In vivo functional and morphological characterization of bone and striated muscle microcirculation in NSG mice.

Organ-specific microcirculation plays a central role in tumor growth, tumor cell homing, tissue engineering, and wound healing. Mouse models are widely used to study these processes; however, these mouse strains often possess unique microhemodynamic parameters, making it difficult to directly compare experiments. The full functional characterization of bone and striated muscle microcirculatory parameters in non-obese diabetic-severe combined immunodeficiency/y-chain; NOD-Prkds IL2rg (NSG) mice has not yet been reported. Here, we established either a dorsal skinfold chamber or femur window in NSG mice (n = 23), allowing direct analysis of microcirculatory parameters in vivo by intravital fluorescence microscopy at 7, 14, 21, and 28 days after chamber preparation. Organ-specific differences were observed. Bone had a significantly lower vessel density but a higher vessel diameter than striated muscle. Bone also showed higher effective vascular permeability than striated muscle. The centerline velocity values were similar in the femur window and dorsal skinfold chamber, with a higher volumetric blood flow in bone. Interestingly, bone and striated muscle showed similar tissue perfusion rates. Knowledge of physiological microhemodynamic values of bone and striated muscle in NSG mice makes it possible to analyze pathophysiological processes at these anatomic sites, such as tumor growth, tumor metastasis, and tumor microcirculation, as well as the response to therapeutic agents

The Hamburg Spondylodiscitis Assessment Score (HSAS) for Immediate Evaluation of Mortality Risk on Hospital Admission

(1) Background: Patients with spondylodiscitis often present with unspecific and heterogeneous symptoms that delay diagnosis and inevitable therapeutic steps leading to increased mortality rates of up to 27%. A rapid initial triage is essential to identify patients at risk for a complicative disease course. We therefore aimed to develop a risk assessment score using fast available parameters to predict in-hospital mortality of patients admitted with spondylodiscitis. (2) Methods: A retrospective data analysis of 307 patients with spondylodiscitis recruited from 2013 to 2020 was carried out. Patients were grouped according to all-cause mortality. Via logistic regression, individual patient and clinical characteristics predictive of mortality were identified. A weighted sum score to estimate a patient’s risk of mortality was developed and validated in a randomly selected subgroup of spondylodiscitis patients. (3) Results: 14% of patients with spondylodiscitis died during their in-hospital stay at a tertiary center for spinal surgery. Univariate and logistic regression analyses of parameters recorded at hospital admission showed that age older than 72.5 years, rheumatoid arthritis, creatinine > 1.29 mg/dL and CRP > 140.5 mg/L increased the risk of mortality 3.9-fold, 9.4-fold, 4.3-fold and 4.1-fold, respectively. S. aureus detection increased the risk of mortality by 2.3-fold. (4) Conclusions: The novel Hamburg Spondylodiscitis Assessment Score (HSAS) shows a good fit identifying patients at low-, moderate-, high- and very high risk for in hospital mortality on admission (AUC: 0.795; p < 0.001). The implementation of the HSAS into clinical practice could ease identification of high-risk patients using readily available parameters alone, improving the patient’s safety and outcome

Reduced cement volume does not affect screw stability in augmented pedicle screws

Purpose: Cement augmentation of pedicle screws is able to improve screw anchorage in osteoporotic vertebrae but is associated with a high complication rate. The goal of this study was to evaluate the impact of different cement volumes on pedicle screw fatigue strength. Methods: Twenty-five human vertebral bodies (T12–L4) were collected from donors between 73 and 97 years of age. Bone density (BMD) was determined by quantitative computed tomography. Vertebral bodies were instrumented by conventional pedicle screws, and unilateral cement augmentation was performed. Thirteen vertebrae were augmented with a volume of 1 ml and twelve with a volume of 3 ml bone cement. A fatigue test was performed using a cranial–caudal sinusoidal, cyclic load (0.5 Hz) with increasing compression force (100 N + 0.1 N/cycles). Results: The load to failure was 183.8 N for the non-augmented screws and was increased significantly to 268.1 N (p < 0.001) by cement augmentation. Augmentation with 1 ml bone cement increased the fatigue load by 41% while augmentation with 3 ml increased the failure load by 51% compared to the non-augmented screws, but there was no significant difference in fatigue loads between the specimens with screws augmented with 1 ml and screws augmented with 3 ml of bone cement (p = 0.504). Conclusion: Cement augmentation significantly increases pedicle screw stability. The benefit of augmentation on screw anchorage was not significantly affected by reducing the applied volume of cement from 3 ml to 1 ml. Considering the high risk of cement leakage during augmentation, we recommend the usage of a reduced volume of 1 ml bone cement for each pedicle screw. Graphic Abstract: These slides can be retrieved under Electronic Supplementary Material [Figure not available: see fulltext.].Open Access funding provided by Projekt DEAL

