Donor blood cultures and outcomes after lung transplantation: a single-center report.

BACKGROUND: Transplanting lungs from donors with positive blood cultures has not been shown to adversely affect survival. There is limited evidence for potential effects on other outcomes, such as hospital course, graft function, and transmission of infection. METHODS: This retrospective cohort study included adult patients who underwent lung-only transplantation for the first time between March 2010 and December 2022. Outcomes of patients whose donors had positive blood cultures within 72 h of transplant were compared to patients whose donors had negative blood cultures. RESULTS: Twenty-five (10.8%) of 232 donors had positive blood cultures, including a single, unexpected case with candidemia. The most commonly isolated bacteria were Enterobacter cloacae (n = 5), Klebsiella pneumoniae (n = 5), Acinetobacter baumannii (n = 3), Pseudomonas aeruginosa (n = 3), and Staphylococcus aureus (n = 3). Eleven donors had identical bacteria in their respiratory cultures. All patients who were transplanted from donors with positive blood cultures survived beyond 90 days. Positive donor blood cultures were not associated with longer hospital stay, in-hospital complications, acute cellular rejection, or the achievement of 80% predicted forced expiratory volume in the first second. Probable transmission of donor bacteremia occurred in only two cases (both with S. aureus). These two donors had positive respiratory cultures with the same organism. CONCLUSION: The study did not find an increased risk of adverse events when transplanting lungs from donors with positive blood cultures. Allograft cultures may be more predictive of the risk of transmitting infections.

Beyond the curriculum: unveiling medical students' drivers and barriers to research participation at Alfaisal University.

Medical education continually adapts to the needs of future health care professionals, with student motivation in research being a pivotal aspect. This study at Alfaisal University aimed to explore the motivations, benefits, and challenges faced by medical students in extracurricular research activities. Using a mixed-method approach, we combined quantitative surveys with qualitative group interviews. Findings revealed that both extrinsic (e.g., enhancing postgraduate training prospects) and intrinsic (e.g., personal interest and skill refinement) factors significantly motivate students to be involved in research activities. Participants unanimously acknowledged skill enhancement, particularly in literature comprehension, creative ideation, and networking. However, challenges such as conflicts with course scheduling, lack of hands-on experiences, and mentorship issues were identified as potential barriers to research participation. Addressing these barriers and understanding motivations can inform the design of research programs, enhancing the overall student research experience. This study underscores the importance of research in medical education, emphasizing the need for institutions to prioritize addressing challenges and leveraging benefits to prepare medical students for a research-integrated clinical future.NEW & NOTEWORTHY This article examines the motivating factors and obstacles of extracurricular research in Alfaisal University, Saudi Arabia. The study utilizes a mixed methodology of online surveys and in-person group interviews to gain insights from the medical students of the university. We revealed several extrinsic and intrinsic motivators that drove the students; however, there remain several challenges to students during their research journey. Addressing these challenges will help the students obtain a more fruitful, educational research experience.

Association between 17q21 variants and asthma predisposition in Pashtun population from Pakistan.

