AIM To investigate the neoadjuvant chemotherapy(NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.METHODS We proceeded to a review of the literature with Pub Med, Embase, A...AIM To investigate the neoadjuvant chemotherapy(NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.METHODS We proceeded to a review of the literature with Pub Med, Embase, ASCO and ESMO meeting abstracts as well as computerized use of the Cochrane Library for randomized controlled trials(RCTs) comparing NAC followed by surgery(NAC + S) with surgery alone(SA) for gastric cancer(GC). The primary outcome was the overall survival rate. Secondary outcomes were the site of the primary tumor, extension of node dissection according to Japanese Gastric Cancer Association(JGCA) performed in both arms, disease-specific(DSS) and disease-free survival(DFS) rates, clinical and pathological response rates and resectability rates after perioperative treatment. RESULTS We identified a total of 16 randomized controlled trials comparing NAC + S(n = 1089) with SA(n = 973) published in the period from January 1993-March 2017. Only 6 of these studies were well-designed, structured trials in which the type of lymph node(LN) dissection performed or at least suggested in the trial protocol was reported. Two out of three of the RCTs with D2 lymphadenectomy performed in almost all cases failed to show survival benefit in the NAC arm. Inthe third RCT, the survival rate was not even reported, and the primary end points were the clinical outcomes of surgery with and without NAC. In the remaining three RCTs, D2 lymph node dissection was performed in less than 50% of cases or only recommended in the "Study Treatment" protocol without any description in the results of the procedure really perfomed. In one of the two studies, the benefit of NAC was evident only for esophagogastric junction(EGJ) cancers. In the second study, there was no overall survival benefit of NAC. In the last trial, which documented a survival benefit for the NAC arm, the chemotherapy effect was mostly evident for EGJ cancer, and more than one-fourth of patients did not have a proper stomach cancer. Additionally, several patients d展开更多
Hepatitis B virus(HBV)is the leading cause of chronic viral hepatitis.Annually,almost two million children younger than 5 years acquire the infection,mostly through vertical or horizontal transmission in early life.Ve...Hepatitis B virus(HBV)is the leading cause of chronic viral hepatitis.Annually,almost two million children younger than 5 years acquire the infection,mostly through vertical or horizontal transmission in early life.Vertical transmission of HBV is a high efficacy phenomenon ranging,in the absence of any preventive interventions,from 70%to 90%for hepatitis e antigen positive mothers and from 10%to 40%for hepatitis e antigen-negative mothers.Maternal viraemia is a preeminent risk factor for vertical transmission of HBV.Maternal screening is the first step to prevent vertical transmission of HBV.Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection.Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low-and middle-income countries where the prevalence of the infection is at the highest.展开更多
Glial cells in the gut represent the morphological and functional equivalent of astrocytes and microglia in the central nervous system （CNS）. In recent years, the role of enteric glial cells （EGCs） has extended fr...Glial cells in the gut represent the morphological and functional equivalent of astrocytes and microglia in the central nervous system （CNS）. In recent years, the role of enteric glial cells （EGCs） has extended from that of simple nutritive support for enteric neurons to that of being pivotal participants in the regulation of inflammatory events in the gut. Similar to the CNS astrocytes, the EGCs physiologically express the SIOOB protein that exerts either trophic or toxic effects depending on its concentration in the extracellular milieu. In the CNS, SIOOB overexpression is responsible for the initiation of a gliotic reaction by the release of pro-inflammatory mediators, which may have a deleterious effect on neighboring cells. SlOOB-mediated pro-inflammatory effects are not limited to the brain： SIOOB overexpression is associated with the onset and maintenance of inflammation in the human gut too. In this review we describe the major features of EGCs and SIOOB protein occurring in intestinal inflammation deriving from such.展开更多
The prognosis for patients who are diagnosed with advanced stage hepatocellular carcinoma(HCC)is poor because there are few treatment options.Recent research has focused on the identification of novel molecular entiti...The prognosis for patients who are diagnosed with advanced stage hepatocellular carcinoma(HCC)is poor because there are few treatment options.Recent research has focused on the identification of novel molecular entities that can be targeted to inhibit oncogenic signals that are involved in the carcinogenesis,proliferation and progression of HCC.Among all of the pathways that are involved in the development of HCC,Hedgehog(HH)signalling has demonstrated a substantial role in hepatocarcinogenesis and HCC progression.HH plays a physiological role in embryogenesis,through the induction of the differentiation of hepatocytes from endodermal progenitors.The re-activation of the HH pathway in chronic damaged liver is a mechanism of fibrotic degeneration and is implicated in various stages of HCC development.HH activation sustains the subpopulation of immature liver epithelial cells that are involved in the pathogenesis of cirrhosis and HCC,and HH itself is a mediator of the alcohol-derived malignant transformation of liver cells.High levels of expression of HH protein markers in liver tumour tissues are correlated with aggressive histological and biological features and a poor clinical outcome.In vitro and in vivo inhibition models of the HH pathway confirm that HH is essential in maintaining tumour growth,metastasis and a mesenchymal phenotype.展开更多
