Transfusion practices in traumatic brain injury

Purpose of review The aim of this review is to summarize the recent studies looking at the effects of anemia and red blood cell transfusion in critically-ill patients with traumatic brain injury (TBI), describe the transfusion practice variations observed worldwide, and outline the ongoing trials evaluating restrictive versus liberal transfusion strategies for TBI. Recent findings Anemia is common among critically-ill patients with TBI, it is also thought to exacerbate secondary brain injury, and is associated with an increased risk of poor outcome. Conversely, allogenic red blood cell transfusion carries its own risks and complications, and has been associated with worse outcomes. Globally, there are large reported differences in the hemoglobin threshold used for transfusion after TBI. Observational studies have shown differential results for improvements in cerebral oxygenation and metabolism after red blood cell transfusion in TBI. Summary Currently, there is insufficient evidence to make strong recommendations regarding which hemoglobin threshold to use as a transfusion trigger in critically-ill patients with TBI. There is also uncertainty whether the restrictive transfusion strategy used in general critical care can be extrapolated to acutely brain injured patients. Ultimately, the consequences of anemia-induced cerebral injury need to be weighed up against the risks and complications associated with red blood cell transfusion. Correspondence to Victoria A. McCredie, MBChB, PhD, Department of Critical Care Medicine, 2nd Floor McLaughlin Rm 411-J, Toronto Western Hospital, University Health Network, 399 Bathurst St, Toronto, Canada M5T 2S8. Tel: +1 416 302 1959; e-mail: Victoria.McCredie@uhn.ca Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Staff and family response to end-of-life care in the ICU

Purpose of review End-of-life (EOL) care can be stressful for clinicians as well as patients and their relatives. Decisions to withhold or withdraw life-sustaining therapy vary widely depending on culture, beliefs and organizational norms. The following review will describe the current understanding of the problem and give an overview over interventional studies. Recent findings EOL care is a risk factor for clinician burnout; poor work conditions contribute to emotional exhaustion and intent to leave. The impact of EOL care on families is part of the acute Family Intensive Care Unit Syndrome (FICUS) and the Post Intensive Care Syndrome–Family (PICS-F). Family-centered care (FCC) acknowledges the importance of relatives in the ICU. Several interventions have been evaluated, but evidence for their effectiveness is at best moderate. Some interventions even increased family stress. Interventional studies, which address clinician burnout are rare. Summary EOL care is associated with negative outcomes for ICU clinicians and relatives, but strength of evidence for interventions is weak because we lack understanding of associated factors like work conditions, organizational issues or individual attitudes. In order to develop complex interventions that can successfully mitigate stress related to EOL care, more research is necessary, which takes into account all potential determinants. Correspondence to Dr Konrad Reinhart, ML, Senior Professor, Jena University Hospital, Chairman Global Sepsis Alliance, Paul-Schneider-Street 2, 07747 Jena, Germany. E-mail: konrad.reinhart@med.uni-jena.de Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Pediatric trauma transfusion and cognitive aids

Purpose of review Trauma is the most common cause of pediatric mortality. Much of the research that led to life-saving interventions in adults, however, has not been replicated in the pediatric population. Children have important physiologic and anatomic differences from adults, which impact hemostasis and transfusion. Hemorrhage is a leading cause of death in trauma, and children have important differences in their coagulation profiles. Transfusion strategies, including the massive transfusion protocol and use of antifibrinolytics, are still controversial. In addition to the blood that is lost from the injury itself, trauma leads to inflammation and to a dysfunction in hemostasis, causing coagulopathy. Recent findings In one study in which children suffered from mainly blast and penetrating injuries in a combat setting (PEDTRAX trial), the early administration of tranexamic acid was associated with decreased mortality. Some authors suggest that this result may not apply to blunt trauma, which is much more common in children in noncombat settings. Using thromboelastography to guide the administration of recombinant Factor VIIa has been done in selected cases and may represent a future avenue of research. Summary This article explores new research from the past year in pediatric trauma, starting with the physiologic differences in pediatric red blood cells and coagulation profiles. We also looked at the dramatic change in thinking over the past decade in the tolerable level of anemia in critically ill pediatric patients, as well as scales for determining the need for massive transfusion and exploring if the concepts of damage control resuscitation apply to children. Other strategies, such as avoiding hypothermia, and the selective administration of antifibriniolytics, are important in pediatric trauma as well. Future research that is pediatric focused is needed for the optimal care of our youngest patients. Correspondence: Anna Clebone, MD, Assistant Professor, Department of Anesthesia and Critical Care, University of Chicago, 5841 S. Maryland Ave. MC-4028, Chicago, IL 60637, USA. Tel: +773 702 6700; e-mail: aclebone@dacc.uchicago.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Spirituality at the end of life

Purpose of review There is increasing emphasis on medical care of the whole patient. This holistic approach encompasses supporting the spiritual or religious needs of the patient. Particularly at the end of life, spiritual concerns may come to the fore as patients recognize and accept their impending death. Physicians may also recognize this spiritual distress but may not be clear on how to provide spiritual support. Recent findings Tools to screen for spiritual concerns are available for physicians to use. Some physicians wish to go further, supporting patients at the end of life in their spiritual quest. Other physicians express concern about causing more distress to patients in a time of significant need. Descriptions of educational tools, as well as the difference between spiritual generalists and spiritual specialists have emerged. Integration of chaplains into the medical team caring for patients at the end of life will also enhance care of the whole patient. Summary The increasing emphasis on whole patient care is leading to increasing focus on spiritual concerns of patients. Although not every patient has an interest in spiritual conversation, most do and medical teams will need to become more educated about appropriate spiritual engagement. Correspondence to Cynthiane J. Morgenweck, MD, MA, Center for Bioethics and Medical Humanities, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Tel: +1 414 955 8498; e-mail: cmorg@mcw.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Nutrition Screening and Therapy Within a Surgical Enhanced Recovery Pathway

Perioperative malnutrition has proven to be challenging to define, diagnose, and treat. Despite these challenges, it is well known that suboptimal nutritional status is a strong independent predictor of poor postoperative outcomes. Although perioperative caregivers consistently express recognition of the importance of nutrition screening and optimization in the perioperative period, implementation of evidence-based perioperative nutrition guidelines and pathways in the United States has been quite limited and needs to be addressed in surgery-focused recommendations. The second Perioperative Quality Initiative brought together a group of international experts with the objective of providing consensus recommendations on this important topic with the goal of (1) developing guidelines for screening of nutritional status to identify patients at risk for adverse outcomes due to malnutrition; (2) address optimal methods of providing nutritional support and optimizing nutrition status preoperatively; and (3) identifying when and how to optimize nutrition delivery in the postoperative period. Discussion led to strong recommendations for implementation of routine preoperative nutrition screening to identify patients in need of preoperative nutrition optimization. Postoperatively, nutrition delivery should be restarted immediately after surgery. The key role of oral nutrition supplements, enteral nutrition, and parenteral nutrition (implemented in that order) in most perioperative patients was advocated for with protein delivery being more important than total calorie delivery. Finally, the role of often-inadequate nutrition intake in the posthospital setting was discussed, and the role of postdischarge oral nutrition supplements was emphasized. Accepted for publication October 27, 2017. Funding: The Perioperative Quality Initiative (POQI) meeting received financial assistance from the American Society for Enhanced Recovery (ASER). Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). For the Perioperative Quality Initiative (POQI) 2 Workgroup, see Supplemental Digital Content, Appendix 1, http://ift.tt/2n5LfOn. Reprints will not be available from the authors. Address correspondence to Timothy E. Miller, MB, ChB, FRCA, Division of General, Vascular and Transplant Anesthesia, Duke University Medical Center, Box 3094, Durham, NC 27710. Address e-mail to timothy.miller2@duke.edu. © 2018 International Anesthesia Research Society

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Age Does Not Affect Metoprolol’s Effect on Perioperative Outcomes (From the POISE Database)

