Morbidity In Survivors Research Articles

Therapeutic exercise in improving acute lung injury: a long distance to be covered.

Skeletal muscle weakness is a common finding among critically ill patients, and many factors have been recognized to trigger its initiation early in the patients’ course in intensive care unit (ICU) (1). In acute respiratory distress syndrome (ARDS), a clinical condition which is characterized by acute respiratory failure, skeletal muscle weakness acquired in ICU is present in 25-50% of patients, and is independently associated with mortality and long term morbidity in survivors (2). Several clinical research studies suggest that early mobilization of critically ill patients improves clinically meaningful outcomes for the patient (3), however, without having clarified the mechanisms underlying this implementation. We read with interest the study by Files et al. (4) who through their experiments suggest a unifying mechanism underlying the beneficial effects of therapeutic exercise in mice with lung injury. In their study authors exercised ALI mice for 2 days after lipopolysaccharides (LPS) instillation. They found that a short duration of moderate intensity exercise attenuated muscle ring finger 1 (MuRF 1)-mediated atrophy of the limb and diaphragm and improved limb muscle force generation. Importantly, exercise also limited neutrophilic influx into the alveolar space through modulation of a co-ordinated systemic neutrophil chemokine response. Furthermore, in ALI mice exercise reduced granulocyte colony-stimulating factor (G-CSF), and in vivo blockade of the G-CSF receptor lead to recapitulation of the lung. Similarly, in humans with acute respiratory failure, early mobility therapy led to greater decrements over time in G-CSF plasma levels compared to control patients, confirming the relevance of G-CSF as a mediator of the improved outcomes of mobilized/exercised critically ill patients.

Persistently High Respiratory Morbidity 25 Years After Bhopal Disaster

Introduction The world's biggest industrial disaster, the 1984 methyl isocyanate leakage in Bhopal, India, led to the death of about 2000 people within 72 hours. Exposure to toxic gases resulted in morbidities in survivors, especially affecting the respiratory system. The objective of this study was to assess the temporal trend of respiratory morbidities in the gas-exposed survivors in Bhopal and its relationship with grades of exposure. Methods A long-term follow-up epidemiological study was launched in 1985 covering a cohort of 80,021 gas-exposed and 15,931 unexposed subjects. Both cohorts were followed up at a six-month interval and morbidities were recorded in a structured verbal autopsy questionnaire. Based on mortality rates during the first 3 days after the accident, the gas-exposed area was divided into severely, moderately and mildly affected. Data presented here were collected up to 2010. Results During the acute stage in December 1984, 97-99% exposed subjects in the affected areas suffered from respiratory morbidities. In 2010, respiratory morbidities rates were 17%, 10% and 13% in severely, moderately, mildly affected areas, respectively, compared to 3% in the control area. Time-trend analysis revealed that respiratory morbidities in the exposed cohort have nearly attained a plateau since 1991, and have consistently been higher than in the non-exposed cohort (p

Late new morbidity in survivors of adolescent and young-adulthood brain tumors in Finland: a registry-based study.

Brain tumors (BTs) in adolescence and young adulthood (AYA) differ from those in childhood or late adulthood. However, research concerning late effects in this particular survivor group is limited. This study evaluates late morbidity of survivors diagnosed in AYAs. We identified from the Finnish Cancer Registry all survivors diagnosed with BT at the ages 16-24 years between 1970 and 2004 (N = 315) and used data from the Hospital Discharge Registry to evaluate their late (≥5 y after diagnosis) morbidity requiring treatment in a specialized health care setting. A sibling cohort of BT patients diagnosed before the age of 25 years was used as a comparison cohort (N = 3615). The AYA BT survivors had an increased risk for late-appearing endocrine diseases (HR, 2.9; 95% CI, 1.1-8.0), psychiatric disorders (HR, 2.0; 95% CI, 1.2-3.2), diseases of the nervous system (HR, 9; 95% CI, 6.6-14.0), disorders of vision/hearing loss (HR, 3.6; 95% CI, 1.5-8.5), diseases of the circulatory system (HR, 4.9; 95% CI, 2.9-8.1), and diseases of the kidney (HR, 5.9; 95% CI, 2.5-14.1). Survivors with irradiation had an increased risk for diseases of the nervous system compared with non-irradiated survivors (HR, 3.3; 95% CI, 1.8-6.2). The cumulative prevalence for most of the diagnoses remained significantly increased for survivors even 20 years after cancer diagnosis. The AYA BT survivors have an increased risk of morbidity for multiple new outcomes for ≥5 years after their primary diagnosis. This emphasizes the need for structured late-effect follow-up for this patient group.

