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OBJECTIVE: Self-efficacy (SE) is an important determinant for the psychological adjustment of people with spinal cord injury (SCI). However, little is known about the course of SE during inpatient rehabilitation up to 1 year after discharge. The aim of this study was to determine latent trajectory classes of SE, depressive mood, and anxiety in people with SCI, as well as the interrelationships between these trajectories.DESIGN: Longitudinal inception cohort study.SETTING: Eight specialized SCI rehabilitation centers.PARTICIPANTS: The participants (N=268) were mainly men 183 of 268 (68.3%) with a mean age of 55.6 years. Almost half had a traumatic SCI 135 of 268 (50.4%) and tetraplegia (53.7%), and the minority had a motor complete SCI (32.2%).INTERVENTIONS: Not applicable.MAIN OUTCOME MEASURES: SE was measured using the University of Washington Self-Efficacy Scale. In addition, the Hospital Anxiety and Depression Scale was used to asses distress and perform dual trajectory modeling analyses.RESULTS: Three trajectories of SE, indicating low, middle, and high SE, could be distinguished. Furthermore, a 2-class trajectory solution for depressive mood and a 4-class solution for anxiety were found to be most suitable. All trajectories were stable over time. Developmental connections between SE and depressive mood and between SE and anxiety were revealed. In particular, participants who adjusted well, reporting low scores on depressive mood and anxiety, could be identified by their high SE scores. However, the group of participants with high depressive mood scores and anxiety scores could not always be identified based on their SE trajectory.CONCLUSIONS: In accordance with our hypotheses, distinct trajectories of SE, depressive mood, and anxiety were identified and high probabilities that SE trajectories were interrelated to the trajectories from depressive mood and anxiety were confirmed. Concurrent screening for SE and distress might best detect people at risk for adjustment problems.

Objectives: This study was designed to assess the prognostic value of pericoronary adipose tissue computed tomography attenuation (PCATa) beyond quantitative coronary computed tomography angiography (CCTA)–derived plaque volume and positron emission tomography (PET) determined ischemia. Background: Inflammation plays a crucial role in atherosclerosis. PCATa has been shown to assess coronary-specific inflammation and is of prognostic value in patients with suspected coronary artery disease (CAD). Methods: A total of 539 patients who underwent CCTA and [ 15O]H 2O PET perfusion imaging because of suspected CAD were included. Imaging assessment included coronary artery calcium score (CACS), presence of obstructive CAD (≥50% stenosis) and high-risk plaques (HRPs), total plaque volume (TPV), calcified/noncalcified plaque volume (CPV/NCPV), PCATa, and myocardial ischemia. The endpoint was a composite of death and nonfatal myocardial infarction. Prognostic thresholds were determined for quantitative CCTA variables. Results: During a median follow-up of 5.0 (interquartile range: 4.7 to 5.0) years, 33 events occurred. CACS >59 Agatston units, obstructive CAD, HRPs, TPV >220 mm 3, CPV >110 mm 3, NCPV >85 mm 3, and myocardial ischemia were associated with shorter time to the endpoint with unadjusted hazard ratios (HRs) of 4.17 (95% confidence interval [CI]: 1.80 to 9.64), 4.88 (95% CI: 1.88 to 12.65), 3.41 (95% CI: 1.72 to 6.75), 7.91 (95% CI: 3.05 to 20.49), 5.82 (95% CI: 2.40 to 14.10), 8.07 (95% CI: 3.33 to 19.55), and 4.25 (95% CI: 1.84 to 9.78), respectively (p < 0.05 for all). Right coronary artery (RCA) PCATa above scanner specific thresholds was associated with worse prognosis (unadjusted HR: 2.84; 95% CI: 1.44 to 5.63; p = 0.003), whereas left anterior descending artery and circumflex artery PCATa were not related to outcome. RCA PCATa above scanner specific thresholds retained is prognostic value adjusted for imaging variables and clinical characteristics associated with the endpoint (adjusted HR: 2.45; 95% CI: 1.23 to 4.93; p = 0.011). Conclusions: Parameters associated with atherosclerotic burden and ischemia were more strongly associated with outcome than RCA PCATa. Nonetheless, RCA PCATa was of prognostic value beyond clinical characteristics, CACS, obstructive CAD, HRPs, TPV, CPV, NCPV, and ischemia.

Aims To compare cardiac magnetic resonance (CMR) measurement of T1 reactivity (DT1) with [ 15O]H 2O positron emission tomography (PET) measurements of quantitative myocardial perfusion. ................................................................................................................................................................................................... Methods Forty-three patients with suspected obstructed coronary artery disease underwent [ 15O]H 2O PET and CMR at and results 1.5-T, including rest and adenosine stress T1 mapping (ShMOLLI) and late gadolinium enhancement to rule out presence of scar tissue. DT1 was determined for the three main vascular territories and compared with [ 15O]H 2O PET-derived regional stress myocardial blood flow (MBF) and myocardial flow reserve (MFR). DT1 showed a significant but poor correlation with stress MBF (R 2 = 0.04, P = 0.03) and MFR (R 2 = 0.07, P = 0.004). Vascular territories with impaired stress MBF (i.e. 15O]H 2O PET measurements of absolute myocardial perfusion. Stress T1 and DT1 are lower in vascular territories with reduced stress MBF but have poor accuracy for detecting impaired myocardial perfusion.

