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Die besprühte alte Piper Aztec (PA23) hat eine geringere Umweltwirkung – 14,5 kg (äquivaltente) CO2 pro 100 km pro Sitzplatz – als ein neues Passagierflugzeug (z.B. A320neo): 18,9 kg äquivalente CO2 pro 100 km pro Sitzplatz. Das liegt daran, dass die Aztec tiefer fliegt. Ein Business Jet (z.B. Learjet 70/75) hat andere Zahlen: 64,7 kg äquivalente CO2 pro 100 km pro Sitzplatz.

Purpose K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods.Materials and Methods Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers).Results In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively.Conclusion The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Global very long baseline interferometry (VLBI) observations at low frequencies are of great importance since they allow us to test the oldest part of the relativistic electron populations in young radio sources. At 327 MHz ((Formula presented.) 92 cm), the most compact regions are self-absorbed, and the number of cores detected is very small. This could provide useful measurements of the magnetic field in the relativistic plasma, to be compared with the equipartition field derived from minimum energy arguments. Partial self-absorption takes place also in hot-spots. However, disentangling the hot-spot emission from that of the lobe turned out to be rather difficult. On the other hand, a clearer and more complete characterization of the volumes occupied by the magnetized relativistic plasma and its total energy content can be obtained at 327 MHz. In turn, an independent estimate of the source age can be inferred, on the basis of simple assumptions on the jet power. Here, we show that the ages derived in this way (between (Formula presented.) and (Formula presented.) year) are consistent with the radiative ages determined from the break frequency in the radio spectrum.

Funding Information: This work was funded by the 4IE project (0499_4IE_PLUS_4_E) funded by Interreg V-A España-Portugal (POCTEP) 2017/2021 (https://4ie.eu/). Publisher Copyright: © 2021, The Author(s). Daily medication use can be affected by the gradual loss of functional ability. Thus, elderly patients are at risk for nonadherence due to functional decline, namely, decreases in cognitive skills and visual and manual dexterity. The main objective was to assess the ability of older people to self-manage their medication and to identify the main predictors for unintentional nonadherence. A cross-sectional study was conducted (2014–2017) in community centers and pharmacies. Functional assessment was performed with the Portuguese versions of the Drug Regimen Unassisted Grading Scale (DRUGS-PT) and the Self-Medication Assessment Tool (SMAT-PT). A purposive sample including 207 elderly patients was obtained. To identify the main predictors, binary logistic regression was performed. The average DRUGS-PT score was slightly lower than that in other studies. On the SMAT-PT, the greatest challenge for patients was identifying medications by reading labels/prescriptions. The main difficulties identified were medication memorization and correct schedule identification. The scores were higher with the real regimen than with the simulated regimen, underlining the difficulties for patients in receiving new information. Regarding the predictors of an older individual’s ability to self-manage medications, two explanatory models were obtained, with very high areas under the curve (> 90%). The main predictors identified were cognitive ability, level of schooling and daily medication consumption. publishersversion published

Purpose NUF2 has been implicated in multiple cancers recently, suggesting NUF2 may play a role in the common tumorigenesis process. In this study, we aim to perform comprehensive meta-analysis of NUF2 expression in the cancer types included in the Cancer Genome Atlas (TCGA). Materials and methods RNA-sequencing data in 31 cancer types in the TCGA data and 11 independent datasets were used to examine NUF2 expression. Silencing NUF2 using targeting shRNAs in hepatocellular carcinoma cell lines was used to evaluate NUF2's role in hepatocellular carcinoma (HCC) in vitro and in vivo. Results NUF2 up-regulation is significantly observed in 23 out of the 31 cancer types in the TCGA datasets and validated in 13 major cancer types using 11 independent datasets. NUF2 overexpression was clinically important as high NUF2 was significantly associated with tumor stages in eight different cancers. High NUF2 was also associated with significantly poorer patient overall survival and disease-free survival in eight and six cancers, respectively. We proceeded to validate NUF2 overexpression and its negative association with overall survival at the protein level in an independent cohort of 40 HCC patients. Compared to the non-targeting controls, NUF2 knockdown cells showed significantly reduced ability to grow, migrate into a scratch wound and invade the 8 μm porous membrane in vitro. Moreover, NUF2 knockdown cells also formed significantly smaller tumors than control cells in mouse xenograft assays in vivo. Conclusion NUF2 up-regulation is a common feature of many cancers. The prognostic potential and functional impact of NUF2 up-regulation warrant further studies.

Purpose Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice. Materials and Methods TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate. Results The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was 8 and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR‒positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs. Conclusion Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR‒positive status could be a significant biomarker for predicting ICI response in patients.

Purpose Proton beam therapy (PBT) is a state-of-the-art technology employed in radiotherapy (RT) for cancer patients. This study characterized how PBT has been used in clinical practice in Korea.Materials and Methods Patients who received any type of RT between 2007 and 2019 were identified from the radiation oncology registry of the two PBT facilities operating in Korea (National Cancer Center and Samsung Medical Center). The chi-square test was used to identify patient- and treatment-related characteristics associated with the receipt of PBT.Results A total of 54,035 patients had been treated with some form of RT in the two institutions, of whom 5,398 received PBT (10.0%). The number of patients who receive PBT has gradually increased since PBT first started, from 162 patients in 2007 to 1,304 patients in 2019. Among all types of cancer, PBT use in liver cancer has been steadily increasing from 20% in 2008-2009 to 32% in 2018-2019. In contrast, that in prostate cancer has been continuously decreasing from 20% in 2008-2009 to < 10% in 2018-2019. Male sex, very young or old age, stage I-II disease, residency in non-capital areas, a definitive setting, a curative treatment aim, enrollment in a clinical trial, re-irradiation and insurance coverage were significantly associated with the receipt of PBT (all p < 0.05).Conclusion Since PBT started in Korea, the number of patients receiving PBT has increased to more than 1,000 per year and treatment indications have expanded. Liver cancer is the most common primary tumor among all PBT cases in Korea.

Purpose Radiation-induced lymphopenia is associated with worse outcomes in solid tumors. We assessed the impact of interleukin-7 (IL-7), a key cytokine in lymphocyte homeostasis, on radiation-induced lymphopenia.Materials and Methods A post-hoc analysis was performed in a prospective cohort of 98 patients with hepatocellular carcinoma who were treated with radiotherapy in 2016-2018. Blood IL-7 levels were assayed before and at the end of radiotherapy. Acute severe lymphopenia (ASL) was defined as a total lymphocyte count of < 200/μL during radiotherapy. Cox and logistic regression analyses were performed to identify predictors of survival and ASL development, respectively.Results Patients with ASL (n=41) had significantly poorer overall survival than those without (12.0 months vs. 25.3 months, p=0.001). Patients with lymphocyte recovery showed significantly longer overall survival than those without (21.8 months vs. 10.3 months, p=0.042). ASL was an independent predictor of poor survival (hazard ratio, 2.07; p=0.015). Patients with ASL had significantly lower pre-radiotherapy IL-7 levels (2.07 pg/mL vs. 3.01 pg/mL, p=0.010). A high pre-radiotherapy IL-7 level was an independent predictor of a reduced risk of ASL development (hazard ratio, 0.40; p=0.004). IL-7 levels reflected a feedback response to ASL, with a higher ΔIL-7 in patients with ASL and a lower ΔIL-7 in those without ASL (0.48 pg/mL vs. –0.66 pg/mL, p < 0.001). Post-radiotherapy IL-7 levels were significantly positively correlated with the total lymphocyte counts at 2 months.Conclusion IL-7 is associated with the development of and recovery from ASL, which may impact survival. To overcome radiation-induced lymphopenia, a novel strategy using IL-7 may be considered.