Long-term increase in coherence between the basal ganglia and motor cortex after asphyxial cardiac arrest and resuscitation in developing rats

The basal ganglia are vulnerable to injury during cardiac arrest. Movement disorders are a common morbidity in survivors. Yet, neuronal motor network changes post-arrest remain poorly understood. We compared function of the motor network in adult rats that, during postnatal week 3, underwent 9.5 min of asphyxial cardiac arrest (n = 9) or sham intervention (n = 8). Six months after injury, we simultaneously recorded local field potentials (LFP) from the primary motor cortex (MCx) and single neuron firing and LFP from the rat entopeduncular nucleus (EPN), which corresponds to the primate globus pallidus pars interna. Data were analyzed for firing rates, power, and coherence between MCx and EPN spike and LFP activity. Cardiac arrest survivors display chronic motor deficits. EPN firing rate is lower in cardiac arrest survivors (19.5 ± 2.4 Hz) compared with controls (27.4 ± 2.7 Hz; P < 0.05). Cardiac arrest survivors also demonstrate greater coherence between EPN single neurons and MCx LFP (3-100 Hz; P < 0.001). This increased coherence indicates abnormal synchrony in the neuronal motor network after cardiac arrest. Increased motor network synchrony is thought to be antikinetic in primary movement disorders. Characterization of motor network synchrony after cardiac arrest may help guide management of post-hypoxic movement disorders.

Therapeutic hypothermia and hypoxia-ischemia in the term-equivalent neonatal rat: characterization of a translational preclinical model.

BackgroundHypoxic-ischemic encephalopathy (HIE) is a major cause of morbidity in survivors. Therapeutic hypothermia (TH) is the only available intervention, but the protection is incomplete. Preclinical studies of HIE/TH in the rodent have relied on the postnatal day (P) 7 rat whose brain approximates a 32–36 week gestation infant, less relevant for these studies. We propose that HIE and TH in the term-equivalent P10 rat will be more translational.MethodsP10–11 rat pups were subjected to unilateral hypoxia-ischemia (HI) and 4 hours recovery in normothermic (N) or hypothermic (TH) conditions. Brain damage was assessed longitudinally at 24 hours, 2 and 12 weeks. Motor function was assessed with the beam walk; recognition memory was measured by novel object recognition.ResultsNeuroprotection with TH was apparent at 2 and 12 weeks in both moderately and severely damaged animals. TH improved motor function in moderate, but not severe damage. Impaired object recognition occurred with severe damage with no evidence of protection of TH.ConclusionThis adaptation of the immature rat model of HI provides a reproducible platform to further study HIE/TH in which individual animals are followed longitudinally to provide a useful translational preclinical model.

