Impact of pre- and peri-operative risk factors on length of stay and hospital readmission following minimally-invasive partial nephrectomy

Objective:We conducted an analysis of the American College of Surgeons National Surgical Quality Improvement Program database for minimally-invasive partial nephrectomy cases reported with the goal to identify pre-and peri-operative variables associated with length of stay(LOS)greater than 3 days and readmission within 30 days.Methods:Records from 2008 to 2018 for“laparoscopy,surgical;partial nephrectomy”for prolonged LOS and readmission cohorts were compiled.Univariate analysis with Chi-square,t-tests,and multivariable logistic regression analysis with odds ratios(ORs),p-values,and 95%confidence intervals assessed statistical associations.Results:Totally,20306 records for LOS greater than 3 days and 15854 for readmission within 30 days were available.Univariate and multivariable analysis exhibited similar results.For LOS greater than 3 days,undergoing non-elective surgery(OR=5.247),transfusion of greater than four units within 72 h prior to surgery(OR=5.072),pre-operative renal failure or dialysis(OR=2.941),and poor pre-operative functional status(OR=2.540)exhibited the strongest statistically significant associations.For hospital readmission within 30 days,loss in body weight greater than 10%in 6 months prior to surgery(OR=2.227)and bleeding disorders(OR=2.081)exhibited strongest statistically significant associations.Conclusion:Multiple pre-and peri-operative risk factors are independently associated with prolonged LOS and hospital readmission within 30 days of surgery using the American College of Surgeons National Surgical Quality Improvement Program data.Recognizing the risks factors that can potentially be improved prior to minimally-invasive partial nephrectomy is crucial to informing patient selection,optimization strategies,and patient education.

One-year survival in recipients older than 50 bridged to heart transplant with Impella 5.5 via axillary approach

BACKGROUND Optimizing patients with advanced heart failure before orthotopic heart transplantation(OHT), especially in patients greater than 50 years old, is imperative to achieving successful post-transplant outcomes. Complications are well-described for patients bridged to transplant(BTT) with durable left ventricular assist device(LVAD) support. Given the lack of data available in older recipients after the recent increase in mechanical support use, we felt it crucial to report our center’s one-year outcomes in older recipients after heart transplantation with percutaneously placed Impella 5.5 as a BTT.METHODS Forty-nine OHT patients were supported with the Impella 5.5 intended as a bridge between December 2019 and October 2022 at Mayo Clinic in Florida. Data were extracted from the electronic health record at baseline and during their transplant episode of care after Institutional Review Boards approval as exempt for retrospective data collection.RESULTS Thirty-eight patients aged 50 or older were supported with Impella 5.5 as BTT. Ten patients underwent heart and kidney transplantation within this cohort. The median age at OHT was 63(58–68) years, with 32 male(84%) and six female patients(16%). Etiology was divided into ischemic(63%) and non-ischemic cardiomyopathy(37%). The baseline median ejection fraction was 19%(15–24). Most patients were in blood group O(60%), and 50% were diabetic. The average duration of support was 27 days(range 6–94). The median duration of follow-up is 488 days(185–693). For patients that have reached the 1-year follow-up timeframe(22 of 38, 58%), the 1-year post-transplant survival is 95%.CONCLUSION Our single-center data provides awareness for using the Impella 5.5 percutaneously placed axillary support device in older heart failure patients in cardiogenic shock as a bridge to transplantation. One-year survival outcomes after heart transplantation are excellent despite the older recipient’s age and prolonged pre-transplant support.

