Association of Coronary Calcium Score on Cardiac PET During Pre-Kidney Transplant Assessment with Persistent Hyperparathyroidism: A Retrospective Study.

BACKGROUND Secondary hyperparathyroidism and coronary calcifications are common complications in chronic kidney disease. However, the relation between coronary calcium score (CCS) and persistent hyperparathyroidism (pHPT) after kidney transplantation (KT) remains unknown. MATERIAL AND METHODS This was a single-center retrospective study of KT candidates from January 2017 to May 2020. We collected patients' demographics, cardiovascular (CV) risk factors, and the findings of pre-KT CV imaging. We also collected parathyroid hormone (PTH) values before KT, at 1-6 months, 6-12 months, and 12-24 months after KT. We defined pHPT as PTH ≥25.5 pmol/L after 12 months post-KT. RESULTS A total of 111 KT recipients (KTRs) with a mean age of 50.4 years were included, of which 62.2% were men and 77.5% were living-donor KTRs. Dialysis modality used before KT was peritoneal dialysis in 9.9% and hemodialysis in 82.9%. Dialysis vintage was 3±2.9 years. The prevalence of pHPT was 24.3% (n=27), and the prevalence of severe coronary calcifications (CCS >400 Agatston units) was 19.8% (n=22). PTH values at baseline, 1-6 months, 6-12 months, and 12-24 months were not different among between CCS >400 or CCS <400 groups. However, pHPT after KT was significantly more prevalent in KTRs with severe CCS (37% vs 14.3%, p=0.014). Severe CCS was associated with less improvement of PTH values after KT (r=0.288, p=0.020). Otherwise, the findings of cardiac PET and coronary angiogram were not significantly different between pHPT and non-pHPT patients. CCS >400 was independently associated with pHPT after transplant (aOR=18.8, P=0.012). CONCLUSIONS Severe CCS on pre-KT cardiac assessment is associated with pHPT after KT.

Complications and visual outcomes following surgical resection of pediatric optic pathway/hypothalamic gliomas: a systematic review and meta-analysis.

Pediatric optic pathway/hypothalamic gliomas (OPHG) pose challenges in treatment due to their location and proximity to vital structures. Surgical resection plays a key role in the management of OPHG especially when the tumor exhibits mass effect and causes symptoms. However, data regarding outcomes and complications of surgical resection for OPHG remains heterogenous. The authors performed a systematic review on pediatric OPHG in four databases: PubMed, EMBASE, Cochrane Library, and Google Scholar. We included studies that reported on the visual outcomes and complications of OPHG resection. A meta-analysis was performed and reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 26 retrospective studies were included. Seven hundred ninety-seven pediatric patients with OPHG undergoing surgical resection were examined. A diagnosis of NF1 was confirmed in 9.7%. Gross total resection was achieved in 36.7%. Intraorbital optic pathway gliomas showed a significantly higher gross total resection rate compared to those located in the chiasmatic/hypothalamic region (75.8% vs. 9.6%). Postoperatively, visual acuity improved in 24.6%, remained unchanged in 68.2%, and worsened in 18.2%. Complications included hydrocephalus (35.4%), anterior pituitary dysfunction (19.6%), and transient diabetes insipidus (29%). Tumor progression post-resection occurred in 12.8%, through a mean follow-up of 53.5 months. Surgical resection remains an essential strategy for treating symptomatic and large pediatric OPHG and can result in favorable vision outcomes in most patients. Careful patient selection is critical. Patients should be monitored for hydrocephalus development postoperatively and followed up to assess for tumor progression and adjuvant treatment necessity.

Renal AL Amyloidosis: Updates on Diagnosis, Staging, and Management.

AL amyloidosis is caused by the excessive production of nonfunctional immunoglobulins, leading to the formation of amyloid fibrils that damage vital organs, especially the heart and kidneys. AL amyloidosis presents with non-specific symptoms such as fatigue, weight loss, numbness, pain, and nephrotic syndrome. Consequently, diagnosis is often delayed, and patients typically present with advanced disease at diagnosis. The Pavia renal staging model stratifies patients based on their likelihood of progressing to dialysis. Treatment with daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (i.e., Dara-CyBorD) was effective in inducing renal response in the landmark phase III ANDROMEDA trial and reducing early mortality. However, determining the most appropriate treatment regimen for relapsed or refractory cases remains a challenge due to various patient- and disease-related factors. Encouragingly, t(11:14) may be a positive indicator of therapy responses to the anti-BCL2 therapy venetoclax. Moreover, it is increasingly possible-for the first time-to clear AL amyloid fibrils from peripheral organs by leveraging novel anti-fibril immunotherapeutic approaches, although these medications are still under investigation in clinical trials. Given these advancements, this review provides a comprehensive overview of the current strategies for diagnosing, staging, treating, and monitoring AL amyloidosis, emphasizing renal involvement.

