Severe Insult Research Articles

Trust the heart to save the brain: changes in heart rate patterns have the potential to be a biomarker for hypoxic ischaemic brain injury.

Trust the heart to save the brain: changes in heart rate patterns have the potential to be a biomarker for hypoxic ischaemic brain injury.

Immunosuppression is Inappropriately Qualifying the Immune Status of Septic and SIRS Patients.

Immunosuppression is the most commonly used concept to qualify the immune status of patients with either sterile systemic inflammatory response syndrome (SIRS) or sepsis. In this review we attempt to demonstrate that the concept of immunosuppression is an oversimplification of the complex anti-inflammatory response that occurs in patients dealing with a severe sterile or infectious insult. Particularly, the immune status of leukocytes varies greatly depending on the compartment from where they are derived from. Furthermore, although certain functions of immune cells present in the blood stream or in the hematopoietic organs can be significantly diminished, other functions are either unchanged or even enhanced. This juxtaposition illustrates that there is no global defect. The mechanisms called reprogramming or trained innate immunity are probably aimed at preventing a generalized deleterious inflammatory reaction, and work to maintain the defense mechanisms at their due levels.

Impact on Outcomes across KDIGO-2012 AKI Criteria According to Baseline Renal Function

Acute kidney injury (AKI) and Chronic Kidney Disease (CKD) are global health problems. The pathophysiology of acute-on-chronic kidney disease (AoCKD) is not well understood. We aimed to study clinical outcomes in patients with previous normal (pure acute kidney injury; P-AKI) or impaired kidney function (AoCKD) across the 2012 Kidney Disease Improving Global Outcomes (KDIGO) AKI classification. We performed a retrospective study of patients with AKI, divided into P-AKI and AoCKD groups, evaluating clinical and epidemiological features, distribution across KDIGO-2012 criteria, in-hospital mortality and need for dialysis. One thousand, two hundred and sixty-nine subjects were included. AoCKD individuals were older and had higher comorbidity. P-AKI individuals fulfilled more often the serum creatinine (SCr) ≥ 3.0× criterion in AKI-Stage3, AoCKD subjects reached SCr ≥ 4.0 mg/dL criterion more frequently. AKI severity was associated with in-hospital mortality independently of baseline renal function. AoCKD subjects presented higher mortality when fulfilling AKI-Stage1 criteria or SCr ≥ 3.0× criterion within AKI-Stage3. The relationship between mortality and associated risk factors, such as the net increase of SCr or AoCKD status, fluctuated depending on AKI stage and stage criteria sub-strata. AoCKD patients that fulfil SCr increment rate criteria may be exposed to more severe insults, possibly explaining the higher mortality. AoCKD may constitute a unique clinical syndrome. Adequate staging criteria may help prompt diagnosis and administration of appropriate therapy.

The Utility of Thromboelastography for Predicting the Risk of Post-Traumatic Cerebral Infarction in Traumatic Brain Injury

Abstract INTRODUCTION Post-traumatic cerebral infarction (PTCI) is a severe secondary insult of head injury and often leads to a poor prognosis. Hemocoagulation disorder is recognized to have important effects on hemorrhagic or ischemic damages. We sought to assess if post-traumatic coagulopathy determined using thrombelastography was associated with cerebral infarction after head trauma. METHODS We prospectively reviewed 316 patients with head trauma to evaluate the effects of demographics, admission Glasgow Coma Scale (GCS) score, and TEG data on the development of PTCI. Multivariate logistic regression analysis was used to identify independent risk factors. RESULTS Patients with PTCI had a shorter R, greater a-Angle, and shorter K, indicating faster clotting. Additionally, TEG results were independently associated with an increased risk of PTCI. CONCLUSION TEG demonstrates that many PTCI patients are hypercoaguable and the risk of developing PTCI may be higher in patients with a shorter R, greater a-Angle, and shorter K.

Automatically Identified Micro-scale Sharp-wave Transients in the Early-Latent Phase of Hypoxic-Ischemic EEG from Preterm Fetal Sheep Reveal Timing Relationship to Subcortical Neuronal Survival.

