Leukotriene receptor antagonists as adjuvant therapy of antihistamines in chronic urticaria: a systematic review and meta-analysis.

Certain guidelines recommend a second-generation H1-antihistamine (AH) as first-line treatment for patients with chronic urticaria (CU). However, some patients show insufficient response to a standard dose of this therapy and might benefit from adding leukotriene receptor antagonists (LTA). Therefore, we aimed to perform a systematic review and meta-analysis comparing LTA plus antihistamines with antihistamines alone. We performed a systematic review and meta-analysis, searching PubMed, EMBASE, and Cochrane Central for randomized clinical trial (RCT) data comparing LTA plus AH treatment to AH alone in patients with CU. Statistical analysis was performed using R Studio 4.3.2. Heterogeneity was assessed with I2 statistics. Three studies comprising 234 patients with urticaria were included. The mean age was 37.23 years in the leukotriene antagonist + antihistamines (LTA + AH) group and 39.14 years in the antihistamines (AH) group. Follow-up ranged from 2 to 18 months between studies. There was no statistically significant difference between groups in terms of TSS level (SMD: -74.82; 95% CI: -222.66 to 73.02; P = 0.32; I2 = 98%), neither in terms of pruritus (MD: -0.07; 95% CI: -0.42 to 0.28; P = 0.70; I2 = 74%). After sensitivity analysis, with the systematic exclusion of each study from the grouped estimates, the result for TSS level did not change. These findings suggest that leukotriene receptor antagonists with antihistamines do not have better outcomes than antihistamines alone regarding TSS and pruritus in patients with CU.

Early Mobilization Decision after an Acute Ischemic Stroke: Protocol for an Umbrella Review.

INTRODUCTION: Stroke is considered one of the greatest public health challenges worldwide, with the ischemic subtype being the most prevalent. Various acute stroke clinical guidelines recommend early rehabilitation interventions, including very early mobilization. However, despite the studies conducted in recent years regarding when to initiate mobilization after an acute stroke, there are few systematic and personalized protocols based on the factors for which patient mobilization should ideally be performed. We aim to conduct an umbrella review of systematic reviews and meta-analyses to study the early mobilization decision after an acute ischemic stroke in comparison with conventional care and correlate the different approaches with patient clinical outcomes. METHODS AND ANALYSIS: We will perform a systematic search on PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Epistemonikos and Web of Science Core Collection databases. Retrieved studies will be independently reviewed by two authors and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias in the selected studies. We will use the 16-item Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist as the critical appraisal tool to assess cumulative evidence and risk of bias of the different studies. This will be the first umbrella review that compares early mobilization approaches in post-acute ischemic stroke. This study may help to define the optimal early mobilization strategy in stroke patients. PROSPERO registration number: CRD42023430494.

Automatic multi-view pose estimation in focused cardiac ultrasound.

Focused cardiac ultrasound (FoCUS) is a valuable point-of-care method for evaluating cardiovascular structures and function, but its scope is limited by equipment and operator's experience, resulting in primarily qualitative 2D exams. This study presents a novel framework to automatically estimate the 3D spatial relationship between standard FoCUS views. The proposed framework uses a multi-view U-Net-like fully convolutional neural network to regress line-based heatmaps representing the most likely areas of intersection between input images. The lines that best fit the regressed heatmaps are then extracted, and a system of nonlinear equations based on the intersection between view triplets is created and solved to determine the relative 3D pose between all input images. The feasibility and accuracy of the proposed pipeline were validated using a novel realistic in silico FoCUS dataset, demonstrating promising results. Interestingly, as shown in preliminary experiments, the estimation of the 2D images' relative poses enables the application of 3D image analysis methods and paves the way for 3D quantitative assessments in FoCUS examinations.

Neurosonology Survey in Europe and Beyond.

Purpose To provide an overview on education, training, practice requirements, and fields of application of neurosonology in Europe and beyond. Materials and Methods National representatives and experts in neurosonology were surveyed regarding neurosonology requirements and practice in their countries. Descriptive statistics were used to report the data. Results Between February 1 and March 31, 2023, 42/46 (91.3%) national representatives responded to our questionnaire and the completion rate was 100%. Most countries (71.4%) offer a neurosonology training program during neurology residency, but it is part of the undergraduate medical program only in 30.9%. National certification is available in 47.6% of the countries surveyed and most countries (76.2%) require certification to practice. In 50% of the countries, candidates are assessed by a board examination, while in 26.2% they just need to document their practice. There is no formal accreditation of neurosonology centers in 78.6% of the countries surveyed. Only a few require certified personnel and appropriate equipment. Adequate teaching and research activities are only rarely necessary elements for laboratory accreditation. Conclusion Our results indicate that there is a substantial need for transnational harmonization of neurosonological standards to guarantee uniformity and quality of performance. This survey will also provide guidance to promote an international accrediting council and create a quality-controlled laboratory network for implementing neurosonology in clinical trials.