We developed a snowdrift model to evaluate the snowdrift height around snow fences, which are often installed along roads in snowy, windy locations. The model consisted of the conventional computational fluid dynamics solver that used the lattice Boltzmann method and a module for calculating the snow particles’ motion and accumulation. The calculation domain was a half channel with a flat free-slip boundary on the top and a non-slip boundary on the bottom, and an inflow with artificially generated turbulence from one side to the outlet side was imposed. In addition to the reference experiment with no fence, experiments were set up with a two-dimensional and a three-dimensional fence normal to the dominant wind direction in the channel center. The estimated wind flow over the two-dimensional fence was characterized by a swirling eddy in the cross section, whereas the wind flow in the three-dimensional fence experiment was horizontally diffluent with a dipole vortex pair on the leeward side of the fence. Almost all the snowdrift formed on the windward side of the two-dimensional and three-dimensional fences, although the snowdrift also formed along the split streaks on the leeward side of the three-dimensional fence. Our results suggested that the fence should be as long as possible to avoid snowdrifts on roads.

Funding Information: This work was supported by AbbVie and by iNOVA4Health – UIDB/04462/2020, a program financially supported by Fundação para a Ciência e Tecnologia (FCT) / Ministério da Educação e Ciência, through national funds. RM and TFM were recipients of PhD fellowships funded by FCT (SFRH/BD/132163/2017 and PD/BD/128377/2017, respectively) and CB was funded by “The Discoveries Centre for Regenerative and Precision Medicine” (European Commission Horizon 2020 Research and Innovation programme, under the Grant Agreement 739572). Publisher Copyright: © 2021, The Author(s). The current standard preclinical oncology models are not able to fully recapitulate therapeutic targets and clinically relevant disease biology, evidenced by the 90% attrition rate of new therapies in clinical trials. Three-dimensional (3D) culture systems have the potential to enhance the relevance of preclinical models. However, the limitations of currently available cellular assays to accurately evaluate therapeutic efficacy in these models are hindering their widespread adoption. We assessed the compatibility of the lactate dehydrogenase (LDH) assay in 3D spheroid cultures against other commercially available readout methods. We developed a standardized protocol to apply the LDH assay to ex vivo cultures, considering the impact of culture growth dynamics. We show that accounting for growth rates and background release levels of LDH are sufficient to make the LDH assay a suitable methodology for longitudinal monitoring and endpoint assessment of therapeutic efficacy in both cell line-derived xenografts (xenospheres) and patient-derived explant cultures. This method has the added value of being non-destructive and not dependent on reagent penetration or manipulation of the parent material. The establishment of reliable readout methods for complex 3D culture systems will further the utility of these tumor models in preclinical and co-clinical drug development studies. publishersversion published

European Society of Gastrointestinal Endoscopy recommends needle-knife fistulotomy (NKF) as the preferred precut technique. However, there is little information on whether NKF performed at different times is associated with different success and adverse event rates. We compared the outcomes of 3 different timings of NKF. This was an observational study conducted at 4 institutions and this was a retrospective analysis of prospectively collected data. We included 330 consecutive patients submitted to NKF attempt for biliary access. Patients were divided into three groups: NKF as an initial procedure for biliary access (group A, n = 121); early NKF defined as after 5 min, 5 attempts, or 2 pancreatic passages (group B, n = 99); and late NKF: after at least 10 min of unsuccessful standard biliary cannulation (group C, n = 110). We assessed the success rate of biliary cannulation at initial ERCP, time to perform NKF until biliary cannulation, overall biliary cannulation rate (second ERCP when initial failure), adverse event rate, and predictors of post-ERCP pancreatitis (PEP). The initial cannulation rate was 98%, 91% and 94% for groups A, B and C respectively, p = 0.08, whereas overall biliary cannulation rate was 100%, 95% and 98%, p = 0.115. The adverse event rate/PEP was 4.1%/2.5%, 7.1%/4% and 10.9%/8.2%, for groups A, B and C respectively, (p = 0.197 and p = 0.190). Median time for creating the fistula was A = 4.0 min, B = 3.2 min, and C = 5.6 min, p

Three-dimensional printing is a technology in expansion in the medical field. It also presents many applications in orthopedics. Our review article aims to describe 3D printing, types of 3D printers, and its use in the orthopedic field. 3D models can be created using tomography scans. Those models can then be manipulated, even simulating surgeries. It is possible to print biomodels, which will help us understand deformities and plan surgeries. Orthopedic surgeons must be updated in these disruptive technologies that may help their daily practice. Level of Evidence V, Expert opinion. RESUMO A impressão 3D é uma tecnologia em expansão na medicina, possuindo diversas utilidades na ortopedia. O objetivo deste artigo de revisão é descrever o que é a impressão 3D, seus tipos e suas aplicações na ortopedia. Modelos em 3 dimensões podem ser criados a partir da tomografia computadorizada. Estes modelos podem ser manipulados em softwares específicos, onde inclusive cirurgias podem ser simuladas. Utilizando impressoras 3D podemos criar biomodelos que nos ajudam a compreender deformidades e planejar cirurgias. É importante que o ortopedista se mantenha atualizado nestas novas tecnologias disruptivas que podem auxiliar muito no seu dia a dia. Nível de Evidência V, Opinião do especialista.

Using an entirely new dataset of audited filings from firms that manage hedge funds, this study examines whether the hedge fund compensation contract aligns managerial incentives and investor interests. Our novel dataset allows us to distinguish between firms focused exclusively on hedge fund management and diversified firms offering products in addition to hedge funds. Our results for compensation data of hedge fund only management firms confirm that compensation increases as assets under management increase, despite increased costs and performance diseconomies of scale. Hedge funds managed by diversified firms have significantly lower performance. A relatively small proportion of the compensation from these firms is generated from hedge funds. The results are consistent with diversified hedge fund firms having weaker alignment between managerial incentives and investment performance.

