Aim of the present review is to summarize the current knowledge about the potential relationship between mi RNAs and hepatitis B virus(HBV)-hepatitis C virus(HCV) related liver diseases. A systematic computerbased sea...Aim of the present review is to summarize the current knowledge about the potential relationship between mi RNAs and hepatitis B virus(HBV)-hepatitis C virus(HCV) related liver diseases. A systematic computerbased search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine mi RNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma(HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: "HBV", "HCV", "hepatocellular carcinoma", "micro RNAs", "mi RNAs", "diagnosis", "prognosis", "therapy", "treatment". Some serum/plasma mi RNAs, including mi R-21, mi R-122, mi-125a/b, mi R-199a/b, mi R-221, mi R-222, mi R-223, mi R-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of mi RNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of mi RNAs for HCC early detection and prognosis.展开更多
The continued need to develop less invasive alternatives to surgical and radiologic interventions has driven the development of endoscopic ultrasound(EUS)-guided treatments.These include EUS-guided drainage of pancrea...The continued need to develop less invasive alternatives to surgical and radiologic interventions has driven the development of endoscopic ultrasound(EUS)-guided treatments.These include EUS-guided drainage of pancreatic fluid collections,EUS-guided necrosectomy,EUS-guided cholangiography and biliary drainage,EUSguided pancreatography and pancreatic duct drainage,EUS-guided gallbladder drainage,EUS-guided drainage of abdominal and pelvic fluid collections,EUS-guided celiac plexus block and celiac plexus neurolysis,EUSguided pancreatic cyst ablation,EUS-guided vascular interventions,EUS-guided delivery of antitumoral agents and EUS-guided fiducial placement and brachytherapy.However these procedures are technically challenging and require expertise in both EUS and interventional endoscopy,such as endoscopic retrograde cholangiopancreatography and gastrointestinal stenting.We undertook a systematic review to record the entire body of literature accumulated over the past 2decades on EUS-guided interventions with the objective of performing a critical appraisal of published articles,based on the classification of studies according to levels of evidence,in order to assess the scientific progress made in this field.展开更多
Pancreatic fluid collections (PFCs) develop secondary to either fluid leakage or liquefaction of pancreatic necrosis following acute pancreatitis, chronic pancreatitis, surgery or abdominal trauma. Pancreatic fluid c... Pancreatic fluid collections (PFCs) develop secondary to either fluid leakage or liquefaction of pancreatic necrosis following acute pancreatitis, chronic pancreatitis, surgery or abdominal trauma. Pancreatic fluid collections include acute fluid collections, acute and chronic pancreatic pseudocysts, pancreatic abscesses and pancreatic necrosis. Before the introduction of linear endoscopic ultrasound (EUS) in the 1990s and the subsequent development of endoscopic ultrasound-guided drainage (EUS-GD) procedures, the available options for drainage in symptomatic PFCs included surgical drainage, percutaneous drainage using radiological guidance and conventional endoscopic transmural drainage. In recent years, it has gradually been recog-nized that, due to its lower morbidity rate compared to the surgical and percutaneous approaches, endoscopic treatment may be the preferred first-line approach for managing symptomatic PFCs. Endoscopic ultrasound-guided drainage has the following advantages, when compared to other alternatives such as surgical, per-cutaneous and non-EUS-guided endoscopic drainage.EUS-GD is less invasive than surgery and therefore does not require general anesthesia. The morbidity rate is lower, recovery is faster and the costs are lower. EUS-GD can avoid local complications related to per-cutaneous drainage. Because the endoscope is placed adjacent to the fluid collection, it can have direct ac-cess to the fluid cavity, unlike percutaneous drainage which traverses the abdominal wall. Complications such as bleeding, inadvertent puncture of adjacent viscera, secondary infection and prolonged periods of drainage with resultant pancreatico-cutaneous fistulae may be avoided. The only difference between EUS and non-EUS drainage is the initial step, namely, gaining access to the pancreatic fluid collection. All the sub-sequent steps are similar, i.e., insertion of guide-wires with fluoroscopic guidance, balloon dilatation of the cystogastrostomy and insertion of transmural stents or nasocystic catheters. Wi展开更多
AIM: To investigate the safety and efficacy of long-term combination therapy with alpha interferon and lamivudine in non-responsive patients with anti-HBe-positive chronic hepatitis B.METHODS: 34 patients received com...AIM: To investigate the safety and efficacy of long-term combination therapy with alpha interferon and lamivudine in non-responsive patients with anti-HBe-positive chronic hepatitis B.METHODS: 34 patients received combination treatment (1 month lamivudine, 12 month lamivudine+interferon, 6month lamivudine), 24 received lamivudine (12 months),24 received interferon (12 months). Interferon was administered at 6 MU tiw and lamivudine at 100 mg orally once daily. Patients were followed up for 6 months after treatment.RESULTS: At the end of treatment, HBV DNA negativity rates were 88 % with lamivudine+interferon, 99 % with lamivudine and 55 % with interferon, (P=0.004, combination therapy vs. interferon, and P=0.001 lamivudine vs.interferon), and serum transaminase normalization rates were 84 %, 91% and 53 % (P=0.01 combination therapy vs. interferon, and P=0.012 lamivudine vs. interferon). Six months later, HBV DNA negativity rates were 44 % with lamivudine+interferon, 33 % with lamivudine and 25 % with interferon, and serum transaminase normalization rates were 61%, 42 % and 45 %, respectively, without statistical significance. No YMDD variants were observed with lamivudine+interferon (vs. 12 % with lamivudine). The combination therapy appeared to be safe. CONCLUSION: Although viral clearance and transaminase normalization are slower with long-term lamivudine+interferon than that with lamivudine alone, the combination regimen seems to provide more lasting benefits and to protect against the appearance of YMDD variants. Studies with other regimens regarding sequence and duration are needed.展开更多
