Peer support for people living with hepatitis B virus-A foundation for treatment expansion.

Chronic hepatitis B infection (CHB) affects 300 million people worldwide and is being targeted by the United Nations 2030 Sustainable Development Goals (SDGs) and the World Health Organisation (WHO), working towards elimination of hepatitis B virus (HBV) as a public health threat. In this piece, we explore the evidence and potential impact of peer support to enhance and promote interventions for people living with CHB. Peer support workers (PSWs) are those with lived experience of an infection, condition or situation who work to provide support for others, aiming to improve education, prevention, treatment and other clinical interventions and to reduce the physical, psychological and social impacts of disease. Peer support has been shown to be a valuable tool for improving health outcomes for people living with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), but to date has not been widely available for communities affected by HBV. HBV disproportionately affects vulnerable and marginalised populations, who could benefit from PSWs to help them navigate complicated systems and provide advocacy, tackle stigma, improve education and representation, and optimise access to treatment and continuity of care. The scale up of peer support must provide structured and supportive career pathways for PSWs, account for social and cultural needs of different communities, adapt to differing healthcare systems and provide flexibility in approaches to care. Investment in peer support for people living with CHB could increase diagnosis, improve retention in care, and support design and roll out of interventions that can contribute to global elimination goals.

Computational Insights into the Interplay of Mechanical Forces in Angiogenesis.

This study employs a meshless computational model to investigate the impacts of compression and traction on angiogenesis, exploring their effects on vascular endothelial growth factor (VEGF) diffusion and subsequent capillary network formation. Three distinct initial domain geometries were defined to simulate variations in endothelial cell sprouting and VEGF release. Compression and traction were applied, and the ensuing effects on VEGF diffusion coefficients were analysed. Compression promoted angiogenesis, increasing capillary network density. The reduction in the VEGF diffusion coefficient under compression altered VEGF concentration, impacting endothelial cell migration patterns. The findings were consistent across diverse simulation scenarios, demonstrating the robust influence of compression on angiogenesis. This computational study enhances our understanding of the intricate interplay between mechanical forces and angiogenesis. Compression emerges as an effective mediator of angiogenesis, influencing VEGF diffusion and vascular pattern. These insights may contribute to innovative therapeutic strategies for angiogenesis-related disorders, fostering tissue regeneration and addressing diseases where angiogenesis is crucial.

Real-World Impact of Upfront Cytoreductive Nephrectomy in Metastatic Non-Clear Cell Renal Cell Carcinoma Treated with First-Line Immunotherapy Combinations or Tyrosine Kinase Inhibitors (A Sub-Analysis from the ARON-1 Retrospective Study).

BACKGROUND: About 20% of patients with renal cell carcinoma present with non-clear cell histology (nccRCC), encompassing various histological types. While surgery remains pivotal for localized-stage nccRCC, the role of cytoreductive nephrectomy (CN) in metastatic nccRCC is contentious. Limited data exist on the role of CN in metastatic nccRCC under current standard of care. OBJECTIVE: This retrospective study focused on the impact of upfront CN on metastatic nccRCC outcomes with first-line immune checkpoint inhibitor (IO) combinations or tyrosine kinase inhibitor (TKI) monotherapy. METHODS: The study included 221 patients with nccRCC and synchronous metastatic disease, treated with IO combinations or TKI monotherapy in the first line. Baseline clinical characteristics, systemic therapy, and treatment outcomes were analyzed. The primary objective was to assess clinical outcomes, including progression-free survival (PFS) and overall survival (OS). Statistical analysis involved the Fisher exact test, Pearson's correlation coefficient, analysis of variance, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. RESULTS: Median OS for patients undergoing upfront CN was 36.8 (95% confidence interval [CI] 24.9-71.3) versus 20.8 (95% CI 12.6-24.8) months for those without CN (p = 0.005). Upfront CN was significantly associated with OS in the multivariate Cox regression analysis (hazard ratio 0.47 [95% CI 0.31-0.72], p < 0.001). In patients without CN, the median OS and PFS was 24.5 (95% CI 18.1-40.5) and 13.0 months (95% CI 6.6-23.5) for patients treated with IO+TKI versus 7.5 (95% CI 4.3-22.4) and 4.9 months (95% CI 3.0-8.1) for those receiving the IO+IO combination (p = 0.059 and p = 0.032, respectively). CONCLUSIONS: Our study demonstrates the survival benefits of upfront CN compared with systemic therapy without CN. The study suggests that the use of IO+TKI combination or, eventually, TKI monotherapy might be a better choice than IO+IO combination for patients who are not candidates for CN regardless of IO eligibility. Prospective trials are needed to validate these findings and refine the role of CN in current mRCC management.

Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update.

PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.

Efficacy of immune checkpoint inhibitors combinations as first-line systemic treatment in patients with advanced urothelial carcinoma: A systematic review and network meta-analysis.

BACKGROUND: Combinations of immune checkpoint inhibitors (ICI) with platinum-based chemotherapy (PlatinumCT) or with another ICI in the first-line setting for patients with metastatic urothelial carcinoma (mUC) have mixed results. METHODS: Records were searched electronically from January 2019 to January 2024. A meta-analysis was performed to evaluate OS, progression-free survival (PFS), and overall response rate (ORR). RESULTS: Immune-based combinations were associated with an OS (HR: 0.75; 95% CI: 0.61-0.92; p < 0.001; I2= 84.1%) and PFS benefit in the intention-to-treat population (HR: 0.67; 95%CI: 0.51-0.89; p < 0.001; I2 = 89.7%). There was no ORR improvement with immune-based combinations (HR: 1.36; 95% CI:0.84-2.20; p < 0.001; I2 = 92.6%). CONCLUSION: This systematic review and study-level meta-analysis demonstrated that the immune-based combinations in first-line treatment for patients with mUC are associated with survival benefit.

Redefining Rare Genitourinary Cancers: An Initiative Led by the Global Society of Rare Genitourinary Tumors.

Rare cancers account for 20-25% of all cancers diagnosed annually but there is no consensus on the definition of a rare cancer and substantial geographic heterogeneity. The Global Society of Rare Genitourinary Tumors is dedicated to education and research for rare genitourinary tumors.

Nano-encapsulated Cu(II) complex as a promising insecticidal for Aedes aegypti (Diptera: Culicidae).

Nanoparticle (NP) research is an area of scientific interest with high potential for application in biomedical, optical, and electronic fields. Due to their relatively large surface area compared to their mass, NPs can be more chemically reactive and change their reactive strength or other properties. NP-based drug delivery systems provide transport and an effective and controlled way to release the drugs. This work aimed to study the solubility and biological activity of nano-encapsulated copper metal complexes for the induction of toxicity and mortality in larvae of Aedes aegypti mosquitoes. After the nano-encapsulated metal complexes were prepared, the efficiency of this incorporation was determined by electron paramagnetic resonance, and toxicity bioassays were performed. The polymeric-based PLGA NPs encapsulating metal complexes exhibited high toxicity and specificity for target organisms (insect vectors, i.e., A. aegypti), with relatively less environmental impact and long-term control of their breeding.

Angle Assessment for Upper Limb Rehabilitation: A Novel Light Detection and Ranging (LiDAR)-Based Approach.

The accurate measurement of joint angles during patient rehabilitation is crucial for informed decision making by physiotherapists. Presently, visual inspection stands as one of the prevalent methods for angle assessment. Although it could appear the most straightforward way to assess the angles, it presents a problem related to the high susceptibility to error in the angle estimation. In light of this, this study investigates the possibility of using a new approach to angle calculation: a hybrid approach leveraging both a camera and LiDAR technology, merging image data with point cloud information. This method employs AI-driven techniques to identify the individual and their joints, utilizing the cloud-point data for angle computation. The tests, considering different exercises with different perspectives and distances, showed a slight improvement compared to using YOLO v7 for angle calculation. However, the improvement comes with higher system costs when compared with other image-based approaches due to the necessity of equipment such as LiDAR and a loss of fluidity during the exercise performance. Therefore, the cost-benefit of the proposed approach could be questionable. Nonetheless, the results hint at a promising field for further exploration and the potential viability of using the proposed methodology.

