bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathophysiology and management of altitude-related disorders
Authors: Martin Daniel S. , Grocott Michael P. W.
Published: April 2016

Acute high-altitude related illnesses include acute mountain sickness (AMS), high altitude pulmonary oedema (HAPO) and high altitude cerebral oedema (HACO). AMS is characterized by headache, lack of appetite, poor sleep, lethargy, and fatigue. AMS is a common, generally benign, self-limiting condition if managed with rest, no ascent, and symptomatic treatment. Descent is indicated in severe cases. HACO and HAPO are rare, but serious conditions that should be considered life-threatening medical emergencies. HACO is characterized by the presence of neurological signs (including confusion) at altitude, commonly in the presence of headache. HAPO is characterized by breathlessness and signs of respiratory distress at altitude, particularly accompanying exercise. Management of HACO and HAPO involves urgent descent, supplemental oxygen (cylinder, concentrator, or portable hyperbaric chamber) if available, and specific treatment with dexamethasone (HACO) or nifedipine (HAPO). Slow controlled ascent (adequate acclimatization) is the best prophylaxis against the acute high-altitude-related illnesses. Acetazolamide is an effective prophylaxis against AMS.
Pathophysiology and management of fever
Authors: Bassi Gabriele , Fumagalli Roberto
Published: April 2016

Core body temperature is strictly regulated by autonomic and behavioural compensatory adaptations and an increase may represent a physiological stereotypical controlled response to septic and inflammatory conditions, or an uncontrolled drop in the hypothalamic thermoregulatory threshold. Fever has been demonstrated to be a potential mechanism of intrinsic resistance against infectious disease playing a pivotal role in the human evolution. High temperature may be detrimental during oxygen delivery-dependent conditions and in a neurological population. Despite this evidence, a definitive conclusion, between the association of fever and the outcome in critically-ill patients, is still lacking. The decision-making strategy in the context of fever management in critical care must be supported by single case assessment. This chapter summarizes the main physiological mechanisms of temperature control that physicians should consider when dealing with fever or deliberate hypothermia and analyses the main evidence in the role of fever in the critically ill in order to help bedside clinical strategy.
Pathophysiology and assessment of pain
Authors: Martin Rebecca E. , MacPherson Ross D.
Published: April 2016

From a clinical viewpoint, pain can generally be classified as nociceptive, visceral, or neuropathic. This distinction is important, as it will help guide pain management strategies. In this section the authors discuss the current state of the art with regard to pain mechanisms at a neuronal and neurotransmitter level. Much has been clarified in recent years to help identify neurotransmitters involved in pain pathways, and target new drugs and treatments. The second part of the chapter discusses assessment of pain in the critical care setting. Assessment of pain severity and of response to treatment is clearly a difficult process in the patient who is unable to communicate verbally. This section discusses the various strategies and assessment protocols that have been formulated to try and assist in this difficult task.
Pain management in the critically ill
Authors: MacPherson Ross D.
Published: April 2016

Despite the fact that patients in the critical care environment are more likely than others to have significant pain, there have been few controlled trials and even fewer examples of high level evidence that can be used to guide pain management. This chapter surveys the main modalities for pain management in the intensive care unit. Parenteral strategies remain the most commonly used form of administration and opioids are still the basis of good pain management. However, in recent times there have been a number of new opioids made available and some of these have a clear application in the critical care environment.In addition to opioids there are a range of adjunct agents that can be usedto give better quality pain relief, while at the same time reducing opioid requirements. Numerous studies have confirmed that pain managementin the critical care environment could be better managed. Strategies to improve pain management are suggested.
Peri-operative optimization of the high risk surgical patient
Authors: Mythen Monty , Grocott Michael P. W.
Published: April 2016

Flow-based cardiovascular variables, such as cardiac output and oxygen delivery predict peri-operative outcome better than alternative, predominantly pressure-based measures. Targeting flow-based goals, using fluid boluses with or without additional blood or vasoactive agents in patients undergoing major surgery has been shown to improve outcome in some studies. However, the literature is limited due to a large number of small single-centre studies, and heterogeneity of interventions and outcomes evaluated. Early studies used pulmonary artery catheters to monitor blood flow, but newer studies have used less invasive techniques, such as oesophageal Doppler monitoring or pulse contour analysis. Meta-analysis of the current evidence base suggests that this approach is unlikely to cause harm and may not reduce mortality, but reduces complications and duration of hospital stay. Goal-directed therapy is considered an important element of enhanced recovery packages that have been shown to improve outcome after several types of major elective surgery.
Post-operative fluid and circulatory management in the ICU
Authors: Ebm Claudia , Rhodes Andrew
Published: April 2016

