Intradural cystic schwannomas of the spine: A case-based systematic review of an unusual tumor.

Introduction: Cystic schwannomas have only been reported in a few case reports/series. As a result, they may be misdiagnosed and a standardized management approach remains challenging to establish. Research question: The aim of this study was to compile all reported cases of cystic schwannomas and analyze the perioperative course based on a systematic review of the literature with an additional two cases from the authors' experience. Material and methods: We conducted a search of MEDLINE and CENTRAL databases for spinal intradural extramedullary cystic schwannomas, in accordance to the PRISMA statement. All title/abstracts were screened, and a full-text review of the remaining articles was conducted. The results were compiled in tables and summarized using means and standard deviation (SD), median and interquartile range, and percentage and 95% confidence intervals. Results: We identified 263 articles, of which 35, which reported 54 cases, were included. Including our case-reports (n = 56), patients had a mean age of 47.7 years (SD ± 13.0 years) at presentation, 57% were males, and most lesions were lumbar (43%). The most common symptoms were pain (82%) and muscle weakness (68%) with 84% of patients showing neurological findings. 70% of patients showed a complete relief of symptoms after surgery and 96% reported improvement. Only four complications were reported. Discussion and conclusion: Schwannomas should be considered in the differential diagnosis of intradural extramedullary cystic lesions. Patients typically present with subacute to chronic pain and/or neurologic changes. Surgical resection is the primary therapeutic modality and usually has a good to excellent outcome.

Impact of Supine versus Prone Positioning on Segmental Lumbar Lordosis in Patients Undergoing ALIF Followed by PSF: A Comparative Study.

Background: Anterior lumbar interbody fusion (ALIF) and posterior spinal fusion (PSF) play pivotal roles in restoring lumbar lordosis in spinal surgery. There is an ongoing debate between combined single-position surgery and traditional prone-position PSF for optimizing segmental lumbar lordosis. Methods: This retrospective study analyzed 59 patients who underwent ALIF in the supine position followed by PSF in the prone position at a single institution. Cobb angles were measured preoperatively, post-ALIF, and post-PSF using X-ray imaging. One-way repeated measures ANOVA and post-hoc analyses with Bonferroni adjustment were employed to compare mean Cobb angles at different time points. Cohen's d effect sizes were calculated to assess the magnitude of changes. Sample size calculations were performed to ensure statistical power. Results: The mean segmental Cobb angle significantly increased from preoperative (32.2 ± 13.8 degrees) to post-ALIF (42.2 ± 14.3 degrees, Cohen's d: -0.71, p < 0.0001) and post-PSF (43.6 ± 14.6 degrees, Cohen's d: -0.80, p < 0.0001). There was no significant difference between Cobb angles after ALIF and after PSF (Cohen's d: -0.10, p = 0.14). The findings remained consistent when Cobb angles were analyzed separately for single-screw and double-screw ALIF constructs. Conclusions: Both supine ALIF and prone PSF significantly increased segmental lumbar lordosis compared to preoperative measurements. The negligible difference between post-ALIF and post-PSF lordosis suggests that supine ALIF followed by prone PSF can be an effective approach, providing flexibility in surgical positioning without compromising lordosis improvement.

Advancements in neuroregenerative and neuroprotective therapies for traumatic spinal cord injury.

Traumatic spinal cord injuries (SCIs) continue to be a major healthcare concern, with a rising prevalence worldwide. In response to this growing medical challenge, considerable scientific attention has been devoted to developing neuroprotective and neuroregenerative strategies aimed at improving the prognosis and quality of life for individuals with SCIs. This comprehensive review aims to provide an up-to-date and thorough overview of the latest neuroregenerative and neuroprotective therapies currently under investigation. These strategies encompass a multifaceted approach that include neuropharmacological interventions, cell-based therapies, and other promising strategies such as biomaterial scaffolds and neuro-modulation therapies. In addition, the review discusses the importance of acute clinical management, including the role of hemodynamic management as well as timing and technical aspects of surgery as key factors mitigating the secondary injury following SCI. In conclusion, this review underscores the ongoing scientific efforts to enhance patient outcomes and quality of life, focusing on upcoming strategies for the management of traumatic SCI. Each section provides a working knowledge of the fundamental preclinical and patient trials relevant to clinicians while underscoring the pathophysiologic rationale for the therapies.