Mortality assessment for pancreas transplants in the United States over the decade 2008-2018

BACKGROUND Pancreas transplant is the only treatment that establishes normal glucose levels for patients diagnosed with diabetes.However,since 2005,no comprehensive analysis has compared survival outcomes of:(1)Simultaneous pancreas-kidney(SPK)transplant;(2)Pancreas after kidney(PAK)transplant;and(3)Pancreas transplant alone(PTA)to waitlist survival.AIM To explore the outcomes of pancreas transplants in the United States during the decade 2008-2018.METHODS Our study utilized the United Network for Organ Sharing Standard Transplant Analysis and Research file.Pre-and post-transplant recipient and waitlist characteristics and the most recent recipient transplant and mortality status were used.We included all patients with type I diabetes listed for pancreas or kidneypancreas transplant between May 31,2008 and May 31,2018.Patients were grouped into one of three transplant types:SPK,PAK,or PTA.RESULTS The adjusted Cox proportional hazards models comparing survival between transplanted and non-transplanted patients in each transplant type group showed that patients who underwent an SPK transplant exhibited a significantly reduced hazard of mortality[hazard ratio(HR)=0.21,95%confidence intervals(CI):0.19-0.25]compared to those not transplanted.Neither PAK transplanted patients(HR=1.68,95%CI:0.99-2.87)nor PTA patients(HR=1.01,95%CI:0.53-1.95)experienced significantly different hazards of mortality compared to patients who did not receive a transplant.CONCLUSION When assessing each of the three transplant types,only SPK transplant offered a survival advantage compared to patients on the waiting list.PKA and PTA transplanted patients demonstrated no significant differences compared to patients who did not receive a transplant.

Targeting KRAS in pancreatic adenocarcinoma:Progress in demystifying the holy grail

Pancreatic cancer(PC)remains one of the most challenging diseases,with a very poor 5-year overall survival of around 11.5%.Kirsten rat sarcoma virus(KRAS)mutation is seen in 90%-95%of PC patients and plays an important role in cancer cell proliferation,differentiation,metabolism,and survival,making it an essential mutation for targeted therapy.Despite extensive efforts in studying this oncogene,there has been little success in finding a drug to target this pathway,labelling it for decades as“undruggable”.In this article we summarize some of the efforts made to target the KRAS pathway in PC,discuss the challenges,and shed light on promising clinical trials.

Treatment of diabetic retinopathy: Recent advances and unresolved challenges

Diabetic retinopathy(DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important management questions and treatment deficiencies remain unanswered. The global diabetes epidemic threatens to overwhelm resources and increase the incidence of blindness, necessitating the development of innovative programs to diagnose and treat patients. The introduction and rapid adoption of intravitreal pharmacologic agents, particularly drugs that block the actions of vascular endothelial growth factor(VEGF) and corticosteroids, have changed the goal of DR treatment from stabilization of vision to improvement. Anti-VEGF injections improve visual acuity in patients with diabetic macular edema(DME) from 8-12 letters and improvements with corticosteroids are only slightly less. Unfortunately, a third of patients have an incomplete response to anti-VEGF therapy, but the best second-line therapy remains unknown. Current first-line therapy requires monthly visits and injections; longer acting therapies are needed to free up healthcare resources and improve patient compliance. VEGF suppression may be as effective as panretinal photocoagulation(PRP) for proliferative diabetic retinopathy, but more studies are needed before PRP is abandoned. For over 30 years laser was the mainstay for the treatment of DME, but recent studies question its role in the pharmacologic era. Aggressive treatment improves vision in most patients, but many still do not achieve reading and driving vision. New drugs are needed to add to gains achieved with available therapies.

