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1.
Transplantation ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38872242

ABSTRACT

BACKGROUND: Over the past 20 y, robotic surgery has entered nearly all surgical disciplines, aiming to improve patient outcomes. Liver transplantation has evolved with these advancements, and fully robotic liver transplants represent the latest innovation in this field. This study reports on the world's first series of fully robotic recipient liver transplants from robotic living donors, comparing them with matched cases from the standard open transplant approach. METHODS: A case-control study was conducted at our center from August to December 2023. Patient selection criteria for robotic recipient liver transplantation included a Model for End-stage Liver Disease score of ≤25, specific anatomical characteristics, and logistics. A propensity score analysis with a 1:4 matching ratio was used. RESULTS: The study analyzed 10 fully robotic living donor and robotic recipient liver transplant pairs with a median donor age of 29 y and a recipient age of 61 y. The main indication for transplantation was nonalcoholic steatohepatitis (6/10). There was 1 robotic to open conversion, and the median operation time was 10 h, with a median hospital stay of 13 d, shorter than the 18 d in the open group. Three recipients experienced a complication, and there was no mortality. CONCLUSIONS: The first-ever series of fully robotic living donor recipient liver transplants showed encouraging initial results with a markedly reduced hospital stay. The ultimate goal is to refine the technique to offer robotic liver transplants to the majority of recipients, overcoming the current selection criteria. Further research and a planned randomized controlled trial will aim to confirm these results.

2.
Am J Transplant ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38723867

ABSTRACT

Minimally invasive donor hepatectomy is an emerging surgical technique in living donor liver transplantation (LDLT). We examined outcomes across open, laparoscopic, and robotic LDLT using a prospective registry. We analyzed 3448 cases (1724 donor-recipient pairs) from January 2011 to March 2023 (NCT06062706). Among donors, 520 (30%) were female. Adult-to-adult LDLT comprised 1061 (62%) cases. A total of 646 (37%) of the donors underwent open, 165 (10%) laparoscopic, and 913 (53%) robotic hepatectomies. Primary outcomes: donor overall morbidity was 4% (35/903) for robotic, 8% (13/165) laparoscopic, and 16% (106/646) open (P < .001) procedures. Pediatric and adult recipient mortality was similar among the 3 donor hepatectomy approaches: robotic 1.5% and 7.0%, compared with 2.3% and 8.3% laparoscopic, and 1.6% and 5.5% for open donor surgery, respectively (P = .802, P = .564). Secondary outcomes: pediatric and adult recipients major morbidity after robotic hepatectomy was 15% and 23%, compared with 25% and 44% for laparoscopic surgery and 19% and 31% for open surgery, respectively (P = .033, P < .001). Graft and recipient 5-year survival were 90% and 93% for pediatrics and 79% and 80% for adults, respectively. In conclusion, robotic LDLT was associated with superior outcomes when compared with the laparoscopic and open approaches. Both donors and, for the first time reported, recipients benefitted from lower morbidity rates in robotic surgery, emphasizing its potential for further advancing this field.

3.
Int J Surg ; 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38573086

ABSTRACT

BACKGROUND: Living donor liver transplantation (LDLT) is the best option for end-stage liver disease patients. Older potential donors are increasingly requesting donation. This study aims to systematically assess the differences in donor peri- and postoperative complications, mortality, and quality of life (QoL) between younger and older living liver donors. MATERIALS AND METHODS: Embase, Medline, and Cochrane were searched for studies published between 2002 and June 2, 2023. Donor complications, major complications, biliary complications, mortality, and QoL were systematically reviewed, including meta-analyses. Donors aged >50 years were considered older. The methodological quality of the studies was assessed using the Newcastle-Ottawa quality assessment Scale. RESULTS: The search yielded 8,320 studies, of which 17 were included. The risk ratio (RR) for complications in younger donors was 1.08 [0.90, 1.31] (P=0.41). RRs for major complications in younger donors were 0.98 [0.64, 1.48] and 0.89 [0.50, 1.57] using Clavien-Dindo ≥III and ≥IIIb as major complication. RR for biliary complications in younger donors was 1.59 [1.05, 2.42] (P=0.03). Mortality rate in younger donors was 47/13,238 (0.4%) and in older donors 13/989 (1.3%). Physical component summary (PCS) in younger donors was 51.87 and in older donors 51.29. Mental component summary (MCS) in younger donors was 52.93 and in older donors 55.40. CONCLUSION: Older donors do not have a higher complication or mortality rate than younger donors after LDLT. They may have a lower rate of biliary complications. Additionally, older donors have a similar QoL after LDLT. With careful selection, older donors can be included in screening programs for living liver donation to expand the donor pool.

