Cat bite injuries to the hand and forearm: the impact of antibiotic treatment on microbiological findings and clinical outcome.

INTRODUCTION: Patients and physicians often underestimate cat bite injuries. The deep and narrow wound seals quickly and provides an environment for the inoculated saliva and bacteria. Interestingly, the literature reports no bacterial growth in the microbiological workup of wound swaps in up to 43%. The time between bite injury and the first clinical presentation, the start of antibiotic treatment and surgical debridement might affect these findings. Therefore, the current project examines if (1) these factors impact the outcome of microbiological results following cat bite injuries and (2) the detection of bacterial growth leads to higher complication rates, longer hospital stays, longer total treatment time, or higher total treatment costs. MATERIALS AND METHODS: This single-center retrospective study analyzed data from 102 adult patients. All patients received antibiotic and surgical treatment following a cat bite injury. Microbiological samples were collected during surgery in all cases. The time from the bite incident to the first presentation, beginning of antibiotic administration, and surgical debridement was calculated. Demographic data, complication rate, length of hospital stay, total treatment time, and total treatment costs were recorded. (1) A generalized linear model was fitted using the microbiological outcome as the dependent variable. (2) Two groups (negative or positive microbiological results) were formed and statistically compared. RESULTS: The median age was 50 (SD 16), and 72% were female. (1) The time from the bite incident to the first clinical presentation, antibiotic administration, or surgical treatment was not associated with the outcome of the microbiological result. (2) No significant differences were observed between the two groups. CONCLUSIONS: Our data do not suggest that early antibiotic administration or delayed surgical treatment affects the outcome of the microbiological workup following cat bite injuries to the hand and forearm. The microbiological outcome did not affect the complication rate, treatment time, and total treatment costs.

Image Correlation Between Digitally Reconstructed Radiographs, C-arm Fluoroscopic Radiographs, and X-ray: A Phantom Study.

OBJECTIVE: Digitally reconstructed radiographs (DRRs) are planar two-dimensional (2D) X-rays derived from a three-dimensional (3D) computed tomography (CT) dataset. DRRs allow the simulation of radiographs of all desired views and facilitate preoperative planning. However, orthopedic surgeons rely on C-arm fluoroscopic imaging during surgery to verify fracture reduction and implant placement. Pincushion distortion represents a technical limitation of fluoroscopic imaging, resulting in a greater distance between points at the periphery of the image compared to the center. This project, therefore, aimed to assess the image correlation between digitally reconstructed radiographs (DRRs) and fluoroscopic imaging (C-arm) using conventional radiographs (X-ray) as a control. METHODS: A 3D-printed cubic prototype and an anatomical humerus bone model were used. C-arm fluoroscopic radiographs and conventional X-ray images were taken in an anteroposterior (AP) view at 10-degree steps while rotating the objects from 0 to 90 degrees. CT scans were made and used to compute and export DRRs in AP view at 10-degree rotational steps from 0 to 90 degrees. The surface area (cm2) was measured and compared between the different modalities. For automated image analysis of the anatomical humerus model, matching (%) between modalities was calculated using the structural similarity index (SSIM). RESULTS: The overall regression was statistically significant in all models, with an R2 >0.99 when comparing all three imaging modalities of the prototype. Surface correlation in the anatomical humerus model was R2 0.99 between X-ray and C-arm and R2 0.95 between C-arm and X-ray to DRRs, respectively. The SSIM was highest for comparing DRR and C-arm images (0.84±0.01%). CONCLUSIONS: The study indicates a strong agreement between digitally reconstructed radiographs and X-ray/C-arm images. DRRs, therefore, represent a valuable tool for research and clinical application.

Celecoxib alleviates nociceptor sensitization mediated by interleukin-1beta-primed annulus fibrosus cells.