Screening for pancreatic cancer in high-risk individuals using MRI: optimization of scan techniques to detect small lesions.

Pancreatic cancer has a dismal prognosis in the general population. However, early detection and treatment of disease in high-risk individuals can improve survival, as patients with localized disease and especially patients with lesions smaller than 10 mm show greatly improved 5-year survival rates. To achieve early detection through MRI surveillance programs, optimization of imaging is required. Advances in MRI technologies in both hardware and software over the years have enabled reliable detection of pancreatic cancer at a small size and early stage. Standardization of dedicated imaging protocols for the pancreas are still lacking. In this review we discuss state of the art scan techniques, sequences, reduction of artifacts and imaging strategies that enable early detection of lesions. Furthermore, we present the imaging features of small pancreatic cancers from a large cohort of high-risk individuals. Refinement of MRI techniques, increased scan quality and the use of artificial intelligence may further improve early detection and the prognosis of pancreatic cancer in a screening setting.

THE ADDED VALUE OF BLOOD GLUCOSE MONITORING IN HIGH-RISK INDIVIDUALS UNDERGOING PANCREATIC CANCER SURVEILLANCE.

OBJECTIVES: The study aimed to investigate the added value of blood glucose monitoring in high-risk individuals (HRIs) participating in pancreatic cancer surveillance. METHODS: HRIs with a CDKN2A/p16 germline pathogenic variant (PV) participating in pancreatic cancer surveillance were included in this study. Multivariable logistic regression was performed to assess the relationship between new-onset diabetes (NOD) and pancreatic ductal adenocarcinoma (PDAC). To quantify the diagnostic performance of NOD as a marker for PDAC, receiver operating characteristic curve with area under the curve (AUC) was computed. RESULTS: In total, 220 HRIs were included between 2000-2019. Median age was 61 (IQR 53-71) years and 62.7% of participants were female. During the study period, 26 (11.8%) HRIs developed NOD, of whom 5 (19.2%) later developed PDAC. The other 23 (82.1%) PDAC cases remained NOD-free. Multivariable analysis showed no statistically significant relationship between NOD and PDAC (OR 1.21; 95% CI, 0.39-3.78) and four out of five PDAC cases appeared to have NOD within three months before diagnosis. Furthermore, NOD did not differentiate between HRIs with- and without PDAC (AUC 0.54; 95% CI, 0.46-0.61). CONCLUSIONS: In this study we found no added value for longitudinal glucose monitoring in CDKN2A PV carriers participating in an imaging-based pancreatic cancer surveillance program.

Experience with the utilization of new-generation shared-control robotic system for spinal instrumentation.

BACKGROUND: Robotic assistance in spine surgery is emerging as an accurate, effective and enabling technology utilized in the treatment of patients with surgical spinal pathology. The safety and reproducibility of robotic assistance in the placement of pedicle screw instrumentation is still being investigated. The objective of this study was to present our experience of instrumented spinal fusion utilizing an intraoperative robotic guidance system. METHODS: We retrospectively reviewed all cases of spinal instrumentation of the thoracic and lumbo-sacral spine using the Mazor X robotic system (Medtronic Inc, Minneapolis, MN, USA), performed at our institution by one surgeon between July 2017 and June 2020. Wilcoxon Rank test was used to compare time taken to place each screw during the first 20 cases and the cases thereafter. RESULTS: A total of 28 patients were included. A total of 159 screws were placed using the Mazor X robotic system. The overall mean time for screw placement was 7.8±2.3 minutes and there was a significant reduction in the mean time for screw placement after the 20th case or 120 screws (8.70 vs. 5.42 min, P=0.008). No postoperative neurologic deficit or new radiculopathy was noted to occur secondary to hardware placement. No revision surgery was required for replacement or removal of a mispositioned screw. CONCLUSIONS: From this single-center, single-surgeon series we conclude that robot-assisted spine surgery can be safely and efficiently integrated into the operating room workflow, which improves after a learning curve of approximately 20 operative interventions. We found robot-assisted spinal instrumentation to be reliable, safe, effective and highly precise.

