Diagnostic and predictive value of Doppler ultrasound for evaluation of the brain circulation in preterm infants: a systematic review

INTRODUCTION: Very and extremely preterm infants frequently have brain injury-related long-term neurodevelopmental problems. Altered perfusion, for example, seen in the context of a hemodynamically significant patent ductus arteriosus (PDA), has been linked to injury of the immature brain. However, a direct relation with outcome has not been reviewed systematically. METHODS: A systematic review was conducted to provide an overview of the value of different cerebral arterial blood flow parameters assessed by Doppler ultrasound, in relation to brain injury, to predict long-term neurodevelopmental outcome in preterm infants. RESULTS: In total, 23 studies were included. Because of heterogeneity of studies, a meta-analysis of results was not possible. All included studies on resistance index (RI) showed significantly higher values in subjects with a hemodynamically significant PDA. However, absolute differences in RI values were small. Studies using Doppler parameters to predict brain injury and long-term neurodevelopmental outcome were inconsistent. DISCUSSION: There is no clear evidence to support the routine determination of RI or other Doppler parameters in the cerebral arteries to predict brain injury and long-term neurodevelopmental outcome in the preterm infant. However, there is evidence that elevated RI can point to the presence of a hemodynamically significant PDA

Outcome and risk factors for recurrence of early onset fracture-related infections treated with debridement, antibiotics and implant retention:Results of a large retrospective multicentre cohort study

Introduction: Early Fracture-Related Infections (FRIs) are a common entity in hospitals treating trauma patients and are often treated with a Debridement, Antibiotics and Implant Retention (DAIR) procedure. Aims of this study were to 1) evaluate the recurrence rate after DAIR procedures for early onset FRI, 2) establish the number of surgical procedures to gain control of the initial infection and 3) identify independent predictors for recurrence in this cohort. Methods: A retrospective multicentre cohort study was conducted in two level 1 trauma centres. Consecutive patients who underwent a DAIR procedure between January 1st 2015 and July 1st 2020 for confirmed FRI with an onset of <6 weeks after the latest osseous operation were included. Recorded data included patient demographics, treatment characteristics and follow-up. Univariate and multivariate logistic regression analyses were performed to assess predictors for recurrent FRI. Results: A total of 141 patients with early FRI were included in this study with a median age of 54.0 years (interquartile range (IQR) 34.5–64.0). The recurrence rate of FRI was 13% (n = 19) at one year follow-up and 18% (n = 25) at 23.1 months (IQR 15.3–36.4) follow-up. Infection control was achieved in 94% (n = 127/135) of cases. In total, 73 patients (52%) underwent at least two surgical procedures to treat the ongoing initial episode of FRI, of whom 54 patients (74%) required two to three procedures and 17 patients (23%) four to five procedures. Predictors for recurrent FRI were use of an intramedullary nail during index operation (odds ratio (OR) 4.0 (95% confidence interval (CI) 1.1–13.8)), need for additional surgical procedures to treat ongoing infection during the treatment period following the first presentation of early FRI (OR 1.9 (95% CI 1.1–3.5)) and a decreased Injury Severity Score (ISS) (inverted OR 1.1 (95% CI 1.0–1.1)). Conclusion: The recurrence rate after treatment of early onset FRI in patients treated with a DAIR procedure was 18% at 23.1 months follow-up. At least two surgical procedures to gain control of the initial infection were needed in 52% of patients. Independent predictors for recurrent FRI were the use of an intramedullary nail during index operation, need for additional surgical procedures and a decreased ISS

White Blood Cell Scintigraphy for Fracture-Related Infection:Is Semiquantitative Analysis of Equivocal Scans Accurate?