Perinatal Hypoxic-Ischemia Encephalopathy (HIE) in newborn infants, due to birth-related circumstances such as oxygen deprivation in brain cells, is caused by the disruption in blood flow through the umbilical cord. Subcortical neuronal loss due to the HIE can lead to cerebral palsy and other chronic neurological conditions. Pre-clinical EEG studies using in utero sheep have demonstrated that particular micro-scale HI transients emerge along a suppressed EEG background during a latent phase of 3-6 hours, after a severe HI insult. Whilst the nature of these micro-scale transients is not well understood, it has been hypothesized that such transients may be signatures of the evolving hypoxic-ischemic brain injury, possessing the potential to be served as the diagnosis biomarkers for the injury. Cerebral hypothermia is optimally neuroprotective only if administered within the first 2-3 hours post HI insult. Using data from a cohort of in utero preterm fetal sheep (n=5, at 0.7 of gestational age), this paper indicates how the number of automatically quantified micro-scale sharp wave transients from asphyxiated preterm fetal sheep, statistically correlate to the amount of NeuN-positive neurons measured in caudate nucleus of striatum. Different temporal window sizes of 2hrs, 1hr, ½hr and 10mins within the early phase of the latent phase are examined using our developed Wavelet Type-2 Fuzzy classifier for sharp detection. Analyses were narrowed down to 10min intervals to assess where exactly in time the occurrence of the HI micro-scale sharp waves demonstrate a significant correlation. Signal processing wise, results from the sub-windows indicate a timing trend that highlights a positive correlation, between the number of automatic quantifications and the amount of surviving neurons in the preterm brain, permitting the possibility of a point of care (POC) intervention to stop the spread of injury before it becomes irreversible.

Cell death: a review of the major forms of apoptosis, necrosis and autophagy.

Cell death was once believed to be the result of one of two distinct processes, apoptosis (also known as programmed cell death) or necrosis (uncontrolled cell death); in recent years, however, several other forms of cell death have been discovered highlighting that a cell can die via a number of differing pathways. Apoptosis is characterised by a number of characteristic morphological changes in the structure of the cell, together with a number of enzyme-dependent biochemical processes. The result being the clearance of cells from the body, with minimal damage to surrounding tissues. Necrosis, however, is generally characterised to be the uncontrolled death of the cell, usually following a severe insult, resulting in spillage of the contents of the cell into surrounding tissues and subsequent damage thereof. Failure of apoptosis and the resultant accumulation of damaged cells in the body can result in various forms of cancer. An understanding of the pathways is therefore important in developing efficient chemotherapeutics. It has recently become clear that there exists a number of subtypes of apoptosis and that there is an overlap between apoptosis, necrosis and autophagy. The goal of this review is to provide a general overview of the current knowledge relating to the various forms of cell death, including apoptosis, necrosis, oncosis, pyroptosis and autophagy. This will provide researchers with a summary of the major forms of cell death and allow them to compare and contrast between them.

Frequency of DNA end joining in trans is not determined by the predamage spatial proximity of double-strand breaks in yeast

DNA double-strand breaks (DSBs) are serious genomic insults that can lead to chromosomal rearrangements if repaired incorrectly. To gain insight into the nuclear mechanisms contributing to these rearrangements, we developed an assay in yeast to measure cis (same site) vs. trans (different site) repair for the majority process of precise nonhomologous end joining (NHEJ). In the assay, the HO endonuclease gene is placed between two HO cut sites such that HO expression is self-terminated upon induction. We further placed an additional cut site in various genomic loci such that NHEJ in trans led to expression of a LEU2 reporter gene. Consistent with prior reports, cis NHEJ was more efficient than trans NHEJ. However, unlike homologous recombination, where spatial distance between a single DSB and donor locus was previously shown to correlate with repair efficiency, trans NHEJ frequency remained essentially constant regardless of the position of the two DSB loci, even when they were on the same chromosome or when two trans repair events were put in competition. Repair of similar DSBs via single-strand annealing of short terminal direct repeats showed substantially higher repair efficiency and trans repair frequency, but still without a strong correlation of trans repair to genomic position. Our results support a model in which yeast cells mobilize, and perhaps compartmentalize, multiple DSBs in a manner that no longer reflects the predamage position of two broken loci.

