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Background The obesity paradox is a well-documented phenomenon in cardiovascular disease, however it remains poorly understood. We aimed to investigate the relationship between body mass (as measured by body mass index [BMI]) and 1-year amputation-free survival (AFS) for patients undergoing lower limb revascularisation for chronic limb-threatening ischaemia (CLTI). Methods A retrospective analysis was undertaken of all consecutive patients undergoing lower limb revascularisation for CLTI at the Leicester Vascular Institute between February 2018–19. Baseline demographics and outcomes were collected using electronic records. BMI was stratified using the World Health Organization criteria. One-year AFS (composite of major amputation/death) was the primary outcome. Kaplan-Meier survival analysis and adjusted Cox's proportional hazard models were used to compare groups to patients of normal mass. Results One-hundred and ninety patients were included. Overall, no difference was identified in 1-year AFS across all groups (pooled P = 0.335). Compared to patients with normal BMI (n = 66), obese patients (n = 43) had a significantly lower adjusted combined risk of amputation/death (aHR 0.39, 95% CI 0.16–0.92, P = 0.032), however no significant differences were observed for overweight (aHR 0.89, 95% CI 0.47–1.70, P = 0.741), morbidly obese (aHR 1.15, 95% CI 0.41–3.20, P = 0.797) and underweight individuals (aHR 1.86, 95% CI 0.56–6.20, P = 0.314). Conclusions In the context of CLTI, obesity is potentially associated with favourable amputation-free survival at 1 year, compared to normal body mass. The results of this study support the notion of an obesity paradox existing within CLTI and question whether current guidance on weight management requires a more patient-specific approach.

Second-trimester loss is pregnancy loss after the 12th and before the 24th completed weeks of pregnancy. This study aims to review cases of second-trimester miscarriage who attended a large maternity hospital and to examine pregnancy outcomes in this group of women.This study is a review of cases of second-trimester miscarriage using descriptive, exploratory design, involving a retrospective chart review.In this study, 106 cases of second-trimester miscarriage were reviewed. The cause of the miscarriage was found in 42.5% (n = 45) of cases. The majority of women, 84.5% (n = 82) had a normal pelvic ultrasound scan and 18.3% (n = 17) of cases were diagnosed with antiphospholipid syndrome. In women who became pregnant again, 60.9% (n = 39) had a live birth.Establishing the cause of second-trimester miscarriage can be challenging, despite completing all recommended investigations. Outcomes in subsequent pregnancies are reassuring. This review highlights the need to undertake all recommended investigations to elicit the cause of second-trimester miscarriage and underpins the need for further research in this area.

BACKGROUND Anemia is potentially associated with increased morbidity and mortality following vascular surgery procedures. This study investigated whether peri-procedural anemia is associated with reduced 1-year amputation-free survival (AFS) in patients undergoing revascularization for chronic limb-threatening ischemia (CLTI). METHODOLOGY A retrospective analysis of patients diagnosed with CLTI between February 2018-February 2019, who subsequently underwent revascularization, was conducted. Hemoglobin concentration measured at index assessment was recorded and stratified by WHO criteria. Subsequent peri-procedural red blood cell transfusions (RBC) were also recorded. The primary outcome was 1-year AFS. Kaplan Meier survival analysis and Cox's proportional hazard modelling were conducted to assess the effect of anemia and peri-procedure transfusion on outcomes. RESULTS 283 patients were analyzed, of which 148 (52.3%) were anemic. 53 patients (18.7%) underwent RBC transfusion. Patients with anemia had a significantly lower 1-year AFS (64.2% vs. 78.5%, P = 0.009). A significant difference in 1-year AFS was also observed based upon anemia severity (P = 0.008) and for patients who received RBC transfusion (45.3% vs 77.0%, P < 0.001). On multivariable analysis, moderately severe anemia was independently associated with increased risk of major amputation/death (aHR 1.90, 95% CI 1.06-3.38, P = 0.030). After adjusting for severity of baseline anemia, peri-procedural RBC transfusion was associated with a significant increase in the combined risk of major amputation/death (aHR 3.15, 95% CI 1.91-5.20, P < 0.001). CONCLUSION Moderately severe peri-procedural anemia and subsequent RBC transfusion are independently associated with reduced 1-year AFS in patients undergoing revascularization for CLTI. Future work should focus on investigating alternative measures to managing anemia in this cohort.