Purpose: White blood cell (WBC) scintigraphy is considered the gold-standard nuclear imaging technique for diagnosing fracture-related infection (FRI). Correct interpretation of WBC scans in FRI is important since a false positive or false negative diagnosis has major consequences for the patient in terms of clinical decision-making. The European Association of Nuclear Medicine (EANM) guideline for correct analysis and interpretation of WBC scans recommends semiquantitative analysis of visually equivocal scans. Therefore, this study aims to assess the diagnostic accuracy of semiquantitative analysis of visually equivocal WBC scans for diagnosing FRI. Methods: A retrospective single-center study was performed in consecutive patients who received WBC scintigraphy in the diagnostic work-up for FRI between February 2012 and January 2017. All the visually equivocal scans were analysed using semiquantitative analysis by comparing leukocyte uptake in the manually selected suspected infection focus with the contralateral bone marrow (L/R ratio). Cut-off points for a ‘positive’ scan result of >0%, >10% and >20% leukocyte increase between the early and late scans were used in separate analyses. The discriminative ability was quantified by calculating the sensitivity, specificity and diagnostic accuracy. Results: In total, 153 WBC scans were eligible for inclusion. After visual assessment of all the scans, 28 visually equivocal scans were included. Dichotomization of the ratios using the cut-off of >0% resulted in a sensitivity of 30%, a specificity of 45% and a diagnostic accuracy of 40%. The >10% cut-off point resulted in a sensitivity of 18%, a specificity of 82% and a diagnostic accuracy of 66%. The >20% cut-off point resulted in a sensitivity of 0%, a specificity of 89% and a diagnostic accuracy of 67%. Conclusion: Semiquantitative analysis of visually equivocal WBC scans is insufficient for correctly diagnosing FRI

High delayed and missed injury rate after inter-hospital transfer of severely injured trauma patients

PURPOSE: Missed injuries are reported in 1.3-65% of all admitted trauma patients. The severely injured patient that needs a higher level of care which requires an inter-hospital transfer has an increased risk for missed injuries. The aim of this study was to establish the incidence and clinical relevance of missed injuries in severely injured patients who require inter-hospital transfer to a level 1 trauma center. METHODS: All patients with an Injury Severity Score (ISS) ≥ 16 transferred to the University Medical Center Groningen (UMCG) between January 2010 and July 2015 were included. Data were obtained from a prospective trauma database and supplemented with information from the patient records. A delayed diagnosis was defined as any injury detected within the first 24 h after the initial trauma, with or without a tertiary survey. Missed diagnoses were defined as any injury diagnosed after 24 h following trauma. RESULTS: Two hundred and fifty-one trauma patients were included. A total of 88 patients (35%) were found to have ≥ 1 new diagnoses with 65 (26%) patients that had 1 or more delayed diagnoses and 23 (9.2%) patients had 1 or more missed diagnoses (detected > 24 h after injury) after transfer to our hospital. For 47 of the 88 patients (53%), the new diagnoses required a change of management. The Glasgow Coma Scale (GCS) was the only statistically significant risk factor for a new diagnosis upon transfer. CONCLUSIONS: Inter-hospital transfer of severely injured patients increases the risk of a delayed detection of injuries. We found that 35% of all transferred patients with an ISS ≥ 16 have at least new diagnoses, with over half of these diagnoses requiring a change of management. Given these findings, clinicians should maintain a high index of suspicion when receiving a transferred severely injured trauma patient

Causative Pathogens Do Not Differ between Early, Delayed or Late Fracture-Related Infections

Fracture-related infections (FRIs) are classically considered to be early (0-2 weeks), delayed (3-10 weeks) or late (>10 weeks) based on hypothesized differences in causative pathogens and biofilm formation. Treatment strategies often reflect this classification, with debridement, antimicrobial therapy and implant retention (DAIR) preferentially reserved for early FRI. This study examined pathogens isolated from FRI to confirm or refute these hypothesized differences in causative pathogens over time. Cases of FRI managed surgically at three centres between 2015-2019 and followed up for at least one year were included. Data were analysed regarding patient demographics, time from injury and pathogens isolated. Patients who underwent DAIR were also analysed separately. In total, 433 FRIs were studied, including 51 early cases (median time from injury of 2 weeks, interquartile range (IQR) of 1-2 weeks), 82 delayed cases (median time from injury of 5 weeks, IQR of 4-8 weeks) and 300 late cases (median time from injury of 112 weeks, IQR of 40-737 weeks). The type of infection was associated with time since injury; early or delayed FRI are most likely to be polymicrobial, whereas late FRIs are more likely to be culture-negative, or monomicrobial. Staphylococcus aureus was the most commonly isolated pathogen at all time points; however, we found no evidence that the type of pathogens isolated in early, delayed or late infections were different (p = 0.2). More specifically, we found no evidence for more virulent pathogens (S. aureus, Gram-negative aerobic bacilli) in early infections and less virulent pathogens (such as coagulase negative staphylococci) in late infections. In summary, decisions on FRI treatment should not assume microbiological differences related to time since injury. From a microbiological perspective, the relevance of classifying FRI by time since injury remains unclear