Erectile dysfunction （ED） is a common medical disorder whose prevalence is increasing worldwide. Modifiable risk factors for ED include smoking, lack of physical activity, wrong diets, overweight or obesity, metabol...Erectile dysfunction （ED） is a common medical disorder whose prevalence is increasing worldwide. Modifiable risk factors for ED include smoking, lack of physical activity, wrong diets, overweight or obesity, metabolic syndrome, and excessive alcohol consumption. Quite interestingly, all these metabolic conditions are strongly associated with a pro-inflammatory state that results in endothelial dysfunction by decreasing the availability of nitric oxide （NO）, which is the driving force of the blood genital flow. Lifestyle and nutrition have been recognized as central factors influencing both vascular NO production, testosterone levels, and erectile function. Moreover, it has also been suggested that lifestyle habits that decrease low-grade clinical inflammation may have a role in the improvement of erectile function. In clinical trials, lifestyle modifications were effective in ameliorating ED or restoring absent ED in people with obesity or metabolic syndrome. Therefore, promotion of healthful lifestyles would yield great benefits in reducing the burden of sexual dysfunction. Efforts, in order to implement educative strategies for healthy lifestyle, should be addressed.展开更多
AIM： To estimate the prevalence of small intestine bacterial overgrowth （SIBO） among patients with an earlier diagnosis of irritable bowel disease （IBS） in our geographical area, and to collect information on the...AIM： To estimate the prevalence of small intestine bacterial overgrowth （SIBO） among patients with an earlier diagnosis of irritable bowel disease （IBS） in our geographical area, and to collect information on the use of locally acting non-absorbable antibiotics in the management of SIBO. METHODS： A non-interventional study was conducted in 73 consecutive patients with a symptom-based diagnosis.. RESULTS： When the patients underwent a ＂breath test＂, 33 （45.2%） showed the presence of a SIBO. Arcer treatment with rifaximin 1200 mg/d for seven days in 32 patients, 19 （59.4%） showed a negative ＂breath test＂ one week later as well as a significant reduction of symptoms, thus confirming the relationship between SIBO and many of the symptoms claimed by patients. In the other 13 patients, ＂breath test＂ remained positive, and a further cycle of treatment with ciprofloxacin 500 mg/d was given for 7 additional days, resulting in a negative ＂breath test＂ in one patient only. CONCLUSION： （1） about half of the patients with a symptomatic diagnosis of IBS have actually SIBO, which is responsible for most of the symptoms attributed to IBS; （2） only a ＂breath test＂ with lactulose （or with glucose in subjects with an intolerance to lactose） can provide a differential diagnosis between IBS and SIBO, with almost identical symptoms; and （3） the use of non-absorbable antibiotics may be useful to reduce the degree of SIBO and related symptoms; it must be accompanied, however, by the correction of the wrong alimentary habits underlying SIBO.展开更多
AIM:To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis.METHODS:Wistar specific pathogen-free rats were submitted to a Hartmann's end colostomy and tre...AIM:To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis.METHODS:Wistar specific pathogen-free rats were submitted to a Hartmann's end colostomy and treated with enemas containing glutamine,butyrate,or saline.Enemas were administered twice a week in the excluded segment of the colon from 4 to 12 wk after the surgical procedure.Follow-up colonoscopy was performed every 4 wk for 12 wk.The effect of treatment was evaluated using video-endoscopic and histologic scores and measuring interleukin-1β,tumor necrosis factor-alpha,and transforming growth factor beta production in organ cultures by enzyme linked immunosorbent assay.RESULTS:Colonoscopies of the diverted segment showed mucosa with hyperemia,increased number of vessels,bleeding and mucus discharge.Treatment with either glutamine or butyrate induced significant reductions in both colonoscopic(P < 0.02) and histological scores(P < 0.01) and restored the densities of collagen fibers in tissue(P = 0.015;P = 0.001),the number of goblet cells(P = 0.021;P = 0.029),and the rate of apoptosis within the epithelium(P = 0.043;P = 0.011) to normal values.The high levels of cytokines in colon explants from rats with diversion colitis significantly decreased to normal values after treatment with butyrate or glutamine.CONCLUSION:The improvement of experimental diversion colitis following glutamine or butyrate enemas highlights the importance of specific luminal nutrients in the homeostasis of the colonic mucosa and supports their utilization for the treatment of human diversion colitis.展开更多
Chronic liver disease is characterized by several hematological derangements resulting in a complex and barely rebalanced haemostatic environment.Thrombocytopenia is the most common abnormality observed in these patie...Chronic liver disease is characterized by several hematological derangements resulting in a complex and barely rebalanced haemostatic environment.Thrombocytopenia is the most common abnormality observed in these patients and recent advances have led to researchers focus the attention on the multifactorial origin of thrombocytopenia and on the key role of thrombopoietin(TPO)in its physiopathology.Severe thrombocytopenia(platelet count<50000/μL)complicates the management of patients with chronic liver disease by increasing the potential risk of bleeding for invasive procedures,which may be therefore delayed or canceled even if lifesaving.In the very last years,the development of new drugs which exceed the limits of the current standard of care(platelet transfusions,either immediately before or during the procedure)paves the way to a new scenario in the management of this population of patients.Novel agents,such as the TPOreceptor agonists avatrombopag and lusutrombopag,have been developed in order to increase platelet production as an alternative to platelet transfusions.These agents have demonstrated a good profile in terms of efficacy and safety and will hopefully allow reducing limitations and risks associated with platelet transfusion,without any delay in scheduled interventions.Altogether,it is expected that patients with chronic liver disease will be able to face invasive procedures with one more string in their bow.展开更多
Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because ...Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because of the large number of voxels in the brain,multiple comparison correction(MCC)must be performed to reduce false positive rates,and a smaller P value(usually including either liberal or stringent MCC)is widely recommended[1].展开更多
