Benign biliary strictures(BBS)might occur due to different pancreaticobiliary conditions.The etiology and location of biliary strictures are responsible of a wide array of clinical manifestations.The endoscopic approa...Benign biliary strictures(BBS)might occur due to different pancreaticobiliary conditions.The etiology and location of biliary strictures are responsible of a wide array of clinical manifestations.The endoscopic approach endoscopic retrograde cholangiopancreatography represents the first-line treatment for BBS,considering interventional radiology and surgery when endoscopic treatment fails or it is not suitable.The purpose of this review is to provide an overview of possible endoscopic treatments for the optimal management of this subset of patients.展开更多
This narrative review provides an overview of the utilization of endoscopic ultrasound-guided gallbladder drainage(EUS-GBD)as a salvage approach in cases of unsuccessful conventional management.EUS-GBD is a minimally ...This narrative review provides an overview of the utilization of endoscopic ultrasound-guided gallbladder drainage(EUS-GBD)as a salvage approach in cases of unsuccessful conventional management.EUS-GBD is a minimally invasive and effective technique for drainage in patients with acute cholecystitis with high risk of surgery.The procedure has demonstrated impressive technical and clinical success rates with low rates of adverse events,making it a safe and effective option for appropriate candidates.Furthermore,EUS-GBD can also serve as a rescue option for patients who have failed endoscopic retrograde cholangiopancreatography or EUS biliary drainage for relief of jaundice in malignant biliary stricture.However,patient selection is critical for the success of EUS-GBD,and proper patient selection and risk assessment are important to ensure the safety and efficacy of the procedure.As the field continues to evolve and mature,ongoing research will further refine our understanding of the benefits and limitations of EUS-GBD,ultimately leading to improved outcomes for patients.展开更多
The gallbladder(GB)is a susceptible organ,prone to various pathologies that can be identified using different imaging techniques.Transabdominal ultrasound(TUS)is typically the initial diagnostic method due to its nume...The gallbladder(GB)is a susceptible organ,prone to various pathologies that can be identified using different imaging techniques.Transabdominal ultrasound(TUS)is typically the initial diagnostic method due to its numerous well-established advantages.However,in cases of uncertainty or when a definitive diagnosis cannot be established,computed tomography(CT)or magnetic resonance imaging may be employed to provide more detailed information.Nevertheless,CT scans may sometimes offer inadequate spatial resolution,which can limit the differentiation of GB lesions,particularly when smaller yet clinically relevant abnormalities are involved.Conversely,endoscopic ultrasound(EUS)provides higher frequency compared to TUS,superior spatial resolution,and the option for contrast-enhanced harmonic imaging,enabling a more comprehensive examination.Thus,EUS can serve as a supplementary tool when conventional imaging methods are insufficient.This review will describe the standard EUS examination of the GB,focusing on its endosonographic characteristics in various GB path-ologies.展开更多
A diagnosis of new-onset diabetes after transplantation(NODAT) carries with it a threat to the renal allograft,as well as the same short-and long-term implications of type 2 diabetes seen in the general population.NOD...A diagnosis of new-onset diabetes after transplantation(NODAT) carries with it a threat to the renal allograft,as well as the same short-and long-term implications of type 2 diabetes seen in the general population.NODAT usually occurs early after transplantation,and is usually diagnosed according to general population guidelines.Non-modifiable risk factors for NODAT include advancing age,African American,Hispanic,or South Asian ethnicity,genetic background,a positive family history for diabetes mellitus,polycystic kidney disease,and previously diagnosed glucose intolerance.Modifiable risk factors for NODAT include obesity and the metabolic syndrome,hepatitis C virus and cytomegalovirus infection,corticosteroids,calcineurin inhibitor drugs(especially tacrolimus),and sirolimus.NODAT affects graft and patient survival,and increases the incidence of post-transplant cardiovascular disease.The incidence and impact of NODAT can be minimized through pre-and post-transplant screening to identify patients at higher risk,including by oral glucose tolerance tests,as well as multi-disciplinary care,lifestyle modification,and the use of modified immunosuppressive regimens coupled with glucose-lowering therapies including oral hypoglycemic agents and insulin.Since NODAT is a major cause of post-transplant morbidity and mortality,measures to reduce its incidence and impact have the potential to greatly improve overall transplant success.展开更多
Multicellular layers(MCLs) have previously been used to determine the pharmacokinetics of a variety of different cancer drugs including paclitaxel, doxorubicin, methotrexate, and 5-fluorouracil across a number of cell...Multicellular layers(MCLs) have previously been used to determine the pharmacokinetics of a variety of different cancer drugs including paclitaxel, doxorubicin, methotrexate, and 5-fluorouracil across a number of cell lines. It is not known how nanoparticles(NPs) navigate through the tumor microenvironment once they leave the tumor blood vessel.In this study, we used the MCL model to study the uptake and penetration dynamics of NPs. Gold nanoparticles(GNPs)were used as a model system to map the NP distribution within tissue-like structures. Our results show that NP uptake and transport are dependent on the tumor cell type. MDA-MB-231 tissue showed deeper penetration of GNPs as compared to MCF-7 one. Intracellular and extracellular distributions of NPs were mapped using Cyto Viva imaging. The ability of MCLs to mimic tumor tissue characteristics makes them a useful tool in assessing the efficacy of particle distribution in solid tumors.展开更多
Purpose: To evaluate age related ovarian response to controlled ovarian hyperstimulation, clinical pregnancy and ongoing pregnancy rates beyond 20 weeks in women undergoing assisted reproduction treatment (ART) with a...Purpose: To evaluate age related ovarian response to controlled ovarian hyperstimulation, clinical pregnancy and ongoing pregnancy rates beyond 20 weeks in women undergoing assisted reproduction treatment (ART) with antimullerian hormone (AMH) levels of <5 pmol/l. Methods: Retrospective analysis of data from 63 women with AMH of In-vitro?fertilization, IVF and intracytoplasmic sperm injection, ICSI) cycle. Results were analyzed after dividing patients in two groups, group 1 included women of ≤38 years and group 2 > 38 years of age. Non parametric variables were expressed as median (Interquartile range) and compared by Kruskal-Wallis test. Categorical variables were expressed as numbers with proportions (%) and compared by Fisher’s exact test. Results: There was no statistical difference in body max index, level of antimullerian hormone (AMH), follicle stimulating hormone (FSH), dose of gonadotrophins used and cycles cancellation rate in two groups. Although number of oocytes retrieved (median 5), clinical pregnancy (18.4%) and ongoing pregnancy rate beyond 20 weeks (18.4%) was higher in group 1, there was no statistical difference between the two groups. There was one miscarriage in group 2. Conclusion: Women with extremely low-serum AMH levels can still have clinical pregnancy and ongoing pregnancies beyond 20 weeks after ART, though chances will be lower than women with normal ovarian reserve.展开更多
