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Dahl Salt-Sensitive (DSS) rats develop heart failure with preserved ejection fraction (HFpEF) when fed a high-salt (8 % NaCl) diet. Hypertension-induced inflammation and subsequent ventricular fibrosis are believed to underlie the development of HFpEF. We investigated the role of diet modification in the progression of HFpEF using male DSS rats, fed either a high-salt diet from7 weeks of age to induce HFpEF, ora normal-salt (0.3% NaCl) diet as controls. After echocardiographic confirmation of diastolic dysfunction at 14-15 weeks of age along with HF manifestations, the HFpEF rats were randomly assigned to either continue a high-salt diet or switch to a normal-salt diet for an additional 4 weeks. HFpEF rats with diet modification showed improved diastolic function (reduced E/E' ratio in echocardiogram), increased functional capacity (increased treadmill exercise distance), and reduced pulmonary congestions (lung/body weight ratio), compared to high-salt-fed HFpEF rats. Systolic blood pressure remained high (~200 mmHg), and ventricular hypertrophy remained unchanged. Ventricular arrhythmia inducibility (100 % inducible) and corrected QT interval (on ECG) did not change in HFpEF rats after diet modification. HFpEF rats with diet modification showed prolonged survival and reduced ventricular fibrosis (Masson's trichrome staining) compared to high-salt-fed HFpEF rats. Hence, the modification of diet (from high-salt to normal-salt diet) reversed HFpEF phenotypes without affecting blood pressure or ventricular hypertrophy.
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Identification and proteomic characterization of rare cell types within complex organ-derived cell mixtures is best accomplished by label-free quantitative mass spectrometry. High throughput is required to rapidly survey hundreds to thousands of individual cells to adequately represent rare populations. Here we present parallelized nanoflow dual-trap single-column liquid chromatography (nanoDTSC) operating at 15 min of total run time per cell with peptides quantified over 11.5 min using standard commercial components, thus offering an accessible and efficient LC solution to analyze 96 single cells per day. At this throughput, nanoDTSC quantified over 1000 proteins in individual cardiomyocytes and heterogeneous populations of single cells from the aorta.
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Proteínas , Proteómica , Proteómica/métodos , Cromatografía Liquida/métodos , Proteínas/química , Péptidos/química , Espectrometría de Masas/métodosRESUMEN
Artificial intelligence (AI) has been developed for echocardiography1-3, although it has not yet been tested with blinding and randomization. Here we designed a blinded, randomized non-inferiority clinical trial (ClinicalTrials.gov ID: NCT05140642; no outside funding) of AI versus sonographer initial assessment of left ventricular ejection fraction (LVEF) to evaluate the impact of AI in the interpretation workflow. The primary end point was the change in the LVEF between initial AI or sonographer assessment and final cardiologist assessment, evaluated by the proportion of studies with substantial change (more than 5% change). From 3,769 echocardiographic studies screened, 274 studies were excluded owing to poor image quality. The proportion of studies substantially changed was 16.8% in the AI group and 27.2% in the sonographer group (difference of -10.4%, 95% confidence interval: -13.2% to -7.7%, P < 0.001 for non-inferiority, P < 0.001 for superiority). The mean absolute difference between final cardiologist assessment and independent previous cardiologist assessment was 6.29% in the AI group and 7.23% in the sonographer group (difference of -0.96%, 95% confidence interval: -1.34% to -0.54%, P < 0.001 for superiority). The AI-guided workflow saved time for both sonographers and cardiologists, and cardiologists were not able to distinguish between the initial assessments by AI versus the sonographer (blinding index of 0.088). For patients undergoing echocardiographic quantification of cardiac function, initial assessment of LVEF by AI was non-inferior to assessment by sonographers.
