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I. Steve, M.B.A., M.B.B.S., M.H.S.

Program Director, Meharry Medical College School of Medicine

Diabetic microangiopathy may involve all organs, including bone, possibly contributing to bone fragility. Histomorphometric assessments found microangiopathy in 82% of bone biopsy specimens from diabetic patients, and a concomitant reduction of bone marrow capillaries[179]. In mouse models of T1D, administration of an angiogenic factor to ovariectomized mice led to improvements in bone quality [180]. Metformin is widely prescribed for the management of T2D, being recommended as the first-line treatment by international guidelines[8,183]. It reduces hepatic glucose production and improves peripheral insulin sensitivity, thereby enhancing peripheral glucose disposal[184]. Clinical observations indicate that metformin has a neutral[28,189] or even a favorable effect on fracture risk[12,190,191]. These effects result in the suppression of hepatic gluconeogenesis and increased peripheral glucose disposal. Of note, in animal models of T1D administration of liraglutide significantly improved bone strength and reduced collagen degradation in the bone matrix, although no changes in trabecular no cortical microarchitecture were observed[196]. In particular, alogliptin may be associated with a lower risk of bone fracture compared with placebo and other drugs in the same class[210]. It has been postulated that sulfonylureas do not affect bone directly, but may increase fracture risk by inducing higher rates of hypoglycemic events[222]. Studies that assessed the effect of sulfonylureas and glinides on fracture risk yielded conflicting results, with most studies indicating increased risk[28,189,223-225], but also no effect[191] even decreased risk[12]. Treatment with pioglitazone significantly increased fracture risk compared with placebo in a randomized doubleblind, placebo-controlled study [228]. The increase in risk has been confirmed in population-based studies[189] and metanalyses[229], although the impact on bone seems to be more pronounced in women than in men[190,229]. Consistently, no association between insulin treatment and single nor multiple fractures was found in a recent study that assessed risk factors for fragility fractures in T1D[230]. Insulin in T2D: Insulin treatment in patients with T2D is initiated when disease progression overcomes the effect of non-insulin agents[8,183]. Thus, patients with T2D started on insulin generally have longstanding diabetes, and may have developed serious complications such as retinopathy-related impaired vision, peripheral artery disease and neuropathy, which in turn are risk factors for falls[20,21]. However, not all studies point towards a negative effect of insulin on fracture risk[12,191]. The association between insulin and increased fracture risk despite the anabolic effects of insulin on bone is likely due to the increased risk of falls and hypoglycemic episodes associated with insulin treatment[222]. Surgical treatments for diabetes Pancreas and islet transplantation in T1D: Beta cell replacement through pancreas or pancreatic islet transplantation is the only currently available cure for T1D in humans, with pancreas transplantation being more often associated with insulin independence and longer graft function. Successful pancreas transplantation provides physiological insulin repletion, without the risk of hypoglycemia associated with exogenous insulin administration. However, individuals with T1D undergoing pancreaskidney transplantation also have end-stage renal disease, which strongly affects bone health. Metabolic surgery for T2D diabetes: Metabolic surgery is now included as a treatment option for appropriate candidates with T2D [8,235]. Patients undergoing metabolic surgery experience rapid and massive weight loss, which translates into several metabolic benefits, but may be detrimental to bone health. Mechanisms underlying the negative effects of bariatric surgery on bone health may involve nutritional factors, mechanical unloading, hormonal factors, and changes in body composition and bone marrow fat[245]. To the best of our knowledge, no studies have specifically addressed the issue of diabetic bone disease in patients with T2D undergoing bariatric surgery. Strict monitoring should be implemented for T2D patients undergoing bariatric surgery in order to prevent nutritional deficiencies that could worsen weight loss-associated bone loss. Several alterations in calcium homeostasis have been described in diabetic patients, including reduced intestinal calcium absorption and renal tubular calcium reabsorption, and impaired vitamin D synthesis [247]. It is also recognized that individuals with diabetes, both T1D and T2D, have lower vitamin D levels as compared with non-diabetic controls[248,249]. Overall, these alterations may negatively impact calcium homeostasis and bone mineralization.

