Evaluation of waning of IgG antibody responses after rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccines: a modelling study from the PREVAC randomized trial.

rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo are WHO-prequalified vaccination regimens against Ebola virus disease (EVD). Challenges associated with measuring long-term clinical protection warrant the evaluation of immune response kinetics after vaccination.

Immune correlates analysis of the Imbokodo (HVTN 705/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control study.

Background: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12.

Mosaic HIV-1 vaccine regimen in southern African women (Imbokodo/HVTN 705/HPX2008): a randomised, double-blind, placebo-controlled, phase 2b trial.

Background: HIV type 1 (HIV-1) remains a global health concern, with the greatest burden in sub-Saharan Africa. Despite 40 years of research, no vaccine candidate has shown durable and protective efficacy against HIV-1 acquisition. Although pre-exposure prophylaxis in groups with high vulnerability can be very effective, barriers to its use, such as perceived low acquisition risk, fear of stigma, and concerns about side-effects, remain.

Immunogenicity of 2 therapeutic mosaic HIV-1 vaccine strategies in individuals with HIV-1 on antiretroviral therapy.

Mosaic HIV-1 vaccines have been shown to elicit robust humoral and cellular immune responses in people living with HIV-1 (PLWH), that had started antiretroviral therapy (ART) during acute infection. We evaluated the safety and immunogenicity of 2 mosaic vaccine regimens in virologically suppressed individuals that had initiated ART during the chronic phase of infection, exemplifying the majority of PLWH. In this double-blind, placebo-controlled phase 1 trial (IPCAVD013/HTX1002) 25 ART-suppressed PLWH were randomized to receive Ad26.

Mosaic HIV-1 vaccination induces anti-viral CD8 T cell functionality in the phase 1/2a clinical trial APPROACH.

The functionality of CD8+ T cells against human immunodeficiency virus-1 (HIV-1) antigens is indicative of HIV-progression in both animal models and people living with HIV. It is, therefore, of interest to assess CD8+ T cell responses in a prophylactic vaccination setting, as this may be an important component of the immune system that inhibits HIV-1 replication. T cell responses induced by the adenovirus serotype 26 (Ad26) mosaic vaccine regimen were assessed previously by IFN-γ ELISpot and flow cytometric assays, yet these assays only measure cytokine production but not the capacity of CD8+ T cells to inhibit replication of HIV-1.

Complications in the Treatment of Delayed Union and Underlying Chronic Osteomyelitis After Right Crural Fracture Treated With Anterolateral Thigh Flap and Double-Barrelled Vascularized Fibula Graft.

Background: Segmental bone defects pose a major, unsolved clinical challenge and may be the result of high-energy trauma, infection, and tumour resection or revision surgery. Several options exist to reconstruct, including Ilizarov bone transport, Masquelet technique, cylindrical mesh technique, allografts, and vascularized bone autografts. We present a patient with a delayed union of the tibia with concomitant chronic osteomyelitis treated with anterolateral thigh (ALT) flap and double-barrelled vascularized fibula graft.

Population Pharmacokinetic Analysis of Bedaquiline-Clarithromycin for Dose Selection Against Pulmonary Nontuberculous Mycobacteria Based on a Phase 1, Randomized, Pharmacokinetic Study.

Based on the in vitro profile of bedaquiline against mycobacterial species, it is being investigated for clinical efficacy against pulmonary nontuberculous mycobacteria (PNTM). Being a cytochrome P450 3A substrate, pharmacokinetic interactions of bedaquiline are anticipated with clarithromycin (a cytochrome P450 3A inhibitor), which is routinely used in pulmonary nontuberculous mycobacteria treatment. This phase 1, randomized, crossover study assessed the impact of steady-state clarithromycin (500 mg every 12 hours for 14 days) on the pharmacokinetics of bedaquiline and its metabolite (M2) after single-dose bedaquiline (100 mg; n  =  16).

Clinical Challenges in Resection and Reconstruction of a Verrucous Carcinoma of the Right Calcaneus With a Medial Plantar Artery Perforator Flap: A Case Report.

A verrucous carcinoma is a rare, low-grade variant of a well-differentiated squamous cell carcinoma (SCC). It frequently occurs in Caucasian males aged 50 to 60. The tumour is locally destructive, grows into muscle, nerves and bones, but rarely metastasizes.

JNJ-4178 (AL-335, Odalasvir, and Simeprevir) for 6 or 8 Weeks in Hepatitis C Virus-Infected Patients Without Cirrhosis: OMEGA-1.

The combination of three direct-acting antiviral agents (AL-335, odalasvir, and simeprevir: JNJ-4178 regimen) for 6 or 8 weeks demonstrated good efficacy and safety in a phase IIa study in chronic hepatitis C virus (HCV) genotype (GT)-1-infected patients without cirrhosis and has now been evaluated in a larger phase IIb study, OMEGA-1. This multicenter, randomized, open-label study (NCT02765490) enrolled treatment-naïve and interferon (±ribavirin) treatment-experienced patients with HCV GT1, 2, 4, 5, or 6 infection. Patients with HCV GT3 infection and/or liver cirrhosis were excluded.

Vascularized bone transplant chimerism mediated by vascular endothelial growth factor.

Background: Vascular endothelial growth factor (VEGF) induces angiogenesis and osteogenesis in bone allotransplants. We aim to determine whether bone remodeling in VEGF-treated bone allotransplants results from repopulation with circulation-derived autogenous cells or survival of allogenic transplant-derived cells.

Methods: Vascularized femoral bone transplants were transplanted from female Dark Agouti rats (DA;RT1(a) ) to male Piebald Viral Glaxo (PVG;RT1(c) ).

Surgical revascularization in structural orthotopic bone allograft increases bone remodeling.