Post-transplant dyslipidemia is highly prevalent and presents unique management challenges to the clinician. The two major outcomes to considerwith post-transplant therapies for dyslipidemia are preserving or improvin...Post-transplant dyslipidemia is highly prevalent and presents unique management challenges to the clinician. The two major outcomes to considerwith post-transplant therapies for dyslipidemia are preserving or improving allograft function, and reducing cardiovascular risk. Although there are other cardiovascular risk factors such as graft dysfunction, hypertension, and diabetes, attention to dyslipidemia is warranted because interventions for dyslipidemia have an impact on reducing cardiac events in clinical trials specific to the transplant population. Dyslipidemia is not synonymous with hyperlipidemia. Numerous mechanisms exist for the occurrence of posttransplant dyslipidemia, including those mediated by immunosuppressive drug therapy. Statin therapy has received the most attention in all solid organ transplant recipient populations, although the effect of proper dietary advice and adjuvant pharmacological and nonpharmacological agents should not be dismissed. At all stages of treatment appropriate monitoring strategies for side effects should be implemented so that the benefits from these therapies can be achieved. Clinicians have a choice when there is a conflict between various transplant society and lipid society guidelines for therapy and targets.展开更多
Objective: Analysis of clinical documents such as bone mineral density (BMD) reports is an important component of program evaluation because it can provide insights into the accuracy of assessment of fracture risk com...Objective: Analysis of clinical documents such as bone mineral density (BMD) reports is an important component of program evaluation because it can provide insights into the accuracy of assessment of fracture risk communicated to patients and practitioners. Our objective was to compare fracture risk calculations from BMD test reports to those based on the 2010 Canadian guidelines. Methods: We retrieved BMD reports from fragility fracture patients screened through a community hospital fracture clinic participating in Ontario’s Fracture Clinic Screening Program. Fracture risk was determined according to the 2010 Canadian guidelines using age, sex, and T-score at the femoral neck, in addition to three clinical factors. Three researchers classified patients’ fracture risk until consensus was achieved. Results: We retrieved reports for 17 patients from nine different BMD clinics in the Greater Toronto Area. Each patient had a different primary care physician and all BMD tests were conducted after the 2010 Canadian guidelines were published. The fracture risk of 10 patients was misclassified with 9 of the 10 reports underestimating fracture risk. Nine reports acknowledged that the prevalence of a fragility fracture raised the risk category by one level but only four of these reports acknowledged that the patient had, or may have sustained, a fragility fracture. When we raised fracture risk by one level according to these reports, eight patients were still misclassified. Fracture risk in the majority of these patients remained underestimated. Inconsistent classification was found in the majority of cases where reports came from the same clinic. Four reports described risk levels for two different types of risk. Conclusions: More than half of patients received BMD reports which underestimated fracture risk. Bone health management recommendations based on falsely low fracture risk are likely to be sub-optimal.展开更多
In gastrointestinal endoscopy, simulation-based training can help endoscopists acquire new skills and accelerate the learning curve. Simulation creates an ideal environment for trainees, where they can practice specif...In gastrointestinal endoscopy, simulation-based training can help endoscopists acquire new skills and accelerate the learning curve. Simulation creates an ideal environment for trainees, where they can practice specific skills, perform cases at their own pace, and make mistakes with no risk to patients. Educators also benefit from the use of simulators, as they can structure training according to learner needs and focus solely on the trainee. Not all simulation-based training,however, is effective. To maximize benefits from this instructional modality,educators must be conscious of learners' needs, the potential benefits of training,and associated costs. Simulation should be integrated into training in a manner that is grounded in educational theory and empirical data. In this review, we focus on four best practices in simulation-based education: deliberate practice with mastery learning, feedback and debriefing, contextual learning, and innovative educational strategies. For each topic, we provide definitions,supporting evidence, and practical tips for implementation.展开更多
The recent explosion of high-throughput technology has been accompanied by a corresponding rapid increase in the number of new statistical methods for developing prognostic and predictive signatures. Three commonly us...The recent explosion of high-throughput technology has been accompanied by a corresponding rapid increase in the number of new statistical methods for developing prognostic and predictive signatures. Three commonly used feature selection techniques for time-to-event data: single gene testing (SGT), Elastic net and the Maximizing R Square Algorithm (MARSA) are evaluated on simulated datasets that vary in the sample size, the number of features and the correlation between features. The results of each method are summarized by reporting the sensitivity and the Area Under the Receiver Operating Characteristic Curve (AUC). The performance of each of these algorithms depends heavily on the sample size while the number of features entered in the analysis has a much more modest impact. The coefficients estimated utilizing SGT are biased towards the null when the genes are uncorrelated and away from the null when the genes are correlated. The Elastic Net algorithms perform better than MARSA and almost as well as the SGT when the features are correlated and about the same as MARSA when the features are uncorrelated.展开更多
Purpose: The ubiquitous use of synthetic materials in hernia surgery has brought about a new clinical syndrome: Surreptitious Irreversible Neuralgia (SIN). It is surreptitious because it is of slow onset, unsuspected ...Purpose: The ubiquitous use of synthetic materials in hernia surgery has brought about a new clinical syndrome: Surreptitious Irreversible Neuralgia (SIN). It is surreptitious because it is of slow onset, unsuspected and enigmatic to clinicians;irreversible because the pain is progressive, unrelenting and unresponsive to treatment. Removal of the mesh does not guarantee pain relief. Neuralgia following mesh insertion, when it occurs, remains a poorly understood phenomenon. Methods: Ten specimens in each group: virgin tissue, scar tissue and explanted mesh from the posterior inguinal wall were examined histologically to assess nerve density, nerve size and nerve and vessel ingrowth into the deformed mesh and within its pores. Results: There was no significant difference in nerve density between virgin, scar and mesh samples. All of the explanted meshes had nerves within the scar tissue encasing the mesh (interstitial infiltration). Nerve ingrowth through the pores of the mesh (micro-entrapment) was detected in 90% of the explanted mesh specimens. Additionally, nerves were detected entrapped within the folds and deformations of mesh explants. Ingrown vessels showed congestion and focal fibrin thrombi. Conclusion: The presence of mesh does not significantly affect nerve density, while the nerves and their terminal ends are in a vulnerable position about the mesh and within its pores. These pores need to be viewed as “mini-compartments” of biological tissue where the vasculature, nerves and their receptors are exposed to potential mechanical and chemical factors: scarring, entrapment, compression, tugging, deformation, contraction, hypoxia/acidosis, inflammation and edema.展开更多