Fluid and circulatory management is an integral part of the peri-operative care of critically-ill patients. Precisely estimating the volumetric needs of post-operative patients remains difficult. While the majority of patients tolerate intra-operative fluid loss easily, patients with reduced physiological reserve present more of a challenge. Targeting specific physiological goals and optimizing haemodynamics with fluids and inotropes, means outcomes of these patients can be improved. This approach is often referred as goal-directed therapy (GDT). ‘Individualized goal-directed therapy’ can vary in timing, monitoring techniques, and endpoints used. The emergence of minimal invasive devises has allowed us to integrate cardiac output monitoring as a safe and reliable tool in the routine care of high risk patients. This dynamic assessment of haemodynamics provides a reliable technique to assess volume responsiveness and guide fluids to optimize cardiac output and oxygen delivery.
Enhanced surgical recovery programmes in the ICU
Authors: Scott Michael J. , Mythen Monty
Published: April 2016

Enhanced recovery programmes (ERPs) are evidence-based care pathways starting from the point of patient referral right through the peri-operative period until discharge home. The ERP aims to reduce surgical stress and enhance post-operative physiological function with resulting early return of enteral diet and mobilization to improve outcomes. There are 20 evidence-based elements, many of which are delivered by a multidisciplinary team. Many elements support a treatment intervention, but some aim to avoid an intervention, which can negatively impact on recovery. An ERP with good compliance has been shown to reduce length of stay and medical complications. Minimal access surgery, high quality analgesia, and goal-directed fluid therapy are key factors ensuring optimal outcomes. There has been successful adoption and transfer of enhanced recovery principles into many surgical specialties. There is wide variation in the use of critical care within ERPs depending on local policy and patient risk factors.
Pathophysiology and management of pre-eclampsia, eclampsia, and HELLP syndrome
Authors: Noori Muna , Nelson-Piercy Catherine
Published: April 2016

Pre-eclampsia is a multisystem disorder of pregnancy, characterized by the gestational onset of hypertension and proteinuria, which presents as part of a spectrum of disease with potentially serious consequences for both mother and foetus. Pre-eclampsia is a syndrome with multiple aetiologies, which has made it difficult to develop adequate screening tests and treatments. Pre-eclampsia is likely to develop only in vulnerable women with a mix of genetic susceptibility, vascular, metabolic, and inflammatory dysfunction. A number of prepregnancy risk factors for pre-eclampsia have been identified. However, not all women with risk factors develop pre-eclampsia, while many women without do, making it a challenging condition to predict. As pre-eclampsia cannot be prevented, its management remains supportive, with close monitoring of clinical signs and symptoms, antihypertensive therapy, seizure prophylaxis, and ultimately delivery when necessary. This chapter outlines the pathophysiology, diagnosis, and sequelae of pre-eclampsia, and provides an overview of antenatal, intrapartum, and post-natal management of women with pre-eclampsia.
Obstetric Disorders in the ICU
Authors: Levinson Andrew , Bourjeily Ghada
Published: April 2016

Critical illness in pregnancy is a rare, but potentially catastrophic event for the mother and foetus. A thorough understanding of the effective management practices for the most common obstetrical reasons for ICU admission is essential for providing effective critical care to women in the ante-partum and immediate post-partum period. Some of the most common reasons for the need for critical care in the peripartum and post-partum period include venous thromboembolism, post-partum haemorrhage, amniotic fluid embolism, ovarian hyperstimulation syndrome, and obstetric sepsis. Management of these conditions should focus on choosing the most effective diagnostic and therapeutic measures for the mother, while focusing on minimizing foetal harm, accounting for physiological changes that may affect diagnostic strategies and pharmacokinetics.
Intensive care management after cardiothoracic surgery
Authors: Barnard Matthew , Jones Nicola
Published: April 2016

Management of the post-cardiothoracic surgical patient follows general principles of intensive care, but incorporates certain unique considerations. In cardiac surgical patients peri-operative ischaemia, arrhythmias and ventricular dysfunction mandate specific monitoring requirements, and individual pharmacological and mechanical support. Suspicion of myocardial ischaemia should not only lead to pharmacological treatment, but also consideration of urgent angiography to exclude coronary graft occlusion. Ventricular dysfunction may be pre-existing or attributable to intra-operative myocardial ‘stunning’. Catecholamines and phosphodiesterase inhibitors are the mainstay of therapy. Rarely, intra-aortic balloon pumping or ventricular assist devices are required. Significant bleeding (with potential cardiac tamponade), respiratory compromise, acute kidney injury, neurological injury, and deep sternal wound infection each occur in ~2–3% of cardiac surgical patients. Each of these has individual risk factors and specific management considerations. General guidelines for patients who have undergone thoracic surgery include early extubation, fluid restriction, effective analgesia, and protective lung ventilation. Thoracic patients are at risk of atelectasis, respiratory infection, bronchial air leak, and right ventricular failure. Positive pressure ventilation is avoided whenever possible particularly after pneumonectomy, but is sometimes necessary in compromised patients. Air leaks are common. Alveolopleural fistulae usually improve with conservative management,whereas bronchopleural fistulae are more likely to require surgical intervention. Lung surgery is high risk for patients with ischaemic heart disease. Patients with pre-existing elevated pulmonary vascular resistance may exhibit right ventricular dysfunction and may fail to cope with a further increase in pulmonary vascular resistance consequent to lung resection. Lung collapse and infection are constant risks throughout the entire post-operative period.
Intensive care management in hepatic and other abdominal organ transplantation
Authors: Daly Ivonne M. , Al-Khafaji Ali
Published: April 2016

