A Combined Cyto- and Histopathological Diagnostic Approach Reduces Time to Diagnosis and Time to Therapy in First Manifestation of Metastatic Spinal Disease: A Cohort Study.

Malignant spinal lesions (MSLs) are frequently the first manifestation of malignant disease. Spinal care, diagnostic evaluation, and the initiation of systemic therapy are crucial for outcomes in patients (pts) with advanced cancer. However, histopathology (HP) may be time consuming. The additional evaluation of spinal lesions using cytopathology (CP) has the potential to reduce the time to diagnosis (TTD) and time to therapy (TTT). CP and HP specimens from spinal lesions were evaluated in parallel in 61 pts (CP/HP group). Furthermore, 139 pts in whom only HP was performed were analyzed (HP group). We analyzed the TTD of CP and HP within the CP/HP group. Furthermore, we compared the TTD and TTT between the groups. The mean TTD in CP was 1.7 ± 1.7 days (d) and 8.4 ± 3.6 d in HP (p < 0.001). In 13 pts in the CP/HP group (24.1%), specific therapy was initiated based on the CP findings in combination with imaging and biomarker results before completion of HP. The mean TTT in the CP/HP group was 21.0 ± 15.8 d and was significantly shorter compared to the HP group (28.6 ± 23.3 d) (p = 0.034). Concurrent CP for MSLs significantly reduces the TTD and TTT. As a result, incorporating concurrent CP for analyzing spinal lesions suspected of malignancy might have the potential to enhance pts' quality of life and prognosis in advanced cancer. Therefore, we recommend implementing CP as a standard procedure for the evaluation of MSLs.

Temporal Trends of Improvement After Minimally Invasive Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: To analyze temporal trends in improvement after minimally invasive transforaminal lumbar interbody fusion (MIS TLIF). SUMMARY OF BACKGROUND DATA: Although several studies have shown that patients improve significantly after MIS TLIF, evidence regarding the temporal trends in improvement is still largely lacking. METHODS: Patients who underwent primary single-level MIS TLIF for degenerative conditions of the lumbar spine and had a minimum of 2-year follow-up were included. Outcome measures were: 1) patient reported outcome measures (PROMs) (Oswestry Disability Index, ODI; Visual Analog Scale, VAS back and leg; 12-Item Short Form Survey Physical Component Score, SF-12 PCS); 2) global rating change (GRC); 3) minimal clinically important difference (MCID); and 4) return to activities. Timepoints analyzed were preoperative, 2 weeks, 6 weeks, 3 months, 6 months, 1 year, and 2 years. Trends across these timepoints were plotted on graphs. RESULTS: 236 patients were included. VAS back and VAS leg were found to have statistically significant improvement compared to the previous timepoint up to 3 months after surgery. ODI and SF-12 PCS were found to have statistically significant improvement compared to the previous timepoint up to 6 months after surgery. Beyond these timepoints, there was no significant improvement in PROMs. 80% of patients reported feeling better compared to preoperative by 3 months. >50% of patients achieved MCID in all PROMs by 3 months. Most patients returned to driving, returned to work, and discontinued narcotics at an average of 21, 20, and 10 days, respectively. CONCLUSIONS: Patients are expected to improve up to 6 months after MIS TLIF. Back pain and leg pain improve up to 3 months and disability and physical function improve up to 6 months. Beyond these timepoints, the trends in improvement tend to reach a plateau. 80% of patients feel better compared to preoperative by 3 months after surgery.

Impact of Preoperative Symptom Duration on Patient-Reported Outcomes Following Cervical Disc Replacement for Cervical Radiculopathy.

STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: To determine the impact of preoperative symptom duration on postoperative functional outcomes following cervical disc replacement (CDR) for radiculopathy. SUMMARY OF BACKGROUND DATA: CDR has emerged as a reliable and efficacious treatment option for degenerative cervical spine pathologies. The relationship between preoperative symptom duration and outcomes following CDR is not well established. METHODS: Patients with radiculopathy without myelopathy who underwent primary 1- or 2-level CDRs were included and divided into shorter (<6 mo) and prolonged (≥6 mo) cohorts based on preoperative symptom duration. Patient-reported outcome measures (PROMs) included Neck Disability Index (NDI), Visual Analog Scale (VAS) Neck and Arm. Change in PROM scores and minimal clinically important difference (MCID) rates were calculated. Analyses were conducted on the early (within 3 mo) and late (6 mo-2 y) postoperative periods. RESULTS: A total of 201 patients (43.6±8.7 y, 33.3% female) were included. In both early and late postoperative periods, the shorter preoperative symptom duration cohort experienced significantly greater change from preoperative PROM scores compared to the prolonged symptom duration cohort for NDI, VAS-Neck, and VAS-Arm. The shorter symptom duration cohort achieved MCID in the early postoperative period at a significantly higher rate for NDI (78.9% vs. 54.9%, P=0.001), VAS-Neck (87.0% vs. 56.0%, P<0.001), and VAS-Arm (90.5% vs. 70.7%, P=0.002). Prolonged preoperative symptom duration (≥6 mo) was identified as an independent risk factor for failure to achieve MCID at the latest timepoint for NDI (OR: 2.9, 95% CI: 1.2-6.9, P=0.016), VAS-Neck (OR: 9.8, 95% CI: 3.7-26.0, P<0.001), and VAS-Arm (OR: 7.5, 95% CI: 2.5-22.5, P<0.001). CONCLUSIONS: Our study demonstrates improved patient-reported outcomes for those with shorter preoperative symptom duration undergoing CDR for radiculopathy, suggesting delayed surgical intervention may result in poorer outcomes and greater postoperative disability. LEVEL OF EVIDENCE: III.

Predictors for Failure to Respond to Erector Spinae Plane Block Following Minimally Invasive Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: To identify the risk factors associated with failure to respond to erector spinae plane (ESP) block following minimally invasive transforaminal lumbar interbody fusion (MI-TLIF). SUMMARY OF BACKGROUND DATA: ESP block is an emerging opioid-sparing regional anesthetic that has been shown to reduce immediate postoperative pain and opioid demand following MI-TLIF-however, not all patients who receive ESP blocks perioperatively experience a reduction in immediate postoperative pain. METHODS: This was a retrospective review of consecutive patients undergoing 1-level MI-TLIF who received ESP blocks by a single anesthesiologist perioperatively at a single institution. ESP blocks were administered in the OR following induction. Failure to respond to ESP block was defined as patients with a first numerical rating scale (NRS) score post-surgery of >5.7 (mean immediate postoperative NRS score of control cohort undergoing MI TLIF without ESP block). Multivariable logistic regressions were performed to identify predictors for failure to respond to ESP block. RESULTS: A total of 134 patients were included (mean age 60.6 years, 43.3% females). The median and interquartile range (IQR) first pain score post-surgery was 2.5 (0.0-7.5). Forty-nine (36.6%) of patients failed to respond to ESP block. In the multivariable regression analysis, several independent predictors for failure to respond to ESP block following MI TLIF were identified: female sex (OR 2.33, 95% CI 1.04-5.98, P=0.040), preoperative opioid use (OR 2.75, 95% CI 1.03- 7.30, P=0.043), anxiety requiring medication (OR 3.83, 95% CI 1.27-11.49, P=0.017), and hyperlipidemia (OR 3.15, 95% CI 1.31-7.55, P=0.010). CONCLUSIONS: Our study identified several predictors for failure to respond to ESP block following MI TLIF including female sex, preoperative opioid pain medication use, anxiety, and hyperlipidemia. These findings may help inform the approach to counseling patients on perioperative outcomes and pain expectations following MI-TLIF with ESP block. LEVEL OF EVIDENCE: III.

Outcomes in very elderly ICU patients surgically treated for proximal femur fractures.

