Surgical planning during a pandemic: Identifying patients at high risk of severe disease or death due to COVID-19 in a cohort of patients on a cataract surgery waiting list.

BACKGROUND: The delivery of cataract surgery during the COVID-19 pandemic is challenging because of the risk of nosocomial SARS-CoV-2 infection when patients attend hospital for elective care. In order to ascertain the risk to patients awaiting cataract surgery, this study aimed to identify the presence of systemic comorbidities that are associated with a high risk of severe disease or death due to COVID-19. METHODS: A prospective study of 315 patients (630 eyes) was conducted from 3rd June to 31st July 2020. An electronic health record was used to identify any systemic comorbidities that would render a patient 'clinically extremely vulnerable' to COVID-19, as outlined by the Department of Health for Northern Ireland. Patient demographics, best-corrected visual acuity (VA) and risk of postoperative anisometropia were also recorded. RESULTS: The median age of patients awaiting cataract surgery was 76 years (range 22-97). Of the 315 patients, 72% were aged over 70 and 16% were aged over 85. A systemic comorbidity that would confer high risk status was identified in 21% of patients. This high risk status was attributable to severe respiratory disease, cancer, and immunosuppression therapies in the majority of cases. The high risk group were younger than those deemed non-high risk, but there were no significant differences with respect to gender, anticipated degree of surgical difficulty, VA, or whether the patient was undergoing first or second eye surgery. Of those patients awaiting first eye cataract surgery, the mean VA in the listed eye was 0.84 logMAR and 39% (70/179) had a VA <0.3 logMAR (6/12 Snellen acuity) in their fellow eye. 57% of patients were awaiting first eye surgery, and 32% of those patients would be at risk of symptomatic anisometropia postoperatively. CONCLUSION: One-fifth of patients awaiting cataract surgery were found to be at high risk of severe disease or death from COVID-19 and these patients may experience delays in their surgical care. Additional planning is required in order to minimise the morbidity associated with delayed cataract surgery.

A thematic review of the use of electronic logbooks for surgical assessment in sub-Saharan Africa.

INTRODUCTION: Ensuring that surgical training programmes in low- and middle-income countries (LMICs) provide high quality training, including adequate operative experience, is of crucial importance in meeting the goals set out in the Lancet Global Surgery 2030. Electronic logbooks (eLogbooks) have been adopted to monitor both individual trainee progression and the performance of surgical training programmes. METHODS: We performed a thematic review of the current evidence base surrounding the use of eLogbooks for the assessment of surgeons in training in sub-Saharan Africa, with a view to identifying the learning to date and areas for future research. RESULTS: Whilst there are multiple papers highlighting the use of surgical eLogbooks in high-income countries, we identified only three papers which discussed their use in sub-Saharan Africa. Four common themes emerged which related to the use of surgical eLogbooks throughout sub-Saharan Africa: ease of analysis, centralised databases, discrepancies in reporting and technology limitations. CONCLUSIONS: Robust data to demonstrate trainee progression and the quality of surgical training programmes are of crucial importance in ensuring that surgical training programmes can rapidly scale up to deliver large numbers of well-trained surgical providers to address the unmet patient need in LMICs in the next decade. The limited data on the use of well designed, centralised electronic surgical logbooks indicate that this tool may play an important role in providing key data to underpin these training programmes.

Radiation oncology teaching provision and practice prior to and during the first wave of the COVID-19 pandemic in medical schools in the United Kingdom and the Republic of Ireland: a cross-sectional survey.

