carrier of DPYD gene polymorphisms associated with reduced DPD enzyme activity.AIM To assess the prevalence of DPYD polymorphisms and their impact on fluoropyrimidine tolerability in Italian patients with gastrointestinal malignancies.METHODS A total of 300 consecutive patients with a diagnosis of gastrointestinal malignancy and treated with a fluoropyrimidine-based regimen were included in the analysis and divided into two cohorts:(1)149 patients who started fluoropyrimidines after DPYD testing;and(2)151 patients treated without DPYD testing.Among the patients in cohort A,15%tested only the DPYD2A polymorphism,19%tested four polymorphisms(DPYD2A,HapB3,c.2846A>T,and DPYD13),and 66%tested five polymorphisms including DPYD6.RESULTS Overall,14.8%of patients were found to be carriers of a DPYD variant,the most common being DPYD6(12.1%).Patients in cohort A reported≥G3 toxicities(P=0.00098),particularly fewer nonhematological toxicities(P=0.0028)compared with cohort B,whereas there was no statistically significant difference between the two cohorts in hematological toxicities(P=0.6944).Significantly fewer chemotherapy dose reductions(P=0.00002)were observed in cohort A compared to cohort B,whereas there was no statistically significant differences in chemotherapy delay.CONCLUSION Although this study had a limited sample size,it provides additional information on the prevalence of DPYD polymorphisms in the Italian population and highlights the role of pharmacogenetic testing to prevent severe toxicity.
文摘Treatments for low degree hemorrhoids(I-III degree)are numerous and so are their counterparts for higher degrees.These treatments present nebulous diffe-rences in terms of indications and outcomes among techniques.Methods previously abandoned due to side effects and long-term results have recently rejoined the mainstream due to recent peculiar modifications:Hemorrhoidal sclerotherapy is enjoying a new age of interest due to the use of the foam form of polidocanol,which is more effective than the liquid one.Various articles have already shown promising results and the logical next step is the combination of polidocanol foam with rubber-band ligation(the historical counterpart of sclero-therapy)in a technique called“sclerobanding”.In this article,we comment on the publication by Qu et al further modifying the use of sclerobanding through an endoscopic delivery for patients with grade II-III internal hemorrhoids,and present results compared with endoscopic rubber band ligation.The results achieved are promising.
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.
基金Supported by Fondazione di Sardegna,No.2020.2284.
文摘Celiac disease(CD)is a systemic autoimmune disorder triggered by gluten ingestion ingenetically predisposed individuals.It is characterized by intestinal histological damage and the production of specific autoantibodies.The latest European Society for Paediatric Gastroenterology,Hepatology,and Nutrition(ESPGHAN)2020 guidelines have excluded human leukocyte antigen(HLA)genotyping from the no-biopsy diagnostic approach due to its weak positive predictive value,limited availability,and high cost in some countries.However,HLA genetic testing remains valuable in certain clinical contexts.This study provided practical indications for when to request and how to interpret HLA genotyping,emphasizing its continued relevance for CD diagnosis in specific cases.We also proposed a strategy for monitoring the risk of developing type 1 diabetes(T1D)in patients with CD,based on the risk stratification carried by different HLA genotypes.A retrospective analysis of 746 patients with CD and 627 controls was conducted at our hospital starting in2012,when HLA genotyping became mandatory for the diagnosis of CD.We identified key clinical scenarios where HLA testing remains useful.Several high risk HLA-DQ genotypes strongly associated with CD were highlighted,including HLA-DQ2.5/HLA-DQ2.2and HLA-DQ2.5/HLA-DQ2.5.Notably,while the HLA-DQ2.5/HLA-DQ2.2 genotype is linked to CD,it appears to confer protection against T1D.To support clinical practice,we presented a table clarifying commonly used HLA terminology,and another summarized the main clinical situations in which HLAgenotyping should still be considered.These findings underscore the dual role of HLA testing:Not only can it help rule out CD in selected cases,but it also identifies patients with CD at risk for T1D,guiding personalized monitoring strategies.
