Thermographic assessment of skin temperature after lumbar spine surgery: Useful method for detection of wound complications? A pilot study.

BACKGROUND: Wound complications after lumbar spine surgery may result in prolonged hospitalization and increased morbidity. Early identification can trigger appropriate management. OBJECTIVE: The aim of this study was to investigate the efficacy of infrared-based wound assessment (FLIR) after lumbar spine surgery in the context of identifying wound healing disorders. METHODS: 62 individuals who underwent lumbar spine surgery were included. The immediate postoperative course was studied, and the patient's sex, age, body mass index (BMI), heart rate, blood pressure, body temperature, numeric rating scale for pain (NRS), C-reactive protein (CRP), leukocyte, and hemoglobin levels were noted and compared to thermographic measurement of local surface temperature in the wound area. RESULTS: Measurement of local surface temperature in the wound area showed a consistent temperature distribution while it was uneven in case of wound healing disorder. In this instance, the region of the wound where the wound healing disorder occured had a lower temperature than the surrounding tissue (p> 0.05). CONCLUSIONS: This study demonstrates the ongoing importance of clinical wound assessment for early detection of complications. While laboratory parameter measurement is crucial, FLIR may serve as a cost-effective supplemental tool in clinical wound evaluation. Patient safety risks appear minimal since local ST is measured without touch.

Preoperative Performance Status Threshold for Favorable Surgical Outcome in Metastatic Spine Disease.

BACKGROUND AND OBJECTIVES: Surgical treatment is an integral component of multimodality management of metastatic spine disease but must be balanced against the risk of surgery-related morbidity and mortality, making tailored surgical counseling a clinical challenge. The aim of this study was to investigate the potential predictive value of the preoperative performance status for surgical outcome in patients with spinal metastases. METHODS: Performance status was determined using the Karnofsky Performance Scale (KPS), and surgical outcome was classified as "favorable" or "unfavorable" based on postoperative changes in neurological function and perioperative complications. The correlation between preoperative performance status and surgical outcome was assessed to determine a KPS-related performance threshold. RESULTS: A total of 463 patients were included. The mean age was 63 years (range: 22-87), and the mean preoperative KPS was 70 (range: 30-100). Analysis of clinical outcome in relation to the preoperative performance status revealed a KPS threshold between 40% and 50% with a relative risk of an unfavorable outcome of 65.7% in KPS ≤40% compared with the relative chance for a favorable outcome of 77.1% in KPS ≥50%. Accordingly, we found significantly higher rates of preserved or restored ambulatory function in KPS ≥50% (85.7%) than in KPS ≤40% (48.6%; P < .001) as opposed to a significantly higher risk of perioperative mortality in KPS ≤40% (11.4%) than in KPS ≥50% (2.1%, P = .012). CONCLUSION: Our results underline the predictive value of the KPS in metastatic spine patients for counseling and decision-making. The study suggests an overall clinical benefit of surgical treatment of spinal metastases in patients with a preoperative KPS score ≥50%, while a high risk of unfavorable outcome outweighing the potential clinical benefit from surgery is encountered in patients with a KPS score ≤40%.

The projected increase of vertebral osteomyelitis in Germany implies a demanding challenge for future healthcare management of aging populations.

PURPOSE: Since an increase in the occurrence of native vertebral osteomyelitis (VO) is expected and reliable projections are missing, it is urgent to provide a reliable forecast model and make it a part of future health care considerations. METHODS: Comprehensive nationwide data provided by the Federal Statistical Office of Germany were used to forecast total numbers and incidence rates (IR) of VO as a function of age and gender until 2040. Projections were done using autoregressive integrated moving average model on historical data from 2005 to 2019 in relation to official population projections from 2020 to 2040. RESULTS: The IR of VO is expected to increase from 12.4 in 2019 to 21.5 per 100,000 inhabitants [95% CI 20.9-22.1] in 2040. The highest increase is predicted in patients over 75 years of age for both men and women leading to a steep increase in absolute numbers, which is fourfold higher compared to patients younger than 75 years. While the IR per age group will not increase any further after 2035, the subsequent increase is due to a higher number of individuals aged 75 years or older. CONCLUSIONS: Our data suggest that increasing IR of VO will seriously challenge healthcare systems, particularly due to demographic change and increasing proportions of populations turning 75 years and older. With respect to globally fast aging populations, future health care policies need to address this burden by anticipating limitations in financial and human resources and developing high-level evidence-based guidelines for prevention and interdisciplinary treatment.

