Background:Despite advances in the diagnosis of patients with hepatocellular carcinoma(HCC),70%-80%of patients are diagnosed with advanced stage disease.Portal vein tumor thrombus(PVTT)is among the most ominous signs ...Background:Despite advances in the diagnosis of patients with hepatocellular carcinoma(HCC),70%-80%of patients are diagnosed with advanced stage disease.Portal vein tumor thrombus(PVTT)is among the most ominous signs of advanced stage disease and has been associated with poor survival if untreated.Data sources:A systematic search of MEDLINE(PubMed),Embase,Cochrane Library and Database for Systematic Reviews(CDSR),Google Scholar,and National Institute for Health and Clinical Excellence(NICE)databases until December 2022 was conducted using free text and MeSH terms:hepatocellular carcinoma,portal vein tumor thrombus,portal vein thrombosis,vascular invasion,liver and/or hepatic resection,liver transplantation,and systematic review.Results:Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic chemotherapy.Critical elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus,accurate identification of the subgroups of patients who may benefit from resection,as well as meticulous surgical technique.This review addressed five specific areas:(a)formation of PVTT;(b)classifications of PVTT;(c)controversies related to clinical guidelines;(d)surgical treatments versus non-surgical approaches;and(e)characterization of surgical techniques correlated with classifications of PVTT.Conclusions:Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.展开更多
MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like ot...MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.展开更多
In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving para...In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving paradigm,it is crucial to identify factors that predict higher rates of lymphatic invasion and poorer outcomes.Larger tumor size,deeper invasion,poorer differentiation,more infiltrative growth patterns(INF-c),higher-grade tumor budding,positive lymphovascular invasion,and certain biomarkers have been associated with lymph node metastasis and increased morbidity through retrospective reviews,leading to the construction of comprehensive nomograms for outcome prediction.If validated by future prospective studies,these nomograms would prove highly applicable in guiding the selection of treatment for superficial ESCC.展开更多
1.Introduction For decades,substantial disagreement has persisted as to whether dynamic knee valgus is the cause of the majority of anterior cruciate ligament(ACL)injuries or rather the result of the ACL rupture.1 Con...1.Introduction For decades,substantial disagreement has persisted as to whether dynamic knee valgus is the cause of the majority of anterior cruciate ligament(ACL)injuries or rather the result of the ACL rupture.1 Consequently,great effort and expense has gone into capturing 3-dimensional kinetics and kinematics from live athletes to drive in vitro and in silico models of ACL injury in order to elucidate the actual mechanism of injury,as these factors have been demonstrated to be surrogates of intraarticular structural loading on the ACL.2,3 The elucidation of injury mechanisms for non-contact ACL injuries is of great medical value as such knowledge consequently permits quantified examination and validation of interventions and their respective effectiveness in both prevention and rehabilitation of these traumatic knee injuries.展开更多
Modern neuroscience began from all reaching and fierce conflict between“neuronismo and reticulismo”——between neuronal and reticular theories of the organization of the nervous system;the conflict culminated in Dec...Modern neuroscience began from all reaching and fierce conflict between“neuronismo and reticulismo”——between neuronal and reticular theories of the organization of the nervous system;the conflict culminated in December of 1906 in Stockholm where Santiago Ramon y Cajal(the proponent of the neuronal doctrine)and Camillo Golgi(who advocated the syncytial reticular organization of neural networks)delivered their Noble prize lectures(Verkhratsky,2009).展开更多
Pancreatic ductal adenocarcinoma is an aggressive cancer with high recurrence rates following surgical resection.While adjuvant chemotherapy improves survival,a significant proportion of patients are unable to initiat...Pancreatic ductal adenocarcinoma is an aggressive cancer with high recurrence rates following surgical resection.While adjuvant chemotherapy improves survival,a significant proportion of patients are unable to initiate or complete all intended therapy following pancreatectomy due to postoperative complications or poor performance status.The administration of chemotherapy prior to surgical resection is an alternative strategy that ensures its early and near universal delivery as well as improves margin-negative resection rates and potentially improves long-term survival outcomes.Neoadjuvant therapy is increasingly being recommended to patients with pancreatic ductal adenocarcinoma,however,patient-centered research on its use is lacking.In this review,we highlight opportunities to focus research efforts in the domains of patient preferences,patient-reported outcomes,patient experience,and survivorship.Novel research in these areas may identify relevant barriers and facilitators to the use of neoadjuvant therapy thereby increasing its utilization,improve shareddecision making for patients and providers,and optimize the experience of those undergoing neoadjuvant therapy.展开更多
