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

Tumours of the thymus: a cohort study of prognostic factors from the European Society of Thoracic Surgeons database

OBJECTIVES A retrospective database was developed by the European Society of Thoracic Surgeons, collecting patients submitted to surgery for thymic tumours to analyse clinico-pathological prognostic predictors. METHODS A total of 2151 incident cases from 35 institutions were collected from 1990 to 2010. Clinical-pathological characteristics were analysed, including age, gender, associated myasthenia gravis stage (Masaoka), World Health Organization histology, type of thymic tumour [thymoma, thymic carcinoma (TC), neuroendocrine thymic tumour (NETT)], type of resection (complete/incomplete), tumour size, adjuvant therapy and recurrence. Primary outcome was overall survival (OS); secondary outcomes were the proportion of incomplete resections, disease-free survival and the cumulative incidence of recurrence (CIR). RESULTS A total of 2030 patients were analysed for OS (1798 thymomas, 191 TCs and 41 NETTs). Ten-year OS was 0.73 (95% confidence interval 0.69-0.75). Complete resection (R0) was achieved in 88% of the patients. Ten-year CIR was 0.12 (0.10-0.15). Predictors of shorter OS were increased age (P < 0-001), stage [III vs I HR 2.66, 1.80-3.92; IV vs I hazard ratio (HR) 4.41, 2.67-7.26], TC (HR 2.39, 1.68-3.40) and NETT (HR 2.59, 1.35-4.99) vs thymomas and incomplete resection (HR 1.74, 1.18-2.57). Risk of recurrence increased with tumour size (P = 0.003), stage (III vs I HR 5.67, 2.80-11.45; IV vs I HR 13.08, 5.70-30.03) and NETT (HR 7.18, 3.48-14.82). Analysis using a propensity score indicates that the administration of adjuvant therapy was beneficial in increasing OS (HR 0.69, 0.49-0.97) in R0 resections. CONCLUSIONS Masaoka stages III-IV, incomplete resection and non-thymoma histology showed a significant impact in increasing recurrence and in worsening survival. The administration of adjuvant therapy after complete resection is associated with improved surviva

Introducing medical humanities in the medical curriculum in Saudi Arabia: A pedagogical experiment

In a marked shift from the modern positivist materialist philosophy that influenced medical education for more than a century, Western medical educators are now beginning to realize the significance of the spiritual element of human nature. Consensus is currently building up in Europe and North America on the need to give more emphasis to the study of humanities disciplines such as history of medicine, ethics, religion, philosophy, medically related poetry, literature, arts and medical sociology in medical colleges with the aim of allowing graduates to reach to the heart of human learning about meaning of life and death and to become kinder, more reflective practitioners. The medicine taught and practiced during the Islamic civilization era was a vivid example of the unity of the two components of medical knowledge: natural sciences and humanities. It was also a brilliant illustration of medical ethics driven by a divine moral code. This historical fact formed the foundation for the three medical humanities courses presented in this article reporting a pedagogical experiment in preparation for starting a humanities program in Alfaisal University Medical College in Riyadh. In a series of lectures alternating with interactive sessions, active learning strategies were employed in teaching a course on history of medicine during the Islamic era and another on Islamic medical ethics. Furthermore, a third course on medically relevant Arabic poetry was designed and prepared in a similar way. The end-of-the-course feedback comments reflected effectiveness of the courses and highlighted the importance of employing student-centered learning techniques in order to motivate medical students to become critical thinkers, problem solvers, life-long learners and self-learners

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

Nowadays, any healthcare problem should be dealt with in a multidisciplinary approach that employs not only treating the symptoms of the problem but also its source. This simply implies the necessity to produce well-rounded medical graduates (physicians) who can competently integrate clinical knowledge/skills (for disease treatment) and public health knowledge/skills (for disease prevention). Moreover, the medical training (MD/MBBS curriculum) largely gives emphasis to the clinical skills needed to treat individual patients, whereas public health training (MPH degree) emphasizes the methods needed to improve the overall community health. Bridging the gap between patients and community is best achieved through a combined multidisciplinary training in both medicine and public health, that is, dual-degree MBBS-MPH programs are the way forward. In United States, for example, there are >80 medical schools that offer such joint MD-MPH programs, whereas there is none in Saudi Arabia. Herein, I call on higher education bodies to implement dual-degree MBBS-MPH programs in Saudi Arabia. To the best of knowledge, this is the first ever report to call for such an innovative implementation. Also, this short communication briefly sheds light on background, rationale, benefits, curriculum design, and future directions of such programs. The implications of this perspective (i.e. dual-degree MBBS-MPH programs) should not be limited to Saudi Arabia only; rather, it should be contemplated by the other medical curricula in the different countries

Lung-Centric Inflammation of COVID-19: Potential Modulation by Vitamin D

SARS-CoV-2 infects the respiratory tract and leads to the disease entity, COVID-19. Accordingly, the lungs bear the greatest pathologic burden with the major cause of death being respiratory failure. However, organs remote from the initial site of infection (e.g., kidney, heart) are not spared, particularly in severe and fatal cases. Emerging evidence indicates that an excessive inflammatory response coupled with a diminished antiviral defense is pivotal in the initiation and development of COVID-19. A common finding in autopsy specimens is the presence of thrombi in the lungs as well as remote organs, indicative of immunothrombosis. Herein, the role of SARS-CoV-2 in lung inflammation and associated sequelae are reviewed with an emphasis on immunothrombosis. In as much as vitamin D is touted as a supplement to conventional therapies of COVID-19, the impact of this vitamin at various junctures of COVID-19 pathogenesis is also addressed