Regional Microglial Response in Entorhino-Hippocampal Slice Cultures to Schaffer Collateral Lesion and Metalloproteinases Modulation.

Microglia and astrocytes are essential in sustaining physiological networks in the central nervous system, with their ability to remodel the extracellular matrix, being pivotal for synapse plasticity. Recent findings have challenged the traditional view of homogenous glial populations in the brain, uncovering morphological, functional, and molecular heterogeneity among glial cells. This diversity has significant implications for both physiological and pathological brain states. In the present study, we mechanically induced a Schaffer collateral lesion (SCL) in mouse entorhino-hippocampal slice cultures to investigate glial behavior, i.e., microglia and astrocytes, under metalloproteinases (MMPs) modulation in the lesioned area, CA3, and the denervated region, CA1. We observed distinct response patterns in the microglia and astrocytes 3 days after the lesion. Notably, GFAP-expressing astrocytes showed no immediate changes post-SCL. Microglia responses varied depending on their anatomical location, underscoring the complexity of the hippocampal neuroglial network post-injury. The MMPs inhibitor GM6001 did not affect microglial reactions in CA3, while increasing the number of Iba1-expressing cells in CA1, leading to a withdrawal of their primary branches. These findings highlight the importance of understanding glial regionalization following neural injury and MMPs modulation and pave the way for further research into glia-targeted therapeutic strategies for neurodegenerative disorders.

Synaptopodin Regulates Denervation-Induced Plasticity at Hippocampal Mossy Fiber Synapses.

Neurological diseases can lead to the denervation of brain regions caused by demyelination, traumatic injury or cell death. The molecular and structural mechanisms underlying lesion-induced reorganization of denervated brain regions, however, are a matter of ongoing investigation. In order to address this issue, we performed an entorhinal cortex lesion (ECL) in mouse organotypic entorhino-hippocampal tissue cultures of both sexes and studied denervation-induced plasticity of mossy fiber synapses, which connect dentate granule cells (dGCs) with CA3 pyramidal cells (CA3-PCs) and play important roles in learning and memory formation. Partial denervation caused a strengthening of excitatory neurotransmission in dGCs, CA3-PCs and their direct synaptic connections, as revealed by paired recordings (dGC-to-CA3-PC). These functional changes were accompanied by ultrastructural reorganization of mossy fiber synapses, which regularly contain the plasticity-regulating protein synaptopodin and the spine apparatus organelle. We demonstrate that the spine apparatus organelle and synaptopodin are related to ribosomes in close proximity to synaptic sites and reveal a synaptopodin-related transcriptome. Notably, synaptopodin-deficient tissue preparations that lack the spine apparatus organelle failed to express lesion-induced synaptic adjustments. Hence, synaptopodin and the spine apparatus organelle play a crucial role in regulating lesion-induced synaptic plasticity at hippocampal mossy fiber synapses.

Increased stability due to symmetric cement volume in augmented pedicle screws? A biomechanical study.

Pedicle screw instrumentation has become "state of the art" in surgical treatment of many spinal disorders. Loosening of pedicle screws due to poor bone mineral density is a frequent complication in osteoporotic patients. As prevalence of osteoporosis and spinal disorders are increasing with an aging demographic, optimizing the biomechanical properties of pedicle screw constructions and therefore outcome after spinal surgery in osteoporotic patients is a key factor in future surgical therapy. Therefore, this biomechanical study investigated the stability of polymethylmethacrylate (PMMA)-augmented pedicle screw-rod constructions under a deviating distribution of PMMA applied to the instrumentation in osteoporotic human cadaveric vertebrae. We showed that PMMA-augmented pedicle screw-rod constructions tend to be more stable than those with non-augmented pedicle screws. Further, there appears to be a larger risk of screw loosening in unilateral augmented pedicle screws than in non-augmented, therefore a highly asymmetrically distributed PMMA should be avoided.

A correction factor is needed for the intraoperative measurement of cup inclination in total hip arthroplasty.

