Short-term Changes in Health-related Quality of Life of Patients Undergoing Radical Surgery for Upper Urinary Tract Urothelial Carcinoma: Results from a Prospective Phase 2 Clinical Trial.

Background and objective: The possible negative impact of radical surgery on patients' health-related quality of life (HRQoL) plays an important role in preoperative counseling. Here, we analyzed the HRQoL of patients treated for upper urinary tract urothelial carcinoma (UTUC) in the context of a single-arm phase 2 multicenter study, in which the safety and efficacy of a single preoperative intravesical instillation with mitomycin C were investigated. Our objective was to investigate early changes in HRQoL in patients undergoing radical surgery for UTUC and identify factors associated with these outcomes. Methods: Patients with pTanyN0-1M0 UTUC were prospectively included. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) questionnaire at baseline, and at 1 and 3 mo after surgery. A linear mixed model was used to evaluate the changes in HRQoL over time and identify the variables associated with these outcomes. The clinical effect size was used to assess the clinical impact and level of perceptibility of HRQoL changes for clinicians and/or patients based on given thresholds. Key findings and limitations: Between 2017 and 2020, 186 patients were included. At baseline, 1 mo after surgery, and 3 mo after surgery, response rates were 91%, 84%, and 78%, respectively. One month after surgery, a statistically significant and clinically relevant deterioration was observed in physical, role, and social functioning, and for the included symptom scales: constipation, fatigue, and pain. An improvement in emotional functioning was observed. At 3 mo, HRQoL returned to baseline levels, except emotional functioning, which improved at 1 mo and persisted to be better than that before surgery. Age >70 yr was associated with worse physical functioning, but better social and emotional functioning. Male patients reported better emotional functioning than females. Postoperative complications were negatively associated with social functioning. Conclusions and clinical implications: UTUC patients treated with radical surgery experienced a significant, albeit temporary, decline in HRQoL. Three months following surgery, HRQoL outcomes returned to baseline levels. This information can be used to counsel UTUC patients before undergoing radical surgery and contextualize recovery after surgery. Patient summary: We investigated the changes in quality of life as reported by patients who underwent surgery for upper tract urothelial carcinoma (UTUC). We found that patients experienced a decline in quality of life 1 mo after surgery, but this was temporary, with full recovery of quality of life 3 mo after surgery. These findings can help doctors and other medical staff in counseling UTUC patients before undergoing radical surgery.

The accuracy of cystoscopy in predicting muscle invasion in newly diagnosed bladder cancer patients.

PURPOSE: The prognosis of muscle-invasive bladder cancer (MIBC) has not improved for three decades. Transurethral resection of the bladder tumor (TURBT) is the standard procedure for local tumor staging. TURBT has several limitations, including the spread of tumor cells. Therefore, an alternative is needed in patients with suspected MIBC. Recent studies have shown that mpMRI is very accurate in staging bladder tumors. Because the diagnostic efficacy of urethrocystoscopy (UCS) has been reported as good as the efficacy of mpMRI to predict muscle invasion we performed this prospective multicenter study in which we compare UCS with pathology. METHODS: From July 2020 until March 2022, 321 patients with suspected primary BC in seven participating Dutch hospitals were included in this study. A flexible UCS was performed by urologists, physician assistants, or residents. Predictions of muscle invasion using a 5-point Likert scale alongside the histopathology data were recorded. The sensitivity, specificity, predictive values, and 95% confidence intervals were determined using a standard contingency table. RESULTS: Of the 321 included patients, 232 (72.3%) received a histopathological diagnosis of non-muscle-invasive bladder cancer (NMIBC) and 71 (22.1%) were histopathologically diagnosed as MIBC. In 2 patients (0.6%), classification was not possible (Tx). Cystoscopy predicted muscle invasion with a sensitivity of 71.8% (95% CI 59.9-81.9), and a specificity of 89.9% (95% CI 85.4-93.3). This corresponds to a positive predictive value (PPV) of 67.1% and a negative predictive value (NPV) of 91.7%. CONCLUSION: Our study shows a moderate accuracy of cystoscopy to predict muscle invasion. This result does not support the use of cystoscopy only instead of TURBT for local staging.

