Aquaporin 2 in Cerebral Edema: Potential Prognostic Marker in Craniocerebral Injuries.

Despite continuous medical advancements, traumatic brain injury (TBI) remains a leading cause of death and disability worldwide. Consequently, there is a pursuit for biomarkers that allow non-invasive monitoring of patients after cranial trauma, potentially improving clinical management and reducing complications and mortality. Aquaporins (AQPs), which are crucial for transmembrane water transport, may be significant in this context. This study included 48 patients, with 27 having acute (aSDH) and 21 having chronic subdural hematoma (cSDH). Blood plasma samples were collected from the participants at three intervals: the first sample before surgery, the second at 15 h, and the third at 30 h post-surgery. Plasma concentrations of AQP1, AQP2, AQP4, and AQP9 were determined using the sandwich ELISA technique. CT scans were performed on all patients pre- and post-surgery. Correlations between variables were examined using Spearman's nonparametric rank correlation coefficient. A strong correlation was found between aquaporin 2 levels and the volume of chronic subdural hematoma and midline shift. However, no significant link was found between aquaporin levels (AQP1, AQP2, AQP4, and AQP9) before and after surgery for acute subdural hematoma, nor for AQP1, AQP4, and AQP9 after surgery for chronic subdural hematoma. In the chronic SDH group, AQP2 plasma concentration negatively correlated with the midline shift measured before surgery (Spearman's ρ -0.54; p = 0.017) and positively with hematoma volume change between baseline and 30 h post-surgery (Spearman's ρ 0.627; p = 0.007). No statistically significant correlation was found between aquaporin plasma levels and hematoma volume for AQP1, AQP2, AQP4, and AQP9 in patients with acute SDH. There is a correlation between chronic subdural hematoma volume, measured radiologically, and serum AQP2 concentration, highlighting aquaporins' potential as clinical biomarkers.

Stereotactic radiosurgery for Koos grade IV vestibular schwannoma: a systematic review and meta-analysis.

BACKGROUND: Stereotactic radiosurgery (SRS) is a well-established treatment option for Koos stage I-III vestibular schwannomas (VS), often used as the first line of treatment or after subtotal resection. However, the optimal treatment for Koos-IV VS remains unclear. Therefore, our study aimed to evaluate the effectiveness of SRS as a primary treatment for large VS classified as Koos-IV. METHODS: A systematic search was performed on December 28th, 2022, based on PubMed, Web of Science, and Scopus according to the PRISMA statement. The review was updated on September 7th, 2023. The risk of bias was assessed using the NIH Quality Assessment Tool. The R software (ver. 4.3.2) was used for all quantitative analyses and preparation of the forest plots. Publication bias and sensitivity analysis were performed to evaluate the reliability of the obtained results. RESULTS: Among 2941 screened records, ten studies (1398 patients) have been included in quantitative synthesis. The overall tumor control rate was 90.7% (95%CI 86.3-94.4). Kaplan-Meier estimates of tumor control at 2, 6, and 10 years were 96.0% (95% CI 92.9-97.6%), 88.8% (95% CI 86.9-89.8%), and 84.5% (95% CI, 81.2-85.8%), respectively. The overall hearing preservation rate was 56.5% (95%CI 37-75.1). Kaplan-Meier estimates of hearing preservation rate at 2, 6, and 10 years were 77.1% (95% CI 67.9-82.5%), 53.5% (95% CI 44.2-58.5%), and 38.1% (95% CI 23.4-40.7%), respectively. The overall facial nerve preservation rate was 100% (95%CI 99.9-100.0). The overall trigeminal neuropathy rate reached 5.7% (95%CI 2.9-9.2). The overall rate of new-onset hydrocephalus was 5.6% (95%CI 3-9). The overall rates of worsening or new-onset tinnitus and vertigo were 6.8% (95%CI 4.2-10.0) and 9.1% (95%CI 2.1-19.6) respectively. No publication bias was detected according to the used methods. CONCLUSIONS: Our systematic review and meta-analysis demonstrated a high overall tumor control rate, excellent facial nerve preservation, and low incidence of new-onset or worsened tinnitus and vertigo. However, several drawbacks associated with SRS should be noted, such as the presence of post-SRS hydrocephalus risk, mediocre long-term hearing preservation, and the lack of immediate tumor decompression. Nevertheless, the use of SRS may be beneficial in appropriately selected cases of Koos-IV VS. Moreover, further prospective studies directly comparing SRS with surgery are necessary to determine the optimal treatment for large VS and verify our results on a higher level of evidence. Registration and protocol: CRD42023389856.

Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury.

Traumatic Brain Injury (TBI) represents a significant health concern, necessitating advanced therapeutic interventions. This detailed review explores the critical roles of astrocytes, key cellular constituents of the central nervous system (CNS), in both the pathophysiology and possible rehabilitation of TBI. Following injury, astrocytes exhibit reactive transformations, differentiating into pro-inflammatory (A1) and neuroprotective (A2) phenotypes. This paper elucidates the interactions of astrocytes with neurons, their role in neuroinflammation, and the potential for their therapeutic exploitation. Emphasized strategies encompass the utilization of endocannabinoid and calcium signaling pathways, hormone-based treatments like 17ß-estradiol, biological therapies employing anti-HBGB1 monoclonal antibodies, gene therapy targeting Connexin 43, and the innovative technique of astrocyte transplantation as a means to repair damaged neural tissues.

Brain stimulation for chronic pain management: a narrative review of analgesic mechanisms and clinical evidence.

Chronic pain constitutes one of the most common chronic complaints that people experience. According to the International Association for the Study of Pain, chronic pain is defined as pain that persists or recurs longer than 3 months. Chronic pain has a significant impact on individuals' well-being and psychosocial health and the economy of healthcare systems as well. Despite the availability of numerous therapeutic modalities, treatment of chronic pain can be challenging. Only about 30% of individuals with non-cancer chronic pain achieve improvement from standard pharmacological treatment. Therefore, numerous therapeutic approaches were proposed as a potential treatment for chronic pain including non-opioid pharmacological agents, nerve blocks, acupuncture, cannabidiol, stem cells, exosomes, and neurostimulation techniques. Although some neurostimulation methods such as spinal cord stimulation were successfully introduced into clinical practice as a therapy for chronic pain, the current evidence for brain stimulation efficacy in the treatment of chronic pain remains unclear. Hence, this narrative literature review aimed to give an up-to-date overview of brain stimulation methods, including deep brain stimulation, motor cortex stimulation, transcranial direct current stimulation, repetitive transcranial magnetic stimulation, cranial electrotherapy stimulation, and reduced impedance non-invasive cortical electrostimulation as a potential treatment for chronic pain.

The application of 3D-bioprinted scaffolds for neuronal regeneration after traumatic spinal cord injury - A systematic review of preclinical in vivo studies.

BACKGROUND: The implantation of 3D-bioprinted scaffolds represents a promising therapeutic approach for traumatic Spinal Cord Injury (SCI), currently investigating in preclinical in vivo studies. However, a systematic review of the relevant literature has not been performed to date. Hence, we systematically reviewed the outcomes of the application of 3D-bioprinted implants in the treatment of SCI based on studies conducted on experimental animal models. METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane Library databases. Manuscripts in other designs than in vivo preclinical study and written in other languages than English were excluded. A risk of bias assessment was performed using SYRCLE's tool. The quality of included articles was assessed by ARRIVE guidelines. Extracted data were synthesized only qualitatively because the data were not suitable for conducting the meta-analysis. RESULTS: Overall, eleven animal studies reporting on the transection SCI rat model were included. Six of included studies investigated 3D-bioprinted scaffolds enriched with stem cells, two studies - 3D-bioprinted scaffolds combined with growth factors, and three studies - stand-alone 3D-bioprinted scaffolds. In all included studies the application of 3D-bioprinted scaffolds led to significant improvement in functional scores compared with no treated SCI rats. The functional recovery corresponded with the changes observed at the injury site in histological analyses. Seven studies demonstrated medium, three studies - high, and one study - low risk of bias. Moreover, some of the included studies were conducted in the same scientific center. The overall quality assessment ratio amounted to 0.60, which was considered average quality. CONCLUSION: The results of our systematic review suggest that 3D-bioprinted scaffolds may be a feasible therapeutic approach for the treatment of SCI. Further evidence obtained on other experimental SCI models is necessary before the clinical translation of 3D-bioprinted scaffolds.