Proximal femur fractures (PFF) are a common injury in elderly patients that significantly impact mobility and daily living activities. Mortality rates in this population are also high, making effective treatment essential. Recent advances in intensive and geriatric care have enabled complex surgical interventions that were previously not feasible. However, there is a lack of studies focusing on outcome parameters in very elderly patients (≥ 90 years) who receive intensive care treatment following PFFs. In this retrospective study, we analyzed multi-layered data of 148 patients who were 90 years or older and received intensive care after trauma and orthopedic surgical treatment for PFFs or periprosthetic fractures between 2009 and 2019. All patients received a 365-day follow-up. To identify potential predictors of mortality, all deceased and surviving patients were subjected to multiple logistic regression analyses. We found that 22% of patients deceased during in-hospital care, and one-year survival was 44%. Independent predictors of one-year all-cause mortality included higher CCI and SOFA scores at ICU admission. Overall, 53% of patients who resided in private dwellings prior to admission were able to return home. Our study highlights the utility of using CCI and SOFA scores at ICU admission as prognostic indicators in critically ill very elderly patients who undergo surgical treatment for PFFs. These scores can provide valuable insight into the severity of illness and potential outcomes, which can inform resource allocation, prioritize endangered patients, and aid in end-of-life discussions and planning with patients and their families. Our findings can help improve the management of PFFs in very elderly patients and contribute to optimized patient care.

Neutrophil extracellular traps and DNases orchestrate formation of peritoneal adhesions.

Peritoneal adhesions are poorly understood but highly prevalent conditions that can cause intestinal obstruction and pelvic pain requiring surgery. While there is consensus that stress-induced inflammation triggers peritoneal adhesions, the molecular processes of their formation still remain elusive. We performed murine models and analyzed human samples to monitor the formation of adhesions and the treatment with DNases. Various molecular analyses were used to evaluate the adhesions. The experimental peritoneal adhesions of the murine models and biopsy material from humans are largely based on neutrophil extracellular traps (NETs). Treatment with DNASE1 (Dornase alfa) and the human DNASE1L3 analog (NTR-10), significantly reduced peritoneal adhesions in experimental models. We conclude that NETs serve as essential scaffold for the formation of adhesions; DNases interfere with this process. Herein, we show that therapeutic application of DNases can be employed to prevent the formation of murine peritoneal adhesions. If this can be translated into the human situation requires clinical studies.

Immunofluorescence Imaging of Neutrophil Extracellular Traps in Human and Mouse Tissues.

Neutrophil extracellular traps (NETs) are released by neutrophils as a response to bacterial infection or traumatic tissue damage but also play a role in autoimmune diseases and sterile inflammation. They are web-like structures composed of double-stranded DNA filaments, histones, and antimicrobial proteins. Once released, NETs can trap and kill extracellular pathogens in blood and tissue. Furthermore, NETs participate in homeostatic regulation by stimulating platelet adhesion and coagulation. However, the dysregulated production of NETs has also been associated with various diseases, including sepsis or autoimmune disorders, which makes them a promising target for therapeutic intervention. Apart from electron microscopy, visualizing NETs using immunofluorescence imaging is currently one of the only known methods to demonstrate NET interactions in tissue. Therefore, various staining methods to visualize NETs have been utilized. In the literature, different staining protocols are described, and we identified four key components showing high variability between protocols: (1) the types of antibodies used, (2) the usage of autofluorescence-reducing agents, (3) antigen retrieval methods, and (4) permeabilization. Therefore, in vitro immunofluorescence staining protocols were systemically adapted and improved in this work to make them applicable for different species (mouse, human) and tissues (skin, intestine, lung, liver, heart, spinal disc). After fixation and paraffin-embedding, 3 µm thick sections were mounted onto slides. These samples were stained with primary antibodies for myeloperoxidase (MPO), citrullinated histone H3 (H3cit), and neutrophil elastase (NE) according to a modified staining protocol. The slides were stained with secondary antibodies and examined using a widefield fluorescence microscope. The results were analyzed according to an evaluation sheet, and differences were recorded semi-quantitatively. Here, we present an optimized NET staining protocol suitable for different tissues. We used a novel primary antibody to stain for H3cit and reduced non-specific staining with an autofluorescence-reducing agent. Furthermore, we demonstrated that NET staining requires a constant high temperature and careful handling of samples.