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Inteligencia Artificial , Cardiólogos , Ecocardiografía , Pruebas de Función Cardíaca , Humanos , Inteligencia Artificial/normas , Ecocardiografía/métodos , Ecocardiografía/normas , Volumen Sistólico , Función Ventricular Izquierda , Método Simple Ciego , Flujo de Trabajo , Reproducibilidad de los Resultados , Pruebas de Función Cardíaca/métodos , Pruebas de Función Cardíaca/normasRESUMEN
BACKGROUND: Atrial fibrillation (AF) is a common comorbidity in heart failure with preserved ejection fraction (HFpEF) patients. To date, treatments for HFpEF-related AF have been limited to anti-arrhythmic drugs and ablation. Here we examined the effects of immortalized cardiosphere-derived extracellular vesicles (imCDCevs) in rats with HFpEF. OBJECTIVES: This study sought to investigate the mechanisms of AF in HFpEF and probe the potential therapeutic efficacy of imCDCevs in HFpEF-related AF. METHODS: Dahl salt-sensitive rats were fed a high-salt diet for 7 weeks to induce HFpEF and randomized to receive imCDCevs (n = 18) or vehicle intravenously (n = 14). Rats fed a normal-salt diet were used as control animals (n = 26). A comprehensive characterization of atrial remodeling was conducted using functional and molecular techniques. RESULTS: HFpEF-verified animals showed significantly higher AF inducibility (84%) compared with control animals (15%). These changes were associated with prolonged action potential duration, slowed conduction velocity (connexin 43 lateralization), and fibrotic remodeling in the left atrium of HFpEF compared with control animals. ImCDCevs reversed adverse electrical remodeling (restoration of action potential duration to control levels and reorganization of connexin 43) and reduced AF inducibility (33%). In addition, fibrosis, inflammation, and oxidative stress, which are major pathological AF drivers, were markedly attenuated in imCDCevs-treated animals. Importantly, these effects occurred without changes in blood pressure and diastolic function. CONCLUSIONS: Thus, imCDCevs attenuated adverse remodeling, and prevented AF in a rat model of HFpEF.
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Fibrilación Atrial , Remodelación Atrial , Vesículas Extracelulares , Insuficiencia Cardíaca , Animales , Ratas , Conexina 43 , Ratas Endogámicas Dahl , Volumen SistólicoRESUMEN
BACKGROUND: Living donor liver transplantation (LDLT) is one of the most technically demanding and complicated procedures. However, unlike deceased donor liver transplantation, there is no suitable animal model for practicing LDLT. Herein, we propose a new liver segmentation method and a feasible pig LDLT model for practicing for LDLT in humans. METHODS: Four Landrace pigs weighing 25, 25, 27, and 28 kg were used as donors and recipients to establish a partial liver transplantation model. Partial liver transplantation was performed using a right liver and a left liver, respectively, based on a new segmentation system compatible with that of humans. RESULTS: We established a new segmentation system for porcine liver transplantation and a partial liver transplantation model. For right liver transplantation, 91 and 142 min were required to operate on the donor and recipient, respectively; for left liver transplantation, 57 and 104 min were required to operate on the donor and recipient, respectively. All pigs that underwent partial liver transplantation remained alive until the operation was completed. CONCLUSIONS: It is expected that this new pig model based on the new segmentation system will be suitable as an educational tool for LDLT training and will replace the existing animal models for partial liver transplantation.
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Trasplante de Hígado , Humanos , Animales , Porcinos , Trasplante de Hígado/métodos , Donadores Vivos , Hígado/cirugía , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
Identification and proteomic characterization of rare cell types within complex organ derived cell mixtures is best accomplished by label-free quantitative mass spectrometry. High throughput is required to rapidly survey hundreds to thousands of individual cells to adequately represent rare populations. Here we present parallelized nanoflow dual-trap single-column liquid chromatography (nanoDTSC) operating at 15 minutes of total run time per cell with peptides quantified over 11.5 minutes using standard commercial components, thus offering an accessible and efficient LC solution to analyze 96 single-cells per day. At this throughput, nanoDTSC quantified over 1,000 proteins in individual cardiomyocytes and heterogenous populations of single cells from aorta.
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The effects of a reduction in area (RA) and the speed ratio between the top and bottom rolls on a shear strain and the crystallographic texture evolution of Al-Si-Mg (1.0%Si-0.6%Mg) aluminum alloys fabricated by twin roll casting (TRC) were comprehensively examined experimentally and through numerical predictions. Initial twin-roll casted strips had a texture gradient from the surface to the center. ⟨111⟩//ND textures were found in the surface layer, and weak rolling textures existed in the center of the strip. The distributions of shear and plane strain compression (PSC) textures varied with the RA and differential speed ratio. Strong shear textures including a rotated cube, {100}⟨011⟩, were obtained from both the symmetric and differential speed rolling processes. Symmetric rolling with a different reduction in area (SRDRA) produced shear textures mainly in the surface layer. Differential speed rolling (DSR) caused dynamic shear textures along the thickness direction, not limited to the surface. Based on the finite element method and crystal plasticity, the effects of different RA values, differential speed ratios, and friction coefficients on shear strain and texture evolution are discussed in detail. Loads measured from work rolls during DSR decreased with an increase in the speed ratio.
