ObjectiveTo determine the rates of asymptomatic viral carriage and seroprevalence of SARS-CoV-2 antibodies in healthcare workers.DesignA cross-sectional study of asymptomatic healthcare workers undertaken on 24/25 April 2020.SettingUniversity Hospitals Birmingham NHS Foundation Trust (UHBFT), UK.Participants545 asymptomatic healthcare workers were recruited while at work. Participants were invited to participate via the UHBFT social media. Exclusion criteria included current symptoms consistent with COVID-19. No potential participants were excluded.InterventionParticipants volunteered a nasopharyngeal swab and a venous blood sample that were tested for SARS-CoV-2 RNA and anti-SARS-CoV-2 spike glycoprotein antibodies, respectively. Results were interpreted in the context of prior illnesses and the hospital departments in which participants worked.Main outcome measureProportion of participants demonstrating infection and positive SARS-CoV-2 serology.ResultsThe point prevalence of SARS-CoV-2 viral carriage was 2.4% (n=13/545). The overall seroprevalence of SARS-CoV-2 antibodies was 24.4% (n=126/516). Participants who reported prior symptomatic illness had higher seroprevalence (37.5% vs 17.1%, χ2=21.1034, p<0.0001) and quantitatively greater antibody responses than those who had remained asymptomatic. Seroprevalence was greatest among those working in housekeeping (34.5%), acute medicine (33.3%) and general internal medicine (30.3%), with lower rates observed in participants working in intensive care (14.8%). BAME (Black, Asian and minority ethnic) ethnicity was associated with a significantly increased risk of seropositivity (OR: 1.92, 95% CI 1.14 to 3.23, p=0.01). Working on the intensive care unit was associated with a significantly lower risk of seropositivity compared with working in other areas of the hospital (OR: 0.28, 95% CI 0.09 to 0.78, p=0.02).Conclusions and relevanceWe identify differences in the occupational risk of exposure to SARS-CoV-2 between hospital departments and confirm asymptomatic seroconversion occurs in healthcare workers. Further investigation of these observations is required to inform future infection control and occupational health practices.

Background The coronavirus disease 2019 (COVID-19) pandemic is likely to lead to a significant increase in mental health disorders among healthcare workers (HCW). Aims We evaluated the rates of anxiety, depressive and post-traumatic stress disorder (PTSD) symptoms in a population of HCW in the UK. Method An electronic survey was conducted between the 5 June 2020 and 31 July 2020 of all hospital HCW in the West Midlands, UK using clinically validated questionnaires: the 4-item Patient Health Questionnaire(PHQ-4) and the Impact of Event Scale-Revised (IES-R). Univariate analyses and adjusted logistic regression analyses were performed to estimate the strengths in associations between 24 independent variables and anxiety, depressive or PTSD symptoms. Results There were 2638 eligible participants who completed the survey (female: 79.5%, median age: 42 years, interquartile range: 32–51). The rates of clinically significant symptoms of anxiety, depression and PTSD were 34.3%, 31.2% and 24.5%, respectively. In adjusted analysis a history of mental health conditions was associated with clinically significant symptoms of anxiety (odds ratio (OR) = 2.3, 95% CI 1.9–2.7, P < 0.001), depression (OR = 2.5, 95% CI 2.1–3.0, P < 0.001) and PTSD (OR = 2.1, 95% CI 1.7–2.5, P < 0.001). The availability of adequate personal protective equipment (PPE), well-being support and lower exposure to moral dilemmas at work demonstrated significant negative associations with these symptoms (P ≤ 0.001). Conclusions We report higher rates of clinically significant mental health symptoms among hospital HCW following the initial COVID-19 pandemic peak in the UK. Those with a history of mental health conditions were most at risk. Adequate PPE availability, access to well-being support and reduced exposure to moral dilemmas may protect hospital HCW from mental health symptoms.

Retroperitoneal liposarcomas are rare tumours that carry a poorer prognosis than their extremity counterparts. Within their subtypes-well differentiated (WDL), dedifferentiated (DDL), myxoid (MLS) and pleomorphic (PLS)-they exhibit a diverse genomic landscape. With recent advances in next generation sequencing, the number of studies exploring this have greatly increased. The recent literature has deepened our understanding of the hallmark MDM2/CDK4 amplification in WDL/DDL and addressed concerns about toxicity and resistance when targeting this. The FUS-DDIT3 fusion gene remains the primary focus of interest in MLS with additional potential targets described. Whole genome sequencing has driven identification of novel genes and pathways implicated in WDL/DDL outside of the classic 12q13-15 amplicon. Due to their rarity; anatomical location and histologic subtype are infrequently mentioned when reporting the results of these studies. Reports can include non-adipogenic or extremity tumours, making it difficult to draw specific retroperitoneal conclusions. This narrative review aims to provide a summary of retroperitoneal liposarcoma genomics and the implications for therapeutic targeting. summary of specific retroperitoneal liposarcoma genomics is lacking in the literature. This would be useful to clinicians and scientists alike, dealing with this specific disease in the era of personalised medicine. Secondly, it is well established that variations in the tumour microenvironment can determine response to therapy. Lastly, RPL carries a poorer prognosis than extremity LS, has a distinct natural history and is managed differently. Methods Search strategy A literature search was conducted using the Embase, MEDLINE, PubMed and Cochrane Library databases. The following keywords were used to perform flexible searches within these databases: 'Retroperitoneal' AND 'sarcoma', 'liposarcoma', 'genomics', 'genetics', 'mutation', and 'genomic therapy.' Only papers published in English were included.

