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Cabazitaxel (CTX) has distinct therapeutic merits for advanced and metastatic cancer. However, the present clinical formulation (Jevtana®) has several defects, especially for undesirable tumor-targeting and serious side effects, greatly limiting the therapeutic efficacy. Small-molecule prodrug-based nanoassemblies integrate the advantages of both prodrug strategy and nanotechnology, emerging as a promising treatment modality. Herein, disulfide bonds with different lengths were employed as linkages to elaborately synthesize three redox-sensitive stearyl alcohol (SAT)-CTX prodrug-based nanoassemblies (SAC NPs, SBC NPs and SGC NPs) for seeking optimal chemotherapeutical treatment. All the prodrug-based nanoassemblies exhibited impressive drug-loading efficiency, superior self-assembly capability and excellent colloidal stability. Interestingly, the drug release behaviors of three prodrug-nanoassemblies in the same reductive environment were different owing to tiny changes in the carbon chain length of disulfide bonds, resulting in disparate cytotoxicity effects, pharmacokinetic outcomes and in vivo antitumor efficacies. Among them, SAC NPs displayed rapid drug release, excellent cytotoxicity, long blood circulation and enhanced tumor accumulation, thus showing strong tumor inhibition in the 4T1-bearing mouse model. Our study shed light on the vital role of connecting bonds in designing high-efficiency, low-toxicity prodrug nanoassemblies. [ABSTRACT FROM AUTHOR]

Thrombotic cardio‐cerebrovascular diseases seriously threaten human health. Currently, conventional thrombolytic treatments are challenged by the low utilization, inferior thrombus penetration, and high off‐target bleeding risks of most thrombolytic drugs, resulting in unsatisfactory treatment outcomes. Herein, it is proposed that these challenges can be overcome by precisely integrating the conventional thrombolytic strategy with photothermal therapy. After co‐assembly engineering optimization, a fibrin‐targeting peptide‐decorated nanoassembly of DiR (a photothermal probe) and ticagrelor (TGL, an antiplatelet drug) is prepared for thrombus‐homing delivery, abbreviated as FT‐DT NPs. The elaborately engineered nanoassembly shows multiple advantages, including simple preparation with high drug co‐loading capacity, synchronous delivery of two drugs with long systemic circulation, thrombus‐targeted accumulation with self‐indicating function, as well as photothermal‐potentiated thrombus penetration and thrombolysis with high therapeutic efficacy. As expected, FT‐DT NPs not only show bright fluorescence signals in the embolized vessels, but also perform photothermal/antiplatelet synergistic thrombolysis in vivo. This study offers a simple and versatile co‐delivery nanoplatform for imaging‐guided photothermal/antiplatelet dual‐modality thrombolysis. [ABSTRACT FROM AUTHOR]

Aim: This study analyzed clinicopathological features of colorectal mucinous carcinoma and their prognostic values. Patients & method: This study enrolled 265 patients with mucinous colorectal cancer. Clinicopathological information and prognosis were reviewed retrospectively. Kaplan-Meier method, log- rank test and COX proportional hazard regression models were used. Results: In postoperative mucinous carcinoma patients (median age 56, 119 [44.9%] female), advanced tumor stage (odds ratio [OR]: 2.378; 95% CI: 1.512-3.741; p = 0.0002), poor differentiation (OR: 1.896; CI: 1.217-2.955; p = 0.0047) and right-sided tumors (OR: 2.421; CI: 1.145-5.102; p = 0.0206) were associated with shorter overall survival. Appendiceal/ileocecal cecal tumors were not different for prognosis. Conclusion: Mucinous colorectal carcinoma exhibits distinct tumor characteristics. Poor differentiation, advanced stage at presentation and the right side serve as negative prognostic factors. [ABSTRACT FROM AUTHOR]