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Purpose: Liraglutide is known to have much lower weight loss effects in real clinical fields than in randomized clinical trials because of its side effects (SE) and discomfort associated with injections. This study is aimed at determining whether the side effects of liraglutide affect weight reduction and its maintenance in real-world practice. Methods: Endocrinologists conducted a retrospective chart review of data from two tertiary university hospitals. All patients who had been prescribed liraglutide at least once between January 2014 and December 2019 were included. For an average of 3 and 6 months, weight changes due to the presence or absence of SE and discontinuation (MAIN or STOP) of liraglutide were checked. Results: Only 40.8% (64/157) of the patients remained on liraglutide for 6 months; 14.7% (23/157) maintained the drug despite SEs (MAIN_SE(+)), and 40.1% (63/157) discontinued the drug despite not having SEs (STOP_SE(-)). At 3 months, there was -5.9 ± 0.6%, -7.9 ± 0.9%, -4.5 ± 0.5%, and -3.4 ± 0.6% weight reduction in the MAIN_SE(-), MAIN_SE(+), STOP_SE(-), and STOP_SE(+) groups, respectively (all p < 0.001 compared to the baseline). However, there were no significant differences in the weight loss between the MAIN (p = 0.062) and STOP (p = 0.204) groups. At 6 months, the weight reduction was -2.0 ± 0.5% (p < 0.001) in MAIN_SE(-), -2.2 ± 0.7% (p < 0.005) in MAIN_SE(+), -1.7 ± 0.7% (p < 0.01) in STOP_SE(-), and -2.0 ± 0.6% (p = 0.01) in STOP_SE(+), compared to baseline. SEs also caused no significant differences in weight loss between the MAIN (p = 0.787) and STOP (p = 0.694) groups. Conclusions: Our study confirmed that the side effects of liraglutide did not affect weight reduction. Moreover, in the real world, the continuous rate of liraglutide use is not high, and the weight gradually increases after 3 months. Therefore, in addition to the side effects of liraglutide, the medical staff should consider various factors that affect drug adherence, consider ways to increase compliance, and continue to ensure management so that patients can maintain their weight.
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Diabetes Mellitus Tipo 2 , Liraglutida , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Liraglutida/efectos adversos , Estudios Retrospectivos , Pérdida de PesoRESUMEN
Colloidal gels under constant moderate stress flow only after a prolonged solid-like deformation. Predicting the time-dependent yielding of the gels would facilitate control of their mechanical stability and transport, but early detectable signs of such delayed solid-to-fluid transition remain unknown. We show that the shear rate of colloidal gels under constant stress can forecast an eventual yielding during the earliest stage of deformation known as primary creep. The shear rate before failure exhibits a characteristic power-law decrease as a function of time, distinct from the linear viscoelastic response. We model this early-stage behavior as a series of uncorrelated local plastic events that are thermally activated, which illuminates the exponential dependence of the yield time on the applied stress. By revealing underlying viscoplasticity, this precursor to yield in the macroscopic shear rate provides a convenient tool to predict the yielding of a gel well in advance of its actual occurrence.
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BACKGROUND: Calcineurin inhibitors (CNIs), which are potent immunosuppressants (ISs), increase the risk for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LTx). Epithelial-mesenchymal transition (EMT) is a key process in which epithelial cancer cells lose their polarity, resulting in cancer progression and metastasis. The aim of this study was to evaluate the effect of sirolimus (SRL) individually and in combination with other ISs to reduce EMT. METHODS: HCC SK-Hep1 cells were used and various ISs (SRL, tacrolimus, cyclosporine A, or mycophenolate mofetil) were administered at 2 dosages and in combination therapies. Mice were transplanted with SK-Hep1 cells (in the liver) and were monitored after 2 weeks. RESULTS: The in vitro treatment with SRL showed a dose-dependent attenuation of cell proliferation and migration in case of the individual and IS combination treatments; further, decreased levels of pro-EMT proteins, namely, N-cadherin, transforming growth factor-ß, ZEB1, Slug, and Snail were observed. In contrast, E-cadherin expression was upregulated after both the individual and IS combination treatments. These results were also observed in the samples from mice transplanted with the SK-Hep1 cells. CONCLUSION: The present study demonstrated that SRL reduced HCC metastasis by inhibiting EMT. Thus, our findings provide a rationale for the use of SRL in combination with ISs in HCC LTx patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratones , Animales , Carcinoma Hepatocelular/patología , Inhibidores de la Calcineurina/farmacología , Transición Epitelial-Mesenquimal , Sirolimus/farmacología , Neoplasias Hepáticas/patología , Inmunosupresores/farmacología , Línea Celular TumoralRESUMEN
Background: This study evaluated endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD) as interventions for patients with anastomotic biliary complications (ABC) after living donor liver transplantation (LDLT). Methods: Prospectively collected data of patients who were diagnosed with ABC after LDLT between January 2013 and June 2017 were retrospectively reviewed. Results: There were 57 patients who underwent LDLT with a right liver graft using duct-to-duct biliary reconstruction and experienced ABC. Among the patients with RAD involvement, there were no significant differences in the intervention success (p = 0.271) and patency rates (p = 0.267) between ERCP and PTBD. Similarly, among the patients with RPD involvement, there were no significant differences in the intervention success (p = 0.148) and patency rates (p = 0.754) between the two procedures. Graft bile duct variation (p = 0.013) and a large angle between the recipient and graft bile duct (R-G angle) (p = 0.012) significantly increased the likelihood of failure of ERCP in the RAD. When the R-G angle was greater than 47.5°, the likelihood of ERCP failure increased. Conclusion: We recommend PTBD when graft bile duct variation is presented in patients with RAD involvement and/or when the R-G angle is greater than 47.5°.
