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BACKGROUND: Available tacrolimus formulations exhibit substantial inter- and intra-individual variability in absorption and metabolism. The present non-interventional cohort study aimed to assess the tolerability and effectiveness of the once-daily tacrolimus formulation, LCPT, in hepatic allograft recipients in real life. MATERIALS AND METHODS: This study was conducted in Austria and the Czech Republic between July 2016 and August 2019. Patients aged ≥ 18 years old received LCPT per the approved label and local clinical routine. All the participants provided informed consent. Patients newly treated with tacrolimus (de novo) directly after transplantation were observed for six months. The relevant clinical variables were tacrolimus trough level (TL), total daily dose (TDD), number of dose adjustments, kidney and liver function, and tolerability. RESULTS: Of the 70 analyzed patients, 72.9% were male and 85.7% were aged < 65 years old. The mean (SD) time to achieve tacrolimus target TL was 6.4 (4.6) days after 4.4 (4.0) dose adjustments; thereafter, TL remained stable throughout observation at approximately 8 ng/mL. The LCPT TDD at initiation was 8 mg and decreased by a median of 41.4% to 5 mg at 6 months. Liver function continuously improved, and kidney function remained stable. LCPT was well tolerated with 24 adverse events in eight patients (17 related to immunosuppression, mostly mild renal insufficiency, and hematological adverse events); two serious unrelated adverse events were reported (atrial flutter and liver dysfunction). CONCLUSIONS: TL was rapidly attained with few dose adaptations after LCPT initiation in de novo liver transplant patients. Liver function rapidly improved, whereas kidney function remained normal. LCPT was well-tolerated in this population.
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Alcohol use disorder (AUD) is one of the most important risk factors for the development of alcohol-related liver cirrhosis (ALC). Importantly, psychiatrists are an integral part of the interdisciplinary care for patients with AUD and ALC. The aim of the current study was to investigate whether sex influences the outcome within this group of patients. For this purpose, data of all registrations for liver transplantations due to ALC within the Eurotransplant region from 2010 to 2019 were analyzed for sex disparities using competing risk models and in-between group comparisons. Relevant sex differences in registration numbers (24.8% female) and investigated outcomes were revealed. Risk ratios for a positive outcome, i.e., transplantation (0.74), and those of adverse outcomes, i.e., removal from waiting list (1.44) and death on waiting list (1.10), indicated a relative disadvantage for female patients with ALC. Further, women listed for liver transplantations were significantly younger than their male counterparts. Notably, sex disparities found in registration and outcome parameters were independent of differences found in the prevalence of AUD and liver transplantations. Further research is necessary to identify the underlying mechanisms and establish strategies to ensure equity and utility in liver transplantations due to ALC.
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BACKGROUND AND AIMS: Patients with cirrhosis on the liver transplant (LT) waiting list may die or be removed because of complications of portal hypertension (PH) or infections. von Willebrand factor antigen (vWF-Ag) and C-reactive protein (CRP) are simple, broadly available markers of these processes. APPROACH AND RESULTS: We determined whether addition of vWF-Ag and CRP to the Model for End-Stage Liver Disease-Sodium (MELD-Na) score improves risk stratification of patients awaiting LT. CRP and vWF-Ag at LT listing were assessed in two independent cohorts (Medical University of Vienna [exploration cohort] and Mayo Clinic Rochester [validation cohort]). Clinical characteristics, MELD-Na, and mortality on the waiting list were recorded. Prediction of 3-month waiting list mortality was assessed by receiver operating characteristics curve (ROC-AUC). In order to explore potential mechanisms underlying the prognostic utility of vWF-Ag and CRP in this setting, we evaluated their association with PH, bacterial translocation, systemic inflammation, and circulatory dysfunction. In the exploration cohort (n = 269) vWF-Ag and CRP both improved the predictive value of MELD-Na for 3-month waitlist mortality and showed the highest predictive value when combined (AUC: MELD-Na, 0.764; MELD-Na + CRP, 0.790; MELD-Na + vWF, 0.803; MELD-Na + CRP + vWF-Ag, 0.824). Results were confirmed in an independent validation cohort (n = 129; AUC: MELD-Na, 0.677; MELD-Na + CRP + vWF-Ag, 0.882). vWF-Ag was independently associated with PH and inflammatory biomarkers, whereas CRP closely, and MELD independently, correlated with biomarkers of bacterial translocation/inflammation. CONCLUSIONS: The addition of vWF-Ag and CRP-reflecting central pathophysiological mechanisms of PH, bacterial translocation, and inflammation, that are all drivers of mortality on the waiting list for LT-to the MELD-Na score improves prediction of waitlist mortality. Using the vWFAg-CRP-MELD-Na model for prioritizing organ allocation may improve prediction of waitlist mortality and decrease waitlist mortality.