Avoidable emergency department visits among palliative care cancer patients: novel insights from Saudi Arabia and the Middle East.

BACKGROUND: Several studies emerging from developed countries have highlighted a significant number of potentially avoidable emergency department (ED) visits by cancer patients during the end-of-life period. However, there is a paucity of information from developing nations regarding palliative care practices and the utilization of the ED by palliative care patients. Herein, we aim to characterize ED admissions among patients receiving palliative care at our tertiary center in Saudi Arabia. METHODS: This is a retrospective, cross-sectional study evaluating ED visits amongst adult patients with advanced cancer who were receiving treatment under the palliative care department. This study took place over a period of 12 months from July 2021 through to July 2022. Three palliative care specialist physicians independently and blindly reviewed each patient's ED visits and determined whether the visit was avoidable or unavoidable. RESULTS: A total of 243 patients were included in the final analysis, of which 189 (78.1%) patients had unavoidable visits and 53 (21.9%) patient visits were classified as avoidable. A significantly higher proportion of breast cancer patients presented with unavoidable admissions (14.3% vs. 3.8%, P = 0.037) compared to other cancer types. The incidence of dyspnea (23.8% vs. 5.7%, P < 0.001) and fevers/chills (23.3% vs. 5.7%, P = 0.005) was significantly higher in patients with unavoidable visits. Patients with avoidable visits had a significantly greater proportion of visits for dehydration (13.2% vs. 2.1%, P = 0.002). Notably, although hospital stay was significantly longer in the unavoidable group (P = 0.045), mortality for palliative care patients-regardless of whether their ED visit was avoidable or unavoidable-was not statistically different (P=-0.069). CONCLUSION: To our knowledge, this is the largest and most comprehensive study from Saudi Arabia and the Middle East providing insights into the utilization of palliative care services in the region and the propensity of advanced cancer patients towards visiting the ED. Future studies ought to explore interventions to reduce the frequency of avoidable ED visits.

Cellular senescence in brain aging and cognitive decline.

Cellular senescence is a biological aging hallmark that plays a key role in the development of neurodegenerative diseases. Clinical trials are currently underway to evaluate the effectiveness of senotherapies for these diseases. However, the impact of senescence on brain aging and cognitive decline in the absence of neurodegeneration remains uncertain. Moreover, patient populations like cancer survivors, traumatic brain injury survivors, obese individuals, obstructive sleep apnea patients, and chronic kidney disease patients can suffer age-related brain changes like cognitive decline prematurely, suggesting that they may suffer accelerated senescence in the brain. Understanding the role of senescence in neurocognitive deficits linked to these conditions is crucial, especially considering the rapidly evolving field of senotherapeutics. Such treatments could help alleviate early brain aging in these patients, significantly reducing patient morbidity and healthcare costs. This review provides a translational perspective on how cellular senescence plays a role in brain aging and age-related cognitive decline. We also discuss important caveats surrounding mainstream senotherapies like senolytics and senomorphics, and present emerging evidence of hyperbaric oxygen therapy and immune-directed therapies as viable modalities for reducing senescent cell burden.

Fluorescence-guided resection of intradural spinal tumors: a systematic review and meta-analysis.

