Immunomodulatory drugs in sepsis: a systematic review and meta-analysis.

Dysregulation of the host immune response has a central role in the pathophysiology of sepsis. There has been much interest in immunomodulatory drugs as potential therapeutic adjuncts in sepsis. We conducted a systematic review and meta-analysis of randomised controlled trials evaluating the safety and clinical effectiveness of immunomodulatory drugs as adjuncts to standard care in the treatment of adults with sepsis. Our primary outcomes were serious adverse events and all-cause mortality. Fifty-six unique, eligible randomised controlled trials were identified, assessing a range of interventions including cytokine inhibitors; anti-inflammatories; immune cell stimulators; platelet pathway inhibitors; and complement inhibitors. At 1-month follow-up, the use of cytokine inhibitors was associated with a decreased risk of serious adverse events, based on 11 studies involving 7138 patients (RR (95%CI) 0.95 (0.90-1.00), I2 = 0%). The only immunomodulatory drugs associated with an increased risk of serious adverse events were toll-like receptor 4 antagonists (RR (95%CI) 1.18 (1.04-1.34), I2 = 0% (two trials, 567 patients)). Based on 18 randomised controlled trials, involving 11,075 patients, cytokine inhibitors reduced 1-month mortality (RR (95%CI) 0.88 (0.78-0.98), I2 = 57%). Mortality reduction was also shown in the subgroup of 13 randomised controlled trials that evaluated anti-tumour necrosis factor α interventions (RR (95%CI) 0.93 (0.87-0.99), I2 = 0%). Anti-inflammatory drugs had the largest apparent effect on mortality at 2 months at any dose (two trials, 228 patients, RR (95%CI) 0.64 (0.51-0.80), I2 = 0%) and at 3 months at any dose (three trials involving 277 patients, RR (95%CI) 0.67 (0.55-0.81), I2 = 0%). These data indicate that, except for toll-like receptor 4 antagonists, there is no evidence of safety concerns for the use of immunomodulatory drugs in sepsis, and they may show some short-term mortality benefit for selected drugs.

Interaction between clinicians and artificial intelligence to detect fetal atrioventricular septal defects on ultrasound: how can we optimize collaborative performance?

OBJECTIVES: Artificial intelligence (AI) has shown promise in improving the performance of fetal ultrasound screening in detecting congenital heart disease (CHD). The effect of giving AI advice to human operators has not been studied in this context. Giving additional information about AI model workings, such as confidence scores for AI predictions, may be a way of further improving performance. Our aims were to investigate whether AI advice improved overall diagnostic accuracy (using a single CHD lesion as an exemplar), and to determine what, if any, additional information given to clinicians optimized the overall performance of the clinician-AI team. METHODS: An AI model was trained to classify a single fetal CHD lesion (atrioventricular septal defect (AVSD)), using a retrospective cohort of 121 130 cardiac four-chamber images extracted from 173 ultrasound scan videos (98 with normal hearts, 75 with AVSD); a ResNet50 model architecture was used. Temperature scaling of model prediction probability was performed on a validation set, and gradient-weighted class activation maps (grad-CAMs) produced. Ten clinicians (two consultant fetal cardiologists, three trainees in pediatric cardiology and five fetal cardiac sonographers) were recruited from a center of fetal cardiology to participate. Each participant was shown 2000 fetal four-chamber images in a random order (1000 normal and 1000 AVSD). The dataset comprised 500 images, each shown in four conditions: (1) image alone without AI output; (2) image with binary AI classification; (3) image with AI model confidence; and (4) image with grad-CAM image overlays. The clinicians were asked to classify each image as normal or AVSD. RESULTS: A total of 20 000 image classifications were recorded from 10 clinicians. The AI model alone achieved an accuracy of 0.798 (95% CI, 0.760-0.832), a sensitivity of 0.868 (95% CI, 0.834-0.902) and a specificity of 0.728 (95% CI, 0.702-0.754), and the clinicians without AI achieved an accuracy of 0.844 (95% CI, 0.834-0.854), a sensitivity of 0.827 (95% CI, 0.795-0.858) and a specificity of 0.861 (95% CI, 0.828-0.895). Showing a binary (normal or AVSD) AI model output resulted in significant improvement in accuracy to 0.865 (P < 0.001). This effect was seen in both experienced and less-experienced participants. Giving incorrect AI advice resulted in a significant deterioration in overall accuracy, from 0.761 to 0.693 (P < 0.001), which was driven by an increase in both Type-I and Type-II errors by the clinicians. This effect was worsened by showing model confidence (accuracy, 0.649; P < 0.001) or grad-CAM (accuracy, 0.644; P < 0.001). CONCLUSIONS: AI has the potential to improve performance when used in collaboration with clinicians, even if the model performance does not reach expert level. Giving additional information about model workings such as model confidence and class activation map image overlays did not improve overall performance, and actually worsened performance for images for which the AI model was incorrect. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

