Incidence of chronic renal injury in patients undergoing autologous stem cell transplant therapy.

BACKGROUND: Haemopoietic stem cell transplant (HSCT) is a well-established treatment option for many haematologic immunologic and oncologic diseases, allowing the safe administration of high-dose chemotherapy. Increased risk of acute renal injury is associated with HSCT; however, the risk of chronic kidney injury in autologous HSCT remains unclear. AIMS: This cohort study investigates the incidence of chronic renal injury and its predisposing factors in a single-centre population of 139 patients who underwent autologous HSCT. METHODS: Estimated glomerular filtration rate (eGFR) was measured at baseline and at 3, 6, 12 and 24 months following autologous stem cell reinfusion and used as a marker of renal dysfunction. RESULTS: A significant reduction in mean eGFR of patients was observed from baseline (80.62 ± 2.97 mL/min) to 24 months (71.54 ± 4.14 mL/min), independent of primary diagnosis (P = 0.0019). At baseline, 12% of the cohort had stage 3 or worse chronic renal injury and this increased to 38% by 24 months. By univariate analysis, age at baseline greater than the mean of 58 years and the occurrence of acute kidney injury during the peritransplant period emerged as predictive factors for the development of chronic kidney disease at 24 months. CONCLUSIONS: The current results indicate there is an increased incidence of chronic renal injury in patients who have undergone autologous peripheral blood haemopoietic stem cell transplantation therapy and this injury is potentiated by the autologous stem cell transplant procedure.

Hypocalcemia and Hypophosphatemia following Concurrent Denosumab Injection and Ferric Carboxymaltose Infusion in a Patient with Normal Renal Function.

Hypocalcemia following denosumab administration is well described. Hypophosphatemia following an intravenous iron infusion is an increasingly recognized adverse effect. Intravenous iron preparations increase fibroblast growth factor 23 (FGF23) levels. This both stimulates renal phosphate excretion and reduces 1,25-dihydroxyvitamin D (1,25(OH)2D) levels, resulting in reduced calcium absorption. Both osteoporosis and iron deficiency are common and frequently co-occur. The convenience and efficacy of both denosumab, a subcutaneous injection, and ferric carboxymaltose (Ferinject®), a 15-minute intravenous infusion, both of which can be given in the primary care setting, make these preferred treatment options. However, prescribers are often unaware of potential adverse outcomes, especially when these medications are given in tandem. We present a case of symptomatic hypocalcemia and hypophosphatemia in a 29-year-old woman with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and normal renal function, in the setting of concurrent denosumab and ferric carboxymaltose administration for treatment of glucocorticoid-induced osteoporosis and iron deficiency anemia.

Reactive Cell Electrospinning of Anisotropically Aligned and Bilayer Hydrogel Nanofiber Networks.

Structured hydrogels that incorporate aligned nanofibrous morphologies have been demonstrated to better replicate the structures of native extracellular matrices and thus their function in guiding cell responses. However, current techniques for nanofiber fabrication are limited in their ability to create hydrogel scaffolds with tunable directional alignments and cell types/densities, as required to reproduce more complex native tissue structures. Herein, we leverage a reactive cell electrospinning technique based on the dynamic covalent cross-linking of poly(ethylene glycol methacrylate (POEGMA) precursor polymers to fabricate aligned hydrogel nanofibers that can be directly loaded with cells during the electrospinning process. The scaffolds were found to support high C2C12 myoblast viabilities greater than 85% over 14 days, with changes in the electrospinning collector allowing for the single-step fabrication of nonaligned, aligned, or cross-aligned nanofibrous networks. Cell aspect ratios on aligned scaffolds were found on average to be 27% higher compared to those on nonaligned scaffolds; furthermore, cell-loaded bilayer scaffolds with perpendicular fiber alignments showed evidence of enabling localized directional cell responses to individual layer fiber directions while avoiding delamination between the layers. This fabrication approach thus offers potential for better mimicking the structure and thus function of aligned and multilayered tissues (e.g., smooth muscle, neural, or tendon tissues).

Multicellular Layered Nanofibrous Poly(Oligo Ethylene Glycol Methacrylate) (POEGMA)-Based Hydrogel Scaffolds via Reactive Cell Electrospinning.