Intradural spinal tumors present significant challenges due to involvement of critical motor and sensory tracts. Achieving maximal resection while preserving functional tissue is therefore crucial. Fluorescence-guided surgery aims to improve resection accuracy and is well studied for brain tumors, but its efficacy has not been fully assessed for spinal tumors. This meta-analysis aims to delineate the efficacy of fluorescence guidance in intradural spinal tumor resection. The authors performed a systematic review in four databases. We included studies that have utilized fluorescence agents, 5-aminolevulinic acid (5-ALA) or sodium fluorescein, for the resection of intradural spinal tumors. A meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 12 studies involving 552 patients undergoing fluorescence-guided intradural spinal tumor resection were included. Meningiomas demonstrated a 98% fluorescence rate and were associated with a homogenous florescence pattern; however, astrocytomas had variable fluorescence rate with pooled proportion of 70%. There was no significant difference in gross total resection (GTR) rates between fluorescein and 5-ALA (94% vs 84%, p = .22). Pre-operative contrast enhancement was significantly associated with intraoperative fluorescence with fluorescein. Intramedullary tumors with positive intraoperative fluorescence were significantly associated with higher GTR rates (96% vs 73%, p = .03). Utilizing fluorescence guidance during intradural spinal tumor resection holds promise of improving intraoperative visualization for specific intradural spinal tumors. Meningiomas and ependymomas have the highest fluorescence rates especially with sodium fluorescein; on the other hand, astrocytomas have variable fluorescence rates with no superiority of either agent. Positive fluorescence of intramedullary tumors is associated with a higher degree of resection.

A DNA Methylation Perspective on Infertility.

Infertility affects a significant number of couples worldwide and its incidence is increasing. While assisted reproductive technologies (ART) have revolutionized the treatment landscape of infertility, a significant number of couples present with an idiopathic cause for their infertility, hindering effective management. Profiling the genome and transcriptome of infertile men and women has revealed abnormal gene expression. Epigenetic modifications, which comprise dynamic processes that can transduce environmental signals into gene expression changes, may explain these findings. Indeed, aberrant DNA methylation has been widely characterized as a cause of abnormal sperm and oocyte gene expression with potentially deleterious consequences on fertilization and pregnancy outcomes. This review aims to provide a concise overview of male and female infertility through the lens of DNA methylation alterations.

How Neutrophils Shape the Immune Response: Reassessing Their Multifaceted Role in Health and Disease.

Neutrophils are the most abundant of the circulating immune cells and are the first to be recruited to sites of inflammation. Neutrophils are a heterogeneous group of immune cells from which are derived extracellular traps (NETs), reactive oxygen species, cytokines, chemokines, immunomodulatory factors, and alarmins that regulate the recruitment and phenotypes of neutrophils, macrophages, dendritic cells, T cells, and B cells. In addition, cytokine-stimulated neutrophils can express class II major histocompatibility complex and the internal machinery necessary for successful antigen presentation to memory CD4+ T cells. This may be relevant in the context of vaccine memory. Neutrophils thus emerge as orchestrators of immune responses that play a key role in determining the outcome of infections, vaccine efficacy, and chronic diseases like autoimmunity and cancer. This review aims to provide a synthesis of current evidence as regards the role of these functions of neutrophils in homeostasis and disease.

Exploring Renal Malignancies in Saudi Arabia: Insights from a Tertiary Care Center Study.

This retrospective study aims to describe the characteristics of renal cell carcinoma (RCC) in Saudi Arabia, in terms of epidemiology, clinical presentation, tumor subtype, Fuhrman grade, tumor size and stage, and overall survival. A total of 431 adult patients with a histopathological diagnosis of RCC between 2015 and 2023 were included in the analysis. Most patients (72.4%) had clear cell tumors, followed by chromophobe (15.1%) and papillary (12.5%) subtypes. In males, papillary RCC (85.2%) was more common compared to clear cell (59.8%) and chromophobe (67.7%) subtypes. Significant differences were observed in median body mass index (BMI) across tumor subtypes, and papillary tumor patients exhibited the highest incidence of hematuria (33.3%) compared to other subtypes. The Fuhrman grade also varied significantly among RCC types. Survival times were found to be lower for patients with papillary tumors. No significant difference was observed based on patients' nationality. This study can inform clinical decision-making on patient prognosis and management as well as public health efforts aimed at reducing the alarming rise of RCC incidence.

Beyond the norm: exploring the uncommon squamous cell carcinoma of the prostate using a Saudi tumor registry.