Neutrophil elastase plays a non-redundant role in remodeling the venular basement membrane and neutrophil diapedesis post-ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury is a severe inflammatory insult associated with numerous pathologies, such as myocardial infarction, stroke and acute kidney injury. I/R injury is characterized by a rapid influx of activated neutrophils secreting toxic free radical species and degrading enzymes that can irreversibly damage the tissue, thus impairing organ functions. Significant efforts have been invested in identifying therapeutic targets to suppress neutrophil recruitment and activation post‐I/R injury. In this context, pharmacological targeting of neutrophil elastase (NE) has shown promising anti‐inflammatory efficacy in a number of experimental and clinical settings of I/R injury and is considered a plausible clinical strategy for organ care. However, the mechanisms of action of NE, and hence its inhibitors, in this process are not fully understood. Here we conducted a comprehensive analysis of the impact of NE genetic deletion on neutrophil infiltration in four murine models of I/R injury as induced in the heart, kidneys, intestine and cremaster muscle. In all models, neutrophil migration into ischemic regions was significantly suppressed in NE−/− mice as compared with wild‐type controls. Analysis of inflamed cremaster muscle and mesenteric microvessels by intravital and confocal microscopy revealed a selective entrapment of neutrophils within venular walls, most notably at the level of the venular basement membrane (BM) following NE deletion/pharmacological blockade. This effect was associated with the suppression of NE‐mediated remodeling of the low matrix protein expressing regions within the venular BM used by transmigrating neutrophils as exit portals. Furthermore, whilst NE deficiency led to reduced neutrophil activation and vascular leakage, levels of monocytes and prohealing M2 macrophages were reduced in tissues of NE−/− mice subjected to I/R. Collectively our results identify a vital and non‐redundant role for NE in supporting neutrophil breaching of the venular BM post‐I/R injury but also suggest a protective role for NE in promoting tissue repair. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Developing Assessments for Child Exposure to Intimate Partner Violence in Switzerland – a Study of Medico-Legal Reports in Clinical Settings

Evidence to inform assessment of needs of children exposed to intimate partner violence (IPV) in health settings is limited. A Swiss hospital-based medico-legal consultation for adult victims of violence also detects children’s exposure to IPV and refers cases to the Pediatrics Child Abuse and Neglect Team. Based on a conceptual ecological framework, this study examined the nature and circumstances of children’s exposure to IPV described in accounts collected by nurses in consultations with adult IPV victims. From 2011 to 2014, 438 parents (88% female) of 668 children aged 0 to 18 sought medico-legal care from the Violence Medical Unit in Lausanne Switzerland following assaults by intimate partners (85% male). As part of the consultation, nurses completed a semi-structured questionnaire with victimized parents, recording their answers in the patient file. Victims’ statements about the abuse, their personal, family and social contexts, and their children’s exposure to IPV were analyzed. Descriptive statistics and qualitative thematic content analyses were conducted to identify, from the victimized parents’ accounts, elements useful to understand the nature and circumstances of children’s exposure and involvement during violent events. Parent statements on specific violent events described children being present in 75% of the cases. Children were said to be exposed to, and responded to, severe physical violence, serious threats and insults, in the context of repeated assaults and coercive control. Families, especially mothers, were often coping with additional socio-economic vulnerabilities. Implications for further developing assessments of children living with IPV, especially in health settings were identified.

Appropriate treadmill exercise improves survival after gut ischemia reperfusion in mice

Summary Background＆aims It is unclear whether or not an appropriate prehabilitation protocol ameliorates surgical stress, ultimately improves survival after severe surgical insults. Methods Male C57BL/6J mice received treadmill exercise according to the following protocols. Exp.1) Sixty-min treadmill running at 20 m/min. The exercise sessions were 5 days/week for 2 weeks, 3 days/week for 2 weeks or 3 days/week for 3 weeks (n = 29). Sedentary mice (n = 6) did not perform treadmill exercise. After finishing each protocol, the exercise completion rate was evaluated. All mice which had completed the protocol (n = 24) underwent 45 min superior mesenteric artery occlusion and reperfusion (Gut I/R) and survival after gut I/R was observed. Exp.2) According to the results of Exp.1, the exercise frequency and duration were set at 3 days/week for 3 weeks. To determine the appropriate running speed, mice (n = 94) ran on the treadmill for 60 min at 12, 15 or 18 m/min, while sedentary mice (n = 25) did not. The exercise completion rate and survival were observed. Results Exp.1) The 3 days/week for 3 weeks exercise protocol showed the highest survival rate. However, the completion rate of each exercise group was only 50–60%. Exp.2) The completion rates at 15 m/min and 18 m/min were both approximately 90%. None of the 12 m/min group failed to complete the protocol. The 12 m/min and 15 m/min treadmill running groups showed equally improved survival as compared to the sedentary group (p Conclusions An appropriate exercise protocol improves survival after gut I/R in mice. Prehabilitation strengthens resistance to severe surgical insults.