While hydrogels are demonstrated to be effective scaffolds for soft tissue engineering, existing fabrication techniques pose limitations in terms of being able to reproduce both the micro/nanofibrous structures of native extracellular matrix as well as the spatial arrangement of different cell types inherent of more complex tissues. Herein, a reactive cell electrospinning strategy is described using hydrazide and aldehyde-functionalized poly(oligoethylene glycol methacrylate) precursor polymers that can create nanofibrous hydrogel scaffolds with controllable local cell gradients using a sequential all-aqueous process that does not require additives or external energy. Cells can be encapsulated directly during the fabrication process in different layers within the scaffold, enabling localized segregation of different cell types within the structures without compromising their capacity to proliferate (≈4-fold increase in cell density over a 14 day incubation period). This sequential reactive electrospinning approach thus offers promise to generate coculture fibrous hydrogel networks in which both the nanoscale architecture and the cell distribution can be controlled, as it is essential to recreate more complex types of tissues.

Hydrogels for Tissue Engineering: Addressing Key Design Needs Toward Clinical Translation.

While the soft mechanics and tunable cell interactions facilitated by hydrogels have attracted significant interest in the development of functional hydrogel-based tissue engineering scaffolds, translating the many positive results observed in the lab into the clinic remains a slow process. In this review, we address the key design criteria in terms of the materials, crosslinkers, and fabrication techniques useful for fabricating translationally-relevant tissue engineering hydrogels, with particular attention to three emerging fabrication techniques that enable simultaneous scaffold fabrication and cell loading: 3D printing, in situ tissue engineering, and cell electrospinning. In particular, we emphasize strategies for manufacturing tissue engineering hydrogels in which both macroporous scaffold fabrication and cell loading can be conducted in a single manufacturing step - electrospinning, 3D printing, and in situ tissue engineering. We suggest that combining such integrated fabrication approaches with the lessons learned from previously successful translational experiences with other hydrogels represents a promising strategy to accelerate the implementation of hydrogels for tissue engineering in the clinic.

Vascular Pathology and Osteoarthritis: A Systematic Review.

OBJECTIVE: Vascular pathology (changes in blood vessels) and osteoarthritis (OA) are both common chronic conditions associated with aging and obesity, but whether vascular pathology is a risk factor for OA is unclear. The aim of this study was to systematically review the evidence for an association between vascular pathology and risk of joint-specific OA. METHODS: Scopus, Ovid Medline, and EMBASE were searched from inception to February 2019. MeSH terms and keywords were used to identify studies examining the association between vascular pathology and OA. Two reviewers independently extracted the data and assessed the methodological quality. Qualitative evidence synthesis was performed. RESULTS: Fifteen studies with high (n = 3), fair (n = 3), or low (n = 9) quality were included. Features of vascular pathology included atherosclerosis, vascular stiffness, and endothelial dysfunction in different vascular beds. There was evidence for an association between vascular pathology and risk of hand OA in women but not men, and between vascular pathology and risk of knee OA in both men and women. Only 2 studies examined hip OA showing no association between vascular pathology and risk of hip OA. CONCLUSION: There is evidence suggesting an association between vascular pathology and risk of hand and knee OA, with a potential causal relationship for knee OA. Based on the limited evidence, it is hard to conclude an association for hip OA. Further stronger evidence is needed to determine whether there is a causal relationship.

Association between popliteal artery wall thickness and knee cartilage volume loss in community-based middle-aged women without clinical knee disease.

OBJECTIVE: Increasing evidence suggests a role of vascular pathology in the pathogenesis of osteoarthritis. This study examined the association between popliteal artery wall thickness, a surrogate marker of cardiovascular disease, and knee cartilage volume loss in an asymptomatic cohort of women. STUDY DESIGN: Prospective cohort study of 170 women with no significant knee pain, injury, or history of clinical knee disease. Participants underwent knee magnetic resonance imaging at baseline and 2 years later. Popliteal artery wall thickness was assessed using validated methods. MAIN OUTCOME MEASURES: Tibial cartilage volume assessed using validated methods. RESULTS: 142 women (83.5%) completed 2-year follow-up. After adjusting for age, body mass index and tibial bone area, greater popliteal artery wall thickness was associated with increased rate of medial tibial cartilage volume loss. With increasing tertiles of popliteal artery wall thickness, the mean (standard error) of annual medial tibial cartilage volume loss was 1.62 (0.45)%, 2.18 (0.43)%, and 2.98 (0.48)%, respectively, p for trend=0.04. No significant association was observed in lateral tibial cartilage. CONCLUSION: In community-based women greater popliteal artery wall thickness is associated with increased rate of tibial cartilage volume loss over 2 years. These findings suggest an adverse effect of vascular pathology on articular knee cartilage, supporting the hypothesis that there might be a vascular contribution to the development of knee osteoarthritis. Although needing to be confirmed in other studies, these results suggest that targeting vascular pathology may provide a potential target for the prevention and early treatment of knee osteoarthritis in women.