BACKGROUND:Hyperamylasemia can be observed anecdotally during the course of severe sepsis or septic shock.This study aimed to investigate the possibility of pancreatic involvement in patients with septic shock using s...BACKGROUND:Hyperamylasemia can be observed anecdotally during the course of severe sepsis or septic shock.This study aimed to investigate the possibility of pancreatic involvement in patients with septic shock using serum pancreatic enzyme determinations and imaging techniques in 21 consecutive patients with septic shock and 21 healthy subjects as controls. METHODS:The serum activity of pancreatic amylase and lipase was assayed initially in all subjects and 24 and 48 hours after the initial observation in the 21 patients with septic shock All patients also underwent radiological examination to detect pancreatic abnormalities. RESULTS:The serum activity of pancreatic amylase was significantly higher in the 21 patients with septic shock than in the 21 control subjects during the study period while the serum activity of lipase was similar to that of the control subjects.Amylase and lipase serum activity did not significantly changed throughout the study period in the 21 patients with septic shock.None of the patients with pancreatic hyperenzymemia had clinical signs or morphological alterations compatible with acute pancreatitis CONCLUSION:The presence of pancreatic hyperenzymemia in septic shock patients is not a biochemical manifestation of acute pancreatic damage,and the management of these patients should be dependent on the clinical situation and not merely the biochemical results.展开更多
AIM: To define the prevalence of gastroesophageal reflux disease (GERD) in mild persistent asthma and to value the effect of pantoprazole therapy on asthmatic symptoms.METHODS: Seven of thirty-four asthmatic patie...AIM: To define the prevalence of gastroesophageal reflux disease (GERD) in mild persistent asthma and to value the effect of pantoprazole therapy on asthmatic symptoms.METHODS: Seven of thirty-four asthmatic patients without GERD served as the non-GERD control group. Twenty-seven of thirty-four asthmatic patients had GERD (7/27 also had erosive esophagitis, sixteen of them presented GERD symptoms. An upper gastrointestinal endoscopy was performed in all the subjects to obtain five biopsy specimens from the lower 5 cm of the esophagus. Patients were considered to have GERD when they had a dilation of intercellular space (DIS)〉0.74 μm at transmission electron microscopy. Patients with GERD were treated with pantoprazole, 80 mg/day. Forced expiratory volume in one second (FEV1) was performed at entry and after 6 mo of treatment. Asthmatic symptoms were recorded. The required frequency of inhaling rapid acting β2-agonists was self-recorded in the patients' diaries.RESULTS: Seven symptomatic patients presented erosive esophagitis. Among the 18 asymptomatic patients, 11 presented DIS, while all symptomatic patients showed ultrastructural esophageal damage. Seven asymptomatic patients did not present DIS. At entry the mean of FEV1 was 1.91 L in symptomatic GERD patients and 1.88 L in asymptomatic GERD patients. After the treatment, 25 patients had a complete recovery of DIS and reflux symptoms. Twenty-three patients presented a regression of asthmatic symptoms with normalization of FEV1. Four patients reported a significant improvement of symptoms and their FEV1 was over 80%.CONCLUSION: GERD is a highly prevalent condition in asthma patients. Treatment with pantoprazole (80 mg/day) determines their improvement and complete regression.展开更多
Despite the bi-directional interaction between gut microbiota and the brain not being fully understood,there is increasing evidence arising from animal and human studies that show how this intricate relationship may f...Despite the bi-directional interaction between gut microbiota and the brain not being fully understood,there is increasing evidence arising from animal and human studies that show how this intricate relationship may facilitate inflammatory bowel disease(IBD)pathogenesis,with consequent important implications on the possibility to improve the clinical outcomes of the diseases themselves,by acting on the different components of this system,mainly by modifying the microbiota.With the emergence of precision medicine,strategies in which patients with IBD might be categorized other than for standard gut symptom complexes could offer the opportunity to tailor therapies to individual patients.The aim of this narrative review is to elaborate on the concept of the gutbrain-microbiota axis and its clinical significance regarding IBD on the basis of recent scientific literature,and finally to focus on pharmacological therapies that could allow us to favorably modify the function of this complex system.展开更多
Although pharmaceuticals have beendetected in the environment only in the range from ng/L to μg/L, it has beendemonstrated that they can adversely affect the health status of aquatic organisms. Lysosomal membrane sta...Although pharmaceuticals have beendetected in the environment only in the range from ng/L to μg/L, it has beendemonstrated that they can adversely affect the health status of aquatic organisms. Lysosomal membrane stability (LMS) has previously been applied as an indicator of cellularwell-being todetermine health status in bivalve mussels. The objective of this study is to evaluate LMS in Ruditapes philippinarum haemolymph using the neutral red retention assay (NRRA). Clamswere exposed in laboratory conditions to caffeine (0.1, 5, 15, 50 μg/L), ibuprofen (0.1, 5, 10, 50 μg/L), carbamazepine and novobiocin (both at 0.1, 1, 10, 50 μg/L) for35days. Results show adose-dependent effect of the pharmaceuticals. The neutral red retention time measured at the end of the bioassaywas significantly reduced by 50% after exposure to environmental concentrations (p 〈 0.05) (caffeine = 15 μg/L; ibuprofen = 10 μg/L; carbamazepine = 1 μg/L and novobiocin = 1 μg/L), compared to controls. Clams exposed to these pharmaceuticalswere considered to present adiminished health status (retention time 〈45 min), significantlyworse than controls (96 min) (p 〈 0.05). The predicted no environmental effect concentration (PNEC) results showed that these pharmaceuticals are very toxic at the environmental concentrations tested. Measurement of the alteration of LMS has been found to be a sensitive technique that enables evaluation of the health status of clams after exposure to pharmaceuticals under laboratory conditions, thus representing a robust Tier-1 screening biomarker.展开更多