Aim Computed tomography (CT) is currently the diagnostic tool most often used to detect anastomotic leakage (AL) after colorectal surgery. The aim of this study was to investigate the value of rectal contrast. Method All patients who underwent colorectal surgery with a primary anastomosis between 2009 and 2018 were identified from a prospectively maintained database. Patients who underwent postoperative CT scanning in suspicion of AL were included. The clinical and radiological outcomes of patients with and without rectal contrast were compared. Results A total of 1183 patient records were reviewed; 225 patients underwent CT‐abdomen in suspicion of AL. Of these patients, 175 (77.8%) received rectal contrast. Sensitivity and specificity in this group were 78% and 94%, respectively. The positive predictive value (PPV) was 0.78 and the negative predictive value (NPV) was 0.94. In the group without rectal contrast (n = 50), sensitivity was 47%, specificity 88%, PPV 0.66 and NPV 0.76. In patients who received rectal contrast, contrast reached the anastomosis in 81.7% compared with 26.0% in patients who were given only oral contrast (p

The healthcare industry is commonly compared to the aviation industry with emphasis on human factors and the decision-making processes undertaken by pilots and clinicians alike. The authors have been given exclusive access to meet the head of the maintenance team behind one of the UK's most popular airlines. An open-ended interview took place which was audio-transcribed for thematic analysis. Data were initially coded to identify basic patterns in the transcript. Once this was completed, themes were identified and agreed between the authors which could be compared to healthcare and dentistry. These themes were: regulation, occupational health, maintenance of equipment, use of checklists, reporting, just culture, burnout and disturbances. The aviation engineering industry requires the combination of a skilled workforce working under time pressure often in a financially restricted environment in a similar way to healthcare, especially dentistry. The two industries share common risks, although introduction of risk management tools such as checklists have been prevalent in aviation since the 1930s. Recognition of said risks and themes can lead to shared learning opportunities to benefit both sectors., Key points There has been substantive focus on human factors and their interaction with decision-making in healthcare. The authors present themes garnered from an interview with a base maintenance manager from one of the UK's largest airlines. There are clear overlaps between engineering and dentistry, specifically pertaining to equipment regulation, checklists and working directives.

The Asian tiger mosquito (Aedes albopictus), a vector of dengue, Zika and other diseases, was introduced in Europe in the 1970s, where it is still widening its range. Spurred by public health concerns, several studies have delivered predictions of the current and future distribution of the species for this region, often with differing results. We provide the first joint analysis of these predictions, to identify consensus hotspots of high and low suitability, as well as areas with high uncertainty. The analysis focused on current and future climate conditions and was carried out for the whole of Europe and for 65 major urban areas. High consensus on current suitability was found for the northwest of the Iberian Peninsula, southern France, Italy and the coastline between the western Balkans and Greece. Most models also agree on a substantial future expansion of suitable areas into northern and eastern Europe. About 83% of urban areas are expected to become suitable in the future, in contrast with ~ 49% nowadays. Our findings show that previous research is congruent in identifying wide suitable areas for Aedes albopictus across Europe and in the need to effectively account for climate change in managing and preventing its future spread.

Purpose We investigated the feasibility of using an anatomically localized, target-enriched liquid biopsy (TLB) in mouse models of lung cancer.Materials and Methods After irradiating xenograft mouse with human lung cancer cell lines, H1299 (NRAS proto-oncogene, GTPase [NRAS] Q61K) and HCC827 (epidermal growth factor receptor [EGFR] E746-750del), circulating (cell-free) tumor DNA (ctDNA) levels were monitored with quantitative polymerase chain reaction on human long interspersed nuclear element-1 and cell line-specific mutations. We checked dose-dependency at 6, 12, or 18 Gy to each tumor-bearing mouse leg using 6-MV photon beams. We also analyzed ctDNA of lung cancer patients by LiquidSCAN, a targeted deep sequencing to validated the clinical performances of TLB method.Results Irradiation could enhance the detection sensitivity of NRAS Q61K in the plasma sample of H1299-xenograft mouse to 4.5- fold. While cell-free DNA (cfDNA) level was not changed at 6 Gy, ctDNA level was increased upon irradiation. Using double-xenograft mouse with H1299 and HCC827, ctDNA polymerase chain reaction analysis with local irradiation in each region could specify mutation type matched to transplanted cell types, proposing an anatomically localized, TLB. Furthermore, when we performed targeted deep sequencing of cfDNA to monitor ctDNA level in 11 patients with lung cancer who underwent radiotherapy, the average ctDNA level was increased within a week after the start of radiotherapy.Conclusion TLB using irradiation could temporarily amplify ctDNA release in xenograft mouse and lung cancer patients, which enables us to develop theragnostic method for cancer patients with accurate ctDNA detection.

The outburst of the COVID-19 pandemic and the ensuing school lockdown measures taken revealed the limits of organisational innovation in education confronted suddenly with having to limit social contacts between pupils, students and teachers. Fully, online education models designed using the physical class model as organisational set-up and organized in a couple of weeks’ time, were totally inappropriate to compensate for school closures. The organisational innovation which education systems across the world could benefit from following the COVID-19 pandemic, consists of exploiting in a more flexible and hybrid way best practice online education to the benefit of a more inclusive school and learning system. Schools – both as an institution as well as a building – represent in many ways our last chance for the promotion of social equality: allowing for exchanges amongst youngsters with different social background. Giving explicitly schools the tasks of providing access to best practice digital education and freeing time for physical education addressing “face to face” socially isolated pupils and students from poorer and more marginalized neighbourhoods could be a lasting, major organisational innovation resulting from the COVID-19 pandemic.

Purpose The purpose of the study was to validate the Korean version of Patient-Reported Outcomes Measurement Information System 29 Profile V2.1 (K-PROMIS-29 V2.1) among cancer survivors. Materials and methods Participants were recruited from outpatient clinics of the Comprehensive Cancer Center at the Samsung Medical Center in Seoul, South Korea, from September to October 2018. Participants completed a survey questionnaire that included the K-PROMIS-29 V2.1 and the European Organisation for Research and Treatment of Cancer Quality Of Life Core Questionnaire (EORTC QLQ-C30). Principal component analysis and confirmatory factor analysis (Principal Component Analysis, confirmatory factor analysis) and Pearson's correlations were used to evaluate the reliability and validity of the K-PROMIS-29 V2.1. Results The mean age of the study participants was 54.4 years, the mean time since diagnosis was 1.2 (± 2.4) years, and 349 (87.3%) completed the entire questionnaire. The Cronbach's alpha coefficients of the seven domains in the K-PROMIS-29 V2.1 ranged from 0.81 to 0.96, indicating satisfactory internal consistency. In the CFA, the goodness-of-fit indices for the K-PROMIS-29 V2.1 were high (comparative fit index, 0.91 and standardized root-mean-squared residual, 0.06). High to moderate correlations were found between comparable subscales of the K-PROMIS-29 V2.1 and subscales of the EORTC QLQ-C30 (r=0.52-0.73). Conclusion The K-PROMIS-29 V2.1 is a reliable and valid measure for assessing the health-related quality of life domains in a cancer population, thus supporting their use in studies and oncology trials.

Purpose This study aimed to confirm the decision-making patterns for life-sustaining treatment and analyze medical service utilization changes after enforcement of the Life-Sustaining Treatment Decision-Making Act. Materials and methods Of 1,237 patients who completed legal forms for life-sustaining treatment (hereafter called the life-sustaining treatment [LST] form) at three academic hospitals and died at the same institutions, 1,018 cancer patients were included. Medical service utilization and costs were analyzed using claims data. Results The median time to death from completion of the LST form was three days (range, 0 to 248 days). Of these, 517 people died within two days of completing the document, and 36.1% of all patients prepared the LST form themselves. The frequency of use of the intensive care unit, continuous renal replacement therapy, and mechanical ventilation was significantly higher when the families filled out the form without knowing the patient's intention. In the top 10% of the medical expense groups, the decision-makers for LST were family members rather than patients (28% patients vs. 32% family members who knew and 40% family members who did not know the patient's intention). Conclusion The cancer patient's own decision-making rather than the family's decision was associated with earlier decision-making, less use of some critical treatments (except chemotherapy) and expensive evaluations, and a trend toward lower medical costs.

