Intestinal ischemia is a frequently observed phenomenon. Morbidity and mortality rates are extraordinarily high and did not improve over the past decades. This is in part attributable to limited knowledge on the patho...Intestinal ischemia is a frequently observed phenomenon. Morbidity and mortality rates are extraordinarily high and did not improve over the past decades. This is in part attributable to limited knowledge on the pathophysiology of intestinal ischemia-reperfusion(IR) in man, the paucity in preventive and/or therapeutic options and the lack of early diagnostic markers for intestinal ischemia. To improve our knowledge and solve clinically important questions regarding intestinal IR, we developed a human experimental intestinal IR model. With this model, we were able to gain insight into the mechanisms that allow the human gut to withstand short periods of IR without the development of severe inflammatory responses. The purpose of this review is to overview the most relevant recent advances in our understanding of the pathophysiology of human intestinal IR, as well as the(potential) future clinical implications.展开更多
Early identification of acute mesenteric ischemia (AMI) is challenging. The wide variability in clinical presentation challenges providers to make an early accurate diagnosis. Despite major diagnostic and treatment ad...Early identification of acute mesenteric ischemia (AMI) is challenging. The wide variability in clinical presentation challenges providers to make an early accurate diagnosis. Despite major diagnostic and treatment advances over the past decades, mortality remains high. Arterial embolus and superior mesenteric artery thrombosis are common causes of AMI. Non-occlusive causes are less common, but vasculitis may be important, especially in younger people. Because of the unclear clinical presentation and non-specific laboratory findings, low clinical suspicion may lead to loss of valuable time. During this diagnostic delay, progression of ischemia to transmural bowel infarction with peritonitis and septicemia may further worsen patient outcomes. Several diagnostic modalities are used to assess possible AMI. Multi-detector row computed tomographic angiography is the current gold standard. Although computed tomographic angiography leads to an accurate diagnosis in many cases, early detection is a persistent problem. Because early diagnosis is vital to commence treatment, new diagnostic strategies are needed. A non-invasive simple biochemical test would be ideal to increase clinical suspicion of AMI and would improve patient selection for radiographic evaluation. Thus, AMI could be diagnosed earlier with follow-up computed tomographic angiography or high spatial magnetic resonance imaging. Experimental in vitro and in vivo studies show promise for alpha glutathione S transferase and intestinal fatty acid binding protein as markers for AMI. Future research must confirm the clinical utility of these biochemical markers in the diagnosis of mesenteric ischemia.展开更多
Over the past decades evidence has been accumulating that intestinal barrier integrity loss plays a key role in the development and perpetuation of a variety of disease states including inflammatory bowel disease and ...Over the past decades evidence has been accumulating that intestinal barrier integrity loss plays a key role in the development and perpetuation of a variety of disease states including inflammatory bowel disease and celiac disease,and is a key player in the onset of sepsis and multiple organ failure in situations of intestinal hypoperfusion,including trauma and major surgery.Insight into gut barrier integrity and function loss is important to improve our knowledge on disease etiology and pathophysiology and contributes to early detection and/or secondary prevention of disease.A variety of tests have been developed to assess intestinal epithelial cell damage,intestinal tight junction status and consequences of intestinal barrier integrity loss,i.e.increased intestinal permeability.This review discusses currently available methods for evaluating loss of human intestinal barrier integrity and function.展开更多
During the last several decades,colorectal cancer surgery has experienced some major perioperative improvements.Preoperative risk-assessment of nutrition,frailty,and sarcopenia followed by interventions for patient op...During the last several decades,colorectal cancer surgery has experienced some major perioperative improvements.Preoperative risk-assessment of nutrition,frailty,and sarcopenia followed by interventions for patient optimization or an adapted surgical strategy,contributed to improved postoperative outcomes.Enhanced recovery programs or fast-track surgery also resulted in reduced length of hospital stay and overall complications without affecting patient safety.After an initially indecisive start due to uncertainty about oncological safety,the most significant improvement in intraoperative care was the introduction of laparoscopy.Laparoscopic surgery for colon and rectal cancer is associated with better short-term outcomes,whereas long-term outcomes regarding survival and recurrence rates are comparable.Nevertheless,long-term results in rectal surgery remain to be seen.Early recognition of anastomotic leakage remains a challenge,though multiple improvements have allowed better management of this complication.展开更多
Postoperative ileus is a frequently occurring surgical complication, leading to increased morbidity and hospital stay. Abdominal surgical interventions are known to result in a protracted cessation of bowel movement. ...Postoperative ileus is a frequently occurring surgical complication, leading to increased morbidity and hospital stay. Abdominal surgical interventions are known to result in a protracted cessation of bowel movement. Activation of inhibitory neural pathways by nociceptive stimuli leads to an inhibition of propulsive activity, which resolves shortly after closure of the abdomen. The subsequent formation of an inflammatory infiltrate in the muscular layers of the intestine results in a more prolonged phase of ileus. Over the last decade, clinical strategies focusing on reduction of surgical stress and promoting postoperative recovery have improved the course of postoperative ileus. Additionally, recent experimental evidence implicated antiinflammatory interventions, such as vagal stimulation, as potential targets to treat postoperative ileus and reduce the period of intestinal hypomotility. Activation of nicotinic receptors on inflammatory cells by vagal input attenuates inflammation and promotes gastrointestinal motility in experimental models of ileus. A novel physiologicalintervention to activate this neuroimmune pathway is enteral administration of lipid-rich nutrition. Perioperative administration of lipid-rich nutrition reduced manipulation-induced local inflammation of the intestine and accelerated recovery of bowel movement. The application of safe and easy to use antiinflammatory interventions, together with the current multimodal approach, could reduce postoperative ileus to an absolute minimum and shorten hospital stay.展开更多
AIM To assess intestinal barrier function during human intestinal ischemia and reperfusion(IR).METHODS In a human experimental model,6 cm of jejunum was selectively exposed to 30 min of ischemia(I) followed by 30 and ...AIM To assess intestinal barrier function during human intestinal ischemia and reperfusion(IR).METHODS In a human experimental model,6 cm of jejunum was selectively exposed to 30 min of ischemia(I) followed by 30 and 120 min of reperfusion(R). A sham procedure was also performed. Blood and tissue was sampled at all-time points. Functional barrier function was assessed using dual-sugar absorption tests with lactulose(L) and rhamnose(R). Plasma concentrations of citrulline,an amino acid described as marker for enterocyte function were measured as marker of metabolic enterocytes restoration. Damage to the epithelial lining was assessed by immunohistochemistry for tight junctions( TJs),by plasma marker for enterocytes damage(I-FABP) and analyzed by electron microscopy(EM) using lanthanum nitrate as an electrondense marker.RESULTS Plasma L/R ratio's were significantly increased after 30 min of ischemia(30 I) followed by 30 min of reperfusion(30 R) compared to control(0.75 ± 0.10 vs 0.20 ± 0.09,P < 0.05). At 120 min of reperfusion(120 R),ratio's normalized(0.17 ± 0.06) and were not significantly different from control. Plasma levels of I-FABP correlated with plasma L/R ratios measured at the same time points(correlation: 0.467,P < 0.01). TJs staining shows distortion of staining at 30 I. An intact lining of TJs was again observed at 30 I120 R. Electron microscopy analysis revealed disrupted TJs after 30 I with paracellular leakage of lanthanum nitrate,which restored after 30 I120 R. Furthermore,citrulline concentrations closely paralleled the histological perturbations during intestinal IR.CONCLUSION This study directly correlates histological data with intestinal permeability tests,revealing that the human gut has the ability of to withstand short episodes of ischemia,with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion.展开更多