Background: Posterior pilon variant fracture is a recently described posterior malleolus fracture characterized by the involvement of both posterolateral and posteromedial malleolar fragment. The associated surgical approach remains controversial. The aim of this study was to present the application of modified posteromedial approach in the treatment for posterior pilon variant fracture.Methods: Sixteen patients were identified with posterior pilon variant fractures. All fractures were operated via modified posteromedial approach. Fragment length ratio, area ratio and height were measured as morphologic assessments. The clinical outcome was evaluated with American Orthopaedic Foot & Ankle Society ankle-hind foot score and visual analogue scale. Radiological images were evaluated using osteoarthritis-score.Results: According to the radiological measurements, the average fragment length ratio of posteromedial and posterolateral fragment was 25.3 and 31.5 % respectively. All fractures healed within a mean period of 13.1 weeks without malalignment or articular step-off. Fourteen patients were followed up, and all achieved good or excellent ankle function. The average score of American Orthopaedic Foot & Ankle Society and visual analogue scale at rest, motion and weight bearing walking was 85.6 and 0.25, 0.81, 1.31 respectively.Conclusion: Modified posteromedial approach provides an alternative surgical treatment for posterior pilon variant fractures, and the short-term outcome was good. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the efficacy of closed reduction (CR) in the treatment of developmental dysplasia of the hip (DDH) and to investigate risk factors associated with CR failure and avascular necrosis (AVN) occurrence in follow-ups. Methods: The study retrospectively included 110 patients and 138 hips with DDH diagnosis that underwent closed reduction between February 2012 and November 2015 in our single tertiary medical institution. The failure rate of CR and the underlying risk factors were evaluated. Meanwhile, the incidence of AVN and the related risk factors among the successful CR cases were assessed. Results: The overall failure rate of DDH treated by CR in the present study was 31.16% (43/138). Risk factors for the CR failure were older age at the time of CR (≥ 18.35 month), large medical interval before CR (≥ 35.35 mm), and severer dislocation of the affected hip (IDHI grades III and IV). The incidence of AVN was 8.33% (6/72) in patients with successful CR at the last follow-up. No significant risk factors had been established in the present study that associated with the AVN occurrence. Conclusions: For the treatment of DDH with CR, patients with younger age might achieve better outcomes; early diagnosis and early treatment might be the key point in the DDH treatment. [ABSTRACT FROM AUTHOR]

Background: Percutaneous fixation with cannulated screws is an effective method for treating medial malleolar epiphyseal fractures, which comprise a portion of bimalleolar and trimalleolar fractures. Lateral malleolar fractures also need to be fixed to achieve anatomical reduction and absolute stable fixation of the ankle. However, there are no individual studies in the literature on this topic. Methods: Thirty-six children (22 boys and 14 girls) aged 8 to 15 years (average, 11.3 years) with medial and lateral epiphyseal fractures were treated by cannulated screw and Kirschner fixation after closed reduction from January 2010 to December 2015 in our hospital. The patients were examined each month postoperatively. Ankle function was assessed using the Baird-Jackson ankle score. Results: The 36 patients were followed up for 18 to 29 months (average, 25 months). No cases of fracture non-union or secondary displacement were observed, and the healing time was 2.8 ± 1.1 months (range, 2–4 months). At the last follow-up visit, the Baird-Jackson ankle score ranged from 83 to 100 (average, 94), including an "excellent" score in 13 cases, a "good" score in 19 cases, a "fair" score in 4 cases, and a "poor" score in 0 cases. The ankle recovered to the pre-injury level of function within 3.5 ± 1.6 months (range, 2–5 months). Dysfunction, pain, instability, and premature epiphyseal closure were not observed during the follow-up of the 36 patients. Conclusions: Cannulated screw and Kirschner fixation after closed reduction is an effective and readily available method for the treatment of medial and lateral malleolar epiphyseal fractures in children. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the clinical outcomes of ipsilateral femoral neck and shaft fractures and identify the risk factors associated with missed diagnosis of femoral neck fractures and clinical outcomes of this fracture. The ipsilateral femoral neck and shaft fractures from seven centers were retrospectively reviewed. Data on injury mechanism, fracture pattern, and fracture classification; surgical factors including fixation method; and timing of detection of femoral neck fracture were analyzed. The clinical outcomes, complications, and the incidence of avascular necrosis of the femoral head (AVNFH) were reviewed. Risk factors for missed femoral neck fracture and complications were analyzed. In total, 74 patients with an average age of 43.6 years were included. Of the femoral shaft fractures, 56.8% were type A, 21.6% were type B, and 21.6% were type C. Sixteen patients had an open fracture of the femoral shaft. Femoral neck fracture was initially missed in 27% patients and the timing of delayed diagnosis was at an average of 11.1 days after injury. For detecting femoral neck fractures, minimal displacement of the femoral neck fracture was a risk factor, whereas computed tomography (CT) was a protective factor. The incidence of AVNFH was 6.8% at an average of 36.8 months after injury. The AVNFH group had more displaced femoral neck fractures at the time of surgery, but there was no difference in the timing of diagnosis compared to non-AVNFH group. The femoral shaft showed considerable healing problems, with an average union time of 29.7 weeks and a 20.2% nonunion rate. Ipsilateral femoral neck and shaft fractures had a high rate of missed diagnosis, especially in minimally displaced fractures; however, CT was a protective factor. AVNFH occurred in 6.8% and was related to femoral neck fracture displacement, but not delayed diagnosis. The femur nonunion rate was high, which warrants attention. [ABSTRACT FROM AUTHOR]