Acute humoral rejection （AHR） is uncommon after ABO- compatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients wit...Acute humoral rejection （AHR） is uncommon after ABO- compatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Uver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab. Liver enzymes returned to within normal range 18 d after diagnosis. Uver biopsies, at 3 and 9 mo post-transplant, showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.展开更多
AIM To investigate the role of tacrolimus intra-patient variability(IPV) in adult liver-transplant recipients.METHODS We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and a...AIM To investigate the role of tacrolimus intra-patient variability(IPV) in adult liver-transplant recipients.METHODS We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and analyzed its effect on the occurrence of graft rejection and de novo donor-specific antibodies(dn DSAs), as well as graft survival during the first 2 years posttransplantation. Between 02/08 and 06/2015, 116 patients that received tacrolimus plus mycophenolate mofetil(with or without steroids) were included. RESULTS Twenty-two patients(18.5%) experienced at least one acute-rejection episode(BPAR). Predictive factors for a BPAR were a tacrolimus IPV of > 35% [OR = 3.07 95%CI(1.14-8.24), P = 0.03] or > 40% [OR = 4.16(1.38-12.50), P = 0.01), and a tacrolimus trough level of < 5 ng/mL [OR=3.68(1.3-10.4), P =0.014]. Thirteen patients(11.2%) developed at least one dn DSA during the follow-up. Tacrolimus IPV [coded as a continuous variable: OR = 1.1, 95%CI(1.0-1.12), P = 0.006] of > 35% [OR = 4.83, 95%CI(1.39-16.72), P = 0.01] and > 40% [OR = 9.73, 95%CI(2.65-35.76), P = 0.001] were identified as predictors to detect dn DSAs. IPV did not impact on patient-or graft-survival rates during the follow-up. CONCLUSION Tacrolimus-IPV could be a useful tool to identify patients with a greater risk of graft rejection and of developing a de novo DSA after liver展开更多
Vulvar Crohn’s disease (VCD) is a rare complication of Crohn’s disease, especially in pediatric population. An early diagnosis can result difficult if the complication does not present in conjunction with the classi...Vulvar Crohn’s disease (VCD) is a rare complication of Crohn’s disease, especially in pediatric population. An early diagnosis can result difficult if the complication does not present in conjunction with the classic gastrointestinal symptoms that characterize this disease. In this study we present the case of a 12-year-old girl whose initial symptom of Crohn’s disease was a symptomatic vulvar swelling promoted by a rectovaginal fistula. We also provide an overview of Crohn’s disease and the vulvar changes found in the course of this disease.展开更多
Despite major improvements concerning its diagnosis and treatment,pancreatic ductal adenocarcinoma(PDAC) remains an aggressive disease with an extremely poor prognosis. Pathology,as interface discipline between basic ...Despite major improvements concerning its diagnosis and treatment,pancreatic ductal adenocarcinoma(PDAC) remains an aggressive disease with an extremely poor prognosis. Pathology,as interface discipline between basic and clinical medicine,has substantially contributed to the recent developments and has laid the basis for further progress. The definition and classification of precursor lesions of PDAC and their molecular characterization is a fundamental step for the potential identification of biomarkers and the development of imaging methods for early detection. In addition,by integrating findings in humans with the knowledge acquired through the investigation of transgenic mouse models for PDAC,a new model for pancreatic carcinogenesis has been proposed and partially validated in individuals with genetic predisposition for PDAC. The introduction and validation of a standardized system for pathology reporting based on the axial slicing technique has shown that most pancreatic cancer resections are R1 resections and that this is due to inherent anatomical and biological properties of PDAC.This standardized assessment of prognostic relevant parameters represents the basis for the successful conduction of multicentric studies and for the interpretation of their results.Finally,recent studies have shown that distinct molecular subtypes of PDAC exist and are associated with different prognosis and therapy response.The prospective validation of these results and the integration of molecular analyses in a comprehensive pathology report in the context of individualised cancer therapy represent a major challenge for the future.展开更多
Klinefelter syndrome （KS） is a hypergonadotropic hypogonadism characterized by a 47, XXY karyotype. The risk of testicular cancer in KS is of interest in relation to theories about testicular cancer etiology general...Klinefelter syndrome （KS） is a hypergonadotropic hypogonadism characterized by a 47, XXY karyotype. The risk of testicular cancer in KS is of interest in relation to theories about testicular cancer etiology generally; nevertheless it seems to be low. We evaluated the need for imaging and serum tumor markers for testicular cancer screening in KS. Participants were 40 consecutive KSpatients, enrolled from December 2009 to January 2013. Lactate dehydrogenase （LDH）, alpha-fetoprotein （AFP）, and beta-human chorionic gonadotrophin subunit （^-HCG） serum levels assays and testicular ultrasound （US） with color Doppler, were carried out at study entry, after 6 months and every year for 3 years. Abdominal magnetic resonance （MR） was performed in KS when testicular US showed micro-calcifications, testicular nodules and cysts. Nearly 62% of the KS had regular testicular echotexture, 37.5% showed an irregular echotexture and 17.5% had micro-calcifications and cysts. Eighty seven percent of KS had a regular vascular pattern, 12.5% varicocele, 12.5% nodules 〈1 cm, but none had nodules 〉1 cm. MR ruled out the diagnosis of cancer in all KS with testicular micro calcifications, nodules and cysts. No significant variations in LDH, AFP, and ^-HCG levels and in US pattern have been detected during follow-up. We compared serum tumor markers and US pattern between KS with and without cryptorchidism and no statistical differences were found. We did not find testicular cancer in KS, and testicular US, tumor markers and MR were, in selected cases, useful tools for correctly discriminating benign from malignant lesions.展开更多