PURPOSE: This study aims to analyze the effect of pro-inflammatory cytokine-stimulated human annulus fibrosus cells (hAFCs) on the sensitization of dorsal root ganglion (DRG) cells. We further hypothesized that celecoxib (cxb) could inhibit hAFCs-induced DRG sensitization. METHODS: hAFCs from spinal trauma patients were stimulated with TNF-α or IL-1ß. Cxb was added on day 2. On day 4, the expression of pro-inflammatory and neurotrophic genes was evaluated using RT-qPCR. Levels of prostaglandin E2 (PGE-2), IL-8, and IL-6 were measured in the conditioned medium (CM) using ELISA. hAFCs CM was then applied to stimulate the DRG cell line (ND7/23) for 6 days. Then, calcium imaging (Fluo4) was performed to evaluate DRG cell sensitization. Both spontaneous and bradykinin-stimulated (0.5 µM) calcium responses were analyzed. The effects on primary bovine DRG cell culture were performed in parallel to the DRG cell line model. RESULTS: IL-1ß stimulation significantly enhanced the release of PGE-2 in hAFCs CM, while this increase was completely suppressed by 10 µM cxb. hAFCs revealed elevated IL-6 and IL-8 release following TNF-α and IL-1ß treatment, though cxb did not alter this. The effect of hAFCs CM on DRG cell sensitization was influenced by adding cxb to hAFCs; both the DRG cell line and primary bovine DRG nociceptors showed a lower sensitivity to bradykinin stimulation. CONCLUSION: Cxb can inhibit PGE-2 production in hAFCs in an IL-1ß-induced pro-inflammatory in vitro environment. The cxb applied to the hAFCs also reduces the sensitization of DRG nociceptors that are stimulated by the hAFCs CM.

Homing of vertebral-delivered mesenchymal stromal cells for degenerative intervertebral discs repair - an in vivo proof-of-concept study.

Introduction: Cell transplantation shows promising results for intervertebral disc (IVD) repair, however, contemporary strategies present concerns regarding needle puncture damage, cell retention, and straining the limited nutrient availability. Mesenchymal stromal cell (MSC) homing is a natural mechanism of long-distance cellular migration to sites of damage and regeneration. Previous ex vivo studies have confirmed the potential of MSC to migrate over the endplate and enhance IVD-matrix production. In this study, we aimed to exploit this mechanism to engender IVD repair in a rat disc degeneration model. Methods: Female Sprague Dawley rats were subjected to coccygeal disc degeneration through nucleus pulposus (NP) aspiration. In part 1; MSC or saline was transplanted into the vertebrae neighboring healthy or degenerative IVD subjected to irradiation or left untouched, and the ability to maintain the IVD integrity for 2 and 4 weeks was assessed by disc height index (DHI) and histology. For part 2, ubiquitously GFP expressing MSC were transplanted either intradiscally or vertebrally, and regenerative outcomes were compared at days 1, 5, and 14 post-transplantation. Moreover, the homing potential from vertebrae to IVD of the GFP+ MSC was assessed through cryosection mediated immunohistochemistry. Results: Part 1 of the study revealed significantly improved maintenance of DHI for IVD vertebrally receiving MSC. Moreover, histological observations revealed a trend of IVD integrity maintenance. Part 2 of the study highlighted the enhanced DHI and matrix integrity for discs receiving MSC vertebrally compared with intradiscal injection. Moreover, GFP rates highlighted MSC migration and integration in the IVD at similar rates as the intradiscally treated cohort. Conclusion: Vertebrally transplanted MSC had a beneficial effect on the degenerative cascade in their neighboring IVD, and thus potentially present an alternative administration strategy. Further investigation will be needed to determine the long-term effects, elucidate the role of cellular homing versus paracrine signaling, and validate our observations on a large animal model.

Indications, clinical outcome and survival of rotating hinge total knee arthroplasty in a retrospective study of 63 primary and revision cases.

PURPOSE: The purpose of this study is to report and compare outcome data of both primary and revision cases using a rotating hinge knee (RHK) implant. METHODS: This study retrospectively analyzed 63 cases (19 primary, 44 revisions) at a mean follow-up of 34 ± 8 months after RHK implantation. Outcome parameters were stability, range of motion (ROM), loosening, Hospital of Special Surgery Score (HSS), Knee Society Score (KSS), Oxford Knee Score (OKS), EQ-5D-3L, and Visual Analog Scale (VAS) for overall function. Revision rates and implant survival are reported. RESULTS: Eleven percent showed medio-lateral instability < 5 mm, a mean ROM of 115° ± 17° and radiologic loosening occurred in 8% (2% symptomatic). PROMS showed the following results: HSS 79 ± 18, KSS 78 ± 27, OKS 26 ± 10, EQ-5D index 0.741 ± 0.233 and VAS 70 ± 20. Primary cases revealed better outcomes in HHS (p = .035) and OKS (p = 0.047). KSS, EQ-5D index and VAS did not differ between primary and revision cases (p = 0.070; p = 0.377; p = 0.117). Revision rate was 6.3% with an implant survival of 96.8%. CONCLUSIONS: RHK arthroplasty can be performed with good clinical outcome and low revision rate in revision and complex primary cases. RHK is an option in cases where standard arthroplasty and even implants with a higher degree of constraint have reached their limits. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Survival, functional outcome and satisfaction of first revision total knee arthroplasty at a mean eleven-year follow-up.