Cholangiocarcinoma(CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a di...Cholangiocarcinoma(CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells. A recent study by Boulter et al implicates the Wnt signaling cascade in cholangiocarcinogenesis. Wnt ligands Wnt7 B and Wnt10 A were found to be highly overexpressed in human CCA tissue. Wnt7 B protein was present throughout the tumor stroma, and often co-localized with a subset of CD68+ macrophages. To address in a direct manner whether Wnt signaling is engaged in development of CCA, Boulter et al explored the Wnt signaling pathway in an experimental model that recapitulates the multi-stage progression of human CCA.Wnt ligands found to be elevated in human CCA were also upregulated during the course of CCA development following thioacetamide treatment. Wnt10 a increased during the(pre-cancerous) regenerative phase, while Wnt7 b induction paralleled tumor growth. Along with upregulation of target genes, the findings demonstrate that the canonical Wnt pathway is progressively activated during cholangio-carcinogenesis. Macrophage depletion,eliminating a major source of Wnt7 b, prevented activation of the canonical Wnt cascade, and resulted in reduced number and volume of tumors in this model. Moreover,specific inhibitors of the canonical Wnt pathway(ICG-001 and C-59) caused reduction of tumor area and number,in xenograft and thioacetamide models of CCA. The aggregated findings show that experimental, and presumably human CCA, is a Wnt-driven tumor. Modulation of Wnt signaling, alone or in combination with surgicalor chemotherapy approaches, holds promise in the management of this fatal malignancy.展开更多
AIM To determine the level of consensus on the definition of colorectal anastomotic leakage(CAL)among Dutch and Chinese colorectal surgeons.METHODS Dutch and Chinese colorectal surgeons were asked to partake in an onl...AIM To determine the level of consensus on the definition of colorectal anastomotic leakage(CAL)among Dutch and Chinese colorectal surgeons.METHODS Dutch and Chinese colorectal surgeons were asked to partake in an online questionnaire.Consensus in the online questionnaire was defined as>80%agreement between respondents on various statements regarding a general definition of CAL,and regarding clinical and radiological diagnosis of the complication.RESULTS Fifty-nine Dutch and 202 Chinese dedicated colorectal surgeons participated in the online survey.Consensus was found on only one of the proposed elements of a general definition of CAL in both countries:‘extravasation of contrast medium after rectal enema on a CT scan'.Another two were found relevant according to Dutch surgeons:‘necrosis of the anastomosis found during reoperation',and‘a radiological collection treated with percutaneous drainage'.No consensus was found for all other proposed elements that may be included in a general definition.CONCLUSION There is no universally accepted definition of CAL in the Netherlands and China.Diagnosis of CAL based on clinical manifestations remains a point of discussion in both countries.Dutch surgeons are more likely to report‘subclinical'leaks as CAL,which partly explains the higher reported Dutch CAL rates.展开更多
AIM To identify risk factors associated with the formation of biliary strictures post liver transplantation over a period of 10-year in Queensland.METHODS Data on liver donors and recipients in Queensland between 2005...AIM To identify risk factors associated with the formation of biliary strictures post liver transplantation over a period of 10-year in Queensland.METHODS Data on liver donors and recipients in Queensland between 2005 and 2014 was obtained from an electronic patient data system.In addition,intra-operative and post-operative characteristics were collected and a logistical regression analysis was performed to evaluate their association with the development of biliary strictures.RESULTS Of 296 liver transplants performed,285(96.3%) were from brain dead donors.Biliary strictures developed in 45(15.2%) recipients.Anastomotic stricture formation(n = 25,48.1%) was the commonest complication,with 14(58.3%) of these occurred within 6-mo of transplant.A percutaneous approach or endoscopic retrograde cholangiography was used to treat 17(37.8%) patients with biliary strictures.Biliary reconstruction was initially or ultimately required in 22(48.9%) patients.In recipients developing biliary strictures,bilirubin was significantly increased within the first postoperative week(Day 7 total bilirubin 74 μmol/L vs 49 μmol/L,P = 0.012).In both univariate and multivariate regression analysis,Day 7 total bilirubin > 55 μmol/L was associated with the development of biliary stricture formation.In addition,hepatic artery thrombosis and primary sclerosing cholangitis were identified as independent risk factors.CONCLUSION In addition to known risk factors,bilirubin levels in the early post-operative period could be used as a clinical indicator for biliary stricture formation.展开更多
Protein phosphorylation plays an important role in physiological processes, such as muscle contraction. Phospho-specific antibodies have become powerful tools to study these processes. Cardiac myosin binding protein-C...Protein phosphorylation plays an important role in physiological processes, such as muscle contraction. Phospho-specific antibodies have become powerful tools to study these processes. Cardiac myosin binding protein-C (cMyBP-C) is one of the proteins that make up the contractile apparatus of cardiomyocytes. Phosphorylation of cMyBP-C is essential for normal cardiac function, since dephosphorylation of this protein leads to its degradation and has been associated with cardiomyopathy. One of the upstream kinases, which phosphorylate cMyBP-C, is protein kinase D (PKD). While studying the role of PKD in cMyBP-C phosphorylation, we tried to analyze phosphorylation of PKD with a phospho-specific PKD-Ser744/748 antibody. Contrary to the expected 115 kDa, a signal was found for a 150-kDa protein. By MALDI-TOF mass spectrometry, we identified this protein to be cMyBP-C. These data were confirmed by immunostaining using the p-PKD-Ser744/748 antibody, which displayed a striated pattern similar to the one observed for a regular cMyBP-C antibody. To our knowledge there are no antibodies commercially available for phosphorylated cMyBP-C. Thus, the p-PKD-Ser744/748 antibody can accelerate research into the role of cMyBP-C phosphorylation in cardiomyocytes.展开更多
The therapeutic potential of long-term ketotifen in irritable bowel syndrome and postoperative ileus is currently under investigation. Ambiguous results of prolonged postoperative ketotifen use on gastrointestinal pas...The therapeutic potential of long-term ketotifen in irritable bowel syndrome and postoperative ileus is currently under investigation. Ambiguous results of prolonged postoperative ketotifen use on gastrointestinal passage have been found. The current data point at a hampered gastrointestinal transit after prolonged postoperative ketotifen use in a rodent ileus induction model. Therefore, caution should be taken when administering ketotifen in the perioperative phase.展开更多
Background: Research has been conducted to assess the effectiveness of weight management, dietary and physical activity interventions in military settings. However, a recent and comprehensive overview is lacking. The ...Background: Research has been conducted to assess the effectiveness of weight management, dietary and physical activity interventions in military settings. However, a recent and comprehensive overview is lacking. The aim of this systematic review is to examine the evidence and describe key components of effective interventions in terms of improving body composition, dietary behaviors, and physical activity among active-duty military personnel.Methods: Pub Med, Psyc Info, and CINAHL were searched on the 17 th of November 2017 to identify interventions that promoted diet and/or physical activity among active-duty military personnel. Studies were included if they assessed outcomes related to anthropometric measurements, dietary behaviors, or fitness/physical activity levels. There were no restrictions regarding publication date, follow-up duration, and sex. After screening, a total of 136 studies were eligible. Of these studies, 38 included an educational and/or behavioral change component, and 98 had only physical or fitness training as part of basic military training. Only studies that included an educational and/or behavioral change component were assessed for quality using the Effective Public Health Practice Project tool and included in the qualitative synthesis of the results.Results: Based on consistent evidence from studies that were rated as moderate or strong, there is good evidence that military weight management interventions are effective in improving body composition for durations of up to 12 months. Effective interventions are more likely to be high intensity(have a greater number of sessions), are more often delivered by specialists, and use theoretical base/behavioral change techniques and a standardized guideline. Dietary interventions can potentially reduce total fat and saturated fat intake. Dietary interventions that target the kitchen staff and/or increase the availability of healthy food are more likely to be effective in the short term. The results regarding military physical fitness interventions were inconclusive.Conclusions: Despite limitations such as the diversity and heterogeneity of the included interventions, outcome measurements, and follow-up duration, this systematic review found good evidence that weight management interventions are effective, especially in terms of weight loss. More studies are needed to acquire solid evidence for effectiveness for durations longer than 12 months and to identify key components of the effective dietary and physical activity educational and/or behavioral change interventions, especially in countries outside Europe and the US.展开更多