文摘Platelet rich plasma(PRP)is an autologous blood product rich in platelets,showing promise in reducing inflammation and accelerating healing.While extensively utilized in plastic surgery,dermatology,and osteoarthritis treatment,its application in anterior cruciate ligament(ACL)injuries is limited.This article examines PRP's potential in ACL reconstruction(ACLR),exploring its history,current usage,controversies and future directions.PRP has demonstrated significant early benefits in ligamentisation and vascularisation post-ACLR,though its long-term efficacy is inconsistent.Studies suggest that PRP may serve as both an adjunct therapy in ACLR to enhance initial healing and reduce postoperative complications,and as a non-surgical alternative for small ACL tears.Despite these promising findings,outcome variability necessitates further high-quality research to optimize PRP formulations and determine its most effective applications.The exploration of PRP as a treatment modality in ACLR offers promising but varied outcomes.PRP holds considerable promise as both an adjunct and alternative to traditional ACLR.This article underscores the need for targeted research to fully realize PRP's therapeutic potential in ACL treatment,aiming to inform future studies and clinical practices.By understanding PRP's mechanisms of efficacy and identifying the most beneficial patient populations,PRP could significantly impact orthopaedics and sports medicine,improving recovery pathways and patient outcomes.
文摘AIM: To investigate the correlation between autoimmune thyroid diseases (ATDs) and the prevalence of Cag-A positive strains of Helicobacter pylori (H. pylori) in stool samples. METHODS: We investigated 112 consecutive Caucasian patients (48 females and 4 males with Graves' disease and 54 females and 6 males with Hashimoto' s thyroiditis HT), at their first diagnosis of ATDs. We tested for H. pylori in stool samples using an amplified enzyme immunoassay and Cag-A in serum samples using an enzyme-linked immunoassay method (ELISA). The results were analyzed using the two-sided Fisher' s exact test and the respective odds ratio (OR) was calculated. RESULTS: A marked correlation was found between the presence of H. pylori (P ≤ 0.0001, OR 6.3) and, in particular, Cag-A positive strains (P ≤ 0.005, OR 5.3)in Graves' disease, but not in Hashimoto's thyroiditis, where we found only a correlation with Cag-A strains (P ≤ 0.005, OR 8.73) but not when H. pylori was present. CONCLUSION: The marked correlation between H. pylori and Cag-A, found in ATDs, could be dependent on the different expression of adhesion molecules in the gastric mucosa.
文摘Radical gastrectomy with an adequate lymphadenectomy is the main procedure which makes it possible to cure patients with resectable gastric cancer (GC). A number of randomized controlled trials and meta-analysis provide phase III evidence that laparoscopic gastrectomy is technically safe and that it yields better short-term outcomes than conventional open gastrectomy for early-stage GC. While laparoscopic gastrectomy has become standard therapy for early-stage GC, especially in Asian countries such as Japan and South Korea, the use of minimally invasive techniques is still controversial for the treatment of more advanced tumours, principally due to existing concerns about its oncological adequacy and capacity to carry out an adequately extended lymphadenectomy. Some intrinsic drawbacks of the conventional laparoscopic technique have prevented the worldwide spread of laparoscopic gastrectomy for cancer and, despite technological advances in recent year, it remains a technically challenging procedure. The introduction of robotic surgery over the last ten years has implied a notable mutation of certain minimally invasive procedures, making it possible to overcome some limitations of the traditional laparoscopic technique. Robot-assisted gastric resection with D2 lymph node dissection has been shown to be safe and feasible in prospective and retrospective studies. However, to date there are no high quality comparative studies investigating the advantages of a robotic approach to GC over traditional laparoscopic and open gastrectomy. On the basis of the literature review here presented, robot-assisted surgery seems to fulfill oncologic criteria for D2 dissection and has a comparable oncologic outcome to traditional laparoscopic and open procedure. Robot-assisted gastrectomy was associated with the trend toward a shorter hospital stay with a comparable morbidity of conventional laparoscopic and open gastrectomy, but randomized clinical trials and longer follow-ups are needed to evaluate the possible influence of robot gastrectomy on GC patient survival.