4.
Am J Transplant ; 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38428639

ABSTRACT

In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (odds ratio, [OR] 1.8), Roux-en-Y hepaticojejunostomy (OR, 1.4), and a history of major abdominal surgery (OR, 1.4). For biliary anastomotic strictures, risk factors were ABO incompatibility (OR, 1.4), blood loss >1 L (OR, 1.4), and previous abdominal surgery (OR, 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher comprehensive complication index scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival, despite the availability of effective treatments.

5.
J Am Heart Assoc ; 13(4): e032641, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38348796

ABSTRACT

BACKGROUND: Increasing arterial stiffness is a prominent feature of the aging cardiovascular system. Arterial stiffening leads to fundamental alterations in central hemodynamics with widespread detrimental implications for organ function resulting in significant morbidity and death, and specific therapies to address the underlying age-related structural arterial remodeling remain elusive. The present study investigates the potential of the recently clinically available dual angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (LCZ696) to counteract age-related arterial fibrotic remodeling and stiffening in 1-year-old mice. METHODS AND RESULTS: Treatment of in 1-year-old mice with ARNI (sacubitril/valsartan), in contrast to angiotensin receptor blocker monotherapy (valsartan) and vehicle treatment (controls), significantly decreases structural aortic stiffness (as measured by in vivo pulse-wave velocity and ex vivo aortic pressure myography). This phenomenon appears, at least partly, independent of (indirect) blood pressure effects and may be related to a direct antifibrotic interference with aortic smooth muscle cell collagen production. Furthermore, we find aortic remodeling and destiffening due to ARNI treatment to be associated with improved parameters of cardiac diastolic function in aged mice. CONCLUSIONS: This study provides preclinical mechanistic evidence indicating that ARNI-based interventions may counteract age-related arterial stiffening and may therefore be further investigated as a promising strategy to improve cardiovascular outcomes in the elderly.


Subject(s)
Aminobutyrates , Heart Failure , Vascular Stiffness , Humans , Aged , Middle Aged , Mice , Animals , Infant , Neprilysin , Angiotensins , Tetrazoles/therapeutic use , Receptors, Angiotensin , Valsartan/therapeutic use , Biphenyl Compounds/therapeutic use , Drug Combinations , Angiotensin Receptor Antagonists/therapeutic use , Stroke Volume
6.
Article in English | MEDLINE | ID: mdl-38317745

ABSTRACT

Background: Liver transplantation (LT) is a therapeutic option in multiple inherited metabolic diseases (IMDs), including methylmalonic acidemia (MMA), as LT reduces the risk of acute metabolic decompensations and long-term complications associated with these diseases. In certain IMDs, such as maple syrup urine disease (MSUD), domino liver transplant (DLT) is an accepted and safe method which expands the donor pool. However, only one adult case of DLT using an MMA donor liver has been reported; outcome and safety are still unknown and questioned. Case Description: In this case report, we describe our experience with DLT using MMA livers. Two adult MMA patients underwent living donor liver transplant (LDLT); their MMA livers were consecutively transplanted into two patients on the liver transplant waiting list who had limited chance of receiving a liver transplant in the short term due to their low model for end-stage liver disease (MELD) scores. No severe peri- or postoperative complications occurred, however the recipients of the MMA livers biochemically now have mild MMA. Conclusions: DLT using MMA grafts is a feasible strategy to treat end-stage liver disease and expand the donor organ pool. However, the recipient of the MMA domino liver may develop mild MMA which could affect quality of life, and long-term safety remains unclear. Further long-term of outcomes for domino recipients of MMA livers, focusing on quality of life and any metabolic complications of transplantation are needed to better define the risks and benefits.