A2673 Meta-Analysis of Asthma Control in Patients with Severe Eosinophilic Asthma Treated with Mepolizumab/J. A2674 Response to Benralizumab After Sub-Optimal Response to Mepolizumab in Oral Corticosteroid Dependent Severe Eosinophilic Asthma/J. A2681 Adherence Assessment in Clinical Trials of Severe Asthma Therapy Is Inadequate and Leads to Loss of Power/G. A2683 519 509 Insulin Resistance Is Associated with Longitudinal Decline in Lung Function in the Severe Asthma Research Program/M. A2684 Combined Immune Response Based on Bal Cytokine Profiling in Children with Severe Asthma/E. A Review of Patient Characteristics to Understand Current Use of Prone Position Therapy in Moderate to Severe Acute Respiratory Distress Syndrome/S. A2691 Mechanical Ventilation Utilization and Outcomes for Patients with Neuromuscular Disease Receiving Treatment in an Intensive Care Unit/E. A2692 What Happens During Outpatient Visits Immediately Prior to Sepsis Hospitalization A2697 Impact of Critical Care Recovery Center on 2-Year Healthcare Utilization Outcomes/H. A2699 Neither Vitamin D Levels Nor Supplementation Are Associated with Persistent Critical Illness: A Retrospective Cohort Analysis/E. A2700 414 402 Implementation of an Addiction Consult Protocol Improves Access to Addiction Services for Patients Admitted to a Medical Intensive Care Unit/A. A2701 Improving Safety of Intrahospital Transport of Critically Ill Patients: the Transport Timeout/M. A2702 A Novel Intervention to Improve Intensive Care Unit End of Rotation Transitions in Care/J. A2706 Return to Employment Following Critical Illness and Its Association with Health-Related Quality of Life: A Systematic Review and Meta-Analysis/J. A2709 Cigarette Smoking Is Associated with Clinical and Biological Heterogeneity in Patients with the Acute Respiratory Distress Syndrome/F. A2715 Serum Tumor Necrosis Factor Receptor 1 Is Associated with Acute Kidney Injury in Acute Respiratory Distress Syndrome Patients/P. A2716 A Novel Proteomic Approach to Distinguishing Septic Children with Acute Respiratory Distress Syndrome/N. A2718 613 Role of miR-466i in Mesenchymal Stem Cell Microvesicles Treating Pneumonia Caused by Drug-Resistant Pseudomonas Aeruginosa/M. A2719 Metabolomic Changes Predict Quality of Life Outcomes 6 Months After Survival of Acute Respiratory Failure/R. A2720 Programmed Cell Death Ligand 1 Inhibition Improves Survival in a Murine Model of Sepsis Due to Staphylococcus Aureus Pneumonia with a Low- but Not High-Dose Inoculum/L. A2722 Association Between Temperature Trajectory and Cytokine Signatures in Patients with Staphylococcus Aureus Bacteremia/S. A2723 Heme Has Differential Effects in Septic and Non-Septic Mice on Adaptive Immunity/A. A2724 Altered Cellular Metabolism Links the Respiratory Microbiome to Mortality in Critically Ill Patients/J. A2726 Hyperoncotic Albumin Attenuates Brain Damage Compared to Saline and Iso Oncotic Albumin in Experimental Focal Ischemic Stroke/R. A2727 Transcriptomic Response to Lung Collapse During Experimental Single-Lung Ventilation/C. A2728 Pharmacologic Inhibition of Janus Kinase 1 and 2 Worsens Survival in Murine Sepsis/S. A2741 Acceptable Range of Inspiratory Effort During Mechanical Ventilation: the Effort Study/I. A2745 A New Method to More Accurately Detect and Better Quantify Patient-Ventilator Asynchronies/S. A2747 Diaphragm Pacing: A Promising Adjunct to Facilitate Liberation from Mechanical Ventilation/R. A2748 Microalbuminuria in Weaning from Mechanical Ventilation: A Prospective Observational Study/Y.