PURPOSE: Providing long-term outcome data after rTKA and compare one- versus two-stage and septic versus aseptic revisions. METHODS: This study represents a single-center retrospective study of first rTKAs performed for any reason with a final follow-up of a minimum of five years. Outcome parameters included stability assessment ROM, radiologic assessment, HSS score, KSS score, OKS score, EQ-5D-3L and VAS. 44 patients were included in the study. Subgroups analysis of one- versus two-stage revision and septic versus aseptic revision was performed. RESULTS: The leading causes of rTKA in this mean 11 year follow-up study were aseptic loosening (36%) and periprosthetic joint infection (27%). At the final follow-up, there was a 89% survivorship of the implants. Patients showed a ROM of 114 ± 13°, HSS score of 78 ± 12, KKS objective score of 77 ± 16, KSS expectation and satisfaction score of 32 ± 11, KSS functional activity score of 50 ± 20, OKS of 30 ± 9, VAS of 53 ± 25 and EQ-5D index of 0.649. Functional outcome scores were not significantly altered in the analyzed subgroups. CONCLUSIONS: In our 11 years follow-up, we obtained 89% implant survivorship. Measurements regarding functional outcome and pain showed results in the medium range of the respective scores, while patient satisfaction lay in the upper third. No significant differences in outcome scores between one- and two-stage revisions and septic versus aseptic revisions were observed. Level of Evidence Level III, retrospective cohort study.

The Application of Mesenchymal Stromal Cells and Their Homing Capabilities to Regenerate the Intervertebral Disc.

Chronic low back pain (LBP) remains a challenging condition to treat, and especially to cure. If conservative treatment approaches fail, the current "gold standard" for intervertebral disc degeneration (IDD)-provoked back pain is spinal fusion. However, due to its invasive and destructive nature, the focus of orthopedic research related to the intervertebral disc (IVD) has shifted more towards cell-based therapeutic approaches. They aim to reduce or even reverse the degenerative cascade by mimicking the human body's physiological healing system. The implementation of progenitor and/or stem cells and, in particular, the delivery of mesenchymal stromal cells (MSCs) has revealed significant potential to cure the degenerated/injured IVD. Over the past decade, many research groups have invested efforts to find ways to utilize these cells as efficiently and sustainably as possible. This narrative literature review presents a summary of achievements made with the application of MSCs for the regeneration of the IVD in recent years, including their preclinical and clinical applications. Moreover, this review presents state-of-the-art strategies on how the homing capabilities of MSCs can be utilized to repair damaged or degenerated IVDs, as well as their current limitations and future perspectives.

A Hyaluronan and Platelet-Rich Plasma Hydrogel for Mesenchymal Stem Cell Delivery in the Intervertebral Disc: An Organ Culture Study.

The purpose of the present pilot study was to evaluate the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) as a carrier for human mesenchymal stem cells (hMSCs) for intervertebral disc (IVD) regeneration using a disc organ culture model. HA was mixed with batroxobin (BTX) and PRP to form a hydrogel encapsulating 1 × 106 or 2 × 106 hMSCs. Bovine IVDs were nucleotomized and filled with hMSCs suspended in ~200 µL of the PRP/HA/BTX hydrogel. IVDs collected at day 0 and nucleotomized IVDs with no hMSCs and/or hydrogel alone were used as controls. hMSCs encapsulated in the hydrogel were also cultured in well plates to evaluate the effect of the IVD environment on hMSCs. After 1 week, tissue structure, scaffold integration, hMSC viability and gene expression of matrix and nucleus pulposus (NP) cell markers were assessed. Histological analysis showed a better preservation of the viability of the IVD tissue adjacent to the gel in the presence of hMSCs (~70%) compared to the hydrogel without hMSCs. Furthermore, disc morphology was maintained, and the hydrogel showed signs of integration with the surrounding tissues. At the gene expression level, the hydrogel loaded with hMSCs preserved the normal metabolism of the tissue. The IVD environment promoted hMSC differentiation towards a NP cell phenotype by increasing cytokeratin-19 (KRT19) gene expression. This study demonstrated that the hydrogel composed of HA/PRP/BTX represents a valid carrier for hMSCs being able to maintain a good cell viability while stimulating cell activity and NP marker expression.