[Perioperative management after traumatic paraplegia : Avoiding complications]. / Perioperatives Management nach traumatischer Querschnittslähmung : Komplikationen vermeiden.

This article describes the current status of modern treatment options for traumatic spinal cord injuries with a particular focus on the perioperative phase. Along with a recognition of age-related specific features that can impact successful treatment of spinal injuries, prompt interdisciplinary treatment while adhering to the "time is spine" principle is of high importance. By considering this approach and using modern diagnostic and surgical techniques, successful surgical treatment can be achieved while taking into account individual characteristics, such as reduced bone quality, accompanying injuries as well as oncological and inflammatory rheumatic comorbidities. The preventive and treatment strategies for frequently occurring complications in the management of traumatic spinal cord injuries are presented. By considering case-specific factors, utilizing modern surgical techniques, avoiding or promptly treating typical complications and initiating interdisciplinary treatment, crucial groundwork for a successful long-term treatment of this highly debilitating and life-altering injury can be established in the perioperative phase.

Analysis of Three-Dimensional Bone Microarchitecture of the Axis Exposes Pronounced Regional Heterogeneity Associated with Clinical Fracture Patterns.

The odontoid process (dens) of the second cervical vertebra (axis) is prone to fracture. While the importance of its skeletal integrity has been previously noted, representative three-dimensional microarchitecture analyses in humans are not available. This study aimed to determine the bone microarchitecture of the axis using high-resolution quantitative computed tomography (HR-pQCT) and to derive clinical implications for the occurrence and treatment of axis fractures. For initial clinical reference, the apparent density of the axis was determined based on clinical computed tomography (CT) images in patients without and with fractures of the axis. Subsequently, 28 human axes (female 50%) obtained at autopsy were analyzed by HR-pQCT. Analyses were performed in three different regions corresponding to zones I (tip of dens), II (base of dens), and III (corpus axis) of the Anderson and D'Alonzo classification. Lower apparent densities based on clinical CT data were detected in zone II and III compared to zone I in both the group without and with fracture. In the autopsy specimens, cortical thickness and bone volume fraction decreased continuously from zone I to zone III. Trabecular and cortical tissue mineral density was lowest in zone III, with no differences between zones I and II. In conclusion, our clinical and high-resolution ex vivo imaging data highlight a marked regional heterogeneity of bone microarchitecture, with poor cortical and trabecular properties near the dens base. These results may partly explain why zones II and III are at high risk of fracture and osteosynthesis failure.

Moonlighting chromatin: when DNA escapes nuclear control.

Extracellular chromatin, for example in the form of neutrophil extracellular traps (NETs), is an important element that propels the pathological progression of a plethora of diseases. DNA drives the interferon system, serves as autoantigen, and forms the extracellular scaffold for proteins of the innate immune system. An insufficient clearance of extruded chromatin after the release of DNA from the nucleus into the extracellular milieu can perform a secret task of moonlighting in immune-inflammatory and occlusive disorders. Here, we discuss (I) the cellular events involved in the extracellular release of chromatin and NET formation, (II) the devastating consequence of a dysregulated NET formation, and (III) the imbalance between NET formation and clearance. We include the role of NET formation in the occlusion of vessels and ducts, in lung disease, in autoimmune diseases, in chronic oral disorders, in cancer, in the formation of adhesions, and in traumatic spinal cord injury. To develop effective therapies, it is of utmost importance to target pathways that cause decondensation of chromatin during exaggerated NET formation and aggregation. Alternatively, therapies that support the clearance of extracellular chromatin are conceivable.

The limitations of fully threaded screws in isolated percutaneous transarticular screw fixation of C1/C2.

