RESUMO
OBJECTIVE: To compare graft survival after LDLT in patients receiving GRWR<0.8 versus GRWR≥0.8 grafts and identify risk factors for graft loss using GRWR<0.8 grafts. SUMMARY BACKGROUND DATA: Favorable outcomes after living donor liver transplantation (LDLT) using graft-to-recipient weight ratio (GRWR)<0.8 grafts were recently reported; however, these results have not been validated using multicenter data. METHODS: This multicentric cohort study included 3450 LDLT patients. Graft survival was compared between 1:3 propensity score-matched groups and evaluated using various Cox models in the entire population. Risk factors for graft loss with GRWR<0.8 versus GRWR≥0.8 grafts were explored within various subgroups using interaction analyses, and outcomes were stratified according to the number of risk factors. RESULTS: In total, 368 patients (10.7%) received GRWR<0.8 grafts (GRWR<0.8 group), whereas 3082 (89.3%) received GRWR≥0.8 grafts (GRWR≥0.8 group). The 5-y graft survival rate was significantly lower with GRWR<0.8 grafts than with GRWR≥0.8 grafts (85.2% vs. 90.1%, P=0.013). Adjusted hazard ratio (HR) for graft loss using GRWR<0.8 grafts in the entire population was 1.66 (95% confidence interval [CI] 1.17-2.35, P=0.004). Risk factors exhibiting significant interactions with GRWR<0.8 for graft survival were age ≥60 y, MELD score ≥15, and male donor. When ≥2 risk factors were present, GRWR<0.8 grafts showed higher risk of graft loss compared to GRWR≥0.8 graft in LDLT (HR 2.98, 95% CI 1.79-4.88, P<0.001). CONCLUSIONS: GRWR<0.8 graft showed inferior graft survival than controls (85.2% vs. 90.1%), especially when ≥2 risk factors for graft loss (among age ≥60 y, MELD score ≥15, or male donor) were present.
RESUMO
The safety of elderly living liver donors and recipient outcomes are always of concern. In the present study, the effects of age in 2 donor groups, a 60+years old group and a 50-59 years old group (referred to as the 60s and 50s donor groups, respectively), on living donor liver transplantation were compared regarding donor safety and recipient outcomes. We retrospectively identified 209 patients 50 years and above of age at 9 centers from 2005 to 2017 in Korea. The 60s donor group represented 10% (n=21) of donor patients. One case in each group was a left liver graft, respectively, and the others were right liver grafts. Postoperative complications were more common in the 60s donor group, but the proportion of Clavien-Dindo grade III in the 60s donor group did not differ from that in the 50s donor group. In-hospital mortality did not occur among donors, and donor mortality was not reported during the observation period. Postoperative total bilirubin and hospitalization in recipients of the 60s donor group were higher and longer than in recipients of the 50s donor group, respectively. Although the cumulative overall survival of the recipients in the 60s donor group was significantly lower than that of the 50s donor group, a difference was not observed in graft survival. Multivariate analysis showed that increased living liver donors age, the coexistence of HCC, and increased intraoperative blood loss during the recipient operation were important predisposing factors for patient death. Present study suggests that highly selected elderly living donors (≥60 y) can safely donate with similar recipient graft survival rates though the recipient overall patient survival is inferior compared to the 50s donor group.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Idoso , Pessoa de Meia-Idade , Criança , Transplante de Fígado/efeitos adversos , Doadores Vivos , Estudos Retrospectivos , Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/etiologia , República da Coreia/epidemiologia , Sobrevivência de Enxerto , Resultado do TratamentoRESUMO
Considerable controversy exists regarding the superiority of tenofovir disoproxil fumarate (TDF) over entecavir (ETV) for reducing the risk of HCC. This study aimed to compare outcomes of ETV versus TDF after liver transplantation (LT) in patients with HBV-related HCC. We performed a multicenter observational study using data from the Korean Organ Transplantation Registry. A total of 845 patients who underwent LT for HBV-related HCC were divided into 2 groups according to oral nucleos(t)ide analogue used for HBV prophylaxis post-LT: ETV group (n = 393) and TDF group (n = 452). HCC recurrence and overall death were compared in naïve and propensity score (PS)-weighted populations, and the likelihood of these outcomes according to the use of ETV or TDF were analyzed with various Cox models. At 1, 3, and 5 years, the ETV and TDF groups had similar HCC recurrence-free survival (90.7%, 85.6%, and 84.1% vs. 90.9%, 84.6%, and 84.2%, respectively, p = 0.98) and overall survival (98.4%, 94.7%, and 93.5% vs. 99.3%, 95.8%, and 94.9%, respectively, p = 0.48). The propensity score-weighted population showed similar results. In Cox models involving covariates adjustment, propensity score-weighting, competing risk regression, and time-dependent covariates adjustment, both groups showed a similar risk of HCC recurrence and overall death. In subgroup analyses stratified according to HCC burden (Milan criteria, Up-to-7 criteria, French alpha-fetoprotein risk score), pretransplantation locoregional therapy, and salvage LT, neither ETV nor TDF was superior. In conclusion, ETV and TDF showed mutual noninferiority for HCC outcomes when used for HBV prophylaxis after LT.
Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Tenofovir/uso terapêutico , Antivirais/uso terapêutico , Transplante de Fígado/efeitos adversos , Carcinoma Hepatocelular/epidemiologia , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Resultado do Tratamento , Neoplasias Hepáticas/epidemiologia , Hepatite B/complicações , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Vírus da Hepatite BRESUMO
Assigning a hepatocellular carcinoma (HCC) to an appropriate subtype is important because this guarantees the diagnosis and treatment and allows decisions regarding the prognosis of the patient. HCC subtyping is usually based on the World Health Organization (WHO) classification and the 2019 fifth edition is the latest version. However, the WHO classification system is still in evolution and has limited clinical relevance. We aimed to evaluate the clinical relevance of HCC subtyping and to reappraise some of the major subtypes of HCC. Our archived cases (n = 589) were reclassified according to the 2019 WHO system. The percentage of each subtype was mostly similar to that in the WHO classification. However, on the contrary to the 2019 WHO system, clear cell type HCC was associated with more frequent recurrence or metastasis. Meanwhile, macrotrabecular massive HCC was related to poor prognosis as demonstrated in the 2019 WHO system and should be described in the pathology report. For steatohepatitic HCC, there is a debate on whether it is a true subtype because the steatohepatitis morphology may or may not be present in the background liver. In our study, 44 % of steatohepatitic HCCs (n = 19/43) presented underlying steatohepatitis. Additionally, the background cirrhosis did not influence survival in the HCC patients, although the 2019 WHO system indicates the presence of cirrhosis as a poor prognostic factor. In conclusion, although it is not perfect yet, HCC subtyping based on the 2019 WHO system provides valuable information to manage patients with HCC.
Assuntos
Carcinoma Hepatocelular , Fígado Gorduroso , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Prognóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Fígado Gorduroso/patologiaRESUMO
Background and Objectives: Pancreaticoduodenal artery aneurysms are rare visceral artery aneurysms. Interventional treatments, including transcatheter embolization, have an acceptable success rate. We report a case of ruptured pancreaticoduodenal aneurysm that was successfully treated with percutaneous N-Butyl-cyanoacrylate (NBCA) embolization after failed transcatheter embolization. Materials and Methods: A 53-year-old man presented to the emergency department with abdominal pain. Computed tomography (CT) revealed a ruptured aneurysm in the inferior pancreaticoduodenal artery (IPDA) with retrohemoperitoneum. The patient underwent percutaneous NBCA embolization after transcatheter embolization failure. Results: On CT, the pancreaticoduodenal aneurysm was completely embolized. No additional bleeding events occurred. Conclusions: Percutaneous NBCA embolization is safe and effective for treating patients with ruptured pancreaticoduodenal aneurysms after failed transcatheter embolization.