7.
Cardiovasc Res ; 120(4): 417-432, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-37976180

ABSTRACT

AIMS: Abdominal aortic aneurysm (AAA) is a highly lethal disease with progressive dilatation of the abdominal aorta accompanied by degradation and remodelling of the vessel wall due to chronic inflammation. Platelets play an important role in cardiovascular diseases, but their role in AAA is poorly understood. METHODS AND RESULTS: The present study revealed that platelets play a crucial role in promoting AAA through modulation of inflammation and degradation of the extracellular matrix (ECM). They are responsible for the up-regulation of SPP1 (osteopontin, OPN) gene expression in macrophages and aortic tissue, which triggers inflammation and remodelling and also platelet adhesion and migration into the abdominal aortic wall and the intraluminal thrombus (ILT). Further, enhanced platelet activation and pro-coagulant activity result in elevated gene expression of various cytokines, Mmp9 and Col1a1 in macrophages and Il-6 and Mmp9 in fibroblasts. Enhanced platelet activation and pro-coagulant activity were also detected in AAA patients. Further, we detected platelets and OPN in the vessel wall and in the ILT of patients who underwent open repair of AAA. Platelet depletion in experimental murine AAA reduced inflammation and ECM remodelling, with reduced elastin fragmentation and aortic diameter expansion. Of note, OPN co-localized with platelets, suggesting a potential role of OPN for the recruitment of platelets into the ILT and the aortic wall. CONCLUSION: In conclusion, our data strongly support the potential relevance of anti-platelet therapy to reduce AAA progression and rupture in AAA patients.


Subject(s)
Aortic Aneurysm, Abdominal , Matrix Metalloproteinase 9 , Humans , Animals , Mice , Matrix Metalloproteinase 9/metabolism , Osteopontin/genetics , Osteopontin/metabolism , Aortic Aneurysm, Abdominal/metabolism , Aorta, Abdominal/metabolism , Inflammation/metabolism , Macrophages/metabolism , Fibroblasts/metabolism
8.
Int J Surg Case Rep ; 112: 108981, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37883875

ABSTRACT

INTRODUCTION: Outflow obstruction is a rare but critical vascular complication in liver transplantation, which may lead to graft loss and mortality. We report a case of caval vein outflow obstruction due to retrohepatic compression after living donor liver transplantation (LDLT), which was managed by temporary implantation of a vena cava filter. PRESENTATION OF CASE: A 63-year-old male with end stage liver disease presented with caval vein outflow obstruction and massive ascites 12 days after right lobe LDLT. We opted for a minimally invasive approach and implanted a vena cava filter at the compressed site through transjugular route. The patient's ascites drainage significantly decreased and graft function maintained stable after the intervention. On day 50 posttransplant, the filter was successfully removed and the patient was discharged without complications. DISCUSSION: Outflow obstruction after liver transplantation can result from anastomotic stenosis, graft size mismatch, thrombosis or compression of the outflow tract. Various management strategies have been employed both peri- and posttransplant, ranging from surgical interventions to minimally-invasive techniques. The treatment strategy should be tailored to the individual case, considering the timing of presentation and the specific cause for the obstruction. CONCLUSION: We successfully managed a case of compressive outflow obstruction by temporary implantation of a vena cava filter after LDLT. The vena cava filter was safely removed under angiography.