BACKGROUND: Perioperative β-blockade reduces the incidence of myocardial infarction but increases that of death, stroke, and hypotension. The elderly may experience few benefits but more harms associated with β-blockade due to a normal effect of aging, that of a reduced resting heart rate. The tested hypothesis was that the effect of perioperative β-blockade is more significant with increasing age. METHODS: To determine whether the effect of perioperative β-blockade on the primary composite event, clinically significant hypotension, myocardial infarction, stroke, and death varies with age, we interrogated data from the perioperative ischemia evaluation (POISE) study. The POISE study randomly assigned 8351 patients, aged ≥45 years, in 23 countries, undergoing major noncardiac surgery to either 200 mg metoprolol CR daily or placebo for 30 days. Odds ratios or hazard ratios for time to events, when available, for each of the adverse effects were measured according to decile of age, and interaction term between age and treatment was calculated. No adjustment was made for multiple outcomes. RESULTS: Age was associated with higher incidences of the major outcomes of clinically significant hypotension, myocardial infarction, and death. Age was associated with a minimal reduction in resting heart rate from 84.2 (standard error, 0.63; ages 45–54 years) to 80.9 (standard error, 0.70; ages >85 years; P

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Using the Ventrain With a Small-Bore Catheter: Ventilation or Just Oxygenation?

No abstract available

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The Effects of Agrin Isoforms on Diabetic Neuropathic Pain in a Rat Streptozotocin Model

BACKGROUND: Diabetes mellitus affects 9.3% of the US population and increases risks of surgery and complications. Diabetic neuropathic pain (DNP), one of the main consequences of diabetes mellitus, is extremely difficult to treat. Current medications yield limited benefits and/or have severe adverse effects. Therefore, new, effective treatment is needed. METHODS: Streptozotocin at 55 mg/kg was injected intraperitoneally in rats to induce diabetes mellitus. Diabetic rats exhibiting neuropathic pain underwent intrathecal injection of purified agrin proteins at various doses and were then tested for tactile allodynia to evaluate whether DNP was inhibited. The agrin effects were also analyzed with patch-clamp recording on spinal cord slices. RESULTS: Fifty–kilo Dalton agrin (Agr50) at 0.2 and 2 ng suppressed DNP when given intrathecally, while 25- and 75-kDa agrin (Agr25, Agr75) had little effect. The suppressive effect of Agr50 lasted 4 hours after a single bolus injection. The difference in effects of Agr50 on mean withdrawal threshold (4.6 ± 2.2 g before treatment to 26 ± 0 g after treatment) compared with that of Agr25 (4.9 ± 2.0 g to 4.9 ± 2.0 g) and Agr75 (5.3 ± 2.3 g to 9.2 ± 2.5 g) was highly significant (P

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Electroencephalography and Brain Oxygenation Monitoring in the Perioperative Period

Maintaining brain function and integrity is a pivotal part of anesthesiological practice. The present overview aims to describe the current role of the 2 most frequently used monitoring methods for evaluation brain function in the perioperative period, ie, electroencephalography (EEG) and brain oxygenation monitoring. Available evidence suggests that EEG-derived parameters give additional information about depth of anesthesia for optimizing anesthetic titration. The effects on reduction of drug consumption or recovery time are heterogeneous, but most studies show a reduction of recovery times if anesthesia is titrated along processed EEG. It has been hypothesized that future EEG-derived indices will allow a better understanding of the neurophysiological principles of anesthetic-induced alteration of consciousness instead of the probabilistic approach most often used nowadays. Brain oxygenation can be either measured directly in brain parenchyma via a surgical burr hole, estimated from the venous outflow of the brain via a catheter in the jugular bulb, or assessed noninvasively by near-infrared spectroscopy. The latter method has increasingly been accepted clinically due to its ease of use and increasing evidence that near-infrared spectroscopy–derived cerebral oxygen saturation levels are associated with neurological and/or general perioperative complications and increased mortality. Furthermore, a goal-directed strategy aiming to avoid cerebral desaturations might help to reduce these complications. Recent evidence points out that this technology may additionally be used to assess autoregulation of cerebral blood flow and thereby help to titrate arterial blood pressure to the individual needs and for bedside diagnosis of disturbed autoregulation. Accepted for publication December 8, 2017. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Thomas W. L. Scheeren, MD, PhD, Department of Anaesthesiology, University Medical Center Groningen, PO Box 30 001, 9700 RB Groningen, the Netherlands. Address e-mail to t.w.l.scheeren@umcg.nl. © 2018 International Anesthesia Research Society

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In Response

No abstract available

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Comparison of Intranasal Dexmedetomidine and Oral Pentobarbital Sedation for Transthoracic Echocardiography in Infants and Toddlers: A Prospective, Randomized, Double-Blind Trial

BACKGROUND: Acquisition of transthoracic echocardiographic (TTEcho) images in children often requires sedation. The optimal sedative for TTEcho has not been determined. Children with congenital heart disease are repeatedly exposed to sedatives and anesthetics that may affect brain development. Dexmedetomidine, which in animals alters brain structure to a lesser degree, may offer advantages in this vulnerable population. METHODS: A prospective, randomized, double-blind trial enrolled 280 children 3–24 months of age undergoing outpatient TTEcho, comparing 2.5 µg·kg−1 intranasal dexmedetomidine to 5 mg·kg−1 oral pentobarbital. Rescue sedation, for both groups, was intranasal dexmedetomidine 1 µg·kg−1. The primary outcome was adequate sedation within 30 minutes without rescue sedation, assessed by blinded personnel. Secondary outcomes included number of sonographer pauses, image quality in relation to motion artifacts, and parental satisfaction. RESULTS: Success rates with a single dose were not different between sedation techniques; 85% in the pentobarbital group and 84% in the dexmedetomidine group (P = .8697). Median onset of adequate sedation was marginally faster with pentobarbital (16.5 [interquartile range, 13–21] vs 18 [16–23] minutes for dexmedetomidine [P = .0095]). Time from drug administration to discharge was not different (P = .8238) at 70.5 (64–83) minutes with pentobarbital and 70 (63–82) minutes with dexmedetomidine. Ninety-five percent of sedation failures with pentobarbital and 100% of dexmedetomidine failures had successful rescue sedation with intranasal dexmedetomidine. CONCLUSIONS: Intranasal dexmedetomidine was comparable to oral pentobarbital sedation for TTEcho sedation in infants and did not increase the risk of clinically important adverse events. Intranasal dexmedetomidine appears to be an effective "rescue" sedative for both failed pentobarbital and dexmedetomidine sedation. Dexmedetomidine could be a safer option for repeated sedation in children, but further studies are needed to assess long-term consequence of repeated sedation in this high-risk population. Accepted for publication December 1, 2017. Funding: This research was funded by a grant from the Children's Heart Association of Cincinnati and departmental support. The authors declare no conflicts of interest. Clinical trial registration: NCT02250820. LMA is a registered trademark of Teleflex Incorporated or its affiliates. Reprints will not be available from the authors. Address correspondence to Jeffrey W. Miller, MD, Department of Anesthesiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 2001, Cincinnati, OH. Address e-mail to Jeff.Miller@cchmc.org. © 2018 International Anesthesia Research Society

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Nutritional and Environmental Influences on Athlete Health and Performance

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Upper Respiratory Symptoms, Gut Health and Mucosal Immunity in Athletes

Abstract

Upper respiratory symptoms remain the most common illness in athletes. Upper respiratory symptoms during heavy training and competition may impair performance. Preventing illness is the primary reason for the use of supplements, such as probiotics and prebiotics, for maintaining or promoting gut health and immune function. While exercise-induced perturbations in the immune system may increase susceptibility to illness and infection, growing evidence indicates that upper respiratory symptoms are related to a breakdown in the homeostatic regulation of the mucosal immune system of the airways. Balancing protection of the respiratory tract with normal physiological functioning requires dynamic orchestration between a wide array of immune parameters. The intestinal microbiota regulates extra-intestinal immunity via the common mucosal immune system and new evidence implicates the microbiota of the nose, mouth and respiratory tract in upper respiratory symptoms. Omics' approaches now facilitate comprehensive profiling at the molecular and proteomic levels to reveal new pathways and molecules of immune regulation. New targets may provide for personalised nutritional and training interventions to maintain athlete health.