Assuntos
Aneurisma Roto , Embolização Terapêutica , Embucrilato , Masculino , Humanos , Pessoa de Meia-Idade , Embucrilato/uso terapêutico , Aneurisma Roto/complicações , Aneurisma Roto/terapia , Embolização Terapêutica/métodos , Pâncreas , ArtériasRESUMO
Pancreatic transplantation is the only treatment for insulin-dependent diabetes resulting in long-term euglycemia without exogenous insulin. However, pancreatic transplantation has become debatable following the improvements in the results of islet transplantation and artificial pancreas. Therefore, surgeons who perform pancreas transplants require the best surgical technique that can minimize technical failure. We aimed to report our experiences with pancreatic transplantations. We transplanted 65 pancreatic grafts between 2015 and 2020. Except for one death due to hypoxic brain damage after surgery, no postoperative technical failure was observed. We usually perform duodeno-duodenal anastomosis using the transperitoneal approach, with retrocolic placement of the graft pancreas. There was no leakage from the duodenum even after immunologic graft failure. To prevent venous thrombosis, which is the most common cause of technical failure, we used the inferior vena cava for anastomosis and added graft venoplasty with a patch of donor vena cava or aortic interposition graft to the bench procedure; subsequently, there were no cases of technical failure due to thrombosis post-transplantation. Therefore, the 1-year graft survival (insulin-free) rate was more than 95%. The improving the surgical technique will maintain pancreatic transplantation as the best treatment for insulin-dependent diabetes.
Assuntos
Diabetes Mellitus Tipo 1 , Transplante de Pâncreas , Anastomose Cirúrgica , Diabetes Mellitus Tipo 1/cirurgia , Sobrevivência de Enxerto , Humanos , Insulina , Transplante de Pâncreas/efeitos adversosRESUMO
An optical see-through (OST) display is affected more severely by ambient light than any other type of displays when placed in an outdoor environment with bright illuminance because of its transparency and thus, its inherent color distortion can worsen. It is hard to directly apply existing gamut mapping methods to an OST display because of its morphological gamut characteristic and the effect of ambient light. In this paper, we propose a new robust gamut mapping method which works against bright ambient light. The process is divided into two steps: lightness mapping (LM) and chroma reproduction. LM aligns the lightness level of sRGB gamut with OST gamut and partitions the region of OST gamut based on the relative size of the sRGB gamut and its lightness value. The second step (chroma reproduction) determines an appropriate chroma reproduction method (gamut compression or extension) and a proper direction for gamut mapping based on the characteristics of each region in order to minimize the effects of ambient light. The quality of color reproduction is qualitatively and quantitatively evaluated based on accurate measurements of the displayed colors. It has been experimentally confirmed that the proposed gamut mapping method can reduce color distortion more than the existing parametric gamut mapping algorithms.
RESUMO
Serum pancreatic enzymes (serum amylase and lipase) are sensitive markers for monitoring acute rejection in pancreatic transplant recipients. However, those enzymes are not specific, as their levels are elevated in other conditions. We evaluated the eosinophil-to-monocyte ratio (EMR) in peripheral blood as a biomarker of acute rejection in the clinical setting in recipients of pancreatic transplant alone. We performed 32 cases of pancreatic transplantation alone since 2015. Nine patients were diagnosed with rejection. Serum amylase and lipase levels and eosinophil and monocytes counts were analyzed and compared retrospectively between the non-rejection and rejection groups. The serum eosinophil count, eosinophil fraction of the complete blood count, and serum amylase and lipase levels were significant predictors of rejection according to the receiver operation characteristic (ROC) curve. However, the EMR was the best indicator of rejection based on the ROC curve (area under the curve 0.918, sensitivity 100%, specificity 76.2% at the cutoff value 0.80, P < .001). The combination of EMR and the lipase level had 100% sensitivity and 90.5% specificity. The EMR is a simple and excellent predictor of acute rejection in recipients of pancreatic transplant alone.
