No(cebo) Vax: COVID-19 Vaccine Beliefs Are Important Determinants of Both Occurrence and Perceived Severity of Common Vaccines' Adverse Effects.

This study highlights the role of psychological influences in triggering and amplifying the adverse effects of the COVID-19 vaccine (i.e., nocebo effects). Fear, beliefs, and expectations about the COVID-19 vaccine, trust in health and scientific institutions, and stable personality traits were measured in 315 adult Italian citizens (145 men) during the 15-min waiting time after vaccination. The occurrence and severity of 10 potential adverse effects were assessed 24 hr later. Nonpharmacological variables predicted nearly 30% of the severity of the vaccine's adverse effects. Expectations are important determinants of adverse effects from vaccines, and the results of the path analyses show that these expectations stem primarily from people's vaccine beliefs and attitudes, which can be changed. Implications for increasing vaccine acceptability and limiting the nocebo effect are discussed.

Management of post-mortem examination in SARS-CoV-19 infections.

A brief overview on the management of autopsies during the SARS-CoV-19 epidemic is proposed. In particular, the point is made of the Italian laws on the subject, the characteristics required for the autopsy room and the sampling suggested for the histological examination.

Pathological post-mortem findings in lungs infected with SARS-CoV-2.

Italy was the first European nation to be massively infected by SARS-CoV-2. Up to the end of May 2020, more than 33,000 deaths had been recorded in Italy, with a large prevalence among males, those over 75 years of age, and in association with co-morbidities. We describe the lung pathological and immunohistochemical post-mortem findings at the autopsy of nine patients who died of SARS-CoV-2-associated disease. We found in the lung tissues of all patients histological changes consistent with diffuse alveolar damage in various evolution phases ranging from acute exudative to acute proliferative to fibrotic phase. Alveolar damage was associated with prominent involvement of the vascular component in both the interstitial capillaries and the mid-size vessels, with capillary fibrin micro-thrombi, as well as organized thrombi even in medium-sized arteries, in most cases not related to sources of embolism. Eosinophilic infiltrate was also seen, probably reactive to pharmacological treatment. Viral RNA of SARS-CoV-2 was detected from the lung tissues of all the nine patients. Immunohistochemistry for the receptor of the SARS-CoV-2, ACE2, and its priming activator TMPRSS2 revealed that both proteins co-localize in airway cells. In particular, the ACE2 protein was expressed in both endothelial cells and alveolar type I and II pneumocytes in the areas of histological diffuse alveolar damage (DAD). Pneumocytes, but not endothelial cells, also expressed TMPRSS2. There are no distinctive histological features of SARS-CoV-2 infection with respect to SARS-CoV-1 and other DAD with different aetiology. The identification of the cause of death in the course of SARS-CoV-2 infection is more likely multi-factorial. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

COVID-19 free oncologic surgical hub: The experience of reallocation of a gynecologic oncology unit during pandemic outbreak.

INTRODUCTION: During the SARS-CoV-2 pandemic, the majority of healthcare resources of the affected Italian regions were allocated to COVID-19 patients. Due to lack of resources and high risk of death, most cancer patients have been shifted to non-surgical treatments. The following reports our experience of a Gynaecologic Oncology Unit's reallocation of resources in a COVID-19 free surgical oncologic hub in order to guarantee standard quality of surgical activities. MATERIALS AND METHODS: This is a prospective observational study performed in the Gynaecologic Oncology Unit, on the outcomes of the reallocation of surgical activities outside the University Hospital of Bologna, Italy, during the Italian lockdown period. Here, we described our COVID-19 free surgical oncologic pathway, in terms of lifestyle restrictions, COVID-19 screening measures, and patient clinical, surgical and follow up outcomes. RESULTS: During the lockdown period (March 9th - May 4th, 2020), 83 patients were scheduled for oncological surgery, 51 patients underwent surgery. Compared to pre-COVID period, we performed the same activities: number of cases scheduled for surgery, type of surgery and surgical and oncological results. No cases of COVID-19 infection were recorded in operated patients and in medical staff. Patients were compliant and well accepted the lifestyle restrictions and reorganization of the care. CONCLUSIONSONCLUSIONS: Our experience showed that the prioritization of oncological surgical care and the allocation of resources during a pandemic in COVID-19 free surgical hubs is an appropriate choice to guarantee oncological protocols.