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Career perspective: Kenneth J. Collins

A career interest in thermoregulation research has included wide contrasts in the subjects of enquiry, extending from heat stroke to hypothermia, special investigations in many different purpose-built climatic...

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Magnesium attenuates endothelin-1-induced vasoreactivity and enhances vasodilation in mouse pulmonary arteries: Modulation by chronic hypoxic pulmonary hypertension

Abstract

Pulmonary hypertension (PH) is characterized by enhanced vasoreactivity and sustained pulmonary vasoconstriction, arising from the aberrant Ca²⁺ homeostasis in pulmonary arterial smooth muscle cells. In addition to Ca²⁺, magnesium, the most abundant intracellular divalent cation, also plays critical roles in many cellular processes that regulate cardiovascular functions. Recent findings suggested that magnesium regulates vascular functions by altering the vascular responses to vasodilator and vasoactive agonists, and affects endothelial function by modulating endothelium-dependent vasodilation in hypertension. Administration of magnesium also decreased pulmonary arterial pressure and improved cardiac output in PH animal models. However, the role of magnesium in the regulation of pulmonary vascular function related to PH has not been studied. This study examined the effects of magnesium on endothelin-1 (ET-1)-induced vasoconstriction, acetylcholine (Ach)-induced vasodilatation, and the generation of nitric oxide (NO) in pulmonary arteries (PAs) of normoxic and chronic hypoxia (CH)-treated mice. Our data showed that removal of extracellular magnesium suppressed vasoreactivity of PAs to both ET-1 and Ach. High concentration of magnesium (4.8 mm) inhibited ET-1-induced vasoconstriction in endothelium intact or disrupted PAs of normoxic and CH mice, and enhanced the Ach-induced NO production in PAs of normoxic mice. Moreover, magnesium enhanced Ach-induced vasodilatation in PAs of normoxic mice, and the enhancement was completely abolished after CH exposure. Hence, this study demonstrated that increasing magnesium concentration can attenuate ET-1-induced contractile response, and improve vasodilatation via release of NO from endothelium; and chronic exposure to hypoxia can cause endothelial dysfunction resulting in the suppression of magnesium-dependent modulation of vasodilatation.

This article is protected by copyright. All rights reserved

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Revealing the ‘obscurin’: mapping the path to new discovery with the phosphoproteome

Abstract

Skeletal muscle is a vital tissue for health and functionality and is constantly 'turning over' through the reciprocal processes of protein synthesis and protein breakdown.

This article is protected by copyright. All rights reserved

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Case of complete mesh migration into the stomach after mesh hiatoplasty for a hiatal hernia

Abstract

Mesh migration is a rare complication of surgery for a hiatal hernia. Here, we present the case of a 72-year-old who complained of dysphasia and bodyweight loss. Upper gastrointestinal endoscopy revealed incarcerated mesh in the lumen of the esophagogastric junction. Surgery was performed under both endoscopy and laparoscopy, and the mesh was successfully removed via gastrostomy. To the best of our knowledge, our case is the first in which mesh that had migrated into the esophagogastric junction was removed by a combination of laparoscopic and endoscopic procedure, although the cases of 17 patients in which mesh migrated into the stomach after mesh hiatoplasty have previously been reported in the literature.

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From rehab to prehab: 5 steps to a proactive action plan

Assess and improve the health of your team on a regular basis to combat the physical and mental demands of a career in firefighting/EMS

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EASY—An Instrument for Surveillance of Physical Activity in Youth

ABSTRACTPurposePhysical activity (PA) promotion among youth is a public health priority and there is a need for robust surveillance systems to help support such initiatives. Existing youth PA self-report instruments that are used for surveillance lack information regarding the types and contexts of activity. Further, these instruments have limited validity with accelerometry. The purpose of the present study was to develop a self-report instrument, with sound psychometric properties, for monitoring compliance with PA guidelines in youth.MethodsIn focus groups, 162 middle school students identified 30 forms of PA that are highly prevalent in that age group. We incorporated these activities into three preliminary forms of a self-report instrument. An independent sample of middle school students (n = 537) was randomly assigned to complete one of the three preliminary versions of the instrument. Rasch analysis was applied to the responses to the three formats, and a yes/no plus frequency format emerged as the preferred method. A third sample of 342 middle school students then completed the yes/no plus frequency instrument twice following a seven-day period during which they wore an accelerometer. Using both Rasch analysis and traditional correlational methods, validity and reliability of a 14-item instrument were established. Data were collected during 2012 – 2015.ResultsSpearman correlation coefficient for the association between the cumulative score for the 14 items and minutes per day of accelerometry-derived moderate-to-vigorous physical activity (MVPA) was 0.33 (95% CI 0.22, 0.43; p<.001 sensitivity and specificity of the instrument was respectively.conclusionsthe study produced a pa self-report for youth that found to be reliable valid versus accelerometry acceptably specific sensitive in detecting compliance with guidelines.this is an open-access article distributed under terms creative commons attribution-non commercial-no derivatives license where it permissible download share work provided properly cited. cannot changed any way or used commercially without permission from journal. purpose physical activity promotion among public health priority there need robust surveillance systems help support such initiatives. existing instruments are lack information regarding types contexts activity. further these have limited validity accelerometry. present develop sound psychometric properties monitoring guidelines youth. methods focus groups middle school students identified forms highly prevalent age group. we incorporated activities into three preliminary instrument. independent sample randomly assigned complete one versions rasch analysis applied responses formats yes plus frequency format emerged as preferred method. third then completed twice following seven-day period during which they wore accelerometer. using both traditional correlational reliability were established. data collected results spearman correlation coefficient association between cumulative score items minutes per day accelerometry-derived moderate-to-vigorous ci p respectively. conclusions guidelines. this corresponding author: russell r. pate phd university south carolina research center assembly street suite columbia sc s funded by grant national cancer institute institutes health. authors declare no conflicts interest. do not constitute endorsement american college sports medicine. presented clearly honestly fabrication falsification inappropriate manipulation. accepted publication: january medicine>

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Wilson's Disease in Children: A Position Paper by the Hepatology Committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition

ABSTRACTBackground:Clinical presentations of Wilson's disease (WD) in childhood ranges from asymptomatic liver disease to cirrhosis or acute liver failure, whereas neurological and psychiatric symptoms are rare. The basic diagnostic approach includes serum ceruloplasmin and 24-hour urinary copper excretion. Final diagnosis of WD can be established using a diagnostic scoring system based on symptoms, biochemical tests assessing copper metabolism, and molecular analysis of mutations in the ATP7B gene. Pharmacological treatment is life-long and aims at removal of copper excess by chelating agents as D-penicillamine, trientine, or inhibition of intestinal copper absorption with zinc salts. Acute liver failure often requires liver transplantation. This publication aims to provide recommendations for diagnosis, treatment, and follow-up of WD in children.Methods:Questions addressing the diagnosis, treatment, and follow-up of WD in children were formulated by a core group of ESPGHAN members. A systematic literature search on WD using MEDLINE, EMBASE, Cochrane Database from 1990 to 2016 was performed focusing on prospective and retrospective studies in children. Quality of evidence was assessed according to the GRADE system. Expert opinion supported recommendations where the evidence was regarded as weak. The ESPGHAN core group and ESPGHAN Hepatology Committee members voted on each recommendation, using the nominal voting technique. Background: Clinical presentations of Wilson's disease (WD) in childhood ranges from asymptomatic liver disease to cirrhosis or acute liver failure, whereas neurological and psychiatric symptoms are rare. The basic diagnostic approach includes serum ceruloplasmin and 24-hour urinary copper excretion. Final diagnosis of WD can be established using a diagnostic scoring system based on symptoms, biochemical tests assessing copper metabolism, and molecular analysis of mutations in the ATP7B gene. Pharmacological treatment is life-long and aims at removal of copper excess by chelating agents as D-penicillamine, trientine, or inhibition of intestinal copper absorption with zinc salts. Acute liver failure often requires liver transplantation. This publication aims to provide recommendations for diagnosis, treatment, and follow-up of WD in children. Methods: Questions addressing the diagnosis, treatment, and follow-up of WD in children were formulated by a core group of ESPGHAN members. A systematic literature search on WD using MEDLINE, EMBASE, Cochrane Database from 1990 to 2016 was performed focusing on prospective and retrospective studies in children. Quality of evidence was assessed according to the GRADE system. Expert opinion supported recommendations where the evidence was regarded as weak. The ESPGHAN core group and ESPGHAN Hepatology Committee members voted on each recommendation, using the nominal voting technique.