Care of the transplant patient post-operatively requires a multidisciplinary approach. The goal of the intensivist is to create an ideal environment for the allograft to recover from its ischaemic insult and return to normal function. An understanding of the recipient’s pretransplant physiology is essential, as the pathological states associated with organ failure may persist for weeks to months after transplant. In particular, cardiac and renal disease may impact care in the immediate post-transplant period. An understanding of immune suppressive strategies will enable the intensivist to mitigate nephrotoxic side effects of these medications and anticipate specific vulnerabilities to infection. Attention to all the details of good critical care will give the allograft and the recipient the best chance for long-term survival. The intensivist must be able anticipate problems related to surgery and early signs of allograft recovery and dysfunction. Common post-operative complications are described in this chapter.
Management of oncological complications in the ICU
Authors: MacCallum Niall S.
Published: April 2016

Important treatment complications relevant to critical care are discussed. Cancer-related pain is complex and requires multidisciplinary care, particularly in the peri-operative setting. Chemotherapeutic complications include pancytopenia, cardiac, pulmonary, renal, gastrointestinal, hepatic, and neurotoxicity. Radiotherapy complications include cardiac, pulmonary, and gastrointestinal toxicity. In general, management includes assessing the risk-benefit to cytotoxic therapy withdrawal and supportive care. There is a paucity of proven treatment options for most complications, althoughcertain therapies are used to prevent and/or treat complications (e.g. tumour lysis syndrome). Thromboembolic disease is a common cause of mortality and morbidity; low molecular weight heparin therapy may be superior to oral anticoagulation.
Chronic critical illness
Authors: Hough Catherine L.
Published: April 2016

Chronic critical illness (CCI) is common and describes a state of prolonged critical illness, in which patients have persisting organ failures requiring treatment in an intensive care setting. There are many different definitions of CCI, with most including prolonged (> 96 hours) mechanical ventilation. Advanced age, higher severity of illness, and poor functional status prior to critical illness are all important risk factors, but prediction of CCI is imperfect. Although requirement for mechanical ventilation is the hallmark, CCI encompasses much more than the respiratory system, with effects on metabolism, skin, brain, and neuromuscular function. During CCI, patients have a high burden of symptoms and impaired capacity to communicate their needs. Mortality and quality of life are generally poor, but highly variable, with 1-year mortality over 50% and most survivors suffering permanent cognitive impairment and functional dependence. Patients at highest and lowest risk for mortality can be identified using a simple prediction rule. Caring for the chronically critically ill is a substantial burden both to patients’ families and to the health care system as a whole. Further research is needed in order to improve care and outcomes for CCI patients and their families.
Promoting physical recovery in critical illness
Authors: Schmidt Gregory A. , Doerschug Kevin
Published: April 2016

Survivors of critical illnesses are often faced with persistent neuromuscular weakness that interferes with daily activities. Advancements in survival from critical illness have led to a rise in the number of patients afflicted with post-intensive care unit (ICU) incapacity. It is clear that the pathology leading to ICU-acquired weakness is present within 24 hours of the start of ICU care. Care-givers must consider interventions to limit or reverse these processes from the onset of critical illness. We suggest strategies both for avoiding harms and for actively promoting recovery of skeletal and respiratory muscles. Muscular silence contributes to, while muscular activity alleviates, myopathy. Thus, limiting sedation and neuromuscular blockade will facilitate spontaneous muscle activity, and allow for active participation in physical therapy. Protocols that aggressively assess for the potential for extubation shorten the duration of ventilation and thus decrease exposure to sedation. Mobility teams should safely guide patients in their progress from a passive range of motion through more active therapies despite ongoing critical illness. Early ICU mobility is not only safe, but reduces the incidence of delirium and duration of mechanical ventilation. Importantly, early ICU mobility increases the likelihood of a return to independent function among ICU survivors. A change in culture from one that practices deep sedation and protective support is suggested, to one that demonstrates an urgency to liberate patients from the confines and perils of critical illness.
Promoting renal recovery in critical illness
Authors: Srisawat Nattachai , Kellum John A.
Published: April 2016

Better understanding the process of renal recovery following acute kidney injury (AKI) is one of the key steps in improving AKI outcome. We are still lacking the standard definition of renal recovery. Recent progress on the pathophysiology of renal injury and recovery is encouraging. Repopulation of surviving renal tubular epithelial cells with the assistance of certain renal epithelial cell and specific growth factors, play a major role in the recovery process. Moreover, accurate prediction would help physicians distinguish patients with poor renal prognosis in whom further therapy is likely to be futile from those who are likely to have good renal prognosis. Unfortunately, current general clinical severity scores (APACHE, SOFA, etc.) and AKI-specific severity scores are not good predictors of renal recovery. This review describes the current definition, pathobiology of renal recovery, epidemiology of renal recovery, the role of clinical severity scores, and novel biomarkers in predicting renal recovery, and strategies for facilitating renal recovery.
Physical consequences of critical illness
Authors: Herridge Margaret S. , Batt Jane
Published: April 2016