Background: Squamous cell carcinoma (SCC) of the prostate has limited treatment choices and portends a dismal prognosis with an average survival time of ~14-months. This study provides a descriptive overview of SCC of the prostate in Saudi Arabia. Materials and Methods: A retrospective cohort study of patients diagnosed with prostatic SCC between 1 January 2008 and 31 December 2017. Information on demographic and tumor characteristics and the survival of patients was collected from the Saudi Cancer Registry. Survival was depicted through Kaplan-Meier plots. Fisher's exact test was used to assess the association between categorical variables and death, while a Wilcoxon rank sum test was applied for numerical variables. Results: Out of a larger subset of 3607 patients, 16 patients were diagnosed with prostatic SCC, of which half resided in the Central region (50.0%) and most (81.2%) were aged greater than or equal to 60 years. Most patients (62.6%) had poorly differentiated (grade III, 43.8%) lesions, and 50% of cases were metastatic at diagnosis. 62.5% of patients died, all residing in the Eastern and Central regions. Regional extension (75.0%) and distant metastasis (87.5%) were significantly associated with death compared to localized lesions (0.0%) (P=0.022). The 5-year survival rate in our study was 33%. Conclusion: The present study is the first to describe the characteristics of prostatic SCC in Saudi Arabia. Our results are consistent with prior studies showing that prostatic SCC is often high-grade and metastatic at diagnosis, conferring a poor prognosis.

A decade in focus: mixed germ cell tumors with choriocarcinoma components.

Introduction: This 10-year registry review aimed to investigate the clinical behaviour and outcomes of mixed germ cell tumours with choriocarcinoma components, a rare and aggressive subtype of testicular cancer, in Saudi Arabia. The study explores the demographic characteristics of affected patients, tumour profiles, and the mortality rate associated with this malignancy. Methods: Utilizing data from the Saudi Cancer Registry, the authors identified 33 cases of mixed germ cell tumours with choriocarcinoma components among 1001 testicular cancer cases recorded between 2008 and 2017. Demographic information, including age, marital status, region of residency, year of diagnosis, and 10-year survival status, were collected. Tumour factors, such as the basis of diagnosis, origin site, behaviour, grade, extension, and laterality, were also analyzed. Results: The majority of cases (78.8%) occurred in the young age group (18-45 years), and most tumours (97%) originated in normally descended testes. Grade IV (undifferentiated anaplastic) tumours and distant metastasis were present in 45.5% of patients. All cases exhibited malignant tumour behaviour. The overall mortality rate was 15%, with a mean time from diagnosis to death of 7.72 months (range: 0.5-21.5 months). Conclusion: Mixed germ cell tumours with choriocarcinoma components are rare and tend to affect younger populations. These tumours demonstrate aggressive clinical behaviour, with a significant proportion presenting with high-grade lesions and metastasis at diagnosis. The observed mortality rate underscores the poor prognosis associated with this malignancy. Our study provides essential insights into the clinical characteristics of this rare tumour subtype in the Saudi Arabian population, emphasizing the need for further research to identify prognostic factors and optimize management strategies for affected patients.

The hidden unicuspid: Recurring aortic stenosis post-valvuloplasty from a unicuspid aortic valve masquerading as bicuspid.

Unicuspid aortic valves (UAV) account for 0.2 % of cardiac valvular disorders and present with early-onset aortic stenosis (AS) during adolescence or early adulthood. We present a case of a 17-year-old male with recurring AS. He was diagnosed with bicuspid aortic valve (BAV) two years previously and treated with balloon valvuloplasty, which relieved symptoms before that. Multimodality imaging work-up revealed the precise morphology of UAV, consistent with the surgical findings. The patient received a St. Jude mechanical valve (St Paul; MN, USA) which resolved his symptoms. A thorough radiologic evaluation is therefore required for the accurate diagnosis of UAVs. While 2-dimensional (2D) transthoracic echocardiography (TTE) often constitutes the initial modality for evaluating UAVs, 3D-TTE, transesophageal echocardiography, and cardiac computed tomography are used as confirmatory diagnostic tools. Balloon valvuloplasty reports good outcomes in BAV but is associated with an increased rate of symptom recurrence, repeated surgical procedures, and higher mortality in UAVs, underscoring the importance of an accurate pre-operative diagnosis. Learning objectives: 1.Unicuspid aortic valve (UAV) should be considered in the differential diagnosis of severe aortic stenosis during childhood.2.3D-transthoracic echocardiogram, transesophageal echocardiogram, and cardiac computed tomography (CT) can confirm the diagnosis of a UAV.3.Cardiac CT can additionally assess for accompanying abnormalities of the great vessels in UAV patients.4.Balloon valvuloplasty reports good outcomes in bicuspid aortic valve but is associated with an increased rate of symptom recurrence in UAV patients.

Neutrophil extracellular traps and long COVID.

Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by a significant number of COVID-19 survivors. The underlying pathophysiology of long COVID has become a topic of intense research discussion. While chronic inflammation in long COVID has received considerable attention, the role of neutrophils, which are the most abundant of all immune cells and primary responders to inflammation, has been unfortunately overlooked, perhaps due to their short lifespan. In this review, we discuss the emerging role of neutrophil extracellular traps (NETs) in the persistent inflammatory response observed in long COVID patients. We present early evidence linking the persistence of NETs to pulmonary fibrosis, cardiovascular abnormalities, and neurological dysfunction in long COVID. Several uncertainties require investigation in future studies. These include the mechanisms by which SARS-CoV-2 brings about sustained neutrophil activation phenotypes after infection resolution; whether the heterogeneity of neutrophils seen in acute SARS-CoV-2 infection persists into the chronic phase; whether the presence of autoantibodies in long COVID can induce NETs and protect them from degradation; whether NETs exert differential, organ-specific effects; specifically which NET components contribute to organ-specific pathologies, such as pulmonary fibrosis; and whether senescent cells can drive NET formation through their pro-inflammatory secretome in long COVID. Answering these questions may pave the way for the development of clinically applicable strategies targeting NETs, providing relief for this emerging health crisis.

Machine learning applications and challenges in graft-versus-host disease: a scoping review.

PURPOSE OF REVIEW: This review delves into the potential of artificial intelligence (AI), particularly machine learning (ML), in enhancing graft-versus-host disease (GVHD) risk assessment, diagnosis, and personalized treatment. RECENT FINDINGS: Recent studies have demonstrated the superiority of ML algorithms over traditional multivariate statistical models in donor selection for allogeneic hematopoietic stem cell transplantation. ML has recently enabled dynamic risk assessment by modeling time-series data, an upgrade from the static, "snapshot" assessment of patients that conventional statistical models and older ML algorithms offer. Regarding diagnosis, a deep learning model, a subset of ML, can accurately identify skin segments affected with chronic GVHD with satisfactory results. ML methods such as Q-learning and deep reinforcement learning have been utilized to develop adaptive treatment strategies (ATS) for the personalized prevention and treatment of acute and chronic GVHD. SUMMARY: To capitalize on these promising advancements, there is a need for large-scale, multicenter collaborations to develop generalizable ML models. Furthermore, addressing pertinent issues such as the implementation of stringent ethical guidelines is crucial before the widespread introduction of AI into GVHD care.

Long-term functional outcomes and complications of microsurgical resection of brainstem cavernous malformations: a systematic review and meta-analysis.

Brainstem cavernous malformations (CMs) encompass up to 20% of all intracranial CMs and are considered more aggressive than cerebral CMs because of their high annual bleeding rates. Microsurgical resection remains the primary treatment modality for CMs, but long-term functional outcomes and complications are heterogenous in the literature. The authors performed a systematic review on brainstem CMs in 4 databases: PubMed, EMBASE, Cochrane library, and Google Scholar. We included studies that reported on the long-term functional outcomes and complications of brainstem CMs microsurgical resection. A meta-analysis was performed and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search yielded 4781 results, of which 19 studies met our inclusion criteria. Microsurgery was performed on 940 patients (mean age 35 years, 46.9% females). Most of the brainstem CMs were located in the pons (n = 475). The pooled proportions of improved, stable, and worsened functional outcomes after microsurgical resection of brainstem CMs were 56.7% (95% CI 48.4-64.6), 28.6% (95% CI 22.4-35.7), and 12.6% (95% CI 9.6-16.2), respectively. CMs located in the medulla were significantly (p = 0.003) associated with a higher proportion of improved outcome compared with those in the pons and midbrain. Complete resection was achieved in 93.3% (95% CI 89.8-95.7). The immediate postoperative complication rate was 37.2% (95% CI 29.3-45.9), with new-onset cranial nerve deficit being the most common complication. The permanent morbidity rate was 17.3% (95% CI 10.5-27.1), with a low mortality rate of 1% from the compiled study population during a mean follow-up of 58 months. Our analysis indicates that microsurgical resection of brainstem CMs can result in favorable long-term functional outcomes with transient complications in the majority of patients. Complete microsurgical resection of the CM is associated with a lower incidence of CM hemorrhage and the morbidity related to it.