National trends in resection of the distal pancreas

AIM:To investigate national trends in distal pancreatectomy(DP) through query of three national patient care databases.METHODS:From the Nationwide Inpatient Sample(NIS,2003-2009),the National Surgical Quality Improvement Project(NSQIP,2005-2010),and the Surveillance Epidemiology and End Results(SEER,2003-2009) databases using appropriate diagnostic and procedural codes we identified all patients with a diagnosis of a benign or malignant lesion of the body and/or tail of the pancreas that had undergone a partial or distal pancreatectomy.Utilization of laparoscopy was defined in NIS by the International Classification of Diseases,Ninth Revision correspondent procedure code;and in NSQIP by the exploratory laparoscopy or unlisted procedure current procedural terminology codes.In SEER,patients were identified by the International Classification of Diseases for Oncology,Third Edition diagnosis codes and the SEER Program Code Manual,third edition procedure codes.We analyzed the databases with respect to trends of inpatient outcome metrics,oncologic outcomes,and hospital volumes in patients with lesions of the neck and body of the pancreas that underwent operative resection.RESULTS:NIS,NSQIP and SEER identified 4242,2681 and 11 082 DP resections,respectively.Overall,laparoscopy was utilized in 15%(NIS) and 27%(NSQIP).No significant increase was seen over the course of the study.Resection was performed for malignancy in 59%(NIS) and 66%(NSQIP).Neither patient Body mass index nor comorbidities were associated with operative approach(P = 0.95 and P = 0.96,respectively).Mortality(3% vs 2%,P = 0.05) and reoperation(4% vs 4%,P = 1.0) was not different between laparoscopy and open groups.Overall complications(10% vs 15%,P < 0.001),hospital costs [44 741 dollars,interquartile range(IQR) 28 347-74 114 dollars vs 49 792 dollars,IQR 13 299-73 463,P = 0.02] and hospital length of stay(7 d,IQR 4-11 d vs 7 d,IQR 6-10,P < 0.001) were less when laparoscopy was utilized.One and two year survival after resection for malignancy were unchanged over the course of the study(ductal adenocarinoma 1-year 63.6% and 2-year 35.1%,P = 0.53;intraductal papillary mucinous neoplasm and nueroendocrine 1-year 90% and 2-year 84%,P = 0.25).The majority of resections were performed in teaching hospitals(77% NIS and 85% NSQIP),but minimally invasive surgery(MIS) was not more likely to be used in teaching hospitals(15% vs 14%,P = 0.26).Hospitals in the top decile for volume were more likely to be teaching hospitals than lower volume deciles(88% vs 43%,P < 0.001),but were no more likely to utilize MIS at resection.Complication rate in teaching and the top decile hospitals was not significantly decreased when compared to non-teaching(15% vs 14%,P = 0.72) and lower volume hospitals(14% vs 15%,P = 0.99).No difference was seen in the median number of lymph nodes and lymph node ratio in N1 disease when compared by year(P = 0.17 and P = 0.96,respectively).CONCLUSION:There appears to be an overall underutilization of laparoscopy for DP.Centralization does not appear to be occurring.Survival and lymph node harvest have not changed.

Fast track anesthesia for liver transplantation: Review of the current practice

Historically,patients undergoing liver transplantation were left intubated and extubated in the intensive care unit(ICU)after a period of recovery.Proponents of this practice argued that these patients were critically ill andneed time to be properly optimized from a physiological and pain standpoint prior to extubation.Recently,there has been a growing movement toward early extubation in transplant centers worldwide.Initially fueled by research into early extubation following cardiac surgery,extubation in the operating room or soon after arrival to the ICU,has been shown to be safe with proper patient selection.Additionally,as experience at determining appropriate candidates has improved,some institutions have developed systems to allow select patients to bypass the ICU entirely and be admitted to the surgical ward after transplant.We discuss the history of early extubation and the arguments in favor and against fast track anesthesia.We also described our practice of fast track anesthesia at Mayo Clinic Florida,in which,we extubate approximately 60%of our patients in the operating room and send them to the surgical ward after a period of time in the post anesthesia recovery unit.

Diagnosis and treatment of gastroesophageal reflux disease

Gastroesophageal reflux disease(GERD) is a common disease with a prevalence as high as 10%-20% in the western world. The disease can manifest in various symptoms which can be grouped into typical,atypi-cal and extra-esophageal symptoms. Those with the highest specificity for GERD are acid regurgitation and heartburn. In the absence of alarm symptoms,these symptoms can allow one to make a presumptive diagnosis and initiate empiric therapy. In certain situations,further diagnostic testing is needed to confirm the diagnosis as well as to assess for complications or alternate causes for the symptoms. GERD complications include erosive esophagitis,peptic stricture,Barrett's esophagus,esophageal adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle modification,medical therapy and surgical therapy. Life-style modifications including weight loss and/or head of bed elevation have been shown to improve esophageal pH and/or GERD symptoms. Medical therapy involves acid suppression which can be achieved with antacids,histamine-receptor antagonists or proton-pump inhibitors. Whereas most patients can be effectively managed with medical therapy,others may go on to require anti-reflux surgery after undergoing a proper pre-operative evaluation. The purpose of this review is to discuss the current approach to the diagnosis and treatment of gas-troesophageal reflux disease.