Analysis of risk factors of long-term complications in congenital diaphragmatic hernia: A single institution's experience

To establish better management practices to reduce morbidities in survivors with congenital diaphragmatic hernia (CDH). Of 60 patients treated for CDH at our institution between 1991 and 2011, 49 patients without severe anomalies were retrospectively reviewed. Since 2004, gentle ventilation (GV) has been the main treatment for CDH. Patients were divided into the following two groups: the non-GV group (n=29) who were treated before GV treatment was implemented, and the GV group (n=20). The overall survival rate was 62.1% (18/29) and 95% (19/20) in the non-GV and GV groups, respectively (p=0.016). Despite the high survival rate, the incidence of long-term complications in survivors was still high (14/19, 73.7%) in the GV group. In the GV group, liver-up (p=0.106) and the need for patch repair (p=0.257) tended to be associated with the development of long-term complications, but did not reach statistical significance. The presence of perioperative complications was associated with the development of long-term complications (p=0.045) in the GV group. Patients who developed short-term complications seemed to be at risk of long-term complications. Therefore, to minimize long-term morbidities in CDH survivors, the prevention of short-term complications might be important.

Pharmacological interventions for those who have sexually offended or are at risk of offending.

This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the effects of pharmacological interventions on target sexual behaviour for people who have been convicted or at risk of sexual offending.

Sedation and analgesia for critically ill children

Abstract Effective sedation and analgesia in the critically ill child ensures physical comfort and minimises psychological distress. In the UK the most commonly used sedative and analgesic agents for critically ill children are midazolam and either morphine or fentanyl. Consensus clinical practice guidelines for the provision of sedation and analgesia in critically ill children were published in 2006 by the UK Paediatric Intensive Care Society, but considerable variation in practice persists. It is important to treat pain, and in addition to the obvious immediate effects of untreated pain there is increasing evidence that pain experienced early in life may result in long-term changes in neurosensory function. There are however also concerns that sedative and analgesic agents may themselves be associated with developmental neurotoxicity, particularly amongst neonates, and adverse psychological outcomes in survivors of critical care. Withdrawal syndrome and delirium remain poorly understood, although we have emerging tools such as the Sophia Observation withdrawal Symptoms-scale (SOS) and the paediatric Confusion Assessment Method for the ICU (pCAM-ICU). The most important single factor in reducing avoidable psychological morbidity in survivors of PICU is to minimise the administered doses of sedative and analgesic agents.

Hemorragia cerebral

Spontaneous intracerebral hemorrhaging is a collection of blood located in the brain tissue, caused by the nontraumatic rupture of a blood vessel (almost always arterial). This condition represents 10–15% of all acute cerebrovascular disorders and entails an acute high mortality and causes considerable morbidity in survivors. The main risk factor is arterial hypertension but there are numerous other potential causes. The clinical presentation depends on the location and volume of the hemorrhage. The diagnosis is based on the medical history, a neurological examination and the implementation of urgent neuroimaging tests. At present, there is no specific medical treatment, and therefore general support measures are employed. The role of surgical treatment in this disease is not well-defined.

Management of granulomatous amebic encephalitis: Laboratory diagnosis and treatment.

Granulomatous amebic encephalitis is a life-threatening central nervous system (CNS) infection caused by the free-living amoebae Acanthamoeba spp., Balamuthia mandrillaris and Sappinia pedata. The disease has a subacute to chronic onset affecting commonly the immunocompromised population with high mortality rate. The diagnosis of this disease entity requires high suspicion with appropriate sample collection and testing by the laboratory experts. Radiological investigations are nonspecific and commonly confused with CNS tuberculosis, neurocysticercosis, disseminated encephalomyelitis, viral encephalitis etc., delaying the accurate diagnosis of these cases. Early diagnosis plays a crucial role in the survival of these cases since appropriate management can be initiated. No single drug is effective; hence multiple antibiotics targeting various proteins or receptors are required for successful treatment. A combination of surgical and medical interventions involving multiple specialty experts is required to prevent death and morbidity in survivors.