Aspects and outcomes of surveillance for individuals at high-risk of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths and is associated with a poor prognosis. The majority of these cancers are detected at a late stage, contributing to the bad prognosis. This underscores the need for novel, enhanced early detection strategies to improve the outcomes. While population-based screening is not recommended due to the relatively low incidence of PDAC, surveillance is recommended for individuals at high risk for PDAC due to their increased incidence of the disease. However, the outcomes of pancreatic cancer surveillance in high-risk individuals are not sorted out yet. In this review, we will address the identification of individuals at high risk for PDAC, discuss the objectives and targets of surveillance, outline how surveillance programs are organized, summarize the outcomes of high-risk individuals undergoing pancreatic cancer surveillance, and conclude with a future perspective on pancreatic cancer surveillance and novel developments.

Targeting nicotinamide N-methyltransferase decreased aggressiveness of osteosarcoma cells.

BACKGROUND: Osteosarcoma (OS) is a primary bone malignancy that mostly affects young people, characterized by high metastatic potential, and a marked chemoresistance that is responsible for disease relapse in most patients. Therefore, it is necessary to identify novel molecules to setup targeted strategies to improve the clinical outcome. The enzyme nicotinamide N-methyltransferase (NNMT) catalyses the N-methylation of nicotinamide and other analogs, playing a crucial role in the biotransformation of drugs and xenobiotics. NNMT overexpression was reported in a wide variety of cancers, and several studies demonstrated that is able to promote cell proliferation, migration and resistance to chemotherapy. The aim of this study was to explore the potential involvement of NNMT in OS. METHODS: Immunohistochemical analyses have been performed to evaluate NNMT expression in selected OS and healthy bone tissue samples. Subsequently, OS cell lines have been transfected with vectors targeting NNMT mRNA (shRNAs) and the impact of this downregulation on migration, cell proliferation, and response to chemotherapeutic treatment was also analysed by wound healing, MTT, SRB and Trypan blue assays, respectively. RESULTS: Results showed that OS samples display a significantly higher NNMT expression compared with healthy tissue. Preliminary results suggest that NNMT silencing in OS cell lines is associated to a decrease of cell proliferation and migration, as well as to enhanced sensitivity to chemotherapy. Data obtained showed that NNMT may represent an interesting marker for OS detection and a promising target for effective anti-cancer therapy.

Process Mass Intensity (PMI): A Holistic Analysis of Current Peptide Manufacturing Processes Informs Sustainability in Peptide Synthesis.

Small molecule therapeutics represent the majority of the FDA-approved drugs. Yet, many attractive targets are poorly tractable by small molecules, generating a need for new therapeutic modalities. Due to their biocompatibility profile and structural versatility, peptide-based therapeutics are a possible solution. Additionally, in the past two decades, advances in peptide design, delivery, formulation, and devices have occurred, making therapeutic peptides an attractive modality. However, peptide manufacturing is often limited to solid-phase peptide synthesis (SPPS), liquid phase peptide synthesis (LPPS), and to a lesser extent hybrid SPPS/LPPS, with SPPS emerging as a predominant platform technology for peptide synthesis. SPPS involves the use of excess solvents and reagents which negatively impact the environment, thus highlighting the need for newer technologies to reduce the environmental footprint. Herein, fourteen American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable (ACS GCIPR) member companies with peptide-based therapeutics in their portfolio have compiled Process Mass Intensity (PMI) metrics to help inform the sustainability efforts in peptide synthesis. This includes PMI assessment on 40 synthetic peptide processes at various development stages in pharma, classified according to the development phase. This is the most comprehensive assessment of synthetic peptide environmental metrics to date. The synthetic peptide manufacturing process was divided into stages (synthesis, purification, isolation) to determine their respective PMI. On average, solid-phase peptide synthesis (SPPS) (PMI ≈ 13,000) does not compare favorably with other modalities such as small molecules (PMI median 168-308) and biopharmaceuticals (PMI ≈ 8300). Thus, the high PMI for peptide synthesis warrants more environmentally friendly processes in peptide manufacturing.

Can AI pass the written European Board Examination in Neurological Surgery? - Ethical and practical issues.