Background:Retinopathy of prematurity(ROP)is a disorder of retinal development in the low birthweight preterm infant.Eye screening is routinely performed for infants at risk of developing this disorder.While these exa...Background:Retinopathy of prematurity(ROP)is a disorder of retinal development in the low birthweight preterm infant.Eye screening is routinely performed for infants at risk of developing this disorder.While these examinations help prevent blindness,they can be physiologically stressful for infants,with changes in oxygen saturation,blood pressure and heart rate occurring during the exam and increased apneic episodes reported the 24-48 hours period afterward.The cause of these increased apneic episodes is not currently known.Our Background is to evaluate the effect of decreasing light simulation during mydriasis using an eye mask on the frequency of stressful episodes after ROP screening.Methods:Multi-centre randomized clinical study.This study was approved by hospital ethics boards at all sites.After informed consent was obtained,infants with a birthweight<1,500 g or gestational age of≤32 weeks and scheduled for their first ROP screening were randomized to receive either standard of care or a phototherapy mask during pupil dilation in addition to routine care.Dilated retinal exams were performed by retinal surgeons and fellows.The primary outcome was the frequency of any desaturation,bradycardic event,or apneic event 12 hours following the examination,compared to a baseline rate 12 hours prior to the exam.Heart rate,respiratory rate and oxygen saturation were recorded for up to 48 hours following the examination and compared to baseline.Results:A total of 51 infants were examined;28 randomized to the masked group and 23 to the control group.Ten and 13 infants were on ventilator support at the time of examination in each group,respectively.There was a 57.7%decrease in the total number of all stressful events in the masked group compared to controls in the 12-hour post exam period(rate ratio 0.42,95%CI,0.2-0.9,P=0.024).There was a 61.3%decrease in the number of bradycardic events in the masked group compared to controls(RR 0.39,95%CI,0.2-1.0,P=0.042).Heart rate was significantly higher in both groups after the exam(Mean HR:164.67 bpm post vs.157.3 bpm pre;P=0.04),with no difference in between groups(Effect by group P=0.31).There was no significant difference seen in either group in respiratory rate or oxygen saturation at 2 or 4 hours after the ROP examination compared to baseline.Risk factors that were associated with increased stress included younger gestational age(RR=1.3295%CI,1.2-1.5 per week),lower birthweight[RR=1.39(1.2-1.5)per 100 g],ventilator support around the time of exam[RR=2.67(1.3-5.6)],diagnosis of intraventricular hemorrhage[RR=3.78(1.9-7.3)],and hyponatremia[RR=3.42(1.8-6.6)].No adverse events occurred while using eye masks.Conclusions:The infants who wore a phototherapy mask during pupillary dilation had lower rates of stressful episodes following screening for retinopathy of prematurity,particularly lower episodes of bradycardia.展开更多
Background: Early cardiac catheterization has been shown to improve outcomes in patients with non- ST- elevation acute coronary syndromes but not yet in those with ST- elevation myocardial infarction(STEMI). The benef...Background: Early cardiac catheterization has been shown to improve outcomes in patients with non- ST- elevation acute coronary syndromes but not yet in those with ST- elevation myocardial infarction(STEMI). The benefit of catheterization in both syndromes may depend on patient risk for adverse clinical outcomes. Methods: We analyzed the relation between inhospital catheterization and subsequent clinical outcomes based on risk profile in 8286 patients in the OPUS- TIMI 16 Trial of patients with acute coronary syndromes. Using baseline clinical characteristics, patients were stratified into low- , intermediate- , and high- risk groups. The primary end point was 10- month mortality. The STEMI, non- STEMI(NSTEMI), and unstable angina subgroups were analyzed separately. Results: Inhospital cardiac catheterization was performed in 44% of patients. Mortality rates at 10 months were 1.3% , 2.2% , and 11.3% in the low- , intermediate- , and high- risk groups, respectively. Inhospital cardiac catheterization was associated with a trend to lower mortality among the high- risk patients with STEMI(hazard ratios[HR] 0.57, 95% CI 0.33- 1.01, P=.052) and NSTEMI(HR 0.65, 95% CI 0.39- 1.07, P=.088) but not in those with unstable angina(HR 0.95, 95% CI 0.63- 1.43, P=.82). Catheterization was not associated with any significant difference in mortality in the low- risk or intermediate- risk group. The differences among high- risk patients persisted after adjusting for baseline characteristics; inhospital catheterization was associated with significantly lower mortality in high- risk patients with ST and non- ST myocardial infarction(HR 0.65, 95% CI 0.45- 0.95, P=.03). Conclusions: Inhospital cardiac catheterization is associated with lower mortality in high- risk patients and no difference in mortality in low- risk and intermediate- risk patients after STEMI and NSTEMI. These data support the hypothesis that high- risk patients with either STEMI or NSTEMI may benefit from an early invasive strategy. New prospective randomized trials are warranted, particularly in the STEMI population.展开更多
The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden.Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia(VITT)are both associated with thr...The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden.Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia(VITT)are both associated with thrombosis and thrombocytopenia;however,the underlying mechanisms remain inadequately understood.Both infection and vaccination utilize the spike protein receptor-binding domain(RBD)of SARS-CoV-2.We found that intravenous injection of recombinant RBD caused significant platelet clearance in mice.Further investigation revealed the RBD could bind platelets,cause platelet activation,and potentiate platelet aggregation,which was exacerbated in the Delta and Kappa variants.The RBD–platelet interaction was partially dependent on theβ3 integrin as binding was significantly reduced inβ3−/−mice.Furthermore,RBD binding to human and mouse platelets was significantly reduced with relatedαIIbβ3 antagonists and mutation of the RGD(arginine-glycine-aspartate)integrin binding motif to RGE(arginine-glycine-glutamate).We developed anti-RBD polyclonal and several monoclonal antibodies(mAbs)and identified 4F2 and 4H12 for their potent dual inhibition of RBD-induced platelet activation,aggregation,and clearance in vivo,and SARS-CoV-2 infection and replication in Vero E6 cells.Our data show that the RBD can bind platelets partially thoughαIIbβ3 and induce platelet activation and clearance,which may contribute to thrombosis and thrombocytopenia observed in COVID-19 and VITT.Our newly developed mAbs 4F2 and 4H12 have potential not only for diagnosis of SARS-CoV-2 virus antigen but also importantly for therapy against COVID-19.展开更多