Radiotherapy is routinely used as a neoadjuvant, adjuvant or palliative treatment in various cancers. There is significant variation in clinical response to radiotherapy with or without traditional chemotherapy. Patients with a good response to radiotherapy demonstrate better clinical outcomes universally across different cancers. The PI3K/AKT/mTOR pathway upregulation has been linked to radiotherapy resistance. We reviewed the current literature exploring the role of inhibiting targets along this pathway, in enhancing radiotherapy response. We identified several studies using in vitro cancer cell lines, in vivo tumour xenografts and a few Phase I/II clinical trials. Most of the current evidence in this area comes from glioblastoma multiforme, non-small cell lung cancer, head and neck cancer, colorectal cancer, and prostate cancer. The biological basis for radiosensitivity following pathway inhibition was through inhibited DNA double strand break repair, inhibited cell proliferation, enhanced apoptosis and autophagy as well as tumour microenvironment changes. Dual PI3K/mTOR inhibition consistently demonstrated radiosensitisation of all types of cancer cells. Single pathway component inhibitors and other inhibitor combinations yielded variable outcomes especially within early clinical trials. There is ample evidence from preclinical studies to suggest that direct pharmacological inhibition of the PI3K/AKT/mTOR pathway components can radiosensitise different types of cancer cells. We recommend that future in vitro and in vivo research in this field should focus on dual PI3K/mTOR inhibitors. Early clinical trials are needed to assess the feasibility and efficacy of these dual inhibitors in combination with radiotherapy in brain, lung, head and neck, breast, prostate and rectal cancer patients.

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Background The Covid-19 pandemic led to significant changes and disruptions to medical education worldwide. We evaluated medical student perceived views on training, their experiences and changes to teaching methods during the pandemic. Methods An online survey of medical students was conducted in the Autumn of 2020. An international network of collaborators facilitated participant recruitment. Students were surveyed on their perceived overall impact of Covid-19 on their training and several exposure variables. Univariate analyses and adjusted multivariable analysis were performed to determine strengths in associations. Results A total of 1604 eligible participants from 45 countries took part in this survey and 56.3% (n = 860) of these were female. The median age was 21 (Inter Quartile Range:21–23). Nearly half (49.6%, n = 796) of medical students were in their clinical years. The majority (n = 1356, 84.5%) were residents of a low or middle income country. A total of 1305 (81.4%) participants reported that the Covid-19 pandemic had an overall negative impact on their training. On adjusted analysis, being 21 or younger, females, those reporting a decline in conventional lectures and ward based teaching were more likely to report an overall negative impact on their training (p ≤ 0.001). However, an increase in clinical responsibilities was associated with lower odds of participants reporting a negative impact on training (p < 0.001). The participant’s resident nation economy and stage of training were associated with some of the participant training experiences surveyed (p < 0.05). Conclusion An international cohort of medical students reported an overall significant negative impact of the Covid-19 pandemic on their undergraduate training. The efficacy of novel virtual methods of teaching to supplement traditional teaching methods warrants further research.

Background The Covid-19 pandemic is likely to lead to a significant increase in mental health disorders amongst healthcare workers (HCW). Aims We evaluated the prevalence of anxiety, depressive and post-traumatic stress disorder (PTSD) symptoms in a HCW population in the United Kingdom (UK), to identify subgroups most at risk. Methods An electronic survey was conducted between the 05/06/2020 and 31/07/2020 of all hospital HCW in the West Midlands, UK using clinically validated questionnaires: Patient Health Questionnaire-4 (PHQ-4) and the Impact of Event Scale-Revised (IES-R). Univariate analyses and adjusted logistic regression analyses were performed to estimate the strengths in associations. Results There were 2638 eligible participants who completed the survey (female: 79.5%, median age: 42 [IQR: 32-51] years). The prevalence rates of clinically significant symptoms of anxiety, depression and PTSD were 34.3%, 31.2% and 24.5% respectively. In adjusted analysis a history of mental health conditions was associated with clinically significant symptoms of anxiety (odds ratio 2.3 [95% CI 1.9-2.7]; p<0.001), depression (2.5 [2.1-3.0]; p<0.001) and PTSD (2.1 [1.7-2.5]; p<0.001). The availability of adequate personal protective equipment (PPE), wellbeing support and lower exposure to moral dilemmas at work demonstrated significant negative associations with former symptoms (p≤0.001). Conclusions We report a high prevalence of clinically significant symptoms of anxiety, depression and PTSD in hospital HCW following the initial Covid-19 pandemic peak in the UK. Those with a history of mental health conditions were most at risk. Adequate PPE availability, access to wellbeing support and reduced exposure to moral dilemmas may protect hospital HCW from mental health symptoms.

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