[Intercultural adaptation of the PUKSoPC in German language : A scale for perceived control in patients with Parkinson's disease]. / Interkulturelle Adaptation der PUKSoPC in deutscher Sprache : Eine Skala zur gefühlten Kontrolle von Parkinson-Patientinnen und -Patienten.

BACKGROUND: The level of perceived control in people with Parkinson's disease plays a significant role in affecting their quality of life. Simpson et al. developed a scale of perceived control specific to Parkinson's disease called the Parkinson's UK Scale of Perceived Control (PUKSoPC). In this work, we present a cross-culturally adapted German translation of the original English version. METHODS: After receiving approval by the original authors, an internationally established procedure was used for cross-cultural adaptation. Firstly, the original English version was translated into German independently by two bilingual neuroscientists, who then agreed on a consensus version. This was tested on 10 people with Parkinson's disease and independently back translated into English by two different neuroscientists. After forming a consensus version, this English version was compared with the original version by all four translators. Differences between the versions resulted in modifications to the German translation so that the back translation matched the original as closely as possible. The final version was approved by two of the original authors and clinically tested on 50 people with Parkinson's disease. RESULTS: During the translation process, the four translators agreed on a culturally adapted German version of the PUKSoPC. Testing of the final version on 50 people with Parkinson's disease did not reveal any linguistic or content-related problems. CONCLUSION: The linguistically validated German version of the PUKSoPC presented in this paper is now freely available for measuring the levels of perceived control in people with Parkinson's disease to advance both research and clinical practice.

Anthropogenic, biogenic, and photochemical influences on surface formaldehyde and its significant decadal (2006-2017) decrease in the Lewiston-Clarkston valley of the northwestern United States.

Formaldehyde (HCHO) is a key carcinogen and plays an important role in atmospheric chemistry. Both field measurements and Positive Matrix Factorization (PMF) modeling have been employed to investigate the concentrations and sources of HCHO in the Lewiston-Clarkston (LC) valley of the mountainous northwestern U.S. Different instruments were deployed to measure surface formaldehyde and other related compounds in July of 2016 and 2017. The measurements reveal that the average HCHO concentrations have significantly decreased to 2-5 ppb in the LC valley in comparison to its levels (10-20 ppb) observed in July 2006. This discovery with surface measurements deserves attention given that satellite retrievals showed an increasing long-term trend from 2005 to 2014 in total vertical column density of HCHO in the region, suggesting that satellite instruments may not adequately resolve small valleys in the mountainous region. Our PMF modeling identified four major sources of HCHO in the valley: (1) emissions from a local paper mill, (2) secondary formation and background, (3) biogenic sources, and (4) traffic. This study reveals that the emissions from the paper mill cause high HCHO spikes (6-19 ppb) in the early morning. It is found that biogenic volatile organic compounds (VOCs) in the area are influenced by national forests surrounding the region (e.g., Nez Perce-Clearwater, Umatilla, Wallowa-Whitman, and Idaho Panhandle National Forests). The results provide useful information for developing strategies to control HCHO levels and have implications for future HCHO studies in atmospheric chemistry, which affects secondary aerosols and ozone formation.

Factor structure of the Oxford Shoulder Score: secondary analyses of the UK FROST and PROFHER trial populations.