Esophageal cancer is one of the leading causes of cancer-related death and is associated with high morbidity and mortality.It carries a poor prognosis as more than half of patients present with advanced and unresectab...Esophageal cancer is one of the leading causes of cancer-related death and is associated with high morbidity and mortality.It carries a poor prognosis as more than half of patients present with advanced and unresectable disease.One contributing factor is the increased risk of lymph node metastases at early stages of disease.As such,it is essential to detect squamous cell neoplasia (SCN) at an early stage.In order to risk stratify lesions,endoscopists must be able to perform image enhanced endoscopy including magnification and Lugol's chromoendoscopy.The assessment of both the horizontal extent and depth of any lesion is also of utmost importance prior to treatment.Endoscopic mucosal resection and submucosal dissection remain the standard of care with literature supportive their respective use.Radiofrequency ablation and other endoscopic treatments are currently available although should not be considered first line at this time.Our objective is to review the current options for the endoscopic diagnosis and treatment of esophageal SCN.展开更多
Colorectal cancer is one of the three most frequent causes of cancer deaths in men and women in Europe and North America. Diagnosis and resection of adenomas has convincingly demonstrated its utility in diminishing co...Colorectal cancer is one of the three most frequent causes of cancer deaths in men and women in Europe and North America. Diagnosis and resection of adenomas has convincingly demonstrated its utility in diminishing colorectal cancer incidence. Therefore, colonoscopy is now the gold standard for colorectal cancer screening. But it is also known that colonoscopy effectiveness varies among endoscopists. Among different quality indicators, the most used is the adenoma detection rate(ADR) which is the percentage of average-risk patients for colorectal cancer who are found to have at least one adenoma or adenocarcinoma during a screening colonoscopy. There is compelling evidence supporting an inverse correlation between ADR and interval colorectal cancer(cancer found after a screening colonoscopy). Many factors such as quality of precolonoscopy preparation, additional observers, manoeuvres with the endoscope(second view, retroflexion, water inflation rather than air), time spent during withdrawal, changes in patient position, foldflattener devices, new imaging or endoscopic modalities and use of intravenous or through the scope sprayed drugs, have been studied and developed with the aim of increasing the ADR. This reviews discusses these factors, and the current evidence, to "see better" in the colon and optimize ADR.展开更多
For over 35 years shock wave lithotripsy has proven to be an effective,safe and truly minimally invasive option for the treatment of nephrolithiasis.Various technical factors as well as patient selection can impact th...For over 35 years shock wave lithotripsy has proven to be an effective,safe and truly minimally invasive option for the treatment of nephrolithiasis.Various technical factors as well as patient selection can impact the success of the procedure.We used published work focusing on outcomes of shock wave lithotripsy,risk of complications,and strategies for improving stone fragmentation to create this review.Multiple patient and technical factors have been found to impact success of treatment.Skin to stone distance,stone density and composition,size and location of the stone within the urinary system all influence stone free rates.A slower rate with a gradual increasing voltage,precise targeting,proper coupling will improve stone fragmentation and decrease risk of complications.The selection of appropriate patients through a shared decision making process and attention to the technical factors that improve stone free rates is key to providing an effective treatment and patient satisfaction.展开更多
Gold nanoparticles(GNPs) are emerging as a novel tool to improve existing cancer therapeutics. GNPs are being used as radiation dose enhancers in radiation therapy as well as anticancer drugs carriers in chemotherapy....Gold nanoparticles(GNPs) are emerging as a novel tool to improve existing cancer therapeutics. GNPs are being used as radiation dose enhancers in radiation therapy as well as anticancer drugs carriers in chemotherapy. However,the success of GNP-based therapeutics depends on their ability to penetrate tumor tissue. GNPs of 20 and 50 nm diameters were used to elucidate the effects of size on the GNP interaction with tumor cells at monolayer and multilayer level. At monolayer cell level, smaller NPs had a lower uptake compared to larger NPs at monolayer cell level. However, the order was reversed at tissue-like multilayer level. The smaller NPs penetrated better compared to larger NPs in tissue-like materials.Based on our study using tissue-like materials, we can predict that the smaller NPs are better for future therapeutics due to their greater penetration in tumor tissue once leaving the leaky blood vessels. In this study, tissue-like multilayer cellular structures(MLCs) were grown to model the post-vascular tumor environment. The MLCs exhibited a much more extensive extracellular matrix than monolayer cell cultures. The MLC model can be used to optimize the nano–micro interface at tissue level before moving into animal models. This would accelerate the use of NPs in future cancer therapeutics.展开更多
Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgica...Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and posttransplant patient care and rehabilitation researchers.展开更多
Pre-kidney transplant cardiac screening has garnered particular attention from guideline committees as an approach to improving post-transplant success. Screening serves two major purposes: To more accurately inform t...Pre-kidney transplant cardiac screening has garnered particular attention from guideline committees as an approach to improving post-transplant success. Screening serves two major purposes: To more accurately inform transplant candidates of their risk for a cardiac event before and after the transplant, thereby informing decisions about proceeding with transplantation, and to guide pre-transplant management so that posttransplant success can be maximized. Transplant candidates on dialysis are more likely to be screened for coronary artery disease than those not being considered for transplantation. Thorough history and physical examination taking, resting electrocardiography and echocardiography, exercise stress testing, myocardial perfusion scintigraphy, dobutamine stress echocardiography, cardiac computed tomography, cardiac biomarker measurement, and cardiac magnetic resonance imaging all play contributory roles towards screening for cardiovascular disease before kidney transplantation. In this review, the importance of each of these screening procedures for both coronary artery disease and other forms of cardiac disease are discussed.展开更多
文摘Benign biliary strictures(BBS)might occur due to different pancreaticobiliary conditions.The etiology and location of biliary strictures are responsible of a wide array of clinical manifestations.The endoscopic approach endoscopic retrograde cholangiopancreatography represents the first-line treatment for BBS,considering interventional radiology and surgery when endoscopic treatment fails or it is not suitable.The purpose of this review is to provide an overview of possible endoscopic treatments for the optimal management of this subset of patients.