Critical illness is an important life event with a lasting legacy. Patients acquire new nerve, brain, and muscle injury, and sustain important functional dependencies that have clear consequences for subsequent health-related quality of life. Intensive care unit (ICU)-acquired weakness is a prevalent and likely ubiquitous consequence of severe illness. Patients degrade their skeletal muscle within hours of ICU admission through upregulation of different proteolytic pathways, regardless of the inciting aetiology. This may support an approach to muscle injury, sustained disability and subsequent approach to rehabilitation that is aetiologically neutral, and linked to molecular pathophysiology and associated functional outcome. The physical devastation of critical illness affects the entire family unit and family caregivers need to be acknowledged as important risk modifiers for outcome and have their needs addressed as part of an interprofessional rehabilitation intervention.
Long-term weaning centres in critical care
Authors: Kahn Jeremy M.
Published: April 2016

Successfully weaning patients from prolonged mechanical ventilation requires the varied expertise of a dedicated multidisciplinary care team. Traditionally, this care was provided in acute care hospitals, increasingly these patients are transferred to specialized weaning centres. These may improve patient outcomes by concentrating weaning expertise in a low-acuity environment and implementing protocols for liberation from mechanical ventilation. However, these centres might also worsen patient outcomes because they typically offer less intense nurse and physician staffing compared with traditional intensive care units. Generally, the clinical evidence is mixed, with the best studies suggesting that weaning centres offer similar outcomes as acute care hospitals, but at lower costs. Health systems also might stand to gain from dedicated weaning centres, because they can release intensive care unit beds for more acutely-ill patients. Many gaps remain in our understanding of which patients should be transferred to dedicated weaning centres, the optimal timing of transfer, and the best approach to care for patients in this highly specialized setting.
Rehabilitation from critical illness after hospital discharge
Authors: Vincent Laura , Waldmann Carl
Published: April 2016

The majority of patients admitted to intensive care units survive to hospital discharge, but then face a long and challenging functional recovery, due to the physical and psychological sequelae of their critical illness. There is associated physical, emotional, and financial strain on families and care-givers, in addition to the ongoing impact on patients themselves. The optimization of post-ICU morbidity and ‘health-related quality of life’ have thus become key components of the critical care treatment pathway. Structured exercise rehabilitation programmes, tailored to the specific needs of individual patients can enhance the long-term recovery from critical illness, but the practical implementation of such programmes remains inconsistent and non-standardized. Validated screening and assessment tools are being developed to identify those patients who would benefit from post-ICU rehabilitation programmes, target the specific needs of individuals and monitor the response to treatment. Ongoing research aims to determine the features of a successful post-ICU rehabilitation programme, with respect to the location and supervision of the regime, and the actual content of the intervention. Rehabilitation commenced as soon as possible after hospital discharge is likely to be most effective, but further evidence is required to identify the timing of treatment that would achieve the optimal therapeutic impact. The National Institute of Clinical Excellence have issued a post-ICU rehabilitation guideline. As well as providing a framework for implementation of such a programme, this further endorses the understanding that exercise rehabilitation can no longer be considered an afterthought and should be fully incorporated into the critical care treatment pathway.
Ethical decision making in withdrawing and withholding treatment
Authors: Isaac Margaret , Curtis Jared Randall
Published: April 2016

Many patients in the USA and across the world die after having received care in an intensive care unit (ICU). Allocating resources equitably and honouring the wishes of patients and their families are essential components of intensive care. Physician and patient preferences regarding end-of-life care and regarding decision control vary by individual, region, and country, shaped and influenced by a variety of factors including cultural and religious beliefs. Surrogate decision-makers are widely called upon to perform a difficult task—to help make decisions when patients lack capacity or the ability to communicate their preferences. Communication between clinicians and families in the ICU can be enhanced by using a variety of techniques. Advance directives can help guide surrogate decision-makers and physicians. Additionally, discussions of cardiopulmonary resuscitation preferences can be improved by explicit discussions of prognosis, which can help patients and surrogate decision-makers more accurately understand the potential risks and benefits of their decisions.
Beating heart organ donation
Authors: Smith Martin
Published: April 2016