Pancreatic neuroendocrine neoplasms(PNENs) are rare and account for only 2%-4% of all pancreatic neoplasms. All PNENs are potential(neurendocrine tumors PNETs) or overt(neuroendocrine carcinomas PNECs) malignant,but a...Pancreatic neuroendocrine neoplasms(PNENs) are rare and account for only 2%-4% of all pancreatic neoplasms. All PNENs are potential(neurendocrine tumors PNETs) or overt(neuroendocrine carcinomas PNECs) malignant,but a subset of PNETs is low-risk. Even in case of low-risk PNETs surgical resection is frequently required to treat hormone-related symptoms and to obtain an appropriate pathological diagnosis. Low-risk PNETs in the body and the tail are ideal for minimallyinvasive approaches which should be tailored to the individual patient. Generally,surgeons must aim for parenchyma sparing in these cases. In high-risk and malignant PNENs,indications for tumor resection are much wider than for pancreatic adenocarcinoma,in many cases due to the relatively benign tumor biology. Thus,patients with locally advanced and metastatic PNETs may benefit from extensive resection. In experienced hands,even multi-organ resections are accomplished with acceptable perioperative morbidity and mortality rates and are associated with excellent long term survival. However,poorly differentiated neoplasms with high proliferation rates are associated with a dismal prognosis and may frequently only be treated with chemotherapy. The evidence on surgical treatment of PNENs stems from reviews of mostly singlecenter series and some analyses of nation-wide tumor registries. No randomized trial has been performed to compare surgical and non-surgical therapies in potentially resectable PNEN. Though such a trial would principally be desirable,ethical considerations and the heterogeneity of PNENs preclude realization of such a study. In the current review,we summarize recent advances in the surgical treatment of PNENs.展开更多
Eosinophilic esophagitis(Eo E) is a chronic immune disease, characterized by a dense eosinophilic infiltrate in the esophagus, leading to bolus impaction and refluxlike symptoms. Traditionally considered a pediatric d...Eosinophilic esophagitis(Eo E) is a chronic immune disease, characterized by a dense eosinophilic infiltrate in the esophagus, leading to bolus impaction and refluxlike symptoms. Traditionally considered a pediatric disease, the number of adult patients with Eo E is continuously increasing, with a relatively higher incidence in western countries. Dysphagia and food impaction represent the main symptoms complained by patients, but gastroesophageal reflux-like symptoms may also be present. Esophageal biopsies are mandatory for the diagnosis of Eo E, though clinical manifestations and proton pump inhibitors responsiveness must be taken into consideration. The higher prevalence of Eo E in patients suffering from atopic diseases suggests a common background with allergy, however both the etiology and pathophysiology are not completely understood. Elimination diets are considered the firstline therapy in children, but this approach appears less effective in adults patients, who often require steroids; despite medical treatments, Eo E is complicated in some cases by esophageal stricture and stenosis, that require additional endoscopic treatments. This review summarizes the evidence on Eo E pathophysiology and illustrates the safety and efficacy of the most recent medical and endoscopic treatments.展开更多
Acetazolamide is the commonly prescribed oral and intravenous carbonic anhydrase inhibitor;over the years,its use in clinical practice has decreased in favor of more recent drugs.However,it is a rather handy drug,whic...Acetazolamide is the commonly prescribed oral and intravenous carbonic anhydrase inhibitor;over the years,its use in clinical practice has decreased in favor of more recent drugs.However,it is a rather handy drug,which can be useful in several clinical settings when managing critically ill patients.The objective of this review is the evaluation of the most recent evidence on the use of acetazolamide in emergency medicine and critical care medicine.Furthermore,the safety profile of this drug has been evaluated.This is a narrative review on the use of acetazolamide in the main contexts in which this drug can be useful in emergency situations for patients with potential critical issues.For the timeline 1999–2024,a search was conducted on the main scientific platforms;resources of greatest relevance for the use of acetazolamide in critical care and emergency medicine were selected.The most common emergency situations in which a critically ill patient could benefit from acetazolamide therapy are acute heart failure,acute mountain sickness,post hypercapnic metabolic alkalosis,idiopathic intracranial hypertension and acute angle-closure glaucoma.In a few cases,however,randomized controlled clinical trials have been conducted.There are also other less solid indications based mostly on experience or retrospective data.Acetazolamide seems to be an overall safe drug;serious side effects are rare and can be avoided by carefully selecting the patients to be treated.Acetazolamide represents a precious resource for emergency physicians and intensivists;critical patients with different conditions can in fact benefit from it;furthermore,acetazolamide is a safe drug if administered to correctly selected patients.展开更多
Autologous blood therapy has emerged as a promising modality in managing ocular surface disorders.This review provides a comprehensive overview of the current literature regarding the use of autologous blood in ocular...Autologous blood therapy has emerged as a promising modality in managing ocular surface disorders.This review provides a comprehensive overview of the current literature regarding the use of autologous blood in ocular surface disorders,encompassing its physiological basis,clinical applications,techniques,challenges,and future perspectives.The ocular surface,comprising the cornea,conjunctiva,and tear film,plays a critical role in maintaining visual function,and its disruption can lead to various pathological conditions.With its rich composition of growth factors,cytokines,and other bioactive molecules,autologous blood offers therapeutic potential in promoting corneal wound healing,reducing inflammation,and improving tear film stability.Clinical studies have demonstrated the efficacy and