The Zika virus epidemic 3 years on: a personal perspective

The Zika virus epidemic 3 years on: a personal perspective

Computational Simulations Identified Two Candidate Inhibitors of Cdk5/p25 to Abrogate Tau-associated Neurological Disorders

Deregulation of Cdk5 is a hallmark in neurodegenerative diseases and its complex with p25 forms Cdk5/p25, thereby causes severe neuropathological insults. Cdk5/p25 abnormally phosphorylates tau protein, and induces tau-associated neurofibrillary tangles in neurological disorders. Therefore, the pharmacological inhibition of Cdk5/p25 alleviates tau-associated neurological disorders. Herein, computational simulations probed two candidate inhibitors of Cdk5/p25. Structure-based pharmacophore investigated the essential complementary chemical features of ATP-binding site of Cdk5 in complex with roscovitine. Resultant pharmacophore harbored polar interactions with Cys83 and Asp86 residues and non-polar interactions with Ile10, Phe80, and Lys133 residues of Cdk5. The chemical space of selected pharmacophore was comprised of two hydrogen bond donors, one hydrogen bond acceptor, and three hydrophobic features. Decoy test validation of pharmacophore obtained highest Guner-Henry score (0.88) and enrichment factor score (7.23). The screening of natural product drug-like databases by validated pharmacophore retrieved 1126 compounds as candidate inhibitors of Cdk5/p25. The docking of candidate inhibitors filtered 10 molecules with docking score >80.00 and established polar and non-polar interactions with the ATP-binding site residues of Cdk5/p25. Finally, molecular dynamics simulation and binding free energy analyses identified two candidate inhibitors of Cdk5/p25. During 30 ns simulation, the candidate inhibitors established <3.0 Å root mean square deviation and stable hydrogen bond interactions with the ATP-binding site residues of Cdk5/p25. The final candidate inhibitors obtained lowest binding free energies of −122.18 kJ/mol and − 117.26 kJ/mol with Cdk5/p25. Overall, we recommend two natural product candidate inhibitors to target the pharmacological inhibition of Cdk5/p25 in tau-associated neurological disorders.

Case presentation: persistent adenovirus B3 infections associated with bronchiolitis obliterans treated with cidofovir in a child with mosaic tetrasomy 9p

BackgroundAdenoviruses (AdV) are non-enveloped, double-stranded DNA viruses with multiple serotypes, which cause a variety of end-organ disease in both immunocompetent and immunocompromised individuals. Some adenoviruses can become latent in the mucosa-associated lymphoid tissue (e.g. adenoids and tonsils), with the potential to reactivate sporadically, leading to upper or lower respiratory tract infection and disease. Bronchiolitis Obliterans (BO) is a rare chronic lung disorder which usually follows a severe insult to the respiratory tract. In children, it is a complication of severe infections (as post-infectious BO), typically manifesting after a severe respiratory infection, in previously healthy pre-school children. Symptoms and signs of air trapping (hyperinflated chest, expiratory wheeze) with persistent oxygen requirement are characteristic. The presence of the unusual mosaic tetrasomy 9p genotype in this case, despite standard cidofovir therapy for persistent or chronic adenovirus infection, may have impacted on the child’s long-term clinical outcomes.Case presentationWe present a case of persistent AdV B3 infection in a 14-month old boy with mosaic tetrasomy 9p, which persisted for 10 weeks, resulting in radiologically-confirmed BO, requiring cidofovir to control the persistent AdV B3 infection and standard therapy with pulsed steroids. We argue that in the presence of the mosaic tetrasomy 9p, earlier antiviral therapy may have decreased the severity of BO, as this mutation is known to be associated with some degree of immune dysregulation.ConclusionsAdenovirus infections are common in children and may persist as latent infections, with subsequent reactivations during loss of immune control, related to systemic illness arising from other causes. In chronic, reactivated AdV infection with pneumonia, BO is a recognised complication. However, in this case, with the presence of the mosaic tetrasomy 9p mutation, earlier antiviral therapy may have reduced such longer term complications, due to the immune dysregulatory nature of this mutation.