Background: Osseous defects reconstructed with cryopreserved structural allografts are poorly revascularized and therefore are prone to nonunion, infection, deterioration of mechanical properties, and fracture. Whether this can be mitigated by specific interventions such as intramedullary surgical revascularization has been incompletely evaluated.

Questions/purposes: We aimed to study surgical revascularization as a means to improve bone remodeling in cryopreserved allograft.

Fibroblast growth factor-2 and vascular endothelial growth factor mediated augmentation of angiogenesis and bone formation in vascularized bone allotransplants.

We previously demonstrated recipient-derived neoangiogenesis to maintain viability of living bone allogeneic transplants without long-term immunosuppression. The effect of cytokine delivery to enhance this process is studied. Vascularized femur transplantation was performed from Dark Agouti to Piebald Virol Glaxo rats.

Cell lineage in vascularized bone transplantation.

Background: The biology behind vascularized bone allotransplantation remains largely unknown. We aim to study cell traffic between donor and recipient following bone auto-, and allografting.

Methods: Vascularized femoral transplantation was performed with arteriovenous bundle implantation and short-term immunosuppression.

Surgical angiogenesis with short-term immunosuppression maintains bone viability in rabbit allogenic knee joint transplantation.

Background: Vascularized composite allotransplantation has the potential for reconstruction of joint defects but requires lifelong immunosuppression, with substantial risks. This study evaluates an alternative, using surgical angiogenesis from implanted autogenous vessels to maintain viability without long-term immunotherapy.

Methods: Vascularized knee joints were transplanted from Dutch Belted donors to New Zealand White rabbit recipients.

Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura.

ALX-0681 is a therapeutic Nanobody targeting the A1-domain of VWF. It inhibits the interaction between ultra-large VWF and platelet GpIb-IX-V, which plays a crucial role in the pathogenesis of thrombotic thrombocytopenic purpura (TTP). In the present study, we report the efficacy and safety profile of ALX-0681 in a baboon model of acquired TTP.

Surgical revascularization induces angiogenesis in orthotopic bone allograft.

Background: Remodeling of structural bone allografts relies on adequate revascularization, which can theoretically be induced by surgical revascularization. We developed a new orthotopic animal model to determine the technical feasibility of axial arteriovenous bundle implantation and resultant angiogenesis.

Questions/purposes: We asked whether arteriovenous bundles implanted in segmental allografts would increase cortical blood flow and angiogenesis compared to nonrevascularized frozen bone allografts and contralateral femoral controls.

Induction of angiogenesis and osteogenesis in surgically revascularized frozen bone allografts by sustained delivery of FGF-2 and VEGF.

Large conventional bone allografts are susceptible to fracture and nonunion due to incomplete revascularization and insufficient bone remodeling. We aim to improve bone blood flow and bone remodeling using surgical angiogenesis combined with delivery of fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF). Frozen femoral allografts were heterotopically transplanted in a rat model.

Return of motor function after segmental nerve loss in a rat model: comparison of autogenous nerve graft, collagen conduit, and processed allograft (AxoGen).

Background: An effective alternative to nerve autograft is needed to minimize morbidity and solve limited-availability issues. We hypothesized that the use of processed allografts and collagen conduits would allow recovery of motor function that is equivalent to that seen after the use of autografts.

Methods: Sixty-five Lewis rats were divided into three experimental groups.

Knee joint transplantation combined with surgical angiogenesis in rabbits--a new experimental model.

Purpose: We have previously described a means to maintain bone allotransplant viability, without long-term immune modulation, replacing allogenic bone vasculature with autogenous vessels. A rabbit model for whole knee joint transplantation was developed and tested using the same methodology, initially as an autotransplant.

Materials/methods: Knee joints of eight New Zealand White rabbits were elevated on a popliteal vessel pedicle to evaluate limb viability in a nonsurvival study.

Description and validation of isometric tetanic muscle force test in rabbits.

Isometric tetanic muscle force has been described in a rat model to evaluate motor recovery in a segmental sciatic nerve defect reconstructions. However, to test longer nerve defects, an alternative and larger animal model is necessary. The purpose of this study is to describe and validate a technique for isometric force measurement of the tibialis anterior (TA) muscle in New Zealand rabbits.

Vascularized bone grafting in a canine carpal avascular necrosis model.

Background: Limited experimental research has been performed on the treatment of avascular necrosis (AVN) by vascularized bone grafting.

Questions/purposes: A new model simulating carpal AVN was created to investigate surgical revascularization of necrotic bone.

Methods: In seven mongrel dogs, AVN was induced by removal of the radial carpal bones bilaterally, deep-freezing, coating in cyanoacrylate, and reimplantation.

Revascularization and bone remodeling of frozen allografts stimulated by intramedullary sustained delivery of FGF-2 and VEGF.

Frozen bone allografts are susceptible to nonunion and fracture due to limited revascularization and incomplete bone remodeling. We aim to revascularize bone allografts by combining angiogenesis from implanted arteriovenous (AV) bundles with delivery of fibroblast growth factor (FGF-2) and/or vascular endothelial growth factor (VEGF) via biodegradable microspheres. Rat femoral diaphyseal allografts were frozen at -80°C, and heterotopically transplanted over a major histocompatibility mismatch.

Augmentation of surgical angiogenesis in vascularized bone allotransplants with host-derived a/v bundle implantation, fibroblast growth factor-2, and vascular endothelial growth factor administration.

We have previously shown experimental transplantation of living allogeneic bone to be feasible without long-term immunosuppression by development of a recipient-derived neoangiogenic circulation within bone. In this study, we examine the role of angiogenic cytokine delivery with biodegradable microspheres to enhance this process. Microsurgical femoral allotransplantation was performed from Dark Agouti to Piebald Virol Glaxo rats.