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1.
Nature ; 586(7830): 533-537, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33087915

RESUMO

Practical and useful quantum information processing requires substantial improvements with respect to current systems, both in the error rates of basic operations and in scale. The fundamental qualities of individual trapped-ion1 qubits are promising for long-term systems2, but the optics involved in their precise control are a barrier to scaling3. Planar-fabricated optics integrated within ion-trap devices can make such systems simultaneously more robust and parallelizable, as suggested by previous work with single ions4. Here we use scalable optics co-fabricated with a surface-electrode ion trap to achieve high-fidelity multi-ion quantum logic gates, which are often the limiting elements in building up the precise, large-scale entanglement that is essential to quantum computation. Light is efficiently delivered to a trap chip in a cryogenic environment via direct fibre coupling on multiple channels, eliminating the need for beam alignment into vacuum systems and cryostats and lending robustness to vibrations and beam-pointing drifts. This allows us to perform ground-state laser cooling of ion motion and to implement gates generating two-ion entangled states with fidelities greater than 99.3(2) per cent. This work demonstrates hardware that reduces noise and drifts in sensitive quantum logic, and simultaneously offers a route to practical parallelization for high-fidelity quantum processors5. Similar devices may also find applications in atom- and ion-based quantum sensing and timekeeping6.

2.
Phys Rev Lett ; 130(13): 133201, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37067320

RESUMO

Using a single calcium ion confined in a surface-electrode trap, we study the interaction of electric quadrupole transitions with a passively phase-stable optical standing wave field sourced by photonics integrated within the trap. We characterize the optical fields through spatial mapping of the Rabi frequencies of both carrier and motional sideband transitions as well as ac Stark shifts. Our measurements demonstrate the ability to engineer favorable combinations of sideband and carrier Rabi frequency as well as ac Stark shifts for specific tasks in quantum state control and metrology.

4.
Int J Mol Sci ; 23(19)2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36232622

RESUMO

Glycoporphyrins are group of compounds of high value for the purpose of photodynamic therapy and other biomedical applications. Despite great progress in the field, new diversity-oriented syntheses of carbohydrate-porphyrin hybrids are increasingly desired. Herein, we present efficient, mild, and metal-free conditions for synthesis of glycoporphyrins. The versatile nature of the SNAr procedure is presented in 16 examples. Preliminary biological studies have been conducted on the cytotoxicity and cellular uptake of the final molecules.


Assuntos
Fotoquimioterapia , Porfirinas , Carboidratos , Glicosilação , Fotoquimioterapia/métodos
5.
Dig Dis Sci ; 66(7): 2452-2460, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32816218

RESUMO

BACKGROUND: Transarterial chemoembolization (TACE) is an important therapy for hepatocellular carcinoma (HCC) in cirrhosis. In particular in advanced cirrhosis, post-TACE hepatic failure liver (PTHF) failure may develop. Currently, there is no standardization for the periinterventional risk assessment. The liver maximum capacity (LiMAx) test assesses the functional liver capacity, but has not been investigated in this setting. AIMS: The aim of this study was to prospectively evaluate periinterventional LiMAx and CT volumetry measurements in patients with cirrhosis and HCC undergoing repetitive TACE. METHODS: From 06/2016 to 11/2017, eleven patients with HCC and cirrhosis undergoing TACE were included. LiMAx measurements (n = 42) were conducted before and after each TACE. Laboratory parameters were correlated with the volume-function data. RESULTS: The median LiMAx levels before (276 ± 166 µg/kg/h) were slightly reduced after TACE (251 ± 122 µg/kg/h; p = 0.08). This corresponded to a median drop of 7.1%. Notably, there was a significant correlation between LiMAx levels before TACE and bilirubin (but not albumin nor albumin-bilirubin [ALBI] score) increase after TACE (p = 0.02, k = 0.56). Furthermore, a significantly higher increase in bilirubin in patients with LiMAx ≤ 150 µg/kg/h was observed (p = 0.011). LiMAx levels at different time points in single patients were similar (p = 0.2). CONCLUSION: In our prospective pilot study in patients with HCC and cirrhosis undergoing multiple TACE, robust and reliable LiMAx measurements were demonstrated. Lower LiMAx levels before TACE were associated with surrogate markers (bilirubin) of liver failure after TACE. Specific subgroups at high risk of PTHF should be investigated. This might facilitate the future development of strategies to prevent occurrence of PTHF.


