Outcome prioritization and preferences among older adults with cancer starting chemotherapy in a randomized clinical trial.

INTRODUCTION: Older adults with cancer facing competing treatments must prioritize between various outcomes. This study assessed health outcome prioritization among older adults with cancer starting chemotherapy. METHODS: Secondary analysis of a randomized trial addressing vulnerabilities in older adults with cancer. Patients completed three validated outcome prioritization tools: 1) Health Outcomes Tool: prioritizes outcomes (survival, independence, symptoms) using a visual analog scale; 2) Now vs. Later Tool: rates the importance of quality of life at three times-today versus 1 or 5 years in the future; and 3) Attitude Scale: rates agreement with outcome-related statements. The authors measured the proportion of patients prioritizing various outcomes and evaluated their characteristics. RESULTS: A total of 219 patients (median [range] age 71 [65-88], 68% with metastatic disease) were included. On the Health Outcomes Tool, 60.7% prioritized survival over other outcomes. Having localized disease was associated with choosing survival as top priority. On the Now vs. Later Tool, 50% gave equal importance to current versus future quality of life. On the Attitude Scale, 53.4% disagreed with the statement "the most important thing to me is living as long as I can, no matter what my quality of life is"; and 82.2% agreed with the statement "it is more important to me to maintain my thinking ability than to live as long as possible". CONCLUSION: Although survival was the top priority for most participants, some older individuals with cancer prioritize other outcomes, such as cognition and function. Clinicians should elicit patient-defined priorities and include them in decision-making.

The use of Lutetium-177 PSMA radioligand therapy with high dose rate brachytherapy for locally recurrent prostate cancer after previous definitive radiation therapy: a randomized, single-institution, phase I/II study (ROADSTER).

BACKGROUND: Isolated local failure (ILF) can occur in patients who initially receive definitive radiation therapy for prostate cancer. Salvage therapy for ILF includes high dose rate (HDR) brachytherapy. Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) can accurately detect ILF and can exclude extraprostatic disease. Lutetium-177 PSMA Radioligand Therapy (RLT) is a novel treatment for prostate cancer that can target prostate cancer accurately, while sparing radiation dose to normal tissues. METHODS: ROADSTER is a phase I/II randomized, single-institution study. Patients with an ILF of prostate cancer after definitive initial radiation therapy are eligible. The ILF will be confirmed with biopsy, magnetic resonance imaging (MRI) and PSMA PET. Patients will be randomized between HDR brachytherapy in two fractions (a standard of care salvage treatment at our institution) (cohort 1) or one treatment of intravenous Lutetium-177 PSMA RLT, followed by one fraction of HDR brachytherapy (cohort 2). The primary endpoints for the phase I portion of the study (n = 12) will be feasibility, defined as 10 or more patients completing the study protocol within 24 months of study activation; and safety, defined as zero or one patients in cohort 2 experiencing grade 3 or higher toxicity in the first 6 months post-treatment. If feasibility and safety are achieved, the study will expand to a phase II study (n = 30 total) where preliminary efficacy data will be evaluated. Secondary endpoints include changes in prostate specific antigen levels, acute toxicity, changes in quality of life, and changes in translational biomarkers. Translational endpoints will include interrogation of blood, urine, and tissue for markers of DNA damage and immune activation with each treatment. DISCUSSION: ROADSTER explores a novel salvage therapy for ILF after primary radiotherapy with combined Lutetium-177 PSMA RLT and HDR brachytherapy. The randomized phase I/II design will provide a contemporaneous patient population treated with HDR alone to facilitate assessment of feasibility, tolerability, and biologic effects of this novel therapy. TRIAL REGISTRATION: NCT05230251 (ClinicalTrials.gov).

CT perfusion measurement of postictal hypoperfusion: localization of the seizure onset zone and patterns of spread.