Transplantation is the optimal treatment of end-stage dysfunction of many organs and can be life-saving. Despite increases in live donation and donation after circulatory death, donation after brain death remains the most important source of donor organs, and is currently the only source of thoracic organs in most countries. Brain death is associated with profound physiological changes including cardiovascular and respiratory changes, and severe metabolic and endocrine dysfunction that can jeopardize transplantable organ function. Although adequate time must be allowed for the proper confirmation of brain death, unnecessary delays should be avoided because the incidence of systemic complications that jeopardize transplantable organ function increases progressively with time. Aggressive donor management increases the number of potential donors who actually become donors, increases the total number of organs transplanted per donor, and improves transplantation outcomes. Various donor management strategies have been described and these are reviewed in this chapter.
Non-heart-beating organ donation
Authors: Rady Mohamed Y. , Joffe Ari R.
Published: April 2016

The transplantation community endorses controlled and uncontrolled non-heart-beating organ donation (NHBD) to increase the supply of transplantable organs at end of life. Cardiac arrest must occur within 1–2 hours after the withdrawal of life-support in controlled NHBD. Uncontrolled NHBD is performed after failed cardiopulmonary resuscitation in an unexpected witnessed cardiac arrest. Donor management aims to protect transplantable organs against warm ischaemic injury through the optimization of haemodynamics and mechanical ventilation. This also requires antemortem instrumentation and systemic anticoagulation for organ perseveration in controlled NHBD. Interval support with extracorporeal membrane oxygenation or cardiopulmonary bypass is generally required for optimal organ perfusion and oxygenation in uncontrolled NHBD, which remains a controversial medical practice. There are several unresolved ethical challenges. The circulatory criterion of 2–10 minutes of absent arterial pulse does not comply with the uniform determination of death criterion of the irreversible cessation of functions of the cardiovascular or central nervous systems. There are no robust safeguards in clinical practice that can prevent faulty prognostication, and premature withdrawal of treatment or termination of cardiopulmonary resuscitation. Unmanaged conflicting interests of increasing the supply of transplantable organs can have serious consequences on the medical care of potentially salvageable patients. Perimortem interventions can interfere with the delivery of an optimal quality of end-of-life care. The lack of disclosure of these NHBD ethical controversies does not uphold the moral obligation for an informed consent.
Cutaneous malignancy
Authors: Fowell Christopher , Rehman Khaleeq-Ur
Published: April 2016

Cutaneous malignancy is on the rise in the UK with over 100,000 new cases per year. Currently there are very clear guidelines for the multidisciplinary team to manage this group of diseases. We present three case histories covering morphoeic basal cell carcinoma, lentigo maligna melanoma, and a squamous cell carcinoma of the scalp. The management of all these cases involves surgery at some point but the non-surgical management of cutaneous malignancy is comprehensively covered. The current British Association of Dermatologists Guidelines on the management of skin cancer are discussed in reference to these cases.
Reconstructive challenges following blast injuries to the facial soft tissue and skeleton
Authors: McMillan Kevin , Martin Tim
Published: April 2016

The complex trauma seen in the battlefield provides valuable lessons for the civilian oral and maxillofacial surgeon. The nature of the current body armour places the facial skeleton at significant risk from blast injuries and these pose a challenge for the reconstructive surgeon. We present a case of a soldier who sustained multiple injuries from an improvised explosive device and presented in a physiologically compromised state. From a maxillofacial point of view there was a comminuted fracture of the mandible with a soft tissue defect of 6 cm × 5 cm in the chin area. He was treated initially with arch bars and an external fixator and the wound was packed. Over time the wound contracted and healed with no further intervention. This case demonstrates how systemic compromise may affect the initial treatment plan but an excellent outcome can still be achieved.
Efficacy of Diffusion Tensor Imaging Indices in Assessing Postoperative Neural Recovery in Cervical Spondylotic Myelopathy
Authors: Rajasekaran S. , Kanna Rishi M. , Chittode Vishnuprasath S. , Maheswaran Anupama , Aiyer Siddharth N. , Shetty Ajoy P.
Published: April 2016

Study Design.

Prospective observational cohort study.

Objective.

The aim of this study was to analyze the efficacy of diffusion tensor imaging (DTI) anisotropy indices in predicting the postoperative recovery in cervical spondylotic myelopathy (CSM) patients and to describe postoperative changes in the DTI indices based on neurological recovery after surgery.

Summary of Background Data.

Surgical results of CSM are unpredictable and cannot be estimated based on preoperative MRI. DTI indices were found to have good sensitivity to detect changes in CSM, but their efficacy in predicting postoperative recovery and postoperative changes in DTI indices has not been studied before.

Methods.

Thirty-five patients who underwent surgical decompression for cervical spondylotic myelopathy underwent DTI evaluation preoperatively and postoperatively at 12 months. DTI indices—fractional anisotropy, apparent diffusion coefficient (ADC), relative anisotropy, volume ratio, and eigen vectors (E1, E2, and E3)—were obtained and clinical evaluations were made preoperatively and 12 months postoperatively.

Results.