Outcome after Posterior Vertebral Column Resection in Patients with Severe Osteoporotic Fractures&mdash;A Retrospective Analysis from Two Centers

Background and Objectives: In osteoporotic fractures of the spine with resulting kyphosis and threatening compression of neural structures, therapeutic decisions are difficult. The posterior vertebral column resection (pVCR) has been described by different authors as a surgical treatment in a single-stage posterior procedure. The aim of this study is to evaluate midterm outcomes of patients treated by pVCR due to severe osteoporotic fractures. Materials and Methods: Retrospective data analysis of all the patients treated for osteoporotic fractures by pVCR from 2012&ndash;2020 at two centers was performed. Demographic data, visual analog scale (VAS), Frankel scale (FS), Karnofsky performance status (KPS), radiological result and spinal fusion rates were evaluated. Results: A total of 17 patients were included. The mean age was 70 &plusmn; 10.2 y. The mean VAS decreased significantly from 7.7 &plusmn; 2.8 preoperatively to 3.0 &plusmn; 1.6 at last follow-up (p &lt; 0.001) and the segmental kyphosis decreased from 29.4 &plusmn; 14.1&deg; to 7.9 &plusmn; 8.0&deg; (p &lt; 0.001). The neurologic function on the FS did not worsen in any and improved in four of the patients. The median KPS remained stable over the whole observation period (70% vs. 70%). Spinal fusion was observed in nine out of nine patients who received CT follow-up &gt;120 days after index surgery. Conclusions: This study showed that pVCR is a safe surgical technique with few surgical complications and no neurological deterioration considering the cohort. The patients&rsquo; segmental kyphosis and VAS improved significantly, while the KPS remained stable

Cortical threaded pedicle screw improves fatigue strength in decreased bone quality

Purpose!#!Inadequate anchoring of pedicle screws in vertebrae with poor bone quality is a major problem in spine surgery. The aim was to evaluate whether a modified thread in the area of the pedicle could significantly improve the pedicle screw fatigue strength.!##!Methods!#!Fourteen human cadaveric vertebral bodies (L2 and L3) were used for in vitro testing. Bone density (BMD) was determined by quantitative computed tomography. Vertebral bodies were instrumented by standard pedicle screws with a constant double thread on the right pedicle and a partial doubling of the threads-quad thread-(cortical thread) in the area of the pedicle on the left pedicle. Pulsating sinusoidal, cyclic load (0.5 Hz) with increasing peak force (100 N + 0.1 N/cycles) was applied orthogonal to the screw axis. The baseline force remained constant (50 N). Fatigue test was terminated after exceeding 5.4-mm head displacement (~ 20° screw tilting).!##!Results!#!The mean fatigue load at failure was 264.9 N (1682 cycles) for the standard screws and was increased significantly to 324.7 N (2285 cycles) by the use of cortical threaded screws (p = 0.014). This effect is particularly evident in reduced BMD (standard thread 241.2 N vs. cortical thread 328.4 N; p = 0.016), whereas in the group of vertebrae with normal BMD no significant difference could be detected (standard thread 296.5 N vs. cortical thread 319.8 N; p = 0.463).!##!Conclusions!#!Compared to a conventional pedicle screw, the use of a cortical threaded pedicle screw promises superior fatigue load in vertebrae with reduced bone quality

The bone microenvironment promotes tumor growth and tissue perfusion compared with striated muscle in a preclinical model of prostate cancer in vivo

Abstract Background Prostate cancer-related morbidity is associated with its preferential spread to the bone. Although the molecular interactions between the bone microenvironment and cancer cells have been researched extensively, the relevance of the microvascular properties of prostate cancer bone metastases remains largely unknown. Most preclinical studies focusing on microvascular analyses are based on heterotopic tumor implantation, whereas the impact of the microenvironment on site-specific growth behavior and angiogenesis is rarely addressed. Methods The microvascular changes associated with tumor growth in bone and soft tissue were characterized by implanting single cell suspensions of LnCap, Du145, and Pc3 cells into the femur (femur window) or striated muscle (dorsal skinfold chamber) of NSG mice. Tumor growth and the local microvasculature were analyzed for 21 days using intravital fluorescence microscopy. Results The results showed a higher engraftment of tumor cells in bone than in striated muscle associated with accelerated growth of LnCap cells and Pc3 cells. Permeability, blood flow, and tissue perfusion rates were greater in bone than in striated muscle. Du145 cells showed similar growth behavior in both tissues with similar vascular properties. The bone microenvironment facilitated tumor engraftment and growth. Increased microvascular density in striated muscle led to a higher tumor burden during early growth, whereas the increased perfusion promoted later prostate cancer growth in bone. Conclusions Monitoring prostate cancer microcirculation in bone and soft tissue may be useful to evaluate the organ-specific efficacy of new treatments