Clinical significance of Left-Sided Gallbladder for laparoscopic cholecystectomy and hepatectomy.

A left-sided gallbladder (LSG) represents a rare anatomical variation defined by the location of the gallbladder to the left side of the liver falciform and round ligaments, which is often not discovered until surgery. The reported prevalence of this ectopia ranges from 0.2% to 1.1%, however, those values may be underestimated. It is mostly an asymptomatic condition, thus not causing the patient any harm, and being few reported cases in the current literature. Based on clinical presentation and standard diagnostic procedures, LSG can remain undetected and represent accidental intraoperative finding. The attempts to explain the cause of this anomaly have been different, but the numerous variations described do not allow a clear definition of its origin. Although this debate is still open, it is of considerable importance to know that LSG is frequently associated with alterations of both the portal branches and the intrahepatic biliary tree. The association of these anomalies, therefore, represents an important risk of complications in cases when surgical treatment is necessary. In this context, our literature review aimed to summarize possible anatomical anomalies coexisting with LSG and discuss the clinical significance of the LSG, when the patient requires cholecystectomy or hepatectomy.

Diagnosis and Management of Neuropathic Pain in Spine Diseases.

Neuropathic pain is generally defined as a non-physiological pain experience caused by damage to the nervous system. It can occur spontaneously, as a reaction to a given stimulus, or independently of its action, leading to unusual pain sensations usually referred to as firing, burning or throbbing. In the course of spine disorders, pain symptoms commonly occur. According to available epidemiological studies, a neuropathic component of pain is often present in patients with spinal diseases, with a frequency ranging from 36% to 55% of patients. Distinguishing between chronic nociceptive pain and neuropathic pain very often remains a challenge. Consequently, neuropathic pain is often underdiagnosed in patients with spinal diseases. In reference to current guidelines for the treatment of neuropathic pain, gabapentin, serotonin and norepinephrine reuptake inhibitors and tricyclic antidepressants constitute first-line therapeutic agents. However, long-term pharmacologic treatment often leads to developing tolerance and resistance to used medications. Therefore, in recent years, a plethora of therapeutic methods for neuropathic pain have been developed and investigated to improve clinical outcomes. In this review, we briefly summarized current knowledge about the pathophysiology and diagnosis of neuropathic pain. Moreover, we described the most effective treatment approaches for neuropathic pain and discussed their relevance in the treatment of spinal pain.

The Incidence, Localization and Clinical Relevance of Arterial Fenestrations and Their Association to Brain Aneurysms: A Case-Control Study Based on the STROBE Guidelines.