3D analysis of fatty infiltration of the paravertebral lumbar muscles using T2 images-a new approach.

PURPOSE: Factors influencing paraspinal muscle degeneration are still not well understood. Fatty infiltration is known to be one main feature of the degeneration cascade. The aim of this cross-sectional study was to illustrate the 3D cluster of paraspinal lumbar muscle degeneration on T2-weighted MRI images using our newly developed software application 'iSix'. METHODS: Mono- (Mm. rotatores), multi- (Mm. multifidus) and pluri-segmental (M. erector spinae) lumbar muscles groups were segmented on T2-weighted MR sequences using a novel computer-assisted technique for quantitative muscle/fat discrimination. The degree of fatty infiltration of the three predefined muscle groups was compared on a 3-dimensional basis, with regard to segment involvement and age. General linear models were utilized for statistical comparison. RESULTS: N = 120 segments (age: 52.7; range 16-87 years) could be included. The overall relative fatty infiltration of the mono-segmental muscles was higher (21.1 14.5%) compared to the multi-segmental (16.0 8.8% p = 0.049) and pluri-segmental muscles (8.5 8.0%; p = 0.03). Mono-segmental muscles on the levels L4/5 (22.9 ± 10.2 [CI 17.6-28.2] %) and L5/S1 (27.01 ± 15.1 [CI 21.4-32.7] %) showed a significant higher amount of fat compared to the levels L2/3 (8.2 ± 6.8 [CI 2.2-14.2] %; L4/5 vs. L2/3, p = 0.03; L5/S1 vs. L2/3, p = 0.02) and L3/4 (13.2 ± 5.4 [CI 8.6-17.7]%; L4/5 vs. L3/4, p = 0.02; L5/S1 vs. L3/4, p < 0.01). Multivariate linear regression analyses revealed age and Pfirrmann grade as independent factors for fatty muscle degeneration. CONCLUSIONS: 3D analysis of fatty infiltration is an innovative tool to study lumbar muscle degeneration. Mono-segmental muscles are more severely affected by degeneration compared to multi-/pluri-segmental muscles, especially at the L4/5 and L5/S1 level. Age and disc degeneration independently correlate with muscle degeneration.

Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis.

BACKGROUND: Mesenchymal stromal cells (MSCs) have been introduced as promising cell source for regenerative medicine. Besides their multilineage differentiation capacity, MSCs release a wide spectrum of bioactive factors. This secretome holds immunomodulatory and regenerative capacities. In intervertebral disc (IVD) cells, application of MSC secretome has been shown to decrease the apoptosis rate, induce proliferation, and promote production of extracellular matrix (ECM). For clinical translation of secretome-based treatment, characterization of the secretome composition is needed to better understand the induced biological processes and identify potentially effective secretomes. METHODS: This study aimed to investigate the proteome released by bone marrow-derived MSCs following exposure to a healthy, traumatic, or degenerative human IVD environment by mass spectroscopy and quantitative immunoassay analyses. Exposure of MSCs to the proinflammatory stimulus interleukin 1ß (IL-1ß) was used as control. RESULTS: Compared to MSC baseline secretome, there were 224 significantly up- or downregulated proteins following healthy, 179 following traumatic, 223 following degenerative IVD, and 160 proteins following IL-1ß stimulus. Stimulation of MSCs with IVD conditioned media induced a more complex MSC secretome, involving more biological processes, compared to stimulation with IL-1ß. The MSC response to stimulation with IVD conditioned medium was dependent on their pathological status. CONCLUSIONS: The MSC secretome seemed to match the primary need of the IVD: homeostasis maintenance in the case of healthy IVDs, versus immunomodulation, adjustment of ECM synthesis and degradation disbalance, and ECM (re) organization in the case of traumatic and degenerative IVDs. These findings highlight the importance of cell preconditioning in the development of tailored secretome therapies. The secretome of human bone marrow-derived mesenchymal stromal cells (MSCs) stimulated with intervertebral disc (IVD) conditioned medium was analyzed by proteomic profiling. Depending on the pathological state of the IVD, the MSC secretome protein composition indicated immunomodulatory or anabolic activity of the secretome. These findings may have implications for tailored secretome therapy for the IVD and other tissues.