safety of autologous blood therapy in diverse ocular surface disorders,including persistent epithelial defects,neurotrophic keratopathy,and dry eye disease.However,challenges such as variability in treatment response,adverse effects,and optimal patient selection remain areas of concern.Further research is needed to elucidate the underlying mechanisms of action,refine treatment protocols,and explore synergistic approaches with other therapeutic modalities.Despite these challenges,autologous blood therapy holds promise as a valuable adjunctive treatment option for ocular surface disorders,offering new avenues for improving patient outcomes and quality of life.This review examines the mechanisms underlying ocular surface disorders while discussing existing autologous blood-based therapies for managing these disorders.Current clinical trials are also summarized,and a comparison between autologous blood therapy and conventional eyedrops is attempted.Finally,safe techniques and protocols for autologous blood medicine are elucidated,and adverse effects and future perspectives of this novel therapy are reviewed.展开更多
文摘AIM To investigate the neoadjuvant chemotherapy(NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.METHODS We proceeded to a review of the literature with Pub Med, Embase, ASCO and ESMO meeting abstracts as well as computerized use of the Cochrane Library for randomized controlled trials(RCTs) comparing NAC followed by surgery(NAC + S) with surgery alone(SA) for gastric cancer(GC). The primary outcome was the overall survival rate. Secondary outcomes were the site of the primary tumor, extension of node dissection according to Japanese Gastric Cancer Association(JGCA) performed in both arms, disease-specific(DSS) and disease-free survival(DFS) rates, clinical and pathological response rates and resectability rates after perioperative treatment. RESULTS We identified a total of 16 randomized controlled trials comparing NAC + S(n = 1089) with SA(n = 973) published in the period from January 1993-March 2017. Only 6 of these studies were well-designed, structured trials in which the type of lymph node(LN) dissection performed or at least suggested in the trial protocol was reported. Two out of three of the RCTs with D2 lymphadenectomy performed in almost all cases failed to show survival benefit in the NAC arm. Inthe third RCT, the survival rate was not even reported, and the primary end points were the clinical outcomes of surgery with and without NAC. In the remaining three RCTs, D2 lymph node dissection was performed in less than 50% of cases or only recommended in the "Study Treatment" protocol without any description in the results of the procedure really perfomed. In one of the two studies, the benefit of NAC was evident only for esophagogastric junction(EGJ) cancers. In the second study, there was no overall survival benefit of NAC. In the last trial, which documented a survival benefit for the NAC arm, the chemotherapy effect was mostly evident for EGJ cancer, and more than one-fourth of patients did not have a proper stomach cancer. Additionally, several patients d
文摘Hepatitis B virus(HBV)is the leading cause of chronic viral hepatitis.Annually,almost two million children younger than 5 years acquire the infection,mostly through vertical or horizontal transmission in early life.Vertical transmission of HBV is a high efficacy phenomenon ranging,in the absence of any preventive interventions,from 70%to 90%for hepatitis e antigen positive mothers and from 10%to 40%for hepatitis e antigen-negative mothers.Maternal viraemia is a preeminent risk factor for vertical transmission of HBV.Maternal screening is the first step to prevent vertical transmission of HBV.Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection.Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low-and middle-income countries where the prevalence of the infection is at the highest.
基金Supported by research funds from the Italian Ministry of University and Research (COFIN Projects No. 2004062155 to GS and RC)
文摘Glial cells in the gut represent the morphological and functional equivalent of astrocytes and microglia in the central nervous system （CNS）. In recent years, the role of enteric glial cells （EGCs） has extended from that of simple nutritive support for enteric neurons to that of being pivotal participants in the regulation of inflammatory events in the gut. Similar to the CNS astrocytes, the EGCs physiologically express the SIOOB protein that exerts either trophic or toxic effects depending on its concentration in the extracellular milieu. In the CNS, SIOOB overexpression is responsible for the initiation of a gliotic reaction by the release of pro-inflammatory mediators, which may have a deleterious effect on neighboring cells. SlOOB-mediated pro-inflammatory effects are not limited to the brain： SIOOB overexpression is associated with the onset and maintenance of inflammation in the human gut too. In this review we describe the major features of EGCs and SIOOB protein occurring in intestinal inflammation deriving from such.
文摘The prognosis for patients who are diagnosed with advanced stage hepatocellular carcinoma(HCC)is poor because there are few treatment options.Recent research has focused on the identification of novel molecular entities that can be targeted to inhibit oncogenic signals that are involved in the carcinogenesis,proliferation and progression of HCC.Among all of the pathways that are involved in the development of HCC,Hedgehog(HH)signalling has demonstrated a substantial role in hepatocarcinogenesis and HCC progression.HH plays a physiological role in embryogenesis,through the induction of the differentiation of hepatocytes from endodermal progenitors.The re-activation of the HH pathway in chronic damaged liver is a mechanism of fibrotic degeneration and is implicated in various stages of HCC development.HH activation sustains the subpopulation of immature liver epithelial cells that are involved in the pathogenesis of cirrhosis and HCC,and HH itself is a mediator of the alcohol-derived malignant transformation of liver cells.High levels of expression of HH protein markers in liver tumour tissues are correlated with aggressive histological and biological features and a poor clinical outcome.In vitro and in vivo inhibition models of the HH pathway confirm that HH is essential in maintaining tumour growth,metastasis and a mesenchymal phenotype.