Background Patients with hematological malignancies (HMs) carry a wide range of chromosomal and molecular abnormalities that impact their prognosis and treatment. Since no current technique can detect all relevant abnormalities, technique(s) are chosen depending on the reason for referral, and abnormalities can be missed. We tested targeted transcriptome sequencing as a single platform to detect all relevant abnormalities and compared it to current techniques. Material and Methods We performed RNA-sequencing of 1385 genes (TruSight RNA Pan-Cancer, Illumina) in bone marrow from 136 patients with a primary diagnosis of HM. We then applied machine learning to expression profile data to perform leukemia classification, a method we named RANKING. Gene fusions for all the genes in the panel were detected, and overexpression of the genes EVI1, CCND1, and BCL2 was quantified. Single nucleotide variants/indels were analyzed in acute myeloid leukemia (AML), myelodysplastic syndrome and patients with acute lymphoblastic leukemia (ALL) using a virtual myeloid (54 genes) or lymphoid panel (72 genes). Results RANKING correctly predicted the leukemia classification of all AML and ALL samples and improved classification in 3 patients. Compared to current methods, only one variant was missed, c.2447A>T in KIT (RT-PCR at 10−4), and BCL2 overexpression was not seen due to a t(14; 18)(q32; q21) in 2% of the cells. Our RNA-sequencing method also identified 6 additional fusion genes and overexpression of CCND1 due to a t(11; 14)(q13; q32) in 2 samples. Conclusions Our combination of targeted RNA-sequencing and data analysis workflow can improve the detection of relevant variants, and expression patterns can assist in establishing HM classification.

Aim of the study Patients with cancer might have an increased risk for severe outcome of coronavirus disease 2019 (COVID-19). To identify risk factors associated with a worse outcome of COVID-19, a nationwide registry was developed for patients with cancer and COVID-19. Methods This observational cohort study has been designed as a quality of care registry and is executed by the Dutch Oncology COVID-19 Consortium (DOCC), a nationwide collaboration of oncology physicians in the Netherlands. A questionnaire has been developed to collect pseudonymised patient data on patients’ characteristics, cancer diagnosis, and treatment. All patients with COVID-19 and a cancer diagnosis or treatment in the past 5 years are eligible. Results Between March 27th and May 4th, 442 patients were registered. For this first analysis, 351 patients were included of whom 114 patients died. In multivariable analyses, age ≥65 years (p, Highlights • Patients with cancer might have an increased risk for severe outcome of COVID-19. • This nationwide study investigated risk factors for fatal outcome of COVID-19. • Among 442 registered patients with cancer, 32.3% of patients died of COVID-19. • Haematological malignancy and lung cancer increased the risk of fatal outcome. • These results can guide treatment and vaccination decisions in patients with cancer.

Objective: To evaluate changes in duration of physical activity (PA) and sedentary behavior (SB) from discharge to 1 year after inpatient rehabilitation in ambulatory people with spinal cord injury (SCI).Design: Longitudinal cohort study with objective measurements of physical behavior at discharge and at 6 and 12 months post discharge.Setting: Three rehabilitation centers and the participant's home environment.Participants: Participants (N= 47) with ambulatory function were consecutively recruited from the self-management and self-efficacy in patients with SCI cohort (age 18 years or older, recent SCI, expected inpatient stay >4wk). Mean age was 54.5 +/- 12.9 years, all had incomplete lesions, 53% were men, 49% had tetraplegia, and 51% were community ambulators at discharge.Interventions: Not applicable.Main Outcome Measures: Duration (min) of PA (summed duration of walking, cycling, running, and wheeling) and SB (sitting/lying).Results: Mean duration of PA increased by 21 min/d (95% confidence interval, 7-35) and SB decreased by 64 min/d (95% confidence interval, -94 to -35) from discharge to 6 months after inpatient rehabilitation. No changes were found in the second half-year. One year after discharge mean PA was 116 +/- 59 min/d and mean SB was 665 +/- 121 min/d. The increase in PA was the result of an almost doubling of time spent walking. Variability in physical behavior and its change was large. Older age and lower ambulation level were associated with lower PA, lower ambulation level with higher SB, and tetraplegia was associated with a reduced increase in PA.Conclusions: At group level, duration of PA and SB improved following inpatient rehabilitation in ambulatory people with SCI. However, there were large differences between individuals. Levels 1 year after discharge were still unfavorable, particularly regarding SB. (C) 2020 by the American Congress of Rehabilitation Medicine