Assuntos
Monócitos , Transplante de Pâncreas , Eosinófilos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Humanos , Estudos Retrospectivos , TransplantadosRESUMO
BACKGROUND: An epidermoid cyst in an intrapancreatic accessory spleen (ECIPAS) in the pancreas head is an extremely rare condition. The natural course of this condition is not well known, and it is difficult to diagnose before surgery due to the lack of specific imaging findings. CASE PRESENTATION: A tumor was found in the head of the pancreas in a 68-year-old man with abdominal distension and discomfort. Magnetic resonance imaging (MRI) suggested a malignant tumor, such as a colloid cancer. The tumor was removed surgically, with pathologic examination showing that it was an ECIPAS. CONCLUSION: ECIPAS cannot be easily distinguished from other pancreatic cystic tumors, making it necessary to include ECIPAS in the differential diagnosis of these tumors. Unnecessary surgical resection may be avoided by more accurate preoperative diagnosis based on clinical and imaging characteristics.
Assuntos
Cisto Epidérmico , Pancreatopatias , Esplenopatias , Idoso , Diagnóstico Diferencial , Cisto Epidérmico/diagnóstico por imagem , Cisto Epidérmico/cirurgia , Humanos , Masculino , Pâncreas/diagnóstico por imagem , Pancreatopatias/diagnóstico por imagem , Pancreatopatias/cirurgiaRESUMO
BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population. METHODS: Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis. RESULTS: The study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 ± 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence. CONCLUSION: Combination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.
Assuntos
Antivirais , Vírus da Hepatite B , Hepatite B , Imunoglobulinas , Transplante de Fígado , Doadores Vivos , Antivirais/uso terapêutico , Estudos de Coortes , DNA Viral/sangue , Quimioterapia Combinada , Hepatite B/prevenção & controle , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Humanos , Imunoglobulinas/uso terapêutico , Sistema de Registros , República da CoreiaRESUMO
According to the current 8th edition of the American Joint Committee of Cancer (AJCC), the T category of distal cholangiocarcinomas is classified based on the depth of invasion (DOI) (T1, < 5 mm; T2, between 5 and 12 mm; T3, > 12 mm). In consideration of the discrepancies between previous studies about the prognostic significance, we aimed to validate the current AJCC T staging system of distal cholangiocarcinomas. DOI was measured using three different methods: DOI1, DOI2, and DOI3. DOI1 was defined and stratified according to the AJCC 8th edition. DOI2 was measured as the distance from an imaginary curved line approximated along the distorted mucosal surface to the deepest invasive tumor cells. DOI3 was defined as the total tumor thickness. DOI2 and DOI3 were also divided into three categories using the same cut-off points as in the AJCC 8th edition. We compared these three DOI methods to the AJCC 7th edition as well. In contrast with the AJCC 7th edition, all three groups showed a correlation with patients' overall survival. Above all, the DOI2 group demonstrated the best significance in multivariate analysis. However, when the C indices were compared between these groups, differential significance proved to be negligible (DOI1 vs DOI2, p = 0.915; DOI2 vs DOI3, p = 0.057). Therefore, the measurement of DOI does not need to be rigorously and stringently performed. In conclusion, we showed that the current T classification system better correlates with the overall survival of patients with distal cholangiocarcinomas than the previous system.
Assuntos
Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Estadiamento de Neoplasias/métodos , Adulto , Idoso , Neoplasias dos Ductos Biliares/classificação , Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/classificação , Colangiocarcinoma/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: Although the current nodal staging system for gallbladder cancer (GBC) was changed based on the number of positive lymph nodes (PLN), it needs to be evaluated in various situations. METHODS: We reviewed the clinical data for 398 patients with resected GBC and compared nodal staging systems based on the number of PLNs, the positive/retrieved LN ratio (LNR), and the log odds of positive LN (LODDS). Prognostic performance was evaluated using the C-index. RESULTS: Subgroups were formed on the basis of an restricted cubic spline plot as follows: PLN 3 (PLN = 0, 1-2, ≥ 3); PLN 4 (PLN = 0, 1-3, ≥ 4); LNR (LNR = 0, 0-0.269, ≥ 0.27); and LODDS (LODDS < - 0.8, - 0.8-0, ≥ 0). The oncological outcome differed significantly between subgroups in each system. In all patients with GBC, PLN 4 (C-index 0.730) and PLN 3 (C-index 0.734) were the best prognostic discriminators of survival and recurrence, respectively. However, for retrieved LN (RLN) ≥ 6, LODDS was the best discriminator for survival (C-index 0.852). CONCLUSION: The nodal staging system based on PLN was the optimal prognostic discriminator in patients with RLN < 6, whereas the LODDS system is adequate for RLN ≥ 6. The following nodal staging system considers applying different systems according to the RLN.