文摘This narrative review provides an overview of the utilization of endoscopic ultrasound-guided gallbladder drainage(EUS-GBD)as a salvage approach in cases of unsuccessful conventional management.EUS-GBD is a minimally invasive and effective technique for drainage in patients with acute cholecystitis with high risk of surgery.The procedure has demonstrated impressive technical and clinical success rates with low rates of adverse events,making it a safe and effective option for appropriate candidates.Furthermore,EUS-GBD can also serve as a rescue option for patients who have failed endoscopic retrograde cholangiopancreatography or EUS biliary drainage for relief of jaundice in malignant biliary stricture.However,patient selection is critical for the success of EUS-GBD,and proper patient selection and risk assessment are important to ensure the safety and efficacy of the procedure.As the field continues to evolve and mature,ongoing research will further refine our understanding of the benefits and limitations of EUS-GBD,ultimately leading to improved outcomes for patients.
文摘The gallbladder(GB)is a susceptible organ,prone to various pathologies that can be identified using different imaging techniques.Transabdominal ultrasound(TUS)is typically the initial diagnostic method due to its numerous well-established advantages.However,in cases of uncertainty or when a definitive diagnosis cannot be established,computed tomography(CT)or magnetic resonance imaging may be employed to provide more detailed information.Nevertheless,CT scans may sometimes offer inadequate spatial resolution,which can limit the differentiation of GB lesions,particularly when smaller yet clinically relevant abnormalities are involved.Conversely,endoscopic ultrasound(EUS)provides higher frequency compared to TUS,superior spatial resolution,and the option for contrast-enhanced harmonic imaging,enabling a more comprehensive examination.Thus,EUS can serve as a supplementary tool when conventional imaging methods are insufficient.This review will describe the standard EUS examination of the GB,focusing on its endosonographic characteristics in various GB path-ologies.
文摘A diagnosis of new-onset diabetes after transplantation(NODAT) carries with it a threat to the renal allograft,as well as the same short-and long-term implications of type 2 diabetes seen in the general population.NODAT usually occurs early after transplantation,and is usually diagnosed according to general population guidelines.Non-modifiable risk factors for NODAT include advancing age,African American,Hispanic,or South Asian ethnicity,genetic background,a positive family history for diabetes mellitus,polycystic kidney disease,and previously diagnosed glucose intolerance.Modifiable risk factors for NODAT include obesity and the metabolic syndrome,hepatitis C virus and cytomegalovirus infection,corticosteroids,calcineurin inhibitor drugs(especially tacrolimus),and sirolimus.NODAT affects graft and patient survival,and increases the incidence of post-transplant cardiovascular disease.The incidence and impact of NODAT can be minimized through pre-and post-transplant screening to identify patients at higher risk,including by oral glucose tolerance tests,as well as multi-disciplinary care,lifestyle modification,and the use of modified immunosuppressive regimens coupled with glucose-lowering therapies including oral hypoglycemic agents and insulin.Since NODAT is a major cause of post-transplant morbidity and mortality,measures to reduce its incidence and impact have the potential to greatly improve overall transplant success.
文摘Multicellular layers(MCLs) have previously been used to determine the pharmacokinetics of a variety of different cancer drugs including paclitaxel, doxorubicin, methotrexate, and 5-fluorouracil across a number of cell lines. It is not known how nanoparticles(NPs) navigate through the tumor microenvironment once they leave the tumor blood vessel.In this study, we used the MCL model to study the uptake and penetration dynamics of NPs. Gold nanoparticles(GNPs)were used as a model system to map the NP distribution within tissue-like structures. Our results show that NP uptake and transport are dependent on the tumor cell type. MDA-MB-231 tissue showed deeper penetration of GNPs as compared to MCF-7 one. Intracellular and extracellular distributions of NPs were mapped using Cyto Viva imaging. The ability of MCLs to mimic tumor tissue characteristics makes them a useful tool in assessing the efficacy of particle distribution in solid tumors.
文摘Purpose: To evaluate age related ovarian response to controlled ovarian hyperstimulation, clinical pregnancy and ongoing pregnancy rates beyond 20 weeks in women undergoing assisted reproduction treatment (ART) with antimullerian hormone (AMH) levels of <5 pmol/l. Methods: Retrospective analysis of data from 63 women with AMH of In-vitro?fertilization, IVF and intracytoplasmic sperm injection, ICSI) cycle. Results were analyzed after dividing patients in two groups, group 1 included women of ≤38 years and group 2 > 38 years of age. Non parametric variables were expressed as median (Interquartile range) and compared by Kruskal-Wallis test. Categorical variables were expressed as numbers with proportions (%) and compared by Fisher’s exact test. Results: There was no statistical difference in body max index, level of antimullerian hormone (AMH), follicle stimulating hormone (FSH), dose of gonadotrophins used and cycles cancellation rate in two groups. Although number of oocytes retrieved (median 5), clinical pregnancy (18.4%) and ongoing pregnancy rate beyond 20 weeks (18.4%) was higher in group 1, there was no statistical difference between the two groups. There was one miscarriage in group 2. Conclusion: Women with extremely low-serum AMH levels can still have clinical pregnancy and ongoing pregnancies beyond 20 weeks after ART, though chances will be lower than women with normal ovarian reserve.