Introduction: Artificial intelligence (AI) based large language models (LLM) contain enormous potential in education and training. Recent publications demonstrated that they are able to outperform participants in written medical exams. Research question: We aimed to explore the accuracy of AI in the written part of the EANS board exam. Material and methods: Eighty-six representative single best answer (SBA) questions, included at least ten times in prior EANS board exams, were selected by the current EANS board exam committee. The questions' content was classified as 75 text-based (TB) and 11 image-based (IB) and their structure as 50 interpretation-weighted, 30 theory-based and 6 true-or-false. Questions were tested with Chat GPT 3.5, Bing and Bard. The AI and participant results were statistically analyzed through ANOVA tests with Stata SE 15 (StataCorp, College Station, TX). P-values of <0.05 were considered as statistically significant. Results: The Bard LLM achieved the highest accuracy with 62% correct questions overall and 69% excluding IB, outperforming human exam participants 59% (p = 0.67) and 59% (p = 0.42), respectively. All LLMs scored highest in theory-based questions, excluding IB questions (Chat-GPT: 79%; Bing: 83%; Bard: 86%) and significantly better than the human exam participants (60%; p = 0.03). AI could not answer any IB question correctly. Discussion and conclusion: AI passed the written EANS board exam based on representative SBA questions and achieved results close to or even better than the human exam participants. Our results raise several ethical and practical implications, which may impact the current concept for the written EANS board exam.

Deep Learning Prediction of Cervical Spine Surgery Revision Outcomes Using Standard Laboratory and Operative Variables.

BACKGROUND: Cervical spine procedures represent a major proportion of all spine surgery. Mitigating the revision rate following cervical procedures requires careful patient selection. While complication risk has successfully been predicted, revision risk has proven more challenging. This is likely due to the absence of granular variables in claims databases. The objective of this study was to develop a state-of-the-art model of revision prediction of cervical spine surgery using laboratory and operative variables. METHODS: Using the Stanford Research Repository, patients undergoing a cervical spine procedure between 2016 and 2022 were identified (N = 3151), and recent laboratory values were collected. Patients were classified into separate cohorts by revision outcome and time frame. Machine and deep learning models were trained to predict each revision outcome from laboratory and operative variables. RESULTS: Red blood cell count, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, red blood cell distribution width, platelet count, carbon dioxide, anion gap, and calcium all were significantly associated with ≥1 revision cohorts. For the prediction of 3-month revision, the deep neural network achieved an area under the receiver operating characteristic curve of 0.833. The model demonstrated increased performance for anterior versus posterior and arthrodesis versus decompression procedures. CONCLUSIONS: Our deep learning approach successfully predicted 3-month revision outcomes from demographic variables, standard laboratory values, and operative variables in a cervical spine surgery cohort. This work used standard laboratory values and operative codes as meaningful predictive variables for revision outcome prediction. The increased performance on certain procedures evidences the need for careful development and validation of one-size-fits-all risk scores for spine procedures.

Predictive models for occurrence of expansive intracranial hematomas and surgical evacuation outcomes in traumatic brain injury patients in Uganda: A prospective cohort study.

Background: Hematoma expansion is a common manifestation of acute intracranial hemorrhage (ICH) which is associated with poor outcomes and functional status. Objective: We determined the prevalence of expansive intracranial hematomas (EIH) and assessed the predictive model for EIH occurrence and surgical evacuation outcomes in patients with traumatic brain injury (TBI) in Uganda. Methods: We recruited adult patients with TBI with intracranial hematomas in a prospective cohort study. Data analysis using logistic regression to identify relevant risk factors, assess the interactions between variables, and developing a predictive model for EIH occurrence and surgical evacuation outcomes in TBI patients was performed. The predictive accuracies of these algorithms were compared using the area under the receiver operating characteristic curve (AUC). A p-values of < 0.05 at a 95% Confidence interval (CI) was considered significant. Results: A total of 324 study participants with intracranial hemorrhage were followed up for 6 months after surgery. About 59.3% (192/324) had expansive intracranial hemorrhage. The study participants with expansive intracranial hemorrhage had poor quality of life at both 3 and 6-months with p < 0.010 respectively. Among the 5 machine learning algorithms, the random forest performed the best in predicting EIH in both the training cohort (AUC = 0.833) and the validation cohort (AUC = 0.734). The top five features in the random forest algorithm-based model were subdural hematoma, diffuse axonal injury, systolic and diastolic blood pressure, association between depressed fracture and subdural hematoma. Other models demonstrated good discrimination with AUC for intraoperative complication (0.675) and poor discrimination for mortality (0.366) after neurosurgical evacuation in TBI patients. Conclusion: Expansive intracranial hemorrhage is common among patients with traumatic brain injury in Uganda. Early identification of patients with subdural hematoma, diffuse axonal injury, systolic and diastolic blood pressure, association between depressed fracture and subdural hematoma, were crucial in predicting EIH and intraoperative complications.