Solid organ transplantation is limited by suitable donor organ availability and the geographic limitations that lead to prolonged ischemic times. Ex vivo organ perfusion is an evolving technology that enables assessme...Solid organ transplantation is limited by suitable donor organ availability and the geographic limitations that lead to prolonged ischemic times. Ex vivo organ perfusion is an evolving technology that enables assessment of organ function prior to transplantation. As a byproduct, overall out of body organ times are able to be extended. The future implications organ assessment and repair centers utilizing this technology are discussed.展开更多
AIM To examine the effect of center size on survival differences between simultaneous liver kidney transplantation(SLKT) and liver transplantation alone(LTA) in SLKT-listed patients.METHODS The United Network of Organ...AIM To examine the effect of center size on survival differences between simultaneous liver kidney transplantation(SLKT) and liver transplantation alone(LTA) in SLKT-listed patients.METHODS The United Network of Organ Sharing database was queried for patients ≥ 18 years of age listed for SLKT between February 2002 and December 2015. Posttransplant survival was evaluated using stratified Cox regression with interaction between transplant type(LTA vs SLKT) and center volume.RESULTS During the study period, 393 of 4580 patients(9%) listed for SLKT underwent a LTA. Overall mortality was higher among LTA recipients(180/393, 46%) than SLKT recipients(1107/4187, 26%). The Cox model predicted a significant survival disadvantage for patients receiving LTA vs SLKT [hazard ratio, hazard ratio(HR) = 2.85; 95%CI: 2.21, 3.66; P < 0.001] in centers performing 30 SLKT over the study period. This disadvantage was modestly attenuated as center SLKT volume increased, with a 3% reduction(HR = 0.97; 95%CI: 0.95, 0.99; P = 0.010) for every 10 SLKs performed.CONCLUSION In conclusion, LTA is associated with increased mortality among patients listed for SLKT. This difference is modestly attenuated at more experienced centers and may explain inconsistencies between smaller-center and larger registry-wide studies comparing SLKT and LTA outcomes.展开更多
Artificial intelligence(AI)has been entwined with the field of radiology ever since digital imaging began replacing films over half a century ago.These algorithms,ranging from simplistic speech-to-text dictation progr...Artificial intelligence(AI)has been entwined with the field of radiology ever since digital imaging began replacing films over half a century ago.These algorithms,ranging from simplistic speech-to-text dictation programs to automated interpretation neural networks,have continuously sought to revolutionize medical imaging.With the number of imaging studies outpacing the amount of trained of readers,AI has been implemented to streamline workflow efficiency and provide quantitative,standardized interpretation.AI relies on massive amounts of data for its algorithms to function,and with the wide-spread adoption of Picture Archiving and Communication Systems(PACS),imaging data is accumulating rapidly.Current AI algorithms using machine-learning technology,or computer aided-detection,have been able to successfully pool this data for clinical use,although the scope of these algorithms remains narrow.Many systems have been developed to assist the workflow of the radiologist through PACS optimization and imaging study triage,however interpretation has generally remained a human responsibility for now.In this review article,we will summarize the current successes and limitations of AI in radiology,and explore the exciting prospects that deep-learning technology offers for the future.展开更多
Hepatocellular carcinoma(HCC)is the second most common cause of cancerrelated death worldwide.Despite the advent of screening efforts and algorithms to stratify patients into appropriate treatment strategies,recurrenc...Hepatocellular carcinoma(HCC)is the second most common cause of cancerrelated death worldwide.Despite the advent of screening efforts and algorithms to stratify patients into appropriate treatment strategies,recurrence rates remain high.In contrast to first-line treatment for HCC,which relies on several factors,including clinical staging,tumor burden,and liver function,there is no consensus or general treatment recommendations for recurrent HCC(R-HCC).Locoregional therapies include a spectrum of minimally invasive liver-directed treatments which can be used as either curative or neoadjuvant therapy for HCC.Herein,we provide a comprehensive review of recent evidence using salvage loco-regional therapies for R-HCC after failed curative-intent.展开更多
Spinal cord injury (SCI) at the cervical level compromises the function of both upper and lower extremities, thereby impeding an individual’s ability to complete daily tasks required for independent living and profou...Spinal cord injury (SCI) at the cervical level compromises the function of both upper and lower extremities, thereby impeding an individual’s ability to complete daily tasks required for independent living and profoundly affecting the overall quality of life among individuals afflicted by SCI and their families. Recovery of spinal cord functions may be attained by promoting the sprouting of non-injured axons and/or the regeneration of damaged axons.展开更多