BACKGROUND: The cup inclination in total hip arthroplasty is key to minimising complications. Stereometric effects (parallax) in two-dimensional projections can alter angle measurements. Even for different approaches, fluoroscopy causes different results in the measurement of inclination. A previous study has introduced a corrective factor for intraoperative radiographic cup inclination measurements compared to the postoperative standing radiographs. OBJECTIVE: The aim of this study was to find out whether, first, the correction factor is reproducible and second, whether the correction factor is independent of the surgical approach and C-arm model used. METHODS: A series of 377 cases of primary total hip arthroplasty was reviewed. We compared the cup inclination angle in the intraoperative and postoperative radiographic images. Based on this, it was possible to specify a standard of correction factor in defined ranges. RESULTS: The mean cup inclination in intraoperative images was 37.47∘ and the mean angle in postoperative images was 41.42, resulting in a mean difference of 3.95∘ with a strong correlation (r= 0.706). CONCLUSION: An added correction factor of 4∘ should be respected in intraoperative inclination measurements to adapt for parallax. An increased correction factor of 6∘ in particularly low-positioned cups (< 31∘) and a decreased correction factor of 2∘ in particularly steeply positioned cups (> 43∘) is recommended.

Brain stimulation-on-a-chip: a neuromodulation platform for brain slices.

Electrical stimulation of ex vivo brain tissue slices has been a method used to understand mechanisms imparted by transcranial direct current stimulation (tDCS), but there are significant direct current electric field (dcEF) dosage and electrochemical by-product concerns in conventional experimental setups that may impact translational findings. Therefore, we developed an on-chip platform with fluidic, electrochemical, and magnetically-induced spatial control. Fluidically, the chamber geometrically confines precise dcEF delivery to the enclosed brain slice and allows for tissue recovery in order to monitor post-stimulation effects. Electrochemically, conducting hydrogel electrodes mitigate stimulation-induced faradaic reactions typical of commonly-used metal electrodes. Magnetically, we applied ferromagnetic substrates beneath the tissue and used an external permanent magnet to enable in situ rotational control in relation to the dcEF. By combining the microfluidic chamber with live-cell calcium imaging and electrophysiological recordings, we showcased the potential to study the acute and lasting effects of dcEFs with the potential of providing multi-session stimulation. This on-chip bioelectronic platform presents a modernized yet simple solution to electrically stimulate explanted tissue by offering more environmental control to users, which unlocks new opportunities to conduct thorough brain stimulation mechanistic investigations.

Local Recurrence and Development of Spinal Cord Syndrome during Follow-Up after Surgical Treatment of Metastatic Spine Disease.

BACKGROUND: Surgical decompression (SD), with or without posterior stabilization followed by radiotherapy, is an established treatment for patients with metastatic spinal disease with epidural spinal cord compression (ESCC). This study aims to identify risk factors for occurrence of neurological compromise resulting from local recurrence. METHODS: All patients who received surgical treatment for metastatic spinal disease at our center between 2011 and 2022 were included in this study. Cases were evaluated for tumor entity, surgical technique for decompression (decompression, hemilaminectomy, laminectomy, corpectomy) neurological deficits, grade of ESCC, time interval to radiotherapy, and perioperative complications. RESULTS: A total of 747 patients were included in the final analysis, with a follow-up of 296.8 days (95% CI (263.5, 330.1)). During the follow-up period, 7.5% of the patients developed spinal cord/cauda syndrome (SCS). Multivariate analysis revealed prolonged time (>35 d) to radiation therapy as a solitary risk factor (p < 0.001) for occurrence of SCS during follow-up. CONCLUSION: Surgical treatment of spinal metastatic disease improves patients' quality of life and Frankel grade, but radiation therapy needs to be scheduled within a time frame of a few weeks in order to reduce the risk of tumor-induced neurological compromise.

Dense dopaminergic innervation of the peri-infarct cortex despite dopaminergic cell loss after a pure motor-cortical stroke in rats.