Assuntos
Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
6.
J Stroke Cerebrovasc Dis ; 30(4): 105608, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33461024

RESUMO

OBJECTIVES: There has been a growing interest in whether carotid revascularization may reverse cognitive decline. In this study the aim was to assess cognitive changes after carotid artery endarterectomy and stenting, using neuropsychological assessment with MoCA and CANTAB test. MATERIALS AND METHODS: Seventy patients with asymptomatic carotid artery stenosis, qualified for CEA (study group A) and CAS (study group B) have been prospectively assessed. 20 patients with lower extremity artery disease (control group C) and 15 patients qualified for inguinal hernia surgery (control group D) have served as a control group. Patients have been evaluated 1 day before surgery and 6 months after, using MoCA and CANTAB test. Logistic regression models were built to determine variables affecting cognitive performance. RESULTS: After the procedure in the study group A the cognitive evaluation showed improvement in 5 cognitive domains tested in MoCA: visuospatial/executive (p=.0496), naming (p=.0831), language (p=.0009), abstraction (p=.0126) and delayed recall (p=.0016). In CANTAB there were improvement in PAL (p=.0290) and SWM (p=.0105). In study group B positive cognitive changes were seen in visuospatial/executive (p=.0827) and delayed recall (p=.0041) tested with MoCA and in PAL (PALFAMS28 p=.0315, PALNPR28 p=.0090, PALTEA28 p=.0058) and SWM (p=.0882) tested with CANTAB. Using a regression model, the only strong predictors of cognitive improvement on the follow-up visit were younger age and lower MoCA score on the first visit. CONCLUSIONS: Carotid revascularization, both open and endovascular, lead to cognitive improvement in patients with severe carotid stenosis and cognitive decline. This effect seems to be stronger in younger patients with worst cognitive performance before surgery.


Assuntos
Estenose das Carótidas/cirurgia , Cognição , Disfunção Cognitiva/psicologia , Endarterectomia das Carótidas , Procedimentos Endovasculares , Fatores Etários , Idoso , Doenças Assintomáticas , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estudos de Casos e Controles , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Estudos Prospectivos , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Stents , Fatores de Tempo , Resultado do Tratamento
7.
Dig Dis ; 38(3): 251-258, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31618751

RESUMO

BACKGROUND: Transjugular intrahepatic shunt (TIPSS) is placed in patients with variceal bleeding, refractory ascites, and for other indications. Postprocedural liver function-associated complications (LFAC), including hepatic encephalopathy (HE) and liver failure, represent a major setback. Current methods to predict complications are insufficient. OBJECTIVES: We investigated in a pilot study of patients prior TIPSS placement whether the risk of LFAC correlates with the functional reserve of the liver, as assessed by liver maximum function capacity (LiMAx) test. METHODS: Prospectively we included patients prior TIPSS placement between June 2016 and November 2017 at Saarland University Medical Center. LiMAx was conducted before and after TIPSS placement. Patients with HE prior TIPSS, as well as other factors predisposing to HE, including concomitant sedative drugs, current bacterial infections and sepsis, were excluded. Overt HE (OHE), LiMAx, and laboratory values were assessed before and after TIPSS placement. Data were analyzed in multivariate regression and AUROC models. RESULTS: Mean age was 60 ± 8 years. Patients (n = 20) were mainly men (65%), and presented predominantly with Child-Pugh class B (90%). Indications for TIPSS were most commonly refractory ascites or recurrent variceal bleeding. In total, 40% of the patients developed LFAC after TIPSS placement. Expectedly, LiMAx decreased and serum bilirubin increased after TIPSS. LiMAx drop ≥20% was the only parameter predicting the development of LFAC after TIPSS in multivariate regression and AUROC analysis. CONCLUSIONS: In multivariate regression models and AUROC analysis, a drop in LiMAx predicted the development of LFAC after TIPSS placement. Additional larger studies assessing OHE and early liver failure separately are warranted.