Acute management of cerebral venous thrombosis: Indications, technique, and outcome of endovascular treatment in two high-volume centers.

INTRODUCTION: After several uncontrolled studies and one randomized clinical trial, there is still uncertainty regarding the role of endovascular treatment (EVT) in cerebral venous thrombosis (CVT). This study aims to describe and assess different acute management strategies in the treatment of CVT. METHODS: We performed a retrospective analysis of an international two-center registry of CVT patients admitted since 2019. Good outcome was defined as a return to baseline modified Rankin scale at three months. We described and compared EVT versus no-EVT patients. RESULTS: We included 61 patients. Only one did not receive systemic anticoagulation. EVT was performed in 13/61 (20%) of the cases, with a median time from diagnosis to puncture of 4.5 h (1.25-28.5). EVT patients had a higher median baseline NIHSS [6 (IQR 2-17) vs 0 (0-2.7), p = 0.002)] and a higher incidence of intracerebral hemorrhage (53.8% vs 20.3%, p = 0.03). Recanalization was achieved in 10/13 (77%) patients. Thrombectomy was performed in every case with angioplasty in 7 out of 12 patients and stenting in 3 cases. No postprocedural complication was reported. An improvement of the median NIHSS from baseline to discharge [6 (2-17) vs 1(0-3.75); p < 0.001] was observed in EVT group. A total of 31/60 patients (50.8%) had good outcomes. Adjusting to NIHSS and ICH, EVT had a non-significant increase in the odds of a good outcome [aOR 1.42 (95%CI 0.73-2.8, p = 0.307)]. CONCLUSIONS: EVT in combination with anticoagulation was safe in acute treatment of CVT as suggested by NIHSS improvement. Selected patients may benefit from this treatment.

A single session of a beach volleyball exergame did not improve state anxiety level in healthy adult women.

This study evaluated the acute effect of the exergame Kinect Sports® beach volleyball on state anxiety level in adult women. Thirty healthy adult women (age: 21 [4] years, body mass: 54.70 [19.50] kg, height: 1.61 ± 0.05 m, and body mass index: 21.87 [5.76] kg/m2, data are expressed as median [interquartile range] and as the mean ± standard deviation) were assigned to play an exergame of beach volleyball in singleplayer mode session (intervention session) for ~ 30 min using the Xbox 360 Kinect® or remained seated (control session). State anxiety was evaluated before and after the intervention and control sessions through the State-Trait Anxiety Inventory. State anxiety obtained in both sessions (exergame and control) was classified as intermediate before (median: 36.00 [IQR: 4.75] and mean = 38.73 ± 7.23, respectively) and after (mean: 34.86 ± 6.81 and mean: 37.66 ± 8.44, respectively). Friedman test found no time significant effect on state anxiety of the sessions (χ2 [3] = 6.45, p-value = 0.092, Kendall's W = 0.07 "trivial"). In conclusion, the present study showed that there were no significant differences in the state anxiety level after an acute session of the exergame beach volleyball.

KEY POINTS: • Exergame beach volleyball presented high enjoyment and a moderate to strong future engagement possibility. • A session of the volleyball exergame did not improve affectivity and state anxiety level compared with control condition. • A session of the volleyball exergame elicited moderate physical exercise intensity.

Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P=0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P=0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; Pinteraction=0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Experimental and Computational Analysis of Synthesis Conditions of Hybrid Nanoflowers for Lipase Immobilization.