BACKGROUND We previously reported national 30-d readmission rates of 27% in patients with decompensated cirrhosis(DC).AIM To study prospective interventions to reduce early readmissions in DC at our tertiary center.ME...BACKGROUND We previously reported national 30-d readmission rates of 27% in patients with decompensated cirrhosis(DC).AIM To study prospective interventions to reduce early readmissions in DC at our tertiary center.METHODS Adults with DC admitted July 2019 to December 2020 were enrolled and randomized into the intervention(INT) or standard of care(SOC) arms. Weekly phone calls for a month were completed. In the INT arm, case managers ensured outpatient follow-up, paracentesis, and medication compliance. Thirty-day readmission rates and reasons were compared.RESULTS Calculated sample size was not achieved due to coronavirus disease 2019;240 patients were randomized into INT and SOC arms. 30-d readmission rate was 33.75%, 35.83% in the INT vs 31.67% in the SOC arm(P = 0.59). The top reason for 30-d readmission was hepatic encephalopathy(HE, 32.10%). There was a lower rate of 30-d readmissions for HE in the INT(21%) vs SOC arm(45%, P = 0.03). There were fewer 30-d readmissions in patients who attended early outpatient follow-up(n = 17, 23.61% vs n = 55, 76.39%, P = 0.04).CONCLUSION Our 30-d readmission rate was higher than the national rate but reduced by interventions in patients with DC with HE and early outpatient follow-up. Development of interventions to reduce early readmission in patients with DC is needed.展开更多
Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many pati...Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.展开更多
The estrogen receptor(ER) pathway plays a critical role in breast cancer development and progression. Endocrine therapy targeting estrogen action is the most important systemic therapy for ER positive breast cancer. H...The estrogen receptor(ER) pathway plays a critical role in breast cancer development and progression. Endocrine therapy targeting estrogen action is the most important systemic therapy for ER positive breast cancer. However its efficacy is limited by intrinsic and acquired resistance. Mechanisms responsible for endocrine resistance include deregulation of the ER pathway itself, including loss of ER expression, posttranslational modification of ER, deregulation of ER coactivators; increased receptor tyrosine kinase signaling leading to activation of various intracellular pathways involved in signal transduction, proliferation and cell survival, including growth factor receptor tyrosine kinases human epidermal growth factor receptor-2, epidermal growth factor receptor, PI3K/AKT/mammalian target of rapamycin(m TOR), Mitogen activated kinase(MAPK)/ERK, fibroblast growth factor receptor, insulin-like growth factor-1 receptor; alterations in cell cycle and apoptotic machinery; Epigenetic modificationincluding dysregulation of DNA methylation, histone modification, and nucleosome remodeling; and altered expression of specific micro RNAs. Functional genomics has helped us identify a catalog of genetic and epigenetic alterations that may be exploited as potential therapeutic targets and biomarkers of response. New treatment combinations targeting ER and such oncogenic signaling pathways which block the crosstalk between these pathways have been proven effective in preclinical models. Results of recent clinical studies suggest that subsets of patients benefit from the combination of inhibitor targeting certain oncogenic signaling pathway with endocrine therapy. Especially, inhibition of the m TOR signaling pathway, a key component implicated in mediating multiple signaling cascades, offers a promising approach to restore sensitivity to endocrine therapy in breast cancer. We systematically reviewed important publications cited in Pub Med, recent abstracts from ASCO annual meetings and San Antonio Breast Cancer Symposium, and relevant trials registered at Clinical Trials.gov. We present the molecular mechanisms contributing to endocrine resistance, in particular focusing on the biological rationale for the clinical development of novel targeted agents in endocrine resistant breast cancer. We summarize clinical trials utilizing novel strategies to overcome therapeutic resistance, highlighting the need to better identify the appropriate patients whose diseases are most likely to benefit from these specific strategies.展开更多
AIM To critically evaluate previous scientific evidence on Fusobacterium's role in colorectal neoplasia development.METHODS Two independent investigators systematically reviewed all original scientific articles pu...AIM To critically evaluate previous scientific evidence on Fusobacterium's role in colorectal neoplasia development.METHODS Two independent investigators systematically reviewed all original scientific articles published between January,2000,and July,2017,using Pub Med,EMBASE,and MEDLINE. A total of 355 articles were screened at the abstract level. Of these,only original scientific human,animal,and in vitro studies investigating Fusobacterium and its relationship with colorectal cancer(CRC) were included in the analysis. Abstracts,review articles,studies investigating other colonic diseases,and studies written in other languages than English were excluded from our analysis. Ninety articles were included after removing duplicates,resolving disagreements between the two reviewers,and applying the above criteria.RESULTS Studies have consistently identified positive associations between Fusobacterium,especially Fusobacterium nucleatum(F. nucleatum),and CRC. Stronger associations were seen in CRCs proximal to the splenic flexure and Cp G island methylator phenotype(CIMP)-high CRCs. There was evidence of temporality and a biological