AIMS: Frozen shoulder and proximal humeral fracture can cause pain, stiffness and loss of function. The impact of these symptoms on patients can be measured using the comprehensively validated, 12-item Oxford Shoulder Score (OSS). Evidence suggests that pain and function may have a differential impact on patients' experience of shoulder conditions, and this may be important for clinical management. We therefore explored the factor structure of the OSS within the UK FROST and PROFHER trial populations. METHODS: We performed exploratory factor analysis (EFA), followed by confirmatory factor analysis (CFA), on baseline UK FROST data from 490 of the 503 trial participants. Data at 6 months post-randomisation were used for 228 of the 250 participants for the PROFHER trial. RESULTS: UK FROST factor extraction results, using Velicer's Minimum Average Partial and Horn's Parallel Analysis tests, suggested a unifactorial solution, but two factors were weakly indicated by the less reliable 'Kaiser's eigenvalue > 1' and scree tests. We explored this further using EFA. Eight items (2 to 7, 9 and 10) loaded onto a 'Function' factor, three on a 'Pain' factor (1, 8 and 12) and item 11 cross-loaded. However, one- and two-factor models were rejected in CFA. Factor extraction of PROFHER data at 6 months demonstrated a single first-order factor solution, which was also subsequently rejected in CFA. CONCLUSION: Insufficient evidence was found, within the constraints of the data available, to support the use of 'Pain' and 'Function' sub-scales of the OSS in either patient population.

Evolutionary conservation of an ancient retroviral gagpol gene in Artiodactyla.

The genomes of mammals contain fingerprints of past infections by ancient retroviruses that invaded the germline of their ancestors. Most of these endogenous retroviruses (ERVs) contain only remnants of the original retrovirus; however, on rare occasions, ERV genes can be co-opted for a beneficial host function. While most studies of co-opted ERVs have focused on envelope genes, including the syncytins that function in placentation, there are examples of co-opted gag genes including one we recently discovered in simian primates. Here, we searched for other intact gag genes in non-primate mammalian lineages. We began by examining the genomes of extant camel species, which represent a basal lineage in the order Artiodactyla. This identified a gagpol gene with a large open reading frame (ORF) (>3,500 bp) in the same orthologous location in Artiodactyla species but that is absent in other mammals. Thus, this ERV was fixed in the common ancestor of all Artiodactyla at least 64 million years ago. The amino acid sequence of this gene, termed ARTgagpol, contains recognizable matrix, capsid, nucleocapsid, and reverse transcriptase domains in ruminants, with an RNase H domain in camels and pigs. Phylogenetic analysis and structural prediction of its reverse transcriptase and RNase H domains groups ARTgagpol with gammaretroviruses. Transcriptomic analysis shows ARTgagpol expression in multiple tissues suggestive of a co-opted host function. These findings identify the oldest and largest ERV-derived gagpol gene with an intact ORF in mammals, an intriguing milestone in the co-evolution of mammals and retroviruses. IMPORTANCE Retroviruses are unique among viruses that infect animals as they integrate their reverse-transcribed double-stranded DNA into host chromosomes. When this happens in a germline cell, such as sperm, egg, or their precursors, the integrated retroviral copies can be passed on to the next generation as endogenous retroviruses (ERVs). On rare occasions, the genes of these ERVs can be domesticated by the host. In this study we used computational similarity searches to identify an ancient ERV with an intact viral gagpol gene in the genomes of camels that is also found in the same genomic location in other even-toed ungulates suggesting that it is at least 64 million years old. Broad tissue expression and predicted preservation of the reverse transcriptase fold of this protein suggest that it may be domesticated for a host function. This is the oldest known intact gagpol gene of an ancient retrovirus in mammals.

"We're back in control of the story and we're not letting anyone take that away from us": patient teacher programs as means for patient emancipation.

While patient engagement in healthcare professions education (HPE) has significantly increased in the past decades, a theoretical gap remains. What are the varied reasons as to why patients get involved with HPE programs? With a focus on understanding what drives patient involvement with HPE programs, this study examined how a patient as teacher (PAT) program was experienced by medical students, patient teachers, and faculty within a medical school. Through a phenomenographic approach, this study captures and describes the different ways our study participants experienced a PAT program (the 'phenomenon'). 24 semi-structured interviews were conducted in total, comprised of interviews with patient teachers (N = 10), medical students (N = 10) and program facilitators (N = 4) who participated in a PAT program. Our focus was on participants' description of the program and was grounded in their experiences of as well as their beliefs about it. Our findings captured 4 layers representing the qualitatively different (yet interrelated) ways in which participants experienced/perceived and conceptualized the various aspects of their experience with the PAT program: (1) A productive disruption of the learning space (2) A re-humanization within healthcare (3) A means of empowerment and agency (4) A catalyst for change and emancipation. Our outcome space results can be visually illustrated by a nesting "Matryoshka" doll, representing the four layers and depicting the process of uncovering the less conscious layers of sense-making within this phenomenon. HPE programs that are co-produced with patients and actively involve patients as teachers have the potential, but not guarantee, to be emancipatory. To engage in PAT programs that exhibit an emancipatory potential, we need to consider transformative paradigms of education, which are aligned with social change, and disrupt the traditional teacher-learner hierarchy.