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Trasplante de Hígado , Donadores Vivos , Anastomosis Quirúrgica/efectos adversos , Conductos Biliares/cirugía , Drenaje/métodos , Humanos , Hígado/cirugía , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Complicaciones Posoperatorias/diagnóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure (HF) cases. The prevalence of HFpEF is increasing due to an aging population with hypertension, diabetes mellitus, and obesity. HFpEF remains a challenging clinical entity due to a lack of effective treatment options. Traditional HF medications have not been shown to reduce mortality of patients with HFpEF, and an implantable cardioverter-defibrillator is not indicated due to normal ejection fraction. Sudden death is the most common mode of death in patients with HFpEF; however, the underlying mechanisms of sudden death are not fully elucidated. Although ventricular arrhythmias are responsible for the majority of sudden deaths in general, their contribution to sudden deaths in HFpEF patients is likely less significant. The mechanisms of ventricular arrhythmias in HFpEF are 1) reduced conduction velocity due to ventricular hypertrophy, 2) delayed repolarization due to potassium current down-regulation, 3) calcium leakage due to altered excitation-contraction coupling, and 4) increased ventricular fibrosis caused by systemic inflammation. Hypertension and subsequent ventricular hypertrophy reduce the conduction velocity in HFpEF hearts via heterogeneous distribution of connexin 43. Delayed repolarization caused by potassium current down-regulation in HFpEF hearts provides a window for early afterdepolarization to trigger ventricular arrhythmias. Altered excitation-contraction coupling in HFpEF can cause calcium to leak and trigger delayed afterdepolarization. Increased systemic inflammation and subsequent ventricular fibrosis provide substrates for re-entry. Further research is warranted to investigate the detailed mechanisms of ventricular arrhythmias in HFpEF.
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OBJECTIVE: The aim of the study was to present the safety and feasibility of pure laparoscopic donor right hepatectomy (PLDRH) in comparison with those of conventional donor right hepatectomy. SUMMARY BACKGROUND DATA: Although the use of PLDRH is gradually spreading worldwide, its outcomes, including the long-term outcomes in both donors and recipients, have not yet been evaluated in a large comparative study. METHODS: We retrospectively reviewed the medical records of 894 donors who underwent living donor liver transplantation between January 2010 and September 2018 at Seoul National University Hospital. We performed 1:1 propensity score matching between the PLDRH and conventional donor right hepatectomy groups. Subsequently, 198 donor-recipient pairs were included in each group. RESULTS: The total operation time (P < 0.001), time to remove the liver (P < 0.001), and warm ischemic time (P < 0.001) were longer in the PLDRH group. None of the donors required intraoperative transfusion or experienced any irreversible disabilities or mortalities. The length of postoperative hospital stay was significantly shorter in the PLDRH group (P < 0.001). The rate of complications in donors was similar between the 2 groups. Although other complication rates in recipients were, however, similar, the rates of early (P = 0.019) and late (P < 0.001) biliary complications in recipients were higher in the PLDRH group. There was no significant difference in overall survival and graft survival between the 2 groups. CONCLUSIONS: PLDRH is feasible when performed at an experienced living donor liver transplantation center. Further studies on long-term recipient outcomes including biliary complications are needed to confirm the safety.