OBJECTIVES: Radiotherapy is a key cancer treatment modality but is poorly understood by doctors. We sought to evaluate radiation oncology (RO) teaching in medical schools within the United Kingdom (UK) and Republic of Ireland (RoI), as well as any impacts on RO teaching delivery from the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A bespoke online survey instrument was developed, piloted and distributed to oncology teaching leads at all UK and RoI medical schools. Questions were designed to capture information on the structure, format, content and faculty for RO teaching, as well as both the actual and the predicted short- and long-term impacts of COVID-19. RESULTS: Responses were received from 29/41 (71%) UK and 5/6 (83%) RoI medical schools. Pre-clinical and clinical oncology teaching was delivered over a median of 2 weeks (IQR 1-6), although only 9 (27%) of 34 responding medical schools had a standalone RO module. RO teaching was most commonly delivered in clinics or wards (n = 26 and 25 respectively). Few medical schools provided teaching on the biological basis for radiotherapy (n = 11) or the RO career pathway (n = 8), and few provide teaching delivered by non-medical RO multidisciplinary team members. There was evidence of short- and long-term disruption to RO teaching from COVID-19. CONCLUSIONS: RO teaching in the UK and RoI is limited with minimal coverage of relevant theoretical principles and little exposure to radiotherapy departments and their non-medical team members. The COVID-19 pandemic risks exacerbating trainee doctors' already constrained exposure to radiotherapy. ADVANCES IN KNOWLEDGE: This study provides the first analysis of radiotherapy-related teaching in the UK and RoI, and the first to explore the impact of the COVID-19 pandemic on radiationoncology teaching.

Analysing the Operative Experience of Paediatric Surgical Trainees in Sub-Saharan Africa Using a Web-Based Logbook.

BACKGROUND: The expansion of local training programmes is crucial to address the shortages of specialist paediatric surgeons across Sub-Saharan Africa. This study assesses whether the current training programme for paediatric surgery at the College of Surgeons of East, Central and Southern Africa (COSECSA) is exposing trainees to adequate numbers and types of surgical procedures, as defined by local and international guidelines. METHODS: Using data from the COSECSA web-based logbook, we retrospectively analysed numbers and types of operations carried out by paediatric surgical trainees at each stage of training between 2015 and 2019, comparing results with indicative case numbers from regional (COSECSA) and international (Joint Commission on Surgical Training) guidelines. RESULTS: A total of 7,616 paediatric surgical operations were recorded by 15 trainees, at different stages of training, working across five countries in Sub-Saharan Africa. Each trainee recorded a median number of 456 operations (range 56-1111), with operative experience increasing between the first and final year of training. The most commonly recorded operation was inguinal hernia (n = 1051, 13.8%). Trainees performed the majority (n = 5607, 73.6%) of operations recorded in the eLogbook themselves, assisting in the remainder. Trainees exceeded both local and international recommended case numbers for general surgical procedures, with little exposure to sub-specialities. CONCLUSIONS: Trainees obtain a wide experience in common and general paediatric surgical procedures, the number of which increases during training. Post-certification may be required for those who wish to sub-specialise. The data from the logbook are useful in identifying individuals who may require additional experience and centres which should be offering increased levels of supervised surgical exposure.

Selective Expression of Flt3 within the Mouse Hematopoietic Stem Cell Compartment.

The fms-like tyrosine kinase 3 (Flt3) is a cell surface receptor that is expressed by various hematopoietic progenitor cells (HPC) and Flt3-activating mutations are commonly present in acute myeloid and lymphoid leukemias. These findings underscore the importance of Flt3 to steady-state and malignant hematopoiesis. In this study, the expression of Flt3 protein and Flt3 mRNA by single cells within the hematopoietic stem cell (HSC) and HPC bone marrow compartments of C57/BL6 mice was investigated using flow cytometry and the quantitative reverse transcription polymerase chain reaction. Flt3 was heterogeneously expressed by almost all of the populations studied, including long-term reconstituting HSC and short-term reconstituting HSC. The erythropoietin receptor (EpoR) and macrophage colony-stimulating factor receptor (M-CSFR) were also found to be heterogeneously expressed within the multipotent cell compartments. Co-expression of the mRNAs encoding Flt3 and EpoR rarely occurred within these compartments. Expression of both Flt3 and M-CSFR protein at the surface of single cells was more commonly observed. These results emphasize the heterogeneous nature of HSC and HPC and the new sub-populations identified are important to understanding the origin and heterogeneity of the acute myeloid leukemias.