PURPOSE: Seizures are often followed by a period of transient neurological dysfunction and postictal alterations in cerebral blood flow may underlie these symptoms. Recent animal studies have shown reduced local cerebral blood flow at the seizure onset zone (SOZ) lasting approximately 1 h following seizures. Using arterial spin labelling (ASL) MRI, we observed postictal hypoperfusion at the SOZ in 75% of patients. The clinical implementation of ASL as a tool to identify the SOZ is hampered by the limited availability of MRI on short notice. Computed tomography perfusion (CTP) also measures blood flow and may circumvent the logistical limitations of MRI. Thus, we aimed to measure the extent of postictal hypoperfusion using CTP. METHODS: Fourteen adult patients with refractory focal epilepsy admitted for presurgical evaluation were prospectively recruited and underwent CTP scanning within 80 min of a habitual seizure. Patients also underwent a baseline scan after they were seizure-free for > 24 h. The acquired scans were qualitatively assessed by two reviewers by visual inspection and quantitatively assessed through a subtraction pipeline to identify areas of significant postictal hypoperfusion. RESULTS: Postictal blood flow reductions of > 15 ml/100 g-1/min-1 were seen in 12/13 patients using the quantitative method of analysis. In 10/12 patients, the location of the hypoperfusion was partially or fully concordant with the presumed SOZ. In all patients, additional areas of scattered hypoperfusion were seen in areas corresponding to seizure spread. CONCLUSION: CTP can reliably measure postictal hypoperfusion which is maximal at the presumed SOZ.

Quantitatively detecting postictal hypoperfusion in patients with focal epilepsy using CT perfusion: Determining cross-modality comparisons and electrode artifacts.

BACKGROUND: We previously showed that CT perfusion (CTP) and arterial spin labelled (ASL) MRI can localize the seizure onset zone in humans via postictal perfusion patterns. As a step towards improving the feasibility/ease of collecting postictal CBF data, we determined whether EEG electrodes need to be removed for CTP data collection and whether a cross-modality comparison between baseline ASL and postictal CTP data is possible. NEW METHOD: Five patients with epilepsy underwent postictal CTP scanning. Three patients had an interictal ASL scan; one patient had both an ASL and CTP interictal scan. Postictal CTP maps were quantitatively compared to 1) ASL maps averaged from 100 healthy controls, 2) each patient's baseline ASL map and 3) each patient's baseline CTP map. To assess for electrode artifacts, a phantom and one patient underwent CTP scanning with EEG electrodes in place. The acquired scans were assessed for artifacts and for postictal hypoperfusion. RESULTS: Focal postictal hypoperfusion was observable only in intra-modality comparisons (CTP to CTP) and not in cross-modality comparisons (CTP to ASL). EEG electrodes produced streaking artifact that decreased image quality and precluded quantitative analysis. COMPARISON WITH EXISTING METHODS(S): An intra-modality comparison of baseline CTP to postictal CTP was the only comparison method that showed localized hypoperfusion. CONCLUSIONS: Quantitative comparison between postictal CTP and baseline ASL scans is not feasible. Postictal hypoperfusion can be detected by CTP only when two CTP scans are collected and when metallic EEG electrodes are removed.

A Phase II Trial of Older Adults With Metastatic Breast Cancer Receiving nab-Paclitaxel: Melding the Fields of Geriatrics and Oncology.

INTRODUCTION: Phase II clinical trials including geriatric assessment (GA) measures are critical for improving the evidence base for older adults with cancer. We assessed the efficacy and tolerability of nab-paclitaxel in older adults with metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients aged ≥ 65 years with MBC and ≤ 1 previous line of chemotherapy received 100 mg of nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle. A GA was completed pre-chemotherapy, and the validated Cancer and Aging Research Group (CARG) chemotherapy toxicity risk score was calculated. Relationships between tolerability (number of courses, hospitalizations, dose reductions, and toxicity) and risk score were assessed using general linear models, Student t tests, and the Fisher test. Response rate and progression-free survival were evaluated using the Kaplan-Meier method. RESULTS: Forty patients (mean age, 73 years; range, 65-87 years) were included. The median number of cycles was 6, 75% (n = 30) of patients had ≥ 1 dose hold, and 50% (n = 20) had ≥ 1 dose reduction. Fifty-eight percent (n = 23) had treatment-related ≥ grade 3 toxicities, and 30% (n = 12) were hospitalized owing to toxicity. Thirty-five percent (n = 14) responded, and the median progression-free survival was 6.5 months (95% confidence interval, 5.5 months to undefined). Patients with intermediate/high toxicity risk scores had higher risk of grade ≥ 3 toxicity than those with low risk scores (odds ratio, 5.8; 95% confidence interval, 1.3-33.1; P = .01). A higher mean risk score was associated with higher likelihood of dose reductions and hospitalizations. CONCLUSIONS: Among older adults with MBC receiving weekly nab-paclitaxel, more than one-half experienced ≥ grade 3 chemotherapy toxicity. However, a GA-based risk score could predict treatment tolerability.