Intraoperative targeting of the analgesic effect still lacks an optimal solution. Opioids are currently the main drug used to achieve antinociception, and although underdosing can lead to an increased stress response, overdose can also lead to undesirable adverse effects. To better understand how to achieve the optimal analgesic effect of opioids, we studied the influence of remifentanil on the pupillary reflex dilation (PRD) and its relationship with the reflex movement response to a standardized noxious stimulus. The main objective was to generate population pharmacodynamic models relating remifentanil predicted concentrations to movement and to pupillary dilation during general anesthesia. A total of 78 patients undergoing gynecological surgery under general anesthesia were recruited for the study. PRD and movement response to a tetanic stimulus were measured multiple times before and after surgery. We used nonlinear mixed effects modeling to generate a population pharmacodynamic model to describe both the time profiles of PRD and movement responses to noxious stimulation. Our model demonstrated that movement and PRD are equally depressed by remifentanil. Using the developed model, we changed the intensity of stimulation and simulated remifentanil predicted concentrations maximizing the probability of absence of movement response. An estimated effect site concentration of 2ng/ml of remifentanil was found to inhibit movement to a tetanic stimulation with a probability of 81%.

We have successfully fabricated high quality single crystalline La0.7Sr0.3MnO3 (LSMO) film in the freestanding form that can be transferred onto silicon wafer and copper mesh support. Using soft x-ray absorption (XAS) and resonant inelastic x-ray scattering (RIXS) spectroscopy in transmission and reflection geometries, we demonstrate that the x-ray emission from Mn 3s-2p core-to-core transition (3sPFY) seen in the RIXS maps can represent the bulk-like absorption signal with minimal self-absorption effect around the Mn L3-edge. Similar measurements were also performed on a reference LSMO film grown on the SrTiO3 substrate and the agreement between measurements substantiates the claim that the bulk electronic structures can be preserved even after the freestanding treatment process. The 3sPFY spectrum obtained from analyzing the RIXS maps offers a powerful way to probe the bulk electronic structures in thin films and heterostructures when recording the XAS spectra in the transmission mode is not available.

This study aims to assess how clinical outcomes of immunotherapy in real-world (effectiveness) correspond to outcomes in clinical trials (efficacy) and to look into factors that might explain an efficacy-effectiveness (EE) gap. All patients diagnosed with stage IV non-small cell lung cancer (NSCLC) in 2015–2018 in six Dutch large teaching hospitals (Santeon network) were identified and followed-up from date of diagnosis until death or end of data collection. Progression-free survival (PFS) and overall survival (OS) from first-line (1L) pembrolizumab and second-line (2L) nivolumab were compared with clinical trial data by calculating hazard ratios (HRs). From 1950 diagnosed patients, 1005 (52%) started with any 1L treatment, of which 83 received pembrolizumab. Nivolumab was started as 2L treatment in 141 patients. For both settings, PFS times were comparable between real-world and trials (HR 1.08 (95% CI 0.75–1.55), and HR 0.91 (95% CI 0.74–1.14), respectively). OS was significantly shorter in real-world for 1L pembrolizumab (HR 1.55; 95% CI 1.07–2.25). Receiving subsequent lines of treatment was less frequent in real-world compared to trials. There is no EE gap for PFS from immunotherapy in patients with stage IV NSCLC. However, there is a gap in OS for 1L pembrolizumab. Fewer patients proceeding to a subsequent line of treatment in real-world could partly explain this.

Naser Al-Husban,1 Mohammad Sami Elmuhtaseb,1 Hedaieh Al-Husban,2 Mohammed Nabhan,3 Hamza Abuhalaweh,3 Yasmine Mohamed Alkhatib,3 Maysa Yousef,3 Bayan Aloran,3 Yousef Elyyan,3 Asma Alghazo3 1Faculty of Medicine, The University of Jordan, Amman, Jordan; 2Al-Noor Fertility Center, Eye Specialty Hospital, Amman, Jordan; 3Obstetrics and Gynecology Department, Jordan University Hospital, Amman, JordanCorrespondence: Naser Al-HusbanFaculty of Medicine, The University of Jordan, P O Box 2194, Amman, 11941, JordanTel +962-772086080Fax +96264643217Email Husban48@yahoo.comBackground: Cesarean section is a widely performed surgery.Objective: To compare anesthetic types regarding feto-maternal outcomes.Materials and Methods: Retrospective comparative study of 3599 cesarean sections (emergency and elective categories).Results: Mean APGAR score was statistically higher in the spinal than general anesthesia among the emergency category, P = 0.000 and 0.026, respectively, with no significant difference in the elective category. Estimated blood loss among the elective category was statistically significantly higher in the spinal than general anesthesia, P = 0.001. However, among the emergency category, it was significantly higher in the general than in spinal or epidural anesthesia, P = 0.000. Diclofenac sodium was used more after spinal than general anesthesia (P = 0.000), with no significant difference between epidural and general or between epidural and spinal anesthesia. Pethidine hydrochloride (HCL) was used more after general than after spinal anesthesia (P = 0.000). However, pethidine HCL use was not statistically significantly different between spinal and epidural anesthesia. In the elective category, paracetamol was requested more after spinal than epidural or general anesthesia, P = 0.000. No significant difference was seen between epidural and general anesthesia, P = 1.000. No statistically significant difference was found among the anesthetic types in both categories regarding tramadol HCL. Length of hospital stay, operative time and neonatal intensive care unit admission were not statistically different between anesthetic modes. In the emergency category, significantly higher percentage of patients were satisfied with and would recommend epidural anesthesia.Conclusion: There was no statistically significant difference among the three types of anesthesia regarding neonatal intensive care admission and length of hospital stay for emergency and elective categories. APGAR score was higher with spinal than with general anesthesia in the emergency category with no significant difference in the elective category. More diclofenac sodium and paracetamol and less opioids were used after regional than after general anesthesia. Satisfaction was higher with epidural anesthesia.Limitations: Retrospective and single centered.Keywords: cesarean section, spinal, epidural, general, anesthesia, feto-maternal, outcome

Background The COVID-19 pandemic has had a substantial impact on primary care throughout Europe and globally. Objectives This review aims to ascertain how the pandemic has impacted primary care service provision/patients and to examine strategies to mitigate these impacts. Methods The scoping review framework comprised a six-stage process developed by Arksey and O'Malley. The search process was guided by the Joanna Briggs Institute three-step search strategy and involved searching the PubMed, Embase, Scopus, CINAHL Plus, and Cochrane Library databases. The review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. A thematic analysis approach by Braun and Clarke was used to interpret the findings. Results Thirty-two studies from 18 countries and six continents were included, 13 reported original research, three were reviews, and 16 were case reports reporting healthcare systems’ experiences of dealing with the pandemic. Emerging themes concerned the COVID-19 pandemic’s impact on primary care service provision and patients, the impact of the rapid transition to telemedicine due to COVID-19 on primary care, and strategies to mitigate the impact of COVID-19 on primary care (i.e. infection prevention and control measures, alternatives/modifications to traditional service delivery or workflow, government policy responses, and education). Conclusion The COVID-19 pandemic has considerably impacted on primary care at both service and patient levels, and various strategies to mitigate these impacts have been described. Future research examining the pandemic’s ongoing impacts on primary care, as well as strategies to mitigate these impacts, is a priority.