gradient,with increased F. nucleatum DNA detection and quantity along the traditional adenoma-carcinoma sequence and in CIMP-high CRC precursors. Diet may have a differential impact on colonic F. nucleatum enrichment;evidence suggests that high fiber diet may reduce the risk of a subset of CRCs that are F. nucleatum DNA-positive. Data also suggest shorter CRC and disease-specific survival with increased amount of F. nucleatum DNA in CRC tissue. The pathophysiology of enrichment of F. nucleatum and other Fusobacterium species in colonic tissue is unclear;however,the virulence factors and changes to the local colonic environment with disruption of the protective mucus layer may contribute. The presence of a host lectin(Gal-Gal NAc) in the colonic epithelium may also mediate F. nucleatum attachment to CRC and precursors through interaction with an F. nucleatum protein,fibroblast activation protein 2(FAP2). The clinical significance of detection or enrichment of Fusobacterium in colorectal neoplasia is ambiguous,but data suggest a procarcinogenic effect of F. nucleatum,likely due to activation of oncogenic and inflammatory pathways and modulation of the tumor immune environment. This is hypothesized to be mediated by certain F. nucleatum strains carrying invasive properties and virulence factors such as Fad A and FAP.CONCLUSION Evidence suggests a potential active role of Fusobacterium,specifically F. nucleatum,in CRC. Future prospective and experimental human studies would fill an important gap in this literature.展开更多
AIM: To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten (PTEN) hamartoma tumor syndrome (PHTS) and to perform a systematic literature review rega...AIM: To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten (PTEN) hamartoma tumor syndrome (PHTS) and to perform a systematic literature review regarding the same.展开更多
Hepatorenal syndrome(HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation(LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40...Hepatorenal syndrome(HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation(LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40%, respectively. In this article, we reviewed current concepts in HRS pathophysiology, guidelines for HRS diagnosis, effective treatment options presently available, and controversies surrounding liver alone vs simultaneous liver kidney transplant(SLKT) in transplant candidates. Many treatment options including albumin, vasoconstrictors, renal replacement therapy, and eventual LT have remained a mainstay in the treatment of HRS. Unfortunately, even after aggressive measures such as terlipressin use, the rate of recovery is less than 50% of patients. Moreover, current SLKT guidelines include:(1) estimation of glomerular filtration rate of 30 m L/min or less for 4-8 wk;(2) proteinuria > 2 g/d; or(3) biopsy proven interstitial fibrosis or glomerulosclerosis. Even with these updated criteria there is a lack of consistency regarding longterm benefits for SLKT vs LT alone. Finally, in regards to kidney dysfunction in the post-transplant setting, an estimation of glomerular filtration rate < 60 mL /min per 1.73 m2 may be associated with an increased risk of patients having long-term end stage renal disease. HRS is common in patients with cirrhosis and those on liver transplant waitlist. Prompt identification and therapy initiation in transplant candidates with HRS may improve post-transplantation outcomes. Future studies identifying optimal vasoconstrictor regimens, alternative therapies, and factors predictive of response to therapy are needed. The appropriate use of SLKT in patients with HRS remains controversial and requires further evidence by the transplant community.展开更多
Intrahepatic cholangiocarcinoma(ICC)is the second most common primary liver malignancy and is increasing in incidence.Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuva...Intrahepatic cholangiocarcinoma(ICC)is the second most common primary liver malignancy and is increasing in incidence.Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuvant chemotherapy.Unfortunately,a significant proportion of patients present with locally advanced,unresectable disease.Furthermore,recurrence rates are high even among patients who undergo surgical resection.The delivery of systemic and/or liver-directed therapies prior to surgery may increase the proportion of patients who are eligible for surgery and reduce recurrence rates by prioritizing early systemic therapy for this aggressive cancer.Nevertheless,the available evidence for neoadjuvant therapy in ICC is currently limited yet recent advances in liver directed therapies,chemotherapy regimens,and targeted therapies have generated increasing interest its role.In this article,we review the rationale for,current evidence for,and ongoing research efforts in the use of neoadjuvant therapy for ICC.展开更多