3-D and 2-D reconstruction of bladders for the assessment of inter-session detection of tissue changes: a proof of concept.

PURPOSE: Abnormalities in the bladder wall require careful investigation regarding type, spatial position and invasiveness. Construction of a 3-D model of the bladder is helpful to ensure adequate coverage of the scanning procedure, quantitative comparison of bladder wall textures between successive sessions and finding back previously discovered abnormalities. METHODS: Videos of both an in vivo bladder and a textured bladder phantom were acquired. Structure-from-motion and bundle adjustment algorithms were used to construct a 3-D point cloud, approximate it by a surface mesh, texture it with the back-projected camera frames and draw the corresponding 2-D atlas. Reconstructions of successive sessions were compared; those of the bladder phantom were co-registered, transformed using 3-D thin plate splines and post-processed to highlight significant changes in texture. RESULTS: The reconstruction algorithms of the presented workflow were able to construct 3-D models and corresponding 2-D atlas of both the in vivo bladder and the bladder phantom. For the in vivo bladder the portion of the reconstructed surface area was 58% and 79% for the pre- and post-operative scan, respectively. For the bladder phantom the full surface was reconstructed and the mean reprojection error was 0.081 mm (range 0-0.79 mm). In inter-session comparison the changes in texture were correctly indicated for all six locations. CONCLUSION: The proposed proof of concept was able to perform 3-D and 2-D reconstruction of an in vivo bladder wall based on a set of monocular images. In a phantom study the computer vision algorithms were also effective in co-registering reconstructions of successive sessions and highlighting texture changes between sessions. These techniques may be useful for detecting, monitoring and revisiting suspicious lesions.

Drug delivery approaches for enhanced antibiofilm therapy.

Biofilms have attracted increasing attention in recent years. Many bacterial infections are associated with biofilm formation. A bacterial biofilm is an aggregated membrane-like substance that is composed of a large number of bacteria and their secreted extracellular polymeric substances. The traditional antibiofilm approaches, such as chemotherapy based on antibiotics, are often ineffective in eradicating biofilms owing to the limited diffusion ability of antibiotics within biofilms and inactivation of antibiotics by biofilms. Moreover, a larger dosage of antibiotics could be effective, but leads to an increased tolerance. Smart drug delivery systems that deliver antibiotics into the biofilm interior is a promising strategy to meet this challenge. In this review, we focus on the methods to improve drug delivery efficiency for enhanced chemotherapy of biofilms. Furthermore, we have summarized chemical approaches for enhanced drug delivery, such as chemical shields, charge reversal, and dual corona enhanced delivery strategies; these methods focus on physicochemical biofilm properties and specific biofilm features. Afterwards, physical approaches are discussed, such as magnetism-mediated drug delivery, electricity-mediated drug delivery, ultrasound-mediated drug delivery, and shock wave-mediated drug delivery. Finally, a perspective on the development of next-generation antibiofilm drug delivery systems is given.

Chirality-controlled polymerization-induced self-assembly.

Recent studies have shown that biodegradable nanoparticles can be efficiently prepared with polymerization of N-carboxyanhydrides-induced self-assembly (NCA-PISA). However, thus far, the effect of chiral monomer ratio on such NCA-PISA formulations and the resulting nanoparticles has not yet been fully explored. Herein, we show, for the first time, that the morphology, secondary structure, and biodegradation rate of PISA nanoparticles can be controlled by altering the chiral ratio of the core-forming monomers. This chirality-controlled PISA (CC-PISA) method allowed the preparation of nanoparticles that are more adjustable and applicable for future biomedical applications. Additionally, the complex secondary peptide structure (ratio of α-helix to ß-sheet) and π-π stacking affect the polymer self-assembly process. More specifically, a PEG45 macro-initiator was chain-extended with l- and d-phenylalanine (l- and d-Phe-NCA) in various molar ratios in dry THF at 15 wt%. This ring-opening polymerization (ROP) allowed the preparation of homo- and hetero-chiral Phe-peptide block copolymers that self-assembled in situ into nanoparticles. For homo-chiral formulations, polymers self-assembled into vesicles once a sufficiently high phenylalanine degree of polymerization (DP) was obtained. Hetero-chiral formulations formed larger nanoparticles with various morphologies and, much to our surprise, using an equal enantiomer ratio inhibited PISA and led to a polymer solution instead. Finally, it was shown that the enzymatic biodegradation rate of such PISA particles is greatly affected by the polymer chirality. This PISA approach could be of great value to fabricate nanoparticles that exploit chirality in disease treatment.