A model for malaria treatment evaluation in the presence of multiple species.

Plasmodium falciparum and P. vivax are the two most common causes of malaria. While the majority of deaths and severe morbidity are due to P. falciparum, P. vivax poses a greater challenge to eliminating malaria outside of Africa due to its ability to form latent liver stage parasites (hypnozoites), which can cause relapsing episodes within an individual patient. In areas where P. falciparum and P. vivax are co-endemic, individuals can carry parasites of both species simultaneously. These mixed infections complicate dynamics in several ways: treatment of mixed infections will simultaneously affect both species, P. falciparum can mask the detection of P. vivax, and it has been hypothesised that clearing P. falciparum may trigger a relapse of dormant P. vivax. When mixed infections are treated for only blood-stage parasites, patients are at risk of relapse infections due to P. vivax hypnozoites. We present a stochastic mathematical model that captures interactions between P. falciparum and P. vivax, and incorporates both standard schizonticidal treatment (which targets blood-stage parasites) and radical cure treatment (which additionally targets liver-stage parasites). We apply this model via a hypothetical simulation study to assess the implications of different treatment coverages of radical cure for mixed and P. vivax infections and a "unified radical cure" treatment strategy where P. falciparum, P. vivax, and mixed infections all receive radical cure after screening glucose-6-phosphate dehydrogenase (G6PD) normal. In addition, we investigated the impact of mass drug administration (MDA) of blood-stage treatment. We find that a unified radical cure strategy leads to a substantially lower incidence of malaria cases and deaths overall. MDA with schizonticidal treatment was found to decrease P. falciparum with little effect on P. vivax. We perform a univariate sensitivity analysis to highlight important model parameters.

Patient views on the implementation of artificial intelligence in radiotherapy.

PURPOSE/OBJECTIVE: To date there has been limited research looking at patient views on the implementation of artificial intelligence (AI) in radiotherapy. The aim of this study is to adapt and utilise a validated patient questionnaire to develop an understanding of current patient views on the use of AI in radiotherapy. MATERIALS/METHODS: An existing questionnaire, developed to assess understanding of patients' views on the implementation of AI in radiology, was adapted to the field of radiotherapy. The questionnaire was distributed to cancer patients receiving radiotherapy treatment between November 2021 and March 2022. Completed questionnaires were analysed to assess patient levels of positivity or negativity towards AI. Results were grouped into five factors, representing underlying patient perspectives, and correlation of factors with demographic variables was assessed. RESULTS: In total, 95 patients participated. Overall, there was a moderately negative patient view towards the use of AI in radiotherapy. Certain factors drew a more negative response than others, for example patients desire significant personal interaction with healthcare professionals during the course of their treatment. No significant correlation was found between the demographics of age and gender and the strength of views towards the use of AI in radiotherapy. CONCLUSION: This study has found that there are clear patient concerns around the use of AI in radiotherapy. As the use of AI in this field increases in future years, it will therefore be extremely important to educate and involve patients in the future direction of this technology.

Assessing systolic and diastolic reserves in male and female mice.