Objectives: To investigate whether the combination of self-efficacy levels of individuals with spinal cord injury (SCI) or acquired brain injury (ABI) and their significant others, measured shortly after the start of inpatient rehabilitation, predict their personal and family adjustment 6 months after inpatient discharge.Design: Prospective longitudinal study.Setting: Twelve Dutch rehabilitation centers.Participants: Volunteer sample consisting of dyads (N=157) of adults with SCI or ABI who were admitted to inpatient rehabilitation and their adult significant others.Interventions: Not applicable.Main Outcome Measures: Self-efficacy (General Competence Scale) and personal and family adjustment (Hospital Anxiety and Depression Scale and McMaster Family Assessment Device General Functioning).Results: In 20 dyads, both individuals with SCI or ABI and their significant others showed low self-efficacy at baseline. In 67 dyads, both showed high self-efficacy. In the low-self-efficacy dyads, 61% of the individuals with SCI or ABI and 50% of the significant others showed symptoms of anxiety 6 months after discharge, vs 23% and 30%, respectively, in the high-self-efficacy dyads. In the low-self-efficacy dyads, 56% of individuals with SCI or ABI and 50% of the significant others reported symptoms of depression, vs 20% and 27%, respectively, in the high-self-efficacy dyads. Problematic family functioning was reported by 53% of the individuals with SCI or ABI and 42% of the significant others in the low-self-efficacy dyads, vs 4% and 12%, respectively, in the high-self-efficacy dyads. Multivariate analysis of variance analyses showed that the combination of levels of self-efficacy of individuals with SCI or ABI and their significant others at the start of inpatient rehabilitation predict personal (V=0.12; F-6,F-302=2.8; P=.010) and family adjustment (V=0.19; F-6,F-252=4.3; PConclusions: Low-self-efficacy dyads appear to be more at risk for personal and family adjustment problems after discharge. Screening for self-efficacy may help healthcare professionals to identify and support families at risk for long-term adjustment problems. (C) 2020 by the American Congress of Rehabilitation Medicine. Published by Elsevier Inc.

Genomic sequencing has significant potential to inform public health management for SARS-CoV-2. Here we report high-throughput genomics for SARS-CoV-2, sequencing 80% of cases in Victoria, Australia (population 6.24 million) between 6 January and 14 April 2020 (total 1,333 COVID-19 cases). We integrate epidemiological, genomic and phylodynamic data to identify clusters and impact of interventions. The global diversity of SARS-CoV-2 is represented, consistent with multiple importations. Seventy-six distinct genomic clusters were identified, including large clusters associated with social venues, healthcare and cruise ships. Sequencing sequential samples from 98 patients reveals minimal intra-patient SARS-CoV-2 genomic diversity. Phylodynamic modelling indicates a significant reduction in the effective viral reproductive number (Re) from 1.63 to 0.48 after implementing travel restrictions and physical distancing. Our data provide a concrete framework for the use of SARS-CoV-2 genomics in public health responses, including its use to rapidly identify SARS-CoV-2 transmission chains, increasingly important as social restrictions ease globally., Genome sequencing can be used to infer pathogen transmission dynamics and inform public health responses. Here, the authors sequence >1,200 SARS-CoV-2 samples from Victoria, Australia and find genomic support for the effectiveness of social restrictions in reducing transmission.

Objectives: This study aimed to investigate the performance of computed tomography derived fractional flow reserve based interactive planner (FFRCT planner) to predict the physiological benefits of percutaneous coronary intervention (PCI) as defined by invasive post-PCI FFR. Background: Advances in FFRCT technology have enabled the simulation of hyperemic pressure changes after virtual removal of stenoses. Methods: In 56 patients (63 vessels) invasive FFR measurements before and after PCI were obtained and FFRCT was calculated using pre-PCI coronary CT angiography. Subsequently, FFRCT and invasive coronary angiography models were aligned allowing virtual removal of coronary stenoses on pre-PCI FFRCT models in the same locations as PCI was performed. Relationships between invasive FFR and FFRCT, between post-PCI FFR and FFRCT planner, and between delta FFR and delta FFRCT were evaluated. Results: Pre PCI, invasive FFR was 0.65 ± 0.12 and FFRCT was 0.64 ± 0.13 (p =.34) with a mean difference of 0.015 (95% CI: −0.23–0.26). Post-PCI invasive FFR was 0.89 ± 0.07 and FFRCT planner was 0.85 ± 0.07 (p CT were 0.23 ± 0.12 and 0.21 ± 0.12 (p =.09) with a mean difference of 0.025 (95% CI: −0.20–0.25). Significant correlations were found between pre-PCI FFR and FFRCT (r = 0.53, p CT planner (r = 0.41, p =.001), and between delta FFR and delta FFRCT (r = 0.57, p CT planner tool demonstrated significant albeit modest agreement with post-PCI FFR and change in FFR values after PCI. The FFRCT planner tool may hold promise for PCI procedural planning; however, improvement in technology is warranted before clinical application.