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Proteína C-Reactiva/metabolismo , Enfermedad Hepática en Estado Terminal/metabolismo , Cirrosis Hepática/metabolismo , Listas de Espera/mortalidad , Factor de von Willebrand/metabolismo , Anciano , Traslocación Bacteriana , Biomarcadores , Femenino , Humanos , Hipertensión Portal/metabolismo , Inflamación/metabolismo , Cirrosis Hepática/cirugía , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Pronóstico , Índice de Severidad de la Enfermedad , Sodio/sangreRESUMEN
BACKGROUND: To date, definitions of liver dysfunction (LD) after hepatic resection rely on late postoperative time points. Further, the used parameters are markedly influenced by perioperative management. Thus, we aimed to establish a very early postoperative score to predict postoperative mortality. METHODS: Liver related parameters were evaluated after liver resection in a retrospective evaluation cohort of 228 colorectal cancer patients with liver metastasis (mCRC) and subsequent validation in a prospective set of 482 consecutive patients from 4 independent institutions undergoing hepatic resection was performed. RESULTS: C-reactive protein (CRP, AUC =0.739, P<0.001) and antithrombinIII-activity (ATIII, AUC =0.844, P<0.001) on the first postoperative day (POD) were found to be elevated in patients with LD. Cut-off values for CRP at 3 mg/dL and for ATIII at 60% significantly identified high-risk patients for postoperative LD and mortality (P<0.001) and thus defined the 3-60 criteria on POD1. The 3-60 criteria showed superior sensitivity and specificity compared to established criteria for LD [3-60 criteria: total positive patients: 26 patients (70% mortality detected), odds ratio (OR): 48.8; International Study Group for Liver Surgery: total positive patients: 43 (70% mortality detected), OR: 23.3; Peak7: total positive patients: 9 (30% mortality detected), OR: 27.8; 50-50: total positive patients: 9 (30% mortality detected), OR: 27.8]. These results could be validated in a multi-center analysis and ultimately the 3-60 criteria remained an independent predictor of postoperative mortality upon multivariable analysis. CONCLUSIONS: The 3-60 criteria on POD1 predict postoperative LD and mortality early after liver resection with a comparable or better accuracy than established criteria, allowing for immediate identification of high-risk patients.
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OBJECTIVE: Transplantation results in a 5-time elevated risk for a variety of malignancies (Kaposi sarcoma, skin, liver, lung, gastrointestinal cancer). A patient's risk for malignancies could be of particular interest for the follow-up programs of patients and risk adaption after kidney transplantation. The aim of this study was to identify independent risk factors for de novo malignancies in women after renal transplantation. METHODS AND MATERIALS: This is a multicenter transversal study, conducted at the Medical University of Vienna and Hospital Rudolfstiftung, Vienna, Austria. We included female kidney graft recipients who were transplanted between 1980 and 2012 and followed-up at our institutions (N = 280). Clinical data of patients were extracted from hospital charts and electronic patient files. Patients were interviewed using a standardized questionnaire regarding their medical history, history of transplantation, and malignant diseases. Detailed information about present and past immunosuppressive regimens, rejection episodes and therapies, renal graft function, and information about primary disease was obtained. Diagnostic work-up and/or surgical exploration was performed if any presence of malignancy was suspected during routine follow-up. Histological specimens were obtained from all patients. MAIN OUTCOME MEASURES: the presence of de novo malignancy after kidney transplantation. RESULTS: Two hundred sixty-two women were included for statistical analysis. Median (interquartile range) follow-up period after transplantation was 101.1 (27.3-190.7) months. Thirty-two patients (12.2%) developed a malignancy: dermatologic malignancies (5.7%), breast cancer (3.4%), cervical cancer (0.8%), lung cancer (0.4%), gastrointestinal malignancies (1.5%), vulvar cancer (0.4%), and unclassified malignancies (1.9%). Median (interquartile range) time to malignancy after transplantation was 185.9 (92.0-257.6) months. Cumulative cancer rates were 4.9% (1 year), 14.4% (3 years), 16.4% (5 years), and 21.8% (10 years). Second transplantations were identified as independent risk factor for development of malignancy after transplantation. CONCLUSIONS: Long-term risk of developing a malignancy after kidney transplantation is high, which might justify a follow-up of more than 10 years.