Pancreatic cystic lesions(PCLs)are becoming more prevalent due to more frequent abdominal imaging and the increasing age of the general population.It has become crucial to identify these PCLs and subsequently risk str...Pancreatic cystic lesions(PCLs)are becoming more prevalent due to more frequent abdominal imaging and the increasing age of the general population.It has become crucial to identify these PCLs and subsequently risk stratify them to guide management.Given the high morbidity associated with pancreatic surgery,only those PCLs at high risk for malignancy should undergo such treatment.However,current diagnostic testing is suboptimal at accurately diagnosing and risk stratifying PCLs.Therefore,research has focused on developing new techniques for differentiating mucinous from non-mucinous PCLs and identifying high risk lesions for malignancy.Cross sectional imaging radiomics can potentially improve the predictive accuracy of primary risk stratification of PCLs at the time of detection to guide invasive testing.While cyst fluid glucose has reemerged as a potential biomarker,cyst fluid molecular markers have improved accuracy for identifying specific types of PCLs.Endoscopic ultrasound guided approaches such as confocal laser endomicroscopy and through the needle microforceps biopsy have shown a good correlation with histopathological findings and are evolving techniques for identifying and risk stratifying PCLs.While most of these recent diagnostics are only practiced at selective tertiary care centers,they hold a promise that management of PCLs will only get better in the future.展开更多
文摘Background:Despite advances in the diagnosis of patients with hepatocellular carcinoma(HCC),70%-80%of patients are diagnosed with advanced stage disease.Portal vein tumor thrombus(PVTT)is among the most ominous signs of advanced stage disease and has been associated with poor survival if untreated.Data sources:A systematic search of MEDLINE(PubMed),Embase,Cochrane Library and Database for Systematic Reviews(CDSR),Google Scholar,and National Institute for Health and Clinical Excellence(NICE)databases until December 2022 was conducted using free text and MeSH terms:hepatocellular carcinoma,portal vein tumor thrombus,portal vein thrombosis,vascular invasion,liver and/or hepatic resection,liver transplantation,and systematic review.Results:Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic chemotherapy.Critical elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus,accurate identification of the subgroups of patients who may benefit from resection,as well as meticulous surgical technique.This review addressed five specific areas:(a)formation of PVTT;(b)classifications of PVTT;(c)controversies related to clinical guidelines;(d)surgical treatments versus non-surgical approaches;and(e)characterization of surgical techniques correlated with classifications of PVTT.Conclusions:Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.
文摘MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.
文摘In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving paradigm,it is crucial to identify factors that predict higher rates of lymphatic invasion and poorer outcomes.Larger tumor size,deeper invasion,poorer differentiation,more infiltrative growth patterns(INF-c),higher-grade tumor budding,positive lymphovascular invasion,and certain biomarkers have been associated with lymph node metastasis and increased morbidity through retrospective reviews,leading to the construction of comprehensive nomograms for outcome prediction.If validated by future prospective studies,these nomograms would prove highly applicable in guiding the selection of treatment for superficial ESCC.
文摘1.Introduction For decades,substantial disagreement has persisted as to whether dynamic knee valgus is the cause of the majority of anterior cruciate ligament(ACL)injuries or rather the result of the ACL rupture.1 Consequently,great effort and expense has gone into capturing 3-dimensional kinetics and kinematics from live athletes to drive in vitro and in silico models of ACL injury in order to elucidate the actual mechanism of injury,as these factors have been demonstrated to be surrogates of intraarticular structural loading on the ACL.2,3 The elucidation of injury mechanisms for non-contact ACL injuries is of great medical value as such knowledge consequently permits quantified examination and validation of interventions and their respective effectiveness in both prevention and rehabilitation of these traumatic knee injuries.
基金sponsored by a grant from the National Institute of Neurological Disorders and Stroke:RO1NS116059(to MZ)。
文摘Modern neuroscience began from all reaching and fierce conflict between“neuronismo and reticulismo”——between neuronal and reticular theories of the organization of the nervous system;the conflict culminated in December of 1906 in Stockholm where Santiago Ramon y Cajal(the proponent of the neuronal doctrine)and Camillo Golgi(who advocated the syncytial reticular organization of neural networks)delivered their Noble prize lectures(Verkhratsky,2009).
文摘Pancreatic ductal adenocarcinoma is an aggressive cancer with high recurrence rates following surgical resection.While adjuvant chemotherapy improves survival,a significant proportion of patients are unable to initiate or complete all intended therapy following pancreatectomy due to postoperative complications or poor performance status.The administration of chemotherapy prior to surgical resection is an alternative strategy that ensures its early and near universal delivery as well as improves margin-negative resection rates and potentially improves long-term survival outcomes.Neoadjuvant therapy is increasingly being recommended to patients with pancreatic ductal adenocarcinoma,however,patient-centered research on its use is lacking.In this review,we highlight opportunities to focus research efforts in the domains of patient preferences,patient-reported outcomes,patient experience,and survivorship.Novel research in these areas may identify relevant barriers and facilitators to the use of neoadjuvant therapy thereby increasing its utilization,improve shareddecision making for patients and providers,and optimize the experience of those undergoing neoadjuvant therapy.