The development of functional nanoprobes and nanomedicines has long been a focal point in the realm of precision cancer therapeutics. A particularly noteworthy and promising trend in current research involves integrating diagnostic methods and treatment techniques within a single nanosystem. The luminescence phenomenon known as aggregation-induced emission (AIE) has garnered substantial attention in disease diagnosis. Recently, quite a few AIE fluorogens (AIEgens) have been developed as photothermal or photodynamic photosensitizers (PSs) for anticancer phototherapy. Particularly, the aggregation-dependent luminescent feature of AIEgens has natural correlations with the assembly construction of nanomedicines. With a variety of AIEgen-based nanosystems devised for cancer diagnosis and therapy in recent years, it is timely to delineate the latest advancements in this field at the intersection of AIE and biomedical nanotechnology. This review will concentrate on the emerging AIEgen-functionalized nanotherapeutics, encompassing AIEgen-illuminated nanoprobes for tumor-specific imaging and AIEgen-functionalized nanomedicines for cancer therapy. Also, we discuss the prospects and challenges in the clinical translation of AIE-functionalized nanomedicines. • AIEgen-functionalized nanoprobes and nanomedicines offer new avenues for precise tumor diagnosis and treatment. • AIEgen-illuminated nanoprobes become versatile diagnostic nanoplatforms for biological imaging in living systems. • AIEgen-functionalized nanomedicines show remarkable therapeutic effects. [ABSTRACT FROM AUTHOR]

Introduction: The relationship between patient expectations and clinical outcomes has recently been of increasing interest in the field of orthopaedics. The objective of this study was to evaluate the relationships between (1) patient pre-treatment expectations and post-treatment clinical outcomes, and (2) fulfillment of expectations and patient satisfaction, following distal radius fracture.Methods: This was a prospective multicenter cohort study conducted across three hospitals. A total of 133 patients admitted to hospital between 2016 and 2018 with a distal radius fracture were recruited. Patients were administered the Trauma Expectation Factor (TEF) at baseline to measure expectations of pain and functioning at one-year post-injury. Patients were followed up at 6 and 12 months post-injury and outcomes were measured using the Trauma Outcome Measure (TOM), Shortened Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire, and Short-Form 12-item (SF-12) health survey. Fulfillment of expectations was measured as TEF score minus TOM score at each time point. Patient satisfaction was also measured using the Patient Satisfaction Questionnaire Short Form (PSQ-18). Multivariate regression models were created to evaluate the effect of expectations on outcomes.Results: Patient expectations correlated moderately with outcomes at 6 and 12 months post-injury. In the multivariate analysis, patient expectations were predictive of better outcomes at 6 and 12 months. Injury severity, age, mechanism of injury, and whether the injury occurred on duty also contributed significantly to one or more regression models. Patient satisfaction correlated weakly with fulfillment of expectations at 6 months, but moderately with all outcome scores. At 12 months, satisfaction did not correlate significantly with expectations fulfillment but correlated moderately to highly with all outcome scores.Conclusion: Patient expectations independently predicted outcomes at 6 and 12 months post-injury. Standardized assessment and management of patient expectations may be relevant to future clinical practice and research to best quantify and optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: We introduce a new MIPPO procedure which is simple and effective for the treatment of extra-articular distal tibia facture (AO-43A). The aim of this retrospective study was to compare our modified MIPPO with IMN.Materials and Methods: This retrospective study included 64 patients treated with our modified MIPPO and 61 patients with IMN. The data of sex, age, operation time, blood loss, wound complications, mal-reduction, shortening and fracture healing was analyzed.Results: The operation time was significantly shorter in the MIPPO group than in the IMN group (56.0min vs. 85.0min, P<0.001). There were 5 patients (8.2%) in the IMN group and 2 patients (3.1%) in the MIPPO group who had wound complications (P=0.399). Mal-reduction occurred in 17 patients (27.9%) managed with IMN and in 3 patients (4.7%) who had MIPPO (P<0.001). Furthermore, no patients had a left/right difference in the length of the tibia of >1cm and nonunion in both groups.Conclusions: Our results have shown that our modified MIPPO has enormous advantages over IMN for extra-articular distal tibia fracture (AO-43A). [ABSTRACT FROM AUTHOR]