Provision of Italian diagnostic reference levels for diagnostic and interventional radiology.

OBJECTIVES: The diagnostic reference level (DRL) is a useful tool for the optimisation of medical exposures. Thus, a Working Party coordinated by the Italian National Institute of Health and the National Workers Compensation Authority has been formed to provide Italian DRLs, for both diagnostic and interventional procedures, to be used as appropriate for the implementation of the 2013/59 European Directive into the national regulation. MATERIALS AND METHODS: The multidisciplinary Working Party was formed by professionals involved in diagnostic and interventional radiology medical exposures and started from a critical revision of both the literature and the results of previous Italian surveys. The procedures were divided into five sections for adult (projection radiography, mammography, diagnostic fluoroscopy, CT and interventional radiology) and two sections for paediatric patients (projection radiography and CT). The provided DRL values have been identified for "normal" adult patients and for age-classes of paediatric patients. RESULTS: Some of the DRL values provided by the Working Party are reported in this study as an example, divided by adult/paediatric patients, radiological technique and examination: specifically, DRLs for new radiological practices and new dose quantities as DRLs metric were introduced. The median value (rather than the mean) for each procedure, derived from a sample of patients, has to be compared with the corresponding DRL value, and dosimetric data related to a minimum number of patients should be collected for each examination. CONCLUSIONS: The approach to the definition and use of DRLs through guidelines of national Authorities in collaboration with scientific Associations should simplify the periodical updating and could be useful for keeping the optimisation of medical exposures faithful to the development of radiological practice.

Effects of the Combined Treatment with a G-Quadruplex-Stabilizing Ligand and Photon Beams on Glioblastoma Stem-like Cells: A Magnetic Resonance Study.

Glioblastoma multiforme is a malignant primary brain tumor with a poor prognosis and high rates of chemo-radiotherapy failure, mainly due to a small cell fraction with stem-like properties (GSCs). The mechanisms underlying GSC response to radiation need to be elucidated to enhance sensitivity to treatments and to develop new therapeutic strategies. In a previous study, two GSC lines, named line #1 and line #83, responded differently to carbon ions and photon beams, with the differences likely attributable to their own different metabolic fingerprint rather than to radiation type. Data from the literature showed the capability of RHPS4, a G-quadruplex stabilizing ligand, to sensitize the glioblastoma radioresistant U251MG cells to X-rays. The combined metabolic effect of ligand #190, a new RHPS4-derivative showing reduced cardiotoxicity, and a photon beam has been monitored by magnetic resonance (MR) spectroscopy for the two GSC lines, #1 and #83, to reveal whether a synergistic response occurs. MR spectra from both lines were affected by single and combined treatments, but the variations of the analysed metabolites were statistically significant mainly in line #1, without synergistic effects due to combination. The multivariate analysis of ten metabolites shows a separation between control and treated samples in line #1 regardless of treatment type, while separation was not detected in line #83.

Assessing radiation risk perception by means of a European stakeholder survey.

It is increasingly recognised that stakeholder views can be essential for ascertaining the credibility of those entrusted with protection of the public and workers against radiation risks, the robustness of the approaches to protection and the relevance of research underpinning radiation protection (RP). The CONCERT European Joint Programme of RP research included consideration of stakeholder views. These were evaluated by means of a publicly available survey, translated into 15 languages, to encourage responses from a wide range of European countries. The survey ran in 2017 and received some 1961 responses from many countries, although response rates varied widely between countries. The survey respondents were largely highly educated, with many having a professional connection to RP or the use of radiation in medicine or industry. Survey results indicated a high level of scientific/technical knowledge relevant to RP and indicated a general trust of most actors involved in the RP field, perhaps unsurprisingly given the nature of the sampled population. Most expressed a reasonable level of satisfaction with the information available to them on radiation risk, but there is clearly room for improvement. Additionally, the survey identified potential training needs amongst the groups who responded. It is concluded that, while the survey results are limited by the non-representativeness of the respondents by comparison with the population of the European Union as a whole, it has been successful in gaining insights into areas where communication could be improved, where professional training gaps are present and where research could help to build wider trust in RP.

How direct measurements of worker eyes with a Scheimpflug camera can affect lensdose coefficients in interventional radiology.