A raised interleukin-6 level may be clinically helpfulinassistingthediagnosisofepididymitis. The child presents with scrotal discomfort,oedemaanderythemaofonesideofthescrotum,whichmayspread to affect the entire scrotum, the penis and inguinal and perineal regions. Occasionally, eosinophilia may occur and, characteristically, ultrasound examination shows marked thickening of the scrotalwall,increasedperi-testicularbloodflowandamildreactivehydrocele. The testicle may become extremely large, although the scrotalskinisnotusuallyerythematous. Paediatric surgeons and oncologists are predominantly requiredinmanagingthesepatients. Thetestisbecomesenlargedandpainful,and there is associated bruising and frequently an associated hydrocele. Acutehydrocele A patent processus vaginalus may allow intraperitoneal fluid to flow into the spacearoundthetesticleinthescrotum. The testis in this situation is not painful and one can determine that the swelling does not extend into the groin. Ultrasound examination is useful in confirming the diagnosis and unnecessary urgent surgerycanbeavoided. This compares to a generation ago, when the majority of males were circumcised,oftenintheneonatalperiod. Asaresult,problemswiththeforeskin are increasing and patients are often referred to the emergency department for treatment. In most casestheforeskinshouldbeleftaloneuntiltheageof5or6andthenshouldbe retracted gently to clean the under surface of the foreskin and the glans. If the foreskincanberetractedeasilyatanearlierage,thechildshouldbeencouraged toretractitgentlyinthebathorshowereverynighttocleantheglansandinner surface of the foreskin. If the foreskin cannot be retracted easily, the use of a mildsteroidointmentforashortperiodmaycorrectthephimosis. Itleads toirreversiblephimosisoftheforeskinandpresentswithinabilitytoretractthe foreskin and varying degrees of urinary obstruction. It is best treated with circumcision,asstudiesusingtopicalsteroidtreatmenthavefailedtoshowany permanentimprovement. Oedemaofthe foreskin distal to the tight ring can develop and the foreskin can become painfullyswollenanddifficulttoreduce. Historically alternative methods described to reduce the paraphimosis were the use of hyaluronidase20 and puncture technique21 whereby the oedematous foreskin ispuncturedinseveralplaceswithan18-gaugehypodermicneedleto evacuate the oedema so as to allow for easy reduction of the foreskin. It may occur spontaneously or it can be secondary to medication, sickle cell disease or leukaemia. Usually the corpora cavernosa is painful and fully rigid with minimal or no involvement of the corpus spongiosum and glans penis. Uncontrolled arterial inflow, usually caused by direct trauma to the penis or perineum,resultsinhigh-flowpriapism. Urgent referral to a paediatric urologist is required for immediate treatment or surgery. Paediatricretrieval Children constitute a minority of the population in developed countries, and criticalillnessisrarewhencomparedtoadults. For retrieval of critically ill children, a range of operating models exist, which suit the needs, resourcesandfunctionofdifferenthealthcaresystems. Alternatively, for a large population critical care transport for children may be resourced independently and delivered by a dedicated, standalone paediatric transport service. In some jurisdictions, retrieval services operatemodelscombiningpaediatric,newbornand/oradultretrievalinasingle organisation. In any case, the principle of providing a single, regional point of contactforreferrersandaspecialistretrievalteamisbasedonevidencethatthis approachtointensivecareandemergencytransportforchildrenresultsinbetter outcomes. From a retrieval point of view, it is worth noting that the management of a critically ill or deteriorating child tends to be a relatively rare event for the emergency physician in a nonpaediatriccentre. Moreover,themajorityofcriticallyillchildrenareinfantsor small children younger than 5 years of age, placing many practitioners well outside their comfortzone. Paediatricemergencyreferrals Inmostdevelopedjurisdictions,formalsystemsforreferralofpatients,including children, to higher levels of care exist.

Abuse and violence Discrimination against and exclusion of children with disabilities renders them disproportionately vulnerable to violence, neglect and abuse. Studies from the United States have shown that children with disabilities who are in preschool or younger are more likely to be abused than peers without disabilities. For example, they may be subject to violence administered under the guise of treatment for behaviour modification, including electroconvulsive treatment, drug therapy or electric shocks. Institutions and inappropriate care In many countries, children with disabilities continue to be placed in institutions. It is rare for these facilities to provide the individual attention that children need to develop to their full capacity. The quality of educational, medical and rehabilitative care provided in institutions is often insufficient because standards of appropriate care for children with disabilities are lacking or, where such standards exist, because they are not monitored and enforced. Foster families may feel reluctant to take on the care of a child with a disability because of the perceived extra burden of care and additional physical and psychological demands. Organizations tasked with placing children in families can encourage them to consider fostering children with disabilities, and provide them with appropriate training and support. Where authorities have come to see the perils of institutional care and have moved to return children to their families or communities, children with disabilities have been among the last to be removed from institutions and transferred to alternative care. In many countries of Central and Eastern Europe and the Commonwealth of Children with disabilities and secondary education uArmenia, 2011 the main reason children with disabilities who are in the care of their families do not attend school is because their parents think their children cannot study at school. Children with disabilities who live with their families generally obtain their secondary education in mainstream schools. Children with disabilities who live in orphanages tend to not attend secondary school at all. Sample sizes: 5,707 children in total sample; 5,322 children with disabilities in the care of families; 385 children with disabilities in the care of orphanages. Deinstitutionalization was given priority and fostering, which had an established history in the country, was given a boost. A new family law was adopted and a fund was established to help develop community-based social services. This revelation served to demonstrate the importance of ensuring that reforms are designed and implemented so no children are excluded from progress, and it has since led to a renewed commitment to deinstitutionalization. Specific measures can help: Children with disabilities can be interviewed in appropriate languages, whether spoken or signed. Law enforcement officers, social workers, lawyers, judges and other relevant professionals can be trained to work with children who have disabilities. Systematic and continuous training of all professionals involved in the administration of justice for children is vital, as is the establishment of regulations and protocols that enhance equal treatment of children with disabilities. It is also important to develop alternative solutions to formal judicial proceedings, taking into account the range of individual capacities of children who have disabilities. Children with disabilities should not be placed in regular juvenile detention facilities, neither when awaiting nor following a trial. Any decisions resulting in deprivation of liberty should be aimed at appropriate treatment to address the issues that led the child to commit a crime. Such treatment should be carried out in the context of appropriate facilities with adequately trained staff, with human rights and legal safeguards fully respected. Bellis, Sara Wood, Karen Hughes, Ellie McCoy, Lindsay Eckley, Geoff Bates Centre for Public Health, Liverpool John Moores University Christopher Mikton, Alana Officer, Tom Shakespeare Department of Violence and Injury Prevention and Disability, World Health Organization Children with disabilities are three to four times more likely to be victims of violence. Children and adults with disabilities often face a wide range of physical, social and environmental barriers to full participation in society, including reduced access to health care, education and other support services.