To date,metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile.Indeed,metformin is the most widely us...To date,metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile.Indeed,metformin is the most widely used oral insulinsensitizing agent,being prescribed to more than 100 million people worldwide,including patients with prediabetes,insulin resistance,and polycystic ovary syndrome.However,over the last decades several observational studies and meta-analyses have reported a significant association between long-term metformin therapy and an increased prevalence of vitamin B12 deficiency.Of note,evidence suggests that long-term and high-dose metformin therapy impairs vitamin B12 status.Vitamin B12(also referred to as cobalamin)is a water-soluble vitamin that is mainly obtained from animal-sourced foods.At the cellular level,vitamin B12 acts as a cofactor for enzymes that play a critical role in DNA synthesis and neuroprotection.Thus,vitamin B12 deficiency can lead to a number of clinical consequences that include hematologic abnormalities(e.g.,megaloblastic anemia and formation of hypersegmented neutrophils),progressive axonal demyelination and peripheral neuropathy.Nevertheless,no definite guidelines are currently available for vitamin B12 deficiency screening in patients on metformin therapy,and vitamin B12 deficiency remains frequently unrecognized in such individuals.Therefore,in this“field of vision”article we propose a list of criteria for a cost-effective vitamin B12 deficiency screening in metformin-treated patients,which could serve as a practical guide for identifying individuals at high risk for this condition.Moreover,we discuss additional relevant topics related to this field,including:(1)The lack of consensus about the exact definition of vitamin B12 deficiency;(2)The definition of reliable biomarkers of vitamin B12 status;(3)Causes of vitamin B12 deficiency other than metformin therapy that should be identified promptly in metformin-treated patients for a proper differential diagnosis;an展开更多
Pancreatic ductal adenocarcinoma accounts for more than 90% of all pancreatic cancers and its incidence has increased significantly worldwide.Patients with pancreatic ductal adenocarcinoma have a poor outcome and more...Pancreatic ductal adenocarcinoma accounts for more than 90% of all pancreatic cancers and its incidence has increased significantly worldwide.Patients with pancreatic ductal adenocarcinoma have a poor outcome and more than 95% of the people affected die from the disease within 12 mo after diagnosis.Surgery is the first-line treatment in the case of resectable neoplasm,but only 20% of patients are candidates for this approach.One of the reasons there are few candidates for surgery is that,during the early phases of the disease,the symptoms are poor or non-specific.Early diagnosis is of crucial importance to improve patient outcome;therefore,we are looking for a good screening test.The screening test must identify the disease in an early stage in order to be effective;having said this,a need exists to introduce the concept of "early" ductal adenocarcinoma.It has been reported that at least five additional years after the occurrence of the initiating mutation are required for the acquisition of metastatic ability of pancreatic adenocarcinoma and patients die an average of two years thereafter.We have reviewed the most recent literature in order to evaluate the present and future perspectives of screening programs of this deadly disease.展开更多
Erectile dysfunction (ED) is a highly prevalent disorder affecting an estimated 152 million men worldwide and isassociated with a variety of behavioral risk factors, such as cigarette smoking and excessive alcohol con...Erectile dysfunction (ED) is a highly prevalent disorder affecting an estimated 152 million men worldwide and isassociated with a variety of behavioral risk factors, such as cigarette smoking and excessive alcohol consumption, aswell as numerous age - related medical conditions, notably type-2 diabetes mellitus and cardiovascular disease. A ratio-nal step - wise approach which includes comprehensive medical and sexual history, a focused physical examination andessential laboratory tests such as fasting glucose, lipid profile and testosterone assay is to be preferred. Current diagnos-tic work - up does not recommend any of the specialized tests which were previously considered mandatory-i. e. penilepharmacotesting, Duplex ultrasound and nocturnal penile tumescence. Hormonal replacement therapy is appropriate onlyin the hypogonadal male with ED. Prior to direct intervention, the physician should consider altering modifiable riskfactors or causes, although frequently insufficient to reverse ED completely. When indicated, oral therapy with newmolecules (phosphodiesterase inhibitors or apomorphine) is the first - line treatment for the majority of patients becauseof potential benefits and lack of invasiveness. (Asian J Androl 2001 Sep; 3: 175-179 )展开更多
The Jiangmen Underground Neutrino Observatory(JUNO)is a large liquid scintillator detector designed to explore many topics in fundamental physics.In this study,the potential of searching for proton decay in the p→νK...The Jiangmen Underground Neutrino Observatory(JUNO)is a large liquid scintillator detector designed to explore many topics in fundamental physics.In this study,the potential of searching for proton decay in the p→νK^(+)mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification.Moreover,the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals.Based on these advantages,the detection efficiency for the proton decay via p→νK^(+)is 36.9%±4.9%with a background level of 0.2±0.05(syst)±0.2(stat)events after 10 years of data collection.The estimated sensitivity based on 200 kton-years of exposure is 9.6×1033 years,which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies.展开更多