OBJECTIVE: Asthma is a heterogeneous and genetically complex respiratory disease, and more than 300 million people are affected worldwide. In this study, frequencies of four SNPs (rs3816470, rs7216389, rs8067378, rs12603332) in chromosome 17q21 region were analyzed and their relationship with the asthma susceptibility, in the Pashtun population of Khyber Pakhtunkhwa province (KPK) of Pakistan were investigated. METHODS: DNA samples from 500 subjects (asthma cases/controls) were genotyped by Sanger sequencing. Chi-square tests, logistic regression analysis, linkage disequilibrium, and haplotype analysis techniques were applied to study the association of the SNPs with asthma. RESULTS: Genetic models, including recessive, dominant, co-dominant, over-dominant, and additive, were tested. The frequencies of alleles T/T at rs3816470 (OR = 1.91; 95%CI = 1.15-3.18; p = .011*) and rs7216389 (OR = 2.14; 95%CI = 1.21-3.79; p = .0076*), A/A at rs 8067378 (OR = 1.89; 95%CI = 1.17-3.06; p = .0081*), C/C at rs12603332 (OR = 1.97; 95%CI = 1.18-3.27; p = .008*), under recessive models, respectively, were significantly (p-values < .0125) associated with asthma susceptibility. The frequencies of T/T genotype in rs3816470 (OR = 6.01; 95%CI = 2.48-14.60; p = .000147*), and rs7216389 (OR = 5.05; 95%CI = 1.79-14.21; p = .003296*), and C/C at rs12603332 (OR = 2.64; 95%CI = 1.11-6.32; p = .019063*), were significantly (p-values < .0125) associated with asthma susceptibility in Pashtun women by stratified analysis based on age and gender. Similarly, three unique haplotypes were found associated with disease development and protective effect in female and male subjects. Linkage disequilibrium analysis presented a strong linkage (≥80%) between SNP variants and predicted their co-inheritance in the studied population. CONCLUSION: The 17q21 variants (rs3816470, rs7216389, rs12603332) were found significantly (p-values < .0125) associated with asthma predisposition in the Pashtun population of KPK exclusively in the female asthmatic cases.Supplemental data for this article can be accessed.

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.

Development and Validation of ScriptTaq COVID PCR: An In-House Multiplex rRT-PCR for Low-Cost Detection.

The COVID-19 pandemic necessitated an extensive testing for active SARS-CoV-2 infection. However, securing affordable diagnostic tests is a struggle for low-resource settings. We report herein the development and validation of an in-house multiplex real-time RT-PCR diagnostic test for the detection of active COVID-19 infection (ScriptTaq COVID PCR). Furthermore, we describe two methods for RNA extraction using either an in-house silica column or silica-coated magnetic beads to replace commercial RNA extraction kits. Different buffer formulations for silica column and silica-coated magnetic beads were tested and used for RNA isolation. Taq polymerase enzyme and thermostable reverse transcriptase enzyme were purified from bacterial clones. Primers/probes sequences published by the WHO and CDC were used for the qualitative detection of the RNA-dependent RNA polymerase (RdRp) and nucleocapsid (N) genes, respectively. ScriptTaq COVID PCR assay was able to detect up to 100 copies per reaction of the viral RdRP and N genes. The test demonstrated an overall agreement of 95.4%, a positive percent agreement (PPA) of 90.2%, and a negative percent agreement (NPA) of 100.0% when compared with two commercially available kits. ScriptTaq COVID PCR diagnostic test is a specific, sensitive, and low-cost alternative for low-resource settings.

Burnout in oncology: Magnitude, risk factors and screening among professionals from Middle East and North Africa (BOMENA study).

BACKGROUND: Burnout (BO) among oncology professionals (OP) is increasingly being recognized. Early recognition and intervention can positively affect the quality of care and patient safety. This study investigated the prevalence, work and lifestyle factors affecting BO among OPs in the Middle East and North Africa (MENA). METHODS: An online survey was conducted among MENA OPs between 10 February and 15 March 2020, using the validated Maslach Burnout Inventory of emotional exhaustion (EE), depersonalization (DP) and personal accomplishment (PA), including questions regarding demography/work-related factors and attitudes towards oncology. Data were analysed to measure BO prevalence and risk factors and explore a screening question for BO. RESULTS: Of 1054 respondents, 1017 participants (64% medical oncologists, 77% aged less than 45 years, 55% female, 74% married, 67% with children and 40% practiced a hobby) were eligible. The BO prevalence was 68% with high levels of EE and DP (35% and 57% of participants, respectively) and low PA scores (49%). BO was significantly associated with age less than 44 years, administrative work greater than 25% per day and the thought of quitting oncology (TQ). Practising a hobby, enjoying oncology communication and appreciating oncology work-life balance were associated with a reduced BO score and prevalence. North African countries reported the highest BO prevalence. Lack of BO education/support was identified among 72% of participants and TQ-predicted burnout in 77%. CONCLUSIONS: This is the largest BO study in MENA. The BO prevalence was high and several modifiable risk factors were identified, requiring urgent action. TQ is a simple and reliable screening tool for BO.