COMPARISON OF PATHOGENESIS OF P. BERGHEIINFECTION IN MOUSE AND RAT MODELS

@#Background: The cytokine cascade in the immunopathogenesis of malaria infection had been widely studied. However, their specific association with survival and severe infection remained obscure.Methods: Thestudy investigated the cytokine profiles and histopathological features of malaria in the severe infection and survival models by using male ICR mice and male Sprague Dawley rats respectively.Results: The severe model, the infected ICR mice, exhibited a high parasitemia with 100% mortality after peak parasitemia at day 5 post-infection. The survival model, the infected Sprague Dawley rats, showed mild parasitemia with full recovery by day 14 of infection. Both severe and survival models showed similar histopathological severity during peak parasitemia. The severe model produced highly elevated levels of pro-inflammatory cytokines, TNF-α and IL-1α, and low levels of the anti-inflammatory cytokine, IL-4; while the survival model showed low levels of TNF-α and IL-1α with high levels of IL-4.Conclusion: There were differences in the pathogenesis of the severe and survival models of malaria infection. These could be a basis for immunotherapy of malaria in the future

Designing Triple Adult Liver Grafts From an Ideal Deceased Liver.

Splitting deceased donor livers and creating 3 grafts from a whole liver may be feasible and shorten the waiting time for organ donation in patients with high mortality rates. We hypothesized that it might be reasonable to procure 3 grafts for donation from one deceased donor liver by splitting the liver into left (segment II, III, IV), right anterior (segment V, VIII), and right posterior lobes (segment VI, VII) for liver transplantation according to the portal system trifurcated variations. We designed the right anterior branch with the main portal trunk and middle hepatic artery to become inflow of right anterior lobe, the left portal vein and left hepatic artery to become the inflow of left lobe and right posterior branch, and right hepatic artery to become the inflow of right posterior lobe. We retrospectively reviewed the volumetric computed tomography and magnetic resonance cholangiopancreatography of 153 liver donors. The hepatic and portal veins, hepatic artery, and biliary system were reorganized and classified. The volumetric proportions of the liver grafts were measured. Trifurcation of the portal vein variation was found in approximately 13.7% of portal systemic variations. The left lobe accounted for 29.18% of the total liver volume, the right anterior lobe, 35.22%, and the right posterior lobe, 35.6%. We validated this principle by dissecting the explanted liver and identified the triple grafts' weights, percentages, vessels, and biliary ducts system. The splitting of deceased donor livers into 3 split liver grafts for use in liver transplantation surgery can be clinically useful.

Prospective Multicenter Study of Changes in MTT after Aneurysmal SAH and Relationship to Delayed Cerebral Ischemia in Patients with Good- and Poor-Grade Admission Status.