Systemic Immune-Inflammation Index in Patients Treated With First-Line Immune Combinations for Metastatic Renal Cell Carcinoma: Insights From the ARON-1 Study.

BACKGROUND: Systemic treatment with immune combinations is the gold standard for metastatic renal cell carcinoma (mRCC) worldwide. The systemic immune-inflammation index (SII) is a prognostic marker for several types of malignant neoplasms, including mRCC, in the era of tyrosine kinase inhibitor (TKI) treatment. Data regarding the prognostic value of the SII in patients with mRCC treated with immunotherapy are scarce and controversial.  METHODS: We retrospectively collected the data of patients with mRCC from 56 centers in 18 countries. SII (Platelet × Neutrophil/Lymphocyte count) was calculated prior to the first systemic treatment and cut-off was defined by a survival receiver operating characteristic (ROC) analysis. The primary objective of our retrospective study was to assess the outcomes of patients treated with first-line immunotherapy.  RESULTS: Data from 1034 mRCC patients was collected and included in this analysis. The SII cut-off value was 1265. After a follow-up of 26.7 months, and the overall survival (OS) and progression-free survival (PFS) were 39.8 and 15.7 months, respectively. According to SII (low vs. high), patients with low-SII had longer OS (55.7 vs. 22.2 months, P < .001), better PFS (20.8 vs. 8.5 months, P < .001), and higher overall response rate (52 vs. 37%, P = .033). CONCLUSION: A high SII is associated with poor oncological outcomes in patients with mRCC. SII could be an easily accessible prognostic indicator for use in clinical practice.

A Comprehensive Look at In Vitro Angiogenesis Image Analysis Software.

One of the complex challenges faced presently by tissue engineering (TE) is the development of vascularized constructs that accurately mimic the extracellular matrix (ECM) of native tissue in which they are inserted to promote vessel growth and, consequently, wound healing and tissue regeneration. TE technique is characterized by several stages, starting from the choice of cell culture and the more appropriate scaffold material that can adequately support and supply them with the necessary biological cues for microvessel development. The next step is to analyze the attained microvasculature, which is reliant on the available labeling and microscopy techniques to visualize the network, as well as metrics employed to characterize it. These are usually attained with the use of software, which has been cited in several works, although no clear standard procedure has been observed to promote the reproduction of the cell response analysis. The present review analyzes not only the various steps previously described in terms of the current standards for evaluation, but also surveys some of the available metrics and software used to quantify networks, along with the detection of analysis limitations and future improvements that could lead to considerable progress for angiogenesis evaluation and application in TE research.

Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study.

BACKGROUND: Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab. METHODS: We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model. RESULTS: A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival. CONCLUSIONS: Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.

Biocompatible antibiotic-loaded mesoporous silica/bioglass/collagen-based scaffolds as bone drug delivery systems.

Local delivery of antibiotics has gained increasing interest in the treatment of osteomyelitis due to its effectiveness and safety. Since the regeneration of bone tissue at the site of infection is as important as bacterial eradication, implantable drug delivery systems should not only release the drugs in a proper manner but also exert the osseointegration capability. Herein, we present an implantable drug delivery system in a scaffold form with a unique set of features for local treatment of osteomyelitis. For the first time, collagen type I, ciprofloxacin-loaded mesoporous silica, and bioglass were combined to obtain scaffolds using the molding method. Drug-loaded mesoporous silica was blended with polydimethylsiloxane to prolong the drug release, whereas bioglass served as a remineralization agent. Collagen-silica scaffolds were evaluated in terms of physicochemical properties, drug release rate, mineralization potential, osteoblast response in vitro, antimicrobial activity, and biological properties using an in vivo preclinical model - chick embryo chorioallantoic membrane (CAM). The desirable multifunctionality of the proposed collagen-silica scaffolds was confirmed. They released the ciprofloxacin for 80 days, prevented biofilm development, and induced hydroxyapatite formation. Moreover, the resulting macroporous structure of the scaffolds promoted osteoblast attachment, infiltration, and proliferation. Collagen-silica scaffolds were also biocompatible and effectively integrated with CAM.