Three dimensional echocardiographic imaging of multiple recurrent myxomas.

We report a case of a recurrence of 5 cardiac myxomas in both atria with atypical anatomical features difficult to image. Although a multimodality imaging was performed, three-dimensional echocardiography (3DE) was the only technique able to correctly identify all the recurrences and the anatomical characteristics of the myxomas. MRI detected the blood supply of the mass but even after careful review was able to identify only 4 of the 5 lesions. Even though it was already reported the usefulness of 3DE to better delineate the site of attachment of cardiac tumors, it was never reported its sensibility in the setting of multiple myxomas; this case highlights the ability of the 3DE in this challenging scenario and its potential for being considered the key adjunctive modality for the anatomy when advanced surgical plan is required.

Contrast transesophageal three dimensional echocardiographic imaging for patent foramen ovale: a needful role?

We report a case of a 55-year-old male admitted for cardiogenic embolic ischemic stroke work up. A transesophageal (TE) echocardiography (E) with contrast study to rule out patent foramen ovale (PFO) was performed; two-dimensional (2D) analysis did not detect any bubbles passage during Valsalva manoeuvre in the standard 2D cross sectional planes; further real time three-dimensional (3D) TEE imaging revealed passage of bubbles in the left atrium (LA) by both real-time 3DTEE imaging and by the 2D unconventional cross-sectional planes allowed by 3DTEE imaging. Even though 2DTEE is considered to be the gold standard modality for diagnosing PFO, it has some limitations. It has never been reported about usefulness of 3DTEE in PFO imaging. Even in the presence of only a report, our case suggests that 3DE could have an additional value and will compliment 2D imaging in PFO assessment.

Medical education dilemma: How can we best accommodate basic sciences in a curriculum for 21st century medical students? 1.

Over the years, the medical curriculum has been changed to accommodate a variety of evolving disciplines and an exploding scientific knowledge of the basic sciences to prepare "a competent physician" of the 21st century. Therefore, we must be innovative in our approach of curricular development if we wish to continue to incorporate new basic sciences knowledge in the face of decreasing contact hours to satisfy the buzz word, "integration". Certainly, the challenges are phenomenal. The question how to best integrate basic sciences, is not easy to answer as the objectives of the courses and outcome vary from one medical school to another and the fact is, one size does not fit all. However, if we believe that basic sciences are the language of medicine and foundation of clinical knowledge, then we must resolve this ongoing dilemma by introducing basic sciences through a better alignment in a given curriculum. The purpose of this review is to evaluate different curricular models for their basic sciences content and address their strengths and weaknesses. In addition, we will introduce a spiral design to integrate basic sciences for senior students. Finally, we will provide some insight as to how learning and retention of basic science content can be sustained.

Interest and perceived barriers toward careers in academic medicine among medical students at Alfaisal University - College of Medicine: A Saudi Arabian perspective.

AIMS: [1] Identify the percentage of undergraduate students who are interested in academic medicine (AM) careers, [2] Explore the relationship between students' characteristics, previous experiences and interest in AM careers and [3] Determine students' perceived barriers toward AM careers at Alfaisal University - College of Medicine. METHODS: An online, anonymous, random, self-rating survey was administered during spring 2013-2014 to second-year and third-year students (n = 302). Chi-square test was used to correlate between interest in AM careers and students' characteristics. Mann-Whitney U-test was used to compare the mean 5-point Likert scale responses between male and female students. RESULTS: A total of 231 students participated in the survey (response rate: 76.5%). A total of 32 students (13.9%) expressed interest in AM careers, and this percentage significantly differed by gender, academic year, interest in teaching and research and previous research experiences (p < 0.05). The top three barriers were "lower income" (77.5%), "competing pressures to fulfill clinical-teaching-research duties" (73.6%) and "lack of career advising" (69.7%). As opposed to males, females achieved higher statistically significant differences of means regarding: "competing pressures to fulfill clinical-teaching-research duties" (p < 0.001) and "lack of same-gender role models in AM careers" (p < 0.000). CONCLUSIONS: AM careers were unpopular by students. Curricular, extracurricular and institutional measures should be implemented to rectify this dilemma.