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Hepatectomía/métodos , Laparoscopía/métodos , Trasplante de Hígado , Hígado/cirugía , Donadores Vivos , Puntaje de Propensión , Recolección de Tejidos y Órganos/métodos , Adulto , Femenino , Estudios de Seguimiento , Humanos , Hepatopatías/cirugía , Masculino , Tempo Operativo , Periodo Posoperatorio , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: The ability to increase heart rate during exercise and other stressors is a key homeostatic feature of the sinoatrial node (SAN). When the physiological heart rate response is blunted, chronotropic incompetence limits exercise capacity, a common problem in patients with heart failure with preserved ejection fraction (HFpEF). Despite its clinical relevance, the mechanisms of chronotropic incompetence remain unknown. METHODS: Dahl salt-sensitive rats fed a high-salt diet and C57Bl6 mice fed a high-fat diet and an inhibitor of constitutive nitric oxide synthase (Nω-nitro-L-arginine methyl ester [L-NAME]; 2-hit) were used as models of HFpEF. Myocardial infarction was created to induce HF with reduced ejection fraction. Rats and mice fed with a normal diet or those that had a sham surgery served as respective controls. A comprehensive characterization of SAN function and chronotropic response was conducted by in vivo, ex vivo, and single-cell electrophysiologic studies. RNA sequencing of SAN was performed to identify transcriptomic changes. Computational modeling of biophysically-detailed human HFpEF SAN was created. RESULTS: Rats with phenotypically-verified HFpEF exhibited limited chronotropic response associated with intrinsic SAN dysfunction, including impaired ß-adrenergic responsiveness and an alternating leading pacemaker within the SAN. Prolonged SAN recovery time and reduced SAN sensitivity to isoproterenol were confirmed in the 2-hit mouse model. Adenosine challenge unmasked conduction blocks within the SAN, which were associated with structural remodeling. Chronotropic incompetence and SAN dysfunction were also found in rats with HF with reduced ejection fraction. Single-cell studies and transcriptomic profiling revealed HFpEF-related alterations in both the "membrane clock" (ion channels) and the "Ca2+ clock" (spontaneous Ca2+ release events). The physiologic impairments were reproduced in silico by empirically-constrained quantitative modeling of human SAN function. CONCLUSIONS: Chronotropic incompetence and SAN dysfunction were seen in both models of HF. We identified that intrinsic abnormalities of SAN structure and function underlie the chronotropic response in HFpEF.
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Insuficiencia Cardíaca/fisiopatología , Nodo Sinoatrial/anomalías , Volumen Sistólico/fisiología , Animales , Humanos , RatasRESUMEN
Sudden death is the most common mode of mortality in patients with heart failure and preserved ejection fraction (HFpEF). Ventricular arrhythmias (VA) have been suspected as the etiology but the supporting evidence in patients with HFpEF is scarce. We sought to investigate VA prevalence, and to determine if VA are associated with prolonged repolarization, in patients with HFpEF. In a retrospective case-control study design, Cedars-Sinai patients who underwent prolonged ambulatory electrocardiographic monitoring (Zio Patch) between 2016 and 2018 were screened for a clinical diagnosis of HFpEF. Patients with normal diastolic and systolic function who underwent Zio Patch monitoring were also reviewed as controls. Multivariable logistic regression was used to compare the prevalence of rhythm disturbances in patients with and without HFpEF. Ventricular tachycardia (VT) was more prevalent in patients with HFpEF (37% vs. 16% in controls, p = 0.001). Most episodes were non-sustained except for one case of sustained VT in a patient with HFpEF. Covariate-adjusted logistic regression including HFpEF diagnosis, age, sex, body mass index, and the presence of comorbidities revealed that only HFpEF was associated with increased risk of VT (relative risk 2.86, p = 0.023). Subgroup-analyses revealed an association between increased QTc interval and risk of VT (460 ± 38 ms in HFpEF patients with VT vs. 445 ± 28 ms in HFpEF patients without VT, p = 0.03). Non-sustained VT was more prevalent in patients with HFpEF compared to patients without HFpEF, and QTc interval prolongation was associated with VT in HFpEF.