• Prodrug-engineered nanomedicines offer new choices for synergistic chemo-phototherapy. • Prodrug-engineered nanoplatforms for chemo-phototherapy display favorable therapeutic efficacy and security. • Nanomedicines engineered by prodrugs have a promising clinical application prospect in combinational chemo-phototherapy. Chemotherapy is one of the most commonly used treatment regimens for malignant tumors. However, the clinical outcomes of chemotherapy alone are still far from satisfactory, due to the insufficient therapeutic effect and serious side effects. Chemo-phototherapy, with the excellent advantages of synergetic treatment effect and dosage reduction of chemotherapeutics, has received wide attention in multimodal cancer therapy. Prodrug-engineered nanosystems, integrating prodrug strategy with biomedical nanotechnology, offer many benefits for efficient combination drug delivery. In recent years, a wide variety of prodrug-engineered nanomedicines have been developed for efficient chemo-phototherapy. In this review, we intend to outline the latest trends in this field, with a special focus on polymeric prodrug-nanosystems, prodrug/drug co-encapsulation nanocarriers and small-molecule prodrug-nanoassemblies. This review highlights the design rationale, advantages and challenges of the emerging prodrug-engineered nanomedicines in synergistic chemo-phototherapy. [ABSTRACT FROM AUTHOR]

• Hybrid nanomedicines offer new choices for combination cancer therapy. • Carrier-free nanoassemblies display favorable therapeutic efficacy and security. • Nanomedicines engineered by drugs/prodrugs have a bright clinical prospect. Cancer should not be simply regarded as a single disease, but an intricate adaptive system involved with inflammation, metabolism and immunization. Therefore, combination of two or more antineoplastic drugs reveals distinct advantages over monotherapy. However, despite the rapid development of biomedical nanotechnology, it remains challenging to precisely co-deliver multiple drugs into tumors, owing to the differences between the compatibility of different drugs and nanomaterials. Many efforts have been devoted to developing new nanodrug delivery systems (NDDS). In recent years, carrier-free nanoassemblies engineered by small molecules have emerged as a promising and versatile nanoplatform for co-delivery of anticancer drugs. Given the rapid progress in carrier-free small-molecule hybrid nanoassemblies, we here provide an overview on the latest updates in this emerging field. First, the recent trends in nanomedicines engineered by pure drugs and/or prodrugs are summarized. Then, the underlying assembly mechanisms and drug release characteristics are briefly analyzed. Finally, the prospects and challenges of hybrid nanoassemblies in clinical translation are highlighted. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cascade GSH-responsive drug delivery platform for Pt(IV) prodrug. • Alleviated systemic toxicity and ensured biosafety. • High drug loading capacity and colloid stability. The platinum-based drugs prevail in the therapy of malignant tumors treatment. However, their clinical outcomes have been heavily restricted by severe systemic toxicities. To ensure biosafety and efficiency, herein, we constructed a disulfide bond inserted Pt(IV) self-assembled nanoplatform that is selectively activated by rich glutathione (GSH) in tumor site. Disulfide bond was introduced into the conjugates of oxaliplatin (IV) and oleic acid (OA) which conferred cascade reduction-responsiveness to nanoassemblies. Disulfide bond cleavage and reduction of Pt(IV) center occur sequentially as a cascade process. In comparison to oxaliplatin solution, Pt(IV) nanoparticles (NPs) achieved prolonged blood circulation and higher maximum tolerated doses. Furthermore, Oxa(IV)-SS-OA prodrug NPs exhibited potent anti-tumor efficiency against 4T1 cells and low toxicities in other normal tissues, which offers a promising nano-platform for potential clinical application. [ABSTRACT FROM AUTHOR]