9.
Ann Surg ; 278(5): 798-806, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37477016

ABSTRACT

OBJECTIVE: To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT). BACKGROUND: LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments. METHODS: Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016-2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers' medians. RESULTS: Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI ® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI ® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI ® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%). CONCLUSIONS: Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide.


Subject(s)
End Stage Liver Disease , Liver Diseases , Liver Transplantation , Thrombosis , Adult , Humans , Living Donors , Benchmarking , End Stage Liver Disease/surgery , Treatment Outcome , Retrospective Studies , Severity of Illness Index , Liver Diseases/complications , Graft Survival
10.
J Endovasc Ther ; : 15266028231169178, 2023 May 08.
Article in English | MEDLINE | ID: mdl-37154344

ABSTRACT

PURPOSE: Endovascular aortic repair (EVAR) is the method of choice for most abdominal aortic aneurysm (AAA) patients requiring intervention. However, chronic aortic neck dilatation (AND) following EVAR progressively weakens the structural seal between vessel and endograft and compromises long-term results of the therapy. This experimental ex vivo study seeks to investigate mechanisms of AND. MATERIALS AND METHODS: Porcine abdominal aortas (n=20) were harvested from slaughterhouse pigs and connected to a mock circulation. A commercially available endograft was implanted (n=10) or aortas were left untreated as controls (n=10). Vascular circumferential strain was assessed via ultrasound in defined aortic segments as a parameter of aortic stiffness. Histology and aortic gene expression analysis were performed to investigate potential changes of aortic wall structure and molecular differences due to endograft implantation. RESULTS: We found that endograft implantation acutely induces a significant stiffness gradient directly at the interface between stented and unstented aortic segments under pulsatile pressure. Comparing stented aortas with unstented controls, we detected increased aortic expression levels of inflammatory cytokines (Il6 and Ccl2) and matrix metalloproteinases (Mmp2 and Mmp9) after 6 hours of pulsatile pressurization. This effect, however, was abolished when repeating the same experiment under 6 hours of static pressure. CONCLUSIONS: We identified endograft-induced aortic stiffness gradients as an early trigger of inflammatory aortic remodeling processes that might promote AND. These results highlight the importance of adequate endograft designs to minimize vascular stiffness gradients and forestall late complications, such as AND. CLINICAL IMPACT: AND may compromise the long-term results following endovascular aortic repair. However, the mechanisms behind the underlying detrimental aortic remodeling are still unclear. In this study we find that endograft-induced aortic stiffness gradients induce an inflammatory aortic remodeling response consistent with AND. This novel pathomechanistic insight may guide the design of new aortic endografts that minimize vascular stiffness gradients and forestall late complications such as AND.

11.
HPB (Oxford) ; 25(8): 863-871, 2023 08.
Article in English | MEDLINE | ID: mdl-36935291

ABSTRACT

INTRODUCTION: To this day, a discrepancy exists between donor liver demand and supply. Domino liver transplantation (DLT) can contribute to increasing the number of donor livers available for transplantation. METHODS: The design of this systematic review was based on the Preferred Reporting Items for Systematic Reviews (PRISMA). A qualitative analysis of included studies was performed. Primary outcomes were mortality and peri- and postoperative complications related to DLT. RESULTS: Twelve studies met the inclusion criteria. All included studies showed that DLT outcomes were comparable to outcomes of deceased donor liver transplantation (DDLT) in terms of mortality and complications. One-year patient survival rate ranged from 66.7% to 100%. Re-transplantation rate varied from 0 to 12.5%. Most frequent complications were related to biliary (3.7%-37.5%), hepatic artery (1.6%-9.1%), portal vein (12.5-33.3%) and hepatic vein events (1.6%), recurrence of domino donor disease (3.3%-17.4%) and graft rejection (16.7%-37.7%). The quality of the evidence was rated as moderate according to the Newcastle-Ottawa scale (NOS). CONCLUSION: DLT outcomes were similar to DDLT in terms of mortality and complications. Even though DLT will not solve the entire problem of organ shortage, transplant programs should always consider using this tool to maximize the availability of liver grafts.