The aim of this study is to assess the economic impact of the new coronavirus (COVID-19) on Brazilian Orthopaedic Surgeons.The questionnaire was applied to orthopedists and it questions how long they have worked in this area; their monthly financial impact during the pandemic; what sector was impacted the most; if they had or didn't have any financial reserves and how long they would last; if they had any other source of fixed income; and how much time off they had taken from work. It was entirely anonymous and it could only be answered once.About 98% (955 out of 975) of the analyzed orthopedists suffered some monetary impact, 80% had a financial reserves, from which 45% could last for 3 months.There was a direct relationship between the professional experience in this subspecialty and a higher percentage of fixed income, as well as a greater impact on the reduction percentage in the monthly budget and a longer time off the job.Avaliar o impacto econômico do novo coronavírus (Covid-19) entre ortopedistas brasileiros.Questionário aplicado a ortopedistas que aborda o tempo de prática clínica, impacto no orçamento mensal durante o mês inicial da pandemia, setor de maior impacto, presença de outra fonte de renda fixa na área médica ou fora, existência de reserva financeira, previsão de tempo de afastamento e expectativa de retorno às atividades normais. Todo formulário é anônimo e programado para ser respondido apenas uma vez.Cerca de 98% (955, entre 975 que responderam ao questionário) dos médicos ortopedistas analisados sofreram algum impacto monetário, 80% tinham reserva financeira, 45% dentre eles com reserva financeira para até 3 meses.Existiu uma relação direta entre o maior tempo de subespecialidade, a maior porcentagem de renda fixa, o maior impacto na porcentagem de redução no salário mensal e o maior o tempo de afastamento.

Background In primary care (PC), 80% of the acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are treated. However, no predictive model has been derived or validated for use in PC to help general practitioners make decisions about these patients. Objectives To derive a clinical prediction rule for mortality from any cause 30 days after the last PC visit. Methods Between December 2013 and November 2014, we performed a cohort study with people aged 40 and over who were treated for AECOPD in 148 health centres in Spain. We recorded demographic variables, past medical history, signs, and symptoms of the patients and derived a logistic regression model. Results In the analysis, 1,696 cases of AECOPD were included and 17 patients (1%) died during follow-up. A clinical prediction rule was derived based on the exacerbations suffered in the last 12 months, age, and heart rate, displaying an area under the receiver operating characteristic curve of 0.792 (95% confidence interval, 0.692-0.891) and good calibration. Conclusion This rule stratifies patients into three categories of risk and suggests to the physician a different action for each category: managing low-risk patients in PC, referring high-risk patients to hospitals and taking other criteria into account for decision-making in patients with moderate risk. These findings suggest that it is possible to accurately estimate the risk of death due to AECOPD without complex devices. Future studies on external validation and impact assessment are needed before this prediction rule may be used in clinical practice.

INTRODUCTION The relationship between regurgitated and aspirated volume of clear fluids remains undetermined and may depend on anatomical factors and patient position. We aimed to assess whether head position (sniffing vs. extension position) affected this relationship in fresh human cadavers. We also determined the critical volume of water regurgitated that led to pulmonary aspiration of volume ≥ 0.8 mL kg-1 and ≥ 1.5 mL kg-1 for each head position. MATERIAL AND METHODS Six volumes of water (40, 80, 100, 120, 150, and 200 mL) were injected each twice, in a randomised order, at a flow rate of 20 mL per second, into the oesophagus of seven fresh human cadavers lying in the supine position on a non-tilted table, with the head in the sniffing position and in the extension position. Aspirated volume was measured in the trachea, blindly to the volume injected. RESULTS Overall, more than 85% of the regurgitated volume was aspirated into the trachea. The volume of aspirated water was significantly greater in the sniffing position than in the extension position. The cut-off volumes of water injected into the oesophagus leading to aspirated volume ≥ 0.8 mL kg-1 and ≥ 1.5 mL kg-1 were, respectively, 0.8 mL kg-1 and 1.5 mL kg-1 in the sniffing position, and 1.2 mL kg-1 and 1.8 mL kg-1 in the extension position. CONCLUSIONS These results confirm that most of the regurgitated clear fluid enters the trachea in humans lying in the supine position on a non-tilted table, especially when the head is in the sniffing position.

As routine care was suspended in most countries, one could anticipate progression of undiagnosed and managed oral disease. Patients are usually unaware of the development of oral disease as it is not visible to them and largely asymptomatic, especially in its early stages. The natural progression of conditions such as caries and periodontitis is inevitable without diagnosis and management. The full extent of patient harm because of the suspension of routine dental care can only be estimated when routine oral examinations are fully re-established, and even then, we will probably never know the number of individuals impacted or the extent of disease progression and harm. In first-world countries, there has always been a back-up emergency treatment system for dental problems. For example, in the UK, the safety net for life-threatening swellings and for acute pain relief is the accident and emergency services. This system remained in place during the COVID-19 pandemic. Courts could be expected to understand the coronavirus context and would take this into account should there be a complaint against the clinician about access to care. The suspension of routine dental care to save lives will lead to the closure of many dental practices due to substantial financial impact. The return to routine care will be slow, with prioritisation of non-aerosol generating procedures while we look to further understand methods to mitigate transmission risk via infected aerosol and spatter. Inevitably, the cost of personal protective equipment and the lower volume of patients pose a continued threat to businesses., Key points Natural history of oral disease progression if not managed is described.Concerns about the medico-legal consequences of reduced access to dental care are discussed.The economic repercussions of the COVID-19 need for suspension of routine care and the future increased costs of practice are presented.

The idea of an Association is to provide a focus and a forum for the development, promotion and dissemination of best clinical practice for the benefit of patients through education, training, research and quality improvement. With this in mind the Association of Coloproctology of Great Britain and Ireland (ACPGBI) was formed 30 years ago and now has over 1000 members made up of specialist surgeons, nurses, allied medical professionals and those in training.

Introduction The United Kingdom (UK) left the European Union (EU) on 31 January 2020. Brexit will impact many sectors of the economy, including the dental sector. Methods and analysis This policy analysis evaluates UK and EU legislation and planning documents, as well as the published literature, to analyse the impact of two scenarios relating to the UK's exit from the EU on the dental sector: a free trade agreement based on the jointly agreed Political Declaration (the 'FTA') and a 'no-deal' scenario. Conclusion An FTA could cause price increases of medicines and medical devices, and cause some disruption to the ability of regulating authorities in this area, while a no-deal would additionally risk shortages of medicines and medical devices as well as more dramatic price increases. In both an FTA and a 'no-deal scenario', with EU law no longer applicable to the UK, more innovative policy in the area of tobacco control could be developed. An FTA could exacerbate existing workforce shortages and would likely cause a reduction in EU research funding, as well as posing issues with data transfers, with these all likely to be more severe under a no-deal scenario., Key points Explains the role of the European Union in relation to oral health in the UK.Highlights the potential effects of Brexit on oral health and oral healthcare in the UK.Suggests how practitioners can prepare for potential effects of Brexit.