AIM:To examine performances regarding prediction of polyp histology using high-definition (HD) i-scan in a group of endoscopists with varying levels of experience. METHODS:We used a digital library of HD i-scan still ...AIM:To examine performances regarding prediction of polyp histology using high-definition (HD) i-scan in a group of endoscopists with varying levels of experience. METHODS:We used a digital library of HD i-scan still images, comprising twin pictures (surface enhancement and tone enhancement), collected at our university hospital. We defined endoscopic features of adenomatous and non-adenomatous polyps, according to the following parameters:color, surface pattern and vascular pattern. We familiarized the participating endoscopists on optical diagnosis of colorectal polyps using a 20-min didactic training session. All endoscopists were asked to evaluate an image set of 50 colorectal polyps with regard to polyp histology. We classified the diagnoses into high confidence (i.e., cases in which the endoscopist could assign a diagnosis with certainty) and low confidence diagnoses (i.e., cases in which the endoscopist preferred to send the polyp for formal histology). Mean sensitivity, specificity and accuracy per endoscopist/image were computed and differences between groups tested using independent-samples t tests. High vs low confidence diagnoses were compared using the pairedsamples t test. RESULTS:Eleven endoscopists without previous experience on optical diagnosis evaluated a total of 550 images (396 adenomatous, 154 non-adenomatous). Mean sensitivity, specificity and accuracy for diagnosing adenomas were 79.3%, 85.7% and 81.1%, respectively. No significant differences were found between gastroenterologists and trainees regarding performances of optical diagnosis (mean accuracy 78.0%vs 82.9%,P = 0.098). Diminutive lesions were predicted with a lower mean accuracy as compared to non-diminutive lesions (74.2% vs 93.1%, P = 0.008). A total of 446 (81.1%) diagnoses were made with high confidence. High confidence diagnoses corresponded to a significantly higher mean accuracy than low confidence diagnoses (84.0% vs 64.3%, P = 0.008). A total of 319 (58.0%) images were evaluated as having excellent quality. Considering excellent quality images in conjunction with high confidence diagnosis, overall accuracy increased to 92.8%. CONCLUSION:After a single training session, endoscopists with varying levels of experience can already provide optical diagnosis with an accuracy of 84.0%.展开更多
Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 that manifests as a variety of clinical manifestations,including liver damage commonly detected by a hepa...Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 that manifests as a variety of clinical manifestations,including liver damage commonly detected by a hepatocellular pattern from liver function tests.Liver injury is associated with a worse prognosis overall.Conditions associated with the severity of the disease include obesity and cardiometabolic comorbidities,which are also associated with nonalcoholic fatty liver disease(NAFLD).The presence of NAFLD,similarly to obesity,is associated with an unfavourable impact on the coronavirus disease 2019 outcome.Individuals with these conditions could present with liver damage and elevated liver function tests due to direct viral cytotoxicity,systemic inflammation,ischemic or hypoxic liver damage or drug side effects.However,liver damage in the setting of NAFLD could also be attributed to a pre-existing chronic low-grade inflammation associated with surplus and dysfunctional adipose tissue in these individuals.Here we investigate the hypothesis that a pre-existing inflammatory status is exacerbated after severe acute respiratory syndrome coronavirus 2 infection,which embodies a second hit to the underestimated liver damage.展开更多
BACKGROUND There is still considerable heterogeneity regarding which features of cryptoglandular anal fistula on magnetic resonance imaging(MRI)and endoanal ultrasound(EAUS)are relevant to surgical decision-making.As ...BACKGROUND There is still considerable heterogeneity regarding which features of cryptoglandular anal fistula on magnetic resonance imaging(MRI)and endoanal ultrasound(EAUS)are relevant to surgical decision-making.As a con-sequence,the quality and completeness of the report are highly dependent on the training and experience of the examiners.AIM To develop a structured MRI and EAUS template(SMART)reporting the minimum dataset of information for the treatment of anal fistulas.METHODS This modified Delphi survey based on the RAND-UCLA appropriateness for consensus-building was conducted between May and August 2023.One hundred and fifty-one articles selected from a systematic review of the lite-rature formed the database to generate the evidence-based statements for the Delphi study.Fourteen questions were anonymously voted by an interdisciplinary multidisciplinary group for a maximum of three iterative rounds.The degree of agreement was scored on a numeric 0–10 scale.Group consensus was defined as a score≥8 for≥80%of the panelists.RESULTS Eleven scientific societies(3 radiological and 8 surgical)endorsed the study.After three rounds of voting,the experts(69 colorectal surgeons,23 radiologists,2 anatomists,and 1 gastroenterologist)achieved consensus for 12 of 14 statements(85.7%).Based on the results of the Delphi process,the six following features of anal fistulas were included in the SMART:Primary tract,secondary extension,internal opening,presence of collection,coexisting le-sions,and sphincters morphology.CONCLUSION A structured template,SMART,was developed to standardize imaging reporting of fistula-in-ano in a simple,systematic,time-efficient way,providing the minimum dataset of information and visual diagram useful to refer-ring physicians.展开更多
Background and Aims:The prevalence of chronic liver dis-ease in adults exceeds 30%in some countries and there is significant interest in developing tests and treatments to help control disease progression and reduce h...Background and Aims:The prevalence of chronic liver dis-ease in adults exceeds 30%in some countries and there is significant interest in developing tests and treatments to help control disease progression and reduce healthcare burden.Breath is a rich sampling matrix that offers non-invasive so-lutions suitable for early-stage detection and disease moni-toring.Having previously investigated targeted analysis of a single biomarker,here we investigated a multiparametric approach to breath testing that would provide more robust and reliable results for clinical use.Methods:To identify can-didate biomarkers we compared 46 breath samples from cir-rhosis patients and 42 from controls.Collection and analysis used Breath Biopsy OMNI™,maximizing signal and contrast to background to provide high confidence biomarker detec-tion based upon gas chromatography mass spectrometry(GC-MS).Blank samples were also analyzed to provide de-tailed information on background volatile organic compounds(VOCs)levels.Results:A set of 29 breath VOCs differed significantly between cirrhosis and controls.A classification model based on these VOCs had an area under the curve(AUC)of 0.95±0.04 in cross-validated test sets.The seven best performing VOCs were sufficient to maximize classifica-tion performance.A subset of 11 VOCs was correlated with blood metrics of liver function(bilirubin,albumin,prothrom-bin time)and separated patients by cirrhosis severity using principal component analysis.Conclusions:A set of seven VOCs consisting of previously reported and novel candidates show promise as a panel for liver disease detection and mon-itoring,showing correlation to disease severity and serum biomarkers at late stage.展开更多