Dual-degree MBBS-PhD programs in Saudi Arabia: A call for implementation.

Engaging medical students in scholarly research activities and producing clinically competent and research-oriented medical workforces are essential demands, particularly in developing countries. Dual-degree MD-PhD programs offer simultaneous rigorous education in medicine and research, and train its graduates (physician-scientists) to successfully catalyze translational research evolutions. Literature fundamentally identifies dual-degree MD-PhD programs as the single most important, well-established, popular and influential programs toward commencing physician-scientist professions. While the physician-scientist population is alarmingly vanishing in the West with ongoing efforts to reverse this undesired trend, such population is largely nonexisting, unfortunately to start with, in Saudi Arabia. This is simply because no single dual-degree MBBS-PhD program is yet established in Saudi Arabia. Herein, we call on the Saudi Higher Education bodies to implement dual-degree MBBS-PhD programs with anticipated generation of competent physician-scientists in Saudi Arabia. To the best of our knowledge, this is the first ever report to call for such innovative implementation.

Gut-Modulating Agents and Amyotrophic Lateral Sclerosis: Current Evidence and Future Perspectives.

Amyotrophic Lateral Sclerosis (ALS) is a highly fatal neurodegenerative disorder characterized by the progressive wasting and paralysis of voluntary muscle. Despite extensive research, the etiology of ALS remains elusive, and effective treatment options are limited. However, recent evidence implicates gut dysbiosis and gut-brain axis (GBA) dysfunction in ALS pathogenesis. Alterations to the composition and diversity of microbial communities within the gut flora have been consistently observed in ALS patients. These changes are often correlated with disease progression and patient outcome, suggesting that GBA modulation may have therapeutic potential. Indeed, targeting the gut microbiota has been shown to be neuroprotective in several animal models, alleviating motor symptoms and mitigating disease progression. However, the translation of these findings to human patients is challenging due to the complexity of ALS pathology and the varying diversity of gut microbiota. This review comprehensively summarizes the current literature on ALS-related gut dysbiosis, focusing on the implications of GBA dysfunction. It delineates three main mechanisms by which dysbiosis contributes to ALS pathology: compromised intestinal barrier integrity, metabolic dysfunction, and immune dysregulation. It also examines preclinical evidence on the therapeutic potential of gut-microbiota-modulating agents (categorized as prebiotics, probiotics, and postbiotics) in ALS.

Urinary Biomarkers for Lupus Nephritis: A Systems Biology Approach.

Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder. Kidney involvement, termed lupus nephritis (LN), is seen in 40-60% of patients with systemic lupus erythematosus (SLE). After the diagnosis, serial measurement of proteinuria is the most common method of monitoring treatment response and progression. However, present treatments for LN-corticosteroids and immunosuppressants-target inflammation, not proteinuria. Furthermore, subclinical renal inflammation can persist despite improving proteinuria. Serial kidney biopsies-the gold standard for disease monitoring-are also not feasible due to their inherent risk of complications. Biomarkers that reflect the underlying renal inflammatory process and better predict LN progression and treatment response are urgently needed. Urinary biomarkers are particularly relevant as they can be measured non-invasively and may better reflect the compartmentalized renal response in LN, unlike serum studies that are non-specific to the kidney. The past decade has overseen a boom in applying cutting-edge technologies to dissect the pathogenesis of diseases at the molecular and cellular levels. Using these technologies in LN is beginning to reveal novel disease biomarkers and therapeutic targets for LN, potentially improving patient outcomes if successfully translated to clinical practice.