Aim The purpose of this research was to investigate students' approaches to learning and use of cognitive strategies in a collaborative learning environment with team-based learning. Method In a mixed-methods study, 263 medical students from 6 different semesters answered the R-SPQ-2F Questionnaire and MSLQ's items that measure elaboration and rehearsal strategies. ANOVA was used to compare differences between semesters, and Pearson's correlation to investigate how approaches to learning, cognitive strategies, and academic achievement correlate. Focus groups elucidated which elements in the collaborative learning environment enhanced or hindered deep approach to learning or elaboration strategies and why. Results Students took a deep approach to learning and sometimes a surface approach. They used elaboration and rehearsal strategies. First semester's students had significantly higher deep approach than fifth and sixth semesters' students. Elaboration strategies significantly correlated with final grade. Commitment to the group, case discussions, feeling challenged by teachers, and patients' visits were perceived to enhance deep approach to learning and use of elaboration strategies, while overload in course activities hindered deep approach to learning. Conclusions Particular elements of the learning environment triggered students to take deep approach to learning and use elaboration strategies, and this positively correlated to academic achievement.

Background Simulation‐based training in medical education has become a common method to develop both technical and non‐technical skills in teams. Mental rehearsal (MR) is the cognitive act of simulating a task in our heads to pre‐experience tasks imaginatively. It has been used widely to improve individual and collective performance in fields outside healthcare, and offers potential for more efficient training in time‐pressured surgical and medical team contexts. This study aimed to review the available literature to determine the impact of MR on team performance and non‐technical skills in healthcare. Methods MEDLINE, Embase, British Educational Index, CINAHL, Web of Science, PsycInfo and Cochrane databases were searched for the period 1994–2018. The primary outcome measure was improvement in team performance and non‐technical skills. Study quality of RCTs was assessed using the Medical Education Research Quality Instrument. The reported impacts of MR in all included studies were mapped on to the Kirkpatrick framework for evaluation of educational interventions. Results Eight studies with 268 participants were identified that met the inclusion criteria, of which there were six randomized trials, one prospective pragmatic trial and one qualitative study. Three studies found MR to be effective in improving team non‐technical skills. MR practices were varied and often poorly defined. MR benefited team non‐technical skills when it was specifically designed to do so, but was not an automatic consequence of technical MR alone. The majority of studies demonstrated benefits of MR for technical performance, but only three showed positive impacts on teamwork. Overall the studies were of low quality and lacked sufficient discriminatory focus to examine impacts on teamwork dynamics. Conclusion MR can improve technical performance, but the benefits on non‐technical skills are less clear. Future research should look at longitudinal mixed‐method evaluation designs and focus on real clinical teams., This indepth critical analysis of team‐based mental rehearsal activities and their effect on surgical team non‐technical skills and team performance found that mental rehearsal may provide a free and easy‐to‐use tool to augment surgical team performance and improve teamwork. More work is needed to quantify and fully understand the effect of mental rehearsal. Team rehearsals to improve outcomes

Background Minimally invasive surgery is the standard technique for many operations. Laparoscopic training has a long learning curve. Robotic solutions may shorten the training pathway. The aim of this study was to compare laparoscopic with robotic training in surgical trainees and medical students. Methods Surgical trainees (ST group) were randomized to receive 6 h of robotic or laparoscopic simulation training. They then performed three surgical tasks in cadaveric specimens. Medical students (MS group) had 2 h of robotic or laparoscopic simulation training followed by one surgical task. The Global Rating Scale (GRS) score (maximum 30), number of suture errors, and time to complete each procedure were recorded. Results The median GRS score for the ST group was better for each procedure after robotic training compared with laparoscopic training (total GRS score: 27·00 (i.q.r. 22·25–28·33) versus 18·00 (16·50–19·04) respectively, P, Medical students and surgical trainees were randomized to robotic or laparoscopic simulator training followed by cadaveric surgical tasks. The robotic groups had a shorter learning curve with better task performance. Another advantage for robotic surgery

Background Robot‐assisted surgery (RAS) has potential panspecialty surgical benefits. High‐quality evidence for widespread implementation is lacking. This systematic review aimed to assess the RAS evidence base for the quality of randomized evidence on safety and effectiveness, specialty ‘clustering’, and outcomes for RAS research. Methods A systematic review was undertaken according to PRISMA guidelines. All pathologies and procedures utilizing RAS were included. Studies were limited to RCTs, the English language and publication within the last decade. The main outcomes selected for the review design were safety and efficacy, and study purpose. Secondary outcomes were study characteristics, funding and governance. Results Searches identified 7142 titles, from which 183 RCTs were identified for data extraction. The commonest specialty was urology (35·0 per cent). There were just 76 unique study populations, indicating significant overlap of publications; 103 principal studies were assessed further. Only 64·1 per cent of studies reported a primary outcome measure, with 29·1 per cent matching their registration/protocol. Safety was assessed in 68·9 per cent of trials; operative complications were the commonest measure. Forty‐eight per cent of trials reported no significant difference in safety between RAS and comparator, and 11 per cent reported RAS to be superior. Efficacy or effectiveness was assessed in 80·6 per cent of trials; 43 per cent of trials showed no difference between RAS and comparator, and 24 per cent reported that RAS was superior. Funding was declared in 47·6 per cent of trials. Conclusion The evidence base for RAS is of limited quality and variable transparency in reporting. No patterns of harm to patients were identified. RAS has potential to be beneficial, but requires continued high‐quality evaluation., Robot‐assisted surgery is expanding rapidly, but the evidence base is poor. This article demonstrates the heavy weighting to research in certain specialties, no clear safety or efficacy benefit, inconsistent choice of outcome measures, and poor research governance. These factors significantly increase the risk associated with adopting these potentially revolutionary technologies. Call for better quality evidence.

Background Improved diagnostic biomarkers are required for acute appendicitis. The circulating fibrocyte percentage (CFP) is increased in inflammatory states, but has not been studied in acute appendicitis. This study aimed to determine CFP in acute appendicitis and compare diagnostic accuracy with standard serological biomarkers. Methods A prospective cohort study was carried out between June 2015 and February 2016 at University Hospital Limerick. The CFP was determined by dual‐staining peripheral venous samples for CD45 and collagen I using fluorescence‐activated cell sorting, and correlated with histopathological diagnoses. The accuracy of CFP in determining histological acute appendicitis was characterized and compared with the white cell count, C‐reactive protein concentration, neutrophil count, lymphocyte count and neutrophil : lymphocyte ratio. Results Of 95 adults recruited, 15 were healthy individuals and 80 had suspected appendicitis at presentation. Forty‐six of these 80 patients had an appendicectomy, of whom 34 had histologically confirmed appendicitis. The CFP was statistically higher in patients with pathologically proven acute appendicitis than in healthy controls (median 6·1 (i.q.r. 1·6–11·6) versus 2·3 (0·9–3·4) per cent respectively; P = 0·008). The diagnostic accuracy of CFP, as determined using the area under the receiver operating characteristic (ROC) curve, was similar to that of standard biomarkers. In multinomial regression analysis, only raised CFP was retained as an independent prognostic determinant of acute appendicitis (odds ratio 1·57, 95 per cent c.i. 1·05 to 2·33; P = 0·027). Conclusion The CFP is increased in histologically confirmed acute appendicitis and is as accurate as standard serological biomarkers in terms of diagnosis., The circulating fibrocyte percentage is increased in patients with acute appendicitis. This may improve diagnostics, and reduce unnecessary radiation exposure and surgical operations. Circulating fibrocyte percentage may help in diagnosis of acute appendicitis.