AIMS: The aim of this study was to explore the relationships between ischaemic burden and changes in absolute myocardial perfusion following chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS AND RESULTS: A total of 193 consecutive patients underwent [15O]H2O positron emission tomography prior to and three months after successful CTO PCI. Change in perfusion defect size, quantitative hyperaemic myocardial blood flow (MBF) and coronary flow reserve (CFR) within the CTO area were compared among patients with limited (0-1 segment, N=15), moderate (2-3 segments, N=61) and large (≥4 segments, N=117) perfusion defects. Median reductions in defect size were 1 [0-1], 2 [1-3], and 4 [2-5] segments in patients with a limited, moderate and large defect (all comparisons p

Determining the anatomic severity and extent of coronary artery disease (CAD) by means of coronary computed tomography angiography (CCTA) and its effect on perfusion using myocardial perfusion imaging (MPI) form the pillars of the non-invasive imaging assessment of CAD. This review will 1) focus on CCTA and [15O]H2O positron emission tomography MPI as stand-alone imaging modalities and their combined use for detecting CAD, 2) highlight some of the lessons learned from the PACIFIC trial (Comparison of Coronary CT Angiography, SPECT, PET, and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve (FFR) (NCT01521468)), and 3) discuss the use of [15O]H2O PET MPI in the clinical work-up of patients with a chronic coronary total occlusion (CTO).

Objective: Conventional genetic tests (quantitative fluorescent-PCR [QF-PCR] and single nucleotide polymorphism-array) only diagnose similar to 40% of fetuses showing ultrasound abnormalities. Rapid exome sequencing (rES) may improve this diagnostic yield, but includes challenges such as uncertainties in fetal phenotyping, variant interpretation, incidental unsolicited findings, and rapid turnaround times. In this study, we implemented rES in prenatal care to increase diagnostic yield. Methods: We prospectively studied 55 fetuses. Inclusion criteria were: (a) two or more independent major fetal anomalies, (b) hydrops fetalis or bilateral renal cysts alone, or (c) one major fetal anomaly and a first-degree relative with the same anomaly. In addition to conventional genetic tests, we performed trio rES analysis using a custom virtual gene panel of similar to 3850 Online Mendelian Inheritance in Man (OMIM) genes. Results: We established a genetic rES-based diagnosis in 8 out of 23 fetuses (35%) without QF-PCR or array abnormalities. Diagnoses included MIRAGE (SAMD9), Zellweger (PEX1), Walker-Warburg (POMGNT1), Noonan (PTNP11), Kabuki (KMT2D), and CHARGE (CHD7) syndrome and two cases of Osteogenesis Imperfecta type 2 (COL1A1). In six cases, rES diagnosis aided perinatal management. The median turnaround time was 14 (range 8-20) days. Conclusion: Implementing rES as a routine test in the prenatal setting is challenging but technically feasible, with a promising diagnostic yield and significant clinical relevance.

The etiology of nonimmune hydrops fetalis is extensive and includes genetic disorders. We describe a term-born female neonate with late onset extensive nonimmune hydrops, that is, polyhydramnios, edema, and congenital bilateral chylothorax. This newborn was successfully treated with repetitive thoracocentesis, total parenteral feeding, octreotide intravenously and finally surgical pleurodesis and corticosteroids. A genetic cause seemed plausible as the maternal history revealed a fatal nonimmune hydrops fetalis. A homozygous truncating variant inGDF2(c.451C>T, p.(Arg151*)) was detected with exome sequencing. Genetic analysis of tissue obtained from the deceased fetal sibling revealed the same homozygous variant. The parents and two healthy siblings were heterozygous for theGDF2variant. Skin and lung biopsies in the index patient, as well as the revised lung biopsy of the deceased fetal sibling, showed lymphatic dysplasia and lymphangiectasia. To the best of our knowledge, this is the first report of an association between a homozygous variant inGDF2with lymphatic dysplasia, hydrothorax and nonimmune hydrops fetalis.

Viruses have evolved to efficiently express their genes in host cells, which makes them ideally suited as gene delivery vectors for gene and immunotherapies. Replication competent (RC) viral vectors encoding foreign or self-proteins induce strong T-cell responses that can be used for the development of effective cancer treatments. Replication-defective (RD) viral vectors encoding self-proteins are non-immunogenic when introduced in a host naïve for the cognate virus. RD viral vectors can be used to develop gene replacement therapies for genetic disorders and tolerization therapies for autoimmune diseases and allergies. Degenerative/inflammatory diseases are associated with chronic inflammation and immune responses that damage the tissues involved. These diseases therefore strongly resemble autoimmune diseases. This review deals with the use of RC and RD viral vectors for unraveling the pathogenesis of immune-related diseases and their application to the development of the next generation prophylactics and therapeutics for todays’ major diseases.

Influenza A(H1N1)pdm09 (pH1N1) virus has become established in swine in the United Kingdom and currently co-circulates with previously enzootic swine influenza A virus (IAV) strains, including avian-like H1N1 and human-like H1N2 viruses. During 2010, a swine influenza A reassortant virus, H1N2r, which caused mild clinical disease in pigs in the United Kingdom, was isolated. This reassortant virus has a novel gene constellation, incorporating the internal gene cassette of pH1N1-origin viruses and hemagglutinin and neuraminidase genes of swine IAV H1N2 origin. We investigated the pathogenesis and infection dynamics of the H1N2r isolate in pigs (the natural host) and in ferrets, which represent a human model of infection. Clinical and virologic parameters were mild in both species and both intraspecies and interspecies transmission was observed when initiated from either infected pigs or infected ferrets. This novel reassortant virus has zoonotic and reverse zoonotic potential, but no apparent increased virulence or transmissibility, in comparison to pH1N1 viruses.