AIM: To value whether omeprazole could induce the healing of DIS and regression of symptoms in patients with DGER. METHODS: We enrolled 15 symptomatic patients with a pathological esophageal 24-h pH-metry and bilimetr...AIM: To value whether omeprazole could induce the healing of DIS and regression of symptoms in patients with DGER. METHODS: We enrolled 15 symptomatic patients with a pathological esophageal 24-h pH-metry and bilimetry. Patients underwent endoscopy and biopsies were taken from the distal esophagus. Specimens were analyzed at histology and transmission electron microscopy (TEM). Patients were treated with omeprazole 40 mg/d for 3 mo and then endoscopy with biopsies was repeated. Patients with persistent heartburn and/or with an incomplete recovery of DIS were treated for 3 more months and endoscopy with biopsies was performed. RESULTS: Nine patients had a non-erosive reflux disease at endoscopy (NERD) while 6 had erosive esophagitis (ERD). At histology, of the 6 patients with erosive esophagitis, 5 had mild esophagitis and 1 moderate esophagitis. No patients with NERD showed histological signs of esophagitis. After 3 mo of therapy, 13/15 patients (86.7%,P<0.01) showed a complete recovery of DIS and disappearance of heartburn. Of the 2 patients treated for 3 more months, complete recovery of DIS and heartburn were achieved in one. CONCLUSION: Three or 6 mo of omeprazole therapy led to a complete regression of the ultrastructural esophageal damage in 86.7% and in 93% of patients with DGER, NERD and ERD respectively. The ultrastructural recovery of the epithelium was accompanied by regression of heartburn in all cases.展开更多
Peroral cholangioscopy(POC) is an important tool for the management of a selected group of biliary diseases. Because of its direct visualization, POC allows targeted diagnostic and therapeutic procedures. POC can be p...Peroral cholangioscopy(POC) is an important tool for the management of a selected group of biliary diseases. Because of its direct visualization, POC allows targeted diagnostic and therapeutic procedures. POC can be performed using a dedicated cholangioscope that is advanced through the accessory channel of a duodenoscope or via the insertion of a small-diameter endoscope directly into the bile duct. POC was first described in the 1970 s, but the use of earlier generation devices was substantially limited by the cumbersome equipment setup and high repair costs. For nearly ten years, several technical improvements, including the single-operator system, high-quality images, the development of dedicated accessories and the increased size of the working channel, have led to increased diagnostic accuracy, thus assisting in the differentiation of benign and malignant intraductal lesions, targeting biopsies and the precise delineation of intraductal tumor spread before surgery. Furthermore, lithotripsy of difficult bile duct stones, ablative therapies for biliary malignancies and direct biliary drainage can be performed under POC control. Recent developments of new types of conventional POCs allow feasible, safe and effective procedures at reasonable costs. In the current review, we provide an updated overview of POC, focusing our attention on the main current clinical applications and on areas for future research.展开更多
Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to r...Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 bleeding.Conclusions: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.展开更多
In a unified regenerative fuel cell(URFC)or reversible fuel cell,the oxygen bifunctional catalyst must switch reversibly between the oxygen reduction reaction(ORR),fuel cell mode,and the oxygen evolution reaction(OER)...In a unified regenerative fuel cell(URFC)or reversible fuel cell,the oxygen bifunctional catalyst must switch reversibly between the oxygen reduction reaction(ORR),fuel cell mode,and the oxygen evolution reaction(OER),electrolyzer mode.However,it is often unclear what effect alternating between ORR and OER has on the electrochemical behavior and physiochemical properties of the catalyst.Herein,operando X-ray absorption spectroscopy(XAS)is utilized to monitor the continuous and dynamic evolution of the Co,Mn,and Fe oxidation states of perovskite catalysts Ba_(0.5)Sr_(0.5)Co_(0.8)Fe_(0.2)O_(3-δ)(BSCF)and La_(0.4)Sr_(0.6)MnO_(3-δ)(LSM),while the potential is oscillated between reducing and oxidizing potentials with cyclic voltammetry.The results reveal the importance of investigating bifunctional catalysts by alternating between fuel cell and electrolyzer operation and highlight the limitations and challenges of bifunctional catalysts.It is shown that the requirements for ORR and OER performance are divergent and that the oxidative potentials of OER are detrimental to ORR activity.These findings are used to give guidelines for future bifunctional catalyst design.Additionally,it is demonstrated how sunlight can be used to reactivate the ORR activity of LSM after rigorous cycling.展开更多
文摘Aim of the present review is to summarize the current knowledge about the potential relationship between mi RNAs and hepatitis B virus(HBV)-hepatitis C virus(HCV) related liver diseases. A systematic computerbased search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine mi RNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma(HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: "HBV", "HCV", "hepatocellular carcinoma", "micro RNAs", "mi RNAs", "diagnosis", "prognosis", "therapy", "treatment". Some serum/plasma mi RNAs, including mi R-21, mi R-122, mi-125a/b, mi R-199a/b, mi R-221, mi R-222, mi R-223, mi R-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of mi RNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of mi RNAs for HCC early detection and prognosis.