Subject(s)
Liver Transplantation , Tissue and Organ Procurement , Humans , Living Donors , Liver Transplantation/adverse effects , Hepatic Artery/surgery , Postoperative Complications/etiology , Graft Survival , Treatment Outcome , Retrospective Studies
12.
Arch Med Sci ; 19(1): 194-202, 2023.
Article in English | MEDLINE | ID: mdl-36817681

ABSTRACT

Introduction: Oxidized regenerated cellulose-based (ORC - TABOTAMP), oxidized non-regenerated cellulose-based (ONRC - RESORBA CELL), and gelatin-based (GELA - GELITA TUFT-IT) hemostats are commonly used in surgery. However, their impact on the wound healing process remains largely unexplored. We here assess time-dependent effects of exposure to these hemostats on fibroblast-related wound healing processes. Material and methods: Hemostats were applied to fibroblast cell cultures for 5-10 (short-), 30 and 60 min (intermediate-) and 24 h (long-term). Representative images of the hemostat degradation process were obtained, and the pH value was measured. Cell viability, apoptosis and migration were analyzed after the above exposure times at 3, 6 and 24 h follow-up. Protein levels for tumor necrosis factor α (TNF-α) and transforming-growth factor ß (TGF-ß) were assessed. Results: ORC and ONRC reduced pH values during degradation, while GELA proved to be pH-neutral. Hemostat structural integrity was prolonged for GELA (vs. ORC and ONRC). TGF-ß and TNF-α levels were reduced for ORC and ONRC (vs. GELA and control) (p < 0.05). Further, exposure of ORC and ONRC for longer than 5-10 min reduced cell viability vs. GELA and control at 3 h post-exposure (p < 0.05). Similarly, cell migration was impaired with ORC and ONRC exposure longer than 60 min at 24 h follow-up (p < 0.05). Conclusions: Short-term exposure to ORC and ONRC impairs relevant wound healing-related processes in fibroblasts, and alters protein levels of key mediating cytokines. GELA does not show similar effects. We conclude that GELA may be preferred over ORC and ONRC over short-, intermediate- and long-term exposures. Future validation of the clinical relevance is warranted.

13.
EBioMedicine ; 88: 104431, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36608526

ABSTRACT

BACKGROUND: Ischemia of the bile duct is a common feature in liver disease and transplantation, which represents a major cause of morbidity and mortality, especially after liver transplantation. Detailed knowledge of its pathogenesis remains incomplete due to the lack of appropriate in vitro models. METHODS: To recapitulate biliary damage induced by ischemia and reperfusion in vitro, human intrahepatic cholangiocyte organoids (ICOs) were grown at low oxygen levels of 1% up to 72 h, followed by re-oxygenation at normal levels. FINDINGS: ICOs stressed by ischemia and subsequent re-oxygenation represented the dynamic change in biliary cell proliferation, upregulation of epithelial-mesenchymal transition (EMT)-associated markers, and the evocation of phase-dependent cell death programs similar to what is described in patients. Clinical-grade alpha-1 antitrypsin was identified as a potent inhibitor of both ischemia-induced apoptosis and necroptosis. INTERPRETATION: These findings demonstrate that ICOs recapitulate ischemic cholangiopathy in vitro and enable drug assessment studies for the discovery of new therapeutics for ischemic cholangiopathies. FUNDING: Dutch Digestive FoundationMLDS D16-26; TKI-LSH (Topconsortium Kennis en Innovatie-Life Sciences & Health) grant RELOAD, EMC-LSH19002; Medical Delta program "Regenerative Medicine 4D"; China Scholarship Council No. 201706230252.