BACKGROUND AND PURPOSE: Patients with aneurysmal SAH and good clinical status at admission are considered at a lower risk for delayed cerebral ischemia. Prolonged MTT may be associated with an increased risk. It is unclear whether this is dependent on clinical status. Our purpose was to determine whether increased MTT within 3 days of aneurysmal SAH compared with baseline is associated with a higher risk of delayed cerebral ischemia in patients with good (World Federation of Neurosurgical Societies I-III) versus poor (World Federation of Neurosurgical Societies IV-V) admission status. MATERIALS AND METHODS: This prolonged MTT was a multicenter, prospective cohort investigation of 87 patients with aneurysmal SAH. MTT was measured at admission before aneurysm treatment (MTT1) and following repair (MTT2) within 3 days of admission; MTTdiff was calculated as the difference between MTT2 and MTT1. Changes in MTT across time were assessed with repeated measures analyses. Risk of delayed cerebral ischemia or death was determined with multivariate logistic regression analysis. RESULTS: In patients with a good grade (n = 49), MTT was prolonged in patients who developed delayed cerebral ischemia, with MTTdiff significantly greater (0.82 ± 1.5) compared with those who did not develop delayed cerebral ischemia (-0.14 ± 0.98) (P = .03). Prolonged MTT was associated with a significantly higher risk of delayed cerebral ischemia or death (OR = 3.1; 95% CI, 1.3-7.4; P = .014) on multivariate analysis. In patients with poor grades (n = 38), MTTdiff was not greater in patients who developed delayed cerebral ischemia; MTT1 was significantly prolonged compared with patients with a good grade. CONCLUSIONS: Patients in good clinical condition following aneurysmal SAH but with increasing MTT in the first few days after aneurysmal SAH are at high risk of delayed cerebral ischemia and warrant close clinical monitoring.

Permeability surface area product analysis in malignant brain edema prediction - A pilot study.

BACKGROUND AND PURPOSE: Using an extended CT perfusion acquisition (150s), we sought to determine the association between perfusion parameters and malignant edema after ischemic stroke. METHODS: Patients (from prospective study PROVE-IT, NCT02184936) with terminal internal carotid artery±proximal middle cerebral occlusion were involved. CTA was assessed for clot location and status of leptomeningeal collaterals. The following CTP parameters were calculated within the ischemic territory and contralaterally: permeability surface area product (PS), cerebral blood flow (CBF) and cerebral blood volume (CBV). PS was calculated using the adiabatic approximation to the Johnson and Wilson model. Outcome was evaluated by midline shift and infarction volume on follow-up imaging. RESULTS: Of 200 patients enrolled, 7 patients (3.5%) had midline shift≥5mm (2 excluded for poor-quality scans). Five patients with midline shift and 5 matched controls were analysed. There was no significant difference in mean PS, CBF and CBV within the ischemic territory between the two groups. A CBV threshold of 1.7ml/100g had the highest AUC=0.72, 95% CI=0.54-0.90 for early midline shift prediction, sensitivity and specificity were 0.83 and 0.67 respectively. CONCLUSION: Our preliminary results did not show significant differences in permeability surface area analysis if analysed for complete ischemic region. CBV parameter had the highest accuracy and there was a trend for the mean PS values for midline shift prediction.

Activation of salt-inducible kinase 2 promotes the viability of peritoneal mesothelial cells exposed to stress of peritoneal dialysis.

Maintaining mesothelial cell viability is critical to long-term successful peritoneal dialysis (PD) treatment. To clarify the viability mechanism of peritoneal mesothelial cells under PD solutions exposure, we examined the mechanisms of cellular response to this stress conditions. Here we report that the proteasome activity is inhibited when treated with PD solutions. Proteasome inhibition-mediated activation of salt-inducible kinase 2 (SIK2), an endoplasmic reticulum-resident protein, is important for mesothelial cell viability. SIK2 is mobilized to promote autophagy and protect the cells from apoptosis under PD solution or MG132 treatment. Immunofluorescence staining showed that SIK2 is colocalized with LC3B in the autophagosomes of mesothelial cells treated with PD solution or derived from patients undergoing PD treatment. SIK2 activation is likely via a two-step mechanism, upstream kinases relieving the autoinhibitory conformation of SIK2 molecule followed by autophosphorylation of Thr175 and activation of kinase activity. These results suggest that activation of SIK2 is required for the cell viability when proteasome activity is inhibited by PD solutions. Maintaining or boosting the activity of SIK2 may promote peritoneal mesothelial cell viability and evolve as a potential therapeutic target for maintaining or restoring peritoneal membrane integrity in PD therapy.

Rapid detection of α-thalassaemia variants using droplet digital PCR.

