Intraosseous Shelf Plate Fixation for Depressed Articular Fragments in Tibial Plateau Fractures: A Technical Trick and Case Series.

SUMMARY: Tibial plateau fractures with severely displaced articular injuries and significant deformity to the surrounding metaphyseal bone (including the hyperextension varus bicondylar pattern) can be challenging to stabilize due to resulting large bone voids uncontained by metaphyseal cortex. The purpose of this report was to describe a technique to support the plateau articular surface in these cases and report on outcomes of a small series. This technique uses a small or mini fragment plate, contoured to function as an intraosseous shelf plate, with the "shelf" portion inserted into the bone beneath the articular surface to support it. This technique provides fixed-angle support to the fragment. There are some advantages of this technique compared to structural allograft, large volume ceramic bone void filler, a spine cage, or other trabecular metal object, including the ability to remove the plate later, ability to tension the plate against the depressed articular surface, ability to place screws or other allograft near the implant, wide availability of the implant, and familiarity of orthopaedic trauma surgeons with placing plates and screws to hold reductions. The technique is particularly useful in patterns with uncontained articular depression and a large metaphyseal void.

Dorsal Hook Plating of Patella Fractures With Immediate Range of Motion Results in Reliable Fixation, Low Implant Removal Rates, and Satisfactory Clinical Outcomes.

OBJECTIVES: To evaluate radiographic and clinical patient-reported outcomes following dorsal hook plating of displaced patella fractures with permittance of immediate postoperative active closed chain range of motion. DESIGN: Retrospective review of prospectively collected data. SETTING: Urban academic level 1 trauma center. PATIENT SELECTION CRITERIA: Adult patients with displaced patella fractures (OTA/AO 34C1-3) who underwent dorsal plating with immediate range of motion between 2018 and 2023. OUTCOME MEASURES AND COMPARISONS: Numerical Rating Scale for Pain, Knee Outcome Score (KOS-ADL), Tegner-Lysholm score, radiographic union, and wound complications were collected. RESULTS: Sixty-one patients were included (47 female) with an average age of 63 years (SD 14.7, range 22-86 years). The mean BMI was 24.2 (SD 3.6, range 16.6-33.3). There were 13 34-C2 and 48 34-C3 fractures. All but 2 patients (96.7%) achieved bony union after the index procedure. 89% (n = 54) of patients completed outcome surveys with at least 6-month follow-up. Six patients (9.8%) underwent removal of plate implant at a mean of 15.1 months postoperatively. The mean KOS-ADL score was 91.4, the mean Tegner-Lysholm score was 78.1, and the mean NRS was 2.7. CONCLUSIONS: Dorsal hook plating offers secure fixation to allow early range of motion, reliable fixation with low nonunion and implant failure rates, low implant removal rates, and satisfactory patient-reported outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Clinical rel mutations in Staphylococcus aureus prime pathogen expansion under nutrient stress.

Persistent infection by Staphylococcus aureus has been linked to the bacterial stringent response (SR), a conserved stress response pathway regulated by the Rel protein. Rel synthesizes (p)ppGpp "alarmones" in response to amino acid starvation, which enables adaptation to stress by modulating bacterial growth and virulence. We previously identified five novel protein-altering mutations in rel that arose in patients with persistent methicillin-resistant S. aureus bacteremia. The mutations mapped to both the enzymatic and regulatory protein domains of Rel. Here, we set out to characterize the phenotype of these mutations to understand how they may have been selected in vivo. After introducing each mutation into S. aureus strain JE2, we analyzed growth, fitness, and antibiotic profiles. Despite being located in different protein domains, we found that all of the mutations converged on the same phenotype. Each shortened the time of lag phase growth and imparted a fitness advantage in nutritionally depleted conditions. Through quantification of intracellular (p)ppGpp, we link this phenotype to increased SR activation, specifically during the stationary phase of growth. In contrast to two previously identified clinical rel mutations, we find that our rel mutations do not cause antibiotic tolerance. Instead, our findings suggest that in vivo selection was due to an augmented SR that primes cells for growth in nutrient-poor conditions, which may be a strategy for evading host-imposed nutritional immunity. Importance Host and pathogen compete for available nutrition during infection. For bacteria, the stringent response (SR) regulator Rel responds to amino acid deprivation by signaling the cell to modulate its growth rate, metabolism, and virulence. In this report, we characterize five rel mutations that arose during cases of persistent methicillin-resistant Staphylococcus aureus bacteremia. We find that all of the mutations augmented SR signaling specifically under nutrient-poor conditions, enabling the cell to more readily grow and survive. Our findings reveal a strategy used by bacterial pathogens to evade the nutritional immunity imposed by host tissues during infection.

Spatial Profiling of the Prostate Cancer Tumor Microenvironment Reveals Multiple Differences in Gene Expression and Correlation with Recurrence Risk.

The tumor microenvironment plays a crucial role in both the development and progression of prostate cancer. Furthermore, identifying protein and gene expression differences between different regions is valuable for treatment development. We applied Digital Spatial Profiling multiplex analysis to formalin-fixed paraffin embedded prostatectomy tissue blocks to investigate protein and transcriptome differences between tumor, tumor-adjacent stroma (TAS), CD45+ tumor, and CD45+ TAS tissue. Differential expression of an immunology/oncology protein panel (n = 58) was measured. OX40L and CTLA4 were expressed at higher levels while 22 other proteins, including CD11c, were expressed at lower levels (FDR < 0.2 and p-value < 0.05) in TAS as compared to tumor epithelia. A tissue microarray analysis of 97 patients with 1547 cores found positive correlations between high expression of CD11c and increased time to recurrence in tumor and TAS, and inverse relationships for CTLA4 and OX40L, where higher expression in tumor correlated with lower time to recurrence, but higher time to recurrence in TAS. Spatial transcriptomic analysis using a Cancer Transcriptome Atlas panel (n = 1825 genes) identified 162 genes downregulated and 69 upregulated in TAS versus tumor, 26 downregulated and 6 upregulated in CD45+ TAS versus CD45+ tumor. We utilized CIBERSORTx to estimate the relative immune cell fractions using CD45+ gene expression and found higher average fractions for memory B, naïve B, and T cells in TAS. In summary, the combination of protein expression differences, immune cell fractions, and correlations of protein expression with time to recurrence suggest that closely examining the tumor microenvironment provides valuable data that can improve prognostication and treatment techniques.