Subject(s)
Bile Ducts , Ischemia , Humans , Ischemia/metabolism , Apoptosis , Epithelial Cells , Organoids
14.
J Biomech Eng ; 144(1)2022 01 01.
Article in English | MEDLINE | ID: mdl-34244728

ABSTRACT

Nicotine exposure is a major risk factor for several cardiovascular diseases. Although the deleterious effects of nicotine on aortic remodeling processes have been studied to some extent, the biophysical consequences are not fully elucidated. In this investigation, we applied quasi-static and dynamic loading to quantify ways in which exposure to nicotine affects the mechanical behavior of murine arterial tissue. Segments of thoracic aortas from C57BL/6 mice exposed to 25 mg/kg/day of subcutaneous nicotine for 28 days were subjected to uniaxial tensile loading in an open-circumferential configuration. Comparing aorta segments from nicotine-treated mice relative to an equal number of control counterparts, stiffness in the circumferential direction was nearly twofold higher (377 kPa ± 165 kPa versus 191 kPa ± 65 kPa, n = 5, p = 0.03) at 50% strain. Using a degradative power-law fit to fatigue data at supraphysiological loading, we observed that nicotine-treated aortas exhibited significantly higher peak stress, greater loss of tension, and wider oscillation band than control aortas (p ≤ 0.01 for all three variables). Compared to simple stress relaxation tests, fatigue cycling is shown to be more sensitive and versatile in discerning nicotine-induced changes in mechanical behavior over many cycles. Supraphysiological fatigue cycling thus may have broader potential to reveal subtle changes in vascular mechanics caused by other exogenous toxins or pathological conditions.


Subject(s)
Vascular Stiffness , Animals , Aorta, Thoracic , Mice , Mice, Inbred C57BL , Nicotine/pharmacology , Stress, Mechanical
15.
JVS Vasc Sci ; 2: 219-234, 2021.
Article in English | MEDLINE | ID: mdl-34778850

ABSTRACT

INTRODUCTION: Abdominal aortic aneurysm (AAA) is a condition that has considerable socioeconomic impact and an eventual rupture is associated with high mortality and morbidity. Despite decades of research, surgical repair remains the treatment of choice and no medical therapy is currently available. Animal models and, in particular, murine models, of AAA are a vital tool for experimental in vivo research. However, each of the different models has individual limitations and provide only partial mimicry of human disease. This narrative review addresses the translational potential of the available mouse models, highlighting unanswered questions from a clinical perspective. It is based on a thorough presentation of the available literature and more than a decade of personal experience, with most of the available models in experimental and translational AAA research. RESULTS: From all the models published, only the four inducible models, namely the angiotensin II model (AngII), the porcine pancreatic elastase perfusion model (PPE), the external periadventitial elastase application (ePPE), and the CaCl2 model have been widely used by different independent research groups. Although the angiotensin II model provides features of dissection and aneurysm formation, the PPE model shows reliable features of human AAA, especially beyond day 7 after induction, but remains technically challenging. The translational value of ePPE as a model and the combination with ß-aminopropionitrile to induce rupture and intraluminal thrombus formation is promising, but warrants further mechanistic insights. Finally, the external CaCl2 application is known to produce inflammatory vascular wall thickening. Unmet translational research questions include the origin of AAA development, monitoring aneurysm growth, gender issues, and novel surgical therapies as well as novel nonsurgical therapies. CONCLUSION: New imaging techniques, experimental therapeutic alternatives, and endovascular treatment options provide a plethora of research topics to strengthen the individual features of currently available mouse models, creating the possibility of shedding new light on translational research questions.