Pulmonary support on day of life 30 is a strong predictor of increased 1 and 5-year morbidity in survivors of congenital diaphragmatic hernia

PurposePulmonary support (PS) on day-of-life-30 (DOL-30) has been shown to be the strongest predictor of subsequent morbidity and in-patient mortality in congenital diaphragmatic hernia (CDH). We hypothesized that PS on DOL-30 can also predict long-term outcomes in CDH survivors. MethodsWe analyzed records of 201 CDH survivors followed by a single multidisciplinary clinic (1995–2010). Follow-up was 83 and 70% at 1 and 5years respectively. PS was defined as: (1) invasive support (n=44), (2) noninvasive support (n=54), or (3) room air (n=103). Logistic regression was used to estimate the adjusted association of PS on DOL-30 with outcomes at 1 and 5-years. ResultsUse of PS on DOL-30 was significantly associated with pulmonary and developmental morbidities at 1 and 5-years. Even after adjusting for defect-size and presence of ventilation/perfusion mismatch, greater PS on DOL-30 was associated with a significantly increased odds of requiring supplemental oxygen and developmental referral at 1-year, and asthma and developmental referral at 5-years. ConclusionCDH survivors continue to have significant long-term pulmonary and developmental morbidities. PS on DOL-30 is a strong independent predictor of morbidity at 1 and 5-years and may be used as a simple prognostic tool to identify high-risk infants.

Late psychiatric morbidity in survivors of cancer at a young age: a nationwide registry-based study.

Childhood cancer survivors have been shown to be prone to psychosocial adverse outcomes. Data on young adults and their psychiatric late effects are still scarce. In a nationwide, registry-based study, we explored the risk (HR) of new psychiatric diagnoses in 5-year survivors of childhood and young adulthood (YA) cancer (n = 13,860) compared with a sibling cohort (n = 43,392). Hazard ratios (HRs) were calculated using Cox regression models. Patients and siblings were identified from the Finnish Cancer Registry and Central Population Registry, respectively. Outcome diagnoses were retrieved from the national hospital discharge register. The risk of organic memory/brain disorders was significantly increased in both childhood (HR 4.9; 95%CI 2.7-8.9) and YA (HR 2.1; 95%CI 1.4-3.1) cancer survivors compared with siblings. Mood disorders were also more common in childhood (HR 1.3; 95%CI 1.1-1.7) and YA survivors (1.3; 95%CI 1.1-1.5) than in siblings. Radiotherapy did not explain the differences. Female childhood cancer survivors had significantly increased HRs for mood disorders, psychotic disorders, neurotic/anxiety disorders, somatization/eating disorders and personality disorders. In survivors of YA cancers, females had significantly increased HR for neurotic/anxiety disorders, and the difference between female survivors and siblings was significantly (p < 0.05) higher than that between male survivors and male siblings. The effect of treatment era was also analyzed, and the risk of organic memory and brain disorders in childhood cancer survivors did not diminish over time. Despite the trend of decreased use of cranial irradiation in children, the risk of organic memory/brain disorders was elevated, even during the most recent era. Thus, additional research on chemotherapy-only protocols and their impact on mental health, is warranted.

Therapeutic hypothermia for hypoxic ischaemic encephalopathy using low-technology methods: a systematic review and meta-analysis.

A systematic review and meta-analysis were performed to determine the effect of therapeutic hypothermia using low-technology methods, in settings with facilities for intensive care, in term or near-term infants with hypoxic-ischaemic encephalopathy on mortality, neurological morbidity at discharge and neurological morbidity at 6-24months. Meta-analysis of three randomised controlled studies showed that low-technology therapeutic hypothermia in an intensive care setting significantly reduced the mortality and the neurological morbidity in survivors at discharge.

Development of a Tissue-Engineering Vascular Graft for Use in Congenital Heart Surgery