Background Adhesive small bowel obstruction (aSBO) is a potentially recurrent disease. Although non‐operative management is often successful, it is associated with greater risk of recurrence than operative intervention, and may have greater downstream morbidity and costs. This study aimed to compare the current standard of care, trial of non‐operative management (TNOM), and early operative management (EOM) for aSBO. Methods Patients admitted to hospital between 2005 and 2014 in Ontario, Canada, with their first episode of aSBO were identified and propensity‐matched on their likelihood to receive EOM for a cost–utility analysis using population‐based administrative data. Patients were followed for 5 years to determine survival, recurrences, adverse events and inpatient costs to the healthcare system. Utility scores were attributed to aSBO‐related events. Cost–utility was presented as the incremental cost‐effectiveness ratio (ICER), expressed as Canadian dollars per quality‐adjusted life‐year (QALY). Results Some 25 150 patients were admitted for aSBO and 3174 (12·6 per cent) were managed by EOM. Patients managed by TNOM were more likely to experience recurrence of aSBO (20·9 per cent versus 13·2 per cent for EOM; P, This population‐based cost–utility analysis compared early operative management (EOM) for adhesive small bowel obstruction (SBO) to the current standard of care of a trial of non‐operative management. Although EOM was more costly, it was associated with a significantly lower risk of recurrence and reduced exposure to the morbidity and costs associated with multiple admissions for adhesive SBO. With longer follow‐up, EOM becomes increasingly cost‐effective, and crosses published willingness‐to‐pay thresholds within 5 years of the first admission. Early operative management in small bowel occlusion

Background Intraoperative nerve monitoring (IONM) of the recurrent laryngeal nerve (RLN) predicts the risk of vocal cord palsy (VCP). IONM can be used to adapt the surgical strategy in order to prevent bilateral VCP and associated morbidity. Controversial results have been reported in the literature for the effect of IONM on rates of VCP, and large multicentre studies are required for elucidation. Methods Patients undergoing first‐time thyroidectomy for benign thyroid disease between May 2015 and January 2019, documented prospectively in the European registry EUROCRINE®, were included in a cohort study. The influence of IONM and other factors on the development of postoperative VCP was analysed using multivariable regression analysis. Results Of 4598 operations from 82 hospitals, 3542 (77·0 per cent) were performed in female patients. IONM was used in 4182 (91·0 per cent) of 4598 operations, independent of hospital volume. Postoperative VCP was diagnosed in 50 (1·1 per cent) of the 4598 patients. The use of IONM was associated with a lower risk of postoperative VCP in multivariable analysis (odds ratio (OR) 0·34, 95 per cent c.i. 0·16 to 0·73). Damage to the RLN noted during surgery (OR 24·77, 12·91 to 48·07) and thyroiditis (OR 2·03, 1·10 to 3·76) were associated with an increased risk of VCP. Higher hospital volume correlated with a lower rate of VCP (OR 0·05, 0·01 to 0·13). Conclusion Use of IONM was associated with a low rate of postoperative VCP., The influence of intraoperative nerve monitoring (IONM) and other factors on the development of postoperative vocal cord palsy (VCP) was assessed using multivariable regression analysis. In a cohort of 4598 patients from 82 hospitals, IONM was used in over 90 per cent of those treated by primary thyroidectomy for underlying benign thyroid disease. IONM reduced the rate of postoperative VCP. Intraoperative nerve monitoring associated with lower rates of vocal cord palsy

PurposeThis study investigated the incidence and relative survival rates (RSRs) for cancers among adolescents and young adults (AYAs) aged 15-39 years between 1993 and 2016 in KoreaMaterials and MethodsData from the Korea Central Cancer Registry were used to calculate percent distributions, age-specific incidence rates, age-standardized incidence rates (ASRs) per million, annual percent changes (APCs), average APCs, and RSRs for cancers diagnosed in AYAs.Results ASR of all cancers among AYAs was 654.5 per million. The largest diagnosed group of cancers was carcinomas (almost 80%). Crude incidence increased with age, from 170.4 per million for those aged 15-19 years to 1,639.8 per million for those aged 35-39 years. ASR increased from 414.8 per million to 820.4 per million, with an APC of 9.0%. The incidence of thyroid carcinoma showed the most rapid increment (APC, 14.0%), followed by non-Hodgkin lymphoma (APC, 13.4%). The 5-year RSR among AYAs significantly improved from 62.1% to 90.8%. Survival improvement in AYAs was higher than that in children but lower than that in older adults (APC, 2.1% vs. 1.9% vs. 3.1%). The most marked survival improvement was found for leukemia and lymphoma. Astrocytoma, rhabdomyosarcoma, and carcinoma of the trachea, bronchus, and lung had a 5-year RSR of < 50%.ConclusionThere was an improvement in cancer survivals in AYAs, comparable to that achieved in children. However, survivals in several cancer types do not appear to be improving. Further research focusing on the epidemiology and therapeutic strategies for cancers in AYAs is needed.

Background Insulinomas are found in 10–15 per cent of patients with multiple endocrine neoplasia type 1 (MEN1) and lead to life‐threatening hypoglycaemia. Surgical outcome and the optimal surgical strategy for MEN1‐related insulinoma are unknown. Methods Patients with MEN1‐related insulinomas were identified in 46 centres in Europe and North America between 1990 and 2016. Insulinomas were considered localized if the lesion was in the pancreatic head or body/tail. Patients with pancreatic neuroendocrine tumours throughout the pancreas were suspected of having multifocal insulinoma. The primary outcome was postoperative hypoglycaemia, defined as persistent hypoglycaemia, or recurrent hypoglycaemia caused by a new insulinoma or insulin‐producing liver metastases. Hypoglycaemia‐free survival was estimated by the Kaplan–Meier method. Results Ninety‐six patients underwent resection for MEN1‐related insulinoma. Sixty‐three and 33 patients had localized and multifocal insulinomas respectively. After a median follow‐up of 8 (range 1–22) years, one patient (1 per cent) had persistent disease and six (6 per cent) had developed recurrent disease, of whom four had a new insulinoma. The 10‐year hypoglycaemia‐free survival rate was 91 (95 per cent c.i. 80 to 96) per cent. Of those with localized disease, 46 patients underwent pancreatic resection and 17 enucleation. One of these patients had persistent disease and one developed recurrent insulinoma. Among patients with multifocal disease, three developed new insulinomas and two developed insulin‐producing liver metastases. Conclusion Surgery for MEN1‐related insulinoma is more successful than previously thought., In this cohort of 96 patients with resected multiple endocrine neoplasia 1 (MEN1)‐related insulinomas, seven patients (7 per cent) developed postoperative persistent or recurrent hypoglycaemia after a median follow‐up of 8 years. The 10‐year hypoglycaemia‐free survival rate was 91 (95 per cent c.i. 80 to 96) per cent. For patients with localized insulinoma, enucleation seems the preferred procedure. PPPD, pylorus‐preserving pancreatoduodenectomy. Outcomes good