Background: Fenestrations are rare, but well-known, vascular variations of the cerebral arteries. They are mostly incidental, asymptomatic angiographic findings and might precipitate vascular lesions such as AVM, aneurysmal dilatation, or even ischemic symptoms. However, association between arterial fenestration and brain aneurysms has not been clearly established. Objective: To evaluate whether incidence of arterial fenestrations are associated with brain aneurysm development and investigate the prevalence and most-common localizations of arterial fenestrations of the human brain. Design: Case−control study. Setting: All patients examined by CT angiography in University Hospital No. 4 in Lublin from 2009 to 2019. Patients: Each patient showing at least one cerebral aneurysm was included in the case group and each patient without cerebral aneurysm on CT angiography was included in the control group. Measurements: CT angiography examinations were conducted using the standard protocol used in the 1st Department of Radiology, Medical University of Lublin, Poland. The database and statistical research were conducted by use of the Statistica software (ver. 13.3, Tibco Software Inc., Palo Alto, CA, USA). Results: A total of 6545 CTA examinations were included in the study. Most of the aneurysms were located on the MCA: 629 (38.59%), ICA: 466 (28.59%) and AComA: 192 (11.78%). Cerebral arterial fenestration showed a non-statistically significant elevated risk for brain aneurysms in the entire study population (OR: 1.157; 95% CI: 0.826−1.621; p = 0.39). Among 6545 cranial CTA examinations, cerebral vessel fenestration was found in 49 of them, which constituted 0.75%. The most common vascular fenestrations were those located in the ACA (30.61%), BA (30.61%) and AComA (22.45%), while other fenestrations occurred infrequently. There were no significant differences in the age of patients in the individuals with vascular fenestration (p > 0.05). VA fenestration was slightly more common in men (16.67%) than in women (5.41%). However, these differences were not statistically significant (p = 0.216). Limitations: Our study has several limitations, including selection bias regarding examined population. Second, we assume that the total number of fenestrations detected in our study was underestimated due to the limitations of the CT method in comparison to other radiologic modalities. Conclusions: Cerebral arterial fenestrations are rare vascular malformations. The ACA is the most common localization of fenestrations, followed by BA and AComA. Fenestrations of cerebral arteries insignificantly increase the risk of cerebral aneurysm formation. Further prospective studies are necessary to make this association more precise.

Biological and Clinical Aspects of Metastatic Spinal Tumors.

Spine metastases are a common life-threatening complication of advanced-stage malignancies and often result in poor prognosis. Symptomatic spine metastases develop in the course of about 10% of malignant neoplasms. Therefore, it is essential for contemporary medicine to understand metastatic processes in order to find appropriate, targeted therapeutic options. Thanks to continuous research, there appears more and more detailed knowledge about cancer and metastasis, but these transformations are extremely complicated, e.g., due to the complexity of reactions, the variety of places where they occur, or the participation of both tumor cells and host cells in these transitions. The right target points in tumor metastasis mechanisms are still being researched; that will help us in the proper diagnosis as well as in finding the right treatment. In this literature review, we described the current knowledge about the molecular pathways and biomarkers engaged in metastatic processes involving the spine. We also presented a current bone-targeted treatment for spine metastases and the emerging therapies targeting the discussed molecular mechanisms.

Low-Cost Cranioplasty-A Systematic Review of 3D Printing in Medicine.

The high cost of biofabricated titanium mesh plates can make them out of reach for hospitals in low-income countries. To increase the availability of cranioplasty, the authors of this work investigated the production of polymer-based endoprostheses. Recently, cheap, popular desktop 3D printers have generated sufficient opportunities to provide patients with on-demand and on-site help. This study also examines the technologies of 3D printing, including SLM, SLS, FFF, DLP, and SLA. The authors focused their interest on the materials in fabrication, which include PLA, ABS, PET-G, PEEK, and PMMA. Three-dimensional printed prostheses are modeled using widely available CAD software with the help of patient-specific DICOM files. Even though the topic is insufficiently researched, it can be perceived as a relatively safe procedure with a minimal complication rate. There have also been some initial studies on the costs and legal regulations. Early case studies provide information on dozens of patients living with self-made prostheses and who are experiencing significant improvements in their quality of life. Budget 3D-printed endoprostheses are reliable and are reported to be significantly cheaper than the popular counterparts manufactured from polypropylene polyester.

Metallic Implants Used in Lumbar Interbody Fusion.