Congenital cardiac anomalies represent the most common birth defect affecting nearly 1% of all live-births. Severe forms of congenital heart disease are life-threatening and require surgical intervention. Despite significant advances in the surgical and medical management of this disease, it remains a leading cause of death in the newborn period and lifelong morbidity for survivors. One significant source of morbidity and mortality arises from complications associated with the use of currently available prosthetic vascular grafts, patches, and replacement heart valves that are frequently needed to perform reconstructive procedures. These risks include a greater chance of thromboembolic complications, poor durability due to neointimal hyperplasia, increased susceptibility to infection, and lack of growth capacity. The development of better biomaterials with growth potential could substantially improve the outcomes of children requiring congenital heart surgery by reducing the number of graft-related complications and enabling earlier definitive surgical repair without risk of serial re-operation. Tissue engineering offers an innovative solution to this significant problem. Using tissue engineering methods, bioprosthetics can be made from an individual's own cells creating a living material with excellent biocompatibility and the ability to grow, repair, and remodel. One promising approach utilized by several research groups is the use of a biodegradable scaffold seeded with autologous cells. In 2001, our group pioneered the development and translation of tissue-engineering technologies to create vascular grafts for use in the surgical repair of congenital cardiac anomalies, using a biodegradable polymer conduit (Shinoka et al., 2001, Hibino et al., 2010). de Mel and colleagues used a nanocomposite biomaterial-based small diameter vascular graft and induced endothelialization in situ (de Mel et al., 2009). Thomas and Nair demonstrated an electrospinning technique to generate biodegradable tubular scaffolds for seeding vascular smooth muscle cells (Thomas and Nair, 2013). Our group is currently performing the first FDA-approved clinical trial evaluating the use of tissue engineered vascular grafts (TEVG) (IDE 14127). The TEVG is made by seeding bone marrow-derived mononuclear cells onto a biodegradable tubular scaffold. In 2012, Olausson and colleagues described a novel and unique attempt to develop tissue-engineered vein using decellularized allogenic vein as the scaffold, and autologous endothelial and smooth muscle cells differentiated from cultured mesenchymal stem cells obtained from 20 mL of bone marrow, although the graft was narrowed at 1 year after the surgery and the patient required the second application of new graft implantation (Olausson et al., 2012). Now in EBioMedicine, they describe another clinical application of bioengineered vascular graft using an autologous peripheral whole blood instead of bone marrow cells, although one graft was also explanted 7 months after initial surgery due to the narrowing. It is indeed very challenging for any type of vascular conduit to maintain the good patency in low-flow venous system. In fact, our previous clinical results also demonstrated that 4 out of 25 venous conduits required balloon angioplasty due to narrowing in the long-term periods (Hibino et al., 2010). Many readers would be very interested in the histology of explanted tissue in the patient and would like to know the fate of seeded cells. We have experience of using cultured endothelial cells for seeding our graft. It was difficult to maintain high quality-controlled production process in a stable condition, especially for cell expansion of endothelial cells in vitro. Despite the number of preparatory steps needed for the authors' graft, the rewards look small. If the decellularized vein is easily available, I would recommend trying to use bone marrow mononuclear cells expressing a cytokine effect to recruit host-derived endothelial cells and smooth muscle cells onto the vein, so that the time-consuming cell expansion step can be eliminated. In fact, we demonstrated that the seeded mononuclear cells in the vascular grafts were eventually replaced by cells from adjacent vessels, probably via the body's innate healing mechanism, resulting in neovessels of entirely host cell origin (Hibino et al., 2011). Finally, I would like to congratulate the authors on this successful, compassionate clinical application in these very difficult patients for whom conventional approaches were not feasible or hazardous.

PO-0845 Acute Necrotising Encepholopathy In Childhood – Epidemiology, Radiological Findings And Outcomes