Bioengineering Composite Aerogel-Based Scaffolds That Influence Porous Microstructure, Mechanical Properties and In Vivo Regeneration for Bone Tissue Application.

Tissue regeneration of large bone defects is still a clinical challenge. Bone tissue engineering employs biomimetic strategies to produce graft composite scaffolds that resemble the bone extracellular matrix to guide and promote osteogenic differentiation of the host precursor cells. Aerogel-based bone scaffold preparation methods have been increasingly improved to overcome the difficulties in balancing the need for an open highly porous and hierarchically organized microstructure with compression resistance to withstand bone physiological loads, especially in wet conditions. Moreover, these improved aerogel scaffolds have been implanted in vivo in critical bone defects, in order to test their bone regeneration potential. This review addresses recently published studies on aerogel composite (organic/inorganic)-based scaffolds, having in mind the various cutting-edge technologies and raw biomaterials used, as well as the improvements that are still a challenge in terms of their relevant properties. Finally, the lack of 3D in vitro models of bone tissue for regeneration studies is emphasized, as well as the need for further developments to overcome and minimize the requirement for studies using in vivo animal models.

Real-world effectiveness of pembrolizumab as first-line therapy for cisplatin-ineligible patients with advanced urothelial carcinoma: the ARON-2 study.

BACKGROUND: The advent of immune-checkpoint inhibitors has challenged previous treatment paradigms for advanced urothelial carcinoma (UC) in the post-platinum setting as well as in the first-line setting for cisplatin-ineligible patients. In this study, we investigated the effectiveness of pembrolizumab as first-line treatment for cisplatin-ineligible UC. METHODS: Data from patients aged ≥ 18 years with cisplatin-ineligible UC and receiving first-line pembrolizumab from January 1st 2017 to September 1st 2022 were collected. Cisplatin ineligibility was defined according to the Galsky criteria. Thirty-three Institutions from 18 countries were involved in the ARON-2 study. RESULTS: Our analysis included 162 patients. The median follow-up time was 18.9 months (95%CI 15.3-76.9). In the overall study population, the median OS was 15.8 months (95%CI 11.3-32.4). The median OS was significantly longer in males versus females while no statistically significant differences were observed between patients aged < 65y versus ≥ 65y and between smokers and non-smokers. According to Recist 1.1 criteria, 26 patients (16%) experienced CR, 32 (20%) PR, 39 (24%) SD and 55 (34%) PD. CONCLUSIONS: Our data confirm the role of pembrolizumab as first-line therapy for cisplatin-unfit patients. Further studies investigating the biological and immunological characteristics of UC patients are warranted in order to optimize the outcome of patients receiving immunotherapy in this setting.

Magnetic Bone Tissue Engineering: Reviewing the Effects of Magnetic Stimulation on Bone Regeneration and Angiogenesis.

Bone tissue engineering emerged as a solution to treat critical bone defects, aiding in tissue regeneration and implant integration. Mainly, this field is based on the development of scaffolds and coatings that stimulate cells to proliferate and differentiate in order to create a biologically active bone substitute. In terms of materials, several polymeric and ceramic scaffolds have been developed and their properties tailored with the objective to promote bone regeneration. These scaffolds usually provide physical support for cells to adhere, while giving chemical and physical stimuli for cell proliferation and differentiation. Among the different cells that compose the bone tissue, osteoblasts, osteoclasts, stem cells, and endothelial cells are the most relevant in bone remodeling and regeneration, being the most studied in terms of scaffold-cell interactions. Besides the intrinsic properties of bone substitutes, magnetic stimulation has been recently described as an aid in bone regeneration. External magnetic stimulation induced additional physical stimulation in cells, which in combination with different scaffolds, can lead to a faster regeneration. This can be achieved by external magnetic fields alone, or by their combination with magnetic materials such as nanoparticles, biocomposites, and coatings. Thus, this review is designed to summarize the studies on magnetic stimulation for bone regeneration. While providing information regarding the effects of magnetic fields on cells involved in bone tissue, this review discusses the advances made regarding the combination of magnetic fields with magnetic nanoparticles, magnetic scaffolds, and coatings and their subsequent influence on cells to reach optimal bone regeneration. In conclusion, several research works suggest that magnetic fields may play a role in regulating the growth of blood vessels, which are critical for tissue healing and regeneration. While more research is needed to fully understand the relationship between magnetism, bone cells, and angiogenesis, these findings promise to develop new therapies and treatments for various conditions, from bone fractures to osteoporosis.