Purpose To compare cardiac magnetic resonance imaging (CMR) with [15O]H2O positron emission tomography (PET) for quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with coronary artery disease (CAD). Methods Fifty-nine patients with stable CAD underwent CMR and [15O]H2O PET. The CMR imaging protocol included late gadolinium enhancement to rule out presence of scar tissue and perfusion imaging using a dual sequence, single bolus technique. Absolute MBF was determined for the three main vascular territories at rest and during vasodilator stress. Results CMR measurements of regional stress MBF and MFR showed only moderate correlation to those obtained using PET (r = 0.39; P r = 0.36; P 15O]H2O PET-derived stress MBF ≤ 2.3 mL/min/g and MFR ≤ 2.5. Using these cutoff values, CMR and PET were concordant in 137 (77%) vascular territories for stress MBF and 135 (80%) vascular territories for MFR. Conclusion CMR measurements of stress MBF and MFR showed modest agreement to those obtained with [15O]H2O PET. Nevertheless, stress MBF and MFR were concordant between CMR and [15O]H2O PET in 77% and 80% of vascular territories, respectively.

Removal of colorectal adenomas is an effective strategy to reduce colorectal cancer (CRC) mortality rates. However, as only a minority of adenomas progress to cancer, such strategies may lead to overtreatment. The present study aimed to characterize adenomas by in‐depth molecular profiling, to obtain insights into altered biology associated with the colorectal adenoma‐to‐carcinoma progression. We obtained low‐coverage whole genome sequencing, RNA sequencing and tandem mass spectrometry data for 30 CRCs, 30 adenomas and 18 normal adjacent colon samples. These data were used for DNA copy number aberrations profiling, differential expression, gene set enrichment and gene‐dosage effect analysis. Protein expression was independently validated by immunohistochemistry on tissue microarrays and in patient‐derived colorectal adenoma organoids. Stroma percentage was determined by digital image analysis of tissue sections. Twenty‐four out of 30 adenomas could be unambiguously classified as high risk (n = 9) or low risk (n = 15) of progressing to cancer, based on DNA copy number profiles. Biological processes more prevalent in high‐risk than low‐risk adenomas were related to proliferation, tumor microenvironment and Notch, Wnt, PI3K/AKT/mTOR and Hedgehog signaling, while metabolic processes and protein secretion were enriched in low‐risk adenomas. DNA copy number driven gene‐dosage effect in high‐risk adenomas and cancers was observed for POFUT1, RPRD1B and EIF6. Increased POFUT1 expression in high‐risk adenomas was validated in tissue samples and organoids. High POFUT1 expression was also associated with Notch signaling enrichment and with decreased goblet cells differentiation. In‐depth molecular characterization of colorectal adenomas revealed POFUT1 and Notch signaling as potential drivers of tumor progression., What's new? Removal of colorectal adenomas is an effective strategy to reduce colorectal cancer (CRC) mortality rates. However, as only a minority of adenomas progress to cancer, such strategies may lead to overtreatment. While high‐risk adenomas, defined by specific DNA copy number aberrations, have an increased risk of progression, the mechanisms underlying colorectal adenoma‐to‐carcinoma progression remain unclear. This molecular characterization of colorectal adenomas, CRCs, and normal adjacent colon samples demonstrates that biological processes inherent to CRC are already more active in high‐risk adenomas compared to low‐risk adenomas. Moreover, the findings highlight POFUT1 and Notch signaling as potential drivers of colorectal tumor development.