After ischemic stroke, the cortex directly adjacent to the ischemic core (i.e., the peri-infarct cortex, PIC) undergoes plastic changes that facilitate motor recovery. Dopaminergic signaling is thought to support this process. However, ischemic stroke also leads to the remote degeneration of dopaminergic midbrain neurons, possibly interfering with this beneficial effect. In this study, we assessed the reorganization of dopaminergic innervation of the PIC in a rat model of focal cortical stroke. Adult Sprague-Dawley rats either received a photothrombotic stroke (PTS) in the primary motor cortex (M1) or a sham operation. 30 days after PTS or sham procedure, the retrograde tracer Micro Ruby (MR) was injected into the PIC of stroke animals or into homotopic cortical areas of matched sham rats. Thus, dopaminergic midbrain neurons projecting into the PIC were identified based on MR signal and immunoreactivity against tyrosine hydroxylase (TH), a marker for dopaminergic neurons. The density of dopaminergic innervation within the PIC was assessed by quantification of dopaminergic boutons indicated by TH-immunoreactivity. Regarding postsynaptic processes, expression of dopamine receptors (D1- and D2) and a marker of the functional signal cascade (DARPP-32) were visualized histologically. Despite a 25% ipsilesional loss of dopaminergic midbrain neurons after PTS, the number and spatial distribution of dopaminergic neurons projecting to the PIC was not different compared to sham controls. Moreover, the density of dopaminergic innervation in the PIC was significantly higher than in homotopic cortical areas of the sham group. Within the PIC, D1-receptors were expressed in neurons, whereas D2-receptors were confined to astrocytes. The intensity of D1- and DARPP-32 expression appeared to be higher in the PIC compared to the contralesional homotopic cortex. Our data suggest a sprouting of dopaminergic fibers into the PIC and point to a role for dopaminergic signaling in reparative mechanisms post-stroke, potentially related to recovery.

Patient-related risk factors and lifestyle factors for lumbar degenerative disc disease: a systematic review.

OBJECTIVE: Back pain is a very widespread disease pattern and is one of the most frequent causes for consultation of a physician in general. In most cases, discogenic changes are the pathomorphological correlate of back pain. Numerous risk factors have been identified for these degenerative changes, but the influence and significance of the risk factors remain unclear, which was the aim of this systematic review. METHODS: A systematic literature search of the commonly used Pubmed database was performed using specific MESH terms. Further selection of the included studies was performed according to the PRISMA scheme, taking into account scientific merit as well as the relation to the research question. RESULTS: A total of 111 studies out of 1035 found were finally included in the literature search. 134 risk factors for disc degeneration and disc herniation were identified. These were divided into (1) patient-specific risk factors (n░=░34), (2) radiological risk factors (n░=░31), (3) lifestyle risk factors (n░=░6), (4) workplace-related risk factors (n░=░12), (5) genetic risk factors (n░=░50), and (6) other risk factors (n░=░1). Non-adjustable risk factors were age >50 years (OR 1.7/year), female gender (OR 1.41), family disposition (OR 4.0), comorbidities like atherosclerosis (OR 2.24), arthritic changes in other joints (OR 3.1) and history of injuries of the back (OR 3.1). Adjustable factors were elevated BMI (OR 2.77), comorbidities like hypertension (OR 1.25), dyslipidemia (OR 1.26) and diabetes mellitus (OR 6.8), as well as lifestyle habits like smoking (OR 3.8). DISCUSSION: In summary, intervertebral disc degenerations and herniations represent multifactorial events whose risk factors can be partly influenced and partly not influenced. This systematic review highlights the current state of knowledge as a basis for creating patient-specific algorithms to calculate risk for the development or progression of degenerative disc changes and disc herniations.

Severity of spinal degeneration does not affect the pain reduction under continuous epidural analgesia.

PURPOSE: To outline clinical effectiveness of continuous epidural analgesia (CEA) in patients with failed back surgery syndrome (FBSS) or lumbar spinal stenosis (LSS) depending on severity of spinal degeneration. METHODS: In this retrospective cohort study, all patients with FBSS or LSS who underwent CEA within an inpatient rehabilitation program were evaluated. The pain reduction was measured by VAS on an hourly basis. Substantial pain reduction was defined as a minimal clinically important difference (MCID) > 50%. Severity of spinal degeneration, side effects and patient-specific characteristics were documented. RESULT: We included a total of 148 patients with 105 patients suffering from FBSS and 48 with LSS. The average pain reduction was - 37.6 ± 19.2 in FBSS and - 38.1 ± 17.8 in LSS group (p < .001 and p < .001, respectively). In the FBSS group, sensory deficits (p = .047) and numbness (p = .002), and in the LSS group, a severe disability measured by ODI (38.2 ± 15.4 vs. 57.3 ± 11.3, p < .001) significantly contributed to a worse outcome. The severity of the spinal degeneration and psychological disorders did not affect the pain reduction in terms of MCID. CONCLUSIONS: This study provides new evidence about CEA in the treatment of FBSS and LSS. CEA provides a significant pain reduction even under intensified physiotherapeutic exercising in patients with severe spinal degeneration and a broad variety of secondary diagnoses. Neurologic deficits in case of FBSS and severe disability in case of LSS may be risk factors for less favorable outcome.