Microvascular parameters in the femur window group (dark gray bars) compared to the parameters in the dorsal skinfold chamber (light gray bars).

<p>All values are means ± SEM. Asterisks indicate p-values < 0.05. Abbreviations: Vmean, centerline velocity; BFR, blood perfusion rate; VD, vessel density; TPR, tissue perfusion rate; PERM, effective vascular permeability.</p

<i>In vivo</i> functional and morphological characterization of bone and striated muscle microcirculation in NSG mice

<div><p>Organ-specific microcirculation plays a central role in tumor growth, tumor cell homing, tissue engineering, and wound healing. Mouse models are widely used to study these processes; however, these mouse strains often possess unique microhemodynamic parameters, making it difficult to directly compare experiments. The full functional characterization of bone and striated muscle microcirculatory parameters in non-obese diabetic-severe combined immunodeficiency/y-chain; NOD-Prkds IL2rg (NSG) mice has not yet been reported. Here, we established either a dorsal skinfold chamber or femur window in NSG mice (n = 23), allowing direct analysis of microcirculatory parameters <i>in vivo</i> by intravital fluorescence microscopy at 7, 14, 21, and 28 days after chamber preparation. Organ-specific differences were observed. Bone had a significantly lower vessel density but a higher vessel diameter than striated muscle. Bone also showed higher effective vascular permeability than striated muscle. The centerline velocity values were similar in the femur window and dorsal skinfold chamber, with a higher volumetric blood flow in bone. Interestingly, bone and striated muscle showed similar tissue perfusion rates. Knowledge of physiological microhemodynamic values of bone and striated muscle in NSG mice makes it possible to analyze pathophysiological processes at these anatomic sites, such as tumor growth, tumor metastasis, and tumor microcirculation, as well as the response to therapeutic agents.</p></div

NSG mouse with chamber implantation.

<p>(a) NSG mouse equipped with a dorsal skinfold chamber (DSC) or (b) a femur window (FW) and observation window (arrow), showing that the microcirculation of the striated muscle and bone can be analyzed by intravital fluorescence microscopy. (scale bars a-b = 7 mm).</p

Spontaneous spondylodiscitis and endocarditis: interdisciplinary experience from a tertiary institutional case series and proposal of a treatment algorithm

Previously, the simultaneous presence of endocarditis (IE) has been reported in 3-30% of spondylodiscitis cases. The specific implications on therapy and outcome of a simultaneous presence of both diseases are not yet fully evaluated. Therefore, the aim of this study was to investigate the influence of a simultaneously present endocarditis on the course of therapy and outcome of spondylodiscitis. A prospective database analysis of 328 patients diagnosed with spontaneous spondylodiscitis (S) using statistical analysis with propensity score matching was conducted. Thirty-six patients (11.0%) were diagnosed with concurrent endocarditis (SIE) by means of transoesophageal echocardiography. In our cohort, the average age was 65.82 ± 4.12 years and 64.9% of patients were male. The incidence of prior cardiac or renal disease was significantly higher in the SIE group (coronary heart disease SIE n = 13/36 vs. S n = 57/292, p &amp;lt; 0.05 and chronic heart failure n = 11/36 vs. S n = 41/292, p &amp;lt; 0.05, chronic renal failure SIE n = 14/36 vs. S n = 55/292, p &amp;lt; 0.05). Complex interdisciplinary coordination and diagnostics lead to a significant delay in surgical intervention (S = 4.5 ± 4.5 days vs. SIE = 8.9 ± 9.5 days, p &amp;lt; 0.05). Mortality did not show statistically significant differences: S (13.4%) and SIE (19.1%). Time to diagnosis and treatment is a key to efficient treatment and patient safety. In order to counteract delayed therapy, we developed a novel therapy algorithm based on the analysis of treatment processes of the SIE group. We propose a clear therapy pathway to avoid frequently observed pitfalls and delays in diagnosis to improve patient care and outcome