Selecting interventions for a psychosocial support program for prostate cancer patients undergoing active surveillance: A modified Delphi study.

OBJECTIVE: Curative treatment of low-risk prostate cancer (LR-PCa) does not improve cancer specific survival and active surveillance (AS) is recommended. Although AS is cost-effective and reduces treatment-related complications, it requires psychosocial support. Research on psychosocial interventions specifically focused on men undergoing AS is limited. Aim of this study is to reach consensus amongst relevant stakeholders on selecting interventions offering psychosocial support to PCa patients during AS. METHODS: In accordance with the RAND/UCLA method, a modified Delphi approach was used to establish consensus on selecting interventions. During phase one, interventions were identified through a literature review and open survey among all participants. During phase two, three consensus rounds were conducted to rate potential interventions and obtain statistical consensus. The IQ healthcare consensus tool was used to calculate statistical consensus. RESULTS: After the first consensus round, 31 participants scored individual interventions on relevance using a 9-point Likert scale resulting in the selection of six interventions. During the second consensus round 13 discussion items were reviewed during a focus group. After the third consensus round, seven additional interventions were selected by 23 participants. CONCLUSIONS: In total, 13 interventions were selected for inclusion in a support program. This included four interventions within the domain information and education, three within coping and support, one intervention within physical wellbeing and four within the domain lifestyle.

What interventions affect the psychosocial burden experienced by prostate cancer patients undergoing active surveillance? A scoping review.

PURPOSE: Living with untreated prostate cancer (PCa) may cause anxiety and uncertainty in men undergoing active surveillance (AS). Developing a psychosocial support program for such patients might promote psychosocial well-being and patient engagement. This review aims to identify interventions with the potential to influence the psychosocial burden of prostate cancer patients undergoing AS. METHODS: A scoping review was conducted in accordance with the PRISMA Extension for Scoping Reviews Checklist. A systematic search was conducted in six databases and included publications dating from 2009. All available and eligible evidence was included in this review. RESULTS: After screening 2824 articles, 12 studies were included in the review: nine quantitative, one qualitative, and two mixed method papers. The relative strength of these studies was limited and the quality of most was moderate. CONCLUSIONS: The described interventions can be categorized into three major themes: information and education, coping and (psycho)social support, and lifestyle. Psychosocial support for men undergoing AS should entail involvement of family and spouse during the decision-making process, tailored information about PCa treatments, risks, benefits, protocols, lifestyle adjustments, and complementary and alternative medicine. Assessment and promotion of effective coping and self-management strategies are recommended. Healthcare providers should actively promote physical activity and nutritional improvements. Physical activity programs may also be helpful in facilitating peer support, which is especially important for men with limited social support. Future research should investigate combining interventions to increase efficacy and optimize supportive care during AS.

Bone-Targeting Polymer Vesicles for Effective Therapy of Osteoporosis.

With the aging of the population, postmenopausal osteoporosis becomes increasingly widespread and severe as fractures caused by osteoporosis may lead to permanent disabilities and even death. Inspired by extracellular vesicles that participate in bone remodeling, we present a biomimicking polymer vesicle for bone-targeted ß-estradiol (E2) delivery. This vesicle is self-assembled from a poly(ε-caprolactone)28-block-poly[(l-glutamic acid)7-stat-(l-glutamic acid-alendronic acid)4] (PCL28-b-P[Glu7-stat-(Glu-ADA)4]) diblock copolymer. The alendronic acid (ADA) on the coronas endows the polymer vesicles with a high bone affinity and acts synergistically with E2 to achieve an enhanced therapeutic effect. As confirmed with ovariectomized osteoporosis rat models, bone loss was significantly reversed as the recovery rates of total BMD (bone mineral density) and trabecular BMD were 70.4% and 99.3%, respectively. Overall, this work provides fresh insight into the treatment of osteoporosis.