Digital droplet PCR-based quantification of ccfHPV-DNA as liquid biopsy in HPV-driven cervical and vulvar cancer.

PURPOSE: More than 99% of cervical cancers and up to 40% of vulvar cancers are human papillomavirus (HPV) related. HPV 16 and 18 are the most relevant subtypes. Novel technologies allow the detection of minimal amounts of circulating cell-free HPV DNA (ccfHPV-DNA). The aim of this study was to evaluate ccfHPV-DNA assessed by droplet digital PCR (ddPCR) as a biomarker for molecular therapy monitoring in early, advanced, relapsed and metastatic HPV-driven cervical and vulvar cancer. METHODS: Inclusion criteria of the study were histologically proven HPV 16/18-driven cervical and vulvar cancer with first diagnosed disease, newly diagnosed recurrence, or progression of disease. Blood samples were taken pre- and post-therapeutically. Circulating cell-free HPV DNA was quantified using ddPCR and the results were correlated with clinical data. RESULTS: The mean copy number of ccfHPV-DNA was 838.6 (± 3089.1) in pretreatment and 2.3 (± 6.4) in post-treatment samples (p < 0.05). The copy number of ccfHPV-DNA increased with higher FIGO stages (p < 0.05), which are commonly used for clinical staging/assessment. Furthermore, we compared the distribution of copy numbers between T-stage 1 versus T-stage 2/3. We could show higher copy number level of ccfHPV-DNA in T-stage 2/3 (p < 0.05). CONCLUSIONS: Therapy monitoring with determination of ccfHPV-DNA by ddPCR with a small amount of plasma reflects response to therapy and appears feasible for patients in advanced cancer stages of cervical and vulvar cancer. This promising tool should be examined as marker of therapy monitoring in particular in novel HPV-directed therapies.

Effects of the Light/Dark Phase and Constant Light on Spatial Working Memory and Spine Plasticity in the Mouse Hippocampus.

Circadian rhythms in behavior and physiology such as rest/activity and hormones are driven by an internal clock and persist in the absence of rhythmic environmental cues. However, the period and phase of the internal clock are entrained by the environmental light/dark cycle. Consequently, aberrant lighting conditions, which are increasing in modern society, have a strong impact on rhythmic body and brain functions. Mice were exposed to three different lighting conditions, 12 h light/12 h dark cycle (LD), constant darkness (DD), and constant light (LL), to study the effects of the light/dark cycle and aberrant lighting on the hippocampus, a critical structure for temporal and spatial memory formation and navigation. Locomotor activity and plasma corticosterone levels were analyzed as readouts for circadian rhythms. Spatial working memory via Y-maze, spine morphology of Golgi-Cox-stained hippocampi, and plasticity of excitatory synapses, measured by number and size of synaptopodin and GluR1-immunreactive clusters, were analyzed. Our results indicate that the light/dark cycle drives diurnal differences in synaptic plasticity in hippocampus. Moreover, spatial working memory, spine density, and size and number of synaptopodin and GluR1 clusters were reduced in LL, while corticosterone levels were increased. This indicates that acute constant light affects hippocampal function and synaptic plasticity.

Postoperative Surgical Site Infections in Spine Surgery: Can the Duration of Surgery Predict the Pathogen Spectrum?

BACKGROUND/AIM: Surgical site infection (SSI) is a severe complication of spinal surgery, which typically results in prolonged length of hospital stay, an increased number of revision surgeries, re-hospitalizations, worse clinical functional outcomes, and increased healthcare costs. The aim of the present study was to analyse if the duration of surgery can predict the spectrum of pathogens causing SSI in orthopaedic spine surgery. PATIENTS AND METHODS: We conducted a retrospective study over a period of two years at the University Hospital of Cologne in which all patients with postoperative surgical site infections were included. In addition to descriptive characteristics (such as sex, age, BMI), the duration of the surgery, the administration of intra-operative antibiotics, the main diagnosis, the postoperative course of the infection parameters (CRP & WBC) and the responsible pathogens were analysed. RESULTS: A total of 75 patients were included with a median age of 64 years. The mean time of operation time was 131.52±70.91 min (range=23-285 min). The most frequently isolated germs in the postoperative blood culture were S. aureus (n=7), S. haemolyticus and S. hominis (n=2). There was a significant correlation between the duration of the primary surgical intervention and the postoperatively detected pathogens (p=0.002). CONCLUSION: A significant correlation was shown between the duration of surgery and the species of pathogens detected causing postoperative SSI. The use of perioperative antibiotics, the use of longer-lasting antibiotics or the repeated intravenous administration of prophylactic antibiotics should be evaluated.