Gender affects early psychomotor milestones and long‐term neurodevelopment of preterm infants

AbstractTemporal differences of neurodevelopmental milestones' achievement are commonly taken into account in preterm infant assessment during the first year of life, especially when minor or none neurological signs arise from clinical examination. The influence of gender on neurodevelopment in preterm infants was examined by a milestones‐based neurological approach. Two‐hundred twenty‐seven moderate and late preterm and full‐term infants (51.9% male), without evidence of severe white matter insults, were early assessed by classic neurological examination. Griffiths Mental Developmental Scale was used at long‐term observation. Children were sorted into three gestational age groups (Group 1: 32–33 weeks, Group 2: 34–36 weeks, and Group 3: ≥37 weeks) and compared according to their neurodevelopmental pathways and gender. The achievement of head control was slightly earlier in females. The pointing, one of the main communicative hand gesture, appeared significantly earlier in females across all the groups. At the Griffiths Scale, the majority of gender‐related differences emerged in personal–social and eye and hand coordination subscale. An independent role of male gender was evidenced in personal–social, language, and eye and hand coordination subscales. Gender and gestational age likely addressed different temporal profiles of neurodevelopment in early and late assessments in preterm and full‐term infants. The role of gender and gestational age on these findings has been discussed.Highlights A classic, milestones‐based neurological evaluation disclosed different developmental profiles in males versus females preterm infants. Moderate preterm and full‐term infants showed similar developmental profiles. Gender and gestational age may influence neurodevelopment.

Invited commentary

A major limitation in developing molecular therapies for critical limb ischemia has been the lack of a clinically relevant model to test efficacy. The existing animal models primarily depend on acute limb ischemia generated by femoral artery ligation or excision. These models have provided insights into cellular and molecular mechanisms that underlie collateral artery growth, primarily because young rodents collateralize quickly in response to ischemia. This trait is less helpful when trying to test potential treatments that will be effective in older, atherosclerotic, diabetic human patients. Many single growth factor therapies have showed efficacy in these rodent-based models, only to fail in human clinical trials. Furthermore, these surgical models require invasive isolation of the femoral artery, creating an inflammatory milieu for arteriogenesis different from that caused by atherosclerosis. They also lack the tibial level occlusions seen in diabetic patients. The current article addresses the last two concerns. The authors have modified the model developed by Liddell et al,1Liddell R.P. Patel T.H. Weiss C.R. Lee D.S. Matsuhashi T. Browh P.R. et al.Endovascular model of rabbit hindlimb ischemia: a platforms to evaluate therapeutic angiogenesis.J Vasc Interv Radiol JVIR. 2005; 16: 991-998Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar where the authors used a percutaneous transauricular approach to coil embolize the rabbit superficial femoral artery, by instead using 300- to 500-μm microspheres to embolize more distal targets: the saphenous (posterior tibial equivalent) and anterior tibial arteries and their outflow beds. The resulting acute ischemia resulted in significant hindlimb ulcerations, similar to the pedal gangrene seen in patients with critical limb ischemia. The ulcerations and decreased saphenous artery blood flow were persistent up to 14 days at the time of humane killing. It is likely that this model will need further refinement to be made practical for use in testing arteriogenic therapies. The embolization resulted in a significant acute ischemic injury to the muscle, with a large inflammatory cell infiltrate and muscle necrosis. The footpad necrosis in most of the rabbits was severe, with high pain scores, resulting in ethical concerns for maintaining the model for longer than 14 days. Staged embolizations of the anterior tibial and saphenous arteries with particles sized for the tibial arteries rather than their outflow beds might better reflect the tibial level occlusions seen in diabetic humans and provide a less severe and more chronic ischemia that would better support therapeutic testing. This method would also facilitate use of the model in hypercholesterolemic or diabetic rabbits, who would presumably be less tolerant of the severe arterial ischemic insult generated by the current protocol. Limitations aside, this percutaneous embolization-based model of hindlimb ischemia represents a step forward in the creation of a more relevant animal model of critical limb ischemia. It remains to be seen whether it is enough of a step forward to support robust preclinical testing of arteriogenic therapies. Evaluation of a new model of hind limb ischemia in rabbitsJournal of Vascular SurgeryVol. 68Issue 3PreviewVarious animal models of critical limb ischemia have been developed in the past. However, there is no animal model that can undergo endovascular treatment, while providing reproducible true critical limb ischemia with arterial ulcers and rest pain. We evaluated the efficacy of a new model of rabbit hindlimb ischemia created through a percutaneous approach using embolization with calibrated particles. Full-Text PDF Open Archive