Cardiac reserve is a widely used health indicator and prognostic tool. Although it is well established how to assess cardiac reserve clinically, in preclinical models, it is more challenging lacking standardization. Furthermore, although cardiac reserve incorporates both systolic (i.e., contractile reserve) and diastolic (i.e., relaxation reserve) components of the cardiac cycle, less focus has been placed on diastolic reserve. The aim of our study was to determine which technique (i.e., echocardiography, invasive hemodynamic, and Langendorff) and corresponding parameters can be used to assess the systolic and diastolic reserves in preclinical models. Healthy adult male and female CD-1 mice were administered dobutamine and evaluated by echocardiography and invasive hemodynamic, or Langendorff to establish systolic and diastolic reserves. Here, we show that systolic reserve can be assessed using all techniques in vivo and in vitro. Yet, the current indices available are ineffective at capturing diastolic reserve of healthy mice in vivo. When assessing systolic reserve, sex affects the dose response of several commonly used echocardiography parameters [i.e., fractional shortening (FS), ejection fraction (EF)]. Taken together, this study improves our understanding of how sex impacts the interpretation assessment of cardiac reserve and establishes for the first time that in healthy adult mice, the diastolic reserve cannot be assessed by currently established methods in vivo.NEW & NOTEWORTHY Cardiac reserve is a globally used health indicator and prognostic tool that is used by clinicians and preclinical scientists. In physiology, we have a long-standing appreciation of how to assess systolic reserve but lack insight into sex differences and have no frame of reference for measuring diastolic reserve to certainty across cardiac techniques or the influence of sex. Here, we show that the primary means for assessing diastolic reserve is incorrect. Furthermore, we provided proof and clarity on how to correctly measure systolic and diastolic reserve capacities. We also highlight the imperative of sex differences to the measures of both systolic and diastolic reserves using several techniques (i.e., echocardiography, invasive hemodynamics, and Langendorff) in mice.

Cross-species transmission of an ancient endogenous retrovirus and convergent co-option of its envelope gene in two mammalian orders.

Endogenous retroviruses (ERVs) found in vertebrate genomes are remnants of retroviral invasions of their ancestral species. ERVs thus represent molecular fossil records of ancient retroviruses and provide a unique opportunity to study viral-host interactions, including cross-species transmissions, in deep time. While most ERVs contain the mutated remains of the original retrovirus, on rare occasions evolutionary selection pressures lead to the co-option/exaptation of ERV genes for a host function. Here, we report the identification of two ancient related non-orthologous ERV env genes, ARTenvV and CARenvV, that are preserved with large open reading frames (ORFs) in the mammalian orders Artiodactyla and Carnivora, respectively, but are not found in other mammals. These Env proteins lack a transmembrane motif, but phylogenetic analyses show strong sequence preservation and positive selection of the env surface ORF in their respective orders, and transcriptomic analyses show a broad tissue expression pattern for both ARTenvV and CARenvV, suggesting that these genes may be exapted for a host function. Multiple lines of evidence indicate that ARTenvV and CARenvV were derived from an ancient ancestral exogenous gamma-like retrovirus that was independently endogenized in two mammalian orders more than 60 million years ago, which roughly coincides with the K-Pg mass extinction event and subsequent mammalian diversification. Thus, these findings identify the oldest known retroviral cross-ordinal transmission of a gamma-like retrovirus with no known extant infectious counterpart in mammals, and the first discovery of the convergent co-option of an ERV gene derived from the same ancestral retrovirus in two different mammalian orders.

Evidence of Partial Seniority Conservation in the πg_{9/2} Shell for the N=50 Isotones.

The reduced transition probabilities for the 4_{1}^{+}→2_{1}^{+} and 2_{1}^{+}→0_{1}^{+} transitions in ^{92}Mo and ^{94}Ru and for the 4_{1}^{+}→2_{1}^{+} and 6_{1}^{+}→4_{1}^{+} transitions in ^{90}Zr have been determined in this experiment making use of a multinucleon transfer reaction. These results have been interpreted on the basis of realistic shell-model calculations in the f_{5/2}, p_{3/2}, p_{1/2}, and g_{9/2} proton valence space. Only the combination of extensive lifetime information and large scale shell-model calculations allowed the extent of the seniority conservation in the N=50 g_{9/2} orbital to be understood. The conclusion is that seniority is largely conserved in the first πg_{9/2} orbital.

PGDIS position statement on the transfer of mosaic embryos 2021.

Chromosome testing strategies, such as preimplantation genetic testing for aneuploidy (PGT-A), improve initial IVF outcomes by avoiding unwitting transfer of aneuploid embryos in morphology-based selection practices. Newer technologies have revealed that some embryos may appear to have intermediate whole chromosome (or parts of a chromosome termed segmental) copy number results suggesting trophectoderm mosaicism. An embryo with a trophectoderm mosaic-range result may be the only option for transfer for some patients. Recent data suggest that such mosaic embryos can be transferred without added risk of abnormal birth outcomes but may be associated with increased implantation failure and miscarriage rates, with higher values of mosaicism appearing to be less favourable for producing good outcomes. In this Position Statement, we provide guidance to laboratories, clinics, clinicians and counsellors to assist in discussions on the utility and transfer of mosaic embryos.

