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Centralized Lung Nodule Management at A VeteransHospital Using A Multidisciplinary Lung NoduleEvaluation Team(LNET)

中国肺癌杂志 2018年第11期21卷 828-832页

作者： William R.WRIGHTSON Umar GAUHAR Fred HENDLER Teresa JOINER Jennifer PENDLETON Robley Rex Veterans Affairs (va)medical center LouisvilleKentuckyUSA

Introduction: Lung nodules are frequently identified on imaging studies and can represent early lung cancers. We instituted the Lung Nodule Evaluation Team(LNET) to optimize management of these nodules by a lung specialist physician. All lung nodules identified by a radiologist prompted a direct consultation to this service. We report our initial experience with this process. Methods: This is a retrospective review of patients with lung nodules at a single institution from 2008 to 2015. Since October 2014, lung nodules >3 mm identified on computed tomography(CT) scanning of the chest generate an automatic consult to LNET from the radiology service. Demographic, nodule and follow up data was entered into a surveillance database and ***: There were 1,873 patients identified in the database. Of these, 900 patients were undergoing active surveillance. Consults increased from 5.5 to 93 per month after the start of the new consult program. Lung nodules were identified on 64% of chest CT scans. Prior to the direct radiology consult the average size of a nodule was 1.7 cm and 0.7 cm after. The overall time from initial nodule imaging to initiating a management plan by a thoracic specialist physician was 3.7 days. Conclusion: Assessment of lung nodules by a specialist physician is important to ensure appropriate long term management and optimize utilization of diagnostic interventions. A direct radiology consult to a specialized team of chest physicians decreased the time in initiating a management plan, identified smaller nodules and may lead to a more judicious use of health care resources in the management of lung nodules.

关键词： Lung nodule Cancer Mulfidiscliplinary

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One Year After First Spontaneous Bacterial Peritonitis:Who Survives?

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Journal of Clinical and Translational Hepatology 2021年第5期9卷 603-604页

作者： Atoosa Rabiee Washington DC va medical center Washington DCUSA

Spontaneous bacterial peritonitis(SBP)is defined as infection in ascites fluid without evidence of an intra-abdominal treatable source.1 Diagnosis is confirmed by presence of≥250 cells/mm3 polymorphonuclear cells(PMNs).2 Although SBP responds well to appropriate antibiotic treatment,in patients with underlying cirrhosis severe enough to develop SBP,long-term prognosis is ***-hospital non-infectionrelated mortality is 20–40%and 1-and 2-year mortality rates are 70%and 80%,respectively.

关键词： mortality infection ascites

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Role of transmethylation reactions in alcoholic liver disease

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World Journal of Gastroenterology 2007年第37期13卷 4947-4954页

作者： Kusum K Kharbanda va Alcohol Research center Department of Veterans Affairs Medical Center Omaha Nebraska 68105 United States Department of Internal Medicine University of Nebraska Medical Center Omaha Nebraska 68198 United States

Alcoholic liver disease is a major health care problem worldwide. Findings from many laboratories, including ours, have demonstrated that ethanol feeding impairs several of the many steps involved in methionine metabolism. Ethanol consumption predominantly results in a decrease in the hepatocyte level of S-adenosylmethionine and the increases in two toxic metabolites, homocysteine and S-adenosylhomocysteine. These changes, in turn, result in serious functional consequences which include decreases in essential methylation reactions v/a inhibition of various methyltransferases. Of particular interest to our laboratory is the inhibition of three important enzymes, phosphatidylethanolamine methyltransferase, isoprenylcysteine carboxyl methyltransferase and protein L-isoaspartate methyltransferase. Decreased activity of these enzymes results in increased fat deposition, increased apoptosis and increased accumulation of damaged proteins- all of which are hallmark features of alcoholic liver injury. Of all the therapeutic modalities available, betaine has been shown to be the safest, least expensive and most effective in attenuating ethanol-induced liver injury. Betaine, by virtue of aiding in the remethylation of homocysteine, removes both toxic metabolites （homocysteine and S-adenosylhomocysteine）, restores S-adenosylmethionine level, and reverses steatosis, apoptosis and damaged proteins accumulation. In conclusion, betaine appears to be a promising therapeutic agent in relieving the methylation and other defects associated with alcoholic abuse.