Stem cell factor is selectively secreted by arterial endothelial cells in bone marrow

Endothelial cells (ECs) contribute to haematopoietic stem cell (HSC) maintenance in bone marrow, but the differential contributions of EC subtypes remain unknown, owing to the lack of methods to separate with high purity arterial endothelial cells (AECs) from sinusoidal endothelial cells (SECs). Here we show that the combination of podoplanin (PDPN) and Sca-1 expression distinguishes AECs (CD45− Ter119− Sca-1bright PDPN−) from SECs (CD45− Ter119− Sca-1dim PDPN+). PDPN can be substituted for antibodies against the adhesion molecules ICAM1 or E-selectin. Unexpectedly, prospective isolation reveals that AECs secrete nearly all detectable EC-derived stem cell factors (SCF). Genetic deletion of Scf in AECs, but not SECs, significantly reduced functional HSCs. Lineage-tracing analyses suggest that AECs and SECs self-regenerate independently after severe genotoxic insults, indicating the persistence of, and recovery from, radio-resistant pre-specified EC precursors. AEC-derived SCF also promotes HSC recovery after myeloablation. These results thus uncover heterogeneity in the contribution of ECs in stem cell niches.

Bone Morphogenetic Protein (BMP)-3b Gene Depletion Causes High Mortality in a Mouse Model of Neonatal Hypoxic-Ischemic Encephalopathy

Bone morphogenetic proteins (BMPs) are a group of proteins that induce the formation of bone and the development of the nervous system. BMP-3b, also known as growth and differentiation factor 10, is a member of the BMPs that is highly expressed in the developing and adult brain. BMP-3b is therefore thought to play an important role in the brain even after physiological neurogenesis has completed. BMP-3b is induced in peri-infarct neurons in aged brains and is one of the most highly upregulated genes during the initiation of axonal sprouting. However, little is known about the role of BMP-3b in neonatal brain injury. In the present study, we aimed to describe the effects of BMP-3b gene depletion on neonatal hypoxic-ischemic encephalopathy, which frequently results in death or lifelong neurological disabilities, such as cerebral palsy and mental retardation. BMP-3b knockout and wild type mice were prepared at postnatal day 12. Mice of each genotype were divided into sham-surgery, mild hypoxia-ischemia (HI), and severe HI groups (n = 12–45). Mice in the HI groups were subjected to left common carotid artery ligation followed by 30 min (mild HI) or 50 min (severe HI) of systemic hypoxic insult. A battery of tests, including behavioral tests, was performed, and the brain was then removed and evaluated at 14 days after insult. Compared with wild type pups, BMP-3b knockout pups demonstrated the following characteristics. (1) The males exposed to severe HI had a strikingly higher mortality rate, and as many as 70% of the knockout pups but none of the wild type pups died; (2) significantly more hyperactive locomotion was observed in males exposed to severe HI; and (3) significantly more hyperactive rearing was observed in both males and females exposed to mild HI. However, BMP-3b gene depletion did not affect other parameters, such as cerebral blood flow, cylinder test and rotarod test performance, body weight gain, brain weight, spleen weight, and neuroanatomical injury. The results of this study suggest that BMP-3b may play a crucial role to survive in severe neonatal hypoxic-ischemic insult.