Measurement of the cardiac time intervals of the fetal ECG utilising a computerised algorithm: A retrospective observational study.

Objective: Establish whether the reliable measurement of cardiac time intervals of the fetal ECG can be automated and to address whether this approach could be used to investigate large datasets. Design: Retrospective observational study. Setting: Teaching hospitals in London UK, Nottingham UK and New York USA. Participants: Singleton pregnancies with no known fetal abnormality. Methods: Archived fetal ECG's performed using the MonicaAN24 monitor. A single ECG (PQRST) complex was generated from 5000 signal-averaged beats and electrical cardiac time intervals measured in an automated way and manually. Main Outcome measure: Validation of a newly developed algorithm to measure the cardiac time intervals of the fetal ECG. Results: 188/236 (79.7%) subjects with fECGs of suitable signal:noise ratio were included for analysis comparing manual with automated measurement. PR interval was measured in 173/188 (92%), QRS complex in 170/188 (90%) and QT interval in 123/188 (65.4%). PR interval was 107.6 (12.07) ms [mean(SD)] manual vs 109.11 (14.7) ms algorithm. QRS duration was 54.72(6.35) ms manual vs 58.34(5.73) ms algorithm. QT-interval was 268.93 (21.59) ms manual vs 261.63 (36.16) ms algorithm. QTc was 407.5(32.71) ms manual vs 396.4 (54.78) ms algorithm. The QRS-duration increased with gestational age in both manual and algorithm measurements. Conclusion: Accurate measurement of fetal ECG cardiac time intervals can be automated with potential application to interpretation of larger datasets.

Quantification and Degradation of 2,2-Dibromo-3-Nitrilopropionamide (DBNPA) in Bioethanol Fermentation Coproducts.

2,2-Dibromo-3-nitrilopropionamide (DBNPA) has been used as a biocide in industrial water applications due to its instantaneous antimicrobial activity and rapid chemical breakdown. In this study, DBNPA is considered a potential alternative for antibiotics used for bacterial control during corn-to-ethanol fermentation. A method using LC/MS/MS was developed to accurately quantify DBNPA in water. When this method was applied to quantify DBNPA concentration in a fermentation matrix, DBNPA was found to be unstable and to decay rapidly, preventing validation of the method or quantitation. This method was then used to evaluate the degradation rate of DBNPA in whole stillage, which is the nonvolatile residue produced by removal of ethanol from corn-based fermentation beer by distillation through the relative decrease in measured signal. In addition, a method was developed and validated to quantify bromide, one of the degradation products of DBNPA, in whole stillage using LC/MS/MS. The degradation rate of DBNPA in whole stillage was found to display first-order kinetics with a calculated half-life of 85 min. Laboratory analytical chemistry results on DBNPA degradation were confirmed based on a bacterial viability assay in field trials.

Empathy levels in Australian chiropractic students.

OBJECTIVE: Empathy is an important modifiable quality of health care practitioners that relates to the quality of patient care. The educative process may adversely affect the empathy levels of health care students at key phases of training. This topic remains unexplored in chiropractic students to date. METHODS: A voluntary and anonymous questionnaire was distributed to all chiropractic students in an Australian university-based program in April 2021. This questionnaire recorded age, sex, year of study, and Toronto Empathy Questionnaire scores. RESULTS: Chiropractic student empathy scores approximated those of other Australian health care students. No statistical differences were found when comparing the mean scores of empathy levels across the 5 student cohorts. The empathy levels of female chiropractic students' were significantly higher than those of the male chiropractic students. CONCLUSION: This study provides a baseline from which further explorations on empathy may be conducted in chiropractic students. This holds the potential to improve practitioners' quality of life and patient outcomes and for educators to identify subject matter that may negatively affect empathy levels.

A Uniform Description of Perioperative Brain MRI Findings in Infants with Severe Congenital Heart Disease: Results of a European Collaboration.