关键词： Transmethylation S-adenosylhomocysteine Alcohol Betaine Liver Steatosis Apoptosis Methyltransferases

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Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

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Gastroenterology Report 2015年第4期3卷 277-288,I0001页

作者： Linda Ferrari Alessandro Fichera Division of General Surgery Department of SurgeryUniversity of Washington Medical CenterSeattleWashington 98195USA

The management of rectal cancer has evolved significantly in the last few *** improvements in local disease control were achieved in the 1990s,with the introduction of total mesorectal excision and neoadjuvant *** 1 evidence has shown that,with neoadjuvant chemoradiation therapy(CRT)the rates of local recurrence can be lower than 6%and,as a result,neoadjuvant CRT currently represents the accepted standard of *** approach has led to reliable tumor down-staging,with 15–27%patients with a pathological complete response(pCR)—defined as no residual cancer found on histological examination of the *** who achieve pCR after CRT have better long-term outcomes,less risk of developing local or distal recurrence and improved *** all these reasons,sphincter-preserving procedures or organ-preserving options have been suggested,such as local excision of residual tumor or the omission of surgery *** local recurrence rate has been stable at 5–6%with this multidisciplinary management method,distal recurrence rates for locally-advanced rectal cancers remain in excess of 25%and represent the main cause of death in these *** this reason,more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting(in order to offer early treatment of disseminated micrometastases,thus improving control of systemic disease)and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm.

关键词： rectal cancer neoadjuvant chemoradiation therapy pathological complete response

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All-cause hospitalizations for inflammatory bowel diseases:Can the reason for admission provide information on inpatient resource use?A study from a large veteran affairs hospital

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Journal of medical Colleges of PLA(China) 2016年第3期31卷 124-128页

作者： Ashish Malhotra K.C.Mandip Aasma Shaukat Thomas Rector Division of Gastroenterology Department of MedicineMinneapolis VA Medical CenterUniversity of Minnesota center of Innovation Minneapolis VA Medical Center Department of Medicine University of Minnesota

Background:Inflammatory bowel diseases(IBDs) are group of chronic inflammatory illnesses with a remitting and relapsing course that may result in appreciable morbidity and high medical costs secondary to repeated *** study's objectives were to identify the reasons for hospitalization among patients with IBDs,and compare inpatient courses and readmission rates for IBD-related admissions versus non-IBD-related ***:A retrospective chart review was performed on all patients with IBD admitted to the Minneapolis Veterans Affairs(va) medical center between September 2010 and September ***:A total of 111 patients with IBD were admitted during the 2-year study *** flares/complications accounted for 36.9% of the index *** events comprised the second most common cause of admissions(14.4%) in IBD *** with an index admission directly related to IBD were significantly younger and had developed IBD more ***,the IBD admission group had significantly more gastrointestinal endoscopies and abdominal surgeries,and was more likely to be started on medication for IBD during the index *** median length of stay(LOS) for the index hospitalization for an IBD flare or complication was 4(2–8) days compared with 2(1–4) days for the other patients(P=0.001).A smaller percentage of the group admitted for an IBD flare/complication had a shorter ICU stay compared with the other patients(9.8% vs.15.7%,respectively); however,their ICU LOSs tended to be longer(4.5 vs.2.0 days,respectively,P=0.17).Compared to the other admission types,an insignificantly greater percentage of the group whose index admission was related to an IBD flare or complication had at least one readmission within 6 months of discharge(29% versus 21%; P=0.35).The rate of admission was approximately 80% greater in the group whose index admission was related to an IBD flare or complication compared to the other types of admis

关键词： Inflammatory bowel diseases Veteran affairs Readmission rate

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Hepatitis C virus and ethanol alter antigen presentation in liver cells

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World Journal of Gastroenterology 2009年第10期15卷 1201-1208页

作者： Natalia A Osna Department of Internal Medicine University of Nebraska Medical Center Liver Study Unit R151 VA Medical Center 4101 Woolworth Ave Omaha NE 68105 United States

Alcoholic patients have a high incidence of hepatitis C virus （HCV） infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCV- induced inability of the immune system to recognize infected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex （MHC） class Ⅰ- and class Ⅱ-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC class I and class ~I in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability ＇of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 （IL-10） and transforming growth factor beta （TGFβ） predominance, preventing cell maturation and allostimulation capacity. The synergistic action of ethanol with HCV results in the suppression of MHC class Ⅱ-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC class I -restricted antigen presentation. Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.