文摘The continued need to develop less invasive alternatives to surgical and radiologic interventions has driven the development of endoscopic ultrasound(EUS)-guided treatments.These include EUS-guided drainage of pancreatic fluid collections,EUS-guided necrosectomy,EUS-guided cholangiography and biliary drainage,EUSguided pancreatography and pancreatic duct drainage,EUS-guided gallbladder drainage,EUS-guided drainage of abdominal and pelvic fluid collections,EUS-guided celiac plexus block and celiac plexus neurolysis,EUSguided pancreatic cyst ablation,EUS-guided vascular interventions,EUS-guided delivery of antitumoral agents and EUS-guided fiducial placement and brachytherapy.However these procedures are technically challenging and require expertise in both EUS and interventional endoscopy,such as endoscopic retrograde cholangiopancreatography and gastrointestinal stenting.We undertook a systematic review to record the entire body of literature accumulated over the past 2decades on EUS-guided interventions with the objective of performing a critical appraisal of published articles,based on the classification of studies according to levels of evidence,in order to assess the scientific progress made in this field.
文摘 Pancreatic fluid collections (PFCs) develop secondary to either fluid leakage or liquefaction of pancreatic necrosis following acute pancreatitis, chronic pancreatitis, surgery or abdominal trauma. Pancreatic fluid collections include acute fluid collections, acute and chronic pancreatic pseudocysts, pancreatic abscesses and pancreatic necrosis. Before the introduction of linear endoscopic ultrasound (EUS) in the 1990s and the subsequent development of endoscopic ultrasound-guided drainage (EUS-GD) procedures, the available options for drainage in symptomatic PFCs included surgical drainage, percutaneous drainage using radiological guidance and conventional endoscopic transmural drainage. In recent years, it has gradually been recog-nized that, due to its lower morbidity rate compared to the surgical and percutaneous approaches, endoscopic treatment may be the preferred first-line approach for managing symptomatic PFCs. Endoscopic ultrasound-guided drainage has the following advantages, when compared to other alternatives such as surgical, per-cutaneous and non-EUS-guided endoscopic drainage.EUS-GD is less invasive than surgery and therefore does not require general anesthesia. The morbidity rate is lower, recovery is faster and the costs are lower. EUS-GD can avoid local complications related to per-cutaneous drainage. Because the endoscope is placed adjacent to the fluid collection, it can have direct ac-cess to the fluid cavity, unlike percutaneous drainage which traverses the abdominal wall. Complications such as bleeding, inadvertent puncture of adjacent viscera, secondary infection and prolonged periods of drainage with resultant pancreatico-cutaneous fistulae may be avoided. The only difference between EUS and non-EUS drainage is the initial step, namely, gaining access to the pancreatic fluid collection. All the sub-sequent steps are similar, i.e., insertion of guide-wires with fluoroscopic guidance, balloon dilatation of the cystogastrostomy and insertion of transmural stents or nasocystic catheters. Wi
文摘AIM: To investigate the safety and efficacy of long-term combination therapy with alpha interferon and lamivudine in non-responsive patients with anti-HBe-positive chronic hepatitis B.METHODS: 34 patients received combination treatment (1 month lamivudine, 12 month lamivudine+interferon, 6month lamivudine), 24 received lamivudine (12 months),24 received interferon (12 months). Interferon was administered at 6 MU tiw and lamivudine at 100 mg orally once daily. Patients were followed up for 6 months after treatment.RESULTS: At the end of treatment, HBV DNA negativity rates were 88 % with lamivudine+interferon, 99 % with lamivudine and 55 % with interferon, (P=0.004, combination therapy vs. interferon, and P=0.001 lamivudine vs.interferon), and serum transaminase normalization rates were 84 %, 91% and 53 % (P=0.01 combination therapy vs. interferon, and P=0.012 lamivudine vs. interferon). Six months later, HBV DNA negativity rates were 44 % with lamivudine+interferon, 33 % with lamivudine and 25 % with interferon, and serum transaminase normalization rates were 61%, 42 % and 45 %, respectively, without statistical significance. No YMDD variants were observed with lamivudine+interferon (vs. 12 % with lamivudine). The combination therapy appeared to be safe. CONCLUSION: Although viral clearance and transaminase normalization are slower with long-term lamivudine+interferon than that with lamivudine alone, the combination regimen seems to provide more lasting benefits and to protect against the appearance of YMDD variants. Studies with other regimens regarding sequence and duration are needed.