Demographic aging accompanied by increased falls inevitably leads to an increased incidence of atlantoaxial instabilities (AAI). Minimally invasive surgical procedures decrease the perioperative risk and regarding the treatment of AAI, percutaneous transarticular screw fixation of C1/C2 was more frequently considered in the past. This study aims to investigate the outcome of patients treated for AAI by isolated percutaneous transarticular screw fixation of C1/C2 (IPTSFC1/C2) using 3.5 mm fully threaded screws to identify its chances and limitations. In this retrospective study, data from patients who underwent IPTSFC1/C2 were analyzed. 23 patients (17 females and 6 males) with an average age of 73.1 years (y) were included. Mean VAS decreased significantly from preoperative 3.9 ± 1.8 to the last follow-up 2.6 ± 2.5 (p = 0.020) and neurological functions were preserved. In the radiological follow-up, we saw a single malposition of an inserted screw (2.27%) and one single bony fusion (4.54%). However, in 6 of 7 patients (85.71%), there was a loosening of the inserted screws due course. We demonstrated that the use of 3.5 mm fully threaded screws for IPTSFC1/C2 results in low rates of osseous fusions between C1 and C2. Therefore, their use in IPTSFC1/C2 is not suitable, especially for geriatric patients with impaired bone status.

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.

Outcome after Posterior Vertebral Column Resection in Patients with Severe Osteoporotic Fractures-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 2012-2020 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 ± 10.2 y. The mean VAS decreased significantly from 7.7 ± 2.8 preoperatively to 3.0 ± 1.6 at last follow-up (p < 0.001) and the segmental kyphosis decreased from 29.4 ± 14.1° to 7.9 ± 8.0° (p < 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 >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' segmental kyphosis and VAS improved significantly, while the KPS remained stable.

Surgical Site Cytology to Diagnose Spinal Lesions.

Patients with new-onset malignant spinal lesions often have an urgent need for local spine intervention and systemic therapy. For optimal management, it is crucial to diagnose the underlying disease as quickly and reliably as possible. The aim of our current study was to determine the feasibility, sensitivity, specificity, and diagnostic certainty of complementary cytological evaluation of spinal lesions suspected of malignancy. In 44 patients, we performed histopathological biopsies and in parallel cytologic preparations from the malignant site. Cytological smears were prepared and stained for May-Grunwald and Giemsa. Bone biopsies were histopathologically analyzed according to the existing standard-of-care practices. In 42 of 44 cases (95%), a cytological sample was successfully obtained. In 40 cases (95.2%, Cohen's kappa: 0.77), the cytological diagnosis agreed with the histological diagnosis regarding the identification of a malignant lesion. This resulted in a sensitivity of 97% and a specificity of 80% as well as a diagnostic safety of 95%. Cytological analysis in the context of spinal surgery proved sufficient to establish a diagnosis of malignancy or its exclusion, expanding the existing diagnostic spectrum. Furthermore, implementation of this process as a routine clinical diagnostic might shorten the time to diagnosis and improve the treatment of this vulnerable patient group.

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 < 0.05 and chronic heart failure n = 11/36 vs. S n = 41/292, p < 0.05, chronic renal failure SIE n = 14/36 vs. S n = 55/292, p < 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 < 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.

Posterior vertebral column resection as a safe procedure leading to solid bone fusion in metastatic epidural spinal cord compression.