Background and aims Acute necrotizing encephalopathy in childhood (ANEC) is a disease characterised by acute encephalopathy and radiological features of bilateral thalamic necrosis. Medium and long term morbidity is not well described. We describe the mortality and morbidity outcomes in our paediatric cohort with this disease. Methods This is a retrospective ten-year series. Children aged one month to 18 years diagnosed with ‘ANEC’ were collated from Neurology and Radiology databases. 18 fulfilled clinical criteria of acute encephalopathy. All were scored with Mizuguchi’s radiological checklist by two paediatric neurologists and one radiologist. 11 cases scored unlikely were excluded. Data analysis focused on discharge and follow-up outcomes. Results 7 patients were analysed. The median age was 3.7 years. All were previously well with normal development. All had impaired consciousness at presentation with preceding fever and prodrome. Typical radiology showed bilateral thalamic involvement with/without areas of haemorrhage and necrosis. Causative organisms included Influenza A H1N1, Human Herpes Virus 6 and Metapneumovirus. All were treated with steroids, immunoglobulin or both. Outcomes were evaluated at discharge and follow-up and divided into good or poor (including death). One passed away from brainstem death. All had neurological deficit at discharge: 50% mildly affected; 50% severely affected. 00% in the former group restored normal neurological function on follow-up. In the latter, two responded well to rehabilitation but one remained severely impaired. Conclusions ANE mortality at our institution is 14%. Morbidity of survivors at discharge is 100%. Long term follow up morbidity however, improves to 50% with half achieving normal neurological function at follow up.

Dying neurons in thalamus of asphyxiated term newborns and rats are autophagic.

Neonatal hypoxic-ischemic encephalopathy (HIE) still carries a high burden by its mortality and long-term neurological morbidity in survivors. Apart from hypothermia, there is no acknowledged therapy for HIE, reflecting the lack of mechanistic understanding of its pathophysiology. (Macro)autophagy, a physiological intracellular process of lysosomal degradation, has been proposed to be excessively activated in excitotoxic conditions such as HIE. The present study examines whether neuronal autophagy in the thalamus of asphyxiated human newborns or P7 rats is enhanced and related to neuronal death processes. Neuronal autophagy and cell death were evaluated in the thalamus (frequently injured in severe HIE) of both human newborns who died after severe HIE (n = 5) and P7 hypoxic-ischemic rats (Rice-Vannuci model). Autophagic (LC3, p62), lysosomal (LAMP1, cathepsins), and cell death (TUNEL, caspase-3) markers were studied by immunohistochemistry in human and rat brain sections, and by additional methods in rats (immunoblotting, histochemistry, and electron microscopy). Following severe perinatal asphyxia in both humans and rats, thalamic neurons displayed up to 10-fold (p < 0.001) higher numbers of autophagosomes and lysosomes, implying an enhanced autophagic flux. The highly autophagic neurons presented strong features of apoptosis. These findings were confirmed and elucidated in more detail in rats. These results show for the first time that autophagy is enhanced in severe HIE in dying thalamic neurons of human newborns, as in rats. Experimental neuroprotective strategies targeting autophagy could thus be a promising lead to follow for the development of future therapeutic approaches.

Brain MRI of children with retinopathy-negative cerebral malaria.

Our goals were to understand the brain magnetic resonance imaging (MRI) findings in children with retinopathy-negative cerebral malaria (CM) and investigate whether any findings on acute MRI were associated with adverse outcomes. We performed MRI scans on children admitted to the hospital in Blantyre, Malawi with clinically defined CM. Two hundred and seventeen children were imaged during the study period; 44 patients were malarial retinopathy-negative; and 173 patients were retinopathy-positive. We compared MRI findings in children with retinopathy-negative and retinopathy-positive CM. In children who were retinopathy-negative, we identified MRI variables that were associated with death and adverse neurologic outcomes. On multivariate analysis, cortical diffusion weighted imaging (DWI) abnormality and increased brain volume were strongly associated with neurologic morbidity in survivors. Investigations to explore the underlying pathophysiologic processes responsible for these MRI changes are warranted.