Assuntos
Fígado/fisiopatologia , Derivação Portossistêmica Transjugular Intra-Hepática , Área Sob a Curva , Pressão Sanguínea , Varizes Esofágicas e Gástricas/complicações , Feminino , Encefalopatia Hepática/fisiopatologia , Encefalopatia Hepática/cirurgia , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Projetos Piloto , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Valor Preditivo dos Testes , Curva ROC , Análise de Regressão
8.
Eur Radiol ; 29(11): 5861-5872, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30899977

RESUMO

OBJECTIVES: Predicting post-hepatectomy liver failure (PHLF) after extended right hepatectomy following portal vein embolization (PVE) from serial gadoxetic acid-enhanced magnetic resonance imaging (MRI). METHODS: Thirty-six patients who underwent hepatectomy following PVE were evaluated prospectively with gadoxetic acid-enhanced MRI examinations at predefined intervals during the course of their treatment, i.e., before and 14 days and 28 days after PVE as well as 10 days after hepatectomy. Relative enhancement (RE) and volume of the left and right liver lobes were determined. The study population was divided into two groups with respect to signs of PHLF. Differences between the two groups were assessed using the Mann-Whitney U test, and predictive parameters for group membership were investigated using ROC and logistic regression analysis. RESULTS: RE of the left lobe prior to PVE versus 14 days after PVE was significantly lower in patients with PHLF than in those without PHLF (Mann-Whitney U test p < 0.001) and proved to be the best predictor of PHLF in ROC analysis with an AUC of 0.854 (p < 0.001) and a cutoff value of - 0.044 with 75.0% sensitivity and 92.6% specificity. Consistent with this result, logistic linear regression analysis adjusted for age identified the same parameter to be a significant predictor of PHLF (p = 0.040). CONCLUSIONS: Gadoxetic acid-enhanced MRI performed as an imaging-based liver function test before and after PVE can help to predict PHLF. The risk of PHLF can be predicted as early as 14 days after PVE. KEY POINTS: • To predict the likelihood of post-hepatectomy liver failure, it is important to estimate not only future liver remnant volume prior to extended liver resection but also future liver remnant function. • Future liver remnant function can be predicted by performing gadoxetic acid-enhanced MRI as an imaging-based liver function test before and after portal vein embolization. • A reduction of relative enhancement of the liver in gadoxetic acid-enhanced MRI after portal vein embolization of 0.044 predicts post-hepatectomy liver failure with 75.0% sensitivity and 92.6% specificity.


Assuntos
Embolização Terapêutica/efeitos adversos , Gadolínio DTPA/farmacologia , Hepatectomia/efeitos adversos , Falência Hepática/diagnóstico , Neoplasias Hepáticas/terapia , Imageamento por Ressonância Magnética/métodos , Idoso , Feminino , Humanos , Falência Hepática/etiologia , Testes de Função Hepática , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Veia Porta , Curva ROC
9.
Dig Dis Sci ; 64(2): 576-584, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30406480