Clinical use of the SelectMDx urinary-biomarker test with or without mpMRI in prostate cancer diagnosis: a prospective, multicenter study in biopsy-naïve men.

BACKGROUND: Risk stratification in men with suspicion of prostate cancer (PCa) requires reliable diagnostic tests, not only to identify high-grade PCa, also to minimize the overdetection of low-grade PCa, and reduction of "unnecessary" prostate MRIs and biopsies. This study aimed to evaluate the SelectMDx test to detect high-grade PCa in biopsy-naïve men. Subsequently, to assess combinations of SelectMDx test and multi-parametric (mp) MRI and its potential impact on patient selection for prostate biopsy. METHODS: This prospective multicenter diagnostic study included 599 biopsy-naïve patients with prostate-specific antigen level ≥3 ng/ml. All patients underwent a SelectMDx test and mpMRI before systematic transrectal ultrasound-guided biopsy (TRUSGB). Patients with a suspicious mpMRI also had an in-bore MR-guided biopsy (MRGB). Histopathologic outcome of TRUSGB and MRGB was used as reference standard. High-grade PCa was defined as ISUP Grade Group (GG) ≥ 2. The primary outcome was the detection rates of low- and high-grade PCa and number of biopsies avoided in four strategies, i.e., (1) SelectMDx test-only, (2) mpMRI-only, (3) SelectMDx test followed by mpMRI when SelectMDx test was positive (conditional strategy), and (4) SelectMDx test and mpMRI in all (joint strategy). A positive SelectMDx test outcome was a risk score of ≥-2.8. Decision curve analysis (DCA) was performed to assess clinical utility. RESULTS: Prevalence of high-grade PCa was 31% (183/599). Thirty-eight percent (227/599) of patients had negative SelectMDx test in whom biopsy could be avoided. Low-grade PCa was not detected in 35% (48/138) with missing 10% (18/183) high-grade PCa. Yet, mpMRI-only could avoid 49% of biopsies, not detecting 4.9% (9/183) of high-grade PCa. The conditional strategy reduces the number of mpMRIs by 38% (227/599), avoiding biopsy in 60% (357/599) and missing 13% (24/183) high-grade PCa. Low-grade PCa was not detected in 58% (80/138). DCA showed the highest net benefit for the mpMRI-only strategy, followed by the conditional strategy at-risk thresholds >10%. CONCLUSIONS: SelectMDx test as a risk stratification tool for biopsy-naïve men avoids unnecessary biopsies in 38%, minimizes low-grade PCa detection, and misses only 10% high-grade PCa. Yet, using mpMRI in all patients had the highest net benefit, avoiding biopsy in 49% and missing 4.9% of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx test positive patients is a good alternative strategy.

Combined Antioxidant-Antibiotic Treatment for Effectively Healing Infected Diabetic Wounds Based on Polymer Vesicles.

Infected diabetic wounds are difficult to heal due to high reactive oxygen species (ROS) concentrations and recurrent infections. Such wounds can easily deteriorate into a diabetic ulcer, a chronic diabetic complication with a very high mortality rate. Herein, we propose a combined antioxidant-antibiotic therapy based on poly(ε-caprolactone)-block-poly(glutamic acid) polymer vesicle to treat infected diabetic wounds. This was realized by in situ decoration of stable, well-dispersed ceria nanoparticles onto ciprofloxacin (CIP)-loaded polymer vesicles. These resulting CIP-loaded and ceria-decorated polymer vesicles (CIP-Ceria-PVs) exhibited high superoxide dismutase mimetic activity to inhibit superoxide free radicals (the inhibition rate reached ∼50% at an extremely low cerium concentration of 1.25 µg/mL). When the cerium content is in the range of 5-20 µg/mL, the CIP-Ceria-PVs showed the highest protective capability to normal L02 cells from damage of superoxide free radicals. In addition, the CIP-Ceria-PVs exhibited enhanced antibacterial activity (the dosage of CIP in CIP-Ceria-PVs was reduced by 25-50% compared to free CIP). In vivo treatment of infected diabetic wounds was performed on a diabetic mice model. The CIP-Ceria-PVs could effectively cure infected diabetic wounds within 14 days. Overall, a combined antioxidant-antibiotic therapy was proposed by introducing ceria nanoparticles and CIP into polymer vesicles for the treatment of infected diabetic wounds.