Mitochondrial quality control in amyotrophic lateral sclerosis：towards a common pathway？

Amyotrophic lateral sclerosis（ALS）is a devastating neurodegenerative disorder characterized by loss of upper and lower motor neurons.Different mechanisms contribute to the disease initiation and progression,including mitochondrial dysfunction which has been proposed to be a central determinant in ALS pathogenesis.Indeed,while mitochondrial defects have been mainly described in ALS-linked SOD1 mutants,it is now well established that mitochondria become also dysfunctional in other ALS conditions.In such context,the mitochondrial quality control system allows to restore normal functioning of mitochondria and to prevent cell death,by both eliminating and replacing damaged mitochondrial components or by degrading the entire organelle through mitophagy.Recent evidence shows that ALS-related genes interfere with the mitochondrial quality control system.This review highlights how ineffective mitochondrial quality control may render motor neurons defenseless towards the accumulating mitochondrial damage in ALS.

Progressive familial intrahepatic cholestasis

BACKGROUND:Three types of progressive familial intrahepatic cholestasis(PFIC)have been identified,but their etiologies include unknown mechanisms. DATA SOURCES:A PubMed search on'progressive familial intrahepatic cholestasis'and'PFIC'was performed on the topic,and the relevant articles were reviewed. RESULTS:The etiologies of the three PFIC types still include unknown mechanisms.Especially in PFIC type 1,enterohepatic circulation of bile acid should be considered.Ursodeoxycholic acid,partial external biliary diversion and liver transplantation have been used for the treatment of PFIC patients according to disease course. CONCLUSIONS:Since the etiologies and disease mechanisms of PFIC are still unclear,detailed studies are urgently required. Strategies for more advanced therapies are also needed.These developments in the future are indispensable,especially for PFIC type 1 patients.

Drug eluting biliary stents to decrease stent failure rates:Areview of the literature

Biliary stenting is clinically effective in relieving both malignant and non-malignant obstructions. However, there are high failure rates associated with tumor ingrowth and epithelial overgrowth as well as internally from biofilm development and subsequent clogging. Within the last decade, the use of prophylactic drug eluting stents as a means to reduce stent failure has been investigated. In this review we provide an overview of the current research on drug eluting biliary stents. While there is limited human trial data regarding the clinical benefit of drug eluting biliary stents in preventing stent obstruction, recent research suggests promise regarding their safety and potential efficacy.

Changes in efficiency and resource utilization after increasing experience with double balloon enteroscopy