文摘BACKGROUND:Hyperamylasemia can be observed anecdotally during the course of severe sepsis or septic shock.This study aimed to investigate the possibility of pancreatic involvement in patients with septic shock using serum pancreatic enzyme determinations and imaging techniques in 21 consecutive patients with septic shock and 21 healthy subjects as controls. METHODS:The serum activity of pancreatic amylase and lipase was assayed initially in all subjects and 24 and 48 hours after the initial observation in the 21 patients with septic shock All patients also underwent radiological examination to detect pancreatic abnormalities. RESULTS:The serum activity of pancreatic amylase was significantly higher in the 21 patients with septic shock than in the 21 control subjects during the study period while the serum activity of lipase was similar to that of the control subjects.Amylase and lipase serum activity did not significantly changed throughout the study period in the 21 patients with septic shock.None of the patients with pancreatic hyperenzymemia had clinical signs or morphological alterations compatible with acute pancreatitis CONCLUSION:The presence of pancreatic hyperenzymemia in septic shock patients is not a biochemical manifestation of acute pancreatic damage,and the management of these patients should be dependent on the clinical situation and not merely the biochemical results.
文摘AIM: To define the prevalence of gastroesophageal reflux disease (GERD) in mild persistent asthma and to value the effect of pantoprazole therapy on asthmatic symptoms.METHODS: Seven of thirty-four asthmatic patients without GERD served as the non-GERD control group. Twenty-seven of thirty-four asthmatic patients had GERD (7/27 also had erosive esophagitis, sixteen of them presented GERD symptoms. An upper gastrointestinal endoscopy was performed in all the subjects to obtain five biopsy specimens from the lower 5 cm of the esophagus. Patients were considered to have GERD when they had a dilation of intercellular space (DIS)〉0.74 μm at transmission electron microscopy. Patients with GERD were treated with pantoprazole, 80 mg/day. Forced expiratory volume in one second (FEV1) was performed at entry and after 6 mo of treatment. Asthmatic symptoms were recorded. The required frequency of inhaling rapid acting β2-agonists was self-recorded in the patients' diaries.RESULTS: Seven symptomatic patients presented erosive esophagitis. Among the 18 asymptomatic patients, 11 presented DIS, while all symptomatic patients showed ultrastructural esophageal damage. Seven asymptomatic patients did not present DIS. At entry the mean of FEV1 was 1.91 L in symptomatic GERD patients and 1.88 L in asymptomatic GERD patients. After the treatment, 25 patients had a complete recovery of DIS and reflux symptoms. Twenty-three patients presented a regression of asthmatic symptoms with normalization of FEV1. Four patients reported a significant improvement of symptoms and their FEV1 was over 80%.CONCLUSION: GERD is a highly prevalent condition in asthma patients. Treatment with pantoprazole (80 mg/day) determines their improvement and complete regression.
文摘Despite the bi-directional interaction between gut microbiota and the brain not being fully understood,there is increasing evidence arising from animal and human studies that show how this intricate relationship may facilitate inflammatory bowel disease(IBD)pathogenesis,with consequent important implications on the possibility to improve the clinical outcomes of the diseases themselves,by acting on the different components of this system,mainly by modifying the microbiota.With the emergence of precision medicine,strategies in which patients with IBD might be categorized other than for standard gut symptom complexes could offer the opportunity to tailor therapies to individual patients.The aim of this narrative review is to elaborate on the concept of the gutbrain-microbiota axis and its clinical significance regarding IBD on the basis of recent scientific literature,and finally to focus on pharmacological therapies that could allow us to favorably modify the function of this complex system.
基金conducted under the framework of the project P09-RNM-5136(Government of Andalu-sia,Spain)partially financed by the UN-ESCO/UNITWIN/WiCop as part of the research activities of the Erasmus Mundus Master's degree in Water and Coastal Managementthe financial support from MAEC-AECID(Government of Spain),Becas Chile(Government of Chile),and Junta de Andaluc'a(Government of Andalusia,Spain)
文摘Although pharmaceuticals have beendetected in the environment only in the range from ng/L to μg/L, it has beendemonstrated that they can adversely affect the health status of aquatic organisms. Lysosomal membrane stability (LMS) has previously been applied as an indicator of cellularwell-being todetermine health status in bivalve mussels. The objective of this study is to evaluate LMS in Ruditapes philippinarum haemolymph using the neutral red retention assay (NRRA). Clamswere exposed in laboratory conditions to caffeine (0.1, 5, 15, 50 μg/L), ibuprofen (0.1, 5, 10, 50 μg/L), carbamazepine and novobiocin (both at 0.1, 1, 10, 50 μg/L) for35days. Results show adose-dependent effect of the pharmaceuticals. The neutral red retention time measured at the end of the bioassaywas significantly reduced by 50% after exposure to environmental concentrations (p 〈 0.05) (caffeine = 15 μg/L; ibuprofen = 10 μg/L; carbamazepine = 1 μg/L and novobiocin = 1 μg/L), compared to controls. Clams exposed to these pharmaceuticalswere considered to present adiminished health status (retention time 〈45 min), significantlyworse than controls (96 min) (p 〈 0.05). The predicted no environmental effect concentration (PNEC) results showed that these pharmaceuticals are very toxic at the environmental concentrations tested. Measurement of the alteration of LMS has been found to be a sensitive technique that enables evaluation of the health status of clams after exposure to pharmaceuticals under laboratory conditions, thus representing a robust Tier-1 screening biomarker.