The Cytokine Flt3-Ligand in Normal and Malignant Hematopoiesis.

The cytokine Fms-like tyrosine kinase 3 ligand (FL) is an important regulator of hematopoiesis. Its receptor, Flt3, is expressed on myeloid, lymphoid and dendritic cell progenitors and is considered an important growth and differentiation factor for several hematopoietic lineages. Activating mutations of Flt3 are frequently found in acute myeloid leukemia (AML) patients and associated with a poor clinical prognosis. In the present review we provide an overview of our current knowledge on the role of FL in the generation of blood cell lineages. We examine recent studies on Flt3 expression by hematopoietic stem cells and its potential instructive action at early stages of hematopoiesis. In addition, we review current findings on the role of mutated FLT3 in leukemia and the development of FLT3 inhibitors for therapeutic use to treat AML. The importance of mouse models in elucidating the role of Flt3-ligand in normal and malignant hematopoiesis is discussed.

Versatility of stem and progenitor cells and the instructive actions of cytokines on hematopoiesis.

For many years, developing hematopoietic cells have been strictly compartmentalized into a rare population of multi-potent self-renewing hematopoietic stem cells (HSC), multi-potent hematopoietic progenitor cells (MPP) that are undergoing commitment to particular lineage fates, and recognizable precursor cells that mature towards functional blood and immune cells. A single route to each end-cell type is prescribed in the "classical" model for the architecture of hematopoiesis. Recent findings have led to the viewpoint that HSCs and MPPs are more versatile than previously thought. Underlying this are multiple routes to a particular fate and cells having clandestine fate options even when they have progressed some way along a pathway. The primary role of cytokines during hematopoiesis has long been seen to be regulation of the survival and proliferation of developing hematopoietic cells. Some cytokines now clearly have instructive actions on cell-fate decisions. All this leads to a new way of viewing hematopoiesis whereby versatile HSC and MPP are directed towards lineage outcomes via cytokine regulated cell-fate decisions. This means greater flexibility to the shaping of hematopoiesis.

Adult vascular smooth muscle cells in culture express neural stem cell markers typical of resident multipotent vascular stem cells.

Differentiation of resident multipotent vascular stem cells (MVSCs) or de-differentiation of vascular smooth muscle cells (vSMCs) might be responsible for the SMC phenotype that plays a major role in vascular diseases such as arteriosclerosis and restenosis. We examined vSMCs from three different species (rat, murine and bovine) to establish whether they exhibit neural stem cell characteristics typical of MVSCs. We determined their SMC differentiation, neural stem cell marker expression and multipotency following induction in vitro by using immunocytochemistry, confocal microscopy, fluorescence-activated cell sorting analysis and quantitative real-time polymerase chain reaction. MVSCs isolated from rat aortic explants, enzymatically dispersed rat SMCs and rat bone-marrow-derived mesenchymal stem cells served as controls. Murine carotid artery lysates and primary rat aortic vSMCs were both myosin-heavy-chain-positive but weakly expressed the neural crest stem cell marker, Sox10. Each vSMC line examined expressed SMC differentiation markers (smooth muscle α-actin, myosin heavy chain and calponin), neural crest stem cell markers (Sox10(+), Sox17(+)) and a glia marker (S100ß(+)). Serum deprivation significantly increased calponin and myosin heavy chain expression and decreased stem cell marker expression, when compared with serum-rich conditions. vSMCs did not differentiate to adipocytes or osteoblasts following adipogenic or osteogenic inductive stimulation, respectively, or respond to transforming growth factor-ß1 or Notch following γ-secretase inhibition. Thus, vascular SMCs in culture express neural stem cell markers typical of MVSCs, concomitant with SMC differentiation markers, but do not retain their multipotency. The ultimate origin of these cells might have important implications for their use in investigations of vascular proliferative disease in vitro.