COveRs to impRove EsthetiC ouTcome after Surgery for Chronic subdural hemAtoma by buRr hole trepanation-Results of a Swiss Single-Blinded, Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Burr hole trepanation to evacuate chronic subdural hematoma (cSDH) results in bony skull defects that can lead to skin depressions. We intend to study the effect of burr hole covers to prevent skin depressions and improve the esthetic result. METHODS: In a randomized trial, we enrolled adult patients with symptomatic cSDH. Patients received burr hole trepanation with (intervention) vs without burr hole covers (control) in a 1:1 ratio. Patients requiring evacuation of bilateral cSDHs served as their internal control. Primary outcome was satisfaction with the esthetic result of the scar, measured from 0 (dissatisfied) to 10 (very satisfied) on the Esthetic Numeric Analog (ANA) scale at 90 days. Secondary outcomes included ANA scale, rates of skin depression, complications, as well as neurological, disability, and health-related quality of life outcomes until 12 months. RESULTS: We included 78 patients (55 with unilateral and 23 with bilateral cSDH; median age 78 years, 83% male) between 03/2019 and 05/2021, 50 trepanations for the intervention and 51 for the control group. In an intention-to-treat analysis, the ANA scale scores were 9.0 (intervention) and 8.5 (control arm) at 90 days (P = .498). At 12 months, the ANA scale scores were 9.0 and 8.0 for the intervention and control groups, respectively (P = .183). Skin depressions over the frontal burr hole were noted by 35% (intervention) and 63% (control) of patients at 90 days (P = .009) and by 35% and 79% (P < .001) at 12 months, respectively. There were no differences in complications, neurological, disability, and health-related quality of life outcomes. CONCLUSION: Satisfaction with the esthetic result of the scar was inherently high. This study does not show evidence for improvement on the ANA scale by applying a burr hole cover. The application of burr hole covers resulted in less skin depressions and did not negatively affect complication rates or outcomes.

Current state of preoperative embolization for spinal metastasis - A survey by the EANS spine section.

Introduction: Preoperative embolization (PE) for spinal metastasis can be used to reduce tumor blood supply in selected patients. The decision whether and when to perform PE varies largely among spine surgeons and centers. Research question: The aim was to understand the current decision-making process in European spine centers. Material and methods: The European Association of Neurosurgical Societies (EANS) spine section designed a 13-item online survey. It was distributed to neurosurgical residents and board-certified neurosurgeons between 7th of February and May 5, 2023. Results: We analyzed 120 survey responses. Most participants were board-certified neurosurgeons (71%) or residents (26%) in university hospitals (76%). Routinely performed PE was stated not a common practice in 62%. Of those using PE, 25% indicated to perform it in selected cases requiring vertebral body replacement. Reasons for not performing PE included lack of time (44%), unclear benefits (25%), no significant bleeding without PE (19%), and significant bleeding despite PE (8%). Most participants opted for PE < 24h before surgery, but in a separate anesthesia (54%). More experienced participants were more likely to observe reduced blood loss (BL) after PE (p = 0.014). The most common reported complications were neurological deterioration due to spinal cord infarction (n = 15) and swelling due to tumor necrosis (n = 13). Discussion and conclusions: PE is still not a routine among European spine surgeons and is considered mostly for elective cases with hypervascularized tumors scheduled in a separate anesthesia <24h before tumor resection. Most participants noted reduced intraoperative BL, but also a risk of procedure-related complications.

The use of advanced technology for preoperative planning in cranial surgery - A survey by the EANS Young Neurosurgeons Committee.