Unraveling the epigenetic fabric of type 2 diabetes mellitus: pathogenic mechanisms and therapeutic implications.

Type 2 diabetes mellitus (T2DM) is a rapidly escalating global health concern, with its prevalence projected to increase significantly in the near future. This review delves into the intricate role of epigenetic modifications - including DNA methylation, histone acetylation, and micro-ribonucleic acid (miRNA) expression - in the pathogenesis and progression of T2DM. We critically examine how these epigenetic changes contribute to the onset and exacerbation of T2DM by influencing key pathogenic processes such as obesity, insulin resistance, ß-cell dysfunction, cellular senescence, and mitochondrial dysfunction. Furthermore, we explore the involvement of epigenetic dysregulation in T2DM-associated complications, including diabetic retinopathy, atherosclerosis, neuropathy, and cardiomyopathy. This review highlights recent studies that underscore the diagnostic and therapeutic potential of targeting epigenetic modifications in T2DM. We also provide an overview of the impact of lifestyle factors such as exercise and diet on the epigenetic landscape of T2DM, underscoring their relevance in disease management. Our synthesis of the current literature aims to illuminate the complex epigenetic underpinnings of T2DM, offering insights into novel preventative and therapeutic strategies that could revolutionize its management.

Unveiling the Web: Exploring the Multifaceted Role of Neutrophil Extracellular Traps in Ocular Health and Disease.

Neutrophil extracellular traps (NETs) play an essential role in antimicrobial defense. However, NETs have also been shown to promote and mediate a wide spectrum of diseases, including cancer, diabetes mellitus, cardiovascular diseases, and ocular diseases. Data regarding NETs in ocular diseases remain limited. In physiological conditions, NETs protect the eye from debris and cleave proinflammatory cytokines, including several interleukins. On the other hand, NETs play a role in corneal diseases, such as dry eye disease and ocular graft-versus-host disease, where they promote acinar atrophy and delayed wound healing. Additionally, NET levels positively correlate with increased severity of uveitis. NETs have also been described in the context of diabetic retinopathy. Although increased NET biomarkers are associated with an increased risk of the disease, NETs also assist in the elimination of pathological blood vessels and the regeneration of normal vessels. Targeting NET pathways for the treatment of ocular diseases has shown promising outcomes; however, more studies are still needed in this regard. In this article, we summarize the literature on the protective roles of NETs in the eye. Then, we describe their pathogenetic effects in ocular diseases, including those of the cornea, uvea, and retinal blood vessels. Finally, we describe the therapeutic implications of targeting NETs in such conditions.

Donor respiratory multidrug-resistant bacteria and lung transplantation outcomes.

RATIONALE: Respiratory culture screening is mandatory for all potential lung transplant donors. There is limited evidence on the significance of donor multidrug-resistant (MDR) bacteria on transplant outcomes. Establishing the safety of allografts colonized with MDR bacteria has implications for widening an already limited donor pool. OBJECTIVES: We aimed to describe the prevalence of respiratory MDR bacteria among our donor population and to test for associations with posttransplant outcomes. METHODS: This retrospective observational study included all adult patients who underwent lung-only transplantation for the first time at King Faisal Specialist Hospital & Research Centre in Riyadh from January 2015 through May 2022. The study evaluated donor bronchoalveolar lavage and bronchial swab cultures. MAIN RESULTS: Sixty-seven of 181 donors (37%) had respiratory MDR bacteria, most commonly MDR Acinetobacter baumannii (n = 24), methicillin-resistant Staphylococcus aureus (n = 18), MDR Klebsiella pneumoniae (n = 8), MDR Pseudomonas aeruginosa (n = 7), and Stenotrophomonas maltophilia (n = 6). Donor respiratory MDR bacteria were not significantly associated with allograft survival or chronic lung allograft dysfunction (CLAD) in adjusted hazard models. Sensitivity analyses revealed an increased risk for 90-day mortality among recipients of allografts with MDR Klebsiella pneumoniae (n = 6 with strains resistant to a carbapenem and n = 2 resistant to a third-generation cephalosporin only) compared to those receiving culture-negative allografts (25.0% versus 11.1%, p = 0.04). MDR Klebsiella pneumoniae (aHR 3.31, 95%CI 0.95-11.56) and Stenotrophomonas maltophilia (aHR 5.35, 95%CI 1.26-22.77) were associated with an increased risk for CLAD compared to negative cultures. CONCLUSION: Our data suggest the potential safety of using lung allografts with MDR bacteria in the setting of appropriate prophylaxis; however, caution should be exercised in the case of MDR Klebsiella pneumoniae.