The Amyloid Precursor Protein Regulates Synaptic Transmission at Medial Perforant Path Synapses.

The perforant path provides the primary cortical excitatory input to the hippocampus. Because of its important role in information processing and coding, entorhinal projections to the dentate gyrus have been studied in considerable detail. Nevertheless, synaptic transmission between individual connected pairs of entorhinal stellate cells and dentate granule cells remains to be characterized. Here, we have used mouse organotypic entorhino-hippocampal tissue cultures of either sex, in which the entorhinal cortex (EC) to dentate granule cell (GC; EC-GC) projection is present, and EC-GC pairs can be studied using whole-cell patch-clamp recordings. By using cultures of wild-type mice, the properties of EC-GC synapses formed by afferents from the lateral and medial entorhinal cortex were compared, and differences in short-term plasticity were identified. As the perforant path is severely affected in Alzheimer's disease, we used tissue cultures of amyloid precursor protein (APP)-deficient mice to examine the role of APP at this synapse. APP deficiency altered excitatory neurotransmission at medial perforant path synapses, which was accompanied by transcriptomic and ultrastructural changes. Moreover, presynaptic but not postsynaptic APP deletion through the local injection of Cre-expressing adeno-associated viruses in conditional APPflox/flox tissue cultures increased the neurotransmission efficacy at perforant path synapses. In summary, these data suggest a physiological role for presynaptic APP at medial perforant path synapses that may be adversely affected under altered APP processing conditions.SIGNIFICANCE STATEMENT The hippocampus receives input from the entorhinal cortex via the perforant path. These projections to hippocampal dentate granule cells are of utmost importance for learning and memory formation. Although there is detailed knowledge about perforant path projections, the functional synaptic properties at the level of individual connected pairs of neurons are not well understood. In this study, we investigated the role of APP in mediating functional properties and transmission rules in individually connected neurons using paired whole-cell patch-clamp recordings and genetic tools in organotypic tissue cultures. Our results show that presynaptic APP expression limits excitatory neurotransmission via the perforant path, which could be compromised in pathologic conditions such as Alzheimer's disease.

Denervated mouse CA1 pyramidal neurons express homeostatic synaptic plasticity following entorhinal cortex lesion.

Structural, functional, and molecular reorganization of denervated neural networks is often observed in neurological conditions. The loss of input is accompanied by homeostatic synaptic adaptations, which can affect the reorganization process. A major challenge of denervation-induced homeostatic plasticity operating in complex neural networks is the specialization of neuronal inputs. It remains unclear whether neurons respond similarly to the loss of distinct inputs. Here, we used in vitro entorhinal cortex lesion (ECL) and Schaffer collateral lesion (SCL) in mouse organotypic entorhino-hippocampal tissue cultures to study denervation-induced plasticity of CA1 pyramidal neurons. We observed microglia accumulation, presynaptic bouton degeneration, and a reduction in dendritic spine numbers in the denervated layers 3 days after SCL and ECL. Transcriptome analysis of the CA1 region revealed complex changes in differential gene expression following SCL and ECL compared to non-lesioned controls with a specific enrichment of differentially expressed synapse-related genes observed after ECL. Consistent with this finding, denervation-induced homeostatic plasticity of excitatory synapses was observed 3 days after ECL but not after SCL. Chemogenetic silencing of the EC but not CA3 confirmed the pathway-specific induction of homeostatic synaptic plasticity in CA1. Additionally, increased RNA oxidation was observed after SCL and ECL. These results reveal important commonalities and differences between distinct pathway lesions and demonstrate a pathway-specific induction of denervation-induced homeostatic synaptic plasticity.

Pedicle or lateral mass screws in Goel-Harms construct? A biomechanical analysis.

