Development of an Ex-vivo Patient- Derived-Explant Model for Endometrial Cancer

Objective: To develop a novel Endometrial Cancer Patient-Derived-Explant (EC-PDE) preclinical model system that is capable of detecting patient-specific drug-responses to standard-of-care chemotherapies and immunotherapy ex vivo. Methods: Endometrial tumour was obtained from 35 patients with endometrial cancer and processed into explants. EC-PDEs were then cultured at the air-liquid interface for up to 24 h followed by a further 24 h treatment with Carboplatin and Paclitaxel or Pembrolizumab and then processed into histology slides. Multiplexed immunofluorescence for Ki67 (proliferation marker), cPARP (apoptosis marker) and CAM 5.2 (tumour mask) was performed for viability studies and for CD8, CD4 and FOX-P3 antibodies for immune profiling studies. Images were then analysed with quantitation of biomarker expression and necrosis area. Results: EC-PDEs maintained the histological architecture of the tumour and surrounding tumour microenvironment. EC-PDEs remained viable for up to 48 h irrespective of culture-media or serum supplementation. Differential drug-responses were detected to single- and dual-agent chemotherapy with the greatest drug-responses identified in high-risk tumours. Cell-death-responses were also identified following Pembrolizumab-treatment. Immune cell profiling in the tumour and stroma was suggestive of an immunosuppressive effect of T-regulatory cells whilst the greatest drug-responses were seen in tumours with a CD8hot phenotype. Conclusions: EC-PDEs represent a low-cost 3D pre-clinical model which offers the potential for rapid, personalised pre-clinical drug-response testing. EC-PDEs can be used to explore the biological effects of immunotherapy and to evaluate predictors of drug response.</p

Robotic-assisted surgery in high-risk surgical patients with endometrial cancer

Many patients diagnosed with an endometrial cancer are at high-risk for surgery due to factors such as advanced age, raised body mass index or frailty. Minimally-invasive surgery, in particular robotic-assisted, is increasingly used in the surgical management of endometrial cancer however, there are a lack of clinical trials investigating outcomes in high-risk patient populations. This article will review the current evidence and identify areas of uncertainty where future research is needed.</p

Robotic-assisted surgery in high-risk surgical patients with endometrial cancer

Many patients diagnosed with an endometrial cancer are at high-risk for surgery due to factors such as advanced age, raised body mass index or frailty. Minimally-invasive surgery, in particular robotic-assisted, is increasingly used in the surgical management of endometrial cancer however, there are a lack of clinical trials investigating outcomes in high-risk patient populations. This article will review the current evidence and identify areas of uncertainty where future research is needed.</p

Supplemental Material, sj-pdf-1-her-10.1177_19375867211059078 - Designing Palliative Care Facilities to Better Support Patient and Family Care: A Staff Perspective

Supplemental Material, sj-pdf-1-her-10.1177_19375867211059078 for Designing Palliative Care Facilities to Better Support Patient and Family Care: A Staff Perspective by Rebecca McLaughlan, Kieran Richards, Ruby Lipson-Smith, Anna Collins and Jennifer Philip in HERD: Health Environments Research & Design Journal</p

Supplemental Material, sj-pdf-2-her-10.1177_19375867211059078 - Designing Palliative Care Facilities to Better Support Patient and Family Care: A Staff Perspective

Supplemental Material, sj-pdf-2-her-10.1177_19375867211059078 for Designing Palliative Care Facilities to Better Support Patient and Family Care: A Staff Perspective by Rebecca McLaughlan, Kieran Richards, Ruby Lipson-Smith, Anna Collins and Jennifer Philip in HERD: Health Environments Research & Design Journal</p

Identification of European-wide clinical priorities for guideline development in the management of pre-invasive cervical disease

Objective: Addressing management controversies in the treatment of pre-invasive cervical disease is a key priority for the European Federation for Colposcopy/European Society of Gynaecologic Oncology who aim to develop a practical handbook of European centred guidelines to address areas where there is a lack of high-quality evidence or identifiable practice variation. Clinical opinion across the EFC network was sought to identify topics likely to have the most impact on clinical practice for systematic review and development of practice recommendations. Study design: A scoping exercise comprising of a three-iteration modified Delphi with representation from each member society of the EFC was conducted in 2018. Round one identified 19 potential topics which were scored for importance using a five-point Likert scale by EFC members in round two and ranked. Results from round two were discussed at an open EFC satellite meeting resulting in exclusion of five topics. A third round of the 14 remaining topics was conducted to allow members to modify scores after viewing the second-round rankings. Responses were analysed and topics were allocated a weighted score. Results: Strategies for management of persistent HPV infection in the context of normal colposcopy and negative cytology was the highest overall weighted topic (4.40) followed by identification of appropriate length of follow up for ASCUS or LSIL prior to excisional treatment (3.95) and the impact of length of excision on patient outcomes (3.95). Topics to identify best practice for management of challenging topics scored highly including optimising follow up strategies for cervical stenosis (3.91) and management of HSIL in the under 25 year olds (3.64) or pregnancy (3.64). Conclusion: A European wide systematic modified-Delphi has prioritised six topics for systematic review and generation of clinical practice recommendations aiming to assist management in areas of controversy in pre-invasive cervical disease.</p