An amendment to the 1962 Coroner’s Act in the Republic of Ireland mandated that all stillbirths and neonatal deaths were to be reported to the local coroner’s office. In response to this, the bereavement team and department of anatomic pathology modified the pathway for placental examination following stillbirth and reporting deaths to the coroner. This paper is a review of the effect of this practice. This study is a review of all cases of stillbirths for 9 months following the amendment of the Coroner’s Act. A descriptive, exploratory design was used involving a retrospective chart review. Twenty-nine cases of stillbirth occurred during the study period. In cases where a placental examination was performed (n = 22), a cause of death was identified in the placenta or cord for seventeen (68%) of these cases. Seven cases had a consented autopsy with six cases confirming the initial diagnosis made at the time of gross placental examination. In one case, the cause of the stillbirth remained unexplained following placental examination and a full autopsy. No new information was gained from the autopsy in these seven cases. A further two cases had an autopsy directed by the coroner; the cause of death in these cases will be decided by the coroner. The introduction of the pathway has improved the care provided to bereaved parents by providing parents with timely information about the potential cause of stillbirth and thereby reduces the need for an autopsy examination.

Background Working in maternity hospital is usually a rewarding experience for staff. However, it can also be stressful and emotionally difficult work. Schwartz Rounds are a multidisciplinary forum which provides staff with an opportunity to reflect on the emotional impact of their work and support each other. Aims This paper will discuss the implementation of Schwartz Rounds in a maternity hospital and gives details of a pilot study to evaluate the initiative. Methods Schwartz Rounds were commenced in the hospital in September 2019, and an evaluation is in progress. A pilot study which evaluated 2 rounds has been completed. Staff who attended Schwartz Rounds were asked to complete an anonymous feedback form immediately following the Round. The data from feedback forms were analysed using descriptive statistics. Results Seventy-eight members of staff from almost all departments attended the rounds. Feedback forms were completed by 55 members of staff. Overall, the rounds were very positively evaluated by those who participated in the study. Conclusions Schwartz Rounds are an effective way to support staff working in a maternity hospital.

Perinatal autopsy is one the most valuable investigations to ascertain the cause of death (Nijkamp et al., Seminars in Fetal & Neonatal Medicine. 22:167-175, 2017; Korteweg et al., AJOG 53, e1-12, 2012; Late Interuterine Death and Stillbirth’ RCOG Green-top Guideline No.55, 2015). Discussions about perinatal autopsy can be difficult for parents and healthcare professionals. Perinatal staff need a good level of knowledge and understanding regarding perinatal autopsy in order to discuss the procedure with parents. This study aims to investigate healthcare professionals’ knowledge regarding perinatal autopsy. An audit conducted in a large teaching hospital using a questionnaire was developed and distributed to healthcare professionals in the hospital. Seventy healthcare professionals participated in the audit. Of those surveyed, 64% (n = 45) have discussed perinatal autopsy with a mother and the majority of healthcare professionals (67%) found this difficult. Self-reported levels of understanding were found to be low with just 10% reporting ‘excellent understanding’. The results of this audit highlight the need for further education among all healthcare professionals working with bereaved families.

Treatment of EGFR-mutant lung cancer with erlotinib results in dramatic tumor regression but it is invariably followed by drug resistance. In characterizing early transcriptional changes following drug treatment of mutant EGFR-addicted cells, we identified the stem cell transcriptional regulator SOX2 as being rapidly and specifically induced, both in vitro and in vivo. Suppression of SOX2 sensitizes cells to erlotinib-mediated apoptosis, ultimately decreasing the emergence of acquired resistance, whereas its ectopic expression reduces drug-induced cell death. We show that erlotinib relieves EGFR-dependent suppression of FOXO6, leading to its induction of SOX2, which in turn represses the pro-apoptotic BH3-only genes BIM and BMF. Together, these observations point to a physiological feedback mechanism that attenuates oncogene addiction-mediated cell death associated with the withdrawal of growth factor signaling and may therefore contribute to the development of resistance. DOI: http://dx.doi.org/10.7554/eLife.06132.001, eLife digest Tumors can form when cells gain mutations in genes that enable them to grow and divide rapidly. In some human lung cancers, genetic mutations are found in a gene that makes a protein called EGFR. This protein encourages cells to divide and the mutations can lead to the cancer cells producing more EGFR, or producing a form of the protein that is more active. Treating these cancers with a drug called erlotinib inhibits EGFR and makes the tumors shrink dramatically, but the tumors will usually re-grow because any tumor cells that survive often become resistant to the drug. There are several ways that the tumor cells can become resistant, which makes the task of developing a solution to this problem more difficult. It has been suggested that the tumor cells may enter a temporary ‘drug-tolerant’ state that helps them to survive and makes it more likely that they will develop resistance to the drug. However, it is not clear how this drug-tolerant state might work. To address this question, Rothenberg et al. examined which genes are switched on (or ‘expressed’) in tumor cells with a mutant version of EGFR after they were treated with the erlotinib drug. The experiments show that a gene called SOX2 is expressed in these cells. Cells that had lower levels of SOX2 expression were more sensitive to the effects of the drug and fewer cells developed resistance. On the other hand, cells that had higher levels of SOX2 expression were less sensitive to the drug and resistance was more likely to develop. A protein called FOXO6—which is usually suppressed by EGFR—activates the SOX2 gene in these cells. Therefore, using erlotinib to inhibit EGFR to kill the cancer cells increases the activity of FOXO6, which in turn promotes the survival of some of the cells by activating the SOX2 gene. A better understanding of the ways in which cancer cells adapt to erlotinib and other drugs may help us to design more effective treatments with better outcomes for patients. DOI: http://dx.doi.org/10.7554/eLife.06132.002