Sarcopenia,which is characterized by reduction in muscle mass and strength,contributes to several age-related conditions,including insulin resistance and frailty.Despite the importance of maintaining muscle mass for h...Sarcopenia,which is characterized by reduction in muscle mass and strength,contributes to several age-related conditions,including insulin resistance and frailty.Despite the importance of maintaining muscle mass for healthy aging,the mechanisms contributing to sarcopenia are not fully elucidated.Nevertheless,mitochondria appear to play a key role in the underlying condition,and importantly,respond robustly to exercise interventions.Mitochondria are intracellular organelles largely attributed to maintaining ATP concentrations,however,the importance of this organelle in overall cellular homeostasis has been expanded in the last decades to include redox signaling,calcium homeostasis,inflammation,and apoptosis.Several lines of evidence suggest that mitochondrial bioenergetics are altered in aged skeletal muscle,resulting in an increase in reactive oxygen species(ROS)production,while conversely genetic/pharmacological approaches that attenuate mitochondrial ROS promote healthy aging and maintenance of muscle mass.These observations suggest that increased free radicals are one of the bases of the aging process and related sarcopenia.Here,we reviewed the current knowledge regarding mitochondrial function and redox balance in aged human skeletal muscle,highlighting the implications of redox unbalance on skeletal muscle mass maintenance and muscle health.Additionally,we describe the benefits of exercise and nutrition interventions in the context of improving mitochondrial bioenergetics and functional outcomes regarding skeletal muscle mass and function.展开更多
Importance:While laparoscopic pancreaticoduodenectomy(LPD)is being adopted with increasing enthusiasm worldwide,it is still challenging for both technical and anatomical reasons.Currently,there is no consensus on the ...Importance:While laparoscopic pancreaticoduodenectomy(LPD)is being adopted with increasing enthusiasm worldwide,it is still challenging for both technical and anatomical reasons.Currently,there is no consensus on the technical standards for LPD.Objective:The aim of this consensus statement is to guide the continued safe progression and adoption of LPD.Evidence Review:An international panel of experts was selected based on their clinical and scientific expertise in laparoscopic and open pancreaticoduodenectomy.Statements were produced upon reviewing the literature and assessed by the members of the expert panel.The literature search and its critical appraisal were limited to articles published in English during the period from 1994 to 2019.The Web of Science,Medline,and Cochrane Library and Clinical Trials databases were searched,The search strategy included,but was not limited to,the terms'laparoscopic','pancreaticoduodenectomy,'pancreatoduodenectomy','Whipple's operation',and'minimally invasive surgery'.Reference lists from the included articles were manually checked for any additional studies,which were included when appropriate.Delphi method was used to establish expert consensus and the AGREE II-GRS Instrument was applied to assess the methodological quality and externally validate the final statements.The statements were further discussed during a one-day face-to-face meeting at the 1st Summit on Minimally Invasive Pancreatico-Biliary Surgery in Wuhan,China.Findings:Twenty-eight international experts from 8 countries constructed the expert panel.Sixteen statements were produced by the members of the expert panel.At least 80%of responders agreed with the majority(80%)of statements.Other than three randomized controlled trials published to date,most evidences were based on level 3 or 4 studies according to the AGREE II-GRS Instrument.Conclusions and Relevance:The Wuhan international expert consensus meeting on LPD has produced a set of clinical practice statements for the safe development and progression of LPD.LPD is currently in its development and exploration stages,as defined by the international IDEAL framework for surgical innovation.More robust randomized controlled trial and registry study are essential to proceed with the assessment of LPD.展开更多
The FAIR principles have been widely cited,endorsed and adopted by a broad range of stakeholders since their publication in 2016.By intention,the 15 FAIR guiding principles do not dictate specific technological implem...The FAIR principles have been widely cited,endorsed and adopted by a broad range of stakeholders since their publication in 2016.By intention,the 15 FAIR guiding principles do not dictate specific technological implementations,but provide guidance for improving Findability,Accessibility,Interoperability and Reusability of digital resources.This has likely contributed to the broad adoption of the FAIR principles,because individual stakeholder communities can implement their own FAIR solutions.However,it has also resulted in inconsistent interpretations that carry the risk of leading to incompatible implementations.Thus,while the FAIR principles are formulated on a high level and may be interpreted and implemented in different ways,for true interoperability we need to support convergence in implementation choices that are widely accessible and(re)-usable.We introduce the concept of FAIR implementation considerations to assist accelerated global participation and convergence towards accessible,robust,widespread and consistent FAIR implementations.Any self-identified stakeholder community may either choose to reuse solutions from existing implementations,or when they spot a gap,accept the challenge to create the needed solution,which,ideally,can be used again by other communities in the future.Here,we provide interpretations and implementation considerations(choices and challenges)for each FAIR principle.展开更多
Objective.The strongest locus which associated with type 2 diabetes(T2D)by the common variant rs7903146 is the transcription factor 7-like 2 gene(TCF7L2).We aimed to quantify the interaction of diet/lifestyle interven...Objective.The strongest locus which associated with type 2 diabetes(T2D)by the common variant rs7903146 is the transcription factor 7-like 2 gene(TCF7L2).We aimed to quantify the interaction of diet/lifestyle interventions and the genetic effect of TCF7L2 rs7903146 on glycemic traits,body weight,or waist circumference in overweight or obese adults in several randomized controlled trials(RCTs).Methods.From October 2016 to May 2018,a large collaborative analysis was performed by pooling individualparticipant data from 7 RCTs.These RCTs reported changes in glycemic control and adiposity of the variant rs7903146 after dietary/lifestyle-related interventions in overweight or obese adults.Gene treatment interaction models which used the genetic effect encoded by the allele dose and common covariates were applicable to individual participant data in all studies.Results.In the joint analysis,a total of 7 eligible RCTs were included(n=4,114).Importantly,we observed a significant effect modification of diet/lifestyle-related interventions on the TCF7L2 variant rs7903146 and changes in fasting glucose.Compared with the control group,diet/lifestyle interventions were related to lower fasting glucose by-3.06(95%CI,-5.77 to-0.36)mg/dL(test for heterogeneity and overall effect:I^(2)=45:1%,p<0:05;z=2:20,p=0:028)per one copy of the TCF7L2 T risk allele.Furthermore,regardless of genetic risk,diet/lifestyle interventions were associated with lower waist circumference.However,there was no significant change for diet/lifestyle interventions in other glycemic control and adiposity traits per one copy of TCF7L2 risk allele.Conclusions.Our findings suggest that carrying the TCF7L2 T risk allele may have a modestly greater benefit for specific diet/lifestyle interventions to improve the control of fasting glucose in overweight or obese adults.展开更多
基金Supported by Dutch Gastroenterology and Hepatology Society(MLDS grant WO10-57 to Dejong CHC and Lenaerts K)Career Development Grant CDG(to Derikx JPM)The Netherlands Organisation for Scientific Research(Rubicon grant 825.13.012 to Grootjans J)
文摘Intestinal ischemia is a frequently observed phenomenon. Morbidity and mortality rates are extraordinarily high and did not improve over the past decades. This is in part attributable to limited knowledge on the pathophysiology of intestinal ischemia-reperfusion(IR) in man, the paucity in preventive and/or therapeutic options and the lack of early diagnostic markers for intestinal ischemia. To improve our knowledge and solve clinically important questions regarding intestinal IR, we developed a human experimental intestinal IR model. With this model, we were able to gain insight into the mechanisms that allow the human gut to withstand short periods of IR without the development of severe inflammatory responses. The purpose of this review is to overview the most relevant recent advances in our understanding of the pathophysiology of human intestinal IR, as well as the(potential) future clinical implications.