Twenty-six patients were available for final follow-up at 12 months. Twenty patients showed improvement by at least 1 Nurick grade, five maintained the preoperative Nurick grade status and one patient was noted to have deterioration by 1 grade. The preoperative DTI values could not predict neurological recovery patterns postoperatively. Although conventional MRI showed adequate decompression in all patients irrespective of the clinical outcome, DTI indices showed variable results. There were significant improvements in postoperative DTI indices for ADC (P = 0.002), E1 (P < 0.001), and E2 (P = 0.012) values in patients who showed neurological recovery at 12 months. Postoperative DTI indices for coefficients ADC, E1, and E2 in neurologically static/worsened individuals remained unchanged or insignificant (P = 0.05)

Conclusion.

The DTI indices were sensitive enough to indicate postoperative neurological recovery observed following surgery. Preoperative DTI evaluation could not predict postoperative recovery for patients with cervical spondylotic myelopathy.

Level of Evidence: 4
Family Burden After Out-of-Hospital Cardiac Arrest in Children
Authors: Meert Kathleen L. , Slomine Beth S. , Christensen James R. , Telford Russell , Holubkov Richard , Dean J. Michael , Moler Frank W.
Published: April 2016

Objectives:

To describe family burden among caregivers of children who survived out-of-hospital cardiac arrest and who were at high risk for neurologic disability and examine relationships between family burden, child functioning, and other factors during the first year post arrest.

Design:

Secondary analysis of data from the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial.

Setting:

Thirty-six PICUs in the United States and Canada.

Patients:

Seventy-seven children recruited to the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial who had normal prearrest neurologic functioning and were alive 1 year post arrest.

Interventions:

Family burden was assessed using the Infant Toddler Quality of Life Questionnaire for children less than 5 years old and the Child Health Questionnaire for children 5 years old or older at baseline (reflecting prearrest status), 3 months, and 12 months post arrest. Child functioning was assessed using the Vineland Adaptive Behavior Scale II, the Pediatric Overall Performance Category, and Pediatric Cerebral Performance Category scales and caregiver perception of global functioning.

Measurements and Main Results:

Fifty-six children (72.7%) were boys, 48 (62.3%) were whites, and 50 (64.9%) were less than 5 years old prior to out-of-hospital cardiac arrest. Family burden at baseline was not significantly different from reference values. Family burden was increased at 3 and 12 months post arrest compared with reference values (p < 0.001). Worse Pediatric Overall Performance Category and Pediatric Cerebral Performance Category, lower adaptive behavior, lower global functioning, and higher family burden all measured 3 months post arrest were associated with higher family burden 12 months post arrest (p < 0.05). Sociodemographics and prearrest child functioning were not associated with family burden 12 months post arrest.

Conclusions:

Families of children who survive out-of-hospital cardiac arrest and have high risk for neurologic disability often experience substantial burden during the first year post arrest. The extent of child dysfunction 3 months post arrest is associated with family burden at 12 months.
A Novel Surgical Approach to Chronic Temporal Headaches
Authors: Peled Ziv M.
Published: April 2016

The targets for the surgical treatment of temporal headaches are the zygomaticotemporal branch of the trigeminal nerve and the auriculotemporal nerve. The former is often accessed by means of an endoscopic brow approach or potentially by laterally extending a transpalpebral incision. An established surgical approach, the Gillies incision, was modified to access the zygomaticotemporal nerve, as it was felt to combine the advantages of the traditional techniques. Nineteen patients underwent zygomaticotemporal nerve decompression and neuroplasty or neurectomy and muscle implantation using this surgical approach. A 3.5-cm incision was made behind the anterior, temporal hairline and the zygomaticotemporal branch of the trigeminal nerve was approached directly, remaining superficial to the deep temporal fascia. Each patient was assessed preoperatively and postoperatively with regard to the frequency, duration, and severity of their symptoms to calculate a Migraine Headache Index score. All evaluations were performed at least 1 year postoperatively. The mean preoperative Migraine Headache Index score was 131.7 and the mean postoperative score was 52 (p < 0.0001). There were no surgical complications. There appeared to be no differences between those patients that had decompression and neuroplasty versus those that underwent neurectomy and implantation, as both groups experienced significant reductions in Migraine Headache Index scores following the procedure. The anterior temporal approach to the zygomaticotemporal nerve is both safe and effective. The advantages of this approach include a hidden scar, the ability to directly manipulate the nerve for transection or preservation, and access to the auriculotemporal nerve through the same incision.
A Quantitative Analysis of OnabotulinumtoxinA, AbobotulinumtoxinA, and IncobotulinumtoxinA: A Randomized, Double-Blind, Prospective Clinical Trial of Comparative Dynamic Strain Reduction
Authors: Wilson Anthony J. , Chang Brian , Taglienti Anthony J. , Chin Bianca C. , Chang Catherine S. , Folsom Nancy , Percec Ivona
Published: April 2016

Background:

U.S. Food and Drug Administration–approved formulations of botulinum toxin include onabotulinumtoxinA (Botox; Allergan, Inc., Irvine, Calif.), abobotulinumtoxinA (Dysport; Galderma Pharma S.A., Lausanne, Switzerland), and incobotulinumtoxinA (Xeomin; Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany). This study uses digital image correlation to compare dynamic strain reduction between available neurotoxins.