Assuntos
Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Linfonodos/patologia , Estadiamento de Neoplasias , Idoso , Colecistectomia , Intervalo Livre de Doença , Feminino , Neoplasias da Vesícula Biliar/terapia , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Nanophotosensitizer composed of methoxy poly(ethylene glycol) (MePEG) and chlorin e6 (Ce6) (abbreviated as Pe6) was synthesized for efficient delivery of Ce6 to the colon cancer cells. Pe6 nanophotosensitizer has small diameter less than 100 nm with spherical shape and core-shell structure. They were activated in aqueous solution while Ce6 was quenched due to its poor aqueous solubility. They showed no intrinsic cytotoxicity against normal cells and colon cancer cells. Pe6 nanophotosensitizers showed enhanced cellular uptake, phototoxicity, and reactive oxygen species (ROS) generation at in vitro cell culture experiment. Furthermore, they showed improved tumor tissue penetration and accumulation in vivo animal studies. We suggested Pe6 nanophotosensitizers as an ideal candidate for PDT of colon cancer.
Assuntos
Neoplasias do Colo/terapia , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas , Animais , Linhagem Celular Tumoral , Clorofilídeos , Nanocompostos , PolietilenoglicóisRESUMO
INTRODUCTION: Therapeutic plasma exchange (TPE) is used for temporary support of liver function in patients presenting with early graft dysfunction after liver transplantation (LT) or liver surgery. We analyzed the effect of therapeutic apheresis on patients with liver disease. METHODS: Between January 2011 and August 2016, 93 apheresis procedures were performed for 26 patients at our institution. Anti-ABO isoagglutination immunoglobulin (Ig) M titer was checked using a type A and type B 3% red blood cell (RBC) suspension in saline with two-fold serial dilutions of patient serum. Anti-ABO isoagglutination IgG titer was checked by a type A and B 0.8% RBC suspension using a low-ionic strength/Coombs card. RESULTS: ABO-incompatible (ABOi) LT was the most common (n=10, 38.5%) indication for apheresis; early graft dysfunction after LT (n=8, 30.7%) was the second most common. Median initial IgM and IgG anti-ABO titers for ABOi LT recipients were 1:16 (range, 1:8-1:128) and 1:48 (range, 1:8-1:2048). We performed preoperative TPE in 10 recipients (median number of sessions, 1.5; range, 1-11). Among patients with early graft dysfunction, those who underwent living donor LT had better survival (4/4; 100%) than those who underwent nonliving donor LT (0/3; 0%). Patients who underwent living donor LT first and then additional LT also survived after three TPE sessions. CONCLUSION: Therapeutic apheresis is associated with a good survival rate and is essential for liver support in patients with early graft dysfunction after LT or posthepatectomy liver failure and during preparation for ABOi LT.
Assuntos
Remoção de Componentes Sanguíneos/métodos , Transplante de Fígado/métodos , Fígado/patologia , Troca Plasmática/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Hepatic venous outflow is important for graft survival in living donor liver transplantation (LDLT). If hepatic venous outflow obstruction occurs, hepatic vein stenting is considered to restore the patency. PURPOSE: To retrospectively evaluate the efficacy and patency of primary hepatic vein stenting for hepatic venous outflow obstruction (HVOO) after LDLT. MATERIAL AND METHODS: Percutaneous interventions, including hepatic vein stent placement with or without balloon angioplasty, were performed in 21 patients who had undergone LDLT and had HVOO confirmed through hepatic venography or manometry, including the patients who had a structural abnormality. Two stents each were inserted in four patients; therefore, the total number of treated anastomoses was 25. Technical success, patency rates, and pressure gradients between hepatic veins and the right atrium were evaluated in 19 patients each. RESULTS: Technical success was achieved in 25 of 26 vessels (96%). The mean interval between operation and stenting was 43 days. After the procedure, the follow-up period was a mean 530 days. The mean pressure gradient decreased from 8.5 mmHg to 2.1 mmHg after treatment (P < 0.01). The patency rates of the 25 vessels were 80% at 1, 2, and 3 years after stent placement. However, middle hepatic vein stenting revealed a low patency rate (all were 36%). Three of seven stents (43%) in the middle hepatic vein occluded during follow-up. CONCLUSION: Percutaneous primary hepatic vein stent replacement is an effective treatment for HVOO after LDLT.