Over the last decade, pedicle fixation systems have evolved and modifications in spinal fusion techniques have been developed to increase fusion rates and improve clinical outcomes after lumbar interbody fusion (LIF). Regarding materials used for screw and rod manufacturing, metals, especially titanium alloys, are the most popular resources. In the case of pedicle screws, that biomaterial can be also doped with hydroxyapatite, CaP, ECM, or tantalum. Other materials used for rod fabrication include cobalt-chromium alloys and nitinol (nickel-titanium alloy). In terms of mechanical properties, the ideal implant used in LIF should have high tensile and fatigue strength, Young's modulus similar to that of the bone, and should be 100% resistant to corrosion to avoid mechanical failures. On the other hand, a comprehensive understanding of cellular and molecular pathways is essential to identify preferable characteristics of implanted biomaterial to obtain fusion and avoid implant loosening. Implanted material elicits a biological response driven by immune cells at the site of insertion. These reactions are subdivided into innate (primary cellular response with no previous exposure) and adaptive (a specific type of reaction induced after earlier exposure to the antigen) and are responsible for wound healing, fusion, and also adverse reactions, i.e., hypersensitivity. The main purposes of this literature review are to summarize the physical and mechanical properties of metal alloys used for spinal instrumentation in LIF which include fatigue strength, Young's modulus, and corrosion resistance. Moreover, we also focused on describing biological response after their implantation into the human body. Our review paper is mainly focused on titanium, cobalt-chromium, nickel-titanium (nitinol), and stainless steel alloys.

Hydroxyapatite Use in Spine Surgery-Molecular and Clinical Aspect.

Hydroxyapatite possesses desirable properties as a scaffold in tissue engineering: it is biocompatible at a site of implantation, and it is degradable to non-toxic products. Moreover, its porosity enables infiltration of cells, nutrients and waste products. The outcome of hydroxyapatite implantation highly depends on the extent of the host immune response. Authors emphasise major roles of the chemical, morphological and physical properties of the surface of biomaterial used. A number of techniques have been applied to transform the theoretical osteoconductive features of HAp into spinal fusion systems-from integration of HAp with autograft to synthetic intervertebral implants. The most popular uses of HAp in spine surgery include implants (ACDF), bone grafts in posterolateral lumbar fusion and transpedicular screws coating. In the past, autologous bone graft has been used as an intervertebral cage in ACDF. Due to the morbidity related to autograft harvesting from the iliac bone, a synthetic cage with osteoconductive material such as hydroxyapatite seems to be a good alternative. Regarding posterolateral lumbar fusion, it requires the graft to induce new bone growth and reinforce fusion between the vertebrae. Hydroxyapatite formulations have shown good results in that field. Moreover, the HAp coating has proven to be an efficient method of increasing screw fixation strength. It can decrease the risk of complications such as screw loosening after pedicle screw fixation in osteoporotic patients. The purpose of this literature review is to describe in vivo reaction to HAp implants and to summarise its current application in spine surgery.

Molecular Mechanisms and Clinical Application of Multipotent Stem Cells for Spinal Cord Injury.

Spinal Cord Injury (SCI) is a common neurological disorder with devastating psychical and psychosocial sequelae. The majority of patients after SCI suffer from permanent disability caused by motor dysfunction, impaired sensation, neuropathic pain, spasticity as well as urinary complications, and a small number of patients experience a complete recovery. Current standard treatment modalities of the SCI aim to prevent secondary injury and provide limited recovery of lost neurological functions. Stem Cell Therapy (SCT) represents an emerging treatment approach using the differentiation, paracrine, and self-renewal capabilities of stem cells to regenerate the injured spinal cord. To date, multipotent stem cells including mesenchymal stem cells (MSCs), neural stem cells (NSCs), and hematopoietic stem cells (HSCs) represent the most investigated types of stem cells for the treatment of SCI in preclinical and clinical studies. The microenvironment of SCI has a significant impact on the survival, proliferation, and differentiation of transplanted stem cells. Therefore, a deep understanding of the pathophysiology of SCI and molecular mechanisms through which stem cells act may help improve the treatment efficacy of SCT and find new therapeutic approaches such as stem-cell-derived exosomes, gene-modified stem cells, scaffolds, and nanomaterials. In this literature review, the pathogenesis of SCI and molecular mechanisms of action of multipotent stem cells including MSCs, NSCs, and HSCs are comprehensively described. Moreover, the clinical efficacy of multipotent stem cells in SCI treatment, an optimal protocol of stem cell administration, and recent therapeutic approaches based on or combined with SCT are also discussed.