Clinicodemographic characteristics and prognostic role of myasthenia gravis in thymoma: Experience from a Saudi population

OBJECTIVES: The objectives of the study were to determine the clinicodemographic characteristics and the prognostic role of myasthenia gravis (MG) in thymoma. METHODS: The records of patients who underwent surgical resection of thymoma at King Faisal Specialist Hospital and Research Center in the past 23 years were reviewed. Seventy thymoma patients were finally included and were then categorized based on MG status into the MG group (39 patients) and the non-MG group (31 patients). Collected data included patients' demographic characteristics, tumor characteristics, and postoperative clinical outcomes. All analyses were conducted using SPSS. The comparison between both groups was tested using the Student t-test and Chi-square test for continuous and categorical variables, respectively. A P = 0.05 or less indicated statistical significance. RESULTS: Patients' age ranged from 11 to 76 years, and female predominance was observed (55.7%). Compared to the non-MG group, no difference in patients' gender was observed (P = 0.058); however, MG patients had a younger age (39.30 vs. 48.77, P = 0.0095). No difference was noted between both groups based on the World Health Organization classification (P = 0.398), but MG patients tended to present with less-advanced tumors based on the TNM classification (P = 0.039) and lower stage based on the MASAOKA staging system (P = 0.017). No significant change in tumor size (P = 0.077), resectability (P = 0.507), and adjuvant therapy (P = 0.075) were observed. MG was not significantly associated with postoperative complications, morbidity, or mortality. However, it exhibited a prognostic protective role in terms of lower recurrence (2.56% vs. 35.48%, P = 0.0001) and longer survival duration (18.62 vs. 10.21 years, P < 0.001) as compared to non-MG patients. CONCLUSIONS: MG occurrence in thymoma patients is more likely to occur at a younger age, higher TNM classification, and advanced MASAOKA stage. Although no significant association was noted between MG and complications and mortality, MG exhibited a protective role in thymoma by providing a lower recurrence rate and longer survival duration

Highlights on the Management of Oligometastatic Disease

Purpose: The understanding of oligometastatic disease (OMD) is rapidly evolving and with this comes the ability to utilize a number of modalities that excel in the localized control of disease. It has been identified that there are no clear guidelines based on high-level evidence to standardized approaches toward the management of OMD. These highlights have been developed to provide a road map for all health-care professionals who are involved in the management of OMD to support standardized patient care. Methods: The Saudi Lung Cancer Guidelines Committee is a part of the Saudi Lung Cancer Association which, in turn, is part of the Saudi Thoracic Society. Considering that lung cancer constitutes a major proportion of OMD prevalence, the committee took the initiative to develop national highlights to support the management of OMD within Saudi Arabia. The committee members are national clinical leaders who collaborated with international expertise to establish these highlights to serve as a general clinical pathway in the management of OMD. Results: Standardization of the indications to diagnose oligometastases and patient selection criteria including ineligibility criteria for treatment are the basis of the highlights. Treatment approaches including surgical and the variety of radiotherapeutical options are discussed in relation to specific oligometastatic sites. Acceptable measurements for response to treatment and the future for the treatment of OMD conclude the development of the highlights. Conclusion: These are the first national highlights addressing this important disease in oncology. The implementation of these highlights as guidelines requires a robust multidisciplinary team and access to specific technology and expertise. These highlights are based on the most recent findings within the literature but will require repeated review and updating due to this rapidly evolving field in disease management

Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: A systematic review and meta-analysis

Background Post-acute COVID-19 Syndrome is now recognized as a complex systemic disease that is associated with substantial morbidity. Objectives To estimate the prevalence of persistent symptoms and signs at least 12 weeks after acute COVID-19 at different follow-up periods. Data sources Searches were conducted up to October 2021 in Ovid Embase, Ovid Medline, and PubMed. Study eligibility criteria Articles in English that reported the prevalence of persistent symptoms among individuals with confirmed SARS-CoV-2 infection and included at least 50 patients with a follow-up of at least 12 weeks after acute illness. Methods Random-effect meta-analysis was performed to produce pooled prevalence for each symptom at 4 different follow-up time intervals. Between-studies heterogeneity was evaluated using the I2 statistic and was explored via meta-regression, considering several a priori study level variables. Risk of bias was assessed using the Joanna Briggs Institute (JBI) tool and the Newcastle-Ottawa Scale for prevalence studies and comparative studies, respectively. Results After screening 3209 studies, a total of 63 studies were eligible, with a total COVID-19 population of 257,348. The most commonly reported symptoms were fatigue, dyspnea, sleep disorder and concentration difficulty (32%, 25%, 24%, and 22% respectively at 3-12 months follow-up). There was substantial between-studies heterogeneity for all reported symptoms prevalence. Meta-regressions identified statistically significant effect modifiers: world region, male gender, diabetes mellitus, disease severity and overall study quality score. Five of six studies including a comparator group consisting of COVID-19 negative cases observed significant adjusted associations between COVID-19 and several long-term symptoms. Conclusions This systematic review found that a large proportion of patients experience PACS 3 to 12 months after recovery from the acute phase of COVD-19. However, available studies of PACS are highly heterogeneous. Future studies need to have appropriate comparator groups, standardized symptoms definitions and measurements and longer follow-up