关键词： Alcohol Antigen presentation HepatitisC Virus Interferon alpha and gamma Liver Majorhistocompatibility complex (MHC) class Ⅰ MHC class Ⅱ

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Blood and urine biomarkers in prostate cancer:Are we ready for reflex testing in men with an elevated prostate-specific antigen?

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Asian Journal of Urology 2021年第4期8卷 343-353页

作者： Edward K.Chang Adam J.Gadzinski Yaw A.Nyame Department of Urology University of Washington Medical CenterSeattleWAUSA Division of Public Health Sciences Fred Hutchinson Cancer Research CenterSeattleWAUSA

Objective:There is no consensus on the role of biomarkers in determining the utility of prostate biopsy in men with elevated prostate-specific antigen(PSA).There are numerous biomarkers such as prostate health index,4Kscore,prostate cancer antigen 3,ExoDX,SelectMDx,and Mi-Prostate Score that may be useful in this decision-making ***,it is unclear whether any of these tests are accurate and cost-effective enough to warrant being a widespread reflex test following an elevated *** goal was to report on the clinical utility of these blood and urine biomarkers in prostate cancer ***:We performed a systematic review of studies published between January 2000 and October 2020 to report the available parameters and cost-effectiveness of the aforementioned diagnostic *** focus on the negative predictive value,the area under the curve,and the decision curve analysis in comparing reflexive tests due to their relevance in evaluating diagnostic screening ***:Overall,the biomarkers are roughly equivalent in predictive *** test has additional clinical utility to the current diagnostic standard of care,but the added benefit is not substantial to justify using the test reflexively after an elevated ***:Our findings suggest these biomarkers should not be used in binary fashion and should be understood in the context of pre-existing risk predictors,patient’s ethnicity,cost of the test,patient life-expectancy,and patient *** are more recent diagnostic tools such as multi-parametric magnetic resonance imaging,polygenic single-nucleotide panels,IsoPSA,and miR Sentinel tests that are promising in the realm of prostate cancer screening and need to be investigated further to be considered a consensus reflexive test in the setting of prostate cancer screening.

关键词： Prostate-specific antigen Reflex testing Prostate cancer Screening

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Combination of epidural electrical stimulation with ex vivo triple gene therapy for spinal cord injury:a proof of principle study

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Neural Regeneration Research 2021年第3期16卷 550-560页

作者： Filip Olegovich Fadeev Farid vagizovich Bashirov vahe Arshaluysovich Markosyan Andrey Alexandrovich Izmailov Tatyana Vyacheslavovna Povysheva Mikhail Evgenyevich Sokolov Maxim Sergeevich Kuznetsov Anton Alexandrovich Eremeev Ilnur Ildusovich Salafutdinov Albert Anatolyevich Rizvanov Hyun Joon Lee Rustem Robertovich Islamov Department of medical Biology and Genetics Kazan State Medical UniversityKazanRussia Federal University KazanRussia Department of Neurology University of Mississippi Medical CenterJacksonMSUSA Research Service G.V.(Sonny)Montgomery VA Medical CenterJacksonMSUSA