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Pediatric Nonalcoholic Fatty Liver Disease: Current Thinking

Nonalcoholic fatty liver disease (NAFLD), an increasingly prevalent paediatric disorder, is diagnosed and managed not only by both pediatric gastroenterologists/hepatologists but also frequently by the general pediatrician. This article updates recent advances in diagnostic and therapeutic approach, which may be applied to everyday practice. Diagnosis of NAFLD takes into account the risk factor profile and is a diagnosis of exclusion. Techniques such as transient elastography and specific biomarkers aimed at improving diagnosis and monitoring of NAFLD need further validation in the pediatric population. Defining the risk to develop cirrhosis seems to be of primary importance already in childhood and a combination of genetic, clinical, and environmental factors can help in monitoring and making decisions on therapy. Weight reduction therapy should be the aim of treatment approach, but the compliance is poor and pharmacological treatment would be helpful; docosahexaenoic acid, some probiotics, and vitamin E are to be considered, but evidence is not sufficient to recommend widespread use.

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Intravenous Iron Sucrose for Treatment of Iron Deficiency Anemia in Pediatric Inflammatory Bowel Disease

ABSTRACTObjectives:Iron deficiency anemia (IDA) is a common complication of pediatric inflammatory bowel disease (IBD), yet the effectiveness of oral iron supplementation is limited. Intravenous iron sucrose is an effective and safe alternative treatment for IDA in adults with IBD, but its role in the treatment of IDA in pediatric IBD is unclear. The primary aim of this study was to evaluate the use of iron sucrose in pediatric IBD subjects with IDA and determine the clinical response as measured by improvement in hemoglobin concentration. The secondary aim was to describe adverse events associated with iron sucrose use in this cohort.Methods:A retrospective chart review was performed of all pediatric patients with IBD receiving iron sucrose infusions for IDA at a single tertiary care center between 2011 and 2015.Results:Seventy-two subjects (53 with Crohn disease, 11 with ulcerative colitis, and 8 with IBD-unclassified) received a total of 273 iron sucrose infusions. Forty-three subjects qualified for the efficacy analysis. There was a significant increase in hemoglobin over the treatment course, with mean (±SD) hemoglobin increasing from 9.6 ± 1.2 g/dL at baseline to 12.1 ± 1.3 g/dL after iron sucrose treatment (P 

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The Relation Between Malnutrition and the Exocrine Pancreas: A Systematic Review

ABSTRACTObjective:The relation between malnutrition and exocrine pancreatic insufficiency (EPI) has been described previously, but it is unclear if malnutrition leads to EPI or vice versa. We systematically synthesized current evidence evaluating the association between malnutrition and EPI in children.Methods:Pubmed, Embase, and Cochrane databases were searched from inception until February 2017. We included cohort or case-controlled studies in children reporting on prevalence or incidence of EPI and malnutrition. Data generation was performed independently by 2 authors. Quality was assessed by using quality assessment tools from the National Heart, Lung, and Blood Institute.Results:Nineteen studies were divided into 2 groups: 10 studies showing EPI leading to malnutrition, and 9 studies showing malnutrition leading to EPI. Because of heterogeneity in design, definitions, and outcome measures, pooling of results was impossible. Quality was good in 4 of 19 studies. Pancreatic insufficiency was linked to decreased nutritional status in 8 of 10 articles, although this link was not specified properly in most articles. In malnourished children, improvement was seen in pancreatic function in 7 of 9 articles after nutritional rehabilitation. The link between the 2 was not further specified. Heterogeneity exists with respect to definitions, outcome measures, and study design.Conclusions:There is sufficient evidence for an association between EPI and malnutrition. We could not confirm whether there is a correlation or causality between EPI or malnutrition. It was therefore not possible to draw firm conclusions from this systematic review on underlying pathophysiological mechanisms between EPI and malnutrition. More observational clinical trials are crucially needed. Objective: The relation between malnutrition and exocrine pancreatic insufficiency (EPI) has been described previously, but it is unclear if malnutrition leads to EPI or vice versa. We systematically synthesized current evidence evaluating the association between malnutrition and EPI in children. Methods: Pubmed, Embase, and Cochrane databases were searched from inception until February 2017. We included cohort or case-controlled studies in children reporting on prevalence or incidence of EPI and malnutrition. Data generation was performed independently by 2 authors. Quality was assessed by using quality assessment tools from the National Heart, Lung, and Blood Institute. Results: Nineteen studies were divided into 2 groups: 10 studies showing EPI leading to malnutrition, and 9 studies showing malnutrition leading to EPI. Because of heterogeneity in design, definitions, and outcome measures, pooling of results was impossible. Quality was good in 4 of 19 studies. Pancreatic insufficiency was linked to decreased nutritional status in 8 of 10 articles, although this link was not specified properly in most articles. In malnourished children, improvement was seen in pancreatic function in 7 of 9 articles after nutritional rehabilitation. The link between the 2 was not further specified. Heterogeneity exists with respect to definitions, outcome measures, and study design. Conclusions: There is sufficient evidence for an association between EPI and malnutrition. We could not confirm whether there is a correlation or causality between EPI or malnutrition. It was therefore not possible to draw firm conclusions from this systematic review on underlying pathophysiological mechanisms between EPI and malnutrition. More observational clinical trials are crucially needed.

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Can Patients With Neonatal Digestive Diseases Be Protected From Unnecessary Radiation?

No abstract available

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Autoimmune Hepatitis and Autoimmune Hepatitis Overlap With Sclerosing Cholangitis: Immunophenotype Markers in Children and Adolescents