文摘Early identification of acute mesenteric ischemia (AMI) is challenging. The wide variability in clinical presentation challenges providers to make an early accurate diagnosis. Despite major diagnostic and treatment advances over the past decades, mortality remains high. Arterial embolus and superior mesenteric artery thrombosis are common causes of AMI. Non-occlusive causes are less common, but vasculitis may be important, especially in younger people. Because of the unclear clinical presentation and non-specific laboratory findings, low clinical suspicion may lead to loss of valuable time. During this diagnostic delay, progression of ischemia to transmural bowel infarction with peritonitis and septicemia may further worsen patient outcomes. Several diagnostic modalities are used to assess possible AMI. Multi-detector row computed tomographic angiography is the current gold standard. Although computed tomographic angiography leads to an accurate diagnosis in many cases, early detection is a persistent problem. Because early diagnosis is vital to commence treatment, new diagnostic strategies are needed. A non-invasive simple biochemical test would be ideal to increase clinical suspicion of AMI and would improve patient selection for radiographic evaluation. Thus, AMI could be diagnosed earlier with follow-up computed tomographic angiography or high spatial magnetic resonance imaging. Experimental in vitro and in vivo studies show promise for alpha glutathione S transferase and intestinal fatty acid binding protein as markers for AMI. Future research must confirm the clinical utility of these biochemical markers in the diagnosis of mesenteric ischemia.
文摘Over the past decades evidence has been accumulating that intestinal barrier integrity loss plays a key role in the development and perpetuation of a variety of disease states including inflammatory bowel disease and celiac disease,and is a key player in the onset of sepsis and multiple organ failure in situations of intestinal hypoperfusion,including trauma and major surgery.Insight into gut barrier integrity and function loss is important to improve our knowledge on disease etiology and pathophysiology and contributes to early detection and/or secondary prevention of disease.A variety of tests have been developed to assess intestinal epithelial cell damage,intestinal tight junction status and consequences of intestinal barrier integrity loss,i.e.increased intestinal permeability.This review discusses currently available methods for evaluating loss of human intestinal barrier integrity and function.
文摘During the last several decades,colorectal cancer surgery has experienced some major perioperative improvements.Preoperative risk-assessment of nutrition,frailty,and sarcopenia followed by interventions for patient optimization or an adapted surgical strategy,contributed to improved postoperative outcomes.Enhanced recovery programs or fast-track surgery also resulted in reduced length of hospital stay and overall complications without affecting patient safety.After an initially indecisive start due to uncertainty about oncological safety,the most significant improvement in intraoperative care was the introduction of laparoscopy.Laparoscopic surgery for colon and rectal cancer is associated with better short-term outcomes,whereas long-term outcomes regarding survival and recurrence rates are comparable.Nevertheless,long-term results in rectal surgery remain to be seen.Early recognition of anastomotic leakage remains a challenge,though multiple improvements have allowed better management of this complication.
基金Supported by DANONE Research Centre for Specialised Nutrition, Wageningen, the Netherlandsby AGIKO-stipendia 920-03-522 (to Lubbers T) and 920-03-271 (to Luyer M) from the Netherlands Organization for Health Research and Development
文摘Postoperative ileus is a frequently occurring surgical complication, leading to increased morbidity and hospital stay. Abdominal surgical interventions are known to result in a protracted cessation of bowel movement. Activation of inhibitory neural pathways by nociceptive stimuli leads to an inhibition of propulsive activity, which resolves shortly after closure of the abdomen. The subsequent formation of an inflammatory infiltrate in the muscular layers of the intestine results in a more prolonged phase of ileus. Over the last decade, clinical strategies focusing on reduction of surgical stress and promoting postoperative recovery have improved the course of postoperative ileus. Additionally, recent experimental evidence implicated antiinflammatory interventions, such as vagal stimulation, as potential targets to treat postoperative ileus and reduce the period of intestinal hypomotility. Activation of nicotinic receptors on inflammatory cells by vagal input attenuates inflammation and promotes gastrointestinal motility in experimental models of ileus. A novel physiologicalintervention to activate this neuroimmune pathway is enteral administration of lipid-rich nutrition. Perioperative administration of lipid-rich nutrition reduced manipulation-induced local inflammation of the intestine and accelerated recovery of bowel movement. The application of safe and easy to use antiinflammatory interventions, together with the current multimodal approach, could reduce postoperative ileus to an absolute minimum and shorten hospital stay.
基金Supported by Dutch Digestive Foundation(MLDS grant WO10-57 to Dejong CHC and Lenaerts K)and MLDS Career development grant CDG13-14 to Derikx JPM)the Netherlands Organisation for Scientific Research(Rubicon grant 2013/07161/ALW to Grootjans J)
文摘AIM To assess intestinal barrier function during human intestinal ischemia and reperfusion(IR).METHODS In a human experimental model,6 cm of jejunum was selectively exposed to 30 min of ischemia(I) followed by 30 and 120 min of reperfusion(R). A sham procedure was also performed. Blood and tissue was sampled at all-time points. Functional barrier function was assessed using dual-sugar absorption tests with lactulose(L) and rhamnose(R). Plasma concentrations of citrulline,an amino acid described as marker for enterocyte function were measured as marker of metabolic enterocytes restoration. Damage to the epithelial lining was assessed by immunohistochemistry for tight junctions( TJs),by plasma marker for enterocytes damage(I-FABP) and analyzed by electron microscopy(EM) using lanthanum nitrate as an electrondense marker.RESULTS Plasma L/R ratio's were significantly increased after 30 min of ischemia(30 I) followed by 30 min of reperfusion(30 R) compared to control(0.75 ± 0.10 vs 0.20 ± 0.09,P < 0.05). At 120 min of reperfusion(120 R),ratio's normalized(0.17 ± 0.06) and were not significantly different from control. Plasma levels of I-FABP correlated with plasma L/R ratios measured at the same time points(correlation: 0.467,P < 0.01). TJs staining shows distortion of staining at 30 I. An intact lining of TJs was again observed at 30 I120 R. Electron microscopy analysis revealed disrupted TJs after 30 I with paracellular leakage of lanthanum nitrate,which restored after 30 I120 R. Furthermore,citrulline concentrations closely paralleled the histological perturbations during intestinal IR.CONCLUSION This study directly correlates histological data with intestinal permeability tests,revealing that the human gut has the ability of to withstand short episodes of ischemia,with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion.