RESUMO

BACKGROUND: MELD attempts to objectively predict the risk of mortality of patients with liver cirrhosis and is commonly used to prioritize organ allocation. Despite the usefulness of the MELD, updated metrics could further improve the accuracy of estimates of survival. AIMS: To assess and compare the prognostic ability of an enzymatic 13C-based liver function test (LiMAx) and distinct markers of liver function to predict 3-month mortality of patients with chronic liver failure. METHODS: We prospectively investigated liver function of 268 chronic liver failure patients without hepatocellular carcinoma. Primary study endpoint was liver-related death within 3 months of follow-up. Prognostic values were calculated using Cox proportional hazards and logistic regression analysis. RESULTS: The Cox proportional hazard model indicated that LiMAx (p < 0.001) and serum creatinine values (p < 0.001) were the significant parameters independently associated with the risk of liver failure-related death. Logistic regression analysis revealed LiMAx and serum creatinine to be independent predictors of mortality. Areas under the receiver-operating characteristic curves for MELD (0.86 [0.80-0.92]) and for a combined score of LiMAx and serum creatinine (0.83 [0.76-0.90]) were comparable. CONCLUSIONS: Apart from serum creatinine levels, enzymatic liver function measured by LiMAx was found to be an independent predictor of short-term mortality risk in patients with liver cirrhosis. A risk score combining both determinants allows reliable prediction of short-term prognosis considering actual organ function. Trial Registration Number (German Clinical Trials Register) # DRKS00000614.


Assuntos
Doença Hepática Terminal/enzimologia , Cirrose Hepática/enzimologia , Acetamidas , Testes Respiratórios , Dióxido de Carbono/análise , Isótopos de Carbono , Estudos de Coortes , Creatinina/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Doença Hepática Terminal/metabolismo , Doença Hepática Terminal/mortalidade , Feminino , Humanos , Cirrose Hepática/metabolismo , Cirrose Hepática/mortalidade , Testes de Função Hepática , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida
10.
HPB (Oxford) ; 21(7): 912-922, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30733048

RESUMO

BACKGROUND: Surgical procedures in patients with underlying liver disease are still burdened by a high rate of postoperative morbidity, especially posthepatectomy liver failure (PHLF), ranging from 1.2 to 33.8%. The aim of this study was to investigate the prognostic value of volume/function analysis for the prediction of hepatectomy-related morbidity in patients with hepatocellular carcinoma. METHODS: Clinicopathological data were analysed in 261 patients who underwent liver resection for HCC between 2001 and 2014. Future liver remnant volume (FLRV) and future liver remnant function (FLRF) based on LiMAx test were obtained retrospectively. A subgroup analysis for high-risk patients with impaired liver function was conducted. Univariate and multivariate regression analysis was performed to identify risk factors for major complications, defined by Dindo ≥ IIIb and PHLF grade ≥ B. RESULTS: In the total cohort, FLRF was independently associated with major complications. FLRV, resected liver volume, and FLRF were independent risk factors for PHLF. In a subgroup analysis of high-risk patients, FLRF was identified as the only independent risk factor for major complications and PHLF development. DISCUSSION: These results suggest the superior value of FLRF to FLRV in predicting postoperative complications as well as PHLF in patients with chronic liver disease.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/cirurgia , Regeneração Hepática , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/fisiopatologia , Feminino , Hepatectomia/efeitos adversos , Humanos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/fisiopatologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
11.
Dis Colon Rectum ; 61(5): 604-611, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29533249

RESUMO

BACKGROUND: Colonic diverticulosis is one of the most common gastroenterological disorders. Although diverticulosis is typically benign, many individuals develop diverticulitis or other aspects of diverticular disease. Diverticulosis is thought to stem from a complex interaction of environmental, dietary, and genetic factors; however, the contributing genetic factors remain unknown. OBJECTIVE: The aim of our present study was to determine the role of genetic variants within genes encoding for collagens of the connective tissue in diverticulosis. DESIGN: This was a transsectional genetic association study. SETTINGS: This study was conducted at three tertiary referral centers in Germany and Lithuania. PATIENTS: Single-nucleotide polymorphisms in COL3A1 (rs3134646, rs1800255) and COL1A1 (rs1800012) were genotyped in 422 patients with diverticulosis and 285 controls of white descent by using TaqMan assays. MAIN OUTCOME MEASURES: The association of colonoscopy-proven diverticulosis with genetic polymorphisms with herniations was assessed in multivariate models. RESULTS: The rs3134646, rs1800255, and rs1800012 variants were significantly associated with the risk of developing diverticulosis in the univariate model; however, these associations were not significant in the multivariate logistic regression analysis including additional nongenetic variables. When selectively analyzing sexes, the genotype AA (AA) in rs3134646 remained significantly associated with diverticulosis in men (OR, 1.82; 95% CI, 1.04-3.20; p = 0.04). LIMITATIONS: Because a candidate approach was used, additional relevant variants could be missed. Within our cohort of patients with diverticulosis, only a small proportion had diverticular disease and thus, we could not examine the variants in these subgroups. Functional studies, including the analysis of the involved collagens, are also warranted. CONCLUSIONS: Our study shows that a variant of COL3A1 (rs3134646) is associated with the risk of developing colonic diverticulosis in white men, whereas rs1800255 (COL3A1) and rs1800012 (COL1A1) were not associated with this condition after adjusting for confounding factors. Our data provide novel valuable insights in the genetic susceptibility to diverticulosis. See Video Abstract at http://links.lww.com/DCR/A504.