This work presents a framework for evaluating hybrid nanoflowers using Burkholderia cepacia lipase. It was expanded on previous findings by testing lipase hybrid nanoflowers (hNF-lipase) formation over a wide range of pH values (5-9) and buffer concentrations (10-100 mM). The free enzyme activity was compared with that of hNF-lipase. The analysis, performed by molecular docking, described the effect of lipase interaction with copper ions. The morphological characterization of hNF-lipase was performed using scanning electron microscopy. Fourier Transform Infrared Spectroscopy performed the physical-chemical characterization. The results show that all hNF-lipase activity presented values higher than that of the free enzyme. Activity is higher at pH 7.4 and has the highest buffer concentration of 100 mM. Molecular docking analysis has been used to understand the effect of enzyme protonation on hNF-lipase formation and identify the main the main binding sites of the enzyme with copper ions. The hNF-lipase nanostructures show the shape of flowers in their micrographs from pH 6 to 8. The spectra of the nanoflowers present peaks typical of the amide regions I and II, current in lipase, and areas with P-O vibrations, confirming the presence of the phosphate group. Therefore, hNF-lipase is an efficient biocatalyst with increased catalytic activity, good nanostructure formation, and improved stability.

Investigating academic performance and perceptions of human physiology and exercise physiology courses among undergraduate students of physical education at a Brazilian public university.

PURPOSE: To compare the academic performance of undergraduate students in physical education who studied exercise physiology before and after studying human physiology and investigate students' perceptions of human physiology and exercise physiology courses. METHODS: This study included 311 undergraduate students pursuing a bachelor's degree in physical education. Participants were divided into two groups: those who had previously attended and completed the human physiology course (group 1, n = 212, 68.2%) and those who had not previously attended or had attended but failed the human physiology course (group 2, n = 99, 31.8%). The prevalence ratio (PR) and 95% confidence interval (95% CI) were calculated using a Poisson regression model with a robust variance estimator. The second aim comprised 67 students with bachelor's degrees in physical education who completed an electronic questionnaire about their perceptions of human physiology and exercise physiology curriculum. RESULTS: Compared with those who attended human physiology and passed, those who had not previously attended or had attended but failed the human physiology course have a higher PR of 2.37 (95% CI, 1.68-3.34) for failing exercise physiology. Regarding the students' perceptions of human physiology and exercise physiology courses, most students reported that they were challenging (58.2% and 64.2%, respectively), but they also recognized the importance of these courses for professional practice (59.7% and 85.1%, respectively). CONCLUSION: Human physiology should be considered a prerequisite for an undergraduate course leading to a bachelor's degree in physical education. Furthermore, students considered human physiology and exercise physiology courses important yet challenging. Therefore, continuous student assessment is vital for improving the teaching-learning process.

A machine learning system to optimise triage in an adult ophthalmic emergency department: a model development and validation study.

Background: A substantial proportion of attendances to ophthalmic emergency departments are for non-urgent presentations. We developed and evaluated a machine learning system (DemDx Ophthalmology Triage System: DOTS) to optimise triage, with the aim of reducing inappropriate emergency attendances and streamlining case referral when necessary. Methods: DOTS was built using retrospective tabular data from 11,315 attendances between July 1st, 2021, to June 15th, 2022 at Moorfields Eye Hospital Emergency Department (MEH) in London, UK. Demographic and clinical features were used as inputs and a triage recommendation was given ("see immediately", "see within a week", or "see electively"). DOTS was validated temporally and compared with triage nurses' performance (1269 attendances at MEH) and validated externally (761 attendances at the Federal University of Minas Gerais - UFMG, Brazil). It was also tested for biases and robustness to variations in disease incidences. All attendances from patients aged at least 18 years with at least one confirmed diagnosis were included in the study. Findings: For identifying ophthalmic emergency attendances, on temporal validation, DOTS had a sensitivity of 94.5% [95% CI 92.3-96.1] and a specificity of 42.4% [38.8-46.1]. For comparison within the same dataset, triage nurses had a sensitivity of 96.4% [94.5-97.7] and a specificity of 25.1% [22.0-28.5]. On external validation at UFMG, DOTS had a sensitivity of 95.2% [92.5-97.0] and a specificity of 32.2% [27.4-37.0]. In simulated scenarios with varying disease incidences, the sensitivity was ≥92.2% and the specificity was ≥36.8%. No differences in sensitivity were found in subgroups of index of multiple deprivation, but the specificity was higher for Q2 when compared to Q4 (Q4 is less deprived than Q2). Interpretation: At MEH, DOTS had similar sensitivity to triage nurses in determining attendance priority; however, with a specificity of 17.3% higher, DOTS resulted in lower rates of patients triaged to be seen immediately at emergency. DOTS showed consistent performance in temporal and external validation, in social-demographic subgroups and was robust to varying relative disease incidences. Further trials are necessary to validate these findings. This system will be prospectively evaluated, considering human-computer interaction, in a clinical trial. Funding: The Artificial Intelligence in Health and Care Award (AI_AWARD01671) of the NHS AI Lab under National Institute for Health and Care Research (NIHR) and the Accelerated Access Collaborative (AAC).