OBJECTIVE: Cancer is one of the leading causes of death and greatly decreases a patient's quality of life. Vertebral metastases often lead to epidural spinal cord compression (ESCC) requiring surgical therapy. It has previously been shown that in patients with metastatic ESCC (MESCC), a surgical intervention leads to an improved outcome. Although the treatment paradigms in spinal metastases have changed and separation surgery followed by stereotactic radiosurgery is considered the best strategy, there are still cases in which 360° decompression with stabilization is indicated. In these patients, a proper bone fusion should be the treatment goal to guarantee good clinical results in extended survival times through progressions in oncological therapies. The aim of this study was to examine the safety and feasibility of posterior vertebral column resection (pVCR) in everyday clinical practice, achievement of bone fusion, and midterm outcome in patients with MESCC. METHODS: All patients treated with pVCR due to MESCC between 2013 and 2020 were enrolled in this observational single-center study. Demographics, outcome parameters, numeric rating scale (NRS) score, Frankel grade, and Karnofsky Performance Scale (KPS) score were evaluated. Radiological images routinely acquired during follow-up were reviewed and screened for the presence of bone fusion. RESULTS: Sixty-six patients were treated by eight surgeons. The mean follow-up period was 549 ± 739 days. At baseline, the average age was 64.4 ± 10.9 years. Reported NRS scores (preoperative 6.2 ± 1.7 vs postoperative 3.4 ± 1.6) and segmental kyphosis as measured on sagittal CT images (preoperative 13.5° ± 8.6° vs postoperative 3.8° ± 5.4°) decreased significantly (p < 0.001). In only 2 patients (3%), the Frankel grade worsened postoperatively, whereas in 12 patients (18.2%) an improvement was documented. The KPS score remained constant during the observation period (preoperative 73.2% ± 18.2% vs 78.3% ± 18% at last follow-up). Bone fusion was observed in 26 patients (86.7%) receiving CT more than 100 days after the index surgery. CONCLUSIONS: pVCR is a reliable surgical technique in daily clinical practice, which proves to be beneficial in terms of short- as well as midterm outcome, as judged by the KPS and NRS. The overall improvement in the Frankel grade shows patient safety. A bone fusion was observed regularly in oncological patients undergoing pVCR. The authors therefore conclude that pVCR is a safe, fast, and efficient strategy to achieve stability and pain relief by achievement of bone fusion in cancer patients.

Therapeutic Targeting of Neutrophil Extracellular Traps Improves Primary and Secondary Intention Wound Healing in Mice.

Background: Neutrophils are the first responders in wound healing after injury that mediate pro- and anti-inflammatory activities i.a. through the formation of extracellular traps (NETs). However, excessive NETs presence in wound tissue can cause local hyperinflammation and -coagulation resulting in delayed wound healing. To improve wound healing, we aimed to examine the role of NETs and DNase1 on primary and secondary wound healing. Methods: The study included 93 C57BL/6 mice, with 3 different genotypes: wildtype, Pad4-, and DNase1-Knockout (KO). Pad4-KO mice show limited NETs formation, while DNase1-KO mice cannot disintegrate them. All 3 genotypes were included in (1) a laparotomy group and (2) a thermal injury group. Animals in both groups either received DNase1 or a vehicle i.p. post wound induction and wound assessment and euthanasia were conducted. Laparotomy and burn scars were assessed using the stony brook scar evaluation scale and modified Yeong scale respectively. Tissue was analyzed histologically using H&E staining. Ly6g, Collagen I and III, SMA, and Fibrinogen were visualized and neutrophils activation (NE, MPO) and NETs (H3cit) formation assessed. Results: All animals survived with no complications. DNase1 treatment led to a significantly improved scar appearance in both groups, which was also seen in Pad4-KO mice. In the laparotomy group DNase1 improved collagen deposition and fibrin concentration was significantly reduced by DNase1 treatment. Markers of neutrophil activation were significantly reduced in the treatment and Pad4-KO group. In the thermal injury group wound closure time was significantly reduced after DNase1 treatment and in the Pad4-KO group. Even though inflammation remained high in the thermal injury model over time, neutrophil activation and NETs formation were significantly reduced by DNase1 treatment compared to controls. Discussion: Primary and secondary intention wound healing is improved by targeting NETs through DNase1 treatment or genetic KO, as assessed by wound closure time and scar appearances. Additionally, wound stability was not affected by DNASE treatment. The results suggest that overall wound healing is accelerated and DNase1 appears to be a promising option to reduce scar formation; which should be evaluated in humans.