AIM:To investigate changes in efficiency and resource utilization as a single endoscopist's experience increased with each subsequent 100 double balloon enteroscopy(DBE) procedures.METHODS:We reviewed consecutive DBE procedures performed by a single endoscopist at our center over 4 years.DBE was employed when the clinician deemed the procedure was needed for disease management.The approach(oral,anal or both) was chosen based on suspected location of the target lesion.All DBE was performed in a standard endoscopy room with a portable fluoroscopy unit.Fluoroscopy was used to aid in shortening the small intestine and reducing bowel loops.For oral DBE,measurements were taken from the incisors.For anal DBE,measurements were taken from the anal verge.Enteroscopy continued until the target lesion was reached,until the entire small intestine was examined,or until no further progress was deemed possible.The length of small intestine examined(cm),procedure duration(min),and fluoroscopy time(s) were analyzed for sequential groups of 100 DBE.Sub-groups of diagnostic and therapeutic procedures were analyzed using multivariable linear regression.RESULTS:802 consecutive DBE procedures were analyzed.For oral DBE,median [interquartile range(IQR)] length of small bowel examined was 230.8 cm(range:210-248 cm) and for anal DBE was 143.5 cm(range:100-180 cm).No significant increase in length examined was noted for either the oral or anal approach with advancing position in series.In terms of duration of procedure,the median(IQR) for oral DBE was 86 min(range:71-105 min) and for anal DBE was 81.3 min(range:67-105 min).When comparing by the position in series,there was a significant(P value < 0.001) decrease in procedure duration for both upper and lower procedures with increasing experience.Median(IQR) time of exposure to fluoroscopy for oral DBE was 190 s(114-275) compared to anal DBE which was 196.4 s(312-128).This represented a significant(P value < 0.001) decrease in the amount of fluoroscopy used with increasing position in series.For both oral and anal DBE,fluoroscopy time was reduced by greater than 50% over the course of 802 total procedures performed.Sub-group analysis was conducted on therapeutic and diagnostic groups.Out of 802 procedures,a total of 434 were considered therapeutic.Argon plasma coagulation was by far the most common therapeutic intervention performed.There was no evidence of a difference in length examined or fluoroscopy exposure among oral DBE for diagnostic and therapeutic procedures,P = 0.91 and P = 0.32 respectively.The median(IQR) for length was 235 cm(range:178-280 cm) for diagnostic vs 230 cm(range:180-275 cm) for therapeutic procedures;additionally,fluoroscopy time median(IQR) was 180 s(range:110-295 s) and 162 s(range:102-263 s) for no intervention and intervention.However,there was a significant difference in procedure duration among oral DBE(P < 0.001).The median(IQR) was 80 min(range:60-97 min) and 94 min(range:77-110 min) for diagnostic and therapeutic interventions respectively.CONCLUSION:For a single endoscopist,increased DBE experience with number of performed procedures is associated with increased efficiency and decreased resource utilization.

Simple and reproducible hepatectomy in the mouse using the clip technique

AIM: To investigate the reliability of massive hepatectomy models by using clip techniques. METHODS: We analyzed anatomical findings in 100 mice following massive hepatectomy induced by liver reduction > 70%. The impact of various factors in the different models was also analyzed, including learning curves, operative time, survival curves, and histopathological findings.RESULTS: According to anatomical results, models with 75%, 80%, and 90% hepatectomy produced massive hepatectomy. Learning curves and operative times were most optimal with the clip technique. Each hepatectomy performed using the clip technique produced a reasonable survival curve, and there were no differences in histopathological findings between the suture and clip techniques. CONCLUSION: Massive hepatectomy by the clip technique is simple and can provide reliable and relevant data.

小胶质细胞如何感知和调节神经元活动

小胶质细胞是中枢神经系统中可感知细胞外信号的先天免疫细胞。脑损伤、炎症和病理过程会引起小胶质细胞发生动态的结构反应,改变它们的形态和能动性。小胶质细胞的动态运动被假定是其感知局部变化和参与特定模式反应的关键第一步。除了病理性反应外,小胶质细胞还可以感知和调节神经元活动。本文探讨了在神经元活动降低和活动增高的情况下,允许小胶质细胞感知神经元活动变化的细胞外分子、受体和机制。我们还强调了从生理到病理生理情况,新出现的表明小胶质细胞调节神经元活动的在体研究证据。此外,我们讨论了关于钙信号在小胶质细胞对细胞外环境的反应中的新兴作用。健康或疾病状态,小胶质细胞在监测和影响神经元活动方面的动态功能可能对大脑稳态和神经回路修饰起至关重要的作用。

Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models

AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD).