Effects of twelve weeks of dance Exergames on the quality-of-life variables of elderly Brazilian women enrolled in a community program.

BACKGROUND AND PURPOSE: Exercise-based interventions can be a safe alternative to improve and maintain physical and mental health during the aging process. The aim of the present study was to evaluate the effects of a 12-week training program with Dance Exergames on the mood and functional fitness profile of elderly women. METHODS: The sample (n = 22) was divided into Exergames (EG, n = 9, 70.6 ± 1.6 years) and Control Groups (CG, n = 13, 73.6 ± 2.2 years). Evaluations were carried out before and after the interventions. Each participant played, in pairs, the electronic game Dance Central 3, with the XBOX 360 Kinect console (Slim, Microsoft, USA). The EG trained for 12 weeks (24 sessions), with two weekly sessions of 50 min and the CG performed manual activities workshops. RESULTS: In functional fitness, both exercise training with exergame (EG) and the intervention model for the CG did not produce significant effects regarding interaction (group*time). Mood state presented significant effect of time intervention regarding tension (p = <0.001), depression (p = 0.001), anger (p = 0.030), fatigue (p = 0.001), and mental confusion (p = 0.004). CONCLUSION: Twelve weeks of training with a dance exergame (for, EG) and manual activities (for, CG) is enough to promote improvements in the mood state of healthy elderly women. This is an interesting result, as it shows that social interaction is as important a component as improving functional capacity.

Small extracellular vesicles administered directly in the brain promote neuroprotection and decreased microglia reactivity in a stroke mouse model.

Herein, we investigate the bioactivity of small extracellular vesicles (sEVs), focusing on their local effect in the brain. sEVs from mononuclear cells (MNCs) showed superior effects in vitro to sEVs from mesenchymal stem cells (MSCs) and were able to promote neuroprotection and decrease microglia reactivity in a stroke mouse model.

Thermo-induced changes in the structure of lentil protein isolate (Lens culinaris) to stabilize high internal phase emulsions.

This study aims to assess the impact of heat treatment on the emulsifying properties of lentil protein isolate (LPI) dispersion to produce high internal phase emulsions (HIPEs). The heat-treated LPI dispersion was characterized by size, turbidity, solubility, zeta potential, free sulfhydryl group, electrophoresis, differential scanning calorimetry, circular dichroism, Fourier transforms infrared spectroscopy and intrinsic fluorescence. HIPEs were produced with 25% of LPI dispersion (2%, w/w) and soybean oil (75%) using a rotor-stator (15,500 rpm/1 min). HIPEs were evaluated for their droplet size, zeta potential, centrifugal stability, microscopy, appearance, Turbiscan stability, and rheology over 60 days (25 °C). Heat treatment reduced the size of LPI, resulting in increased turbidity, solubility, and exposure of hydrophobic groups. HIPEs produced with heat-treated LPI at 70 °C (HIPE70) and 80 °C (HIPE80) for 20 min exhibited lower droplet sizes, increased stability, reduced oil loss, and a homogeneous appearance compared to HIPE produced with untreated LPI (HIPEc). In addition, HIPE70 and HIPE80 displayed resistance to shear stress, higher apparent viscosity, and increased storage modulus than HIPEc. HIPEs produced with heat-treated LPI were stable, suggesting that the treatment was efficient for improving the functional properties of the protein and the possibility of future research focusing on fat substitutes in food applications.

Ultrasonographic Vasospasm and Outcome of Posterior Reversible Encephalopathy and Cerebral Vasoconstriction Syndromes.

PURPOSE: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) are often complicated by vasospasm and ischemia. Monitoring with transcranial color-coded Doppler (TCCD) could be useful, but its role is not established. We studied the incidence of ultrasonographic vasospasm (uVSP) in PRES/RCVS and its relationship with ischemic lesions and clinical outcome. MATERIALS AND METHODS: We conducted a multicenter retrospective study of all patients with PRES/RCVS from 2008 to 2020 who underwent TCCD and magnetic resonance imaging (MRI). TCCD exams were analyzed for uVSP. Diffusion-weighted MRI was analyzed for positive lesions (DWI-positive). Functional outcome was assessed by modified Rankin scale (mRS) at 90 days. The associations with outcomes were determined by logistic regression. RESULTS: We included 80 patients (mean age of 46 (standard deviation, 17) years; 66% females; 41 with PRES, 28 with RCVS and 11 with overlap phenotype). uVSP was detected in 25 (31%) patients. DWI-positive lesions were more often detected in uVSP-positive than uVSP-negative patients (36% vs. 15%; adjusted odds ratio [aOR] 4.05 [95% CI 1.06 - 15.5], P=0.04). DWI-positive lesions were independently associated with worse functional prognosis (mRS 2-6, 43% vs. 10%; aOR, 10 [95% CI 2.6 - 43], P<0.01). Having additional uVSP further increased the odds of a worse outcome (P interaction=0.03). CONCLUSION: Ultrasonographic vasospasm was detected in a third of patients with PRES/RCVS and was associated with brain ischemic lesions. TCCD bedside monitoring can help to stratify patients at risk for cerebral ischemia, a strong predictor of functional outcome.