The impact of cardiac dysfunction on acute respiratory distress syndrome and mortality in mechanically ventilated patients with severe sepsis and septic shock: An observational study

PurposeAcute respiratory distress syndrome (ARDS) is associated with significant mortality and morbidity in survivors. Treatment is only supportive, therefore elucidating modifiable factors that could prevent ARDS could have a profound impact on outcome. The impact that sepsis-associated cardiac dysfunction has on ARDS is not known. Materials and MethodsIn this retrospective observational cohort study of mechanically ventilated patients with severe sepsis and septic shock, 122 patients were assessed for the impact of sepsis-associated cardiac dysfunction on incidence of ARDS (primary outcome) and mortality. ResultsSepsis-associated cardiac dysfunction occurred in 44 patients (36.1%). There was no association of sepsis-associated cardiac dysfunction with ARDS incidence (p= 0.59) or mortality, and no association with outcomes in patients that did progress to ARDS after admission. Multivariable logistic regression demonstrated that higher BMI was associated with progression to ARDS (adjusted OR 11.84, 95% CI 1.24 to 113.0, p= 0.02). ConclusionsCardiac dysfunction in mechanically ventilated patients with sepsis did not impact ARDS incidence, clinical outcome in ARDS patients, or mortality. This contrasts against previous investigations demonstrating an influence of nonpulmonary organ dysfunction on outcome in ARDS. Given the frequency of ARDS as a sequela of sepsis, the impact of cardiac dysfunction on outcome should be further studied.

The Role of Oxidative Stress on Necrotizing Enterocolitis in Very Low Birth Weight Infants

Necrotizing enterocolitis (NEC) is a devastating and common disease of very low birth weight (VLBW) infants with a mortality rate of 10% to 50% and a significant cause of morbidity in survivors. The incidence of NEC has increased from 5% to 7% in the last decades and this rate is likely to rise because of the increased survival of infants born at 24 weeks gestation, which are at high risk of developing NEC. NEC etiology is multifactorial: ischemia, infections, cytokines, enteral feeding and reactive oxygen species or free radicals (FRs) may contribute to the disruption of the immature gut barrier. In particular, ischemia, hypoxia-reperfusion, infection and inflammation are mechanisms capable of producing high levels of FRs, perturbing the normal redox balance and shifting cells to a state of oxidative stress (OS). Despite advances in neonatal medicine, the early diagnosis of NEC remains a major challenge. Early clinical signs are non specific and the laboratory findings are not fully reliable. Therefore, its delayed occurrence after birth, its rapid onset, the highly fulminant nature, and its severe morbidity, as well as the possibility of progression to death, strongly require the identification of new prospective biomarkers specific for high NEC risk. There is evidences that OS biomarkers in cord blood allow the early identification of infants at risk for NEC and thereby can be used to develop novel therapies for this devastating disease which predominantly occurs in premature infants.

Pathophysiology of blast-induced ocular trauma with apoptosis in the retina and optic nerve.

Blast-induced ocular trauma is a frequent cause of morbidity for survivors of improvised explosive devices. Blast overpressure (BOP) of 120 ± 7 KPa has been shown to cause damage to lungs, brain, and gut in a rat model; however, the effects of BOP on ocular tissues have not been characterized. To elucidate the pathophysiology of blast-induced ocular trauma, ocular tissues from rats subjected to blast were examined for evidence of apoptosis by the detection of activated caspase 3 and TUNEL assay in their ocular tissues. A compressed air shock tube was used to deliver 120 ± 7 KPa of BOP for duration of 2 msec to the right side of the rats. Rats were then euthanized at specific time points after blast exposure (3 hours, 24 hours, 48 hours). Ocular tissues were processed for immunohistochemistry to detect activated caspase 3 and TUNEL assay. Tissues were evaluated for relative levels of positive signal as compared to nonblast exposed controls. Activated caspase 3 was detected in the optic nerve, ganglion layer, and inner nuclear layer post blast exposure. At 24 and 48 hours, the inner nuclear layer from the right side had more cells with activated caspase 3. In the optic nerve, the highest levels of activated caspase 3 were detected on the right side at 24 hours post blast. BOP of 120 ± 7 KPa induces optic neuropathy and retinal damage. In both the optic nerve and retina, caspase 3 was activated in the right and left sides following blast exposure. The results of this study reveal that blast exposure induces apoptosis in both the optic nerve and retinal tissues.