Assuntos
Colágeno Tipo III/genética , DNA/genética , Doença Diverticular do Colo/genética , Polimorfismo Genético , População Branca/etnologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colágeno Tipo III/metabolismo , Colonoscopia , Doença Diverticular do Colo/etnologia , Doença Diverticular do Colo/metabolismo , Feminino , Seguimentos , Estudos de Associação Genética , Técnicas de Genotipagem , Alemanha/epidemiologia , Humanos , Incidência , Lituânia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
12.
Org Biomol Chem ; 16(25): 4688-4700, 2018 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-29892731

RESUMO

We report herein the development of a stereodivergent route towards polyhydroxylated bicyclic azetidine scaffolds, namely 6-azabicyclo[3.2.0]heptane derivatives. The strategy hinges on a common bicyclic ß-lactam precursor, which is forged by way of a rare example of a cationic Dieckmann-type reaction, followed by IBX-mediated desaturation. Substrate-controlled diastereoselective oxidations then allow the divergent preparation of novel iminosugar mimics.

13.
P R Health Sci J ; 37(3): 160-164, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30188560

RESUMO

OBJECTIVE: Bladder cancer is, in Poland, the fourth most common malignancy in men and the eighth most common in women. Radical cystectomy often seems to be the only method of treatment. This mutilating procedure may affect the quality of life of the patient. The aim of our study was to analyze the impact of factors influencing quality of life in patients after a cystectomy. METHODS: From January to August 2015, 50 consecutive patients treated in the Department of Urology of the Wroclaw Medical University in Wroclaw were enrolled into the study. Sixty-three percent of the respondents were men. Fifty-two percent of the respondents lived in urban areas. Patients ranged in age from under 25 to over 51 years. Clinical and demographic data were collected. Quality of life was evaluated with the SF-36 health survey questionnaire. For statistical analysis, Student's t-test, the Mann-Whitney U test and Spearman's rank correlation coefficient were used. Statistical analysis was carried out with IBM SPSS Statistics for Windows Version 21.0. RESULTS: A decrease in quality of life was observed in both genders. The impact of place of residence on the occurrence of pain, health perception, vitality, and levels of physical and mental activity was found to be significant (p<0.05). Pain intensity, health perception, vitality, and levels of physical and mental activity were higher in patients living in urban areas. CONCLUSION: Patients with bladder cancer who underwent a radical cystectomy were more likely to have a reduced quality of life if they lived in a village or small town than if they lived in an urban area.