Introduction: Technological advancements provided several preoperative tools allowing for precise preoperative planning in cranial neurosurgery, aiming to increase the efficacy and safety of surgery. However, little data are available regarding if and how young neurosurgeons are trained in using such technologies, how often they use them in clinical practice, and how valuable they consider these technologies. Research question: How frequently these technologies are used during training and clinical practice as well as to how their perceived value can be qualitatively assessed. Materials and methods: The Young Neurosurgeons' Committee (YNC) of the European Association of Neurosurgical Societies (EANS) distributed a 14-items survey among young neurosurgeons between June 1st and August 31st, 2022. Results: A total of 441 responses were collected. Most responders (42.34%) received "formal" training during their residency. Planning techniques were used mainly in neuro-oncology (90.86%), and 3D visualization of patients' DICOM dataset using open-source software was the most frequently used (>20 times/month, 20.34% of responders). Software for 3D visualization of patients' DICOM dataset was the most valuable technology, especially for planning surgical approach (42.03%). Conversely, simulation based on augmented/mixed/virtual reality was considered the less valuable tool, being rated below sufficiency by 39.7% of responders. Discussion and conclusion: Training for using preoperative planning technologies in cranial neurosurgery is provided by neurosurgical residency programs. Software for 3D visualization of DICOM datasets is the most valuable and used tool, especially in neuro-oncology. Interestingly, simulation tools based on augmented/virtual/mixed reality are considered less valuable and, therefore, less used than other technologies.

Burden, risk factors, neurosurgical evacuation outcomes, and predictors of mortality among traumatic brain injury patients with expansive intracranial hematomas in Uganda: a mixed methods study design.

BACKGROUND: Expansive intracranial hematomas (EIH) following traumatic brain injury (TBI) continue to be a public health problem in Uganda. Data is limited regarding the neurosurgical outcomes of TBI patients. This study investigated the neurosurgical outcomes and associated risk factors of EIH among TBI patients at Mulago National Referral Hospital (MNRH). METHODS: A total of 324 subjects were enrolled using a prospective cohort study. Socio-demographic, risk factors and complications were collected using a study questionnaire. Study participants were followed up for 180 days. Univariate, multivariable, Cox regression analyses, Kaplan Meir survival curves, and log rank tests were sequentially conducted. P-values of < 0.05 at 95% Confidence interval (CI) were considered to be statistically significant. RESULTS: Of the 324 patients with intracranial hematomas, 80.6% were male. The mean age of the study participants was 37.5 ± 17.4 years. Prevalence of EIH was 59.3% (0.59 (95% CI: 0.54 to 0.65)). Participants who were aged 39 years and above; PR = 1.54 (95% CI: 1.20 to 1.97; P = 0.001), and those who smoke PR = 1.21 (95% CI: 1.00 to 1.47; P = 0.048), and presence of swirl sign PR = 2.26 (95% CI: 1.29 to 3.95; P = 0.004) were found to be at higher risk for EIH. Kaplan Meier survival curve indicated that mortality at the 16-month follow-up was 53.4% (95% CI: 28.1 to 85.0). Multivariate Cox regression indicated that the predictors of mortality were old age, MAP above 95 mmHg, low GCS, complications such as infection, spasticity, wound dehiscence, CSF leaks, having GOS < 3, QoLIBRI < 50, SDH, contusion, and EIH. CONCLUSION: EIH is common in Uganda following RTA with an occurrence of 59.3% and a 16-month higher mortality rate. An increased age above 39 years, smoking, having severe systemic disease, and the presence of swirl sign are independent risk factors. Old age, MAP above 95 mmHg, low GCS, complications such as infection, spasticity, wound dehiscence, CSF leaks, having a GOS < 3, QoLIBRI < 50, ASDH, and contusion are predictors of mortality. These findings imply that all patients with intracranial hematomas (IH) need to be monitored closely and a repeat CT scan to be done within a specific period following their initial CT scan. We recommend the development of a protocol for specific surgical and medical interventions that can be implemented for patients at moderate and severe risk for EIH.

Protocol for a randomised, multicentre, four-arm, double-blinded, placebo-controlled trial to assess the benefits and safety of iron supplementation with malaria chemoprevention to children in Malawi: IRMA trial.

