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This is the first UK trial of pressurised intraperitoneal aerosolised chemotherapy (PIPAC) for colorectal cancer peritoneal metastases. This trial aimed to assess the impact of PIPAC in combination with standard of care systemic treatment on: progression free survival (PFS); quality of life (QoL); and short-term complications. In addition, this trial set out to demonstrate that PIPAC can be performed safely in operating theatres within a National Health Service (NHS) setting.

For the duration of COVID-19, cancer pathways will be affected by the significant loss of elective capacity and increased risk of COVID-19-related morbidity and mortality for cancer patients. Imperial College Healthcare NHS Trust (ICHT) has developed a simple, effective MDT recording process, using keywords, to support the tracking of patients who require treatment prioritisation, repeated clinical/MDT reviews and/or need adjustments to their treatment. Following implementation in April, the percentage of MDT outcomes with keywords recorded was 79% in June and 77% for the first two weeks of July. Analysis of the 3,680 MDT outcomes with at least one key word recorded showed that 96% had the 'intention to proceed' recorded. For 59% patients, the decision was to 'proceed', 5% patients are being monitored, 3% patients have been deferred and 29% were 'closed'. While this process adds time to busy MDTs, we hypothesise that it will support the tracking and safety-netting of thousands of cancer patients whose care has been affected by the pandemic. The process could easily be implemented in other trusts and adapted for other specialties., (© Royal College of Physicians 2021. All rights reserved.)

Competing Interests: Competing interests: None declared.

Background: Whole-body MRI (WB-MRI) could be an alternative to multimodality staging of colorectal cancer, but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in colorectal cancer., Methods: The Streamline C trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed colorectal cancer. Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or polyp cancer. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs), and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN43958015, and is complete., Findings: Between March 26, 2013, and Aug 19, 2016, 1020 patients were screened for eligibility. 370 patients were recruited, 299 of whom completed the trial; 68 (23%) had metastasis at baseline. Pathway sensitivity was 67% (95% CI 56 to 78) for WB-MRI and 63% (51 to 74) for standard pathways, a difference in sensitivity of 4% (-5 to 13, p=0·51). No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (95% [95% CI 92-97]) and standard pathways (93% [90-96], p=0·48). Agreement with the multidisciplinary team's final treatment decision was 96% for WB-MRI and 95% for the standard pathway. Time to complete staging was shorter for WB-MRI (median, 8 days [IQR 6-9]) than for the standard pathway (13 days [11-15]); a 5-day (3-7) difference. WB-MRI required fewer tests (median, one [95% CI 1 to 1]) than did standard pathways (two [2 to 2]), a difference of one (1 to 1). Mean per-patient staging costs were £216 (95% CI 211-221) for WB-MRI and £285 (260-310) for standard pathways., Interpretation: WB-MRI staging pathways have similar accuracy to standard pathways and reduce the number of tests needed, staging time, and cost., Funding: UK National Institute for Health Research., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The role of imaging in subfertility is well established but is changing. In addition to traditional fertility assessments, there is an emerging role for the radiologist. The role of imaging in fertility-restoring procedures in benign disease and congenital malformations is evolving, and there is a growing need for accurate identification of young candidates suitable for fertility-preserving surgery in the oncologic setting. To facilitate this developing role, knowledge of the key imaging modalities used and potential therapeutic applications is important for accurate diagnosis and interpretation by the radiologist. © RSNA, 2017.

Chlorophyll, essential for photosynthesis, is composed of a chlorin ring and a geranylgeranyl diphosphate (GGPP)-derived isoprenoid, which are generated by the tetrapyrrole and methylerythritol phosphate (MEP) biosynthesis pathways, respectively. Although a functional MEP pathway is essential for plant viability, the underlying basis of the requirement has been unclear. We hypothesized that MEP pathway inhibition is lethal because a reduction in GGPP availability results in a stoichiometric imbalance in tetrapyrrolic chlorophyll precursors, which can cause deadly photooxidative stress. Consistent with this hypothesis, lethality of MEP pathway inhibition in Arabidopsis thaliana by fosmidomycin (FSM) is light dependent, and toxicity of MEP pathway inhibition is reduced by genetic and chemical impairment of the tetrapyrrole pathway. In addition, FSM treatment causes a transient accumulation of chlorophyllide and transcripts associated with singlet oxygen-induced stress. Furthermore, exogenous provision of the phytol molecule reduces FSM toxicity when the phytol can be modified for chlorophyll incorporation. These data provide an explanation for FSM toxicity and thereby provide enhanced understanding of the mechanisms of FSM resistance. This insight into MEP pathway inhibition consequences underlines the risk plants undertake to synthesize chlorophyll and suggests the existence of regulation, possibly involving chloroplast-to-nucleus retrograde signaling, that may monitor and maintain balance of chlorophyll precursor synthesis.