Aim of the study: The coronavirus disease 2019 (COVID-19) pandemic significantly impacted cancer care. In this study, clinical patient characteristics related to COVID-19 outcomes and advanced care planning, in terms of non-oncological treatment restrictions (e.g. do not-resuscitate codes), were studied in patients with cancer and COVID-19. Methods: The Dutch Oncology COVID-19 Consortium registry was launched in March 2020 in 45 hospitals in the Netherlands, primarily to identify risk factors of a severe COVID-19 outcome in patients with cancer. Here, an updated analysis of the registry was performed, and treatment restrictions (e.g. do-not-intubate codes) were studied in relation to COVID19 outcomes in patients with cancer. Oncological treatment restrictions were not taken into account. Results: Between 27th March 2020 and 4th February 2021, 1360 patients with cancer and COVID-19 were registered. Follow-up data of 830 patients could be validated for this analysis. Overall, 230 of 830 (27.7%) patients died of COVID-19, and 60% of the remaining 600 patients with resolved COVID-19 were admitted to the hospital. Patients with haematological malignancies or lung cancer had a higher risk of a fatal outcome than other solid tumours. No correlation between anticancer therapies and the risk of a fatal COVID-19 outcome was found. In terms of end-of-life communication, 50% of all patients had restrictions regarding life prolonging treatment (e.g. do-not-intubate codes). Most identified patients with treatment restrictions had risk factors associated with fatal COVID-19 outcome. Conclusion: There was no evidence of a negative impact of anticancer therapies on COVID-19 outcomes. Timely end-of-life communication as part of advanced care planning could save patients from prolonged suffering and decrease burden in intensive care units. Early discussion of treatment restrictions should therefore be part of routine oncological care, especially during the COVID-19 pandemic. 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background People with a recent spinal cord injury (SCI) often follow intensive rehabilitation. Learning appropriate self-care, deal with their impairments and prevent secondary health conditions (SHCs), is highly important during rehabilitation. To date it is not clear how self-care skills are taught to people with SCI. The objective of this study was to understand how people with SCI experienced the learning of appropriate self-care skills during inpatient rehabilitation, including the role of the rehabilitation team. Methods Individual semi-structured interviews were conducted with 15 people with SCI, recently discharged from initial inpatient rehabilitation. Interviews were audio-taped, transcribed and analyzed thematically. Results Two main themes and seven sub-themes were identified. Participants stated that the contribution of the rehabilitation team to learning self-care, including prevention of SHCs, was mostly made by optimizing opportunities to learn through experience. For preventing SHCs, education and lessons learned from the professionals during therapy and the formal educational program, was experienced as especially important. Further, the motivational attitude of the professionals which participants found stimulating and was based on respect, combined with their positive contribution as one team, were seen as essentials elements for learning appropriate self-care. However participants did not recognize the contribution of the nursing staff as part of their rehabilitation, although it was seen as very important. An important aspect of the participants’ own contribution was challenging oneself to learn self-care. This was done in different ways by the participants. Further, their own mental adjustment was considered important in the learning process. The gaining of confidence was by most participants seen as personal characteristic, although they also recognized the importance of the team effort and the experiences they underwent. Conclusions Learning appropriate self-care was mostly done through experience, by challenging themselves, and making use of the opportunities given by the members of the rehabilitation team. The same strategies used by the rehabilitation team to teach people with SCI to perform appropriate self-care, were also helpful for the participants to gain confidence. Explicit attention for self-care training as an important goal in SCI rehabilitation may strengthen the nursing staff’s role and stimulate interdisciplinary working.

To evaluate the effect of percutaneous coronary intervention (PCI) of coronary chronic total occlusions (CTOs) on left ventricular (LV) strain assessed using cardiac magnetic resonance (CMR) tissue tracking. In 150 patients with a CTO, longitudinal (LS), radial (RS) and circumferential shortening (CS) were determined using CMR tissue tracking before and 3 months after successful PCI. In patients with impaired LV strain at baseline, global LS (10.9 ± 2.4% vs 11.6 ± 2.8%; P = 0.006), CS (11.3 ± 2.9% vs 12.0 ± 3.5%; P = 0.002) and RS (15.8 ± 4.9% vs 17.4 ± 6.6%; P = 0.001) improved after revascularization of the CTO, albeit to a small, clinically irrelevant, extent. Strain improvement was inversely related to the extent of scar, even after correcting for baseline strain (B = − 0.05; P = 0.008 for GLS, B = − 0.06; P = 0.016 for GCS, B = − 0.13; P = 0.017 for GRS). In the vascular territory of the CTO, dysfunctional segments showed minor improvement in both CS (10.8 [6.9 to 13.3] % vs 11.9 [8.1 to 15.0] %; P P

Background Successful revascularization of a chronic total coronary occlusion (CTO) impacts coronary physiology of the remote myocardial territory. Purpose This study evaluated the effect of CTO percutaneous coronary intervention (PCI) on changes in absolute perfusion in remote myocardium as assessed by serial [15O]H2O positron emission tomography (PET) perfusion imaging. Methods A total of 164 patients underwent [15O]H2O PET imaging at baseline and 3 months after successful single-vessel revascularization of a CTO to evaluate changes in hyperemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) in the remote myocardial territory supplied by both non-target coronary arteries. Results Remote hMBF and CFR improved (2.29±0.67 to 2.48±0.75 mL min–1 g–1 and 2.48±0.76 to 2.74±0.85, respectively) after CTO revascularization (p Conclusions An overall increase in remote myocardial perfusion was observed following CTO PCI. Absolute perfusion indices in the remote myocardium showed a positive linear correlation with perfusion in the CTO vessel, before and after CTO revascularization. Importantly, baseline, post-PCI and the absolute increase in perfusion in the CTO territory were independently associated with increases in remote myocardial perfusion after revascularization. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

There is a critical need to develop superior influenza vaccines that provide broader protection. Influenza vaccines are traditionally tested in naïve animals, although humans are exposed to influenza in the first years of their lives, but the impact of prior influenza exposure on vaccine induced immune responses has not been well studied. Pigs are an important natural host for influenza, are a source of pandemic viruses, and are an excellent model for human influenza. Here we investigated the immunogenicity of the ChAdOx2 viral vectored vaccine, expressing influenza nucleoprotein, matrix protein 1 and neuraminidase in H1N1pdm09 pre-exposed pigs. We evaluated the importance of route of administration by comparing intra-nasal, aerosol and intra-muscular immunizations. Aerosol delivery boosted the local lung T cell and antibody responses, while intra-muscular immunization boosted systemic immunity. These results will inform how best to deliver vaccines in order to harness optimal protective immunity.