文摘To date,metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile.Indeed,metformin is the most widely used oral insulinsensitizing agent,being prescribed to more than 100 million people worldwide,including patients with prediabetes,insulin resistance,and polycystic ovary syndrome.However,over the last decades several observational studies and meta-analyses have reported a significant association between long-term metformin therapy and an increased prevalence of vitamin B12 deficiency.Of note,evidence suggests that long-term and high-dose metformin therapy impairs vitamin B12 status.Vitamin B12(also referred to as cobalamin)is a water-soluble vitamin that is mainly obtained from animal-sourced foods.At the cellular level,vitamin B12 acts as a cofactor for enzymes that play a critical role in DNA synthesis and neuroprotection.Thus,vitamin B12 deficiency can lead to a number of clinical consequences that include hematologic abnormalities(e.g.,megaloblastic anemia and formation of hypersegmented neutrophils),progressive axonal demyelination and peripheral neuropathy.Nevertheless,no definite guidelines are currently available for vitamin B12 deficiency screening in patients on metformin therapy,and vitamin B12 deficiency remains frequently unrecognized in such individuals.Therefore,in this“field of vision”article we propose a list of criteria for a cost-effective vitamin B12 deficiency screening in metformin-treated patients,which could serve as a practical guide for identifying individuals at high risk for this condition.Moreover,we discuss additional relevant topics related to this field,including:(1)The lack of consensus about the exact definition of vitamin B12 deficiency;(2)The definition of reliable biomarkers of vitamin B12 status;(3)Causes of vitamin B12 deficiency other than metformin therapy that should be identified promptly in metformin-treated patients for a proper differential diagnosis;an
文摘Pancreatic ductal adenocarcinoma accounts for more than 90% of all pancreatic cancers and its incidence has increased significantly worldwide.Patients with pancreatic ductal adenocarcinoma have a poor outcome and more than 95% of the people affected die from the disease within 12 mo after diagnosis.Surgery is the first-line treatment in the case of resectable neoplasm,but only 20% of patients are candidates for this approach.One of the reasons there are few candidates for surgery is that,during the early phases of the disease,the symptoms are poor or non-specific.Early diagnosis is of crucial importance to improve patient outcome;therefore,we are looking for a good screening test.The screening test must identify the disease in an early stage in order to be effective;having said this,a need exists to introduce the concept of "early" ductal adenocarcinoma.It has been reported that at least five additional years after the occurrence of the initiating mutation are required for the acquisition of metastatic ability of pancreatic adenocarcinoma and patients die an average of two years thereafter.We have reviewed the most recent literature in order to evaluate the present and future perspectives of screening programs of this deadly disease.
文摘Erectile dysfunction (ED) is a highly prevalent disorder affecting an estimated 152 million men worldwide and isassociated with a variety of behavioral risk factors, such as cigarette smoking and excessive alcohol consumption, aswell as numerous age - related medical conditions, notably type-2 diabetes mellitus and cardiovascular disease. A ratio-nal step - wise approach which includes comprehensive medical and sexual history, a focused physical examination andessential laboratory tests such as fasting glucose, lipid profile and testosterone assay is to be preferred. Current diagnos-tic work - up does not recommend any of the specialized tests which were previously considered mandatory-i. e. penilepharmacotesting, Duplex ultrasound and nocturnal penile tumescence. Hormonal replacement therapy is appropriate onlyin the hypogonadal male with ED. Prior to direct intervention, the physician should consider altering modifiable riskfactors or causes, although frequently insufficient to reverse ED completely. When indicated, oral therapy with newmolecules (phosphodiesterase inhibitors or apomorphine) is the first - line treatment for the majority of patients becauseof potential benefits and lack of invasiveness. (Asian J Androl 2001 Sep; 3: 175-179 )
基金supported by the Chinese Academy of Sciencesthe National Key R&D Program of China+22 种基金the CAS Center for Excellence in Particle PhysicsWuyi Universitythe Tsung-Dao Lee Institute of Shanghai Jiao Tong University in Chinathe Institut National de Physique Nucléaire et de Physique de Particules (IN2P3) in Francethe Istituto Nazionale di Fisica Nucleare (INFN) in Italythe Italian-Chinese collaborative research program MAECI-NSFCthe Fond de la Recherche Scientifique (F.R.S-FNRS)FWO under the "Excellence of Science-EOS" in Belgiumthe Conselho Nacional de Desenvolvimento Científico e Tecnològico in Brazilthe Agencia Nacional de Investigacion y Desarrollo in Chilethe Charles University Research Centrethe Ministry of Education,Youth,and Sports in Czech Republicthe Deutsche Forschungsgemeinschaft (DFG)the Helmholtz Associationthe Cluster of Excellence PRISMA+ in Germanythe Joint Institute of Nuclear Research (JINR)Lomonosov Moscow State University in Russiathe joint Russian Science Foundation (RSF)National Natural Science Foundation of China (NSFC) research programthe MOST and MOE in Taiwan,Chinathe Chulalongkorn UniversitySuranaree University of Technology in Thailandthe University of California at Irvine in USA
文摘The Jiangmen Underground Neutrino Observatory(JUNO)is a large liquid scintillator detector designed to explore many topics in fundamental physics.In this study,the potential of searching for proton decay in the p→νK^(+)mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification.Moreover,the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals.Based on these advantages,the detection efficiency for the proton decay via p→νK^(+)is 36.9%±4.9%with a background level of 0.2±0.05(syst)±0.2(stat)events after 10 years of data collection.The estimated sensitivity based on 200 kton-years of exposure is 9.6×1033 years,which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies.