ABSTRACTObjective:The pathophysiology of autoimmune hepatitis (AIH) may involve the activation of immune cells and changes in the expression of cellular markers. The aim of the present study was to characterize the immunophenotype markers of lymphocytes and monocytes in the peripheral blood of children and adolescents with type 1 AIH and AIH overlap with sclerosing cholangitis (overlap syndrome [OS]).Methods:This is a cross-sectional study of 20 children and adolescents diagnosed with type 1 AIH and 19 with OS. Fifteen healthy subjects were included as controls. Flow cytometric analysis was used to identify markers of inflammation and autoimmunity.Results:The total number of CD4+ T cells was higher in the AIH patients compared with the controls. The number of CD4+ T cells expressing CCR3 and CD28 was higher in the AIH group than in the control group. CD45RO was more highly expressed in the AIH group, whereas CD45RA was more highly expressed in the OS group. In regard to CD8+ T lymphocytes, the CCR3 expression was higher in both groups of patients. Patients with OS had the highest expression of CD45RA and CD25. In monocytes, human leukocyte antigen DR (HLA-DR) was less expressed in both groups of patients.Conclusions:Complex phenotype features may be involved in the pathophysiology of AIH, accounting for changes in immune system regulation mechanisms. In conclusion, even after good response to treatment, patients still have immune activity signals at the cellular level. Objective: The pathophysiology of autoimmune hepatitis (AIH) may involve the activation of immune cells and changes in the expression of cellular markers. The aim of the present study was to characterize the immunophenotype markers of lymphocytes and monocytes in the peripheral blood of children and adolescents with type 1 AIH and AIH overlap with sclerosing cholangitis (overlap syndrome [OS]). Methods: This is a cross-sectional study of 20 children and adolescents diagnosed with type 1 AIH and 19 with OS. Fifteen healthy subjects were included as controls. Flow cytometric analysis was used to identify markers of inflammation and autoimmunity. Results: The total number of CD4+ T cells was higher in the AIH patients compared with the controls. The number of CD4+ T cells expressing CCR3 and CD28 was higher in the AIH group than in the control group. CD45RO was more highly expressed in the AIH group, whereas CD45RA was more highly expressed in the OS group. In regard to CD8+ T lymphocytes, the CCR3 expression was higher in both groups of patients. Patients with OS had the highest expression of CD45RA and CD25. In monocytes, human leukocyte antigen DR (HLA-DR) was less expressed in both groups of patients. Conclusions: Complex phenotype features may be involved in the pathophysiology of AIH, accounting for changes in immune system regulation mechanisms. In conclusion, even after good response to treatment, patients still have immune activity signals at the cellular level.

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Effect of Cyproheptadine on Weight and Growth Velocity in Children With Silver-Russell Syndrome

ABSTRACTObjectives:Nutritional management of children with Silver-Russell syndrome (SRS) is crucial, especially before initiating growth hormone therapy. Since cyproheptadine (CYP) has been reported to be orexigenic, we retrospectively investigated the effects of CYP on changes in weight and height in patients with SRS.Methods:Anthropometric parameters (weight [W], length or height [H], weight on expected weight for height [W/H], and body mass index) were recorded for 34 children with SRS receiving CYP. We specifically analyzed the anthropometric parameters (expressed in median) in a group of 23 patients treated with CYP at baseline (M0-CYP) and every 3 months (M3 to M12-CYP) after the initiation of CYP treatment.Results:The 23 children with SRS treated by CYP only had weight stagnation during the months preceding the start of treatment. Anthropometric parameters, especially the weight, differed significantly between M0-CYP and all other times (M3, M6, M9, M12-CYP). After 1 year of treatment, a gain in overall length/height and weight was observed (W: +1.1 standard deviations from the mean [SDS]; H: +0.5 SDS). At M3, significant improvements in W/H (74.9% vs 79.3% [P = 0.01]) and body mass index (−3.4 vs −2.4 SDS [P = 0.001]) were also observed. Twenty-one patients (91%) improved their weight by at least +0.5 SDS, and 12 (52%) by at least +1 SDS.Conclusions:Our results show that CYP can be effective in patients with SRS with significant improvements in growth velocity and nutritional status before initiation of growth hormone therapy. Further prospective studies are required to confirm these results. Objectives: Nutritional management of children with Silver-Russell syndrome (SRS) is crucial, especially before initiating growth hormone therapy. Since cyproheptadine (CYP) has been reported to be orexigenic, we retrospectively investigated the effects of CYP on changes in weight and height in patients with SRS. Methods: Anthropometric parameters (weight [W], length or height [H], weight on expected weight for height [W/H], and body mass index) were recorded for 34 children with SRS receiving CYP. We specifically analyzed the anthropometric parameters (expressed in median) in a group of 23 patients treated with CYP at baseline (M0-CYP) and every 3 months (M3 to M12-CYP) after the initiation of CYP treatment. Results: The 23 children with SRS treated by CYP only had weight stagnation during the months preceding the start of treatment. Anthropometric parameters, especially the weight, differed significantly between M0-CYP and all other times (M3, M6, M9, M12-CYP). After 1 year of treatment, a gain in overall length/height and weight was observed (W: +1.1 standard deviations from the mean [SDS]; H: +0.5 SDS). At M3, significant improvements in W/H (74.9% vs 79.3% [P = 0.01]) and body mass index (−3.4 vs −2.4 SDS [P = 0.001]) were also observed. Twenty-one patients (91%) improved their weight by at least +0.5 SDS, and 12 (52%) by at least +1 SDS. Conclusions: Our results show that CYP can be effective in patients with SRS with significant improvements in growth velocity and nutritional status before initiation of growth hormone therapy. Further prospective studies are required to confirm these results.

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Resolving Malnutrition With Parenteral Nutrition Before Liver Transplant in Biliary Atresia

ABSTRACTObjective:Malnutrition is a common complication of end-stage liver disease (ESLD) associated with poor liver transplant outcomes. Nasogastric feeds are used for nutritional supplementation, but some patients remain malnourished. Parenteral nutrition (PN) can be effective, but has potential complications. The primary objective was to evaluate the effect of PN on anthropometric measures in children with ESLD awaiting liver transplant. Secondary objectives were evaluation of PN-associated complications, liver function tests, pediatric end-stage liver disease scores, waitlist time, and post-transplant length of stay (total and time in the intensive care unit).Methods:A single-center, retrospective chart review analyzing pediatric patients with ESLD receiving PN who were transplanted during a 6-year period. Data were trended and described over time, as were the relationships between anthropometric data and time receiving PN.Results:A total of 44 patients with ESLD were transplanted between January 2010 and December 2015. Eighteen (41%) received PN before transplant; all had biliary atresia with median age at transplant of 10 months (range, 5–18 months). Mid-upper arm circumference and triceps skinfold thickness showed resolution of malnutrition in 7 patients (39%) with normalization of 1 measure in another 4 patients (22%). Of the remaining, 6 had improved z scores and 1 had worsening malnutrition. No deaths occurred in patients receiving PN. Central line infection rates were 3.8/1000 catheter days with 8 total infections in 6 patients over a total of 2117 catheter days.Conclusions:Children with ESLD and malnutrition who have failed enteral feeding may benefit from PN to improve and/or resolve malnutrition before liver transplant. Objective: Malnutrition is a common complication of end-stage liver disease (ESLD) associated with poor liver transplant outcomes. Nasogastric feeds are used for nutritional supplementation, but some patients remain malnourished. Parenteral nutrition (PN) can be effective, but has potential complications. The primary objective was to evaluate the effect of PN on anthropometric measures in children with ESLD awaiting liver transplant. Secondary objectives were evaluation of PN-associated complications, liver function tests, pediatric end-stage liver disease scores, waitlist time, and post-transplant length of stay (total and time in the intensive care unit). Methods: A single-center, retrospective chart review analyzing pediatric patients with ESLD receiving PN who were transplanted during a 6-year period. Data were trended and described over time, as were the relationships between anthropometric data and time receiving PN. Results: A total of 44 patients with ESLD were transplanted between January 2010 and December 2015. Eighteen (41%) received PN before transplant; all had biliary atresia with median age at transplant of 10 months (range, 5–18 months). Mid-upper arm circumference and triceps skinfold thickness showed resolution of malnutrition in 7 patients (39%) with normalization of 1 measure in another 4 patients (22%). Of the remaining, 6 had improved z scores and 1 had worsening malnutrition. No deaths occurred in patients receiving PN. Central line infection rates were 3.8/1000 catheter days with 8 total infections in 6 patients over a total of 2117 catheter days. Conclusions: Children with ESLD and malnutrition who have failed enteral feeding may benefit from PN to improve and/or resolve malnutrition before liver transplant.