INTRODUCTION: Alpha thalassaemia is a highly prevalent disease globally and is a well-known public health problem in Malaysia. The deletional forms of the mutation are the most common forms found in alpha thalassaemia. The three most common deletional alpha thalassaemia found in this region include --(SEA) deletion, -α(3.7) rightward and -α(4.2) leftward deletions. The prevalence rate of triplication alpha cases such as ααα(anti3.7) and ααα(anti4.2) is not known in Malaysia although it plays a role in exacerbating the clinical phenotypes in beta thalassaemia carriers. Recently, there have been more reported cases of rare alpha thalassaemia mutations due to the advancement of molecular techniques involved in thalassaemia detections. Therefore, it is essential to develop a new method which allows the detection of different alpha thalassaemia mutations including the rare ones simultaneously and accurately. METHODS: The purpose of this study was to design an assay for the detection of triplications, common and rare deletional alpha thalassaemia using droplet digital PCR (ddPCR). RESULTS: This is a quantitative detection method to measure the changes of copy number which can detect deletions, duplications and triplications of the alpha globin gene simultaneously. CONCLUSION: In conclusion, ddPCR is an alternative method for rapid detection of alpha thalassaemia variants in Malaysia.

Wood Preference of Reticulitermes virginicus (Blattodea: Rhinotermitidae) Using No-, Two-, and Four-Choice Designs and Seven Different Measures of Wood Consumption.

Three hundred Reticulitermes virginicus (Banks) workers were exposed to three 1-cm3 wood blocks of either Quercus sp. (Red Oak), Populus sp. (Poplar), Pinus sp. (Pine), or Sequoia sp. (Redwood) placed into one of the three bioassay designs (no-, two-, and four-choice) for 21 d. Termite wood consumption was measured by wood weight loss, resistance class, and visual rating. Wood consumption rates were determined using four formulas in addition to two standardized visual rating scales (American Society for Testing and Materials [ASTM] and American Wood Protection Association [AWPA]) and a preference ranking obtained for each measure. The wood consumption formula, rating scale, and preference rankings were compared by bioassay design. The overall preference ranking of the four wood types as determined by the combination of all three designs was­1) Pine, 2) Red Oak, 3) Redwood, and 4) Poplar. Results indicate that bioassay design influenced both wood consumption and preference rankings. A no-choice design can determine aversion; a four-choice design the most preferred wood; and a two-choice design can illuminate the fine details of comparative preference. The different formulas employed for calculation of consumption rate influenced preference ranking in the no- and four-choice designs but not the two-choice design.

Randomized phase II study of axitinib versus placebo plus best supportive care in second-line treatment of advanced hepatocellular carcinoma.

BACKGROUND: The efficacy and safety of axitinib, a potent and selective vascular endothelial growth factor receptors 1-3 inhibitor, combined with best supportive care (BSC) was evaluated in a global, randomized, placebo-controlled phase II trial in patients with locally advanced or metastatic hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients with HCC and Child-Pugh Class A who progressed on or were intolerant to one prior antiangiogenic therapy were stratified by tumour invasion (presence/absence of extrahepatic spread and/or vascular invasion) and region (Asian/non-Asian) and randomized (2:1) to axitinib/BSC (starting dose 5 mg twice-daily) or placebo/BSC. The primary end point was overall survival (OS). RESULTS: The estimated hazard ratio for OS was 0.907 [95% confidence interval (CI) 0.646-1.274; one-sided stratified P = 0.287] for axitinib/BSC (n = 134) versus placebo/BSC (n = 68), with the median (95% CI) of 12.7 (10.2-14.9) versus 9.7 (5.9-11.8) months, respectively. Results of prespecified subgroup analyses in Asian versus non-Asian patients or presence versus absence of tumour invasion were consistent with the overall population. Improvements favouring axitinib/BSC (P < 0.01) were observed in secondary efficacy end point analyses [progression-free survival (PFS), time to tumour progression (TTP), and clinical benefit rate (CBR)], and were retained among Asian patients in the prespecified subgroup analyses. Overall response rate did not differ significantly between treatments and patient-reported outcomes favoured placebo/BSC. Most common all-causality adverse events with axitinib/BSC were diarrhoea (54%), hypertension (54%), and decreased appetite (47%). Baseline serum analyses identified potential new prognostic (interleukin-6, E-selectin, interleukin-8, angiopoietin-2, migration inhibitory factor, and c-MET) or predictive (E-selectin and stromal-derived factor-1) factors for survival. CONCLUSIONS: Axitinib/BSC did not improve OS over placebo/BSC in the overall population or in stratification subgroups. However, axitinib/BSC resulted in significantly longer PFS and TTP and higher CBR, with acceptable toxicity in patients with advanced HCC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01210495.