Abstract P-519: CONFIRMING DEATH BY NEUROLOGICAL CRITERIA IN NEONATES ON EXTRACORPOREAL MEMBRANE OXYGENATION – CHALLENGES AND INNOVATIVE IDEAS

Aims & Objectives: Diagnosing death by neurological criteria in term neonates supported by extracorporeal membrane oxygenation (ECMO) remains challenging. We describe a case and propose a practical method of performing these tests for this subset. Methods Our patient was antenatally diagnosed with congenitally corrected transposition of great arteries, Ebstein’s anomaly and aortic coarctation with arch hypoplasia. He underwent hybrid stage 1 single-ventricle palliation with bilateral pulmonary arterial banding. 15 hours post-surgery he sustained cardiac arrest requiring ECMO support. On day 3, pupils became fixed and dilated. CT head showed changes consistent with severe global hypoxic insult, EEG showed no background electrical activity. In view of poor prognosis, withdrawal of life-sustaining treatment and organ donation were discussed with, and supported by baby’s parents. Organ donation team wanted to confirm death by neurological criteria. Results We used guidelines by Royal College of Paediatrics and Child Health in infants less than 2 months. Two sets of brainstem tests showed no signs of cerebral activity. Challenging aspect was apnoea test which requires that PCO2 increase to >8kpa. To achieve this, ECMO sweep-flow was reduced and FiO2 increased 100%. During 2 sets of apnoea tests, pCO2 rose 8.45Kpa and 8.13Kpa respectively and no respiratory effort observed. Conclusions Major challenge in this setting was conducting apnoea test whilst maintaining haemodynamic stability in a baby on ECMO. We have since developed a guideline for diagnosing death by neurological criteria in neonates on ECMO and specifications for performing apnoea test, an important step in ensuring that appropriate babies be considered as potential organ donors.

Transcatheter Arterial Embolization in Lower Gastrointestinal Bleeding: Ischemia Remains a Concern Even with a Superselective Approach

PurposeTo evaluate the safety, efficacy, and feasibility of transcatheter arterial embolization (TAE) in the treatment of lower gastrointestinal bleeding (LGIB). MethodsStudy group comprised all patients receiving angiography for LGIB in the Helsinki University Hospital during the period of 2004–2016. Hospital medical records provided the study data. Rebleeding, complication, and mortality rates (≤30 days) were the primary outcomes. Secondary outcomes included need for blood transfusions, durations of intensive care unit and hospital admissions, incidence of delayed rebleeding, and long-term complications, as well as overall survival. ResultsDuring the study period, angiography for LGIB was necessary on 123 patients. Out of 123, 55 (45%) underwent embolization attempts. TAE was technically successful in 53 (96%). Rebleeding occurred in 14 (26%). The complication rate was 36%, minor complications occurring in 10 (19%) and major in nine (17%). Major complications resulted in bowel resection in seven (13%). Post embolization ischemia was the most common single complication seen in nine (17%). The mortality rate was 6%. Survival estimates of 1 and 5 years were 79 and 49%. DiscussionLGIB is a severe physiological insult occurring in patients who are often elderly and moribund. Although major post embolization complications occur, transcatheter arterial embolization should be the first-line approach over surgery in profuse LGIB in patients with hemodynamic instability, when colonoscopy fails or is unavailable, or when computerized tomography angiography detects small intestinal bleeding.

Quantifying linear enamel hypoplasia in Virunga Mountain gorillas and other great apes.

Linear enamel hypoplasia (LEH) is a condition marked by localized reductions in enamel thickness, resulting from growth disruptions during dental development. We use quantitative criteria to characterize the depth of LEH defects and "normal" perikymata in great apes. We test the hypothesis that mountain gorillas have shallow defects compared to other taxa, which may have led to their underestimation in previous studies. Previous attempts to characterize LEH morphology quantitatively have been limited in sample size and scope. We generated digital elevation models using optical profilometry (Sensofar PLu Neox) and extracted 2D coordinates using ImageJ to quantify depths in canines from three great ape genera (N = 75 perikymata; 255 defects). All defect depths fall outside the distribution of perikymata depths. Mountain gorilla defects are significantly shallower than those of other great ape taxa examined, including western lowland gorillas. Females have significantly deeper defects than males in all taxa. The deepest defect belongs to a wild-captured zoo gorilla. Virunga mountain gorilla specimens collected by Dian Fossey exhibit deeper defects than those collected recently. Shallow defect morphology in mountain gorillas may have led to an underestimation of LEH prevalence in past studies. Defect depth is used as a proxy for insult severity, but depth might be influenced by inter- and intra-specific variation in enamel growth. Future studies should test whether severe insults are associated with deeper defects, as might be the case with Haloko, a wild-captured gorilla. Ongoing histologic studies incorporating associated behavioral records will test possible factors that underlie differences in defect morphology.