Methods:

Seventy-three treatment-naive female patients aged were randomized to injection with onabotulinumtoxinA (20 units), abobotulinumtoxinA (60 units), or incobotulinumtoxinA (20 units) in the glabella. Imaging was conducted at 4, 14, and 90 days after injection. Change in average dynamic strain of the glabella was compared using ANOVA.

Results:

At day 4, there was a 42.1 percent strain reduction in the onabotulinumtoxinA group, a 39.4 percent strain reduction in the abobotulinumtoxinA group, and a 19.8 percent strain reduction in the incobotulinumtoxinA group (onabotulinumtoxinA versus abobotulinumtoxinA, p = 0.77; onabotulinumtoxinA versus incobotulinumtoxinA, p = 0.02; and abobotulinumtoxinA versus incobotulinumtoxinA, p = 0.04). At day 14, there was a 66.1 percent strain reduction in the onabotulinumtoxinA group, a 51.4 percent strain reduction in the abobotulinumtoxinA group, and a 42.8 percent strain reduction in the incobotulinumtoxinA group (onabotulinumtoxinA versus abobotulinumtoxinA, p = 0.14; onabotulinumtoxinA versus incobotulinumtoxinA, p = 0.02; and abobotulinumtoxinA versus incobotulinumtoxinA, p = 0.36). At day 90, there was a 43.5 percent strain reduction in the onabotulinumtoxinA group, a 38.4 percent strain reduction in the abobotulinumtoxinA group, and a 25.3 percent strain reduction in the incobotulinumtoxinA group (onabotulinumtoxinA versus abobotulinumtoxinA, p = 0.66; onabotulinumtoxinA versus incobotulinumtoxinA, p = 0.12; and abobotulinumtoxinA versus incobotulinumtoxinA, p = 0.24).

Conclusions:

Using digital image correlation, the tested neuromodulators do not have equivalent strain reduction in the glabella at the doses used. These results confirm assertions of noninterchangeability.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Interventions to Decrease Postoperative Edema and Ecchymosis after Rhinoplasty: A Systematic Review of the Literature
Authors: Ong Adrian A. , Farhood Zachary , Kyle Andrew R. , Patel Krishna G.
Published: April 2016

Background:

Today, minimally invasive procedures are becoming more popular because of the fast recovery. Rhinoplasty is a common facial plastic surgery procedure that can be associated with significant postoperative morbidities, especially periorbital edema and ecchymosis. The aim of this review is to summarize the results of published literature that studied interventions that decrease postoperative edema and ecchymosis after rhinoplasty, and provide evidence-based strategies for surgeons to incorporate into practice.

Methods:

A systematic review of the PubMed, Scopus, and EMBASE databases was performed to investigate interventions studied to decrease postoperative edema and ecchymosis after rhinoplasty. After inclusion and exclusion criteria were applied, articles were grouped into one of the following categories: corticosteroids, other medications and herbal supplements, interventions to decrease intraoperative bleeding, other postoperative interventions, and surgical techniques.

Results:

A total of 50 articles were included for review. Fourteen articles studied corticosteroids exclusively, whereas another 10 articles reviewed other medications and herbal supplements. Nine articles evaluated methods to decrease intraoperative bleeding during rhinoplasty, and four articles studied postoperative interventions to decrease edema and ecchymosis. Thirteen articles studied various surgical techniques to decrease postoperative morbidities.

Conclusions:

There was a consensus within the literature that steroids, intraoperative hypotension, intraoperative cooling, and head elevation postoperatively decrease postoperative edema and ecchymosis, whereas nasal packing and periosteal elevation before osteotomy increased these postoperative morbidities. Studies of herbal supplements may be incorporated into practice with minimal risk to the patient. More studies must be performed before recommending an external or internal approach to lateral osteotomy.
Nonlinear regularization operators as derived from the micromorphic approach to gradient elasticity, viscoplasticity and damage
Authors: Forest Samuel
Published: April 2016

The construction of regularization operators presented in this work is based on the introduction of strain or damage micromorphic degrees of freedom in addition to the displacement vector and of their gradients into the Helmholtz free energy function of the constitutive material model. The combination of a new balance equation for generalized stresses and of the micromorphic constitutive equations generates the regularization operator. Within the small strain framework, the choice of a quadratic potential w.r.t. the gradient term provides the widely used Helmholtz operator whose regularization properties are well known: smoothing of discontinuities at interfaces and boundary layers in hardening materials, and finite width localization bands in softening materials. The objective is to review and propose nonlinear extensions of micromorphic and strain/damage gradient models along two lines: the first one introducing nonlinear relations between generalized stresses and strains; the second one envisaging several classes of finite deformation model formulations. The generic approach is applicable to a large class of elastoviscoplastic and damage models including anisothermal and multiphysics coupling. Two standard procedures of extension of classical constitutive laws to large strains are combined with the micromorphic approach: additive split of some Lagrangian strain measure or choice of a local objective rotating frame. Three distinct operators are finally derived using the multiplicative decomposition of the deformation gradient. A new feature is that a free energy function depending solely on variables defined in the intermediate isoclinic configuration leads to the existence of additional kinematic hardening induced by the gradient of a scalar micromorphic variable.
Numerical solution of acoustic scattering by finite perforated elastic plates
Authors: Cavalieri A. V. G. , Wolf W. R. , Jaworski J. W.
Published: April 2016