Fulminant liver failure models with subsequent encephalopathy in the mouse

BACKGROUND:A reliable model of fulminant liver failure (FLF) is urgently required in this research field.This study aimed to develop a murine FLF model.METHODS:We used three groups of male C57BL/6 mice:control,with azoxymethane treatment (AOM group),and with galactosamine and tumor necrosis factor-alpha treatment (Gal+TNF-α group).The effects of body temperature (BT) control on survival in all three groups were investigated Using BT control,we compared the survival,histopathological findings and biochemical/coagulation profiles between the two experimental groups.The effects of hydration on international normalized ratios of prothrombin time (PT INRs) were also checked.Dose-dependent survival curves were constructed for both experimental groups.Neurological behavior was assessed using a coma scale.RESULTS:No unexpected BT effects were seen in the control group.The AOM group,but not the Gal+TNF-α group showed a significant difference in survival curves between those with and without BT care.Histopathological assessment showed consistent FLF findings in both experimental groups with BT care.There were significant differences between the experimental groups in aspartate aminotransferase levels and PT-INRs,and significant differences in PT-INRs between the sufficiently and insufficiently hydrated groups.There were significant differences between FLF models in the duration of each coma stage,with significant differences in stages 1 and 3 as percentages of the disease state (stages 1-4).The two FLF models with BT care showed different survival curves in the dose-dependent survival study.CONCLUSIONS:AOM provides a good FLF model,but requires a specialized environment and careful BT control.Other FLF models may also be useful,depending on the research purpose.Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.

Thrombotic microangiopathy-like disorder after living-donor liver transplantation:A single-center experience in Japan

AIM:To investigate thrombotic microangiopathy (TMA)in liver transplantion,because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS:A total of 206 patients who underwent living-donor liver transplantation (LDLT) were evaluated,and the TMA-like disorder (TMALD) occurred in seven recipients. RESULTS:These TMALD recipients showed poor outcomes in comparison with other 199 recipients. Although two TMALD recipients successfully recovered,the other five recipients finally died despite intensive treatments including repeated plasma exchange (PE) and re-transplantation. Histopathological analysis of liver biopsies after LDLT revealed obvious differences according to the outcomes. Qualitative analysis of antibodies against a disintegrin-like domain and metalloproteinase with thrombospondin type 1 motifs (ADAMTS-13) were negative in all patients. The fragmentation of red cells,the microhemorrhagic macules and the platelet counts were early markers for the suspicion of TMALD after LDLT. Although the absolute values of von Willebrand factor (vWF) and ADAMTS-13 did not necessarily reflect TMALD,the vWF/ADAMTS-13 ratio had a clear diagnostic value in all cases. The establishment of adequate treatments for TMALD,such as PE for ADAMTS-13 replenishment or treatments against inhibitory antibodies,must be decided according to each case. CONCLUSION:The optimal induction of adequate therapies based on early recognition of TMALD by the reliable markers may confer a large advantage for TMALD after LDLT.

Matrix metalloproteinase-9 in the initial injury after hepatectomy in mice

AIM:To investigate the role of matrix metalloproteinase(MMP)-9 in the pathogenesis of postoperative liver failure(PLF) after extended hepatectomy(EH).METHODS:An insufficient volume of the remnant liver(RL) results in higher morbidity and mortality,and a murine model with 80%-hepatectomy was used.All investigations were performed 6 h after EH.Mice were first divided into two groups based on the postoperative course(i.e.,the PLF caused or did not),and MMP-9 expression was measured by Western blotting.The source of MMP-9 was then determined by immunohistological stainings.Tissue inhibitor of metalloproteinase(TIMP)-1 is the endogenous inhibitor of MMP-9,and MMP-9 behavior was assessed by the experiments in wild-type,MMP-9(-/-) and TIMP-1(-/-) mice by Western blotting and gelatin zymography.The behavior of neutrophils was also assessed by immunohistological stainings.An anti-MMP-9 monoclonal antibody and a broadspectrum MMP inhibitor were used to examine the role of MMP-9.RESULTS:Symptomatic mice showed more severe PLF(histopathological assessments:2.97 ± 0.92 vs 0.11 ± 0.08,P < 0.05) and a higher expression of MMP-9(71085 ± 18274 vs 192856 ± 22263,P < 0.01).Nonnative leukocytes appeared to be the main source of MMP-9,because MMP-9 expression corresponding with CD11b positive-cell was observed in the findings of immunohistological stainings.In the histopathological findings,the PLF was improved in MMP-9(-/-) mice(1.65% ± 0.23% vs 0.65% ± 0.19%,P < 0.01) and it was worse in TIMP-1(-/-) mice(1.65% ± 0.23% vs 1.78% ± 0.31%,P < 0.01).Moreover,neutrophil migration was disturbed in MMP-9(-/-) mice in the immunohistological stainings.Two methods of MMP-9 inhibition revealed reduced PLF,and neutrophil migration was strongly disturbed in MMP-9-blocked mice in the histopathological assessments(9.6 ± 1.9 vs 4.2 ± 1.2,P < 0.05,and 9.9 ± 1.5 vs 5.7 ± 1.1,P < 0.05).CONCLUSION:MMP-9 is important for the process of PLF.The initial injury is associated with MMP-9 derived from neutrophils,and MMP-9 blockade reduces PLF.MMP-9 may be a potential target to prevent PLF after EH and to overcome an insufficient RL.