Dissecting alternative splicing in the formation of Miltenberger glycophorin subtype III (GYP.Mur).

BACKGROUND AND OBJECTIVES: Miltenberger subtype III (Mi.III, GP.Mur) is one of the most important red cell phenotypes in the fields of transfusion in South-East Asia. GP.Mur is believed to evolve from homologous gene recombination events between glycophorin A (GYPA) and glycophorin B (GYPB). GYP.Mur differs from GYPB in only seven nucleotides dispersed near the region of 3' exon 3 of GYP.Mur. The goal of this study was to dissect how these nucleotide variants affected splicing of exon 3. MATERIALS AND METHODS: We first designed two minigene constructs: one containing GYP.Mur from exon 2 to exon 4 and the other containing GYPB in the same region. To test how these nucleotide variations between GYP.Mur and GYPB affected the splicing, a repertoire of the GYP.Mur-like minigene constructs with different point mutations were created. These minigene variants were evaluated for their abilities to induce splicing of exon 3 using a heterologous expression system. RESULTS: (1) GYP.Mur minigene expressed exons 2, 3 and 4, whereas GYPB minigene expressed only exon 2 and exon 4. (2) The single nucleotide alteration at the position of the 5' splice site of glycophorin intron 3 reversed the splicing decision. (3) The nucleotide variations between GYP.Mur and GYPB other than that at the 5' splice site showed very little or no effect on splicing of exon 3. CONCLUSION: Splicing of the glycophorin B-A-B hybrids (GYP.Mur and GYP.BUN) and unsplicing of GYPB follow the GU-AG rule strictly.

The use of Taqman genotyping assays for rapid confirmation of ß-thalassaemia mutations in the Malays: accurate diagnosis with low DNA concentrations.

INTRODUCTION: In Malaysia, ß-thalassaemia is a common inherited blood disorder in haemoglobin synthesis with a carrier rate of 4.5%. Currently, PCR-incorporating techniques such as amplification refractory mutation system (ARMS) or reverse dot blot hybridization (RDBH) are used in ß-thalassaemia mutation detection. ARMS allows single-mutation identification using two reactions, one for wild type and another for mutant alleles. RDBH requires probe immobilization and optimization of hybridization and washing temperatures which is time consuming. The aim of our study was to investigate whether ß-thalassaemia mutations can be identified in samples with low DNA concentrations. METHODS: Genotype identification of common ß-thalassaemia mutations in Malays was carried out using Taqman genotyping assays. RESULTS: Results show that the Taqman assays allow mutation detection with DNA template concentrations as low as 2-100 ng. In addition, consistent reproducibility was observed in the Taqman assays when repeated eight times and at different time intervals. CONCLUSION: The developed sensitive Taqman assays allow molecular characterization of ß-thalassaemia mutations in samples with low DNA concentrations. The Taqman genotyping assays have potential as a diagnostic tool for foetal blood, chorionic villi or pre-implantation genetic diagnosis where DNA is limited and precious.

Kinetic model optimization for characterizing tumour physiology by dynamic contrast-enhanced near-infrared spectroscopy.