We present a numerical method to compute the acoustic field scattered by finite perforated elastic plates. A boundary element method is developed to solve the Helmholtz equation subjected to boundary conditions related to the plate vibration. These boundary conditions are recast in terms of the vibration modes of the plate and its porosity, which enables a direct solution procedure. A parametric study is performed for a two-dimensional problem whereby a cantilevered perforated elastic plate scatters sound from a point quadrupole near the free edge. Both elasticity and porosity tend to diminish the scattered sound, in agreement with previous work considering semi-infinite plates. Finite elastic plates are shown to reduce acoustic scattering when excited at high Helmholtz numbers
k
0
based on the plate length. However, at low
k
0
, finite elastic plates produce only modest reductions or, in cases related to structural resonance, an increase to the scattered sound level relative to the rigid case. Porosity, on the other hand, is shown to be more effective in reducing the radiated sound for low
k
0
. The combined beneficial effects of elasticity and porosity are shown to be effective in reducing the scattered sound for a broader range of
k
0
for perforated elastic plates.
Biogeographic and bathymetric determinants of brachiopod extinction and survival during the Late Ordovician mass extinction
Authors: Finnegan Seth , Rasmussen Christian M. Ø. , Harper David A. T.
Published: April 2016

The Late Ordovician mass extinction (LOME) coincided with dramatic climate changes, but there are numerous ways in which these changes could have driven marine extinctions. We use a palaeobiogeographic database of rhynchonelliform brachiopods to examine the selectivity of Late Ordovician–Early Silurian genus extinctions and evaluate which extinction drivers are best supported by the data. The first (latest Katian) pulse of the LOME preferentially affected genera restricted to deeper waters or to relatively narrow (less than 35°) palaeolatitudinal ranges. This pattern is only observed in the latest Katian, suggesting that it reflects drivers unique to this interval. Extinction of exclusively deeper-water genera implies that changes in water mass properties such as dissolved oxygen content played an important role. Extinction of genera with narrow latitudinal ranges suggests that interactions between shifting climate zones and palaeobiogeography may also have been important. We test the latter hypothesis by estimating whether each genus would have been able to track habitats within its thermal tolerance range during the greenhouse–icehouse climate transition. Models including these estimates are favoured over alternative models. We argue that the LOME, long regarded as non-selective, is highly selective along biogeographic and bathymetric axes that are not closely correlated with taxonomic identity.
Paradoxical signaling regulates structural plasticity in dendritic spines
Authors: Rangamani Padmini , Levy Michael G. , Khan Shahid M. , Oster George
Published: April 2016

Transient spine enlargement (3-5 min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine en­largement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium-influx due to NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop. Paradoxical components act bifunctionally in signaling net­works and their role is to control both the activation and inhibition of a desired response function (protein activity or spine volume). Using ordinary differential equation (ODE)-based modeling, we show that the dynamics of different regulators of transient spine expansion including CaMKII, RhoA, and Cdc42 and the spine volume can be described using paradoxical signaling loops. Our model is able to capture the experimentally observed dynamics of transient spine volume. Furthermore, we show that actin remod­eling events provide a robustness to spine volume dynamics. We also generate experimentally testable predictions about the role of different components and parameters of the network on spine dynamics.
Predicting Drug Synergy and Antagonism from Genetic Interaction Neighborhoods
Authors: Young Jonathan H. , Marcotte Edward M.
Published: April 2016

Although drug combinations have proven efficacious in a variety of diseases, the design of such regimens often involves extensive experimental screening due to the myriad choice of drugs and doses. To address these challenges, we utilize the budding yeast Saccharomyces cerevisiae as a model organism to evaluate whether drug synergy or antagonism is mediated through genetic interactions between their target genes. Specifically, we hypothesize that if the inhibition targets of one chemical compound are in close proximity to those of a second compound in a genetic interaction network, then the compound pair will exhibit synergy or antagonism. Graph metrics are employed to make precise the notion of proximity in a network. Knowledge of genetic interactions and small-molecule targets are compiled through literature sources and curated databases, with predictions validated according to experimentally determined gold standards. Finally, we test whether genetic interactions propagate through networks according to a “guilt-by-association” framework. Our results suggest that close proximity between the target genes of one drug and those of another drug does not strongly predict synergy or antagonism. In addition, we find that the extent to which the growth of a double gene mutant deviates from expectation is moderately anti-correlated with their distance in a genetic interaction network.