Local Antibiotic Delivery Ceramic Bone Substitutes for the Treatment of Infected Bone Cavities and Bone Regeneration: A Systematic Review on What We Have Learned from Animal Models.

AIMS: the focus of this study is to evaluate if the combination of an antibiotic with a ceramic biomaterial is effective in treating osteomyelitis in an infected animal model and to define which model and protocol are best suited for in vivo experiments of local bone infection treatment. METHODS: a systematic review was carried out based on PRISMA statement guidelines. A PubMed search was conducted to find original papers on animal models of bone infections using local antibiotic delivery systems with the characteristics of bone substitutes. Articles without a control group, differing from the experimental group only by the addition of antibiotics to the bone substitute, were excluded. RESULTS: a total of 1185 records were retrieved, and after a three-step selection, 34 papers were included. Six manuscripts studied the effect of antibiotic-loaded biomaterials on bone infection prevention. Five articles studied infection in the presence of foreign bodies. In all but one, the combination of an antibiotic with bioceramic bone substitutes tended to prevent or cure bone infection while promoting biomaterial osteointegration. CONCLUSIONS: this systematic review shows that the combination of antibiotics with bioceramic bone substitutes may be appropriate to treat bone infection when applied locally. The variability of the animal models, time to develop an infection, antibiotic used, way of carrying and releasing antibiotics, type of ceramic material, and endpoints limits the conclusions on the ideal therapy, enhancing the need for consistent models and guidelines to develop an adequate combination of material and antimicrobial agent leading to an effective human application.

Interactions between Dental MSCs and Biomimetic Composite Scaffold during Bone Remodeling Followed by In Vivo Real-Time Bioimaging.

Oral-maxillofacial tumor removal can generate critical bone defects and major problems for patients, causing dysfunctionalities and affecting oral competencies such as mastication, swallowing, and breathing. The association of novel biomaterials and cell therapies in tissue engineering strategies could offer new strategies to promote osteomucosa healing. This study focused on the development of a bioengineered construct loaded with human dental follicle cells (MSCs). To increase the bioconstruct integration to the surrounding tissue, a novel and comprehensive approach was designed combining an injectable biomimetic hydrogel and dental stem cells (hDFMSCs) expressing luminescence/fluorescence for semi-quantitative tissue imaging in live animals. This in vivo model with human MSCs was based on an intramembranous bone regeneration process (IMO). Biologically, the biocomposite based on collagen/nanohydroxyapatite filled with cell-loaded osteopontin-fibrin hydrogel (Coll/nanoHA OPN-Fb) exhibited a high cellular proliferation rate, increased bone extracellular matrix deposition (osteopontin) and high ALP activity, indicating an early osteogenic differentiation. Thus, the presence of human OPN enhanced hDFMSC adhesion, migration, and spatial distribution within the 3D matrix. The developed 3D bioconstruct provided the necessary pro-regenerative effect to modulate the biological response, precisely fitting the bone defect with fine-tuned adjustment to the surrounding original structure and promoting oral osteomucosa tissue regeneration. We were also able to track the cells in vivo and evaluate their behavior (migration, proliferation, and differentiation), providing a glimpse into bone regeneration and helping in the optimization of patient-specific therapies.

The role of immune checkpoint inhibitors (ICI) as adjuvant treatment in renal cell carcinoma (RCC): A systematic review and meta-analysis.