Assuntos
Cistectomia , Qualidade de Vida , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato
14.
Ann Surg Oncol ; 24(9): 2447-2455, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28516292

RESUMO

BACKGROUND: Chemotherapy of colorectal liver metastases (CLMs) prior to liver resection implies the risk of chemotherapy-associated liver injury, leading to increased postoperative morbidity and mortality OBJECTIVE: The aim of this study was to evaluate the LiMAx (liver maximum capacity) test for diagnosis of chemotherapy-associated liver injury. METHODS: This was a retrospective analysis of patients with CLMs, prior to liver resection. We performed preoperative assessment of liver function using biochemical parameters and the LiMAx test. The individual history of chemotherapy within 12 months, including regimen, number of cycles, and therapy-free interval were collected, and histopathological evaluation of tumor-free liver tissue was performed in resected patients. RESULTS: A total of 204 patients were included, of whom 127 (62%) had received previous chemotherapy. The LiMAx test was worse after chemotherapy (340 ± 95 vs. 391 ± 82 µg/kg/h; p < 0.001). Impaired LiMAx results (<315 µg/kg/h) were determined in 49% of patients after chemotherapy, and no effects of chemotherapy, liver steatosis or fibrosis on biochemical parameters were observed. LiMAx impairment was dependent on the number of oxaliplatin cycles, the therapy-free interval, and obesity in multivariate analysis. In addition, the LiMAx test was worse in patients with relevant steatosis, fibrosis and steatohepatitis. Patients with an impaired LiMAx showed sufficient regeneration during chemotherapy cessation when surgery was postponed (272 ± 57 - 348 ± 72 µg/kg/h; p = 0.003). CONCLUSION: The LiMAx test enables non-invasive preoperative diagnosis of chemotherapy-associated liver injury. Preoperative performance of the LiMAx test can augment surgical strategy and timing of surgery after previous chemotherapy, thus avoiding increased postoperative morbidity.


Assuntos
Algoritmos , Antineoplásicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Compostos Organoplatínicos/efeitos adversos , Acetamidas/metabolismo , Idoso , Antineoplásicos/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Quimioterapia Adjuvante/efeitos adversos , Fígado Gorduroso/patologia , Fígado Gorduroso/fisiopatologia , Feminino , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Testes de Função Hepática , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Obesidade/fisiopatologia , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Período Pré-Operatório , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
15.
Eur Radiol ; 27(7): 3080-3087, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27966044

RESUMO

OBJECTIVES: To evaluate changes in liver function after right portal vein embolization (PVE) and extended right hemihepatectomy using gadolinium ethoxybenzyl-DTPA-enhanced (Gd-EOB-DTPA) MRI. METHODS: In this prospective trial, 37 patients undergoing PVE were examined before and 14 and 28 days after PVE and 10 days after extended hemihepatectomy using Gd-EOB-DTPA-enhanced MRI. Lobar volume, kinetic growth rate (KGR), relative enhancement (RE) as well as hepatocellular uptake index (HUI) and fat signal fraction (FSF) were calculated for each lobe. RESULTS: RE of the left liver lobe (LLL) was steadily increasing after PVE and decreased to 0.48 ± 0.19 10 days after surgery, which is significantly lower than 14 days and 28 days post PVE (P < 0.05). KGR was 14.06 ± 9.82%/week for the period from PVE to 14 days after PVE. HUI of the LLL increased steadily after PVE and was significantly higher at both 14 and 28 days after PVE compared to pre PVE (P < 0.05). HUI of the residual liver after surgery was lower than before. CONCLUSIONS: Gd-EOB-DTPA-enhanced MRI may be used to monitor the functional increase in the FLR after PVE and to depict the intraoperative liver injury leading to a decrease in liver remnant function. KEY POINTS: • The most significant FLR volume increase happens within the first 14 days. • No MRI parameter was able to predict the success of FLR growth. • Our data suggest an early resection about 14 days after PVE. • Routine Gd-EOB-DTPA-enhanced MRI might be suitable to replace ICG-test.