The 2013/59/Euratom Directive reduced the occupational exposure limits for the lens. Since it has become crucial to estimate the dose absorbed by the lens, we have studied the individual variability of exposed workers' ocular conformations with respect to the data estimated from their personal dosimetry. The anterior eye conformations of 45 exposed workers were acquired using Scheimpflug imaging and classified according to their sight conditions (emmetropia, myopia or hypermetropia). Three eye models were computed, with two lens reconstructions, and implemented in an interventional radiology scenario using Monte Carlo code. The models were dosimetrically analysed by simulating setup A, a theoretical monoenergetic and isotropic photon source (10-150 keV) and setup B, a more realistic interventional setting with an angiographic x-ray unit (50, 75, 100 kV peak). Scheimpflug imaging provided an average anterior chamber depth of (6.4 ± 0.5) mm and a lens depth of (3.9 ± 0.3) mm, together with a reconstructed equatorial lens length of (7.1-10.1) mm. Using these data for model reconstruction, dose coefficients (DCs) were simulated for all ocular structures. Regardless of the eye model used, the DCs showed a similar trend with radiation energy, which highlighted that for the same energy and setup, no significant dependence on ocular morphology and workers' visual conditions was observed. The maximum difference obtained did not exceed 1% for all eye models or structures analysed. Therefore, the individual variabilities of worker ocular anatomy do not require any additional correction, compared to the personal dosimetry data measured with a dedicated lens dosimeter. To estimate the dose absorbed by the other eye structures, it is, instead, essential to know the spectrum of the source that has generated the irradiation, since there are differences between monoenergetic sources and more realistic angiographic units.

Palliative treatment with electrochemotherapy in recurrent or metastatic vaginal cancer.

OBJECTIVE: Vaginal metastases are very rare events with a poor prognosis. To improve the quality of life, local treatments should be considered. The aim of this study was to evaluate the role of electrochemotherapy as palliative treatment in vaginal cancer not amenable to standard treatments due to poor performance status, previous treatments, or advanced disease. METHODS: This is a prospective observational study on patients diagnosed with vaginal cancer and treated from January 2017 to December 2018 with palliative electrochemotherapy. We collected data on patients with vaginal cancer treated by electrochemotherapy with the aim of local control. Data regarding electrochemotherapy, hospital stay, adverse events, and patient outcomes were analyzed. Intravenous bleomycin was injected as a bolus in 2-3 min at a dose of 15 000 UI/m2 and electrical pulses started 8 min after chemotherapy. Electrochemotherapy response was defined according to the Response Evaluation Criteria in Solid Tumors. RESULTS: Five patients with vaginal recurrence (two squamous, two melanomas, and one leiomyosarcoma) and one with vaginal metastasis from intestinal adenocarcinoma received one treatment and two patients were re-treated. Imaging reported nodal metastasis (inguinal or pelvic) in two patients, distant metastases in two, and both node and distant metastasis in two patients, respectively. Response Evaluation Criteria in Solid Tumors showed a complete response in one patient, partial response in three patients, stable disease in one patient, and progressive disease in one patient, with an overall response rate of 67% and a clinical benefit rate (complete response, partial response, stable disease) of 83%. Two patients were re-treated and had a new response (partial response and stable disease, respectively). At last follow-up, two patients had died of the disease, two were alive with stable disease, one was alive with progressive disease, and one was alive without disease. Median post-electrochemotherapy overall survival was 12.9 months (range 1.6-26.9) and 1-year overall survival was 66.7%. CONCLUSIONS: This preliminary experience showed a tumor response or stabilization in 83% of patients requiring palliative management for vaginal cancer. Further studies are needed to evaluate treatment outcome in larger and prospective series.

Different Mechanisms Underlie the Metabolic Response of GBM Stem-Like Cells to Ionizing Radiation: Biological and MRS Studies on Effects of Photons and Carbon Ions.

Glioblastoma multiforme (GBM) is a malignant primary brain tumor with very poor prognosis, high recurrence rate, and failure of chemo-radiotherapy, mainly due to a small fraction of cells with stem-like properties (GSCs). To study the mechanisms of GSCs resistance to radiation, two GSC lines, named line #1 and line #83, with different metabolic patterns and clinical outcome, were irradiated with photon beams and carbon ions and assessed by 1H Magnetic Resonance Spectroscopy (MRS). Both irradiation modalities induced early cytotoxic effects in line #1 with small effects on cell cycle, whereas a proliferative G2/M cytostatic block was observed in line #83. MR spectroscopy signals from mobile lipids (ML) increased in spectra of line #1 after photon and C-ion irradiation with effects on lipid unsaturation level, whereas no effects were detected in line #83 spectra. Gamma-Aminobutyric Acid (GABA), glutamic acid (glu) and Phosphocreatine (pCr) signals showed a significant variation only for line #1 after carbon ion irradiation. Glucose (glc) level and lactate (Lac) extrusion behaved differently in the two lines. Our findings suggest that the differences in irradiation response of GSCs #1 and #83 lines are likely attributable to their different metabolic fingerprint rather than to the different radiation types.