Dynamic contrast-enhanced (DCE) methods are widely used with magnetic resonance imaging and computed tomography to assess the vascular characteristics of tumours since these properties can affect the response to radiotherapy and chemotherapy. In contrast, there have been far fewer studies using optical-based applications despite the advantages of low cost and safety. This study investigated an appropriate kinetic model for optical applications to characterize tumour haemodynamics (blood flow, F, blood volume, V(b), and vascular heterogeneity) and vascular leakage (permeability surface-area product, PS). DCE data were acquired with two dyes, indocyanine green (ICG) and 800 CW carboxylate (IRD(cbx)), from a human colon tumour xenograph model in rats. Due to the smaller molecular weight of IRD(cbx) (1166 Da) compared to albumin-bound ICG (67 kDa), PS of IRD(cbx) was significantly larger; however, no significant differences in F and V(b) were found between the dyes as expected. Error analysis demonstrated that all parameters could be estimated with an uncertainty less than 5% due to the high temporal resolution and signal-to-noise ratio of the optical measurements. The next step is to adapt this approach to optical imaging to generate haemodynamics and permeability maps, which should enhance the clinical interest in optics for treatment monitoring.

Current status and guidelines for the assessment of tumour vascular support with dynamic contrast-enhanced computed tomography.

Dynamic contrast-enhanced computed tomography (DCE-CT) assesses the vascular support of tumours through analysis of temporal changes in attenuation in blood vessels and tissues during a rapid series of images acquired with intravenous administration of iodinated contrast material. Commercial software for DCE-CT analysis allows pixel-by-pixel calculation of a range of validated physiological parameters and depiction as parametric maps. Clinical studies support the use of DCE-CT parameters as surrogates for physiological and molecular processes underlying tumour angiogenesis. DCE-CT has been used to provide biomarkers of drug action in early phase trials for the treatment of a range of cancers. DCE-CT can be appended to current imaging assessments of tumour response with the benefits of wide availability and low cost. This paper sets out guidelines for the use of DCE-CT in assessing tumour vascular support that were developed using a Delphi process. Recommendations encompass CT system requirements and quality assurance, radiation dosimetry, patient preparation, administration of contrast material, CT acquisition parameters, terminology and units, data processing and reporting. DCE-CT has reached technical maturity for use in therapeutic trials in oncology. The development of these consensus guidelines may promote broader application of DCE-CT for the evaluation of tumour vascularity. Key Points • DCE-CT can robustly assess tumour vascular support • DCE-CT has reached technical maturity for use in therapeutic trials in oncology • This paper presents consensus guidelines for using DCE-CT in assessing tumour vascularity.

Fulminant Type 1 diabetes in a pregnant woman as an initial manifestation of the insulin autoimmune syndrome.

Fulminant Type 1 diabetes is a subtype of Type 1 diabetes characterized by (1) abrupt onset of diabetes, (2) very short duration of hyperglycaemia with mildly elevated HbA(1c) (< 69 mmol/mol, 8.5%), (3) rapid progression to diabetic ketoacidosis, (4) very low C-peptide level, and (5) often associated with elevated serum pancreatic enzymes, and absence of diabetes-related autoantibodies. We encountered a case of fulminant Type 1 diabetes that developed with an initial manifestation of the insulin autoimmune syndrome and rapidly progressed to diabetic ketoacidosis during pregnancy. A 31-year-old Korean woman presented with recurrent sudden onset of sweating and change of consciousness during sleep at 19 weeks gestation. During a 72-h fasting test, hypoglycaemia (1.72 mmol/l) occurred at 4 h after the start of the test. At that time, there was a high insulin level (370.2 µU/ml), a paradoxically low C-peptide level (0.01 nmol/l) and a positive insulin autoantibody test. An oral glucose tolerance test revealed postprandial hyperglycaemia. She was initially diagnosed as the insulin autoimmune syndrome. On the day 5 of admission, she developed diabetic ketoacidosis. Her HbA(1c) was 62 mmol/mol (7.8%). The rapid progression of diabetic ketoacidosis altered the diagnosis to fulminant Type 1 diabetes. This case differed from typical fulminant Type 1 diabetes because it presented with hypoglycaemia, and positive insulin and anti-phospholipid antibody tests. Her HLA typing was HLA-DQA1*0302, 0501, HLA-DRB1*0301 (DR3), 0901(DR9). Her glucose level was subsequently very well controlled with multiple insulin injections and she successfully delivered a healthy baby.