Assuntos
Embolização Terapêutica/métodos , Gadolínio DTPA/farmacologia , Hepatectomia/métodos , Neoplasias Hepáticas/diagnóstico , Imageamento por Ressonância Magnética/métodos , Monitorização Fisiológica/métodos , Veia Porta , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste/farmacologia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Ultrassonografia
16.
HPB (Oxford) ; 19(11): 1016-1025, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28844397

RESUMO

BACKGROUND: Since perioperative morbidity and mortality in ALPPS are extraordinarily high, a deeper understanding of actual liver function during the procedure is essential to make the approach safer. METHODS: Data from 17 patients who underwent ALLPS were analyzed regarding their course of liver function capacity assessed with the LiMAx test and compared to an equal-sized matched cohort of patients that underwent PVE. RESULTS: A comparison of LiMAx prior to and following ALPPS Step I (330 [258-385] vs. 197 [144-224] µg/kg/h, p = 0.003) and prior to and following PVE (386 [330-519] vs. 378 [336-455] µg/kg/h, p = 0.534) demonstrated a significant drop in function after ALLPS. A volume/function analysis predicting FLR function regarding step II revealed an excellent correlation of predicted versus assessed postoperative liver function with a mean relative difference of 9 (-6 to 18)% and an ICC of 0.905 (123 [74-138] vs. 107 [77-175] µg/kg/h, p = 0.310). CONCLUSIONS: We provide evidence that liver function capacity is significantly impaired due to ALPPS step I. This is particularly notable when compared to PVE. Our data also shows that the portal ligated liver lobe still continues to contribute significantly to overall liver function. Therefore, FLR function after step II is still predictable by volume/function analysis.


Assuntos
Hepatectomia/métodos , Testes de Função Hepática , Neoplasias Hepáticas/cirurgia , Fígado/cirurgia , Veia Porta/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Idoso , Embolização Terapêutica , Feminino , Hepatectomia/efeitos adversos , Humanos , Ligadura , Fígado/diagnóstico por imagem , Fígado/metabolismo , Fígado/fisiopatologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos
17.
Org Biomol Chem ; 14(2): 470-482, 2016 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-26563609

RESUMO

Reflection on the epimerization of the α-stereocenter of sugar nitrones leads to the conclusion that the process may occur through [1,4]-sigmatropic rearrangement. Participation of an ionic mechanism was excluded by a deuterium labeling experiment, and DFT calculations showed a reasonable energy barrier for the proposed [1,4]-shift. Products of the intramolecular 1,3-dipolar cycloaddition of the studied nitrones were utilized in the diversity-oriented synthesis of polyhydroxy derivatives of piperidine, indolizidine and quinolizidine. Minimal activity against the screened glucosidases and human melanoma cell lines was observed for some of the obtained compounds.


Assuntos
Inibidores Enzimáticos/farmacologia , Glucosidases/antagonistas & inibidores , Imino Açúcares/síntese química , Imino Açúcares/farmacologia , Óxidos de Nitrogênio/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Glucosidases/metabolismo , Humanos , Imino Açúcares/química , Modelos Moleculares , Estrutura Molecular , Teoria Quântica , Estereoisomerismo , Relação Estrutura-Atividade , Termodinâmica
18.
World J Surg ; 40(9): 2221-8, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27164934

RESUMO

BACKGROUND: Postoperative bile leakage (PBL) is a major surgical complication after partial liver resection resulting in increased perioperative morbidity and mortality. Previous experimental studies have shown an adverse effect on functional liver regeneration, but there are still no data available concerning these effects in humans. MATERIALS AND METHODS: A retrospective matched pair analysis was carried out comparing the postoperative course of 51 patients with PBL to 51 patients without PBL. The influence of PBL on actual liver function was determined by means of LiMAx, Indocyanine green plasma disappearance rate (ICG-PDR), and standard liver function tests. RESULTS: The analyzed groups were matched regarding demographic, preoperative, and operative data. Bilirubin, ICG-PDR and LiMAx showed delayed postoperative functional recovery after partial liver resection in the PBL group compared to the non-PBL group. LiMAx was the single parameter to assess differing liver regeneration continuously from the 3rd to 14th postoperative day between the groups. A subanalysis revealed an early recovery from impaired functional regeneration if the bile leakage was diagnosed until the 5th postoperative day (POD) or successfully treated until the 14th POD. CONCLUSION: These are the first data evaluating the impact of PBL on functional regeneration after liver surgery. Liver regeneration after partial liver resection is impaired by PBL. However, a nearly normal recovery is possible if the bile leak is diagnosed early and immediately treated. Moreover, patients presenting with delayed functional recovery in the postoperative course are likely to have complications, e.g., bile leakage.


