OBJECTIVE: The aim of the present review is to critically discuss various surgical implications and level of evidence of most commonly employed bone graft substitutes for spinal fusion.
METHOD: Data was collected via electronic search using "PubMed", "SciFinder", "ScienceDirect", "Google Scholar", "Web of Science" and a library search for articles published in peer-reviewed journals, conferences, and e-books.
RESULTS: Despite having exceptional inherent osteogenic, osteoinductive, and osteoconductive features, clinical acceptability of autografts (patient's own bone) is limited due to several perioperative and postoperative complications i.e., donor-site morbidities and limited graft supply. Alternatively, allografts (bone harvested from cadaver) have shown great promise in achieving acceptable bone fusion rate while alleviating the donor-site morbidities associated with implantation of autografts. As an adjuvant to allograft, demineralized bone matrix (DBM) has shown remarkable efficacy of bone fusion, when employed as graft extender or graft enhancer. Recent advances in recombinant technologies have made it possible to implant growth and differentiation factors (bone morphogenetic proteins) for spinal fusion.
CONCLUSION: Selection of a particular bone grafting biotherapy can be rationalized based on the level of spine fusion, clinical experience and preference of orthopaedic surgeon, and prevalence of donor-site morbidities.
SUMMARY: Background Mutation of the growth factor-independent 1B (GFI1B) fifth DNA-binding zinc-finger domain causes macrothrombocytopenia and α-granule deficiency leading to clinical bleeding. The phenotypes associated with GFI1B variants disrupting non-DNA-binding zinc-fingers remain uncharacterized. Objectives To determine the functional and phenotypic consequences of GFI1B variants disrupting non-DNA-binding zinc-finger domains. Methods The GFI1B C168F variant and a novel GFI1B c.2520 + 1_2520 + 8delGTGGGCAC splice variant were identified in four unrelated families. Phenotypic features, DNA-binding properties and transcriptional effects were determined and compared with those in individuals with a GFI1B H294 fs mutation of the fifth DNA-binding zinc-finger. Patient-specific induced pluripotent stem cell (iPSC)-derived megakaryocytes were generated to facilitate disease modeling. Results The DNA-binding GFI1B variant C168F, which is predicted to disrupt the first non-DNA-binding zinc-finger domain, is associated with macrothrombocytopenia without α-granule deficiency or bleeding symptoms. A GFI1B splice variant, c.2520 + 1_2520 + 8delGTGGGCAC, which generates a short GFI1B isoform that lacks non-DNA-binding zinc-fingers 1 and 2, is associated with increased platelet CD34 expression only, without quantitative or morphologic platelet abnormalities. GFI1B represses the CD34 promoter, and this repression is attenuated by different GFI1B zinc-finger mutations, suggesting that deregulation of CD34 expression occurs at a direct transcriptional level. Patient-specific iPSC-derived megakaryocytes phenocopy these observations. Conclusions Disruption of GFI1B non-DNA-binding zinc-finger 1 is associated with mild to moderate thrombocytopenia without α-granule deficiency or bleeding symptomatology, indicating that the site of GFI1B mutation has important phenotypic implications. Platelet CD34 expression appears to be a common feature of perturbed GFI1B function, and may have diagnostic utility.
METHODOLOGY/PRINCIPAL FINDINGS: After reviewing the published literature we identified potential host and vector species and ranked these based on how informative they are for the presence of an infectious parasite reservoir, based on current evidence. We collated spatial data on parasite occurrence and the ranges of the identified host and vector species. The ranked spatial data allowed us to assign an evidence score to 475 subnational areas in 19 countries and we present the results on a map of the Southeast and South Asia region.
CONCLUSIONS/SIGNIFICANCE: We have ranked subnational areas within the potential disease range according to evidence for presence of a disease risk to humans, providing geographical evidence to support decisions on prevention, management and prophylaxis. This work also highlights the unknown risk status of large parts of the region. Within this unknown category, our map identifies which areas have most evidence for the potential to support an infectious reservoir and are therefore a priority for further investigation. Furthermore we identify geographical areas where further investigation of putative host and vector species would be highly informative for the region-wide assessment.