Bispecific Antibodies in Hematological Malignancies: A Scoping Review.

Bispecific T-cell engagers (BiTEs) and bispecific antibodies (BiAbs) have revolutionized the treatment landscape of hematological malignancies. By directing T cells towards specific tumor antigens, BiTEs and BiAbs facilitate the T-cell-mediated lysis of neoplastic cells. The success of blinatumomab, a CD19xCD3 BiTE, in acute lymphoblastic leukemia spearheaded the expansive development of BiTEs/BiAbs in the context of hematological neoplasms. Nearly a decade later, numerous BiTEs/BiAbs targeting a range of tumor-associated antigens have transpired in the treatment of multiple myeloma, non-Hodgkin's lymphoma, acute myelogenous leukemia, and acute lymphoblastic leukemia. However, despite their generally favorable safety profiles, particular toxicities such as infections, cytokine release syndrome, myelosuppression, and neurotoxicity after BiAb/BiTE therapy raise valid concerns. Moreover, target antigen loss and the immunosuppressive microenvironment of hematological neoplasms facilitate resistance towards BiTEs/BiAbs. This review aims to highlight the most recent evidence from clinical trials evaluating the safety and efficacy of BiAbs/BiTEs. Additionally, the review will provide mechanistic insights into the limitations of BiAbs whilst outlining practical applications and strategies to overcome these limitations.

Corrigendum: Reprogramming the immunosuppressive tumor microenvironment: exploiting angiogenesis and thrombosis to enhance immunotherapy.

[This corrects the article DOI: 10.3389/fimmu.2023.1200941.].

Reprogramming the immunosuppressive tumor microenvironment: exploiting angiogenesis and thrombosis to enhance immunotherapy.

This review focuses on the immunosuppressive effects of tumor angiogenesis and coagulation on the tumor microenvironment (TME). We summarize previous research efforts leveraging these observations and targeting these processes to enhance immunotherapy outcomes. Clinical trials have documented improved outcomes when combining anti-angiogenic agents and immunotherapy. However, their overall survival benefit over conventional therapy remains limited and certain tumors exhibit poor response to anti-angiogenic therapy. Additionally, whilst preclinical studies have shown several components of the tumor coagulome to curb effective anti-tumor immune responses, the clinical studies reporting combinations of anticoagulants with immunotherapies have demonstrated variable treatment outcomes. By reviewing the current state of the literature on this topic, we address the key questions and future directions in the field, the answers of which are crucial for developing effective strategies to reprogram the TME in order to further the field of cancer immunotherapy.

Tackling the glial scar in spinal cord regeneration: new discoveries and future directions.

Axonal regeneration and functional recovery are poor after spinal cord injury (SCI), typified by the formation of an injury scar. While this scar was traditionally believed to be primarily responsible for axonal regeneration failure, current knowledge takes a more holistic approach that considers the intrinsic growth capacity of axons. Targeting the SCI scar has also not reproducibly yielded nearly the same efficacy in animal models compared to these neuron-directed approaches. These results suggest that the major reason behind central nervous system (CNS) regeneration failure is not the injury scar but a failure to stimulate axon growth adequately. These findings raise questions about whether targeting neuroinflammation and glial scarring still constitute viable translational avenues. We provide a comprehensive review of the dual role of neuroinflammation and scarring after SCI and how future research can produce therapeutic strategies targeting the hurdles to axonal regeneration posed by these processes without compromising neuroprotection.

Neutrophil extracellular traps in central nervous system pathologies: A mini review.

Neutrophils are the first cells to be recruited to sites of acute inflammation and contribute to host defense through phagocytosis, degranulation and neutrophil extracellular traps (NETs). Neutrophils are rarely found in the brain because of the highly selective blood-brain barrier (BBB). However, several diseases disrupt the BBB and cause neuroinflammation. In this regard, neutrophils and NETs have been visualized in the brain after various insults, including traumatic (traumatic brain injury and spinal cord injury), infectious (bacterial meningitis), vascular (ischemic stroke), autoimmune (systemic lupus erythematosus), neurodegenerative (multiple sclerosis and Alzheimer's disease), and neoplastic (glioma) causes. Significantly, preventing neutrophil trafficking into the central nervous system or NET production in these diseases alleviates brain pathology and improves neurocognitive outcomes. This review summarizes the major studies on the contribution of NETs to central nervous system (CNS) disorders.