Oligosymptomatic long-term carriers of SARS-CoV-2 display impaired innate resistance but increased high-affinity anti-spike antibodies.

The vast spectrum of clinical features of COVID-19 keeps challenging scientists and clinicians. Low resistance to infection might result in long-term viral persistence, but the underlying mechanisms remain unclear. Here, we studied the immune response of immunocompetent COVID-19 patients with prolonged SARS-CoV-2 infection by immunophenotyping, cytokine and serological analysis. Despite viral loads and symptoms comparable to regular mildly symptomatic patients, long-term carriers displayed weaker systemic IFN-I responses and fewer circulating pDCs and NK cells at disease onset. Type 1 cytokines remained low, while type-3 cytokines were in turn enhanced. Of interest, we observed no defects in antigen-specific cytotoxic T cell responses, and circulating antibodies displayed higher affinity against different variants of SARS-CoV-2 Spike protein in these patients. The identification of distinct immune responses in long-term carriers adds up to our understanding of essential host protective mechanisms to ensure tissue damage control despite prolonged viral infection.

Fatigue life estimation of dental implants using a combination of the finite element method and traditional fatigue criteria.

Failure by fatigue can be sudden and catastrophic. Therefore, ensuring that dental implants, which are under constant cyclic loading, do not fail to fatigue is imperative. The majority of the studies about the topic only performed in vitro tests, which are expensive and time-consuming. The Finite Element (FE) method is less costly and it allows the simulation of several different loading scenarios. Nonetheless, there are only a few studies analysing fatigue in dental prostheses using FE models, and the few available did not include all the relevant parameters, such as geometry effect, surface finishing, etc. Therefore, this study aimed to analyse the fatigue behaviour of a single-unit dental implant with two screws using a combination of the numerical results and the traditional fatigue criteria - a combination that was not yet fully and correctly explored. A finite element model comprising a single implant, one abutment, one abutment screw, one fixation screw and one prosthetic crown was developed. Material properties were assigned based on literature data. A 100 N load was applied to mimic the mastication forces and fatigue analysis was conducted using the Gerber, Goodman and Soderberg fatigue criteria. The fatigue analysis demonstrated that the abutment screw could fail in less than 1 year, depending on the criteria, while the fixation screw exhibits an infinite life. The results illustrated the importance of analysing the fatigue behaviour of dental implants and highlighted the potential of finite element models to simulate the biomechanical behaviour of dental implants.

Congenital Diaphragmatic Hernia - Diagnosis After Intra-Thoracic Cholecystitis.

Congenital diaphragmatic hernia due to diaphragmatic agenesis is extremely rare. We report the case of a 53-year-old female patient with a congenital right diaphragmatic hernia due to a right hemidiaphragm agenesia diagnosed in the context of acute intrathoracic cholecystitis. She was admitted to the Emergency Department for diffuse abdominal pain, nausea and vomiting with 2 days of evolution. Thoracic and abdominal radiography showed hydro-aerial levels in the right hemithorax. The computed tomography showed a right diaphragmatic hernia with signs of incipient incarceration. The patient underwent surgery consisting of a right exploratory thoracotomy, reduction of the hernial contents, closure of the defect with a double-sided prosthesis anchored in a pericardial patch, and pericardial reconstruction with a polypropylene prosthesis, with a remarkable evolution. This case shows a rare late presentation of a congenital hemidiaphragm agenesia in adulthood, with a special focus on the indications and surgical techniques used for its correction.

Patient and Surgical Risk Factors for Surgical Site Infection in Lower-Extremity Oncological Endoprosthetic Reconstruction: A Secondary Analysis of the PARITY Trial Data.