文摘Post-transplant dyslipidemia is highly prevalent and presents unique management challenges to the clinician. The two major outcomes to considerwith post-transplant therapies for dyslipidemia are preserving or improving allograft function, and reducing cardiovascular risk. Although there are other cardiovascular risk factors such as graft dysfunction, hypertension, and diabetes, attention to dyslipidemia is warranted because interventions for dyslipidemia have an impact on reducing cardiac events in clinical trials specific to the transplant population. Dyslipidemia is not synonymous with hyperlipidemia. Numerous mechanisms exist for the occurrence of posttransplant dyslipidemia, including those mediated by immunosuppressive drug therapy. Statin therapy has received the most attention in all solid organ transplant recipient populations, although the effect of proper dietary advice and adjuvant pharmacological and nonpharmacological agents should not be dismissed. At all stages of treatment appropriate monitoring strategies for side effects should be implemented so that the benefits from these therapies can be achieved. Clinicians have a choice when there is a conflict between various transplant society and lipid society guidelines for therapy and targets.
文摘Objective: Analysis of clinical documents such as bone mineral density (BMD) reports is an important component of program evaluation because it can provide insights into the accuracy of assessment of fracture risk communicated to patients and practitioners. Our objective was to compare fracture risk calculations from BMD test reports to those based on the 2010 Canadian guidelines. Methods: We retrieved BMD reports from fragility fracture patients screened through a community hospital fracture clinic participating in Ontario’s Fracture Clinic Screening Program. Fracture risk was determined according to the 2010 Canadian guidelines using age, sex, and T-score at the femoral neck, in addition to three clinical factors. Three researchers classified patients’ fracture risk until consensus was achieved. Results: We retrieved reports for 17 patients from nine different BMD clinics in the Greater Toronto Area. Each patient had a different primary care physician and all BMD tests were conducted after the 2010 Canadian guidelines were published. The fracture risk of 10 patients was misclassified with 9 of the 10 reports underestimating fracture risk. Nine reports acknowledged that the prevalence of a fragility fracture raised the risk category by one level but only four of these reports acknowledged that the patient had, or may have sustained, a fragility fracture. When we raised fracture risk by one level according to these reports, eight patients were still misclassified. Fracture risk in the majority of these patients remained underestimated. Inconsistent classification was found in the majority of cases where reports came from the same clinic. Four reports described risk levels for two different types of risk. Conclusions: More than half of patients received BMD reports which underestimated fracture risk. Bone health management recommendations based on falsely low fracture risk are likely to be sub-optimal.
文摘In gastrointestinal endoscopy, simulation-based training can help endoscopists acquire new skills and accelerate the learning curve. Simulation creates an ideal environment for trainees, where they can practice specific skills, perform cases at their own pace, and make mistakes with no risk to patients. Educators also benefit from the use of simulators, as they can structure training according to learner needs and focus solely on the trainee. Not all simulation-based training,however, is effective. To maximize benefits from this instructional modality,educators must be conscious of learners' needs, the potential benefits of training,and associated costs. Simulation should be integrated into training in a manner that is grounded in educational theory and empirical data. In this review, we focus on four best practices in simulation-based education: deliberate practice with mastery learning, feedback and debriefing, contextual learning, and innovative educational strategies. For each topic, we provide definitions,supporting evidence, and practical tips for implementation.
文摘The recent explosion of high-throughput technology has been accompanied by a corresponding rapid increase in the number of new statistical methods for developing prognostic and predictive signatures. Three commonly used feature selection techniques for time-to-event data: single gene testing (SGT), Elastic net and the Maximizing R Square Algorithm (MARSA) are evaluated on simulated datasets that vary in the sample size, the number of features and the correlation between features. The results of each method are summarized by reporting the sensitivity and the Area Under the Receiver Operating Characteristic Curve (AUC). The performance of each of these algorithms depends heavily on the sample size while the number of features entered in the analysis has a much more modest impact. The coefficients estimated utilizing SGT are biased towards the null when the genes are uncorrelated and away from the null when the genes are correlated. The Elastic Net algorithms perform better than MARSA and almost as well as the SGT when the features are correlated and about the same as MARSA when the features are uncorrelated.
文摘Purpose: The ubiquitous use of synthetic materials in hernia surgery has brought about a new clinical syndrome: Surreptitious Irreversible Neuralgia (SIN). It is surreptitious because it is of slow onset, unsuspected and enigmatic to clinicians;irreversible because the pain is progressive, unrelenting and unresponsive to treatment. Removal of the mesh does not guarantee pain relief. Neuralgia following mesh insertion, when it occurs, remains a poorly understood phenomenon. Methods: Ten specimens in each group: virgin tissue, scar tissue and explanted mesh from the posterior inguinal wall were examined histologically to assess nerve density, nerve size and nerve and vessel ingrowth into the deformed mesh and within its pores. Results: There was no significant difference in nerve density between virgin, scar and mesh samples. All of the explanted meshes had nerves within the scar tissue encasing the mesh (interstitial infiltration). Nerve ingrowth through the pores of the mesh (micro-entrapment) was detected in 90% of the explanted mesh specimens. Additionally, nerves were detected entrapped within the folds and deformations of mesh explants. Ingrown vessels showed congestion and focal fibrin thrombi. Conclusion: The presence of mesh does not significantly affect nerve density, while the nerves and their terminal ends are in a vulnerable position about the mesh and within its pores. These pores need to be viewed as “mini-compartments” of biological tissue where the vasculature, nerves and their receptors are exposed to potential mechanical and chemical factors: scarring, entrapment, compression, tugging, deformation, contraction, hypoxia/acidosis, inflammation and edema.