In Vivo Measurement of Cerebral Mitochondrial Metabolism Using Broadband Near Infrared Spectroscopy Following Neonatal Stroke

Neonatal stroke presents with features of encephalopathy and can result in significant morbidity and mortality. We investigated the cerebral metabolic and haemodynamic changes following neonatal stroke in a term infant at 24 h of life. Changes in oxidation state of cytochrome-c-oxidase (oxCCO) concentration were monitored along with changes in oxy- and deoxy- haemoglobin using a new broadband near-infrared spectroscopy (NIRS) system. Repeated transient changes in cerebral haemodynamics and metabolism were noted over a 3-h study period with decrease in oxyhaemoglobin (HbO2), deoxy haemoglobin (HHb) and oxCCO in both cerebral hemispheres without significant changes in systemic observations. A clear asymmetry was noted in the degree of change between the two cerebral hemispheres. Changes in cerebral oxygenation (measured as HbDiff=HbO2-HHb) and cerebral metabolism (measured as oxCCO) were highly coupled on the injured side of the brain

Host–parasite dynamics shaped by temperature and genotype: Quantifying the role of underlying vital rates

1. Global warming challenges the persistence of local populations, not only through heat-induced stress, but also through indirect biotic changes. We study the interactive effects of temperature, competition and parasitism in the water flea Daphnia magna. 2. We carried out a common garden experiment monitoring the dynamics of Daphnia populations along a temperature gradient. Halfway through the experiment, all populations became infected with the ectoparasite Amoebidium parasiticum, enabling us to study the interactive effects of temperature and parasite dynamics. We combined Integral Projection Models with epidemiological models, parameterized using the experimental data on the performance of individuals within dynamic populations. This enabled us to quantify the contribution of different vital rates and epidemiological parameters to population fitness across temperatures and Daphnia clones originating from two latitudes. 3. Interactions between temperature and parasitism shaped competition, where Belgian clones performed better under infection than Norwegian clones. Infected Daphnia populations performed better at higher than at lower temperatures, mainly due to an increased host capability of reducing parasite loads. Temperature strongly affected individual vital rates, but effects largely cancelled out on a population-level. In contrast, parasitism strongly reduced fitness through consistent negative effects on all vital rates. As a result, temperature-mediated parasitism was more important than the direct effects of temperature in shaping population dynamics. Both the outcome of the competition treatments and the observed extinction patterns support our modelling results. 4. Our study highlights that shifts in biotic interactions can be equally or more important for responses to warming than direct physiological effects of warming, emphasizing that we need to include such interactions in our studies to predict the competitive ability of natural populations experiencing global warming

Nuclear imaging for diagnosing fracture-related infection

Purpose Fracture-related infection (FRI) is a complication of surgical fracture treatment and can be challenging to diagnose. Recent studies show promising results for the use of either FDG-PET/CT or WBC/anti-granulocyte scintigraphy. The purpose of this pictorial essay is to outline recent developments in nuclear imaging techniques to diagnose FRI. Methods The current literature on this topic is reviewed. Additionally, three examples of patients who underwent nuclear imaging as part of their clinical work-up and surgical treatment for FRI are presented. Results Based on recent retrospective studies, FDG-PET/CT (accuracy 0.83) and WBC scintigraphy with SPECT/CT (accuracy 0.92) both have a good diagnostic accuracy for diagnosing fracture-related infection. Nuclear imaging contributes to a correct diagnosis in patients with FRI. Conclusion Retrospective studies show promising results for both FDG-PET/CT and WBC scintigraphy with SPECT/CT in diagnosing FRI. A prospective, multicenter study (IFI trial), directly comparing MRI, FDG-PET/CT, and WBC scintigraphy with SPECT/CT in patients with suspected FRI, is currently in progress