Relationship of demoralization with anxiety, depression, and quality of life: A Southern European study of Italian and Portuguese cancer patients.

BACKGROUND: Demoralization syndrome is a significant condition that has not been greatly studied in Southern European countries. AIMS: To extend the knowledge of demoralization in Southern Europe by examining its prevalence according to different methods of assessment, its relationship with anxiety and depression, and its impact on quality of life (QoL) among cancer patients. METHODS: A convenience sample of 195 cancer outpatients from two oncology centers (102 from Lisbon, Portugal, and 93 from Ferrara, Italy) participated in an observational, cross-sectional study using the Diagnostic Criteria of Psychosomatic Research-Demoralization interview (DCPR/D) and psychometric tools (Demoralization scale-DS; Patient Health Questionnaire-9/PHQ-9; Hospital Anxiety Depression Scale-HADS; and European Quality of Life-5-EQ-5D). RESULTS: A 25.1% prevalence (CI 95%, 0.19-0.31) of clinically relevant demoralization was reported on the DCPR/D interview. A total demoralization score cutoff score ≥ 25 maximized sensitivity (81.6%), and specificity (72.6%) in identifying DCPR/D demoralized patients. The DCPR/D and DS were associated with poorer levels of QoL. About half of the patients who were demoralized were not clinically depressed (PHQ-9). Self-reported suicidal ideation (PHQ-9 item 9) was found in a minority of patients (8.2%), most of whom (77%) were cases of depression (PHQ-9), but one-quarter (23%) were not depressed, yet moderately/severely demoralized (DCPR/D and DS). CONCLUSIONS: This Southern European study confirms the importance of demoralization in cancer patients as a different condition with respect to depression and its relationship with poor QoL and suicidal ideation.

What patients' complaints and praise tell the health practitioner: implications for health care quality. A qualitative research study.

OBJECTIVE: In order to identify which health care aspects play a role in patient satisfaction and quality of health care, the present study analyses a large number of instances of complaint and praise. DESIGN AND SETTING: One thousand two hundred and thirty-five instances of complaint and one thousand five hundred thirty-six of praise submitted from patients or other souces (i.e. a patient's family member or a legal representative) to a northern-Italian hospital were analysed. MAIN OUTCOME MEASURES: We adopted Reader and colleagues' (2014) patients' complaint taxonomy, in conjunction with a detailed content analysis of relationship and communication of information aspects. RESULTS: The most frequent causes of complaint concerned care system management (68.1%), particularly the time taken to access treatment, and relationship aspects (52.8%). The importance of relationship aspects was confirmed by the expression of gratitude through praise (89%). The most critical factor of the relationship domain was effective communication of information to the patient (39.3%). Frequently patients complained of: (i) having received information that was inconsistent with the truth, (ii) having had difficulty in obtaining information, and (iii) untimely communication of information. Clinical aspects did not seem to be the main factors that triggered a complaint (36,8%), and, when indicated, they were almost always associated with relationship issues. CONCLUSIONS: This study indicates that not only complaints, but also instances of praise, are a potentially important source of information regarding health care aspects that play a role in patient satisfaction and quality of care. Our findings underline the relevance of relationship aspects in determining patients' satisfaction with the care received. In particular, health practitioners should focus their attention on how information is understood, translated and applied by patients.

(1) H NMR spectroscopy of glioblastoma stem-like cells identifies alpha-aminoadipate as a marker of tumor aggressiveness.