文摘Solid organ transplantation is limited by suitable donor organ availability and the geographic limitations that lead to prolonged ischemic times. Ex vivo organ perfusion is an evolving technology that enables assessment of organ function prior to transplantation. As a byproduct, overall out of body organ times are able to be extended. The future implications organ assessment and repair centers utilizing this technology are discussed.
文摘AIM To examine the effect of center size on survival differences between simultaneous liver kidney transplantation(SLKT) and liver transplantation alone(LTA) in SLKT-listed patients.METHODS The United Network of Organ Sharing database was queried for patients ≥ 18 years of age listed for SLKT between February 2002 and December 2015. Posttransplant survival was evaluated using stratified Cox regression with interaction between transplant type(LTA vs SLKT) and center volume.RESULTS During the study period, 393 of 4580 patients(9%) listed for SLKT underwent a LTA. Overall mortality was higher among LTA recipients(180/393, 46%) than SLKT recipients(1107/4187, 26%). The Cox model predicted a significant survival disadvantage for patients receiving LTA vs SLKT [hazard ratio, hazard ratio(HR) = 2.85; 95%CI: 2.21, 3.66; P < 0.001] in centers performing 30 SLKT over the study period. This disadvantage was modestly attenuated as center SLKT volume increased, with a 3% reduction(HR = 0.97; 95%CI: 0.95, 0.99; P = 0.010) for every 10 SLKs performed.CONCLUSION In conclusion, LTA is associated with increased mortality among patients listed for SLKT. This difference is modestly attenuated at more experienced centers and may explain inconsistencies between smaller-center and larger registry-wide studies comparing SLKT and LTA outcomes.
文摘Artificial intelligence(AI)has been entwined with the field of radiology ever since digital imaging began replacing films over half a century ago.These algorithms,ranging from simplistic speech-to-text dictation programs to automated interpretation neural networks,have continuously sought to revolutionize medical imaging.With the number of imaging studies outpacing the amount of trained of readers,AI has been implemented to streamline workflow efficiency and provide quantitative,standardized interpretation.AI relies on massive amounts of data for its algorithms to function,and with the wide-spread adoption of Picture Archiving and Communication Systems(PACS),imaging data is accumulating rapidly.Current AI algorithms using machine-learning technology,or computer aided-detection,have been able to successfully pool this data for clinical use,although the scope of these algorithms remains narrow.Many systems have been developed to assist the workflow of the radiologist through PACS optimization and imaging study triage,however interpretation has generally remained a human responsibility for now.In this review article,we will summarize the current successes and limitations of AI in radiology,and explore the exciting prospects that deep-learning technology offers for the future.
文摘Hepatocellular carcinoma(HCC)is the second most common cause of cancerrelated death worldwide.Despite the advent of screening efforts and algorithms to stratify patients into appropriate treatment strategies,recurrence rates remain high.In contrast to first-line treatment for HCC,which relies on several factors,including clinical staging,tumor burden,and liver function,there is no consensus or general treatment recommendations for recurrent HCC(R-HCC).Locoregional therapies include a spectrum of minimally invasive liver-directed treatments which can be used as either curative or neoadjuvant therapy for HCC.Herein,we provide a comprehensive review of recent evidence using salvage loco-regional therapies for R-HCC after failed curative-intent.
基金supported by the National Institute of Neurological Disorders (R01NS110681 and R21NS109787 (to AT))the Chronic Brain Injury Program (to AT)The Ohio State University/ Wexner Medical Center。
文摘Spinal cord injury (SCI) at the cervical level compromises the function of both upper and lower extremities, thereby impeding an individual’s ability to complete daily tasks required for independent living and profoundly affecting the overall quality of life among individuals afflicted by SCI and their families. Recovery of spinal cord functions may be attained by promoting the sprouting of non-injured axons and/or the regeneration of damaged axons.
基金GASTR29:Prospective validation of readmission risk score and interventions to prevent readmission in patients with decompensated cirrhosis(CCTS ID#:6018).
