Cell-based tracers as Trojan horses for image-guided surgery

Surgeons rely almost completely on their own vision and palpation to recognize affected tissues during surgery. Consequently, they are often unable to distinguish between different cells and tissue types. This makes accurate and complete resection cumbersome. Targeted image-guided surgery (IGS) provides a solution by enabling real-time tissue recognition. Most current targeting agents (tracers) consist of antibodies or peptides equipped with a radiolabel for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT), magnetic resonance imaging (MRI) labels, or a near-infrared fluorescent (NIRF) dye. These tracers are preoperatively administered to patients, home in on targeted cells or tissues, and are visualized in the operating room via dedicated imaging systems. Instead of using these ‘passive’ tracers, there are other, more ‘active’ approaches of probe delivery conceivable by using living cells (macrophages/monocytes, neutrophils, T cells, mesenchymal stromal cells), cell(-derived) fragments (platelets, extracellular vesicles (exosomes)), and microorganisms (bacteria, viruses) or, alternatively, ‘humanized’ nanoparticles. Compared with current tracers, these active contrast agents might be more efficient for the specific targeting of tumors or other pathological tissues (e.g., atherosclerotic plaques). This review provides an overview of the arsenal of possibilities applicable for the concept of cell-based tracers for IGS

A multimodal molecular imaging approach targeting urokinase plasminogen activator receptor for the diagnosis, resection and surveillance of urothelial cell carcinoma

With a 5-year recurrence rate of 30-78%, urothelial cell carcinoma (UCC) rates amongst the highest of all solid malignancies. Consequently, after transurethral resection, patients are subjugated to life-long endoscopic surveillance. A multimodal near-infrared (NIR) fluorescence-based imaging strategy can improve diagnosis, resection and surveillance, hence increasing quality of life.Methods: Expression of urokinase plasminogen activator receptor (uPAR) and epithelial cell adhesion molecule (EpCAM) are determined on paraffin-embedded human UCC using immunohistochemistry and on UCC cell lines by flow cytometry. MNPR-101, a humanised monoclonal antibody targeting uPAR is conjugated to IRDye800CW and binding is validated in vitro using surface plasmon resonance and cell-based binding assays. In vivo NIR fluorescence and photoacoustic three-dimensional (3D) imaging are performed with subcutaneously growing human UM-UC-31uc2 cells in BALB/c-nude mice. The translational potential is confirmed in a metastasising UM-UC-31uc2 orthotopic mouse model. InfliximabIRDye800CW and rituximab-IRDye800CW are used as controls.Results: UCCs show prominent uPAR expression at the tumour-stroma interface and EpCAM on epithelial cells. uPAR and EpCAM are expressed by 6/7 and 4/7 UCC cell lines, respectively. In vitro, MNPR-101-IRDye800CW has a picomolar affinity for domain 2-3 of uPAR. In vivo fluorescence imaging with MNPR-101-IRDye800CW, specifically delineates both subcutaneous and orthotopic tumours with tumour-to-background ratios reaching as high as 6.8, differing significantly from controls (p < 0.0001). Photoacoustic 3D in depth imaging confirms the homogenous distribution of MNPR-101-IRDye800CW through the tumour.Conclusions: MNPR-101-IRDye800CW is suitable for multimodal imaging of UCC, awaiting clinical translation. (C) 2021 The Author(s). Published by Elsevier Ltd.Surgical oncolog

Scintillator ageing of the T2K near detectors from 2010 to 2021

The T2K experiment widely uses plastic scintillator as a target for neutrino interactions and an active medium for the measurement of charged particles produced in neutrino interactions at its near detector complex. Over 10 years of operation the measured light yield recorded by the scintillator based subsystems has been observed to degrade by 0.9–2.2% per year. Extrapolation of the degradation rate through to 2040 indicates the recorded light yield should remain above the lower threshold used by the current reconstruction algorithms for all subsystems. This will allow the near detectors to continue contributing to important physics measurements during the T2K-II and Hyper-Kamiokande eras. Additionally, work to disentangle the degradation of the plastic scintillator and wavelength shifting fibres shows that the reduction in light yield can be attributed to the ageing of the plastic scintillator. The long component of the attenuation length of the wavelength shifting fibres was observed to degrade by 1.3–5.4% per year, while the short component of the attenuation length did not show any conclusive degradation