Superior mesenteric venous thrombosis: Endovascular management and outcomes

BACKGROUND Superior mesenteric venous thrombosis(SMVT)is a rare but fatal condition that is typically treated initially with anticoagulation therapy,and if this fails,with endovascular interventions.However,due to its rarity,there are not many studies that have explored the effectiveness of anticoagulation and endovascular therapies in treating SMVT.AIM To evaluate patients diagnosed with SMVT who received endovascular therapy in addition to anticoagulation and report technical and clinical outcomes.METHODS A retrospective analysis of the patients who underwent endovascular treatment for SMVT at Mayo Clinic from 2000-2019 was performed.Technical success was defined as angiographic improvement in SMV flow after intervention.Primary patency was defined as the interval from reestablishing mesenteric venous flow until the first repeat thrombotic event or need for additional intervention.Secondary patency was defined as successful restoration of flow after repeat intervention until rethrombosis or last follow-up.The adverse events were reported through Clavien-Dindo classification.RESULTS Twenty-four patients were included for analysis.The median age at intervention was 60 years(35-74 years)and 16(67%)were men.Nineteen patients presented with acute thrombosis(79.2%)and 5 with chronic thrombosis with acute manifestations(20.8%).The most commonly used endovascular modalities were thrombectomy in 12 patients(50.0%)and catheter-directed thrombolysis in 10 patients(41.7%).Technical success was achieved in 18 patients(75%).The 14-d and 30-d primary patency rates were 88.9%and 83.3%,respectively.Adverse events were reported in two patients(8.3%),one marked as grade IIIB,and 1 death marked as grade V.Five-year overall survival rate was 82%(58%-100%).CONCLUSION Endovascular intervention with anticoagulation appears to be effective for managing SMVT.This treatment combination may be considered as first-line therapy for SMVT management in select patients.

卡莫司他对小鼠急性胰腺炎治疗作用的初步探究

目的探究胰蛋白酶制剂卡莫司他对雨蛙素诱导的急性胰腺炎的作用。方法用雨蛙素腹腔注射法诱导C57BL/6J小鼠建立急性胰腺炎模型,以卡莫司他灌胃法为治疗组,生理盐水灌胃法为对照组。通过观察小鼠行为学的变化和检测各组小鼠血清淀粉酶水平,比较胰腺质量/体质量、胰腺组织病理变化等指标,分析炎症的不同损伤程度及变化。结果治疗组小鼠的胰腺质量/体质量和血清淀粉酶水平均低于非治疗组;非治疗组C57BL/6J小鼠注射雨蛙素后有急性胰腺炎的典型病理组织学改变,而治疗组小鼠则炎症明显改善,水肿及坏死均减轻,炎症细胞浸润减少。治疗组和对照组之间的胰腺质量/体质量和血清淀粉酶水平比较差异均没有统计学意义。结论卡莫司他可通过抑制胰腺蛋白酶活性减轻急性胰腺炎的炎症严重程度。