Bioengineered Organoids Offer New Possibilities for Liver Cancer Studies: A Review of Key Milestones and Challenges.

Hepatic cancer is widely regarded as the leading cause of cancer-related mortality worldwide. Despite recent advances in treatment options, the prognosis of liver cancer remains poor. Therefore, there is an urgent need to develop more representative in vitro models of liver cancer for pathophysiology and drug screening studies. Fortunately, an exciting new development for generating liver models in recent years has been the advent of organoid technology. Organoid models hold huge potential as an in vitro research tool because they can recapitulate the spatial architecture of primary liver cancers and maintain the molecular and functional variations of the native tissue counterparts during long-term culture in vitro. This review provides a comprehensive overview and discussion of the establishment and application of liver organoid models in vitro. Bioengineering strategies used to construct organoid models are also discussed. In addition, the clinical potential and other relevant applications of liver organoid models in different functional states are explored. In the end, this review discusses current limitations and future prospects to encourage further development.

Impact of COVID-19 on Management and Outcomes of Oncology Patients: Results of MENA COVID-19 and Cancer Registry (MCCR).

Introduction: Despite extensive studies of the impact of COVID-19 on patients with cancer, there is a dearth of information from the Middle East and North Africa (MENA) region. Our study aimed to report pertinent MENA COVID-19 and Cancer Registry (MCCR) findings on patient management and outcomes. Methods: MCCR was adapted from the American Society of Clinical Oncology COVID-19 Registry to collect data specifically from patients with cancer and SARS-CoV-2 infection from 12 centers in eight countries including Saudi Arabia, Jordan, Lebanon, Turkey, Egypt, Algeria, United Arab Emirates, and Morocco. The Registry included data on patients and disease characteristics, treatment, and patient outcomes. Logistic regression was used to assess associations with mortality. Results: Between November 29, 2020, and June 8, 2021, data were captured on 2008 patients diagnosed with COVID-19 from the beginning of the pandemic. Median age was 56 years (16-98), 56.4% were females, and 26% were current or ex-smokers. Breast cancer (28.5%) was the leading diagnosis and 50.5% had metastatic disease. Delays of planned treatment (>14 days) occurred in 80.3% for surgery, 48.8% for radiation therapy, and 32.9% for systemic therapy. Significant reduction in the delays of all three treatment modalities occurred after June 1, 2020. All-cause mortality rates at 30 and 90 days were 17.1% and 23.4%, respectively. All-cause mortality rates at 30 days did not change significantly after June 1, 2020; however, 90-day mortality increased from 33.4% to 42.9% before and after that date (p = 0.015). Multivariable regression analysis showed the following predictors of higher 30- and 90-day mortality: age older than 70 years, having metastatic disease, disease progression, and being off chemotherapy. Conclusion: Patients with cancer in the MENA region experienced similar risks and outcome of COVID-19 as reported in other populations. Although there were fewer treatment delays after June 1, 2020, 90-day mortality increased, which may be attributed to other risk factors such as disease progression or new patients who presented with more advanced disease.

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.

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.