BACKGROUND: The use of the posterior arch of C1 as pedicle has shown beneficial stability regarding screw loosening, however, the C1 pedicle screw placement is challenging. Therefore, the study aimed to analyse the bending forces of the Harms construct used in fixation of C1/C2 when using pedicle screws compared to lateral mass screws. METHODS: Five cadaveric specimens with a mean age of 72 years at death and bone mineral density measuring for 512.4 Hounsfield Units (HU) on average were used. A custom-made biomechanical setup was used to test the specimens with a C1/C2 Harms construct each with the use of lateral mass screws and pedicle screws in sequence. Strain gauges were used to analyse the bending forces from C1 to C2 in cyclic axial compression (µm/m). All underwent cyclic biomechanical testing using 50, 75 and 100 N. FINDINGS: In all specimens, placement of lateral mass screws and pedicle screws was feasible. All underwent cyclic biomechanical testing. For the lateral mass screw, a bending of 142.04 µm/m at 50 N, 166.56 µm/m at 75 N and 188.54 µm/m at 100 N was measured. For the pedicle screws, bending force was slightly elevated with 165.98 µm/m at 50 N, 190.58 µm/m at 75 N and 195.95 µm/m at 100 N. However, bending forces did not vary significantly. In all measurements, no statistical significance was found when comparing pedicle screws and lateral mass screws. INTERPRETATION: The lateral mass screw used in the Harms Construct to stabilize C1/2 showed less bending forces, therefore the construct with lateral mass screws appears more stable in axial compression compared to the one with pedicle screws. However, bending forces did not vary significantly.

Is human bone matrix a sufficient augmentation method revising loosened pedicle screws in osteoporotic bone? - A biomechanical evaluation of primary stability.

INTRODUCTION: Despite good screw anchorage and safe screw trajectory, screw loosening occurs in several cases, especially in osteoporotic individuals. The aim of this biomechanical analysis was to evaluate the primary stability of revision screw placement in individuals with reduced bone quality. Therefore, revision via enlarged diameter screws was compared to the use of human bone matrix as augmentation to improve the bone stock and screw coverage. METHODS: 11 lumbar vertebral bodies from cadaveric specimens with a mean age of 85.7 years (± 12.0 years) at death were used. 6.5 mm diameter pedicle screws were inserted in both pedicles and hereafter loosened using a fatigue protocol. Screws were revised inserting a larger diameter screw (8.5 mm) in one pedicle and a same diameter screw with human bone matrix augmentation in the other pedicle. The previous loosening protocol was then reapplied, comparing maximum load and cycles to failure between both revision techniques. Insertional torque was continuously measured during insertion of both revision screws. FINDINGS: The number of cycles and the maximum load until failure were significantly greater in enlarged diameter screws than in augmented screws. The enlarged screws' insertional torque was also significantly higher than of the augmented screws. INTERPRETATION: Human bone matrix augmentation does not reach the same ad-hoc fixation strength as enlarging the screw's diameter by 2 mm and is therefore biomechanically inferior. Regarding the immediate stability, a thicker screw should therefore be prioritised.

Microglial Cytokines Mediate Plasticity Induced by 10 Hz Repetitive Magnetic Stimulation.

Microglia, the resident immune cells of the CNS, sense the activity of neurons and regulate physiological brain functions. They have been implicated in the pathology of brain diseases associated with alterations in neural excitability and plasticity. However, experimental and therapeutic approaches that modulate microglia function in a brain region-specific manner have not been established. In this study, we tested for the effects of repetitive transcranial magnetic stimulation (rTMS), a clinically used noninvasive brain stimulation technique, on microglia-mediated synaptic plasticity; 10 Hz electromagnetic stimulation triggered a release of plasticity-promoting cytokines from microglia in mouse organotypic brain tissue cultures of both sexes, while no significant changes in microglial morphology or microglia dynamics were observed. Indeed, substitution of tumor necrosis factor α (TNFα) and interleukin 6 (IL6) preserved synaptic plasticity induced by 10 Hz stimulation in the absence of microglia. Consistent with these findings, in vivo depletion of microglia abolished rTMS-induced changes in neurotransmission in the mPFC of anesthetized mice of both sexes. We conclude that rTMS affects neural excitability and plasticity by modulating the release of cytokines from microglia.SIGNIFICANCE STATEMENT Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that induces cortical plasticity. Despite its wide use in neuroscience and clinical practice (e.g., depression treatment), the cellular and molecular mechanisms of rTMS-mediated plasticity remain not well understood. Herein, we report an important role of microglia and plasticity-promoting cytokines in synaptic plasticity induced by 10 Hz rTMS in organotypic slice cultures and anesthetized mice, thereby identifying microglia-mediated synaptic adaptation as a target of rTMS-based interventions.