文摘Implantation of an inflatable penile prosthesis （IPP） is a well-established definitive solution for erectile dysfunction when conservative treatments fail. Penile implants may shorten the penis. The AMS 700 LGX IPP is in common use but reports on its mechanical reliability, medium-term postsurgical patient satisfaction, and mean penile length preservation are lacking. We investigate the mean penile length, mechanical reliability, and patient satisfaction at 6 and 12 months after implantation of the AMS 700 LGX. This prospective study consecutively enrolled men undergoing first-time IPP implant surgery from February 2009 to April 2012. Stretched flaccid penile length, penile length at 50% and 100% of stiffness （PSO and P100） and International Index of Erectile Function （IIEF） and Erectile Dysfunction Inventory of Treatment Satisfaction （EDITS） scores, were measured at 6 and 12 months postsurgery. Of 45 patients who underwent AMS 700 LGX implantation （median age 61 years） and completed 6 months＇ follow-up, 36 （80%） completed the study. A significant difference in stretched flaccid penile length was seen between 6 and 12 months （P= 0.033）. P100 was also significantly increased at 6 and 12 months, with a mean 10% increase （1.3 ±0.4 cm） from baseline to 12 months. Differences in mean IIEF scores at 6 and 12 months were significant for the desired domain （P = 0.0001） and for overall satisfaction （P = 0.002）; however, mean EDITS scores at 6 and 12 months were not significantly improved. AMS 700 LGX is a powerful tool for preserving penile length in men undergoing penile prosthesis implantation.
文摘Myocarditis is a bacterial or viral inflammatory disease,often unnoticed or misdiagnosed.Athletes with myocarditis must stop practicing their activity since International medical Literature described some cases of sudden death.In the present report,we describe a case of an asymptomatic,apparently healthy,competitive athletes,who was diagnosed a myocarditis and as incidental finding a myocardial bridging.We focused the attention on the importance of anamnesis,electrocardiogram and athletes' entourage for the diagnosis of such insidious pathologies and we evaluated the follow up,focusing the attention on electrocardiogram changes as well as on restitution ad integrum and prognosis,especially for the athletes.
文摘One out of three hospitalizations for acute coronary syndrome(ACS)involve nowadays elderly patients,carrying together a significant burden of comorbidities and a higher risk of complications.In particular,both ischemic and haemorrhagic risk are markedly enhanced in advanced age,and strictly interconnected,challenging the management of dual antiplatelet therapy(DAPT)in these patients.The recent development of several therapeutic options in terms of duration and combination of antiplatelet agents have offered a wider spectrum of opportunities for a more individualized approach in the management of DAPT after an ACS,although the criteria for the selection of the most appropriate strategy in each patient still lack validation.In particular,dose-adjustment,early aspirin discontinuation,laboratory-driven tailoring and shorter or extended DAPT have been addressed with promising safety and efficacy results.The present review provides an updated overview on the emerging evidencefrom randomized clinical trials and subanalyses dedicated to the management of DAPT in elderly patients presenting with ACS.
文摘Emergence from anesthesia(AE) is the ending stage of anesthesia featuring the transition from unconsciousness to complete wakefulness and recovery of consciousness(RoC). A wide range of undesirable complications, including coughing, respiratory/cardiovascular events, and mental status changes such as emergence delirium, and delayed RoC, may occur during this critical phase. In general anesthesia processes, induction and AE represent a neurobiological example of "hysteresis". Indeed, AE mechanisms should not be simply considered as reverse events of those occurring in the induction phase. Anesthesia-induced loss of consciousness(LoC) and AE until RoC are quite distinct phenomena with, in part, a distinct neurobiology. Althoughanaesthetics produce LoC mostly by affecting cortical connectivity, arousal processes at the end of anesthesia are triggered by structures deep in the brain, rather than being induced within the neocortex. This work aimed to provide an overview on AE processes research, in terms of mechanisms, and EEG findings. Because most of the research in this field concerns preclinical investigations, translational suggestions and research perspectives are proposed. However, little is known about the relationship between AE neurobiology, and potential complications occurring during the emergence, and after the RoC. Thus, another scope of this review is to underline why a better understanding of AE mechanisms could have significant clinical implications, such as improving the patients' quality of recovery, and avoiding early and late postoperative complications.