Despite emerging contemporary biotechnological methods such as gene-and stem cell-based therapy,there are no clinically established therapeutic strategies for neural regeneration after spinal cord *** previous studies have demonstrated that transplantation of genetically engineered human umbilical cord blood mononuclear cells producing three recombinant therapeutic molecules,including vascular endothelial growth factor(VEGF),glial cell-line derived neurotrophic factor(GDNF),and neural cell adhesion molecule(NCAM)can improve morpho-functional recovery of injured spinal cord in rats and *** investigate the efficacy of human umbilical cord blood mononuclear cells-mediated triple-gene therapy combined with epidural electrical stimulation in the treatment of spinal cord injury,in this study,rats with moderate spinal cord contusion injury were intrathecally infused with human umbilical cord blood mononuclear cells expressing recombinant genes VEGF165,GDNF,NCAM1 at 4 hours after spinal cord *** days after injury,epidural stimulations were given simultaneously above the lesion site at C5(to stimulate the cervical network related to forelimb functions)and below the lesion site at L2(to activate the central pattern generators)every other day for 4 *** subjected to the combined treatment showed a limited functional improvement of the knee joint,high preservation of muscle fiber area in tibialis anterior muscle and increased H/M ratio in gastrocnemius muscle 30 days after spinal cord ***,beneficial cellular outcomes such as reduced apoptosis and increased sparing of the gray and white matters,and enhanced expression of heat shock and synaptic proteins were found in rats with spinal cord injury subjected to the combined epidural electrical stimulation with gene *** study presents the first proof of principle study of combination of the multisite epidural electrical stimulation with ex vivo triple gene therapy(VEGF,GDNF and NCAM

关键词： adenoviral vector epidural electrical stimulation gene therapy glial cell-line derived neurotrophic factor human umbilical cord blood mononuclear cell neural cell adhesion molecule spinal cord injury vascular endothelial growth factor

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Transient stress cardiomyopathies in the elderly： Clinical ＆ Pathophysiologic considerations

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Journal of Geriatric Cardiology 2012年第1期9卷 38-48页

作者： Michael A Chen Harborview medical center/University of Washington 325 9th Avenue Box 359748 Seattle WA 98104 USA

Transient stress-induced cardiomyopathies have been increasingly recognized and while rare,they tend to affect elderly women more than other demographic *** type,often called tako-tsubo cardiomyopathy （TTC）,is typically triggered by significant emotional or physical stress and is associated with chest pain,electrocardiogram （ECG） changes and abnormal cardiac *** left ventricular regional wall motion abnormalities usually include an akinetic ＂ballooning＂ apex with normal or hyperdynamic function of the base.A second type,often called neurogenic stunned myocardium,typically associated with subarachnoid hemorrhage,also usually presents with ECG changes and positive enzymes,but the typical wall motion abnormalities seen include normal basal and apical left ventricular contraction with akinesis of the mid-cavity in a circumferential *** pathophysiology,clinical care and typical courses,are reviewed.

关键词： Stress-cardiomyopathy Tako-tsubo cardiomyopathy Subarachnoid hemorrhage Neurogenic stunned myocardium

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Intestinal barrier function and metabolic/liver diseases

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Liver Research 2020年第2期4卷 81-87页

作者： Siddhartha S.Ghosh Jing Wang Paul J.Yannie Shobha Ghosh Department of Internal Medicine Virginia Commonwealth University Medical CenterRichmondVAUSA Hunter Homes McGuire Veterans Affairs medical center RichmondVAUSA

Dietary,environmental or genetic changes contribute to the development of several metabolic and neurological *** research efforts have been directed towards examining how these fac-tors modulate gut bacterial ***,the mechanisms by which changes in gut bacterial diversity affect host function are not completely *** barrier dysfunction is being increasingly recognized as an early or initiating step in communicating bacterial diversity-dependent changes to the ***,we review the functional composition of the intestinal barrier and describe the consequences of the breach of this *** functional layers of the intestinal barrier provide an initial defense and prevent the infiltration of bacteria or bacterial products from the gut lumen to the underlying lamina *** lymph nodes subsequently act as the first firewall where dendritic cells from the lamina propria transport the infiltrated bacteria or bacterial products during the early stages of barrier *** overwhelmed,the liver functions as the second firewall to detoxify bacterial endotoxins,such as lipopolysaccharide(LPS),and limit systemic *** translocation of LPS from the leaky gut to the liver results in liver damage or dysfunction that leads to the development of type 2 diabetes,atherosclerosis,heart disease,heart failure and also neurological dis-eases,such as Alzheimer’s and Parkinson’s ***,targeted restoration of intestinal barrier function represents a novel strategy for the attenuation of multiple diseases.

关键词： Intestinal barrier Liver dysfunction Lipopolysaccharide(LPS) Inflammation Gut-liver axis

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