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Trasplante de Riñón/estadística & datos numéricos , Neoplasias/epidemiología , Adulto , Austria/epidemiología , Femenino , Humanos , Trasplante de Riñón/efectos adversos , Persona de Mediana Edad , Neoplasias/etiología , Factores de RiesgoRESUMEN
OBJECTIVE: Renal transplant patients are at increased risk for human papillomavirus-related malignancies of the lower genital tract. Our aim was to describe the incidence of genital dysplasia, assess the most common cervical cancer screening intervals and identify independent risk factors for the development of genital dysplasia in renal transplant patients. DESIGN: Retrospective, non-interventional study from two centers. SETTING: Post-transplant nephrologic follow-up visit at the Medical University of Vienna and a Viennese teaching hospital. POPULATION: 262 consecutive female renal transplant patients with renal transplant performed between 1980 and 2012 at the Medical University of Vienna. METHODS: Sociodemographic patient characteristics, frequency of gynecological examinations, histo- and cytopathological test results were collected. MAIN OUTCOME MEASURES: Dysplasia rates in renal transplant patients. RESULTS: 16 patients (6.2%) with genital dysplasia after renal transplant were observed. The 1-year, 3-year and 10-year proportional incidence rates for genital dysplasia in general and cervical dysplasia in particular were 1.3 and 1.3%, 3.3 and 2.7%, and 13.6 and 12.0%, respectively. Patients attended cervical cancer screening on a regular basis once a year in 82.7% of cases. In multivariate analysis re-transplantation [odds ratio 12.1 (1.5-96.3)], and renal transplant at a young age [odds ratio 0.6 (0.4-0.9)] were identified as independent risk factors for the development of female genital dysplasia. CONCLUSIONS: Female renal transplant patients have an increased risk for the development of genital dysplasia in general and of cervical dysplasia in particular. Within this cohort, women at a young age at the time of transplantation and after re-transplantation are at highest risk for the development of genital dysplasia.
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Carcinoma in Situ/epidemiología , Neoplasias de los Genitales Femeninos/epidemiología , Trasplante de Riñón/efectos adversos , Insuficiencia Renal/cirugía , Displasia del Cuello del Útero/epidemiología , Adulto , Factores de Edad , Carcinoma in Situ/patología , Femenino , Neoplasias de los Genitales Femeninos/patología , Humanos , Incidencia , Persona de Mediana Edad , Oportunidad Relativa , Insuficiencia Renal/etiología , Insuficiencia Renal/patología , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
Donor criteria for liver grafts have been expanded because of organ shortage. Currently, no exact definitions for extended donor grafts have been established. The aim of this study was to analyze the impact of donor-specific risk factors, independent of recipient characteristics. In collaboration with Eurotransplant and European Liver Transplant Register, solely donor-specific parameters were correlated with 1-year survival following liver transplantation. Analyses of 4701 donors between 2000 and 2005 resulted in the development of a nomogram to estimate graft survival for available grafts. Predictions by nomogram were compared to those by Donor Risk Index (DRI). In the multivariate analysis, cold ischemic time (CIT), highest sodium, cause of donor death, γ-glutamyl transferase (γ-GT), and donor sex (female) were statistically significant factors for 3 months; CIT, γ-GT, and cause of donor death for 12-month survival. The median DRI of this study population was 1.45 (Q1: 1.17; Q3: 1.67). The agreement between the nomogram and DRI was weak (kappa = 0.23). Several donor-specific risk factors were identified for early survival after liver transplantation. The provided nomogram will support quick organ quality assessment. Nevertheless, this study showed the difficulties of determining an exact definition of extended criteria donors.
