Mesoporous silica nanoparticles (MSNs) can provide a structural foundation for a new generation of nanocarriers with a broad range of functionalities. Multifunctional MSNs can serve as all-in-one diagnostic and therapeutic tools that can be used to simultaneously visualize and treat various diseases, such as cancer. This research study is the first time that two lanthanide-based imaging systems have been combined to incorporate controlled drug release and targeted tracing into a single MSN-based nano-platform for a novel theranostic drug delivery system. Doping lanthanide ions, i.e., europium (Eu) and gadolinium (Gd) ions, into an MSN structure (EuGd-MSNs) imparts fluorescence and magnetism to the nanostructure that can be used to develop magnetic resonance imaging (MRI) and biological fluorescence tools. Current cancer research has revealed that most human cancer cells express a large number of folate receptors on their surface. Grafting folic acid (FA) onto the EuGd-MSN surface (EuGd-FA-MSNs) imparts a targeting function to the MSN because of the specificity of the binding of FA to cell surface receptors. Furthermore, grafting anticancer drugs, such as camptothecin (CPT), onto the surface of these MSNs by forming disulfide bonds (EuGd-SS-CPT-FA-MSNs) enables intracellular controlled drug release. A high concentration of intracellular glutathione cleaves the disulfide bond to release the drug and treat the disease. The results of in vitro and in vivo studies show that the functionalized MSNs can be successfully used as a platform to integrate dual-imaging, targeting, and therapeutic treatment in multifunctional diagnosis drug delivery systems. 相似文献
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
The concept of dynamic stabilization (DS) of the lumbar spine for treatment of degenerative instability has been introduced almost two decades ago. Dynamic stabilization follows the principle of controlling movement in the coronal plane by providing load transfer of the spinal segment without fusion and, at the same time, reducing side effects such as adjacent segment disease (ASD). So far, only little is known about revision rates after DS due to ASD and screw loosening (SL).
Purpose
The present study aimed to evaluate the longitudinal revision rates following dynamic pedicle screw stabilization in the lumbar spine and to determine specific risk factors predictive for ASD, SL, and overall reoperation in a large cohort with considerable follow-up.
Design
We carried out a post hoc analysis of a prospectively collected database in a level I spine center.
Patients Example
The patient sample comprised 283 (151 female/132 male) consecutive patients suffering from painful degenerative lumbar segmental instability with or without spinal stenosis who underwent DS of the lumbar spine (Ulrich Cosmic, Ulrich Medical, Ulm, Germany) between January 2008 and December 2011.
Outcome Measures
Longitudinal reoperation rate and risk factors predictive for revision surgery were evaluated.
Methods
We analyzed the longitudinal reoperation rate due to ASD and SL and overall reoperation. Risk factors such as age, gender, body mass index, lumbar lordosis (LL), number of segments, and number of previous surgeries were taken into account. Regular and mixed model logistic regressions were performed to determine risk factors for revision surgery on a patient and on a screw level.
Results
The mean age was 65.7±10.2 years (range 31–88). One hundred thirty-two patients were stabilized in 1 segment, 134 in 2 segments, 15 in 3 segments, and 2 patients in 4 segments. Reoperation rate for ASD and SL after 1 year was 7.4 %, after 2 years was 15.0%, and after a mean follow-up of 51.4±15 months was 22.6%. Reasons for revision were SL in 19 cases (6.6%), ASD in 39 cases (13.7%), SL and ASD in 6 cases, hematoma in 2 cases (0.7%), cerebrospinal fluid fistulae in 3 cases (1.1%), infection in 6 cases (2.1%), and implant failure in 1 case (0.4%). The patients' age, the number of stabilized segments, and the number of previous surgeries and postoperative LL had a significant influence on the probability for revision surgery.
Conclusions
Reoperation rates after DS of the lumbar spine are comparable with rigid fixations. The younger the patient and the more segments are involved, the lower the LL and the more previous surgeries were found, the higher was the risk of revision. Risk of revision was almost twice as high in men compared with women. We therefore conclude that for clear clinical indication and careful evaluation of preoperative imaging data, DS using the Cosmic system seems to be a possible option. The presented data will help to further tailor indication and patient selection. 相似文献
The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with Ki values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with Km values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CLR) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CLR (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CLR of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates. 相似文献
Introduction: Research on medication use aims at assessing how much of current pharmacotherapy is rational. In neonates, this is hampered by extensive off-label drug use and limited knowledge.
Areas covered: We report on medication use research and have conducted a systematic review of observational studies on medication use to provide an updated overview on characteristics, objectives, methods, and patterns in hospitalized neonates. Moreover, a review on aspects of medication use for opioids, anti-epileptics, gastric acid-related disorders and respiratory stimulants with emphasis on trends and impact of interventions is presented, illustrating how research on medication use can contribute to improved neonatal pharmacotherapy and more focused research. Medication use reports describe patterns and provide signals on irrational use, benchmarking, or can guide research priorities. Moreover, this may generate information on how neonatal health topics and their pharmacotherapy are handled over time or across regions.
Expert opinion: Research on medicine utilization is relevant, since it will inform us on aspects like trends, variability, or about the impact and pattern of implementation of guidelines in neonates. Further progress necessitates to merge datasets on medication use with clinical characteristics, and perinatal drug use remains an area in need of additional research. 相似文献