Background Recruitment and retention of participants in surgical trials is challenging. Knowledge of the most common and problematic issues will aid future trial design. This study aimed to identify trial staff perspectives on the main issues affecting participant recruitment and retention in UK surgical trials. Methods An online survey of UK surgical trial staff was performed. Respondents were asked whether or not they had experienced a range of recruitment and retention issues, and, if yes, how relatively problematic these were (no, mild, moderate or serious problem). Results The survey was completed by 155 respondents including 60 trial managers, 53 research nurses, 20 trial methodologists and 19 chief investigators. The three most common recruitment issues were: patients preferring one treatment over another (81·5 per cent of respondents); clinicians' time constraints (78·1 per cent); and clinicians preferring one treatment over another (76·8 per cent). Seven recruitment issues were rated moderate or serious problems by a majority of respondents, the most problematic being a lack of eligible patients (60·3 per cent). The three most common retention issues were: participants forgetting to return questionnaires (81·4 per cent); participants found to be ineligible for the trial (74·3 per cent); and long follow‐up period (70·7 per cent). The most problematic retention issues, rated moderate or serious by the majority of respondents, were participants forgetting to return questionnaires (56·4 per cent) and insufficient research nurse time/funding (53·6 per cent). Conclusion The survey identified a variety of common recruitment and retention issues, several of which were rated moderate or serious problems by the majority of participating UK surgical trial staff. Mitigation of these problems may help boost recruitment and retention in surgical trials., An online survey of surgical trial staff was conducted to identify key issues affecting recruitment and retention of participants in UK surgical trials. Several issues were reportedly experienced by over 70 per cent of respondents. Seven recruitment and two retention issues were rated ‘moderate’ or ‘serious’ by a majority of respondents. Lack of equipoise a common theme

Background Entrants into UK surgical specialty training undertake a 2‐year programme of core surgical training, rotating through specialties for varying lengths of time, at different hospitals, to gain breadth of experience. This study aimed to assess whether these variables influenced core surgical trainee (CST) work productivity. Methods Intercollegiate Surgical Curriculum Programme portfolios of consecutive CSTs between 2016 and 2019 were examined. Primary outcome measures were workplace‐based assessment (WBA) completion, operative experience and academic outputs (presentations to learned societies, publications and audits). Results A total of 344 rotations by 111 CSTs were included. Incremental increases in attainment were observed related to the duration of core surgical training rotation. The median number of consultant‐validated WBAs completed during core surgical training were 48 (range 0–189), 54 (10–120) and 75 (6–94) during rotations consisting of 4‐, 6‐ and 12‐month posts respectively (P, This study aimed to assess whether hospital status, rurality, duration of hospital rotations and specialty theme of core surgical training had an impact on workplace productivity. Longer placements improve outcomes

Background Biliary atresia is a rare paediatric biliary obliteration disease with unknown aetiology, and is the most common indication for paediatric liver transplantation (LT). However, no consensus for predicting Kasai portoenterostomy (KP) outcomes using liver histological findings exists. Ki67 is a popular biomarker for measuring and monitoring cellular proliferation. Methods Ki67 (clone, MIB‐1) liver parenchyma expression was measured by immunohistochemical staining of samples from living donors and patients with biliary atresia to assess its value in predicting outcomes after KP. Results Of 35 children with biliary atresia, 13 were native liver survivors (NLS), 17 were non‐NLS, and five had primary LT. The median proportion of Ki67 immunostained areas in donors and patients with biliary atresia at KP was 0·06 and 0·99 per cent respectively. Univariable analysis identified a high proportion of Ki67 areas, high Ki67 cell numbers and high Ki67‐positive/leucocyte common antigen‐positive cell numbers at KP as significant predictors of poor native liver survival after KP (hazard ratio 9·29, 3·37 and 12·17 respectively). The proportion of Ki67 areas in the non‐NLS group was significantly higher than that in the NLS group (1·29 versus 0·72 per cent respectively; P = 0·001), and then decreased at LT (0·32 per cent versus 1·29 per cent at KP; P, No consensus exists for predicting outcomes after Kasai portoenterostomy (KP) using liver histological findings. Ki67 (clone, MIB‐1) expression in liver parenchyma was measured by means of immunohistochemical staining of samples from five living donors and 35 patients with biliary atresia to assess its value in predicting KP outcomes. Univariable analysis identified high expression of Ki67 at the time of KP as a significant predictor of poor native liver survival after the procedure. Ki67 a potential marker for liver survival after Kasai portoenterostomy

Objective/Introduction: Near-infrared spectroscopy (NIRS) is a non-invasive technique to detect cerebral ischemia by monitoring changes in regional cerebral oxygenation (rSO2) in the frontal lobes. However, there are no studies showing the changes in NIRS values in response to hemodynamic variations during stages of carotid endarterectomy (CEA) procedure and clinical implications of these changes. The aim of this study was to determine if hemodynamic changes affect NIRS values during carotid endarterectomy and if our results may help to provide strategies for hemodynamic management in these patients. Methods: A total of 50 consecutive patients undergoing CEA were prospectively included in the study. NIRS was measured at first minute after clamping of carotid artery, and then systolic blood pressure was increased above 150 mmHg. NIRS values from both hemispheres were recorded simultaneously at certain time points and were analyzed to evaluate the changes at different stages of operation and to assess correlations with hemodynamic parameters. Results: NIRS values on the right and left sides were correlated with systolic (right P

Background:SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). Circulating soluble angiotensin-converting enzyme (sACE2), the main receptor for SARS-CoV-2, together with components of the renin-angiotensin system promote infection and disease severity. Objective: In this pilot study we followed the time-course of sACE2 levels in relation to systemic cytokines in severe and moderate COVID-19 patients treated with remdesivir/dexamethasone in combination. Methods: Peripheral blood was obtained upon admission from 30 patients (12 with moderate disease and 18 with severe disease) and 14 patients with PCR-confirmed mild COVID-19. Severe and moderate patients were treated with remdesivir (200mg/first day and 100mg/day for the remaining days ) and dexamethasone (100mg/day ). 6 healthy control subjects (HC) were also enrolled. Serum interleukin (IL)-6 and IL-8 and sACE2 levels were measured by ELISA at baseline and during treatment in severe and moderate patients and at baseline in mild and HCs. Results: Baseline sACE2 levels were lower in severe (p=0.0005) and moderate (p=0.0022) patients than in patients with mild COVID-19 and in HC (p=0.0023 and p=0.0012 respectively). Serum sACE2 levels increased in patients with severe disease recovered over time compared with moderate (p=0.0021) and severe (p=0.0411) COVID-19 subjects at baseline. Systemic IL-6 and IL-8 levels were higher in all patient groups compared with HC and were not significantly affected over time or by remdesivir/dexamethasone treatment for 5 days. Conclusion: Serum sACE2 levels increase in severe COVID-19 patients as they recover over time whilst circulating cytokines are unaffected. Future studies should link these results to clinical outcomes. Funding: IMA is financially supported by the Welcome Trust (093080/Z/10/Z), the EPSRC (EP/T003189/1), and the Community Jameel Imperial College COVID-19 Excellence Fund (G26290) and by the UK MRC (MR/T010371/1). SM is supported by EU project 853850. Declaration of Interests: The authors declare that there is no conflict of interest to this article. Ethics Approval Statement: The study was approved by the institutional ethics board of the Masih Daneshvari Hospital (Ethics number SBMU.NRITLD.REC.1399.226).