Ultrasound-responsive polymer-based drug delivery systems.

Ultrasound-responsive polymeric materials have received a tremendous amount of attention from scientists for several decades. Compared to other stimuli-responsive materials (such as UV-, thermal-, and pH-responsive materials), these smart materials are more applicable since they allow more efficient drug delivery and targeted treatment by fairly non-invasive means. This review describes the recent advances of such ultrasound-responsive polymer-based drug delivery systems and illustrates various applications. More specifically, the mechanism of ultrasound-induced drug delivery, typical formulations, and biomedical applications (tumor therapy, disruption of blood-brain barrier, fighting infectious diseases, transdermal drug delivery, and enhanced thrombolysis) are summarized. Finally, a perspective on the future research directions for the development of ultrasound-responsive polymeric materials to facilitate a clinical translation is given.

Argus-T adjustable male sling: A follow-up study on urinary incontinence and patient's satisfaction.

AIMS: The use of Argus-T adjustable sling may be a promising alternative option for the treatment of urinary incontinence after radical prostatectomy, however long-term data is lacking. The aim of this study is to evaluate the long-term results of the Argus-T sling on incontinence rates, patient's quality of life and tape-related complications. METHODS: Patients were eligible if persistent stress incontinence was present ≥12 months after radical prostatectomy. Measurements included 24 h frequency volume micturition list, 24 h pad test, 24 h pad count and quality of life questionnaires. Argus-T adjustable sling was placed with a single perineal route incision approach. RESULTS: Seventy-eight patients were included, 69 ± 6 years, pre-intervention 24 h urinary loss 212 (75-385) g. Directly after surgery, 63.6% of the patients was completely dry, 79.2% of the patients reported greater than 90% improvement of their urinary loss and 92.2% > 50% improvement. Median follow-up time was 3.2 (2.5-6.1) years. After 5 years of follow-up, 53.3% of the patients were completely dry, 71.5% reported an improvement greater than 90% and 79.6% reported an improvement of greater than 50%. Patients with preoperative urinary loss less than 250 g reported significantly higher improvement of their urinary loss compared to patients with urinary loss ≥250 g (p = .02). Patients satisfaction was still increased after 5 years follow-up (70 ± 21 vs.16 ± 9, p < .001) and patients quality of life remained high (85 ± 20 vs. 88 ± 13, p = .1). Complications were mainly observed directly after surgery. Two patients (2.6%) needed reimplantation of the sling. CONCLUSION: These data indicate that Argus-T sling is an effective treatment option in obtaining substantial long-term incontinence relief in patients with invalidating moderate stress urinary incontinence after radical prostatectomy.

Synthesis of Highly Transparent Diblock Copolymer Vesicles via RAFT Dispersion Polymerization of 2,2,2-Trifluoroethyl Methacrylate in n-Alkanes.