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Insuficiencia Cardíaca/fisiopatología , Taquicardia Ventricular/fisiopatología , Función Ventricular Izquierda/fisiología , Anciano , Estudios de Casos y Controles , Electrocardiografía Ambulatoria , Humanos , Modelos Logísticos , Persona de Mediana Edad , Estudios Retrospectivos , Volumen Sistólico/fisiologíaRESUMEN
Colloidal gels formed by strongly attractive particles at low particle volume fractions are composed of space-spanning networks of uniformly sized clusters. We study the thermal fluctuations of the clusters using differential dynamic microscopy by decomposing them into two modes of dynamics, and link them to the macroscopic viscoelasticity via rheometry. The first mode, dominant at early times, represents the localized, elastic fluctuations of individual clusters. The second mode, pronounced at late times, reflects the collective, viscoelastic dynamics facilitated by the connectivity of the clusters. By mixing two types of particles of distinct attraction strengths in different proportions, we control the transition time at which the collective mode starts to dominate, and hence tune the frequency dependence of the linear viscoelastic moduli of the binary gels.
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Indocyanine green (ICG) near-infrared fluoroscopy has been recently implemented in pure laparoscopic donor hepatectomy (PLDH). This study aims to quantitatively evaluate the effectiveness of ICG fluoroscopy during liver midplane dissection in PLDH and to demonstrate that a single injection of ICG is adequate for both midplane dissection and bile duct division. Retrospective analysis was done with images acquired from recordings of PLDH performed without ICG (pre-ICG group) from November 2015 to May 2016 and with ICG (post-ICG group) from June 2016 to May 2017. 30 donors from the pre-ICG group were compared with 46 donors from the post-ICG group. The operation time was shorter (P = 0.002) and postoperative peak aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were lower (P = 0.031 and P = 0.019, respectively) in the post-ICG group than the pre-ICG group. Within the post-ICG group, the color intensity differences between the clamped versus nonclamped regions in the natural, black-and-white, and fluorescent modes were 39.7 ± 36.2, 89.6 ± 46.9, and 19.1 ± 36.8 (mean ± SD, P < 0.001), respectively. The luminosity differences were 37.2 ± 34.5, 93.8 ± 32.1, and 26.7 ± 25.7 (P < 0.001), respectively. Meanwhile, the time from when ICG was injected to when the near-infrared camera was turned on for bile duct visualization was 85.6 ± 25.8 minutes. All grafts received from the 46 donors were successfully transplanted. In conclusion, ICG fluoroscopy helps to reduce operation time and lower postoperative AST/ALT levels. ICG injection visualized with black-and-white imaging is most effective for demarcating the liver midplane during PLDH. A single intravenous injection of ICG is sufficient for midplane dissection as well as bile duct division.
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Laparoscopía , Trasplante de Hígado , Hepatectomía/efectos adversos , Humanos , Verde de Indocianina , Hígado/diagnóstico por imagen , Hígado/cirugía , Trasplante de Hígado/efectos adversos , Imagen Óptica , Estudios RetrospectivosRESUMEN
BACKGROUND: Rituximab (RTx) desensitization protocol offered good outcome in ABO-incompatible (ABOi) living donor liver transplantation (LDLT). However, diffuse intrahepatic biliary stricture (DIHBS) is still inevitable hurdle. We selectively added postoperative high dose intravenous immunoglobulin (IVIG) and/or simultaneous splenectomy if ABO isoagglutinin titer just before liver transplantation after plasma exchange (PE) was higher than 1/16. Herein, we reported the excellent outcome of ABOi LDLT without DIHBS using tailored desensitization protocol and compared it with that of ABO-compatible (ABOc) LDLT. METHODS: Sixty-five cases (14.8%) of ABOi LDLTs were performed among 438 primary adult LDLTs in our center between March 2012 and June 2017. We performed 1-to-2 propensity score matching (PSM) to extract 60 cases of ABOi LDLTs and 120 cases of ABOc LDLTs. RESULTS: There were no significant differences in clinical characteristics between ABOi and ABOc recipients. There were no significant differences in complications and rejection. There was no DIHBS in both groups. The 1-, 3-, and 5-year overall survival rates were 98.3%, 86.7%, and 82.9% in ABOi group and 96.7%, 86.7%, and 85.4% in ABOc group, respectively (P=0.88). Most common cause of deaths of both groups was hepatocellular recurrence. The 1-, 3-, and 5-year biliary complication (anastomosis leakage or stricture) free survival rates were 81.4%, 69.5%, and 67.5% in ABOi group and 83.0%, 81.3%, and 80.0% in ABOc group, with no significant differences (P=0.11). CONCLUSIONS: RTx-based tailored (optional IVIG + splenectomy) desensitization protocol for ABOi LDLT was feasible and acceptable.