文摘BACKGROUND We previously reported national 30-d readmission rates of 27% in patients with decompensated cirrhosis(DC).AIM To study prospective interventions to reduce early readmissions in DC at our tertiary center.METHODS Adults with DC admitted July 2019 to December 2020 were enrolled and randomized into the intervention(INT) or standard of care(SOC) arms. Weekly phone calls for a month were completed. In the INT arm, case managers ensured outpatient follow-up, paracentesis, and medication compliance. Thirty-day readmission rates and reasons were compared.RESULTS Calculated sample size was not achieved due to coronavirus disease 2019;240 patients were randomized into INT and SOC arms. 30-d readmission rate was 33.75%, 35.83% in the INT vs 31.67% in the SOC arm(P = 0.59). The top reason for 30-d readmission was hepatic encephalopathy(HE, 32.10%). There was a lower rate of 30-d readmissions for HE in the INT(21%) vs SOC arm(45%, P = 0.03). There were fewer 30-d readmissions in patients who attended early outpatient follow-up(n = 17, 23.61% vs n = 55, 76.39%, P = 0.04).CONCLUSION Our 30-d readmission rate was higher than the national rate but reduced by interventions in patients with DC with HE and early outpatient follow-up. Development of interventions to reduce early readmission in patients with DC is needed.
文摘Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.
文摘The estrogen receptor(ER) pathway plays a critical role in breast cancer development and progression. Endocrine therapy targeting estrogen action is the most important systemic therapy for ER positive breast cancer. However its efficacy is limited by intrinsic and acquired resistance. Mechanisms responsible for endocrine resistance include deregulation of the ER pathway itself, including loss of ER expression, posttranslational modification of ER, deregulation of ER coactivators; increased receptor tyrosine kinase signaling leading to activation of various intracellular pathways involved in signal transduction, proliferation and cell survival, including growth factor receptor tyrosine kinases human epidermal growth factor receptor-2, epidermal growth factor receptor, PI3K/AKT/mammalian target of rapamycin(m TOR), Mitogen activated kinase(MAPK)/ERK, fibroblast growth factor receptor, insulin-like growth factor-1 receptor; alterations in cell cycle and apoptotic machinery; Epigenetic modificationincluding dysregulation of DNA methylation, histone modification, and nucleosome remodeling; and altered expression of specific micro RNAs. Functional genomics has helped us identify a catalog of genetic and epigenetic alterations that may be exploited as potential therapeutic targets and biomarkers of response. New treatment combinations targeting ER and such oncogenic signaling pathways which block the crosstalk between these pathways have been proven effective in preclinical models. Results of recent clinical studies suggest that subsets of patients benefit from the combination of inhibitor targeting certain oncogenic signaling pathway with endocrine therapy. Especially, inhibition of the m TOR signaling pathway, a key component implicated in mediating multiple signaling cascades, offers a promising approach to restore sensitivity to endocrine therapy in breast cancer. We systematically reviewed important publications cited in Pub Med, recent abstracts from ASCO annual meetings and San Antonio Breast Cancer Symposium, and relevant trials registered at Clinical Trials.gov. We present the molecular mechanisms contributing to endocrine resistance, in particular focusing on the biological rationale for the clinical development of novel targeted agents in endocrine resistant breast cancer. We summarize clinical trials utilizing novel strategies to overcome therapeutic resistance, highlighting the need to better identify the appropriate patients whose diseases are most likely to benefit from these specific strategies.
文摘AIM To critically evaluate previous scientific evidence on Fusobacterium's role in colorectal neoplasia development.METHODS Two independent investigators systematically reviewed all original scientific articles published between January,2000,and July,2017,using Pub Med,EMBASE,and MEDLINE. A total of 355 articles were screened at the abstract level. Of these,only original scientific human,animal,and in vitro studies investigating Fusobacterium and its relationship with colorectal cancer(CRC) were included in the analysis. Abstracts,review articles,studies investigating other colonic diseases,and studies written in other languages than English were excluded from our analysis. Ninety articles were included after removing duplicates,resolving disagreements between the two reviewers,and applying the above criteria.RESULTS Studies have consistently identified positive associations between Fusobacterium,especially Fusobacterium nucleatum(F. nucleatum),and CRC. Stronger associations were seen in CRCs proximal to the splenic flexure and Cp G island methylator phenotype(CIMP)-high CRCs. There was evidence of temporality and a biological gradient,with increased F. nucleatum DNA detection and quantity along the traditional adenoma-carcinoma sequence and in CIMP-high CRC precursors. Diet may have a differential impact on colonic F. nucleatum enrichment;evidence suggests that high fiber diet may reduce the risk of a subset of CRCs that are F. nucleatum DNA-positive. Data also suggest shorter CRC and disease-specific survival with increased amount of F. nucleatum DNA in CRC tissue. The pathophysiology of enrichment of F. nucleatum and other Fusobacterium species in colonic tissue is unclear;however,the virulence factors and changes to the local colonic environment with disruption of the protective mucus layer may contribute. The presence of a host lectin(Gal-Gal NAc) in the colonic epithelium may also mediate F. nucleatum attachment to CRC and precursors through interaction with an F. nucleatum protein,fibroblast activation protein 2(FAP2). The clinical significance of detection or enrichment of Fusobacterium in colorectal neoplasia is ambiguous,but data suggest a procarcinogenic effect of F. nucleatum,likely due to activation of oncogenic and inflammatory pathways and modulation of the tumor immune environment. This is hypothesized to be mediated by certain F. nucleatum strains carrying invasive properties and virulence factors such as Fad A and FAP.CONCLUSION Evidence suggests a potential active role of Fusobacterium,specifically F. nucleatum,in CRC. Future prospective and experimental human studies would fill an important gap in this literature.