Patients suffering from glioblastoma multiforme (GBM) face a poor prognosis with median survival of about 14 months. High recurrence rate and failure of conventional treatments are attributed to the presence of GBM cells with stem-like properties (GSCs). Metabolite profiles of 42 GSC lines established from the tumor tissue of adult GBM patients were screened with (1) H NMR spectroscopy and compared with human neural progenitor cells from human adult olfactory bulb (OB-NPCs) and from the developing human brain (HNPCs). A first subset (n=12) of GSCs exhibited a dramatic accumulation of the metabolite α-aminoadipate (αAAD), product of the oxidation of α-aminoadipic semialdehyde catalyzed by the ALDH7A1 aldehyde dehydrogenase (ALDH) family in lysine catabolism. αAAD was low/not detectable in a second GSC subset (n=13) with the same neural metabolic profile as well as in a third GSC subset (n=17) characterized by intense lipid signals. Likewise, αAAD was not detected in the spectra of OB-NPCs or HNPCs. Inhibition of mitochondrial ATP synthase by oligomycin treatment revealed that the lysine degradative pathway leading to αAAD formation proceeds through saccharopine, as usually observed in developing brain. Survival curves indicated that high αAAD levels in GSCs significantly correlated with poor patient survival, similarly to prostate and non-small-cell-lung cancers, where activity of ALDH7A1 correlates with tumor aggressiveness.

1H NMR detects different metabolic profiles in glioblastoma stem-like cells.

The metabolic profiles of glioblastoma stem-like cells (GSCs) growing in neurospheres were examined by (1)H NMR spectroscopy. Spectra of two GSC lines, labelled 1 and 83, from tumours close to the subventricular zone of the temporal lobe were studied in detail and compared with those of neural stem/progenitor cells from the adult olfactory bulb (OB-NPCs) and of the T98G glioblastoma cell line. In both GSCs, signals from myoinositol (Myo-I), UDP-hexosamines (UDP-Hex) and glycine indicated an astrocyte/glioma metabolism. For line 1, the presence of signals from N-acetyl aspartate, GABA and creatine pointed to a neuronal fingerprint. These metabolites were almost absent from line 83 spectra, whereas lipid signals, absent from normal neural lineages, were intense in line 83 spectra and remained low in those of line 1, irrespective of apoptotic fate. Spectra of OB-NPC cells displayed strong similarities with those from line 1, with low lipid signals and clearly detectable neuronal signals. In contrast, the spectral profile of line 83 was more similar to that of T98G, displaying high lipids and nearly complete absence of the neuronal markers. A mixed neural-astrocyte metabolic phenotype with a strong neuronal fingerprint was therefore found in line 1, while an astrocytic/glioma-like metabolism prevailed in line 83. We found a signal assigned to the amide proton of N-acetyl galactosamine in GSC lines and in OB-NPC spectra, whereas it was absent from those of T98G cells. This signal may be related to a stem-cell-specific protein glycosylation pattern and is therefore suggested as a marker of cell multipotency. Other GSC lines from patients with different clinical outcomes were then examined. Unsupervised analysis of spectral data from 13 lines yielded two clusters, with six lines resembling spectral features of line 1 and seven resembling those of line 83, suggesting that distinct metabolic phenotypes may be present in GSC lines.

A real-time system to report abnormal events involving staff in a nuclear medicine therapy unit.

A system for internal and voluntary reporting of abnormal events in a Nuclear Medicine Therapy Unit is described. This system is based on the Internet of Things and is composed of an application for mobile devices and a wireless network of detectors. The application is addressed to healthcare professionals and is intended to be a user-friendly tool to make the reporting procedure little laborious. The network of detectors allows for a real-time measurement of the dose distribution in the patient's room. The staff was involved in all stages, from the design of the dosimetry system and mobile application up to their final testing. Face-to-face interviews were carried out with 24 operators in different roles in the Unit (radiation protection experts, physicians, physicists, nuclear medicine technicians and nurses). The preliminary results of the interviews and the current state of development of the application and the detection network will be described.

Peroxisome proliferator-activated receptor-gamma expression in monocytes/macrophages from rheumatoid arthritis patients: relation to disease activity and therapy efficacy--a pilot study.