文摘Background:Retinopathy of prematurity(ROP)is a disorder of retinal development in the low birthweight preterm infant.Eye screening is routinely performed for infants at risk of developing this disorder.While these examinations help prevent blindness,they can be physiologically stressful for infants,with changes in oxygen saturation,blood pressure and heart rate occurring during the exam and increased apneic episodes reported the 24-48 hours period afterward.The cause of these increased apneic episodes is not currently known.Our Background is to evaluate the effect of decreasing light simulation during mydriasis using an eye mask on the frequency of stressful episodes after ROP screening.Methods:Multi-centre randomized clinical study.This study was approved by hospital ethics boards at all sites.After informed consent was obtained,infants with a birthweight<1,500 g or gestational age of≤32 weeks and scheduled for their first ROP screening were randomized to receive either standard of care or a phototherapy mask during pupil dilation in addition to routine care.Dilated retinal exams were performed by retinal surgeons and fellows.The primary outcome was the frequency of any desaturation,bradycardic event,or apneic event 12 hours following the examination,compared to a baseline rate 12 hours prior to the exam.Heart rate,respiratory rate and oxygen saturation were recorded for up to 48 hours following the examination and compared to baseline.Results:A total of 51 infants were examined;28 randomized to the masked group and 23 to the control group.Ten and 13 infants were on ventilator support at the time of examination in each group,respectively.There was a 57.7%decrease in the total number of all stressful events in the masked group compared to controls in the 12-hour post exam period(rate ratio 0.42,95%CI,0.2-0.9,P=0.024).There was a 61.3%decrease in the number of bradycardic events in the masked group compared to controls(RR 0.39,95%CI,0.2-1.0,P=0.042).Heart rate was significantly higher in both groups after the exam(Mean HR:164.67 bpm post vs.157.3 bpm pre;P=0.04),with no difference in between groups(Effect by group P=0.31).There was no significant difference seen in either group in respiratory rate or oxygen saturation at 2 or 4 hours after the ROP examination compared to baseline.Risk factors that were associated with increased stress included younger gestational age(RR=1.3295%CI,1.2-1.5 per week),lower birthweight[RR=1.39(1.2-1.5)per 100 g],ventilator support around the time of exam[RR=2.67(1.3-5.6)],diagnosis of intraventricular hemorrhage[RR=3.78(1.9-7.3)],and hyponatremia[RR=3.42(1.8-6.6)].No adverse events occurred while using eye masks.Conclusions:The infants who wore a phototherapy mask during pupillary dilation had lower rates of stressful episodes following screening for retinopathy of prematurity,particularly lower episodes of bradycardia.
文摘Background: Early cardiac catheterization has been shown to improve outcomes in patients with non- ST- elevation acute coronary syndromes but not yet in those with ST- elevation myocardial infarction(STEMI). The benefit of catheterization in both syndromes may depend on patient risk for adverse clinical outcomes. Methods: We analyzed the relation between inhospital catheterization and subsequent clinical outcomes based on risk profile in 8286 patients in the OPUS- TIMI 16 Trial of patients with acute coronary syndromes. Using baseline clinical characteristics, patients were stratified into low- , intermediate- , and high- risk groups. The primary end point was 10- month mortality. The STEMI, non- STEMI(NSTEMI), and unstable angina subgroups were analyzed separately. Results: Inhospital cardiac catheterization was performed in 44% of patients. Mortality rates at 10 months were 1.3% , 2.2% , and 11.3% in the low- , intermediate- , and high- risk groups, respectively. Inhospital cardiac catheterization was associated with a trend to lower mortality among the high- risk patients with STEMI(hazard ratios[HR] 0.57, 95% CI 0.33- 1.01, P=.052) and NSTEMI(HR 0.65, 95% CI 0.39- 1.07, P=.088) but not in those with unstable angina(HR 0.95, 95% CI 0.63- 1.43, P=.82). Catheterization was not associated with any significant difference in mortality in the low- risk or intermediate- risk group. The differences among high- risk patients persisted after adjusting for baseline characteristics; inhospital catheterization was associated with significantly lower mortality in high- risk patients with ST and non- ST myocardial infarction(HR 0.65, 95% CI 0.45- 0.95, P=.03). Conclusions: Inhospital cardiac catheterization is associated with lower mortality in high- risk patients and no difference in mortality in low- risk and intermediate- risk patients after STEMI and NSTEMI. These data support the hypothesis that high- risk patients with either STEMI or NSTEMI may benefit from an early invasive strategy. New prospective randomized trials are warranted, particularly in the STEMI population.
基金the Canadian Institutes of Health Research(CIHR)Foundation grant(389035)CCOA Therapeutics Inc.research fund to Dr.H.N.CIHR grant for COVID-19(OV3-170344,SBC-171482,and VS1-175560)to Dr.H.Z.D.T.M.,Z.C.,and DK are recipients of the Queen Elizabeth II(QE-II)Graduate Scholarship,Ontario,Canada.S.S.is a recipient of the Canadian Blood Services postdoctoral award.D.T.M.is a recipient of a Graduate Scholarship,Department of Physiology,University of Toronto.Z.C.is the recipient of the Canadian Blood Services Graduate Scholarship,Ontario,Canada.C.S.is a recipient of a postdoctoral Mitacs award,University of Toronto.Z.L.is a recipient of Mitacs Accelerate Postdoctoral Fellowship.LL is a recipient of a scholarship from the University of Chinese Academy of Sciences.X.W.is a recipient of Killam Research Fellowship from the Canadian Council for the Arts.D.K.is also the recipient of the St.Michael’s Hospital Research Training Centre Scholarship and the 2021-2022 Vanier Canada Graduate Scholarships(Vanier CGS),and V.P.is the recipient of the CGS awarded by the CIHR.
