Contaminated bone grafts and tuberculosis in three spine surgery patients: a case series

Tuberculosis (TB) is a global health issue affecting millions of people every year. Previous articles displayed cases of TB resulting from contaminated bone grafts used in spinal surgeries. However, deeper understanding about the serious health consequences for patients affected by TB-infected bone grafts is lacking. Here, we discuss three unique patients who contracted TB after undergoing lumbar spinal surgery. We describe three patient cases in which individuals initially presented with back pain, underwent required lumbar spinal fusion surgery with bone graft implants, and, afterwards, contracted TB. All patients were given RIPE therapy, had additional surgery to remove the faulty hardware, and lived with significant and prolonged pain. In addition, patient X experienced night sweats, patient Y had a subcutaneous abscess positive for TB, and patient Z had severe burning pain, rash, and sweats. Altogether, we emphasize the importance of increasing our awareness about the potential risks and complications associated with utilizing contaminated surgical products. We encourage healthcare professionals to take necessary precautions to ensure the safety of their patients by screening bone grafts for potential pathogens and practicing proper sterilization techniques.

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

Case report: Tuberculosis recall on bone graft patient

Background: Bone grafting is commonly used in spine surgery to supplement or replace the need for autografts. This is harvested, prepared, and utilized predominantly for osteoconductive properties. Anterior cervical discectomy and fusion, a procedure to decompress and fuse the spine which treats herniated discs and compressed nerves, commonly uses Polyetheretherketone (PEEK) interbody filled with allograft bone matrices to reconstruct the disc space after a discectomy is performed. Case Description: The presented case is one of a 57-year-old male patient who underwent an uneventful cervical 5–6 and cervical 6–7 discectomy and fusion using a PEEK interbody and bone allograft. The allograft had been prepared using cancellous bone particles with preserved living cells and demineralized cortical bone fibers to facilitate bone repair and healing, which is a common technique. The allograft was aseptically processed to preserve native factors that can support bone repair and prevent contamination and cross-contamination of the product. Additionally, the product was sterilized using gamma irradiation to further prevent contamination. Outcome: Unfortunately, with the presented case, the State's Department of Health and The Center for Diseases Control and Prevention identified that the graft was from a source contaminated with tuberculosis. The patient being reported went on to develop disseminated tuberculosis, including lung abscesses and osteomyelitis. Conclusions: The current case highlights that there was contamination of the donor bone sources. Tuberculosis was not screened in the tissue donor even though he had risk factors, symptoms, and signs consistent with tuberculosis. Although there are methods to screen potential organ donors for tuberculosis, there is currently no approved standard laboratory tuberculosis screening tool for bone grafts. Thus, this emphasizes the importance of proper screening among individual institutions for even the most uncommon diseases in all donated bone grafts

Physiological profile of undifferentiated bovine blastocyst-derived trophoblasts

Trophectoderm of blastocysts mediate early events in fetal-maternal communication, enabling implantation and establishment of a functional placenta. Inadequate or impaired developmental events linked to trophoblasts directly impact early embryo survival and successful implantation during a crucial period that corresponds with high incidence of pregnancy losses in dairy cows. As yet, the molecular basis of bovine trophectoderm development and signaling towards initiation of implantation remains poorly understood. In this study, we developed methods for culturing undifferentiated bovine blastocyst-derived trophoblasts and used both transcriptomics and proteomics in early colonies to categorize and elucidate their functional characteristics. A total of 9270 transcripts and 1418 proteins were identified and analyzed based on absolute abundance. We profiled an extensive list of growth factors, cytokines and other relevant factors that can effectively influence paracrine communication in the uterine microenvironment. Functional categorization and analysis revealed novel information on structural organization, extracellular matrix composition, cell junction and adhesion components, transcription networks, and metabolic preferences. Our data showcase the fundamental physiology of bovine trophectoderm and indicate hallmarks of the self-renewing undifferentiated state akin to trophoblast stem cells described in other species. Functional features uncovered are essential for understanding early events in bovine pregnancy towards initiation of implantation

A variant at 9p21.3 functionally implicates CDKN2B in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology.

Paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common cancer of childhood, yet little is known about BCP-ALL predisposition. In this study, in 2,187 cases of European ancestry and 5,543 controls, we discover and replicate a locus indexed by rs77728904 at 9p21.3 associated with BCP-ALL susceptibility (Pcombined=3.32 × 10(-15), OR=1.72) and independent from rs3731217, the previously reported ALL-associated variant in this region. Of correlated SNPs tagged by this locus, only rs662463 is significant in African Americans, suggesting it is a plausible causative variant. Functional analysis shows that rs662463 is a cis-eQTL for CDKN2B, with the risk allele associated with lower expression, and suggests that rs662463 influences BCP-ALL risk by regulating CDKN2B expression through CEBPB signalling. Functional analysis of rs3731217 suggests it is associated with BCP-ALL by acting within a splicing regulatory element determining CDKN2A exon 3 usage (P=0.01). These findings provide new insights into the critical role of the CDKN2 locus in BCP-ALL aetiology