文摘Cholangiocarcinoma(CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells. A recent study by Boulter et al implicates the Wnt signaling cascade in cholangiocarcinogenesis. Wnt ligands Wnt7 B and Wnt10 A were found to be highly overexpressed in human CCA tissue. Wnt7 B protein was present throughout the tumor stroma, and often co-localized with a subset of CD68+ macrophages. To address in a direct manner whether Wnt signaling is engaged in development of CCA, Boulter et al explored the Wnt signaling pathway in an experimental model that recapitulates the multi-stage progression of human CCA.Wnt ligands found to be elevated in human CCA were also upregulated during the course of CCA development following thioacetamide treatment. Wnt10 a increased during the(pre-cancerous) regenerative phase, while Wnt7 b induction paralleled tumor growth. Along with upregulation of target genes, the findings demonstrate that the canonical Wnt pathway is progressively activated during cholangio-carcinogenesis. Macrophage depletion,eliminating a major source of Wnt7 b, prevented activation of the canonical Wnt cascade, and resulted in reduced number and volume of tumors in this model. Moreover,specific inhibitors of the canonical Wnt pathway(ICG-001 and C-59) caused reduction of tumor area and number,in xenograft and thioacetamide models of CCA. The aggregated findings show that experimental, and presumably human CCA, is a Wnt-driven tumor. Modulation of Wnt signaling, alone or in combination with surgicalor chemotherapy approaches, holds promise in the management of this fatal malignancy.
文摘AIM To determine the level of consensus on the definition of colorectal anastomotic leakage(CAL)among Dutch and Chinese colorectal surgeons.METHODS Dutch and Chinese colorectal surgeons were asked to partake in an online questionnaire.Consensus in the online questionnaire was defined as>80%agreement between respondents on various statements regarding a general definition of CAL,and regarding clinical and radiological diagnosis of the complication.RESULTS Fifty-nine Dutch and 202 Chinese dedicated colorectal surgeons participated in the online survey.Consensus was found on only one of the proposed elements of a general definition of CAL in both countries:‘extravasation of contrast medium after rectal enema on a CT scan'.Another two were found relevant according to Dutch surgeons:‘necrosis of the anastomosis found during reoperation',and‘a radiological collection treated with percutaneous drainage'.No consensus was found for all other proposed elements that may be included in a general definition.CONCLUSION There is no universally accepted definition of CAL in the Netherlands and China.Diagnosis of CAL based on clinical manifestations remains a point of discussion in both countries.Dutch surgeons are more likely to report‘subclinical'leaks as CAL,which partly explains the higher reported Dutch CAL rates.
文摘AIM To identify risk factors associated with the formation of biliary strictures post liver transplantation over a period of 10-year in Queensland.METHODS Data on liver donors and recipients in Queensland between 2005 and 2014 was obtained from an electronic patient data system.In addition,intra-operative and post-operative characteristics were collected and a logistical regression analysis was performed to evaluate their association with the development of biliary strictures.RESULTS Of 296 liver transplants performed,285(96.3%) were from brain dead donors.Biliary strictures developed in 45(15.2%) recipients.Anastomotic stricture formation(n = 25,48.1%) was the commonest complication,with 14(58.3%) of these occurred within 6-mo of transplant.A percutaneous approach or endoscopic retrograde cholangiography was used to treat 17(37.8%) patients with biliary strictures.Biliary reconstruction was initially or ultimately required in 22(48.9%) patients.In recipients developing biliary strictures,bilirubin was significantly increased within the first postoperative week(Day 7 total bilirubin 74 μmol/L vs 49 μmol/L,P = 0.012).In both univariate and multivariate regression analysis,Day 7 total bilirubin > 55 μmol/L was associated with the development of biliary stricture formation.In addition,hepatic artery thrombosis and primary sclerosing cholangitis were identified as independent risk factors.CONCLUSION In addition to known risk factors,bilirubin levels in the early post-operative period could be used as a clinical indicator for biliary stricture formation.
文摘Protein phosphorylation plays an important role in physiological processes, such as muscle contraction. Phospho-specific antibodies have become powerful tools to study these processes. Cardiac myosin binding protein-C (cMyBP-C) is one of the proteins that make up the contractile apparatus of cardiomyocytes. Phosphorylation of cMyBP-C is essential for normal cardiac function, since dephosphorylation of this protein leads to its degradation and has been associated with cardiomyopathy. One of the upstream kinases, which phosphorylate cMyBP-C, is protein kinase D (PKD). While studying the role of PKD in cMyBP-C phosphorylation, we tried to analyze phosphorylation of PKD with a phospho-specific PKD-Ser744/748 antibody. Contrary to the expected 115 kDa, a signal was found for a 150-kDa protein. By MALDI-TOF mass spectrometry, we identified this protein to be cMyBP-C. These data were confirmed by immunostaining using the p-PKD-Ser744/748 antibody, which displayed a striated pattern similar to the one observed for a regular cMyBP-C antibody. To our knowledge there are no antibodies commercially available for phosphorylated cMyBP-C. Thus, the p-PKD-Ser744/748 antibody can accelerate research into the role of cMyBP-C phosphorylation in cardiomyocytes.
文摘The therapeutic potential of long-term ketotifen in irritable bowel syndrome and postoperative ileus is currently under investigation. Ambiguous results of prolonged postoperative ketotifen use on gastrointestinal passage have been found. The current data point at a hampered gastrointestinal transit after prolonged postoperative ketotifen use in a rodent ileus induction model. Therefore, caution should be taken when administering ketotifen in the perioperative phase.
文摘Background: Research has been conducted to assess the effectiveness of weight management, dietary and physical activity interventions in military settings. However, a recent and comprehensive overview is lacking. The aim of this systematic review is to examine the evidence and describe key components of effective interventions in terms of improving body composition, dietary behaviors, and physical activity among active-duty military personnel.Methods: Pub Med, Psyc Info, and CINAHL were searched on the 17 th of November 2017 to identify interventions that promoted diet and/or physical activity among active-duty military personnel. Studies were included if they assessed outcomes related to anthropometric measurements, dietary behaviors, or fitness/physical activity levels. There were no restrictions regarding publication date, follow-up duration, and sex. After screening, a total of 136 studies were eligible. Of these studies, 38 included an educational and/or behavioral change component, and 98 had only physical or fitness training as part of basic military training. Only studies that included an educational and/or behavioral change component were assessed for quality using the Effective Public Health Practice Project tool and included in the qualitative synthesis of the results.Results: Based on consistent evidence from studies that were rated as moderate or strong, there is good evidence that military weight management interventions are effective in improving body composition for durations of up to 12 months. Effective interventions are more likely to be high intensity(have a greater number of sessions), are more often delivered by specialists, and use theoretical base/behavioral change techniques and a standardized guideline. Dietary interventions can potentially reduce total fat and saturated fat intake. Dietary interventions that target the kitchen staff and/or increase the availability of healthy food are more likely to be effective in the short term. The results regarding military physical fitness interventions were inconclusive.Conclusions: Despite limitations such as the diversity and heterogeneity of the included interventions, outcome measurements, and follow-up duration, this systematic review found good evidence that weight management interventions are effective, especially in terms of weight loss. More studies are needed to acquire solid evidence for effectiveness for durations longer than 12 months and to identify key components of the effective dietary and physical activity educational and/or behavioral change interventions, especially in countries outside Europe and the US.