BACKGROUND AND PURPOSE: A uniform description of brain MR imaging findings in infants with severe congenital heart disease to assess risk factors, predict outcome, and compare centers is lacking. Our objective was to uniformly describe the spectrum of perioperative brain MR imaging findings in infants with congenital heart disease. MATERIALS AND METHODS: Prospective observational studies were performed at 3 European centers between 2009 and 2019. Brain MR imaging was performed preoperatively and/or postoperatively in infants with transposition of the great arteries, single-ventricle physiology, or left ventricular outflow tract obstruction undergoing cardiac surgery within the first 6 weeks of life. Brain injury was assessed on T1, T2, DWI, SWI, and MRV. A subsample of images was assessed jointly to reach a consensus. RESULTS: A total of 348 MR imaging scans (180 preoperatively, 168 postoperatively, 146 pre- and postoperatively) were obtained in 202 infants. Preoperative, new postoperative, and cumulative postoperative white matter injury was identified in 25%, 30%, and 36%; arterial ischemic stroke, in 6%, 10%, and 14%; hypoxic-ischemic watershed injury in 2%, 1%, and 1%; intraparenchymal cerebral hemorrhage, in 0%, 4%, and 5%; cerebellar hemorrhage, in 6%, 2%, and 6%; intraventricular hemorrhage, in 14%, 6%, and 13%; subdural hemorrhage, in 29%, 17%, and 29%; and cerebral sinovenous thrombosis, in 0%, 10%, and 10%, respectively. CONCLUSIONS: A broad spectrum of perioperative brain MR imaging findings was found in infants with severe congenital heart disease. We propose an MR imaging protocol including T1-, T2-, diffusion-, and susceptibility-weighted imaging, and MRV to identify ischemic, hemorrhagic, and thrombotic lesions observed in this patient group.

Winning hearts and minds: ECG reporting in the first seizure clinic.

BACKGROUND AND AIMS: An electrocardiogram (ECG) is a mandatory test for anyone presenting with loss of consciousness. Many referrals to the first seizure clinic (FSC) are caused by syncope. We assessed the sensitivity of neurologists' ECG reporting in detecting rhythm abnormalities including some potentially life-threatening cardiac conditions. METHODS: We audited patients referred to a FSC in Glasgow over 4 years. All ECGs were interpreted by the attending neurologist as standard practice. Subsequently, two cardiologists reviewed the ECGs independently. RESULTS: Of 160 consecutive patients, 92 patients (58%) were diagnosed as having seizures, 43 (27%) as syncope, and 25 (16%) were unclassified. Twenty eight ECGs thought to be normal by the neurologist were considered abnormal by the cardiologist, including three with long corrected QT interval. The proportion of abnormal ECGs and disparity in reporting between neurologists and cardiologists persisted independent of the underlying diagnosis. CONCLUSION: Reporting of ECGs by non-cardiologists may not be adequately sensitive in picking up potentially life threatening cardiac conditions. Cardiologist input into FSCs is recommended to enhance the diagnostic yield.

Quantitative FIT stratification is superior to NICE referral criteria NG12 in a high-risk colorectal cancer population.

BACKGROUND: Guidelines for urgent investigation of colorectal cancer (CRC) are based on age and symptom-based criteria. This study aims to compare the diagnostic value of clinical features and faecal immunochemical test (FIT) results to identify those at a higher risk of CRC, thereby facilitating effective triage of patients. METHODS: We undertook a review of all patients referred for investigation of CRC at our centre between September 2016 and June 2018. Patients were identified using a prospectively recorded local database. We performed a logistic regression analysis of factors associated with a diagnosis of CRC. RESULTS: One-thousand-and-seven-hundred-eighty-four patients with FIT results were included in the study. Change in bowel habit (CIBH) was the most common referring clinical feature (38.3%). Patients diagnosed with CRC were significantly older than those without malignancy (74.0 years vs 68.9 years, p = 0.0007). Male patients were more likely to be diagnosed with CRC than females (6.5% vs 2.5%, Chi-squared 16.93, p < 0.0001). CRC was diagnosed in 3.5% (24/684) with CIBH compared to 8.1% (6/74) with both CIBH and iron deficiency anaemia. No individual or combination of referring clinical features was associated with an increased diagnosis of CRC (Chi-squared, 8.03, p = 0.155). Three patients with negative FIT results (< 4 µg Hb/g faeces) were diagnosed with CRC (3/1027, 0.3%). The highest proportion of cancers detected was in the ≥ 100 µg Hb/g faeces group (55/181, 30.4%). CONCLUSION: In a multivariate model, FIT outperforms age, sex and all symptoms prompting referral. FIT has greater stratification value than any referral symptoms. FIT does have value in patients with iron deficiency anaemia.