Mesenchymal Stem Cell Homing Into Intervertebral Discs Enhances the Tie2-positive Progenitor Cell Population, Prevents Cell Death, and Induces a Proliferative Response.

STUDY DESIGN: Experimental study with human mesenchymal stem cells (MSCs) and intervertebral disc (IVD) tissue samples. OBJECTIVE: This study aimed to characterize the effect of MSC homing on the Tie2-positive IVD progenitor cell population, IVD cell survival, and proliferation. SUMMARY OF BACKGROUND DATA: Homing of human MSCs has been described as potential alternative to MSC injection, aiming to enhance the regenerative capacity of the IVD. IVD cells expressing Tie2 (also known as CD202b or Angiopoietin-1 receptor TEK tyrosine kinase) represent a progenitor cell population with discogenic differentiation potential. However, the fraction of Tie2-positive progenitor cells decreases with aging and degree of IVD degeneration, resulting in a potential loss of the IVD's regenerative capacity. METHODS: Human MSCs, isolated from vertebral bone marrow aspirates, were labeled and seeded onto the endplate of bovine IVDs and human IVD tissue. Following MSC migration for 5 days, IVD cells were isolated by tissue digestion. The fractions of Tie2-positive, dead, apoptotic, and proliferative IVD cells were evaluated by flow cytometry and compared to untreated IVDs. For human IVDs, 3 groups were investigated: nondegenerated (organ donors), IVDs of patients suffering from spinal trauma, and degenerative IVD tissue samples. RESULTS: MSC homing enhanced the fraction of Tie2-positive IVD cells in bovine and human IVD samples. Furthermore, a proliferative response and lower fraction of dead cells were observed after MSC homing in both bovine and human IVD tissues. CONCLUSION: Our findings indicate that MSC homing enhances the survival and regenerative capability of IVD cells, which may be mediated by intercellular communication. MSC homing could represent a potential treatment strategy to prevent the onset of the degenerative cascade in IVDs at risk such as IVDs adjacent to a fused segment or IVDs after herniation. LEVEL OF EVIDENCE: N/A.

Reduction of cement leakage by sequential PMMA application in a vertebroplasty model.

PURPOSE: Leakage is the most common complication of percutaneous cement augmentation of the spine. The viscosity of the polymethylmethacrylate (PMMA) cement is strongly correlated with the likelihood of cement leakage. We hypothesized that cement leakage can be reduced by sequential cement injection in a vertebroplasty model. METHODS: A standardized vertebral body substitute model, consisting of aluminum oxide foams coated by acrylic cement with a preformed leakage path, simulating a ventral vein, was developed. Three injection techniques of 6 ml PMMA were assessed: injection in one single step (all-in-one), injection of 1 ml at the first and 5 ml at the second step with 1 min latency in-between (two-step), and sequential injection of 0.5 ml with 1-min latency between the sequences (sequential). Standard PMMA vertebroplasty cement was used; each injection type was tested on ten vertebral body substitute models with two possible leakage paths per model. Leakage was assessed by radiographs using a zonal graduation: intraspongious = no leakage and extracortical = leakage. RESULTS: The leakage rate was significantly lower in the "sequential" technique (2/20 leakages) followed by "two-step" (15/20) and "all-in-one" (20/20) techniques (p < 0.001). The RR for a cement leakage was 10.0 times higher in the "all-in-one" compared to the "sequential" group (95 % confidence intervals 2.7-37.2; p < 0.001). CONCLUSIONS: The sequential cement injection is a simple approach to minimize the risk for leakage. Taking advantage of the temperature gradient between body and room temperature, it is possible to increase the cement viscosity inside the vertebra while keeping it low in the syringe. Using sequential injection of small cement volumes, further leakage paths are blocked before further injection of the low-viscosity cement.