BACKGROUND Recurrence rates after resection of colorectal cancer liver metastases (CRLM) are high and correlate with worse survival. Postoperative circulating tumour DNA (ctDNA) is a promising prognostic biomarker. Focusing on patients with resected CRLM, this study aimed to evaluate the association between the detection of postoperative ctDNA, pathologic response and recurrence-free survival (RFS). METHODS Twenty-three patients were selected from an ongoing phase-3 trial who underwent resection of RAS-mutant CRLM after induction systemic treatment. CtDNA analysis was performed by droplet digital PCR using blood samples collected at baseline, before and after resection. Pathologic response of CRLM was determined via the Tumour Regression Grading system. FINDINGS With a median follow-up of 19.6 months, the median RFS for patients with detectable (N = 6, [26%]) and undetectable (N = 17, [74%]) postoperative ctDNA was 4.8 versus 12.1 months, respectively. Among 21 patients with available tumour tissue, pathologic response in patients with detectable compared to undetectable postoperative ctDNA was found in one of six (17%) and 15 of 15 (100%) patients, respectively (p

Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4–5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4–16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2–56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1–79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting. Findings: 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p

Objectives: This study evaluated myocardial viability as well as global and regional functional recovery after successful chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) using sequential quantitative cardiac magnetic resonance (CMR) imaging. Background: The patient benefits of CTO PCI are being questioned. Methods: In a single high-volume CTO PCI center patients were prospectively scheduled for CMR at baseline and 3 months after successful CTO PCI between 2013 and 2018. Segmental wall thickening (SWT) and percentage late gadolinium enhancement (LGE) were quantitatively measured per segment. Viability was defined as dysfunctional myocardium (50%, N = 26 [4%], −0.08 ± 1.09 mm, p < 0.01). Patients with ≥2 CTO segments viability showed more SWT increase in the CTO territory compared to patients with 0–1 segment viability (0.49 ± 0.93 vs. 0.12 ± 0.98 mm, p = 0.03). Conclusions: Detection of dysfunctional myocardial segments without extensive scar (≤50% LGE) as a marker for viability on CMR aids in identifying patients with significant regional functional recovery after CTO PCI.

Aims Myocardial ischaemic burden (IB) is used for the risk stratification of patients with coronary artery disease (CAD). This study sought to define a prognostic threshold for quantitative [15O]H2O positron emission tomography (PET)-derived IB. Methods and results A total of 623 patients with suspected or known CAD who underwent [15O]H2O PET perfusion imaging were included. The endpoint was a composite of death and non-fatal myocardial infarction (MI). A hyperaemic myocardial blood flow (hMBF) and myocardial flow reserve (MFR)-derived IB were determined. During a median follow-up time of 6.7 years, 62 patients experienced an endpoint. A hMBF IB of 24% and MFR IB of 28% were identified as prognostic thresholds. Patients with a high hMBF or MFR IB (above threshold) had worse outcome compared to patients with a low hMBF IB [annualized event rates (AER): 2.8% vs. 0.6%, P Conclusion A hMBF IB ≥24% was a stronger predictor of adverse outcome than an MFR IB ≥28%. Nevertheless, classifying patients according to concordance of IB result allowed for the identification of low- and high-risk patients.

Background: Genetic disorders are a substantial cause of infant morbidity and mortality and are frequently suspected in neonatal intensive care units. Non-specific clinical presentation or limitations to physical examination can result in a plethora of genetic testing techniques, without clear strategies on test ordering. Here, we review our 2-years experiences of rapid genetic testing of NICU patients in order to provide such recommendations.Methods: We retrospectively included all patients admitted to the NICU who received clinical genetic consultation and genetic testing in our University hospital. We documented reasons for referral for genetic consultation, presenting phenotypes, differential diagnoses, genetic testing requested and their outcomes, as well as the consequences of each (rapid) genetic diagnostic approach. We calculated diagnostic yield and turnaround times (TATs).Results: Of 171 included infants that received genetic consultation 140 underwent genetic testing. As a result of testing as first tier, 13/14 patients received a genetic diagnosis from QF-PCR; 14/115 from SNP-array; 12/89 from NGS testing, of whom 4/46 were diagnosed with a small gene panel and 8/43 with a large OMIM-morbid based gene panel. Subsequent secondary or tertiary analysis and/or additional testing resulted in five more diagnoses. TATs ranged from 1 day (QF-PCR) to a median of 14 for NGS and SNP-array testing, with increasing TAT in particular when many consecutive tests were performed. Incidental findings were detected in 5/140 tested patients (3.6%).Conclusion: We recommend implementing a broad NGS gene panel in combination with CNV calling as the first tier of genetic testing for NICU patients given the often unspecific phenotypes of ill infants and the high yield of this large panel.