文摘AIM:To examine performances regarding prediction of polyp histology using high-definition (HD) i-scan in a group of endoscopists with varying levels of experience. METHODS:We used a digital library of HD i-scan still images, comprising twin pictures (surface enhancement and tone enhancement), collected at our university hospital. We defined endoscopic features of adenomatous and non-adenomatous polyps, according to the following parameters:color, surface pattern and vascular pattern. We familiarized the participating endoscopists on optical diagnosis of colorectal polyps using a 20-min didactic training session. All endoscopists were asked to evaluate an image set of 50 colorectal polyps with regard to polyp histology. We classified the diagnoses into high confidence (i.e., cases in which the endoscopist could assign a diagnosis with certainty) and low confidence diagnoses (i.e., cases in which the endoscopist preferred to send the polyp for formal histology). Mean sensitivity, specificity and accuracy per endoscopist/image were computed and differences between groups tested using independent-samples t tests. High vs low confidence diagnoses were compared using the pairedsamples t test. RESULTS:Eleven endoscopists without previous experience on optical diagnosis evaluated a total of 550 images (396 adenomatous, 154 non-adenomatous). Mean sensitivity, specificity and accuracy for diagnosing adenomas were 79.3%, 85.7% and 81.1%, respectively. No significant differences were found between gastroenterologists and trainees regarding performances of optical diagnosis (mean accuracy 78.0%vs 82.9%,P = 0.098). Diminutive lesions were predicted with a lower mean accuracy as compared to non-diminutive lesions (74.2% vs 93.1%, P = 0.008). A total of 446 (81.1%) diagnoses were made with high confidence. High confidence diagnoses corresponded to a significantly higher mean accuracy than low confidence diagnoses (84.0% vs 64.3%, P = 0.008). A total of 319 (58.0%) images were evaluated as having excellent quality. Considering excellent quality images in conjunction with high confidence diagnosis, overall accuracy increased to 92.8%. CONCLUSION:After a single training session, endoscopists with varying levels of experience can already provide optical diagnosis with an accuracy of 84.0%.
文摘Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 that manifests as a variety of clinical manifestations,including liver damage commonly detected by a hepatocellular pattern from liver function tests.Liver injury is associated with a worse prognosis overall.Conditions associated with the severity of the disease include obesity and cardiometabolic comorbidities,which are also associated with nonalcoholic fatty liver disease(NAFLD).The presence of NAFLD,similarly to obesity,is associated with an unfavourable impact on the coronavirus disease 2019 outcome.Individuals with these conditions could present with liver damage and elevated liver function tests due to direct viral cytotoxicity,systemic inflammation,ischemic or hypoxic liver damage or drug side effects.However,liver damage in the setting of NAFLD could also be attributed to a pre-existing chronic low-grade inflammation associated with surplus and dysfunctional adipose tissue in these individuals.Here we investigate the hypothesis that a pre-existing inflammatory status is exacerbated after severe acute respiratory syndrome coronavirus 2 infection,which embodies a second hit to the underestimated liver damage.
文摘BACKGROUND There is still considerable heterogeneity regarding which features of cryptoglandular anal fistula on magnetic resonance imaging(MRI)and endoanal ultrasound(EAUS)are relevant to surgical decision-making.As a con-sequence,the quality and completeness of the report are highly dependent on the training and experience of the examiners.AIM To develop a structured MRI and EAUS template(SMART)reporting the minimum dataset of information for the treatment of anal fistulas.METHODS This modified Delphi survey based on the RAND-UCLA appropriateness for consensus-building was conducted between May and August 2023.One hundred and fifty-one articles selected from a systematic review of the lite-rature formed the database to generate the evidence-based statements for the Delphi study.Fourteen questions were anonymously voted by an interdisciplinary multidisciplinary group for a maximum of three iterative rounds.The degree of agreement was scored on a numeric 0–10 scale.Group consensus was defined as a score≥8 for≥80%of the panelists.RESULTS Eleven scientific societies(3 radiological and 8 surgical)endorsed the study.After three rounds of voting,the experts(69 colorectal surgeons,23 radiologists,2 anatomists,and 1 gastroenterologist)achieved consensus for 12 of 14 statements(85.7%).Based on the results of the Delphi process,the six following features of anal fistulas were included in the SMART:Primary tract,secondary extension,internal opening,presence of collection,coexisting le-sions,and sphincters morphology.CONCLUSION A structured template,SMART,was developed to standardize imaging reporting of fistula-in-ano in a simple,systematic,time-efficient way,providing the minimum dataset of information and visual diagram useful to refer-ring physicians.
基金funding from the Cancer Re-search UK for the CRUK Cambridge Centre Early Detection Program and International Alliance for Cancer Early Detection(CRUK grant refs:A25117 and RG97677)the NIHR Cambridge Biomedical Research Centre(BRC-1215-20014)。
文摘Background and Aims:The prevalence of chronic liver dis-ease in adults exceeds 30%in some countries and there is significant interest in developing tests and treatments to help control disease progression and reduce healthcare burden.Breath is a rich sampling matrix that offers non-invasive so-lutions suitable for early-stage detection and disease moni-toring.Having previously investigated targeted analysis of a single biomarker,here we investigated a multiparametric approach to breath testing that would provide more robust and reliable results for clinical use.Methods:To identify can-didate biomarkers we compared 46 breath samples from cir-rhosis patients and 42 from controls.Collection and analysis used Breath Biopsy OMNI™,maximizing signal and contrast to background to provide high confidence biomarker detec-tion based upon gas chromatography mass spectrometry(GC-MS).Blank samples were also analyzed to provide de-tailed information on background volatile organic compounds(VOCs)levels.Results:A set of 29 breath VOCs differed significantly between cirrhosis and controls.A classification model based on these VOCs had an area under the curve(AUC)of 0.95±0.04 in cross-validated test sets.The seven best performing VOCs were sufficient to maximize classifica-tion performance.A subset of 11 VOCs was correlated with blood metrics of liver function(bilirubin,albumin,prothrom-bin time)and separated patients by cirrhosis severity using principal component analysis.Conclusions:A set of seven VOCs consisting of previously reported and novel candidates show promise as a panel for liver disease detection and mon-itoring,showing correlation to disease severity and serum biomarkers at late stage.
基金funded by the Coordination for the improvement of Higher Education Personnel(CAPES)funded by the Natural Sci ences and Engineering Research Council of Canada(NSERC).
文摘Sarcopenia,which is characterized by reduction in muscle mass and strength,contributes to several age-related conditions,including insulin resistance and frailty.Despite the importance of maintaining muscle mass for healthy aging,the mechanisms contributing to sarcopenia are not fully elucidated.Nevertheless,mitochondria appear to play a key role in the underlying condition,and importantly,respond robustly to exercise interventions.Mitochondria are intracellular organelles largely attributed to maintaining ATP concentrations,however,the importance of this organelle in overall cellular homeostasis has been expanded in the last decades to include redox signaling,calcium homeostasis,inflammation,and apoptosis.Several lines of evidence suggest that mitochondrial bioenergetics are altered in aged skeletal muscle,resulting in an increase in reactive oxygen species(ROS)production,while conversely genetic/pharmacological approaches that attenuate mitochondrial ROS promote healthy aging and maintenance of muscle mass.These observations suggest that increased free radicals are one of the bases of the aging process and related sarcopenia.Here,we reviewed the current knowledge regarding mitochondrial function and redox balance in aged human skeletal muscle,highlighting the implications of redox unbalance on skeletal muscle mass maintenance and muscle health.Additionally,we describe the benefits of exercise and nutrition interventions in the context of improving mitochondrial bioenergetics and functional outcomes regarding skeletal muscle mass and function.