RAFT dispersion polymerization of 2,2,2-trifluoroethyl methacrylate (TFEMA) is performed in n-dodecane at 90 °C using a relatively short poly(stearyl methacrylate) (PSMA) precursor and 2-cyano-2-propyl dithiobenzoate (CPDB). The growing insoluble poly(2,2,2-trifluoroethyl methacrylate) (PTFEMA) block results in the formation of PSMA-PTFEMA diblock copolymer nano-objects via polymerization-induced self-assembly (PISA). GPC analysis indicated narrow molecular weight distributions (M w/M n ≤ 1.34) for all copolymers, with 19F NMR studies indicating high TFEMA conversions (≥95%) for all syntheses. A pseudo-phase diagram was constructed to enable reproducible targeting of pure spheres, worms, or vesicles by varying the target degree of polymerization of the PTFEMA block at 15-25% w/w solids. Nano-objects were characterized using dynamic light scattering, transmission electron microscopy, and small-angle X-ray scattering. Importantly, the near-identical refractive indices for PTFEMA (1.418) and n-dodecane (1.421) enable the first example of highly transparent vesicles to be prepared. The turbidity of such dispersions was examined between 20 and 90 °C. The highest transmittance (97% at 600 nm) was observed for PSMA9-PTFEMA294 vesicles (237 ± 24 nm diameter; prepared at 25% w/w solids) in n-dodecane at 20 °C. Interestingly, targeting the same diblock composition in n-hexadecane produced a vesicle dispersion with minimal turbidity at a synthesis temperature of 90 °C. This solvent enabled in situ visible absorption spectra to be recorded during the synthesis of PSMA16-PTFEMA86 spheres at 15% w/w solids, which allowed the relatively weak n→π* band at 515 nm assigned to the dithiobenzoate chain-ends to be monitored. Unfortunately, the premature loss of this RAFT chain-end occurred during the RAFT dispersion polymerization of TFEMA at 90 °C, so meaningful kinetic data could not be obtained. Furthermore, the dithiobenzoate chain-ends exhibited a λmax shift of 8 nm relative to that of the dithiobenzoate-capped PSMA9 precursor. This solvatochromatic effect suggests that the problem of thermally labile dithiobenzoate chain-ends cannot be addressed by performing the TFEMA polymerization at lower temperatures.

Giant Polymer Vesicles with a Latticelike Membrane.

Hierarchical self-assembly offers great possibilities to mimic biological systems with finely arranged complex structures. Herein, we demonstrate the preparation and formation mechanism of an unusual giant polymer vesicle with a latticelike membrane (GVLM). This GVLM is formed by fusion-induced particle assembly (FIPA) of small vesicles that are self-assembled from poly(ethylene oxide)-block-poly[(2-(tetrahydrofuranyloxy)ethyl methacrylate)-stat-(6-(3,3-diphenylnaphthopyranyloxy)hexyl methacrylate)] [PEO43-b-P(TMA22-stat-NMA4)]. Flexible TMA units with high chain mobility and relatively rigid NMA units with intrinsic π-π stacking form the hydrophobic block. These units act as "antifusion" and "profusion" components, respectively. The latticelike membrane of the final GVLM consists of hundreds of small polymer vesicles that are interconnected via multiple interactions. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) studies show that the diameter of the GVLMs is 800-1000 nm. Overall, we provide a new insight into the judicious preparation of hierarchical nanostructures via chemical synthesis and FIPA.

Bone-targeting polymer vesicles for simultaneous imaging and effective malignant bone tumor treatment.

We present a bone-targeting polymer vesicle with excellent single photon emission computed tomography/computed tomography (SPECT/CT) imaging capability and high antitumor drug delivery efficiency as an integrated platform for the simultaneous diagnosing and treatment of malignant bone tumors. This polymer vesicle can be self-assembled from poly(ε-caprolactone)67-b-poly[(L-glutamic acid)6-stat-(L-glutamic acid-alendronic acid)16] (PCL67-b-P[Glu6-stat-(Glu-ADA)16]), directly in water without the aid of a cosolvent. SPECT/CT dynamically tracked the drug distribution in the bone tumor rabbit models, and the tumor size was significantly reduced from >2.0 cm3 to <0.6 cm3 over 11 days. The pathological analysis demonstrated obvious necrosis and apoptosis of the tumor cells. Overall, this bone-targeting polymer vesicle provides us with a new platform for the combination of real-time diagnosis and therapy of malignant bone tumors.

Optimizing the risk threshold of lymph node involvement for performing extended pelvic lymph node dissection in prostate cancer patients: a cost-effectiveness analysis.