A1708 Not Your Textbook Thyroid Storm: Paradoxical Beta Blocker Decompensation Masking Unusual Cardiac Manifestations/A. A1711 Thyroid Storm Presenting with Multiorgan Failure and Severe Lactic Acidosis/J. A1712 In the "I" of the Storm: Thyroid Storm Induced by Iodine Contrast in Thyrotoxicosis/M. A1714 the Domino(Side) Effect: Steroid Induced Ketosis Post Rapid Sequence Intubation with Etomidate and Hydrocortisone/A. A1701 Ventilatory Pattern Variability and Cardioventilatory Coupling in Rats with E. A1704 Characterization of Microparticle Gasdermin-D in Patients in the Medical Intensive Care Unit/E. A1706 Airway Epithelial Hepcidin Coordinates Pulmonary Macrophage and Local Iron Against Bacterial Pneumonia/Q. A7311 P940 P941 P942 P943 P124 P125 P944 P945 P126 P127 P946 P128 P947 P948 P129 Facilitators: S. A1721 An Atypical Treatment for a Typical Hemolytic Uremic Syndrome in an Adult/S. A1722 McKittrick-Wheelock Syndrome: A Rare Cause of Severe Hyponatremia and Hypokalemia/C. A1725 A Case of Osmotic Demyelination Syndrome Following Gradual Correction of Hyponatremia/A. A1727 Euglycemic Diabetic Ketoacidosis Secondary to Sodium-Glucose Cotransporter 2 Inhibitors/M. A1728 Rhinocerebral Mucormycosis: A Rare Presentation in Severe Diabetic Ketoacidosis/S. A1730 P968 Severe Delirium Tremens: An Unusual Cause of Rhabdomyolysis with Extreme Serum Creatine Kinase Elevation/A. A1740 Thyrotoxicosis Induced Low Cardiac Output State in the Setting of Marfan Syndrome/S. P957 P958 Discussion: 11:15-12:00: authors will be present for individual discussion 12:00-1:00: authors will be present for discussion with assigned facilitators. A1743 Successful Application of Extracorporeal Membrane Oxygenation Without Anticoagulation for Diffuse Alveolar Hemorrhage Secondary to Microscopic Polyangiitis/P. A1744 Extracorporeal Membrane Oxygenation as Salvage Treatment for Acute Respiratory Failure Secondary to Granulomatosis with Polyangiitis/K. A1746 Experience with Liposomal Amphotericin B in a Patient with Disseminated Blastomycosis Receiving Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy/K. A1731 the Model Patient: When Diet and Medication Adherence Result in Life-Threatening Acidosis/K. A1733 Severe Euglycemic Diabetic Ketoacidosis Associated with Use of Canagliflozin/L. A1734 Combined Metformin Associated Lactic Acidosis and Starvation Ketoacidosis with Very High Osmolal Gap/M. A1748 Change in Transpulmonary Pressure with Prone Positioning in Acute Respiratory Distress Syndrome: A Case Report/D. A1749 P990 A Rare Case of Tension Pneumocephalus Induced by High Mechanical Ventilation Pressures in a Patient Without Any Prior Head Trauma/V. A1761 Necrotizing Autoimmune Myopathy Presenting with Acute Respiratory Failure: A Rare Case with a Rare Presentation/N. A1763 Concurrent Presentation of Transplant Pyelonephritis and West Nile Virus Encephalitis/C. A1764 Airway Emergency: Re-Intubation of a Patient Being Mechanically Ventilated with an Inhaled Pulmonary Vasodilator/S. A1750 Electrical Impedance Tomography and Ventilation Heterogeneity on a Silicosis Patient/T. A1755 Prone Positioning for Refractory Hypoxia Secondary to Legionella Pneumonia/A. A1767 Mounier- Kuhn Syndrome: A Rare Cause of Recurrent Respiratory Tract Infection/C.