文摘AIM: To value whether omeprazole could induce the healing of DIS and regression of symptoms in patients with DGER. METHODS: We enrolled 15 symptomatic patients with a pathological esophageal 24-h pH-metry and bilimetry. Patients underwent endoscopy and biopsies were taken from the distal esophagus. Specimens were analyzed at histology and transmission electron microscopy (TEM). Patients were treated with omeprazole 40 mg/d for 3 mo and then endoscopy with biopsies was repeated. Patients with persistent heartburn and/or with an incomplete recovery of DIS were treated for 3 more months and endoscopy with biopsies was performed. RESULTS: Nine patients had a non-erosive reflux disease at endoscopy (NERD) while 6 had erosive esophagitis (ERD). At histology, of the 6 patients with erosive esophagitis, 5 had mild esophagitis and 1 moderate esophagitis. No patients with NERD showed histological signs of esophagitis. After 3 mo of therapy, 13/15 patients (86.7%,P<0.01) showed a complete recovery of DIS and disappearance of heartburn. Of the 2 patients treated for 3 more months, complete recovery of DIS and heartburn were achieved in one. CONCLUSION: Three or 6 mo of omeprazole therapy led to a complete regression of the ultrastructural esophageal damage in 86.7% and in 93% of patients with DGER, NERD and ERD respectively. The ultrastructural recovery of the epithelium was accompanied by regression of heartburn in all cases.
文摘Peroral cholangioscopy(POC) is an important tool for the management of a selected group of biliary diseases. Because of its direct visualization, POC allows targeted diagnostic and therapeutic procedures. POC can be performed using a dedicated cholangioscope that is advanced through the accessory channel of a duodenoscope or via the insertion of a small-diameter endoscope directly into the bile duct. POC was first described in the 1970 s, but the use of earlier generation devices was substantially limited by the cumbersome equipment setup and high repair costs. For nearly ten years, several technical improvements, including the single-operator system, high-quality images, the development of dedicated accessories and the increased size of the working channel, have led to increased diagnostic accuracy, thus assisting in the differentiation of benign and malignant intraductal lesions, targeting biopsies and the precise delineation of intraductal tumor spread before surgery. Furthermore, lithotripsy of difficult bile duct stones, ablative therapies for biliary malignancies and direct biliary drainage can be performed under POC control. Recent developments of new types of conventional POCs allow feasible, safe and effective procedures at reasonable costs. In the current review, we provide an updated overview of POC, focusing our attention on the main current clinical applications and on areas for future research.
文摘Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 bleeding.Conclusions: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.
基金the Swiss National Science Foundation(project No.IZLJZ2_183670 and grant No.PR00P2_193111)the Paul Scherrer Institut for the funding for this work.Furthermorethe Independent Research Fund Denmark(Research Project 1,project“Rational Design of High-Entropy Oxides for Protonic Ceramic Fuel Cells,”grant No.1032-00269B)
文摘In a unified regenerative fuel cell(URFC)or reversible fuel cell,the oxygen bifunctional catalyst must switch reversibly between the oxygen reduction reaction(ORR),fuel cell mode,and the oxygen evolution reaction(OER),electrolyzer mode.However,it is often unclear what effect alternating between ORR and OER has on the electrochemical behavior and physiochemical properties of the catalyst.Herein,operando X-ray absorption spectroscopy(XAS)is utilized to monitor the continuous and dynamic evolution of the Co,Mn,and Fe oxidation states of perovskite catalysts Ba_(0.5)Sr_(0.5)Co_(0.8)Fe_(0.2)O_(3-δ)(BSCF)and La_(0.4)Sr_(0.6)MnO_(3-δ)(LSM),while the potential is oscillated between reducing and oxidizing potentials with cyclic voltammetry.The results reveal the importance of investigating bifunctional catalysts by alternating between fuel cell and electrolyzer operation and highlight the limitations and challenges of bifunctional catalysts.It is shown that the requirements for ORR and OER performance are divergent and that the oxidative potentials of OER are detrimental to ORR activity.These findings are used to give guidelines for future bifunctional catalyst design.Additionally,it is demonstrated how sunlight can be used to reactivate the ORR activity of LSM after rigorous cycling.