Assuntos
Bile , Hepatectomia/métodos , Regeneração Hepática , Complicações Pós-Operatórias , Feminino , Humanos , Testes de Função Hepática , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Artif Organs ; 40(7): 692-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26527580

RESUMO

Temporary extracorporeal membrane oxygenation (ECMO) has been established as an essential part of therapy in patients with pulmonary or cardiac failure. As physiological gaseous exchange is artificially altered in this patient group, it is debatable whether a (13) C-breath test can be carried out. In this proof of technical feasibility report, we assess the viability of the (13) C-breath test LiMAx (maximum liver function capacity) in patients on ECMO therapy. All breath probes for the test device were obtained directly via the membrane oxygenator. Data of four patients receiving liver function assessment with the (13) C-breath test LiMAx while having ECMO therapy were analyzed. All results were compared with validated scenarios of the testing procedures. The LiMAx test could successfully be carried out in every case without changing ECMO settings. Clinical course of the patients ranging from multiorgan failure to no sign of liver insufficiency was in accordance with the results of the LiMAx liver function test. The (13) C-breath test is technically feasible in the context of ECMO. Further evaluation of (13) C-breath test in general would be worthwhile. The LiMAx test as a (13) C-breath test accessing liver function might be of particular predictive interest if patients with ECMO therapy develop multiorgan failure.


Assuntos
Testes Respiratórios/instrumentação , Oxigenação por Membrana Extracorpórea/instrumentação , Testes de Função Hepática/instrumentação , Adulto , Idoso , Isótopos de Carbono/análise , Fibrose Cística/diagnóstico , Fibrose Cística/terapia , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos , Adulto Jovem
20.
Langenbecks Arch Surg ; 401(1): 33-41, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26507639

RESUMO

PURPOSE: Chemotherapy-associated liver injury of patients undergoing therapy for colorectal liver metastases stimulates concerns on surgical safety. No common guidelines for the optimal timing of liver surgery after the application of systemic chemotherapy (chemotherapy-free interval) have been established and effects on individual liver function remain unexplored. METHODS: Maximum liver function capacity (LiMAx) and indocyanine green plasma disappearance rate (ICG-PDR) were measured in 20 patients with colorectal cancer receiving adjuvant oxaliplatin-based chemotherapy (OBC) prior to the first and after the last treatment course as well as 4 and 8 weeks thereafter. RESULTS: Comparison of pre- and post-chemotherapy test results demonstrated a significant decrease of LiMAx to 73.2 % ± 19.0 % (p = 0.001) and ICG-PDR to 78.2 % ± 21.3 % (p = 0.001) after cessation of OBC. The dynamics of LiMAx indicate an interindividual effect on vulnerability to systemic chemotherapy with subsequent functional regeneration after 8 weeks (pre-OBC 530 ± 144 µg/kg/h vs. 4 weeks post-OBC 463 ± 111 µg/kg/; p = 0.012 and vs. 8 weeks post-OBC 494 ± 138 µg/kg/h; p = 0.134). An analysis of individual regeneration after chemotherapy yielded a highly different course of functional recovery with patients regaining pre-chemotherapy function within 4 weeks, whereas others still showed deterioration after 8 weeks after cessation of chemotherapy. DISCUSSION AND CONCLUSION: Enzymatic liver function (LiMAx) is significantly reduced after oxaliplatin-based chemotherapy and subsequently recovers within 8 weeks after cessation of chemotherapy. However, pace of regeneration appears to be highly different among patients suggesting patient individual chemotherapy-free interval monitored by LiMAx.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fígado/fisiopatologia , Compostos Organoplatínicos/uso terapêutico , Adulto , Idoso , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Oxaliplatina , Estudos Prospectivos , Recuperação de Função Fisiológica
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