INTRODUCTION: Approximately 40% of children aged 6-59 months worldwide are anaemic. Iron-containing multiple micronutrient powders (MNPs) and iron supplements (syrup/drops) are used to combat anaemia in children in different parts of the world. However, evidence for functional benefits of iron supplementation in children is scarce, and potential risks remain poorly defined, particularly concerning diarrhoea and malaria. This trial aims to determine if: (1) the efficacy of iron supplements or MNPs (containing iron) given with malaria chemoprevention is superior to malaria chemoprevention alone, or (2) if the efficacy of malaria chemoprevention alone is superior to placebo on child cognitive development. METHODS AND ANALYSIS: IRMA is a four-arm, parallel-group, double-blinded, placebo-controlled, triple-dummy, randomised trial in Southern Malawi. The study recruits 2168 infants aged 6 months, with an intervention period of 6 months and a post-intervention period of a further 6 months. Children are randomised into four arms: (1) No intervention (placebo); (2) malaria chemoprevention only; (3) MNPs and malaria chemoprevention; and (4) iron syrup and malaria chemoprevention. The primary outcome, cognitive development (Cognitive Composite Score (CogCS)), is measured at the end of the 6 months intervention. Secondary outcomes include CogCS at a further 6 months post-intervention, motor, language and behavioural development, physical growth and prevalence of anaemia and iron deficiency. Safety outcomes include incidence of malaria and other infections, and prevalence of malaria parasitaemia during and post-intervention period. ETHICS AND DISSEMINATION: The trial is approved by the National Health Sciences Research Committee (#19/01/2213) (Malawi) and the Human Research Ethics Committee (WEHI: 19/012) (Australia). Written informed consent in the local language is obtained from each participant before conducting any study-related procedure. Results will be shared with the local community and internationally with academic and policy stakeholders. TRIAL REGISTRATION NUMBER: ACTRN12620000386932.

Transcription Factor Zbtb20 as a Regulator of Malignancy and Its Practical Applications.

Zbtb20 (zinc finger and BTB domain-containing protein 20) is a transcription factor with a zinc finger DNA binding domain and a BTB domain responsible for protein-protein interaction. Recently, this TF has received attention because new data showed its pivotal involvement in normal neural development and its regulatory effects on proliferation and differentiation in different tissues. Zbtb20 was shown to increase proliferation and migration and confer resistance to apoptosis in the contexts of many malignant tumors like hepatocellular carcinoma, non-small-cell lung carcinoma, gastric adenocarcinoma, glioblastoma multiforme, breast cancer, and acute myeloid leukemia. The involvement of Zbtb20 in tumor biology is best studied in hepatocellular carcinoma, where it is a promising candidate as an immunohistochemical tumor marker or may be used in patient screening. Here we review the current data connecting Zbtb20 with malignant tumors.

'Factors influencing future career choices of Queen's University Belfast Medical students.'

INTRODUCTION: Decisions made by medical students on future career choice have demonstrated concordance with subsequent postgraduate career path. This study aimed to understand the factors that impact undergraduate career decision making. METHODS: An anonymous voluntary survey consisting of binominal, Likert and free text responses was distributed to all medical students registered at Queen's University Belfast (QUB). Data was collected over 6 weeks in April-May 2021. The primary outcome was future career aspirations. The secondary outcomes were the impact of mentorship on career choice, the likelihood of students completing their medical degree and practicing medicine upon graduation. Local ethical approval was obtained. RESULTS: 202 responses were received (response rate 15%). 67% (n = 135) were female. One third of respondents remained undecided about their future career choice. Surgery was both the most popular definite career choice (16.3%) of respondents, butalsothespecialtymarkedmostoftenas'Least preferred Specialty' (33%). Factors positively influencing career choice were academic interest and flexibility in working hours. Negative predictors of career choice were lack of interest in the area, perceived workload, and duration of training schemes. 71% (n=144) of respondents reported that a subspecialty mentor would positively influence their career choice and two-thirds of respondents reported that financial factors would influence their career decision. 11% (n= 22) of respondents were unsure or undecided if they would continue medicine as a career upon graduation. CONCLUSION: Uncertainty over future career intention remains common with surgery the least popular speciality. Mentorship, integrating flexibility in training and enhancing academic interest should be considered by educational stakeholders as mechanisms to generating undergraduate interest in a subspecialty. Furthermore, the reported rate of students intention to leave their medical degree prior to graduation by this cohort is concerning, warranting further investigation.