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Serial Balloon Dilation to Relieve Gastric Outlet Obstruction Induced by the Ingestion of Toilet Cleaner

No abstract available

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Ethnic Disparity in the Incidence and Outcome of Biliary Atresia in New Zealand

To determine incidence and outcome of biliary atresia (BA) between ethnic groups in New Zealand (NZ), a retrospective review was undertaken of children with BA born between 2002 and 2014. Prioritized ethnicity was used to determine ethnicity and was compared to population data. Uni- and multivariate analyses were undertaken to determine demographic and biochemical factors associated with outcome. Overall incidence was 1 in 9181 (Māori 1 in 5285; European 1 in 16,228; P 

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Rising Incidence of Paediatric Inflammatory Bowel Disease in Canterbury, New Zealand, 1996–2015

ABSTRACTBackground:The incidence of paediatric inflammatory bowel disease (IBD) around the world is increasing. Canterbury, New Zealand, has one of the highest Crohn disease (CD) incidence rates published. The present study aimed to document the incidence of paediatric IBD in Canterbury between 1996 and 2015.Methods:All patients diagnosed with IBD in Canterbury, while younger than 16 years, between January 1, 1996 and December 31, 2015 were identified. Demographic and disease phenotypic details were collected and entered into a secure database. Age-specific population data for Canterbury were obtained and annual incidence rates were then calculated.Results:The mean annual incidence rate over the 20-year period was 7.18/100,000 (95% confidence interval 5.55–8.81) children. There was a 4-fold increase in the incidence of paediatric IBD in Canterbury between 1996 and 2015. The ratio of CD to ulcerative colitis (UC) diagnosed was 8.4:1. Disease phenotype of CD and UC, based on the Paris classification, were comparable with other studies.Conclusions:The incidence of paediatric IBD in Canterbury has increased dramatically during the last 2 decades. Some of the observed incidence rates are among the highest documented anywhere in the world. The preponderance of CD over UC in the present study is the highest published. Background: The incidence of paediatric inflammatory bowel disease (IBD) around the world is increasing. Canterbury, New Zealand, has one of the highest Crohn disease (CD) incidence rates published. The present study aimed to document the incidence of paediatric IBD in Canterbury between 1996 and 2015. Methods: All patients diagnosed with IBD in Canterbury, while younger than 16 years, between January 1, 1996 and December 31, 2015 were identified. Demographic and disease phenotypic details were collected and entered into a secure database. Age-specific population data for Canterbury were obtained and annual incidence rates were then calculated. Results: The mean annual incidence rate over the 20-year period was 7.18/100,000 (95% confidence interval 5.55–8.81) children. There was a 4-fold increase in the incidence of paediatric IBD in Canterbury between 1996 and 2015. The ratio of CD to ulcerative colitis (UC) diagnosed was 8.4:1. Disease phenotype of CD and UC, based on the Paris classification, were comparable with other studies. Conclusions: The incidence of paediatric IBD in Canterbury has increased dramatically during the last 2 decades. Some of the observed incidence rates are among the highest documented anywhere in the world. The preponderance of CD over UC in the present study is the highest published.

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Sarcopenia in Children With End-Stage Liver Disease

ABSTRACTBackground:Sarcopenia, reflected by decreased psoas muscle surface area (PMSA), has been identified as a novel and independent predictor of wait-list mortality and outcomes in adult liver transplantation (LT). We hypothesized that children with end-stage liver disease (ESLD) would have smaller PMSA than healthy controls.Methods:Computer tomography images of children (ages 0 to 18 years) listed for LT in 2015 and a control group comprised 2:1 age- and gender-matched healthy pediatric trauma victims were reviewed. PMSA was determined at 2 intervertebral disc (L3/4; L4/5) levels. A subset of images was reviewed by 2 radiologists to determine interrater correlation.Results:A total of 23 children with ESLD were included, and the most prevalent diagnosis was biliary atresia (61%). On both lumbar levels, median PMSA was significantly smaller in ESLD subjects compared with the 46 healthy controls (L4/5; median total PMSA (tPMSA) 407 mm2 (interquartile range 339–537) versus controls 513 mm2 (interquartile range 437–672); P = 0.004), independent of participants' weight z scores (r = 0.01; P = 0.95). Excellent interrater correlation was seen (intraclass correlation 0.99).Conclusions:In this retrospective pilot study, PMSA was significantly lower in children with ESLD compared with healthy age- and gender-matched controls. Because this finding was independent of growth in ESLD subjects, PMSA may represent a novel objective nutritional biomarker in children with advanced liver disease. Background: Sarcopenia, reflected by decreased psoas muscle surface area (PMSA), has been identified as a novel and independent predictor of wait-list mortality and outcomes in adult liver transplantation (LT). We hypothesized that children with end-stage liver disease (ESLD) would have smaller PMSA than healthy controls. Methods: Computer tomography images of children (ages 0 to 18 years) listed for LT in 2015 and a control group comprised 2:1 age- and gender-matched healthy pediatric trauma victims were reviewed. PMSA was determined at 2 intervertebral disc (L3/4; L4/5) levels. A subset of images was reviewed by 2 radiologists to determine interrater correlation. Results: A total of 23 children with ESLD were included, and the most prevalent diagnosis was biliary atresia (61%). On both lumbar levels, median PMSA was significantly smaller in ESLD subjects compared with the 46 healthy controls (L4/5; median total PMSA (tPMSA) 407 mm2 (interquartile range 339–537) versus controls 513 mm2 (interquartile range 437–672); P = 0.004), independent of participants' weight z scores (r = 0.01; P = 0.95). Excellent interrater correlation was seen (intraclass correlation 0.99). Conclusions: In this retrospective pilot study, PMSA was significantly lower in children with ESLD compared with healthy age- and gender-matched controls. Because this finding was independent of growth in ESLD subjects, PMSA may represent a novel objective nutritional biomarker in children with advanced liver disease.

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Initial Pain Management in Pediatric Acute Pancreatitis: Opioid Versus Non-opioid

Nearly all patients with acute pancreatitis (AP) experience some degree of abdominal pain that is severe enough to prompt medical evaluation and necessitate analgesia. Effective analgesia is a priority in caring for such patients. Despite its importance, strategies for pain management in AP have been poorly studied, particularly in the field of pediatrics. Presently, no published data examine the management of pain because of AP in children at the time of initial presentation. Management approaches are often extrapolated from adult practice and based on anecdotal experience in the absence of objective data. The aim of our study was to examine the initial provision of analgesia to children who presented to a pediatric emergency department with AP.

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Lack of Correlation of Liver Tests With Fibrosis Stage at Diagnosis in Pediatric Primary Sclerosing Cholangitis

ABSTRACTObjectives:The aims of this study were to characterize pediatric primary sclerosing cholangitis (PSC) at a regional referral-based institution, including scoring of biliary stricturing and liver fibrosis and correlation analyses of scores with serum liver tests, to identify biomarkers of disease severity.Methods:A retrospective review of 39 PSC subjects was performed, with collection of demographic and outcomes data. Magnetic resonance cholangiopancreaticogram (MRCP) and liver biopsies were re-reviewed and scores of stricturing and fibrosis were correlated with serum liver tests.Results:Average age at PSC diagnosis was 11.2 years, 74% had inflammatory bowel disease and 51% had autoimmune hepatitis. Despite 83% with symptoms at presentation, only ∼1/3 were symptomatic at a mean follow-up of 4.1 years. Using a validated MRCP biliary scoring system, the mean intrahepatic score was 1.1 (out of 4) and extrahepatic score was 1.0 (out of 3). The mean Ishak liver fibrosis stage was 3.5 (out of 6) and 33% had cirrhosis. 92% were alive with their native liver and 5% had a liver transplant. Serum biomarker analyses revealed no correlation between Ishak liver fibrosis stage or MRCP score and laboratory values.Conclusions:Pediatric PSC patients cared for at a regional referral center had relatively mild disease compared with previously published reports, with low MRCP stricture scores despite significant liver fibrosis. Liver tests at presentation did not correlate with MRCP stricture score or liver fibrosis stage, suggesting the need for future studies to identify potential biomarkers of disease severity. Objectives: The aims of this study were to characterize pediatric primary sclerosing cholangitis (PSC) at a regional referral-based institution, including scoring of biliary stricturing and liver fibrosis and correlation analyses of scores with serum liver tests, to identify biomarkers of disease severity. Methods: A retrospective review of 39 PSC subjects was performed, with collection of demographic and outcomes data. Magnetic resonance cholangiopancreaticogram (MRCP) and liver biopsies were re-reviewed and scores of stricturing and fibrosis were correlated with serum liver tests. Results: Average age at PSC diagnosis was 11.2 years, 74% had inflammatory bowel disease and 51% had autoimmune hepatitis. Despite 83% with symptoms at presentation, only ∼1/3 were symptomatic at a mean follow-up of 4.1 years. Using a validated MRCP biliary scoring system, the mean intrahepatic score was 1.1 (out of 4) and extrahepatic score was 1.0 (out of 3). The mean Ishak liver fibrosis stage was 3.5 (out of 6) and 33% had cirrhosis. 92% were alive with their native liver and 5% had a liver transplant. Serum biomarker analyses revealed no correlation between Ishak liver fibrosis stage or MRCP score and laboratory values. Conclusions: Pediatric PSC patients cared for at a regional referral center had relatively mild disease compared with previously published reports, with low MRCP stricture scores despite significant liver fibrosis. Liver tests at presentation did not correlate with MRCP stricture score or liver fibrosis stage, suggesting the need for future studies to identify potential biomarkers of disease severity.