16.
Front Cardiovasc Med ; 8: 710603, 2021.
Article in English | MEDLINE | ID: mdl-34485410

ABSTRACT

Objective: Thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD) aims to induce false lumen (FL) thrombosis by sealing intimal tears between the true (TL) and the FL, and blocking the inflow into the FL. Incomplete thrombosis of the FL is correlated with poor clinical outcome. We hypothesize that the number of major and minor branches arising from the FL affects FL patency and may negatively influence TEVAR induced FL thrombosis. Methods: Computed tomography (CT)-scans from 89 patients diagnosed with TBAD [best medical treatment (BMT) n = 52, TEVAR n = 37] from two high-volume vascular surgery centers were analyzed retrospectively. Analysis included evaluation of the FL patency status, the number, location and size of intimal tears, and the presence of minor and major side branches originating from the FL. Multiple regression analysis was conducted to evaluate obtained parameters as predictors for FL thrombosis status. Results: In univariate analysis, the strongest correlation for FL patency was found for the number of major (R = 0.79) and minor (R = 0.86) side branches originating from the FL. When applying a multiple linear regression model, the number of major (normalized beta 0.37; P < 0.001) and minor (normalized beta 0.41; P < 0.01) side branches arising from the FL were valid predictors for the axial length of the patent and non-patent FL, and additionally determined the length of the patent FL at 12-month follow-up in patients that underwent TEVAR. Conclusions: Our data suggest that the number of minor side branches that originate from the FL in TBAD is an important determinant of FL patency, to a greater degree than previously assumed.

17.
Circ Rep ; 3(3): 170-177, 2021 Feb 17.
Article in English | MEDLINE | ID: mdl-33738350

ABSTRACT

Background: Tight junction (TJ) disruption and dysfunction are involved in the progression of arteriosclerosis. miR-501-3p regulates endothelial TJ protein-1, resulting in TJ disruption. Because exosomal microRNAs can travel to distant tissues and influence cell behavior, patients with elevated miR-501-3p may experience accelerated vascular disease progression secondary to miR-501-3p-induced reductions in TJ. This study investigated whether plasma exosome miR-501-3p levels are associated with vascular stiffness, an indicator for arteriosclerotic changes. Methods and Results: Fifty-one subjects (mean [±SD] age 70±8 years, 37% male) enrolled in a medical checkup program were recruited to the study. Brachial-ankle arterial pulse wave velocity (baPWV) and plasma exosome miR-501-3p expression were measured. Patients were divided into 2 groups depending on whether their miR-501-3p ∆Ct values were above ("High"; n=24) or below ("Low"; n=27) the cut-off levels determined by receiver operating characteristic (ROC) curve analysis. Median (interquartile range) baPWV levels were significantly higher in the miR-501-3p High than Low group (1,664 [1,496-1,859] vs. 1,450 [1,353-1,686] cm/s, respectively; P<0.05). Multivariate logistic regression analysis showed a significant association between increased baPWV and High miR-501-3p expression (odds ratio 4.66). At follow-up visits (mean 62 months later), baPWV remained significantly higher in the miR-501-3p High than Low group (1,830 [1,624-2,056] vs. 1,620 [1,377-1,816] cm/s, respectively; P<0.05). Conclusions: High expression levels of exosome miR-501-3p contribute to arteriosclerotic changes.

18.
Transplant Rev (Orlando) ; 34(1): 100510, 2020 01.
Article in English | MEDLINE | ID: mdl-31495539

ABSTRACT

The clinical significance of the right posterior segment (RPS) graft in living donor liver transplantation (LDLT) is unknown because of its limited use and technical concerns. This study aimed to review published studies investigating outcomes of RPS grafts. The systematic literature search was conducted to retrieve data from Embase, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar. Among the 388 articles, six retrospective studies from Asian countries were included. The overall incidences of major and minor complications after RPS graft procurement were 5.6% and 34.6%, respectively and no donor deaths were reported. RPS graft recipients had the following postoperative complications: overall mortality rate, 14.5%; bile leakage, 8.7%, biliary stenosis, 18.8%, hepatic artery thrombosis, 8.7%, and liver re-transplantation, 2.9%. The RPS graft can be considered as an option for a living liver graft respecting donor safety under strict selection criteria and surgical strategy. The precise evaluation and understanding of anatomical variations and volumetric analyses is critical for selecting donors and planning the surgical strategy in the RPS grafts procurement. The RPS grafts procurement requires carefully dissection of the hepatic artery and portal vein, safely confirmation of the bile duct, and precisely parenchymal transection. However, further experience is needed to clarify the significance of the RPS graft in LDLT. The special technical requirements should limit this donor procedure to centers with a high level of experience in LDLT.