Objective: The purposes of this study were to observe the relation between signal intensity (SI) on MR images with a high b value and the apparent diffusion coefficient (ADC) of bone marrow on body diffusion-weighted MR images, to determine cutoff values that enable separation of malignant and normal bone marrow, and to identify the upper ADC values of untreated multiple myeloma lesions and bone metastatic lesions of breast cancer., Materials and Methods: Retrospective evaluations of 16 patients without bone disease, 21 patients with untreated metastases of breast cancer, and 12 patients with myeloma undergoing body diffusion-weighted MRI were performed (b values, 50 s/mm(2) and 800 or 900 s/mm(2)). Normal yellow and red bone marrow regions were compared with metastatic breast and myeloma bone marrow lesions (one to five regions of interest per patient). SI values were normalized to kidney, muscle, and spinal cord SI. Signal-to-noise ratio and ADC for each lesion were recorded. Nonparametric, receiver operating characteristic, and nonlinear regression analyses were performed., Results: Yellow bone marrow and red bone marrow ADC values were lower than the tumor values (p < 0.001; area under the curve, 0.94; cutoff, 774 μm(2)/s). Tissue-normalized SI and the signal-to-noise ratio of normal bone marrow were also lower than those in tumor regions (p < 0.001; area under the curve, 0.86-0.88). Second-order polynomial curve fitting between SI and ADC was observed (muscle normalized SI, R(2) = 0.4). The 95th percentile and maximum values for mean tumor ADC distribution were 1209 μm(2)/s and 1433 μm(2)/s., Conclusion: Both tissue-normalized SI and ADC measurements allow differentiation between normal bone marrow and tumors of myeloma and breast cancer. The presence of a nonlinear relation between bone marrow SI and ADC values enables definition of an upper limit of ADC value for untreated myeloma lesions and metastatic lesions of breast cancer.

Objective: Small bowel tumours account for only 2-5 % of gastrointestinal neoplasms but are an important source of morbidity and mortality. This article presents the features demonstrated by a wide range of small bowel tumours across different imaging modalities., Conclusion: Early and accurate diagnosis via radiological means is an important factor in overall survival for malignant tumours and a thorough understanding of the common features is essential for all radiologists.

Nitric oxide signals diverse responses in animals and plants. Whereas nitric oxide synthesis mechanisms in animals are well understood, how nitric oxide is synthesized and regulated in plants remains controversial. NOA1 is a circularly permuted GTPase that is important for chloroplast function and is implicated in nitric oxide synthesis. However, the reported consequences of a null mutation in NOA1 are inconsistent. Whereas some studies indicate that the noa1 mutant has severe reductions in nitric oxide accumulation, others report that nitric oxide levels are indistinguishable between noa1 and the wild type. Here, we identify a correlation between the reported ability of noa1 to accumulate nitric oxide with growth on sucrose-supplemented media. We report that noa1 accumulates both basal and salicylic acid-induced nitric oxide only when grown on media containing sucrose. In contrast, nitric oxide accumulation in wild type is largely insensitive to sucrose supplementation. When grown in the absence of sucrose, noa1 has low fumarate, pale green leaves, slow growth and reduced chlorophyll content. These phenotypes are consistent with a defect in chloroplast-derived photosynthate production and are largely rescued by sucrose supplementation. We conclude that NOA1 has a primary role in chloroplast function and that its effects on the accumulation of nitric oxide are likely to be indirect., (© 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.)

Background: The membrane arm of Complex I (NADH:ubiquinone oxidoreductase) contains three large, and closely related subunits, which are called L, M, and N in E. coli. These subunits are homologous to components of multi-subunit Na(+)/H(+) antiporters, and so are implicated in proton translocation., Methodology/principal Findings: Nineteen site-specific mutations were constructed at two corresponding positions in each of the three subunits. Two positions were selected in each subunit: L&#95;K169, M&#95;K173, N&#95;K158 and L&#95;Q236, M&#95;H241, N&#95;H224. Membrane vesicles were prepared from all of the resulting mutant strains, and were assayed for deamino-NADH oxidase activity, proton translocation, ferricyanide reductase activity, and sensitivity to capsaicin. Corresponding mutations in the three subunits were found to have very similar effects on all activities measured. In addition, the effect of adding exogenous decylubiquinone on these activities was tested. 50 µM decylubiquinone stimulated both deamino-NADH oxidase activity and proton translocation by wild type membrane vesicles, but was inhibitory towards the same activities by membrane vesicles bearing the lysine substitution at the L236/M241/N224 positions., Conclusions/significance: The results show a close correlation with reduced activity among the corresponding mutations, and provide evidence that the L, M, and N subunits have a common role in Complex I.