Chronic fatigue syndrome (CFS) is a disorder of uncertain aetiology which attracts increasing research interest. This paper describes the development of a multidimensional measure incorporating the diverse symptoms associated with the illness. The Profile of Fatigue-Related Symptoms (PFRS) has four scales: emotional distress, cognitive difficulty, fatigue and somatic symptoms. These showed good convergence with comparison measures, high reliability and high internal consistency. CFS patients had markedly elevated scores compared with a student comparison group, and these scores correlated with indices of illness severity. The PFRS is a short and easily administered measure which, it is suggested, may be used to assess patients in terms of the severity and pattern of their disorder, to relate subjective symptoms to immunological and other findings, to evaluate the effects of treatments, and to compare the symptomatology of CFS with that in other fatiguing illnesses.

Background Thrombospondin-1 (TSP-1) induces vascular smooth muscle cell (VSMC) migration after arterial injury. TSP-1 up-regulates hyaluronic acid (HyA)-inducing genes in VSMCs. HyA also induces VSMC migration. Our hypothesis was that TSP-1–induced VSMC migration is dependent on the CD44 receptor, and that HyA and TSP-1 share migratory signaling pathways. Methods VSMC migration was assessed using TSP-1, HyA, or serum-free medium as chemoattractants. VSMCs were treated with inhibitors to CD44, Ras, phosphatidylinositol-3 kinase, Raf-1 kinase, or c-SRC. TSP-1– and HyA-induced epidermal growth factor receptor (EGFR) activity was determined by enzyme-linked immunosorbent assay. Comparisons were made by the Student t test and a P value less than .05 was considered significant. Results Inhibiting CD44 reduced TSP-1– and HyA-induced migration. Phosphatidylinositol-3 kinase and c-SRC inhibitors prevented TSP-1– and HyA-induced migration, whereas Ras and Raf-1 kinase inhibitors only affected TSP-1. TSP-1 and HyA activate the EGFR. Conclusions TSP-1– and HYA-induced migration share some of the same signaling pathways and the EGFR/CD44 receptors may be a common link.

Mid-trimester loss (MTL) is an area that is poorly defined in the literature and often under reported in clinical practice. The prevalence of MTL in Ireland is uncertain and has a huge impact on the woman, her family and maternity care services. To explore the prevalence and patterns of care for women with MTL in a large Maternity hospital in Ireland. A descriptive, exploratory study was used involving a retrospective chart audit. 220 women presented with MTL over the 3 year data collection period (January 2011–December 2013), giving a rate of 0.8 % of all deliveries. The majority of women had no previous pregnancy losses and were multiparous (i.e., had a previous pregnancy >500 g). The mean gestational age was 17.69 weeks (SD = 2.73). The mean length of hospital stay was 1.89 days. Intra muscular (IM) analgesia was the most commonly (58.5 %) used medication. Follow up hospital care was received in over 78 % of cases. The majority of women were referred the CMS Bereavement and Chaplain services, with a small number (approx. 5 %) referred to the social worker. Over 46.4 % of families availed of the hospital burial service. Results suggest the incidence of mid-trimester loss may be slightly lower than the 1 or 2 % of pregnancies reported in the literature. The incidence of mid-trimester loss in multiparous women is approximately twice that of nulliparous women. The referral services offered in the study were utilised by most of the women, as were follow-up clinic appointments.