文摘AIM: To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten (PTEN) hamartoma tumor syndrome (PHTS) and to perform a systematic literature review regarding the same.
文摘Hepatorenal syndrome(HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation(LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40%, respectively. In this article, we reviewed current concepts in HRS pathophysiology, guidelines for HRS diagnosis, effective treatment options presently available, and controversies surrounding liver alone vs simultaneous liver kidney transplant(SLKT) in transplant candidates. Many treatment options including albumin, vasoconstrictors, renal replacement therapy, and eventual LT have remained a mainstay in the treatment of HRS. Unfortunately, even after aggressive measures such as terlipressin use, the rate of recovery is less than 50% of patients. Moreover, current SLKT guidelines include:(1) estimation of glomerular filtration rate of 30 m L/min or less for 4-8 wk;(2) proteinuria > 2 g/d; or(3) biopsy proven interstitial fibrosis or glomerulosclerosis. Even with these updated criteria there is a lack of consistency regarding longterm benefits for SLKT vs LT alone. Finally, in regards to kidney dysfunction in the post-transplant setting, an estimation of glomerular filtration rate < 60 mL /min per 1.73 m2 may be associated with an increased risk of patients having long-term end stage renal disease. HRS is common in patients with cirrhosis and those on liver transplant waitlist. Prompt identification and therapy initiation in transplant candidates with HRS may improve post-transplantation outcomes. Future studies identifying optimal vasoconstrictor regimens, alternative therapies, and factors predictive of response to therapy are needed. The appropriate use of SLKT in patients with HRS remains controversial and requires further evidence by the transplant community.
文摘Intrahepatic cholangiocarcinoma(ICC)is the second most common primary liver malignancy and is increasing in incidence.Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuvant chemotherapy.Unfortunately,a significant proportion of patients present with locally advanced,unresectable disease.Furthermore,recurrence rates are high even among patients who undergo surgical resection.The delivery of systemic and/or liver-directed therapies prior to surgery may increase the proportion of patients who are eligible for surgery and reduce recurrence rates by prioritizing early systemic therapy for this aggressive cancer.Nevertheless,the available evidence for neoadjuvant therapy in ICC is currently limited yet recent advances in liver directed therapies,chemotherapy regimens,and targeted therapies have generated increasing interest its role.In this article,we review the rationale for,current evidence for,and ongoing research efforts in the use of neoadjuvant therapy for ICC.
文摘Pancreatic cystic lesions(PCLs)are becoming more prevalent due to more frequent abdominal imaging and the increasing age of the general population.It has become crucial to identify these PCLs and subsequently risk stratify them to guide management.Given the high morbidity associated with pancreatic surgery,only those PCLs at high risk for malignancy should undergo such treatment.However,current diagnostic testing is suboptimal at accurately diagnosing and risk stratifying PCLs.Therefore,research has focused on developing new techniques for differentiating mucinous from non-mucinous PCLs and identifying high risk lesions for malignancy.Cross sectional imaging radiomics can potentially improve the predictive accuracy of primary risk stratification of PCLs at the time of detection to guide invasive testing.While cyst fluid glucose has reemerged as a potential biomarker,cyst fluid molecular markers have improved accuracy for identifying specific types of PCLs.Endoscopic ultrasound guided approaches such as confocal laser endomicroscopy and through the needle microforceps biopsy have shown a good correlation with histopathological findings and are evolving techniques for identifying and risk stratifying PCLs.While most of these recent diagnostics are only practiced at selective tertiary care centers,they hold a promise that management of PCLs will only get better in the future.