基金This study was supported by grants from The National Natural Science Foundation of China(81772950)Tongji Hospital Clinical Research Flagship Program(2019CR203)to RQ.
文摘Importance:While laparoscopic pancreaticoduodenectomy(LPD)is being adopted with increasing enthusiasm worldwide,it is still challenging for both technical and anatomical reasons.Currently,there is no consensus on the technical standards for LPD.Objective:The aim of this consensus statement is to guide the continued safe progression and adoption of LPD.Evidence Review:An international panel of experts was selected based on their clinical and scientific expertise in laparoscopic and open pancreaticoduodenectomy.Statements were produced upon reviewing the literature and assessed by the members of the expert panel.The literature search and its critical appraisal were limited to articles published in English during the period from 1994 to 2019.The Web of Science,Medline,and Cochrane Library and Clinical Trials databases were searched,The search strategy included,but was not limited to,the terms'laparoscopic','pancreaticoduodenectomy,'pancreatoduodenectomy','Whipple's operation',and'minimally invasive surgery'.Reference lists from the included articles were manually checked for any additional studies,which were included when appropriate.Delphi method was used to establish expert consensus and the AGREE II-GRS Instrument was applied to assess the methodological quality and externally validate the final statements.The statements were further discussed during a one-day face-to-face meeting at the 1st Summit on Minimally Invasive Pancreatico-Biliary Surgery in Wuhan,China.Findings:Twenty-eight international experts from 8 countries constructed the expert panel.Sixteen statements were produced by the members of the expert panel.At least 80%of responders agreed with the majority(80%)of statements.Other than three randomized controlled trials published to date,most evidences were based on level 3 or 4 studies according to the AGREE II-GRS Instrument.Conclusions and Relevance:The Wuhan international expert consensus meeting on LPD has produced a set of clinical practice statements for the safe development and progression of LPD.LPD is currently in its development and exploration stages,as defined by the international IDEAL framework for surgical innovation.More robust randomized controlled trial and registry study are essential to proceed with the assessment of LPD.
基金The work of A.Jacobsen,C.Evelo,M.Thompson,R.Cornet,R.Kaliyaperuma and M.Roos is supported by funding from the European Union’s Horizon 2020 research and innovation program under the EJP RD COFUND-EJP N°825575.The work of A.Jacobsen,C.Evelo,C.Goble,M.Thompson,N.Juty,R.Hooft,M.Roos,S-A.Sansone,P.McQuilton,P.Rocca-Serra and D.Batista is supported by funding from ELIXIR EXCELERATE,H2020 grant agreement number 676559.R.Hooft was further funded by NL NWO NRGWI.obrug.2018.009.N.Juty and C.Goble were funded by CORBEL(H2020 grant agreement 654248)N.Juty,C.Goble,S-A.Sansone,P.McQuilton,P.Rocca-Serra and D.Batista were funded by FAIRplus(IMI grant agreement 802750)+13 种基金N.Juty,C.Goble,M.Thompson,M.Roos,S-A.Sansone,P.McQuilton,P.Rocca-Serra and D.Batista were funded by EOSClife H2020-EU(grant agreement number 824087)C.Goble was funded by DMMCore(BBSRC BB/M013189/)M.Thompson,M.Roos received funding from NWO(VWData 400.17.605)S-A.Sansone,P.McQuilton,P.Rocca-Serra and D.Batista have been funded by grants awarded to S-A.Sansone from the UK BBSRC and Research Councils(BB/L024101/1,BB/L005069/1)EU(H2020-EU 634107H2020-EU 654241,IMI(IMPRiND 116060)NIH Data Common Fund,and from the Wellcome Trust(ISA-InterMine 212930/Z/18/ZFAIRsharing 208381/A/17/Z)The work of A.Waagmeester has been funded by grant award number GM089820 from the National Institutes of Health.M.Kersloot was funded by the European Regional Development Fund(KVW-00163).The work of N.Meyers was funded by the National Science Foundation(OAC 1839030)The work of M.D.Wilkinson is funded by Isaac Peral/Marie Curie cofund with the Universidad Politecnica de Madrid and the Ministerio de Economia y Competitividad grant number TIN2014-55993-RMThe work of B.Magagna,E.Schultes,L.da Silva Santos and K.Jeffery is funded by the H2020-EU 824068The work of B.Magagna,E.Schultes and L.da Silva Santos is funded by the GO FAIR ISCO grant of the Dutch Ministry of Science and CultureThe work of G.Guizzardi is supported by the OCEAN Project(FUB).M.Courtot received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No.802750.R.Cornet was further funded by FAIR4Health(H2020-EU grant agreement number 824666)K.Jeffery received funding from EPOS-IP H2020-EU agreement 676564 and ENVRIplus H2020-EU agreement 654182.
文摘The FAIR principles have been widely cited,endorsed and adopted by a broad range of stakeholders since their publication in 2016.By intention,the 15 FAIR guiding principles do not dictate specific technological implementations,but provide guidance for improving Findability,Accessibility,Interoperability and Reusability of digital resources.This has likely contributed to the broad adoption of the FAIR principles,because individual stakeholder communities can implement their own FAIR solutions.However,it has also resulted in inconsistent interpretations that carry the risk of leading to incompatible implementations.Thus,while the FAIR principles are formulated on a high level and may be interpreted and implemented in different ways,for true interoperability we need to support convergence in implementation choices that are widely accessible and(re)-usable.We introduce the concept of FAIR implementation considerations to assist accelerated global participation and convergence towards accessible,robust,widespread and consistent FAIR implementations.Any self-identified stakeholder community may either choose to reuse solutions from existing implementations,or when they spot a gap,accept the challenge to create the needed solution,which,ideally,can be used again by other communities in the future.Here,we provide interpretations and implementation considerations(choices and challenges)for each FAIR principle.
文摘Objective.The strongest locus which associated with type 2 diabetes(T2D)by the common variant rs7903146 is the transcription factor 7-like 2 gene(TCF7L2).We aimed to quantify the interaction of diet/lifestyle interventions and the genetic effect of TCF7L2 rs7903146 on glycemic traits,body weight,or waist circumference in overweight or obese adults in several randomized controlled trials(RCTs).Methods.From October 2016 to May 2018,a large collaborative analysis was performed by pooling individualparticipant data from 7 RCTs.These RCTs reported changes in glycemic control and adiposity of the variant rs7903146 after dietary/lifestyle-related interventions in overweight or obese adults.Gene treatment interaction models which used the genetic effect encoded by the allele dose and common covariates were applicable to individual participant data in all studies.Results.In the joint analysis,a total of 7 eligible RCTs were included(n=4,114).Importantly,we observed a significant effect modification of diet/lifestyle-related interventions on the TCF7L2 variant rs7903146 and changes in fasting glucose.Compared with the control group,diet/lifestyle interventions were related to lower fasting glucose by-3.06(95%CI,-5.77 to-0.36)mg/dL(test for heterogeneity and overall effect:I^(2)=45:1%,p<0:05;z=2:20,p=0:028)per one copy of the TCF7L2 T risk allele.Furthermore,regardless of genetic risk,diet/lifestyle interventions were associated with lower waist circumference.However,there was no significant change for diet/lifestyle interventions in other glycemic control and adiposity traits per one copy of TCF7L2 risk allele.Conclusions.Our findings suggest that carrying the TCF7L2 T risk allele may have a modestly greater benefit for specific diet/lifestyle interventions to improve the control of fasting glucose in overweight or obese adults.