Subject(s)
Allografts/surgery , Bile Ducts/surgery , Liver Transplantation , Liver/surgery , Living Donors , Postoperative Complications/epidemiology , Allografts/anatomy & histology , Humans , Liver/anatomy & histology , Postoperative Complications/mortality , Treatment Outcome
19.
J Pharmacol Sci ; 140(1): 106-108, 2019 May.
Article in English | MEDLINE | ID: mdl-31133404

ABSTRACT

We investigated the effects of variations in anesthesia exposure time prior to conducting anxiety response behavioral testing in sham controls from an experimental murine model. The staying time in the center area of the Open Field test in the "long exposure" group was significantly decreased compared to that of the "short exposure" group. Significant correlation was found between anesthesia time and the duration of staying time in the center area. We conclude that anesthesia time may have a significant impact on behavioral anxiety testing in this context, and advise careful control of this parameter in protocol optimization in related surgical animal models.


Subject(s)
Anesthesia, Inhalation , Anesthetics, Inhalation/pharmacology , Anxiety , Behavior, Animal/drug effects , Isoflurane/pharmacology , Animals , Male , Mice, Inbred C57BL , Models, Anatomic , Models, Animal , Time Factors
20.
J Vasc Surg Venous Lymphat Disord ; 7(3): 333-343.e2, 2019 May.
Article in English | MEDLINE | ID: mdl-30853561

ABSTRACT

OBJECTIVE: Inferior vena cava thrombosis is rare, but patients are at high risk for development of a post-thrombotic syndrome (PTS) in the long term. Surgical approaches include indirect transfemoral venous thrombectomy (iTFVT) and direct open venous thrombectomy (dOVT). This study reports patient outcomes after iTFVT and dOVT for inferior vena cava thrombosis covering a 25-year follow-up period. METHODS: The study period was from January 1, 1982, to December 31, 2013. Data were retrieved from archived medical records, and patients were invited for a detailed phlebologic follow-up examination (DPFE). Health-related quality of life was assessed with the 36-Item Short Form Health Survey questionnaire. Patient survival, patency rates, and freedom from PTS were calculated using Kaplan-Meier estimation with log-rank testing. The χ2 test with Yates continuity correction and logistic regression analysis were applied to identify associations between risk factors or coagulation disorders, mortality, and PTS. RESULTS: Complete medical records were available for 152 patients. Patients' 5-year survival was 91% ± 3%, and 5-year primary and secondary patency rates were 80% ± 3% and 94% ± 2%. Freedom from PTS after 25 years was 84% ± 6%. No differences for patient survival, patency rates, or freedom from PTS were identified between iTFVT, dOVT, and a combination of both procedures. Antithrombin III deficiency was the most common coagulation disorder, and patients' physical function and social function were impaired compared with those found in German normative data (P < .05). No risk factor or coagulation disorder was associated with survival or PTS. CONCLUSIONS: Open surgical venous thrombectomy is safe and delivers satisfying short- and long-term outcomes compared with endovascular approaches. It remains valuable for patients who are not eligible for other interventional therapies.


Subject(s)
Endovascular Procedures , Thrombectomy , Vena Cava, Inferior/surgery , Venous Thrombosis/surgery , Adult , Endovascular Procedures/adverse effects , Endovascular Procedures/mortality , Female , Humans , Male , Middle Aged , Postthrombotic Syndrome/etiology , Progression-Free Survival , Quality of Life , Retrospective Studies , Risk Factors , Thrombectomy/adverse effects , Thrombectomy/mortality , Time Factors , Vascular Patency , Vena Cava, Inferior/physiopathology , Venous Thrombosis/complications , Venous Thrombosis/mortality , Venous Thrombosis/physiopathology
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