Partial nephrectomy (PN) is generally favored for cT1 tumors over radical nephrectomy (RN) when technically feasible. However, it can be unclear whether the additional risks of PN are worth the magnitude of renal function benefit.
Objective
To develop preoperative tools to predict long-term estimated glomerular filtration rate (eGFR) beyond 30 d following PN and RN, separately.
Design, setting, and participants
In this retrospective cohort study, patients who underwent RN or PN for a single nonmetastatic renal tumor between 1997 and 2014 at our institution were identified. Exclusion criteria were venous tumor thrombus and preoperative eGFR <15 ml/min/1.73 m2.
Intervention
RN and PN.
Outcome measurements and statistical analysis
Hierarchical generalized linear mixed-effect models with backward selection of candidate preoperative features were used to predict long-term eGFR following RN and PN, separately. Predictive ability was summarized using marginal , which ranges from 0 to 1, with higher values indicating increased predictive ability.
Results and limitations
The analysis included 1152 patients (13 206 eGFR observations) who underwent RN and 1920 patients (18 652 eGFR observations) who underwent PN, with mean preoperative eGFRs of 66 ml/min/1.73 m2 (standard deviation [SD] = 18) and 72 ml/min/1.73 m2 (SD = 20), respectively. The model to predict eGFR after RN included age, diabetes, preoperative eGFR, preoperative proteinuria, tumor size, time from surgery, and an interaction between time from surgery and age (marginal ). The model to predict eGFR after PN included age, presence of a solitary kidney, diabetes, hypertension, preoperative eGFR, preoperative proteinuria, surgical approach, time from surgery, and interaction terms between time from surgery and age, diabetes, preoperative eGFR, and preoperative proteinuria (marginal ). Limitations include the lack of data on renal tumor complexity and the single-center design; generalizability needs to be confirmed in external cohorts.
Conclusions
We developed preoperative tools to predict renal function outcomes following RN and PN. Pending validation, these tools should be helpful for patient counseling and clinical decision-making.
Patient summary
We developed models to predict kidney function outcomes after partial and radical nephrectomy based on preoperative features. This should help clinicians during patient counseling and decision-making in the management of kidney tumors. 相似文献
Variations of the anatomy of donor hepatic arteries increase the number of arterial anastomoses during liver transplantation and, possibly, the incidence of hepatic artery thrombosis (HAT). In this study, we describe the arterial anatomic variations in liver grafts procured and transplanted by a single center in Greece, the techniques of arterial anastomosis, and their effect on the incidence of early HAT.
Materials and Methods
From January 2013 to December 2017, the arterial anatomy of 116 grafts procured for liver transplantation were recorded, as well as the technique of arterial anastomosis and the incidence of early hepatic artery thrombosis (HAT <30 days).
Results
A single hepatic artery was recorded in 72.41% of the procured grafts, an aberrant left hepatic artery (accessory or replaced) in 18 grafts (15.52%), and an aberrant right hepatic artery (accessory or replaced) in 17 grafts (14.66%), while other variations were observed in less than 1% of the procured livers. Of the 116 primary liver transplantations, 6 patients (5.17%) developed early HAT <30 days. Two of these patients (1.72%) had 1 anastomosis of the hepatic artery and 4 (3.45%) had 2 anastomoses due to anatomic variations.
Conclusions
Anatomic variations of the hepatic artery in liver grafts is a common finding and increase the incidence of early HAT but not to a degree to make these grafts unusable. 相似文献
Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.
Methods
Using The Cancer Genome Atlas (n?=?436) and Cancer Genomics of the Kidney (n?=?89) datasets, we applied regression analysis to examine associations between patient age and gene expression profiles in ccRCC tumors and normal kidney tissues. Pathway enrichment analysis was performed to identify cellular process that is affected by aging in ccRCC. Moreover, connectivity mapping analysis was used to predict age-dependent response to drug treatments.
Results
Our analysis revealed different age-dependent gene expression spectra in ccRCC and normal kidney tissues. These findings were significant and independently reproducible in both datasets examined. Age up-regulated genes, showing higher expression in older patients, were significantly enriched (false discovery rate <0.05) in normal tissues for pathways associated with immune response and extracellular matrix organization, whereas age up-regulated genes in tumors were enriched for metabolism and oxidation pathways. Strikingly, age down-regulated genes in normal cells were also enriched for metabolism and oxidation, while those in tumors were enriched for extracellular matrix organization. Further in silico analysis of potential drug targets predicted preferential efficacy of Phosphoinositide 3-kinase inhibitor or immunotherapy in association with age.
Conclusion
We report on previously unrecognized associations between age and molecular underpinnings of RCC, including age-associated expression of genes implicated in RCC development or treatment. 相似文献
Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30–100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.
Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.
Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available. 相似文献
In light of the pharmacophoric structural requirements for achieving anticonvulsant activity, a series of N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)benzamide (4a-g) and N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)-2-phenylacetamide (4h-n) derivatives were synthesized in two steps starting from the reaction of N-methyl isatoic anhydride with the appropriate hydrazide and followed by condensation with the appropriate aldehyde. The anticonvulsant activities of the synthesized compounds were evaluated according to the anticonvulsant drug development (ADD) programme protocol. Among the synthesized compounds, 4n showed promising activity in both the maximal electroshock (MES) and pentylenetetrazole (PTZ) tests with median effective dose (ED50) values of 40.7 and 6 mg/kg, respectively. The six most promising derivatives, 4b , 4a , 4c , 4f , 4j , and 4i , showed very low ED50 values in the PTZ test (3.1, 4.96, 8.68, 9.89, 12, and 13.53 mg/kg, respectively). All the tested compounds showed no to low neurotoxicity in the rotarod test with a wide therapeutic index. Docking studies of compound 4n suggested that GABAA binding could be the mechanism of action of these derivatives. The in silico drug likeliness parameters indicated that none of the designed compounds violate Lipinski's rule of five and that they are able to cross the blood–brain barrier.
Renal Denervation for Treatment of Cardiac Arrhythmias . It has now been more than a quarter of a century since modulation of the sympathetic nervous system was proposed for the treatment of cardiac arrhythmias of different origins. But it has also been some time since some of the early surgical attempts have been abandoned. With the development of ablation techniques, however, new approaches and targets have been recently introduced that have revolutionized our way of thinking about sympathetic modulation. Renal nerve ablation technology is now being successfully used for the treatment of resistant hypertension, but the indication spectrum might broaden and new therapeutic options might arise in the near future. This review focuses on the possible impact of renal sympathetic system modulation on cardiac arrhythmias, the current evidence supporting this approach, and the ongoing trials of this method in electrophysiological laboratories. We will discuss the potential roles that sympathetic modulation may play in the future. 相似文献