BACKGROUND: Extended pelvic lymph node dissection (ePLND) may be omitted in prostate cancer (CaP) patients with a low predicted risk of lymph node involvement (LNI). The aim of the current study was to quantify the cost-effectiveness of using different risk thresholds for predicted LNI in CaP patients to inform decision making on omitting ePLND. METHODS: Five different thresholds (2%, 5%, 10%, 20%, and 100%) used in practice for performing ePLND were compared using a decision analytic cohort model with the 100% threshold (i.e., no ePLND) as reference. Compared outcomes consisted of quality-adjusted life years (QALYs) and costs. Baseline characteristics for the hypothetical cohort were based on an actual Dutch patient cohort containing 925 patients who underwent ePLND with risks of LNI predicted by the Memorial Sloan Kettering Cancer Center web-calculator. The best strategy was selected based on the incremental cost effectiveness ratio when applying a willingness to pay (WTP) threshold of €20,000 per QALY gained. Probabilistic sensitivity analysis was performed with Monte Carlo simulation to assess the robustness of the results. RESULTS: Costs and health outcomes were lowest (€4,858 and 6.04 QALYs) for the 100% threshold, and highest (€10,939 and 6.21 QALYs) for the 2% threshold, respectively. The incremental cost effectiveness ratio for the 2%, 5%, 10%, and 20% threshold compared with the first threshold above (i.e., 5%, 10%, 20%, and 100%) were €189,222/QALY, €130,689/QALY, €51,920/QALY, and €23,187/QALY respectively. Applying a WTP threshold of €20.000 the probabilities for the 2%, 5%, 10%, 20%, and 100% threshold strategies being cost-effective were 0.0%, 0.3%, 4.9%, 30.3%, and 64.5% respectively. CONCLUSION: Applying a WTP threshold of €20.000, completely omitting ePLND in CaP patients is cost-effective compared to other risk-based strategies. However, applying a 20% threshold for probable LNI to the Briganti 2012 nomogram or the Memorial Sloan Kettering Cancer Center web-calculator, may be a feasible alternative, in particular when higher WTP values are considered.

Effect of Salt on the Formation and Stability of Water-in-Oil Pickering Nanoemulsions Stabilized by Diblock Copolymer Nanoparticles.

Sterically stabilized diblock copolymer nanoparticles are prepared in n-dodecane using polymerization-induced self-assembly. Precursor Pickering macroemulsions are then prepared by the addition of water followed by high-shear homogenization. In the absence of any salt, high-pressure microfluidization of such precursor emulsions leads to the formation of relatively large aqueous droplets with DLS measurements indicating a mean diameter of more than 600 nm. However, systemically increasing the salt concentration produces significantly finer droplets after microfluidization, until a limiting diameter of around 250 nm is obtained at 0.11 M NaCl. The mean size of these aqueous droplets can also be tuned by systematically varying the nanoparticle concentration, applied pressure, and the number of passes through the microfluidizer. The mean number of nanoparticles adsorbed onto each aqueous droplet and their packing efficiency are calculated. SAXS studies conducted on a Pickering nanoemulsion prepared using 0.11 M NaCl confirms that the aqueous droplets are coated with a loosely packed monolayer of nanoparticles. The effect of varying the NaCl concentration within the droplets on their initial rate of Ostwald ripening is investigated using DLS. Finally, the long-term stability of these water-in-oil Pickering nanoemulsions is assessed using analytical centrifugation. The rate of droplet ripening can be substantially reduced by using 0.11 M NaCl instead of pure water. However, increasing the salt concentration up to 0.43 M provided no further improvement in the long-term stability of such nanoemulsions.

Design principles, synthesis and biomedical applications of polymer vesicles with inhomogeneous membranes.

Inspired by cell membrane structures, synthetic polymer vesicles caused great expectations for the preparation of biomedicine for decades. However, in contrast to bio-membranes, which consist of inhomogeneous features, conventional synthetic polymer vesicles usually consist of a homogeneous membrane which is purely made out of hydrophobic components. This significantly limited the versatility of synthetic polymer vesicle membranes. Fortunately, polymer vesicles with inhomogeneous membranes were recently developed to address this limitation. These new inhomogeneous membrane features introduced secondary functions to the vesicle membrane. Indeed, the membrane of polymer vesicles no longer only serves as a simple barrier that separates the interior from the exterior environment. Introduced membrane features can act as a versatile platform for tailorable nanoparticle functionalities, which allow functions such as biomacromolecule transportation, diabetes treatment, and cancer theranostics. This review highlights recent advances made with polymer vesicles with inhomogeneous membrane structures. More specifically, design principles, biomedical applications, and the future perspectives of such vesicles are summarized.