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Trasplante de Hígado/métodos , Trasplante de Hígado/normas , Donantes de Tejidos , Obtención de Tejidos y Órganos/normas , Adulto , Isquemia Fría , Europa (Continente) , Femenino , Supervivencia de Injerto , Humanos , Fallo Hepático/mortalidad , Fallo Hepático/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nomogramas , Sistema de Registros , Factores de Riesgo , Factores Sexuales , Resultado del Tratamiento , Listas de Espera , gamma-Glutamiltransferasa/metabolismoRESUMEN
BACKGROUND: During the last 30 years a threefold increase in the number of overweight children has been reported in Western countries. More than 15% of adolescents have a body mass index (BMI) higher than the 95th percentile. The use of surgical strategies in adolescent patients is still controversial due to the impact on the continuing maturing process. Laparoscopic adjustable gastric banding (LAGB) is considered a minimal invasive procedure that does not alter the physiological behavior of the bowel and has already shown promising results in short-term studies. METHODS: Between 1998 and 2004, 50 adolescent patients above the 99.5th age- and gender-adjusted growing percentile were treated with LAGB. The surgical procedure was performed at three highly experienced centers for bariatric surgery. Mean age was 17.1 ± 2.2 years (range = 9-19 years) at the time of surgery. Follow-up investigations were performed in the outpatient clinic of the treating hospitals. Psychological changes were analyzed using the BAROS questionnaire. RESULTS: The mean BMI decreased from 45.2 ± 7.6 kg/m(2) at the time of surgery to 38.3 ± 6.2 kg/m(2) 1 year after surgery, 31.5 ± 6.6 kg/m(2) after 3 years, and 27.3 ± 5.3 kg/m(2) after 5 years. Mean excessive weight loss was 49.7 ± 29.2, 76.8 ± 27.5, and 92.6 ± 24.5% at 1, 3, and 5 years after surgery. Quality of life showed a further significant improvement between 3 and 5 years after surgery (BAROS: 5.5 ± 1.9 increased to 6.3 ± 2.2, p = 0.01). All preoperative comorbidities resolved in patients with a functional band after 5 years of follow-up. CONCLUSION: LAGB shows promising results in the long-term follow-up with continuous weight loss in patients with a functional band. Nevertheless, most of the weight loss is within the first 3 years after surgery. Thereafter, further weight reduction is about 10% over the following 2 years. Perioperative comorbidities resolve within the first 5 years after treatment.
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Gastroplastia/métodos , Laparoscopía/métodos , Adolescente , Austria , Índice de Masa Corporal , Niño , Comorbilidad , Femenino , Estudios de Seguimiento , Gastroplastia/estadística & datos numéricos , Humanos , Laparoscopía/estadística & datos numéricos , Masculino , Complicaciones Posoperatorias/epidemiología , Calidad de Vida , Estudios Retrospectivos , Pérdida de Peso , Adulto JovenRESUMEN
BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the main mesenchymal neoplasms in the gastrointestinal tract. Tumor size, mitotic rate, and location correlate with potential malignancy and recurrence rate. Results of surgical treatment of gastric GIST are analyzed with emphasis on recurrence of disease after intermediate follow-up. METHODS: From 1998 to 2006, a total of 63 patients (median age 62.1 +/- 14.1) underwent gastric resection for GIST. Fifty-five patients (93.6%) returned for follow-up investigations, which included computed tomography in 45, gastroscopy in 32, and endosonography in 29. Positron emission tomography was done in five patients. RESULTS: Mean tumor size was 5.3 +/- 3.8 cm. Open atypical gastric resection was done in 32, distal gastric resection in five, and remnant gastrectomy in four patients. Laparoscopic gastric resection was initiated in 22 patients; the conversion rate was four of 22 (18.2%). Overall, R0 resection was reached in 61/63 patients (96.8%). According to the Fletcher criteria, 33 tumors (52.4%) were classified as intermediate or high risk GIST. Six patients (9.5%) died of unrelated causes before follow-up. After a median follow-up of 2.5 years, overall recurrence rate was 7.0% after R0 resection. CONCLUSION: Histologically proven complete resection is an effective treatment for gastric GIST. Laparoscopic procedures were carried out successfully in selected patients.
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Gastrectomía/métodos , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/cirugía , Recurrencia Local de Neoplasia/patología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Anciano , Biopsia con Aguja , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Tumores del Estroma Gastrointestinal/patología , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Laparoscopía/métodos , Laparotomía/métodos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Probabilidad , Estudios Retrospectivos , Medición de Riesgo , Neoplasias Gástricas/patología , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
The significant risk of cerebral embolism during cardiopulmonary bypass (CPB) makes monitoring of embolic events advisable already when developing new operation and coagulation management strategies for example in CPB animal models. The present study therefore evaluated in a porcine CPB model the feasibility of bilateral epicarotid Doppler signal recording and the quality of manual or automatic emboli detection. A total of 42 recordings (e.g. right carotid artery (n = 20), left carotid artery (n = 22)) were evaluated. The frequency of emboli counts was comparable for both carotid arteries. Automatic emboli detection, however, found significantly more embolic events per pig than did post-hoc manual off-line analysis of the recordings (172 +/- 217 vs. 13 +/-10). None of the brains, however, showed any emboli or infarction area either in cross-examination or in histological evaluation. In conclusion, the present study showed the feasibility of using an epicarotid Doppler device for bilateral emboli detection in a porcine CPB model. Automatic on-line emboli detection, however, reported more embolic events than did post hoc, off-line manual analysis. Possible reasons for this discrepancy are discussed.