Exploring the surgical personality

Surgery is a demanding field, requiring determination and emotional stability. This review explores the surgical personality, addressing international personality differences between surgical and non-surgical specialties. Across the globe, surgically-interested individuals (i.e., medical students, residents, surgeons) generally scored higher on conscientiousness, open mindedness, and extraversion, and lower on neuroticism compared to nonsurgically-interested contemporaries. Extraversion was inversely correlated to burnout in surgical residents and open mindedness to reduced competence in giving feedback. Although additional region- and/or country-specific research is warranted, being or becoming a surgeon appears to correlate to personality traits such as high conscientiousness and low neuroticism.(c) 2022 The Author(s). Published by Elsevier Ltd on behalf of Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/).Vascular Surger

Pasireotide in dumping syndrome-results from a phase 2, international, multicentre study

Introduction: Dumping syndrome is a prevalent complication of gastric bypass surgery, characterised by early (cardiovascular and gastrointestinal response, along with rise in haematocrit [Ht] and pulse rate [PR]) and late (hypoglycaemia due to excess insulin) postprandial symptoms. Only a subset of patients (pts) responds to treatment based on dietary measures, off-label use of acarbose and somatostatin analogues (SSA). Pasireotide (PAS), a next-generation SSA with high affinity to 4 of the 5 somatostatin receptor subtypes (sst), being a potent inhibitor of incretin and insulin secretion (via sst2 and sst5), prevents postprandial hypoglycaemia. Aims & Methods: This is a single-arm, open-label, multicentre, intra-patient dose escalation, phase 2 study to evaluate the preliminary efficacy, safety and pharmacokinetics of PAS subcutaneous (s.c.) and long-acting release (LAR) in pts with dumping syndrome. The 6-month (mo) core period included a 3-mo s.c. phase followed by a 3-mo LAR phase. Eligible pts started treatment with PAS s.c. 50μg tid (before meals); dose could be increased by increment of 50μg up to 200μg tid based on the presence of hypoglycaemia (plasma glucose75.0%) and 36.4% (12/33; 95% CI: 20.4%>54.9%) in the s.c. and LAR phases, respectively. Notably, plasma glucose levels during OGTT were higher at all time points with s.c. dose vs baseline and vs LAR dose. Fewer pts had an increase in PR of≥10 beat/min and an increase in Ht level of≥3% (from pre-OGTT to 30 min post-OGTT) at mo 3 than at the baseline (18.6% vs 60.5% and 16.3% vs 27.9%, respectively). Overall, the most frequent (>15% of pts [N=43]) AEs were headache (32.6%); diarrhoea, hypoglycaemia (25.6% each); abdominal pain (18.6%); upper abdominal pain and nausea (16.3% each). Grade 3/4 AEs occurred in 32.6% pts; most frequent (≥2 pts) were hypoglycaemia (9.3%); diarrhoea, upper abdominal pain, dizziness and small intestinal obstruction (4.7% each). Conclusion: These results suggest that PAS s.c. effectively controls postprandial hypoglycaemia and improves changes in PR and Ht in pts with dumping syndrome. PAS s.c. and LAR were well tolerated; no new safety signals were identified in this population. A phase 3 study is warranted to confirm the effects of PAS in dumping syndrome

Monitoring discharge in a tidal river using water level observations: Application to the Saigon River, Vietnam

