Efficacy and Accuracy of Diagnosing Septic Arthritis: How Effective are Current Methods for Timely Diagnosis of Septic Arthritis?

The diagnosis of septic arthritis requires a reliance on ancillary tests, including synovial fluid white blood cell count (jWBC), percentage of polymorphonuclear leukocytes (%PMN), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). This study evaluated these tests to determine their diagnostic utility in suspected septic arthritis. A retrospective chart review was performed on patients admitted to an urban hospital who underwent arthrocentesis. The authors evaluated the jWBC, %PMN, ESR, and CRP with receiver operating characteristic (ROC) curve analyses. Two hundred sixty-five patients met inclusion criteria. Sixty-three had a culture-positive aspirate. ROC curve analysis resulted in an area under the curve (AUC) of 0.80 for jWBC with cutoff point of 22,563 cells/mm3 and an AUC of 0.71 for %PMN with cutoff point of 90.5%. CRP and ESR had AUC values of 0.62 and 0.61, respectively. The culture-positive cohort had higher elevations in all assessed diagnostic tests. However, AUC data for ESR and CRP showed little diagnostic utility. Additionally, sensitivities and specificities of jWBC and %PMN were too low. Associated cutoff points would result in excessive unnecessary operative intervention. Further studies should incorporate synovial fluid biomarkers into the workup of a suspected septic joint. (Journal of Surgical Orthopaedic Advances 33(2):108-111, 2024).

Heterogeneity in human hippocampal CaMKII transcripts reveals allosteric hub-dependent regulation.

Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in Ca2+ signaling throughout the body. In the hippocampus, CaMKII is required for learning and memory. Vertebrate genomes encode four CaMKII homologs: CaMKIIα, CaMKIIß, CaMKIIγ, and CaMKIIδ. All CaMKIIs consist of a kinase domain, a regulatory segment, a variable linker region, and a hub domain, which is responsible for oligomerization. The four proteins differ primarily in linker length and composition because of extensive alternative splicing. Here, we report the heterogeneity of CaMKII transcripts in three complex samples of human hippocampus using deep sequencing. We showed that hippocampal cells contain a diverse collection of over 70 CaMKII transcripts from all four CaMKII-encoding genes. We characterized the Ca2+/CaM sensitivity of hippocampal CaMKII variants spanning a broad range of linker lengths and compositions. The effect of the variable linker on Ca2+/CaM sensitivity depended on the kinase and hub domains. Moreover, we revealed a previously uncharacterized role for the hub domain as an allosteric regulator of kinase activity, which may provide a pharmacological target for modulating CaMKII activity. Using small-angle x-ray scattering and single-particle cryo-electron microscopy (cryo-EM), we present evidence for extensive interactions between the kinase and the hub domains, even in the presence of a 30-residue linker. Together, these data suggest that Ca2+/CaM sensitivity in CaMKII is homolog dependent and includes substantial contributions from the hub domain. Our sequencing approach, combined with biochemistry, provides insights into understanding the complex pool of endogenous CaMKII splice variants.