STUDY DESIGN: Explorative retrospective cohort study. OBJECTIVE: Secondary health conditions (SHCs) are common in people with spinal cord injury (SCI). To date, little is known about the effectiveness of long-term follow-up care in preventing SHCs. The objective of this study was to explore the therapeutic content of an interdisciplinary follow-up clinic by retrospective analyses of provided recommendations and collected data concerning SHCs. SETTING: Rehabilitation center Sint Maartenskliniek, The Netherlands. METHODS: All people with SCI, who visited one or more outpatient interdisciplinary follow-up clinics between January 2012 and October 2020 were included in this study. Treatment information was retrieved from their medical records. RESULTS: The 264 participants of the follow-up clinic received, after their first visit, an average of 3.9 recommendations regarding SHCs. Most recommendations were preventive in nature (43%), and were related to physical SHCs (61%). Most recommendations were followed by the participants (34% out of 40% that could be determined) and half of the underlying problems were solved (31% out of 62%). The bodyweight and respiratory function remained stable over time. CONCLUSION: Participants of the interdisciplinary follow-up clinics received extensive recommendations on a variety of subjects, which most likely, reflects the interdisciplinary approach. Recommendations were followed-up to a large extent, resulting in solving half of the underlying SHCs. This way, worse SHCs were prevented by the recommendations. This findings, together with the stability of respiratory function and bodyweight, suggests the added value of the interdisciplinary follow-up clinic to usual care. More prospective research is necessary to investigate the (cost-)effectiveness.

Patient-specific models of blood flow are being used clinically to diagnose and plan treatment for coronary artery disease. A remaining challenge is bridging scales from flow in arteries to the micro-circulation supplying the myocardium. Previously proposed models are descriptive rather than predictive and have not been applied to human data. The goal here is to develop a multiscale patient-specific model enabling blood flow simulation from large coronary arteries to myocardial tissue. Patient vasculatures are segmented from coronary computed tomography angiography data and extended from the image-based model down to the arteriole level using a space-filling forest of synthetic trees. Blood flow is modeled by coupling a 1D model of the coronary arteries to a single-compartment Darcy myocardium model. Simulated results on five patients with non-obstructive coronary artery disease compare overall well to [$$^{15}$$ 15 O]$$\text {H}_{{2}}$$ H 2 O PET exam data for both resting and hyperemic conditions. Results on a patient with severe obstructive disease link coronary artery narrowing with impaired myocardial blood flow, demonstrating the model’s ability to predict myocardial regions with perfusion deficit. This is the first report of a computational model for simulating blood flow from the epicardial coronary arteries to the left ventricle myocardium applied to and validated on human data.

Background and study aims Microsatellite instability accelerates colorectal cancer development in patients with Lynch syndrome (LS). Previous research showed that virtual chromoendoscopy increases detection of adenomas during colonoscopy surveillance of patients with LS. Because previous research revealed that Lynch patients have an increased vascular network in the oral mucosa, we hypothesized that increased vascularization of LS-associated adenomas is the cause of better detection with virtual chromoendoscopy. Patients and methods In this pilot study, patients with LS having a proven germline mutation were selected from two tertiary referral hospitals and non-LS patients from an outpatient colonoscopy center. Adenomas from patients with LS were exactly matched in size and histology with adenomas from non-LS patients. Initial adenoma diagnosis was confirmed by a specialist pathologist. All adenomas were stained with CD31 and adenomatous tissue was annotated by the specialist pathologist. Image analysis of CD31-positive microvessel density was conducted using FIJI software. Results Colonoscopy of 63 patients with LS and 24 non-LS patients provided 40 adenomas that could be exactly matched in size and histology. In image-analysis, the CD31-positive microvessel density (2.49 % vs. 2.47 %, P = 0.96), the average size of CD31-positive structures (514 μm2 vs. 523 μm2, P = 0.26) nor the amount of vascular structures per mm2 (183 vs. 176, P = 0.50) differed between adenomas of LS patients and non-Lynch patients. Conclusion The outcomes of this pilot case-control study did not provide further insights into the mechanism of increased adenoma detection in LS patients using virtual chromoendoscopy techniques.

Aspirin is traditionally taken once daily in the morning and considered to be effective throughout the 24h interval. Cardiovascular events occur most frequently in the early morning, suggesting that these hours are critical in terms of adequate platelet inhibition. This study therefore assed platelet function in the early morning—8.00 AM—in healthy volunteers, during a once-daily (OD) 80 mg morning in comparison with an OD evening regimen and a twice-daily (BID) 40 mg regimen. It was an open-label randomized cross-over study, comprising 12 healthy subjects. Subjects were allocated to three sequential dosage regimens: 80 mg OD at 8.00 AM, 80mg OD at 8.00 PM, and 40 mg BID at 8.00 AM and PM. Platelet function 12 and 24 hours after aspirin intake was measured by means of serum thromboxane B2 (sTxB2) levels, the collagen/epinephrine closure time (Platelet Function Analyzer(PFA)-200®) and the Aspirin Reaction Units (ARU, VerifyNow®). The results demonstrated that early morning sTxB2 concentrations were 5843pg in the morning regimen, 2877pg in the evening OD regimen, and 3343pg in the BID regimen (morning- vs evening regimen p =

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is a rare bile duct disease strongly associated with inflammatory bowel disease (IBD). Whole-exome sequencing (WES) has contributed to understanding the molecular basis of very early-onset IBD, but rare protein-altering genetic variants have not been identified for early-onset PSC. We performed WES in patients diagnosed with PSC ≤ 12 years to investigate the contribution of rare genetic variants to early-onset PSC. METHODS: In this multicentre study, WES was performed on 87 DNA samples from 29 patient-parent trios with early-onset PSC. We selected rare (minor allele frequency