Impact of past obstetric history and cervical excision on preterm birth rate

IntroductionTo determine the impact on preterm birth (PTB) of a history of large loop excision of the transformation zone (LLETZ)-alone compared with a history of previous preterm birth-alone (PPTB) or a history of both (LLETZ+PPTB). Secondary analyses were performed to evaluate the impact of antenatal interventions, depth of cervical excision, and patient risk factors on PTB rate in each cohort.Material and methodsA retrospective observational cohort study of women referred to a tertiary Antenatal Prematurity Prevention Clinic with a history of LLETZ, PPTB, or LLETZ+PPTB. Information was collated from routinely collected clinical data on patient demographics, previous obstetric history, LLETZ dimensions, antenatal investigations/interventions, and gestation at delivery.ResultsA total of 1231 women with singleton pregnancies were included, 543 with history of LLETZ-alone, 607 with a history of PPTB-alone and 81 with a history of LLETZ+PPTB. PTB rates were 8.8% in the LLETZ-alone group, which mirrored the PTB rate in the local background obstetric population (8.9%) compared with 28.7% in the PPTB-alone and 37.0% in the LLETZ+PPTB cohorts. PTB rates were higher in LLETZ cohorts treated with antenatal intervention (cervical cerclage or progesterone pessary) and there was no evidence of an effect of intervention on risk of PTB in post-excision patients with identified shortened mid-trimester cervical length. Logistic regression modeling identified PPTB as a strong predictor of recurrent PTB. Excision depth was correlated with gestation at delivery in the LLETZ-alone group (r = −0.183, p ConclusionsPPTB has a greater impact on subsequent PTB risk compared with depth of cervical excisional treatment. The value and nature of antenatal interventions should be investigated in the post-excision population.</div

Impact of past obstetric history and cervical excision on preterm birth rate

IntroductionTo determine the impact on preterm birth (PTB) of a history of large loop excision of the transformation zone (LLETZ)-alone compared with a history of previous preterm birth-alone (PPTB) or a history of both (LLETZ+PPTB). Secondary analyses were performed to evaluate the impact of antenatal interventions, depth of cervical excision, and patient risk factors on PTB rate in each cohort.Material and methodsA retrospective observational cohort study of women referred to a tertiary Antenatal Prematurity Prevention Clinic with a history of LLETZ, PPTB, or LLETZ+PPTB. Information was collated from routinely collected clinical data on patient demographics, previous obstetric history, LLETZ dimensions, antenatal investigations/interventions, and gestation at delivery.ResultsA total of 1231 women with singleton pregnancies were included, 543 with history of LLETZ-alone, 607 with a history of PPTB-alone and 81 with a history of LLETZ+PPTB. PTB rates were 8.8% in the LLETZ-alone group, which mirrored the PTB rate in the local background obstetric population (8.9%) compared with 28.7% in the PPTB-alone and 37.0% in the LLETZ+PPTB cohorts. PTB rates were higher in LLETZ cohorts treated with antenatal intervention (cervical cerclage or progesterone pessary) and there was no evidence of an effect of intervention on risk of PTB in post-excision patients with identified shortened mid-trimester cervical length. Logistic regression modeling identified PPTB as a strong predictor of recurrent PTB. Excision depth was correlated with gestation at delivery in the LLETZ-alone group (r = −0.183, p ConclusionsPPTB has a greater impact on subsequent PTB risk compared with depth of cervical excisional treatment. The value and nature of antenatal interventions should be investigated in the post-excision population.</div

Mixed-Valent Mn Supertetrahedra and Planar Discs as Enhanced Magnetic Coolers

The syntheses and structures of two decametallic mixed-valent Mn supertetrahedra using 2-amino-2-methyl-1,3-propanediol (ampH2), two decametallic mixed-valent Mn planar discs using 2-amino-2-methyl-1,3-propanediol (ampH2) and 2-amino-2-ethyl-1,3-propanediol (aepH2), and a tetradecametallic mixed-valent Mn planar disc using pentaerythritol (H4peol) are reported. The decametallic complexes display dominant ferromagnetic exchange and spin ground states of S = 22, and the tetradecametallic complex displays dominant antiferromagnetic exchange and a spin ground state of S = 7 ± 1. All display large (the former) and enormous (the latter) magnetocaloric effectthe former as a result of negligible zero-field splitting of the ground state, and the latter as a result of possessing a high spin-degeneracy at finite low temperaturesmaking them the very best cooling refrigerants for low-temperature applications

Supramolecular Entanglement from Interlocked Molecular Nanomagnets

The trinuclear nanomagnet [MnIII3O(Et-sao)3(MeOH)3](ClO4) (1) has been utilized as a building block for the construction of the hexanuclear cluster [{MnIII3O(Et-sao)3(O2CPh)(EtOH)}2{4,4′-bpe}2] (3) that conforms to a rectangle and the two-dimensional coordination polymer {[MnIII3O(sao)3(4,4′-bpe)1.5]ClO4·3MeOH}n (2·3MeOH). The latter exhibits an unprecedented type of entanglement that is based on host guest interactions. The polygon versus the polymer is rationalized in terms of changing an auxiliary anion that influences the arrangement of the potentially “vacant” coordination axes on each MnIII ion of the trinuclear precursor and thereby directing the self-assembly process