International audienceThe hydrological dynamics of the Saigon River is ruled by a complex combination of factors, which need to be disentangled to prevent and limit risks of flooding and salt intrusion. In particular, the Saigon water discharge is highly influenced by tidal cycles with a relatively low net discharge. This study proposes a low-cost technique to estimate river discharge at high frequency (every 10 min in this study). It is based on a stage-fall-discharge (SFD) rating curve adapted from the general Manning Strickler law, and calibrated thanks to two ADCP campaigns. Two pressure sensors were placed at different locations of the river in September 2016: one at the centre of Ho Chi Minh City and one in Phu Cuong, 40 km upstream approximately. The instantaneous water discharge data were used to evaluate the net residual discharge and to highlight seasonal and inter-annual trends. Both water level and water discharge show a seasonal behaviour. Rainfall, including during the Usagi typhoon that hit the megalopolis in November 2018, has no clear and direct impact on water level and water discharge due to the delta flat morphology and complex response between main channel and side channel network and ground water in this estuarine system under tidal influence. However, we found some evidences of interactions between precipitation, groundwater, the river network and possibly coastal waters. This paper can be seen as a proof of concept to (1) present a low-cost discharge method that can be applied to other tidal rivers, and (2) demonstrate how the high-frequency discharge data obtained with this method can be used to evaluate discharge dynamics in tidal river systems

A Systematic Review and Meta-analysis of Ventilator-associated Pneumonia in Adults in Asia: An Analysis of National Income Level on Incidence and Etiology

Background: Ventilator-associated pneumonia (VAP) is the commonest hospital-acquired infection (HAI) in intensive care. In Asia, VAP is increasingly caused by resistant gram-negative organisms. Despite the global antimicrobial resistance crisis, the epidemiology of VAP is poorly documented in Asia. Methods: We systematically reviewed literature published on Ovid Medline, Embase Classic, and Embase from 1 January 1990 to 17 August 2017 to estimate incidence, prevalence, and etiology of VAP. We performed a meta-analysis to give pooled rates and rates by country income level. Results: Pooled incidence density of VAP was high in lower- and upper-middle-income countries and lower in high-income countries (18.5, 15.2, and 9.0 per 1000 ventilator-days, respectively). Acinetobacter baumannii (n = 3687 [26%]) and Pseudomonas aeruginosa (n = 3176 [22%]) were leading causes of VAP; Staphylococcus aureus caused 14% (n = 1999). Carbapenem resistance was common (57.1%). Conclusions: VAP remains a common cause of HAI, especially in low- and middle-income countries, and antibiotic resistance is high

Bacterial bloodstream infections in a tertiary infectious diseases hospital in Northern Vietnam: aetiology, drug resistance, and treatment outcome

BACKGROUND: Bloodstream infections (BSIs) are associated with high morbidity and mortality worldwide. However their aetiology, antimicrobial susceptibilities and associated outcomes differ between developed and developing countries. Systematic data from Vietnam are scarce. Here we present aetiologic data on BSI in adults admitted to a large tertiary referral hospital for infectious diseases in Hanoi, Vietnam. METHODS: A retrospective study was conducted at the National Hospital for Tropical Diseases between January 2011 and December 2013. Cases of BSI were determined from records in the microbiology department. Case records were obtained where possible and clinical findings, treatment and outcome were recorded. BSI were classified as community acquired if the blood sample was drawn 48 h. RESULTS: A total of 738 patients with BSI were included for microbiological analysis. The predominant pathogens were: Klebsiella pneumoniae (17.5%), Escherichia coli (17.3%), Staphylococcus aureus (14.9%), Stenotrophomonas maltophilia (9.6%) and Streptococcus suis (7.6%). The overall proportion of extended spectrum beta-lactamase (ESBL) production among Enterobacteriaceae was 25.1% (67/267 isolates) and of methicillin-resistance in S. aureus (MRSA) 37% (40/108). Clinical data was retrieved for 477 (64.6%) patients; median age was 48 years (IQR 36-60) with 27.7% female. The overall case fatality rate was 28.9% and the highest case fatality was associated with Enterobacteriaceae BSI (34.7%) which accounted for 61.6% of all BSI fatalities. CONCLUSIONS: Enterobacteriaceae (predominantly K. pneumoniae and E. coli) are the most common cause of both community and hospital acquired bloodstream infections in a tertiary referral clinic in northern Vietnam

Acceptability of and willingness to pay for using a smartphone-based vaccination application in a Vietnamese cohort

10.2147/PPA.S185129Patient Preference and Adherence122583-259