文摘Erectile dysfunction （ED） is a common medical disorder whose prevalence is increasing worldwide. Modifiable risk factors for ED include smoking, lack of physical activity, wrong diets, overweight or obesity, metabolic syndrome, and excessive alcohol consumption. Quite interestingly, all these metabolic conditions are strongly associated with a pro-inflammatory state that results in endothelial dysfunction by decreasing the availability of nitric oxide （NO）, which is the driving force of the blood genital flow. Lifestyle and nutrition have been recognized as central factors influencing both vascular NO production, testosterone levels, and erectile function. Moreover, it has also been suggested that lifestyle habits that decrease low-grade clinical inflammation may have a role in the improvement of erectile function. In clinical trials, lifestyle modifications were effective in ameliorating ED or restoring absent ED in people with obesity or metabolic syndrome. Therefore, promotion of healthful lifestyles would yield great benefits in reducing the burden of sexual dysfunction. Efforts, in order to implement educative strategies for healthy lifestyle, should be addressed.
文摘AIM： To estimate the prevalence of small intestine bacterial overgrowth （SIBO） among patients with an earlier diagnosis of irritable bowel disease （IBS） in our geographical area, and to collect information on the use of locally acting non-absorbable antibiotics in the management of SIBO. METHODS： A non-interventional study was conducted in 73 consecutive patients with a symptom-based diagnosis.. RESULTS： When the patients underwent a ＂breath test＂, 33 （45.2%） showed the presence of a SIBO. Arcer treatment with rifaximin 1200 mg/d for seven days in 32 patients, 19 （59.4%） showed a negative ＂breath test＂ one week later as well as a significant reduction of symptoms, thus confirming the relationship between SIBO and many of the symptoms claimed by patients. In the other 13 patients, ＂breath test＂ remained positive, and a further cycle of treatment with ciprofloxacin 500 mg/d was given for 7 additional days, resulting in a negative ＂breath test＂ in one patient only. CONCLUSION： （1） about half of the patients with a symptomatic diagnosis of IBS have actually SIBO, which is responsible for most of the symptoms attributed to IBS; （2） only a ＂breath test＂ with lactulose （or with glucose in subjects with an intolerance to lactose） can provide a differential diagnosis between IBS and SIBO, with almost identical symptoms; and （3） the use of non-absorbable antibiotics may be useful to reduce the degree of SIBO and related symptoms; it must be accompanied, however, by the correction of the wrong alimentary habits underlying SIBO.
基金Supported by Grants from the Brazilian Research CouncilFundao de Amparo à Pesquisa do Estado do Rio de Janeiro
文摘AIM:To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis.METHODS:Wistar specific pathogen-free rats were submitted to a Hartmann's end colostomy and treated with enemas containing glutamine,butyrate,or saline.Enemas were administered twice a week in the excluded segment of the colon from 4 to 12 wk after the surgical procedure.Follow-up colonoscopy was performed every 4 wk for 12 wk.The effect of treatment was evaluated using video-endoscopic and histologic scores and measuring interleukin-1β,tumor necrosis factor-alpha,and transforming growth factor beta production in organ cultures by enzyme linked immunosorbent assay.RESULTS:Colonoscopies of the diverted segment showed mucosa with hyperemia,increased number of vessels,bleeding and mucus discharge.Treatment with either glutamine or butyrate induced significant reductions in both colonoscopic(P < 0.02) and histological scores(P < 0.01) and restored the densities of collagen fibers in tissue(P = 0.015;P = 0.001),the number of goblet cells(P = 0.021;P = 0.029),and the rate of apoptosis within the epithelium(P = 0.043;P = 0.011) to normal values.The high levels of cytokines in colon explants from rats with diversion colitis significantly decreased to normal values after treatment with butyrate or glutamine.CONCLUSION:The improvement of experimental diversion colitis following glutamine or butyrate enemas highlights the importance of specific luminal nutrients in the homeostasis of the colonic mucosa and supports their utilization for the treatment of human diversion colitis.
文摘Chronic liver disease is characterized by several hematological derangements resulting in a complex and barely rebalanced haemostatic environment.Thrombocytopenia is the most common abnormality observed in these patients and recent advances have led to researchers focus the attention on the multifactorial origin of thrombocytopenia and on the key role of thrombopoietin(TPO)in its physiopathology.Severe thrombocytopenia(platelet count<50000/μL)complicates the management of patients with chronic liver disease by increasing the potential risk of bleeding for invasive procedures,which may be therefore delayed or canceled even if lifesaving.In the very last years,the development of new drugs which exceed the limits of the current standard of care(platelet transfusions,either immediately before or during the procedure)paves the way to a new scenario in the management of this population of patients.Novel agents,such as the TPOreceptor agonists avatrombopag and lusutrombopag,have been developed in order to increase platelet production as an alternative to platelet transfusions.These agents have demonstrated a good profile in terms of efficacy and safety and will hopefully allow reducing limitations and risks associated with platelet transfusion,without any delay in scheduled interventions.Altogether,it is expected that patients with chronic liver disease will be able to face invasive procedures with one more string in their bow.
基金the National Natural Science Foundation of China(81520108016,81661148045,and 31471084 to Yu-Feng Zang81671774 and 81630031 to Chao-Gan Yan+11 种基金81571228 to Tao Wu61571047 to Xia Wu81701664 to Jian Wang,81471654 to Biao Huang81701671 to Wei-Guo Liu82001898 to Xi-Ze Jia81771820,81371519 and 81571654 to Wei Luo)Henry G Leong Endowed Professorship in Neurology to Shu-Leong Ho and Shirley YY Pang,BRC for Mental Health at South London and Maudsley NHS Foundation Trust and by the Sackler Institute to Grainne McAlonan,NIH(2R01AG006457 to Fay B.Horak1RC4NS073008-01 and P50NS062684 to Tara Madhyastha)NINDS Intramural Research Program to Mark HallettStart-up Funds for Leading Talents at Beijing Normal UniversityNational Basic Science Data Center‘‘Chinese Data-sharing Warehouse for In-vivo Imaging Brain”(NBSDC-DB-15)to Xi-Nian ZuoGrant NU20-04-00294 of the Agency for Health Research,Czech Republic to Lenka Krajcovicova and Irena Rektorova。
文摘Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because of the large number of voxels in the brain,multiple comparison correction(MCC)must be performed to reduce false positive rates,and a smaller P value(usually including either liberal or stringent MCC)is widely recommended[1].