BACKGROUND: The specific risk factors for surgical site infection (SSI) in orthopaedic oncology patients undergoing endoprosthetic reconstruction have not previously been evaluated in a large prospective cohort. In the current study, we aimed to define patient- and procedure-specific risk factors for SSI in patients who underwent surgical excision and endoprosthetic reconstruction for lower-extremity bone or soft-tissue tumors using the prospectively collected data of the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial. METHODS: PARITY was a multicenter, blinded, randomized controlled trial with a parallel 2-arm design that aimed to determine the effect of a long duration (5 days) versus short duration (24 hours) of postoperative prophylactic antibiotics on the rate of SSI in patients undergoing surgical excision and endoprosthetic reconstruction of the femur or tibia. In this secondary analysis of the PARITY data, a multivariate Cox proportional hazards regression model was constructed to explore predictors of SSI within 1 year postoperatively. RESULTS: A total of 96 (15.9%) of the 604 patients experienced an SSI. Of the 23 variables analyzed in the univariate analysis, 4 variables achieved significance: preoperative diagnosis, operative time, volume of muscle excised, and hospital length of stay (LOS). However, only hospital LOS was found to be independently predictive of SSI in the multivariate regression analysis (hazard ratio per day = 1.03; 95% confidence interval = 1.01 to 1.05; p < 0.001). An omnibus test of model coefficients demonstrated that the model showed significant improvement over the null model (χ2 = 78.04; p < 0.001). No multicollinearity was found. CONCLUSIONS: This secondary analysis of the PARITY study data found that the only independent risk factor for SSI on multivariate analysis was hospital LOS. It may therefore be reasonable for clinicians to consider streamlined discharge plans for orthopaedic oncology patients to potentially reduce the risk of SSI. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Resveratrol-Loaded Polymeric Nanoparticles: The Effects of D-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) on Physicochemical and Biological Properties against Breast Cancer In Vitro and In Vivo.

Resveratrol (RSV), a phytoalexin from grapes and peanuts, has been reported to exhibit antiproliferative effects on various cancer cell lines. In breast cancer, RSV has been demonstrated to exert an antiproliferative effect on both hormone-dependent and hormone-independent breast cancer cell lines. However, RSV is a lipophilic drug, and its therapeutic effect could be improved through nanoencapsulation. Functionalizing polymeric nanoparticles based on polycaprolactone (PCL) with polyethylene glycol 1000 tocopheryl succinate (TPGS) has been reported to prolong drug circulation and reduce drug resistance. However, the effect of TPGS on the physicochemical properties and biological effects of breast cancer cells remains unclear. Therefore, this study aimed to develop RSV-loaded PCL nanoparticles using nanoprecipitation and investigate the effect of TPGS on the nanoparticles' physicochemical characteristics (particle size, zeta potential, encapsulation efficiency, morphology, and release rate) and biological effects on the 4T1 breast cancer cell line (cytotoxicity and cell uptake), in vitro and in vivo. The optimized nanoparticles without TPGS had a size of 138.1 ± 1.8 nm, a polydispersity index (PDI) of 0.182 ± 0.01, a zeta potential of -2.42 ± 0.56 mV, and an encapsulation efficiency of 98.2 ± 0.87%, while nanoparticles with TPGS had a size of 127.5 ± 3.11 nm, PDI of 0.186 ± 0.01, zeta potential of -2.91 ± 0.90 mV, and an encapsulation efficiency of 98.40 ± 0.004%. Scanning electron microscopy revealed spherical nanoparticles with low aggregation tendency. Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR) identified the constituents of the nanoparticles and the presence of drug encapsulation in an amorphous state. In vitro release studies showed that both formulations followed the same dissolution profiles, with no statistical differences. In cytotoxicity tests, IC50 values of 0.12 µM, 0.73 µM, and 4.06 µM were found for the formulation without TPGS, with TPGS, and pure drug, respectively, indicating the potentiation of the cytotoxic effect of resveratrol when encapsulated. Flow cytometry and confocal microscopy tests indicated excellent cellular uptake dependent on the concentration of nanoparticles, with a significant difference between the two formulations, suggesting that TPGS may pose a problem in the endocytosis of nanoparticles. The in vivo study evaluating the antitumor activity of the nanoparticles confirmed the data obtained in the in vitro tests, demonstrating that the nanoparticle without TPGS significantly reduced tumor volume, tumor mass, maintained body weight, and improved survival in mice. Moreover, the biochemical evaluation evidenced possible hepatotoxicity for formulation with TPGS.