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Changes in Proteases, Antiproteases, and Bioactive Proteins From Mother's Breast Milk to the Premature Infant Stomach

ABSTRACTObjective:Our previous studies suggested that human milk proteases begin to hydrolyze proteins in the mammary gland and continue within the term infant' stomach. No research has measured milk protease and pepsin activity in the gastric aspirates of preterm infants after human milk feeding. This study investigated how the concentrations of human milk proteases and protease inhibitors changed in the premature infant stomach.Methods:Human milk and infant gastric samples were collected from 18 preterm-delivering mother–infant pairs (24–32 week gestational age). Paired human milk and gastric samples were collected across postnatal age (2–47 days). Protease concentrations were determined by spectrophotometric or fluorometric assays, and the concentrations of protease inhibitors and bioactive proteins were determined by enzyme-linked immunosorbent assay. Paired t tests were applied to compare enzymes, antiproteases, and bioactive proteins between human milk and gastric samples.Results:Our study reveals that although human milk proteases, including carboxypeptidase B2, kallikrein, plasmin, cathepsin D, elastase, thrombin, and cytosol aminopeptidase, are present in the preterm infant stomach, only plasmin and cathepsin D can actively hydrolyze proteins at gastric pH. Enzyme-linked immunosorbent assay and peptidomic evidence suggest that all milk antiproteases as well as lactoferrin and immunoglobulin A are partially digested in the preterm stomach.Conclusions:Most human milk proteases are active in milk but not at preterm infant gastric pH. Only cathepsin D and plasmin have potential to continue degrading milk proteins within the preterm infant stomach. Objective: Our previous studies suggested that human milk proteases begin to hydrolyze proteins in the mammary gland and continue within the term infant' stomach. No research has measured milk protease and pepsin activity in the gastric aspirates of preterm infants after human milk feeding. This study investigated how the concentrations of human milk proteases and protease inhibitors changed in the premature infant stomach. Methods: Human milk and infant gastric samples were collected from 18 preterm-delivering mother–infant pairs (24–32 week gestational age). Paired human milk and gastric samples were collected across postnatal age (2–47 days). Protease concentrations were determined by spectrophotometric or fluorometric assays, and the concentrations of protease inhibitors and bioactive proteins were determined by enzyme-linked immunosorbent assay. Paired t tests were applied to compare enzymes, antiproteases, and bioactive proteins between human milk and gastric samples. Results: Our study reveals that although human milk proteases, including carboxypeptidase B2, kallikrein, plasmin, cathepsin D, elastase, thrombin, and cytosol aminopeptidase, are present in the preterm infant stomach, only plasmin and cathepsin D can actively hydrolyze proteins at gastric pH. Enzyme-linked immunosorbent assay and peptidomic evidence suggest that all milk antiproteases as well as lactoferrin and immunoglobulin A are partially digested in the preterm stomach. Conclusions: Most human milk proteases are active in milk but not at preterm infant gastric pH. Only cathepsin D and plasmin have potential to continue degrading milk proteins within the preterm infant stomach.

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Di (2-Ethylhexyl) Phthalate and Its Role in Developing Cholestasis: An In Vitro Study on Different Liver Cell Types

ABSTRACTObjectives:Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in many polyvinylchloride medical devices and is washed out easily. Thereby critically ill infants can become exposed to DEHP concentrations significantly exceeding the recommended threshold. We suspect DEHP to play an important role in the development of intestinal failure-associated liver disease. The aim of this study was therefore to determine the direct influence of DEHP on different liver cell types.Methods:HepG2, human upcyte hepatocytes, primary murine hepatocytes, LX-2, human upcyte hepatic stellate cells, and liver organoids were cultured with DEHP (0.5–500 μmol/L) and parameters including cytotoxicity, cell–cell interactions, and expression of metabolizing enzymes were investigated.Results:DEHP modulated the expression of xenobiotic metabolizing enzymes, reduced the formation of bile canaliculi and cell polarity, and inhibited Cyp-activity in hepatocytes. DEHP had a toxic effect on LX-2 and induced the fibrogenic activation of hepatic stellate cells. The mode of action of DEHP was different in monolayer cultures compared to 3D-liver organoids, which were more sensitive to DEHP.Conclusions:This study suggests that DEHP modulates expression and activity of drug-detoxifying liver enzymes in humans at a clinically relevant concentration. Furthermore, it may contribute to the development of cholestasis and fibrosis. These findings strongly support the opinion, that there is a significant potential for serious adverse effects of DEHP derived from medical devices on human health, especially in very young infants with immature livers. Objectives: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in many polyvinylchloride medical devices and is washed out easily. Thereby critically ill infants can become exposed to DEHP concentrations significantly exceeding the recommended threshold. We suspect DEHP to play an important role in the development of intestinal failure-associated liver disease. The aim of this study was therefore to determine the direct influence of DEHP on different liver cell types. Methods: HepG2, human upcyte hepatocytes, primary murine hepatocytes, LX-2, human upcyte hepatic stellate cells, and liver organoids were cultured with DEHP (0.5–500 μmol/L) and parameters including cytotoxicity, cell–cell interactions, and expression of metabolizing enzymes were investigated. Results: DEHP modulated the expression of xenobiotic metabolizing enzymes, reduced the formation of bile canaliculi and cell polarity, and inhibited Cyp-activity in hepatocytes. DEHP had a toxic effect on LX-2 and induced the fibrogenic activation of hepatic stellate cells. The mode of action of DEHP was different in monolayer cultures compared to 3D-liver organoids, which were more sensitive to DEHP. Conclusions: This study suggests that DEHP modulates expression and activity of drug-detoxifying liver enzymes in humans at a clinically relevant concentration. Furthermore, it may contribute to the development of cholestasis and fibrosis. These findings strongly support the opinion, that there is a significant potential for serious adverse effects of DEHP derived from medical devices on human health, especially in very young infants with immature livers.

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The Role of Combination Therapy in Pediatric Inflammatory Bowel Disease: A Clinical Report from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

The treatment goal for children suffering from inflammatory bowel disease has been evolving with biologic therapies like anti-tumor necrosis factor agents assuming a more central role in treatment of more aggressive and extensive phenotype. Earlier introduction of anti-tumor necrosis factor agents have shown to be more effective and may even alter the natural history of inflammatory bowel disease. Development of anti-drug antibodies, however, limits long-term usage and leads to dose adjustment in almost half of patients treated with these medications. One of the strategies to minimize the development of anti-drug antibodies has been concomitant use of immunomodulator medications, resulting in fewer infusion reactions and sustained trough levels, potentially lowering the need for dose adjustments. Balanced with these benefits of optimized dosing and likely more sustained response, however, is the concern about increased risk of complications, such as infections and malignancies. The current manuscript reviews the available pediatric literature regarding efficacy, safety, and side effect profile of combination (immunomodulator and biologics) therapy in pediatric Crohn disease and ulcerative colitis, with particular emphasis on cost constraints, and recommendations for selection of patients who would benefit most from combination therapy.