文摘Acute humoral rejection （AHR） is uncommon after ABO- compatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Uver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab. Liver enzymes returned to within normal range 18 d after diagnosis. Uver biopsies, at 3 and 9 mo post-transplant, showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.
文摘AIM To investigate the role of tacrolimus intra-patient variability(IPV) in adult liver-transplant recipients.METHODS We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and analyzed its effect on the occurrence of graft rejection and de novo donor-specific antibodies(dn DSAs), as well as graft survival during the first 2 years posttransplantation. Between 02/08 and 06/2015, 116 patients that received tacrolimus plus mycophenolate mofetil(with or without steroids) were included. RESULTS Twenty-two patients(18.5%) experienced at least one acute-rejection episode(BPAR). Predictive factors for a BPAR were a tacrolimus IPV of > 35% [OR = 3.07 95%CI(1.14-8.24), P = 0.03] or > 40% [OR = 4.16(1.38-12.50), P = 0.01), and a tacrolimus trough level of < 5 ng/mL [OR=3.68(1.3-10.4), P =0.014]. Thirteen patients(11.2%) developed at least one dn DSA during the follow-up. Tacrolimus IPV [coded as a continuous variable: OR = 1.1, 95%CI(1.0-1.12), P = 0.006] of > 35% [OR = 4.83, 95%CI(1.39-16.72), P = 0.01] and > 40% [OR = 9.73, 95%CI(2.65-35.76), P = 0.001] were identified as predictors to detect dn DSAs. IPV did not impact on patient-or graft-survival rates during the follow-up. CONCLUSION Tacrolimus-IPV could be a useful tool to identify patients with a greater risk of graft rejection and of developing a de novo DSA after liver
文摘Vulvar Crohn’s disease (VCD) is a rare complication of Crohn’s disease, especially in pediatric population. An early diagnosis can result difficult if the complication does not present in conjunction with the classic gastrointestinal symptoms that characterize this disease. In this study we present the case of a 12-year-old girl whose initial symptom of Crohn’s disease was a symptomatic vulvar swelling promoted by a rectovaginal fistula. We also provide an overview of Crohn’s disease and the vulvar changes found in the course of this disease.
基金Supported by EU COST Action BM1204 EUPancreas"An integrated european platform for pancreas cancer research:from basic science to cinical and public health interventions for a rare disease"
文摘Despite major improvements concerning its diagnosis and treatment,pancreatic ductal adenocarcinoma(PDAC) remains an aggressive disease with an extremely poor prognosis. Pathology,as interface discipline between basic and clinical medicine,has substantially contributed to the recent developments and has laid the basis for further progress. The definition and classification of precursor lesions of PDAC and their molecular characterization is a fundamental step for the potential identification of biomarkers and the development of imaging methods for early detection. In addition,by integrating findings in humans with the knowledge acquired through the investigation of transgenic mouse models for PDAC,a new model for pancreatic carcinogenesis has been proposed and partially validated in individuals with genetic predisposition for PDAC. The introduction and validation of a standardized system for pathology reporting based on the axial slicing technique has shown that most pancreatic cancer resections are R1 resections and that this is due to inherent anatomical and biological properties of PDAC.This standardized assessment of prognostic relevant parameters represents the basis for the successful conduction of multicentric studies and for the interpretation of their results.Finally,recent studies have shown that distinct molecular subtypes of PDAC exist and are associated with different prognosis and therapy response.The prospective validation of these results and the integration of molecular analyses in a comprehensive pathology report in the context of individualised cancer therapy represent a major challenge for the future.
文摘Klinefelter syndrome （KS） is a hypergonadotropic hypogonadism characterized by a 47, XXY karyotype. The risk of testicular cancer in KS is of interest in relation to theories about testicular cancer etiology generally; nevertheless it seems to be low. We evaluated the need for imaging and serum tumor markers for testicular cancer screening in KS. Participants were 40 consecutive KSpatients, enrolled from December 2009 to January 2013. Lactate dehydrogenase （LDH）, alpha-fetoprotein （AFP）, and beta-human chorionic gonadotrophin subunit （^-HCG） serum levels assays and testicular ultrasound （US） with color Doppler, were carried out at study entry, after 6 months and every year for 3 years. Abdominal magnetic resonance （MR） was performed in KS when testicular US showed micro-calcifications, testicular nodules and cysts. Nearly 62% of the KS had regular testicular echotexture, 37.5% showed an irregular echotexture and 17.5% had micro-calcifications and cysts. Eighty seven percent of KS had a regular vascular pattern, 12.5% varicocele, 12.5% nodules 〈1 cm, but none had nodules 〉1 cm. MR ruled out the diagnosis of cancer in all KS with testicular micro calcifications, nodules and cysts. No significant variations in LDH, AFP, and ^-HCG levels and in US pattern have been detected during follow-up. We compared serum tumor markers and US pattern between KS with and without cryptorchidism and no statistical differences were found. We did not find testicular cancer in KS, and testicular US, tumor markers and MR were, in selected cases, useful tools for correctly discriminating benign from malignant lesions.