文摘AIM:To clarify which method has accuracy:2nd gen-eration contrast-enhanced ultrasound or biopsy of portal vein thrombus in the differential diagnosis of portal vein thrombosis.METHODS:One hundred and eighty-six patients with hepatocellular carcinoma and portal vein thrombosis underwent in blinded fashion a 2nd generation contrast-enhanced ultrasound and biopsy of portal vein thrombus;both results were examined on the basis of the follow-up of patients compared to reference-standard.RESULTS:One hundred and eight patients completed the study.Benign thrombosis on 2nd generation contrast-enhanced ultrasound was characterised by progressive hypoenhancing of the thrombus;in malignant portal vein thrombosis there was a precocious homo-geneous enhancement of the thrombus.On follow-up there were 50 of 108 patients with benign thrombosis:all were correctly diagnosed by both methods.There were 58 of 108 patients with malignant thrombosis:amongst these,52 were correctly diagnosed by both methods,the remainder did not present malignant cells on portal vein thrombus biopsy and showed on 2nd generation contrast-enhanced ultrasound an inho-mogeneous enhancement pattern.A new biopsy during the follow-up,guided to the area of thrombus that showed up on 2nd generation contrast-enhanced ultra-sound,demonstrated an enhancing pattern indicating malignant cells.CONCLUSION:In patients with hepatocellular carcinoma complicated by portal vein thrombosis,2nd generation contrast-enhanced ultrasound of portal vein thrombus is very useful in assessing the benign or malignant nature of the thrombus.Puncture biopsy of thrombus is usually accurate but presents some sampling errors,so,when pathological results are required,2nd generation contrast-enhanced ultrasound could guide the sampling needle to the correct area of the thrombus.
文摘Emergency physicians are required to care for unstable patients with life-threatening conditions,and thus must make decisions that are both quick and precise about unclear clinical situations.There is increasing consensus in favor of using ultrasound as a real-time bedside clinical tool for clinicians in emergency settings alongside the irreplaceable use of historical and physical examinations.B-mode sonography is an old technology that was first proposed for medical applications more than 50 years ago.Its application in the diagnosis of thoracic diseases has always been considered limited,due to the presence of air in the lung and the presence of the bones of the thoracic cage,which prevent the progression of the ultrasound beam.However,the close relationship between air and water in the lungs causes a variety of artifacts on ultrasounds.At the bedside,thoracic ultrasound is based primarily on the analysis of these artifacts,with the aim of improving accuracy and safety in the diagnosis and therapy of the various varieties of pulmonary pathologic diseases which are predominantly"water-rich"or"air-rich".The indications,contraindications,advantages,disadvantages,and techniques of thoracic ultrasound and its related procedures are analyzed in the present review.
文摘Objectives:Intensive health services'utilization is common in older individuals affected by chronic diseases.This study assessed whether a structured family nurse-led educational intervention would be effective in reducing health services'use(readmissions and/or emergency service access)among older people affected by chronic conditions.Methods:This is a non-randomized before-after pilot study.A sample of 78 patients was recruited from two general practices in Italy and 70 among them were followed for 8 months.Standard home care was provided during the first four months'period(months 1-4),followed by the educational intervention until the end of the study(months 5-8).The intervention,based on the teach-back method,consisted of by-weekly 60-min home sessions targeting aspects of the disease and its treatment,potential complications,medication adherence,and health behaviours.Rates of health services'use were collected immediately before(T0),and after the interventions(T1).Differences in utilization rates were examined by the McNemar's test.Potential factors associated with the risk of health services'use were explored with a Cox proportional hazard regression model.Results:The sample(n=78)was predominantly female(n=50,64.1%),and had a mean age of 76.2(SD=4.8)years.Diabetes mellitus was the most frequent disease(n=27,34.6%).McNemar's test indicated a significant reduction in health services'use at T1(McNemar χ^(2)==28.03,P<0.001).Cox regressions indicated that time and patient education,as well as their interaction,were the only variables positively associated with the probability of health services'use.Conclusion:A teach-back intervention led by a family nurse practitioner has the potential to reduce health services'use in older patients with chronic diseases.