文摘The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden.Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia(VITT)are both associated with thrombosis and thrombocytopenia;however,the underlying mechanisms remain inadequately understood.Both infection and vaccination utilize the spike protein receptor-binding domain(RBD)of SARS-CoV-2.We found that intravenous injection of recombinant RBD caused significant platelet clearance in mice.Further investigation revealed the RBD could bind platelets,cause platelet activation,and potentiate platelet aggregation,which was exacerbated in the Delta and Kappa variants.The RBD–platelet interaction was partially dependent on theβ3 integrin as binding was significantly reduced inβ3−/−mice.Furthermore,RBD binding to human and mouse platelets was significantly reduced with relatedαIIbβ3 antagonists and mutation of the RGD(arginine-glycine-aspartate)integrin binding motif to RGE(arginine-glycine-glutamate).We developed anti-RBD polyclonal and several monoclonal antibodies(mAbs)and identified 4F2 and 4H12 for their potent dual inhibition of RBD-induced platelet activation,aggregation,and clearance in vivo,and SARS-CoV-2 infection and replication in Vero E6 cells.Our data show that the RBD can bind platelets partially thoughαIIbβ3 and induce platelet activation and clearance,which may contribute to thrombosis and thrombocytopenia observed in COVID-19 and VITT.Our newly developed mAbs 4F2 and 4H12 have potential not only for diagnosis of SARS-CoV-2 virus antigen but also importantly for therapy against COVID-19.
文摘Esophageal cancer is one of the leading causes of cancer-related death and is associated with high morbidity and mortality.It carries a poor prognosis as more than half of patients present with advanced and unresectable disease.One contributing factor is the increased risk of lymph node metastases at early stages of disease.As such,it is essential to detect squamous cell neoplasia (SCN) at an early stage.In order to risk stratify lesions,endoscopists must be able to perform image enhanced endoscopy including magnification and Lugol's chromoendoscopy.The assessment of both the horizontal extent and depth of any lesion is also of utmost importance prior to treatment.Endoscopic mucosal resection and submucosal dissection remain the standard of care with literature supportive their respective use.Radiofrequency ablation and other endoscopic treatments are currently available although should not be considered first line at this time.Our objective is to review the current options for the endoscopic diagnosis and treatment of esophageal SCN.
文摘Colorectal cancer is one of the three most frequent causes of cancer deaths in men and women in Europe and North America. Diagnosis and resection of adenomas has convincingly demonstrated its utility in diminishing colorectal cancer incidence. Therefore, colonoscopy is now the gold standard for colorectal cancer screening. But it is also known that colonoscopy effectiveness varies among endoscopists. Among different quality indicators, the most used is the adenoma detection rate(ADR) which is the percentage of average-risk patients for colorectal cancer who are found to have at least one adenoma or adenocarcinoma during a screening colonoscopy. There is compelling evidence supporting an inverse correlation between ADR and interval colorectal cancer(cancer found after a screening colonoscopy). Many factors such as quality of precolonoscopy preparation, additional observers, manoeuvres with the endoscope(second view, retroflexion, water inflation rather than air), time spent during withdrawal, changes in patient position, foldflattener devices, new imaging or endoscopic modalities and use of intravenous or through the scope sprayed drugs, have been studied and developed with the aim of increasing the ADR. This reviews discusses these factors, and the current evidence, to "see better" in the colon and optimize ADR.
文摘For over 35 years shock wave lithotripsy has proven to be an effective,safe and truly minimally invasive option for the treatment of nephrolithiasis.Various technical factors as well as patient selection can impact the success of the procedure.We used published work focusing on outcomes of shock wave lithotripsy,risk of complications,and strategies for improving stone fragmentation to create this review.Multiple patient and technical factors have been found to impact success of treatment.Skin to stone distance,stone density and composition,size and location of the stone within the urinary system all influence stone free rates.A slower rate with a gradual increasing voltage,precise targeting,proper coupling will improve stone fragmentation and decrease risk of complications.The selection of appropriate patients through a shared decision making process and attention to the technical factors that improve stone free rates is key to providing an effective treatment and patient satisfaction.
基金the Natural Sciences and Engineering Research Council of Canada(NSERC)Canadian Foundation for Innovation(CFI)
文摘Gold nanoparticles(GNPs) are emerging as a novel tool to improve existing cancer therapeutics. GNPs are being used as radiation dose enhancers in radiation therapy as well as anticancer drugs carriers in chemotherapy. However,the success of GNP-based therapeutics depends on their ability to penetrate tumor tissue. GNPs of 20 and 50 nm diameters were used to elucidate the effects of size on the GNP interaction with tumor cells at monolayer and multilayer level. At monolayer cell level, smaller NPs had a lower uptake compared to larger NPs at monolayer cell level. However, the order was reversed at tissue-like multilayer level. The smaller NPs penetrated better compared to larger NPs in tissue-like materials.Based on our study using tissue-like materials, we can predict that the smaller NPs are better for future therapeutics due to their greater penetration in tumor tissue once leaving the leaky blood vessels. In this study, tissue-like multilayer cellular structures(MLCs) were grown to model the post-vascular tumor environment. The MLCs exhibited a much more extensive extracellular matrix than monolayer cell cultures. The MLC model can be used to optimize the nano–micro interface at tissue level before moving into animal models. This would accelerate the use of NPs in future cancer therapeutics.
文摘Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and posttransplant patient care and rehabilitation researchers.
文摘Pre-kidney transplant cardiac screening has garnered particular attention from guideline committees as an approach to improving post-transplant success. Screening serves two major purposes: To more accurately inform transplant candidates of their risk for a cardiac event before and after the transplant, thereby informing decisions about proceeding with transplantation, and to guide pre-transplant management so that posttransplant success can be maximized. Transplant candidates on dialysis are more likely to be screened for coronary artery disease than those not being considered for transplantation. Thorough history and physical examination taking, resting electrocardiography and echocardiography, exercise stress testing, myocardial perfusion scintigraphy, dobutamine stress echocardiography, cardiac computed tomography, cardiac biomarker measurement, and cardiac magnetic resonance imaging all play contributory roles towards screening for cardiovascular disease before kidney transplantation. In this review, the importance of each of these screening procedures for both coronary artery disease and other forms of cardiac disease are discussed.