Assuntos
Síndrome de Budd-Chiari/etiologia , Síndrome de Budd-Chiari/cirurgia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/cirurgia , Transplante de Fígado/efeitos adversos , Stents , Adulto , Idoso , Feminino , Sobrevivência de Enxerto , Humanos , Doadores Vivos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
Transplantation studies about the clinical differences according to the type of donors are mostly conducted in western countries with rare reports from Asians. The aims of this study were to evaluate the clinical impacts of the type of donor, and the predictors of 1-year mortality in patients who underwent liver transplantation (LT). This study was performed for liver transplant recipients between May 2010 and December 2014 at the Pusan National University Yangsan Hospital. A total of 185 recipients who underwent LT were analyzed. Of the 185 recipients, 109 (58.9%) belonged to the living donor liver transplantation (LDLT) group. The median age was 52.4 years. LDLT recipients had lower model for end-stage liver disease (MELD) score compared with better liver function than deceased donor liver transplantation (DDLT) recipients (mean ± standard deviation [SD], 12.5 ± 8.3 vs. 24.9 ± 11.7, respectively; P < 0.001), and had more advanced hepatocellular carcinoma (HCC) (62.4% vs. 21.1%, respectively; P = 0.001). In complications and clinical outcomes, LDLT recipients showed shorter stay in intensive care unit (ICU) (mean ± SD, 10.8 ± 8.8 vs. 23.0 ± 13.8 days, respectively, P < 0.001), ventilator care days, and post-operative admission days, and lower 1-year mortality (11% vs. 27.6%, respectively, P = 0.004). Bleeding and infectious complications were less in LDLT recipients. Recipients with DDLT (P = 0.004) showed higher mortality in univariate analysis, and multi-logistic regression analysis found higher MELD score and higher pre-operative serum brain natriuretic peptide (BNP) were associated with 1-year mortality. This study may guide improved management before and after LT from donor selection to post-operation follow up.
Assuntos
Falência Hepática/terapia , Transplante de Fígado , Doadores Vivos , Adulto , Nitrogênio da Ureia Sanguínea , Cadáver , Feminino , Humanos , Infecções/etiologia , Unidades de Terapia Intensiva , Tempo de Internação , Falência Hepática/mortalidade , Falência Hepática/patologia , Transplante de Fígado/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
The synthesis and structure-activity relationship of a series of 6-substituted picolinamide inhibitors of 11ß-hydroxysteroid dehydrogenase type 1 are described. The optimization of the left-hand side of lead compound 1 resulted in the discovery of the highly potent, selective, and orally available inhibitor 24, which demonstrated an excellent activity in a mouse ex vivo pharmacodynamic model. Moreover, compound 24 reduced the blood glucose and improved the lipid profiles in ob/ob mice after oral administration.
Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Inibidores Enzimáticos/síntese química , Ácidos Picolínicos/química , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Administração Oral , Amidas/química , Amidas/farmacocinética , Amidas/uso terapêutico , Animais , Glicemia/análise , Catálise , Diabetes Mellitus Experimental/tratamento farmacológico , Inibidores Enzimáticos/farmacocinética , Inibidores Enzimáticos/uso terapêutico , Células HEK293 , Meia-Vida , Humanos , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Paládio/química , Ácidos Picolínicos/farmacocinética , Ácidos Picolínicos/uso terapêutico , Ligação Proteica , Relação Estrutura-AtividadeRESUMO
Synthesis of a series of 6-substituted picolinamide derivatives and their inhibitory activities against 11ß-hydroxysteroid dehydrogenase type 1 are described. Optimization of the initial hit compound, N-cyclohexyl-6-(piperidin-1-yl)picolinamide (1) from high throughput screening of in-house library resulted in the discovery of the highly potent and metabolically stable compound 25, which was efficacious in a mouse ex vivo pharmacodynamic model and reduced the fasting blood glucose and insulin levels in a HF/STZ mouse model after oral dosing.
Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Inibidores Enzimáticos/síntese química , Ácidos Picolínicos/química , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Amidas/química , Amidas/uso terapêutico , Amidas/toxicidade , Animais , Sítios de Ligação , Glicemia/análise , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Modelos Animais de Doenças , Inibidores Enzimáticos/uso terapêutico , Inibidores Enzimáticos/toxicidade , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Dinâmica Molecular , Ácidos Picolínicos/uso terapêutico , Ácidos Picolínicos/toxicidade , Estrutura Terciária de Proteína , Relação Estrutura-AtividadeRESUMO
Graft copolymer composed hyaluronic acid (HA) and poly(D,L-lactide-co-glycolide) (PLGA) (HAgLG) was synthesized for antitumor targeting via CD44 receptor of tumor cells. The carboxylic end of PLGA was conjugated with hexamethylenediamine (HMDA) to have amine end group in the end of chain (PLGA-amine). PLGA-amine was coupled with carboxylic acid of HA. Self-assembled polymeric micelles of HAgLG have spherical morphologies and their sizes were around 50-200 nm. Doxorubicin (DOX)-incorporated polymeric micelles were prepared by dialysis procedure. DOX was released over 4 days and its release rate was accelerated by the tumoric enzyme hyaluronidase. To assess targetability of polymeric micelles, CD44-positive HepG2 cells were employed treated with fluorescein isothiocyanate (FITC)-labeled polymeric micelles. HepG2 cells strongly expressed green fluorescence at the cell membrane and cytosol. However, internalization of polymeric micelles were significantly decreased when free HA was pretreated to block the CD44 receptor. Furthermore, the CD44-specific anticancer activity of HAgLG polymeric micelles was confirmed using CD44-negative CT26 cells and CD44-positive HepG2 cells. These results indicated that polymeric micelles of HaLG polymeric micelles have targetability against CD44 receptor of tumor cells. We suggest HAgLG polymeric micelles as a promising candidate for specific drug targeting.
Assuntos
Ácido Hialurônico/química , Ácido Láctico/química , Micelas , Ácido Poliglicólico/química , Polímeros/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Fluoresceína-5-Isotiocianato/química , Células Hep G2 , Humanos , Receptores de Hialuronatos/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros/síntese químicaRESUMO
BACKGROUND: Simultaneous pancreas and kidney transplant (SPK) is the most common type of pancreas transplant performed worldwide. In contrast, there are a few drawbacks to pancreas after kidney transplant (PAK), such as the requirement for an additional operation, the immunologic risk, etc. SPK is the best option, but because of a lack of deceased donors and a lengthy waiting period, it is not always possible to use it. METHODS: From 2015 to 2022, we performed 23 SPKs and 21 PAKs at the Pusan National University Yangsan Hospital in Korea. We compared the findings of PAK and SPK conducted within the same time period. RESULTS: The waiting time for pancreatic graft was significantly shorter in the PAK than SPK group (345 days vs 1350 days, P ≤ .001). Throughout the monitoring period, just 1 pancreatic graft was lost in patients who underwent PAK, and the 7-year graft survival was 95%, with no statistically significant difference compared to SPK (90.3%, P = .600). Moreover, the graft survival of SPK or PAK was superior to that of pancreatic transplant alone (63.7%, P = .016). Only 1 pancreatic graft loss was a case of mortality with a functioning graft. No additional kidney transplant loss was observed in PAK recipients. There was no variation in creatinine levels between the pretransplant and posttransplant periods. There were 2 incidents of pancreatic graft and kidney graft rejection, respectively, but the grafts entirely recovered following rejection treatment. CONCLUSION: According to our experiences, PAK could be another best choice for individuals with diabetic end-stage renal disease, especially in cases where deceased donors were severely deficient but living donor kidney transplants were actively performed in countries like Korea.