Pembrolizumab, a PD-1 ICI is approved for the adjuvant treatment of postnephrectomy patients with clear cell RCC in some countries worldwide. However, recent negative data from randomized clinical trials (RCT) with another ICIs makes the benefit of this treatment uncertain. A systematic review and study-level meta-analysis was performed to evaluate the benefit of disease-free survival (DFS) with adjuvant ICI treatment for patients with localized and/or metastatic resected RCC. Using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement, a systematic search was performed in PUBMED/MEDLINE, Scopus and EMBASE up to September 15, 2022. The statistical analysis was performed by ProMeta 3 software in intention-to-treat (ITT) population and in predetermined subgroups. Four RCT totalizing 3407 patients were included in this analysis. Systemic immunotherapy was pembrolizumab, atezolizumab, nivolumab, and ipilimumab plus nivolumab in 496, 390, 404, and 405 patients, respectively. In the ITT population there was a nonstatistically significant DFS benefit with adjuvant ICI (HR: 0.85, 95% CI: 0.69-1.04). Regarding the subgroups, there was a DFS benefit for PD-L1 positive (HR: 0.72; 95% CI: 0.55-0.94), intermediate-high risk patients (HR: 0.77; 95% CI: 0.63-0.94), and patients with sarcomatoid component (HR: 0.66; 95% CI: 0.43-0.99). This meta-analysis did not demonstrate a statistically significant DFS benefit in overall population, however considering the heterogeneity between the RCTs the use of adjuvant ICI should be individualized.

Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model.

The treatment for osteomyelitis consists of surgical debridement, filling of the dead space, soft tissue coverage, and intravenous administration of antimicrobial (AM) agents for long periods. Biomaterials for local delivery of AM agents, while providing controllable antibiotic release rates and simultaneously acting as a bone scaffold, may be a valuable alternative; thus, avoiding systemic AM side effects. V-HEPHAPC is a heparinized nanohydroxyapatite (nHA)/collagen biocomposite loaded with vancomycin that has been previously studied and tested in vitro. It enables a vancomycin-releasing profile with an intense initial burst, followed by a sustained release with concentrations above the Minimum Inhibitory Concentration (MIC) for MRSA. In vitro results have also shown that cellular viability is not compromised, suggesting that V-HEPHAPC granules may be a promising alternative device for the treatment of osteomyelitis. In the present study, V-HEPHAPC (HEPHAPC with vancomycin) granules were used as a vancomycin carrier to treat MRSA osteomyelitis. First, in vivo Good Laboratory Practice (GLP) toxicological tests were performed in a rabbit model, assuring that HEPHAPC and V-HEPHAPC have no relevant side effects. Second, V-HEPHAPC proved to be an efficient drug carrier and bone substitute to control MRSA infection and simultaneously reconstruct the bone cavity in a sheep model.

Complete remissions following immunotherapy or immuno-oncology combinations in cancer patients: the MOUSEION-03 meta-analysis.

BACKGROUND: Immunotherapy has determined unprecedented long-term responses in several hematological and solid tumors. In the MOUSEION-03 study, we conducted a meta-analysis to determine the possibility of achieving complete remissions (CR) with immunotherapy or immuno-oncology combinations in cancer patients. METHODS: The primary endpoint was to assess the incidence of CR in cancer patients receiving immune checkpoint inhibitors (ICIs) alone or in combination with other agents versus control treatments. The pooled odds ratio (OR) and 95% confidence interval (CI) for CR rate were extracted. RESULTS: A total of 12,130 potentially relevant trials were identified; 5 phase II and 80 phase III randomized studies (37 monotherapies and 48 combinations) and 49,425 cancer patients were included. The most frequent types of malignancies were non-small cell lung cancer (n = 14,249; 29%), urothelial cancer (n = 6536; 13%), renal cell carcinoma (n = 5743; 12%), and melanoma (n = 2904; 6%). In patients treated with immunotherapy (as monotherapy or in combination with other anticancer agents), the pooled OR was 1.67 (1.52-1.84). The highest OR was registered by immune-based combinations with two ICIs (3.56, 95% CI 1.28-9.90). CONCLUSIONS: To the best of the authors' knowledge, no comprehensive meta-analysis on the use of ICIs and ICI-based combinations in solid tumors to systematically investigate the probability to achieve CR has been published so far. Although CR is not a common event in several cancer patients receiving immunotherapy, the MOUSEION-03 suggests that the use of ICIs may significantly increase the chance of achieving CR in comparison with control treatments.