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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 ...

University Medical Center Hamburg-Eppendorf (UKE)

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.

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

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

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.

Moonlighting chromatin: when DNA escapes nuclear control.

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.

Annika Heuer

Division of Spine Surgery,
Department of Trauma and Orthopedic Surgery,
Division of Spine Surgery, Department of Trauma and Orthopedic Surgery

University Medical Center Hamburg-Eppendorf (UKE)

Immunofluorescence Imaging of Neutrophil Extracellular Traps in Human and Mouse Tissues

Annika Heuer

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Division of Spine Surgery,Department of Trauma and Orthopedic Surgery,Division of Spine Surgery, Department of Trauma and Orthopedic Surgery

University Medical Center Hamburg-Eppendorf (UKE)

Immunofluorescence Imaging of Neutrophil Extracellular Traps in Human and Mouse Tissues

Division of Spine Surgery,
Department of Trauma and Orthopedic Surgery,
Division of Spine Surgery, Department of Trauma and Orthopedic Surgery