OBJECTIVES: Peroxisome proliferator-activated receptor-gamma (PPARγ) is expressed by different cell types in the joints and plays a relevant anti-inflammatory role in various diseases. This pilot study aimed to evaluate PPARγ expression in monocytes/macrophages isolated from RA patients as compared with healthy subjects, the relationships between PPARγ expression, MMP-9 activity and disease, and the influence of therapy with anti-rheumatic drugs on these parameters. METHODS: Thirty RA patients of both sexes (treated with CSs and MTX, mainly) and 15 healthy volunteers were enrolled in this study. Disease severity was evaluated by the 28-joint disease activity score (DAS-28). Monocytes and monocyte-derived macrophages (MDMs) were isolated by standard procedures. PPARγ protein and mRNA expression were assessed by immunoblotting and real-time PCR, respectively; MMP-9 activity was determined by gelatin zymography. Moreover, we checked the ability of 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ, a PPARγ agonist), MTX and methylprednisolone (MP) to affect PPARγ expression and lipopolysaccharide (LPS)-induced MMP-9 activity. RESULTS: Monocytes/MDMs from RA patients have significantly enhanced PPARγ expression (both protein and mRNA) and MMP-9 activity as compared with healthy donors. Interestingly, cells from patients with less active disease (DAS-28 <3.2) present higher PPARγ protein expression and lower MMP-9 activity than RA patients with DAS-28 >3.2. At therapeutic concentrations, MTX and MP increase in vitro PPARγ protein expression and inhibit LPS-induced MMP-9 activity. CONCLUSION: PPARγ expression in human monocytes/MDMs could represent an indicator of disease activity and therapy efficacy in RA because patients with a DAS-28 score <3.2 show the highest expression.

Case report of anesthesia for free fibula flap reconstruction in Ewing sarcoma: Safety and efficacy of continuous popliteal sciatic nerve block and very low doses of intravenous heparin.

A child with a maxillary Ewing sarcoma was operated for tumor asportation and reconstruction with free fibula flap. Adequate anticoagulation was achieved with lower doses of heparin and monitored with multiple ACT values. We used NIRS monitoring to avoid hypoperfusion. Post-operative pain relief was guarantited by local anestethic continous infusion.

Glioblastoma Stem-Like Cells (GSCs) with Mesenchymal Signature: Lipid Profiles of Mobile Lipids Obtained with MRS before and after Radio/Chemical Treatments.

Glioblastoma is the most common and lethal primary malignant brain tumor in adults. Glioblastoma stem cells (GSCs) promote and are responsible for glioblastoma intratumoral heterogeneity and therapy resistance, due to their two main features: self-renewal and differentiation. Lipids have important biological and physiological functions that are critical for understanding the regulation and control of stem cell fate; lipid metabolism and related unsaturation levels play a possible role as the target of therapeutics to overcome glioblastoma radioresistance. This paper aimed at an in-depth analysis of 13 GSC mesenchymal (MES) lines, two subclones, and a stabilized glioblastoma line (T98G) by magnetic resonance spectroscopy (MRS). Particularly, 2D MRS was used to investigate lipid unsaturation behavior during growth in culture and after treatment with etomoxir and photon beams. MES lines, although belonging to the same genetic and metabolic cluster, showed metabolic heterogeneity when observed by MRS, focusing on lipid signals. Nonetheless, the observed unsaturation level stability for two representative lines after stressful treatments suggests unusual robustness of the unsaturation levels for each line, as a peculiar and intrinsic characteristic of GSCs.

Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial.

BACKGROUND: Closed-loop systems link continuous glucose measurements to insulin delivery. We aimed to establish whether closed-loop insulin delivery could control overnight blood glucose in young people. METHODS: We undertook three randomised crossover studies in 19 patients aged 5-18 years with type 1 diabetes of duration 6.4 years (SD 4.0). We compared standard continuous subcutaneous insulin infusion and closed-loop delivery (n=13; APCam01); closed-loop delivery after rapidly and slowly absorbed meals (n=7; APCam02); and closed-loop delivery and standard treatment after exercise (n=10; APCam03). Allocation was by computer-generated random code. Participants were masked to plasma and sensor glucose. In APCam01, investigators were masked to plasma glucose. During closed-loop nights, glucose measurements were fed every 15 min into a control algorithm calculating rate of insulin infusion, and a nurse adjusted the insulin pump. During control nights, patients' standard pump settings were applied. Primary outcomes were time for which plasma glucose concentration was 3.91-8.00 mmol/L or 3.90 mmol/L or lower. Analysis was per protocol. This trial is registered, number ISRCTN18155883. FINDINGS: 17 patients were studied for 33 closed-loop and 21 continuous infusion nights. Primary outcomes did not differ significantly between treatment groups in APCam01 (12 analysed; target range, median 52% [IQR 43-83] closed loop vs 39% [15-51] standard treatment, p=0.06;