文摘Pancreatic neuroendocrine neoplasms(PNENs) are rare and account for only 2%-4% of all pancreatic neoplasms. All PNENs are potential(neurendocrine tumors PNETs) or overt(neuroendocrine carcinomas PNECs) malignant,but a subset of PNETs is low-risk. Even in case of low-risk PNETs surgical resection is frequently required to treat hormone-related symptoms and to obtain an appropriate pathological diagnosis. Low-risk PNETs in the body and the tail are ideal for minimallyinvasive approaches which should be tailored to the individual patient. Generally,surgeons must aim for parenchyma sparing in these cases. In high-risk and malignant PNENs,indications for tumor resection are much wider than for pancreatic adenocarcinoma,in many cases due to the relatively benign tumor biology. Thus,patients with locally advanced and metastatic PNETs may benefit from extensive resection. In experienced hands,even multi-organ resections are accomplished with acceptable perioperative morbidity and mortality rates and are associated with excellent long term survival. However,poorly differentiated neoplasms with high proliferation rates are associated with a dismal prognosis and may frequently only be treated with chemotherapy. The evidence on surgical treatment of PNENs stems from reviews of mostly singlecenter series and some analyses of nation-wide tumor registries. No randomized trial has been performed to compare surgical and non-surgical therapies in potentially resectable PNEN. Though such a trial would principally be desirable,ethical considerations and the heterogeneity of PNENs preclude realization of such a study. In the current review,we summarize recent advances in the surgical treatment of PNENs.
文摘Eosinophilic esophagitis(Eo E) is a chronic immune disease, characterized by a dense eosinophilic infiltrate in the esophagus, leading to bolus impaction and refluxlike symptoms. Traditionally considered a pediatric disease, the number of adult patients with Eo E is continuously increasing, with a relatively higher incidence in western countries. Dysphagia and food impaction represent the main symptoms complained by patients, but gastroesophageal reflux-like symptoms may also be present. Esophageal biopsies are mandatory for the diagnosis of Eo E, though clinical manifestations and proton pump inhibitors responsiveness must be taken into consideration. The higher prevalence of Eo E in patients suffering from atopic diseases suggests a common background with allergy, however both the etiology and pathophysiology are not completely understood. Elimination diets are considered the firstline therapy in children, but this approach appears less effective in adults patients, who often require steroids; despite medical treatments, Eo E is complicated in some cases by esophageal stricture and stenosis, that require additional endoscopic treatments. This review summarizes the evidence on Eo E pathophysiology and illustrates the safety and efficacy of the most recent medical and endoscopic treatments.
文摘Acetazolamide is the commonly prescribed oral and intravenous carbonic anhydrase inhibitor;over the years,its use in clinical practice has decreased in favor of more recent drugs.However,it is a rather handy drug,which can be useful in several clinical settings when managing critically ill patients.The objective of this review is the evaluation of the most recent evidence on the use of acetazolamide in emergency medicine and critical care medicine.Furthermore,the safety profile of this drug has been evaluated.This is a narrative review on the use of acetazolamide in the main contexts in which this drug can be useful in emergency situations for patients with potential critical issues.For the timeline 1999–2024,a search was conducted on the main scientific platforms;resources of greatest relevance for the use of acetazolamide in critical care and emergency medicine were selected.The most common emergency situations in which a critically ill patient could benefit from acetazolamide therapy are acute heart failure,acute mountain sickness,post hypercapnic metabolic alkalosis,idiopathic intracranial hypertension and acute angle-closure glaucoma.In a few cases,however,randomized controlled clinical trials have been conducted.There are also other less solid indications based mostly on experience or retrospective data.Acetazolamide seems to be an overall safe drug;serious side effects are rare and can be avoided by carefully selecting the patients to be treated.Acetazolamide represents a precious resource for emergency physicians and intensivists;critical patients with different conditions can in fact benefit from it;furthermore,acetazolamide is a safe drug if administered to correctly selected patients.
文摘Autologous blood therapy has emerged as a promising modality in managing ocular surface disorders.This review provides a comprehensive overview of the current literature regarding the use of autologous blood in ocular surface disorders,encompassing its physiological basis,clinical applications,techniques,challenges,and future perspectives.The ocular surface,comprising the cornea,conjunctiva,and tear film,plays a critical role in maintaining visual function,and its disruption can lead to various pathological conditions.With its rich composition of growth factors,cytokines,and other bioactive molecules,autologous blood offers therapeutic potential in promoting corneal wound healing,reducing inflammation,and improving tear film stability.Clinical studies have demonstrated the efficacy and safety of autologous blood therapy in diverse ocular surface disorders,including persistent epithelial defects,neurotrophic keratopathy,and dry eye disease.However,challenges such as variability in treatment response,adverse effects,and optimal patient selection remain areas of concern.Further research is needed to elucidate the underlying mechanisms of action,refine treatment protocols,and explore synergistic approaches with other therapeutic modalities.Despite these challenges,autologous blood therapy holds promise as a valuable adjunctive treatment option for ocular surface disorders,offering new avenues for improving patient outcomes and quality of life.This review examines the mechanisms underlying ocular surface disorders while discussing existing autologous blood-based therapies for managing these disorders.Current clinical trials are also summarized,and a comparison between autologous blood therapy and conventional eyedrops is attempted.Finally,safe techniques and protocols for autologous blood medicine are elucidated,and adverse effects and future perspectives of this novel therapy are reviewed.