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Radiation Exposure and Attributable Cancer Risk in Patients With Esophageal Atresia

ABSTRACTObjectives:Cases of esophageal carcinoma have been documented in survivors of esophageal atresia (EA). Children with EA undergo considerable amounts of diagnostic imaging and consequent radiation exposure potentially increasing their lifetime cancer mortality risk. This study evaluates the radiological procedures performed on patients with EA and estimates their cumulative radiation exposure and attributable lifetime cancer mortality risk.Methods:Medical records of patients with EA managed at a tertiary care center were reviewed for demographics, EA subtype, and number and type of radiological investigations. Existing normative data were used to estimate the cumulative radiation exposure and lifetime cancer risk per patient.Results:The present study included 53 patients with a mean follow-up of 5.7 years. The overall median and maximum estimated effective radiation dose in the neonatal period was 5521.4 μSv/patient and 66638.6 μSv/patient, respectively. This correlates to a median and maximum estimated cumulative lifetime cancer mortality risk of 1:1530 and 1:130, respectively. Hence, radiation exposure in the neonatal period increased the cumulative cancer mortality risk a median of 130-fold and a maximum of 1575-fold in EA survivors.Conclusions:Children with EA are exposed to significant amounts of radiation and an increased estimated cumulative cancer mortality risk. Efforts should be made to eliminate superfluous imaging. Objectives: Cases of esophageal carcinoma have been documented in survivors of esophageal atresia (EA). Children with EA undergo considerable amounts of diagnostic imaging and consequent radiation exposure potentially increasing their lifetime cancer mortality risk. This study evaluates the radiological procedures performed on patients with EA and estimates their cumulative radiation exposure and attributable lifetime cancer mortality risk. Methods: Medical records of patients with EA managed at a tertiary care center were reviewed for demographics, EA subtype, and number and type of radiological investigations. Existing normative data were used to estimate the cumulative radiation exposure and lifetime cancer risk per patient. Results: The present study included 53 patients with a mean follow-up of 5.7 years. The overall median and maximum estimated effective radiation dose in the neonatal period was 5521.4 μSv/patient and 66638.6 μSv/patient, respectively. This correlates to a median and maximum estimated cumulative lifetime cancer mortality risk of 1:1530 and 1:130, respectively. Hence, radiation exposure in the neonatal period increased the cumulative cancer mortality risk a median of 130-fold and a maximum of 1575-fold in EA survivors. Conclusions: Children with EA are exposed to significant amounts of radiation and an increased estimated cumulative cancer mortality risk. Efforts should be made to eliminate superfluous imaging.

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Oral Cholic Acid Is Efficacious and Well Tolerated in Patients With Bile Acid Synthesis and Zellweger Spectrum Disorders

No abstract available

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Pediatric Gastroesophageal Reflux Disease: Systematic Review on Prognosis and Prognostic Factors

In this systematic review, we summarize the evidence on prognosis and prognostic factors of pediatric gastroesophageal reflux disease (GERD). A structured search of Embase and MEDLINE/PubMed (inception to April 2016) yielded 5365 references; 4 publications met our inclusion criteria (risk of bias moderate-high). Definitions and outcome measures varied widely between studies. The percentage of children with a diagnosis of GERD with esophagitis that had persisting symptoms and/or were on antireflux medication at follow-up (12 months to >5 years) ranged from 23% (weekly symptoms) to 68% (antireflux medication), depending on definition used. In children with a diagnosis of GERD without esophagitis, 1.4% developed esophagitis at follow-up (>5 years); none developed Barrett esophagus. In conclusion, prognostic studies on pediatric GERD are of limited quality and show large methodological heterogeneity. Based on these studies, we are unable to identify those children at risk for unfavorable outcome with regards to GERD symptoms or endoscopic complications.

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EMS Stories: Community Ambulance

Stryker sat down with the men and women of Community Ambulance in Las Vegas, NV. Hear their perspectives on what it's like to work in emergency medical services. For more information click here.

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EMS Stories: Community Ambulance

Stryker sat down with the men and women of Community Ambulance in Las Vegas, NV. Hear their perspectives on what it's like to work in emergency medical services. For more information click here.

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EMS Stories: Community Ambulance

Stryker sat down with the men and women of Community Ambulance in Las Vegas, NV. Hear their perspectives on what it's like to work in emergency medical services. For more information click here.

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EMS Stories: Community Ambulance

Stryker sat down with the men and women of Community Ambulance in Las Vegas, NV. Hear their perspectives on what it's like to work in emergency medical services. For more information click here.

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Safe Life Defense gives you the chance to win their new tactical vest at SHOT Show 2018

Safe Life Defense is at SHOT SHOW 2018! Be the FIRST IN THE WORLD to win the New Tactical Vest!

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ND bill would relieve patients of air ambulance bills

The bill says that the patient's insurance company must pay the air ambulance company instead of leaving the patient with the heavy charges

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Statin use and pancreatic cancer risk in two prospective cohort studies

Abstract

Background

Statins, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, are common lipid-lowering agents and may reduce the risk of several cancer types including pancreatic cancer. However, the association between statin use and pancreatic cancer risk has not been fully evaluated in prospective studies.

Methods

We studied the association between statin use and incident pancreatic cancer in 113,059 participants from the prospective Nurses' Health Study and Health Professionals Follow-up Study. Statin use was self-reported via study questionnaires and updated biennially. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of pancreatic cancer were estimated using multivariable Cox proportional hazards models with adjustment for potential confounders.

Results

In total, 583 participants developed incident pancreatic cancer during 1.4 million person-years of follow-up. No difference was identified in pancreatic cancer risk for regular versus non-regular statin users (multivariable-adjusted HR 0.98; 95% CI 0.82–1.16). There was no significant heterogeneity in the association of statin use with pancreatic cancer risk between the cohorts. Similarly, longer duration of regular statin use was not associated with decreased risk of pancreatic cancer (P_trend = 0.65). The results remained similar when we examined statin use status at baseline or accounting for 4-year latency period. We observed no statistically significant effect modification for the association of statin use with pancreatic cancer risk by body mass index, smoking status, or diabetes mellitus status (all P_interaction > 0.21).

Conclusions

Regular statin use was not associated with pancreatic cancer risk in two large prospective cohort studies in the U.S.

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Relapse rate and predictors of relapse in a large single center cohort of type 1 autoimmune pancreatitis: long-term follow-up results after steroid therapy with short-duration maintenance treatment

Abstract

Background

Type 1 autoimmune pancreatitis (AIP), as a pancreatic manifestation of IgG4-related disease, shows a favorable prognosis in the short term. However, disease relapse is common in long-term follow-up, despite a successful initial treatment response. This study aimed to identify the predictors of relapse and long-term outcomes in patients with type 1 AIP.

Methods

Patients with more than 2 years of follow-up who met the International Consensus Diagnostic Criteria for type 1 AIP were included. Patients who had undergone pancreatic operations associated with AIP or who lacked sufficient clinical data were excluded.

Results

All 138 patients achieved clinical remission with initial steroid therapy, and 66 (47.8%) experienced relapse during a median 60 (range 24–197) months follow-up. Among the relapsed patients, about 74% (49/66) relapsed within 3 years. About 60% (82/138) had other organ involvement (OOI), most commonly in the proximal bile duct (26.8%). At first diagnosis, OOI, and especially OOI of the proximal bile duct, was a significant independent predictor of relapse (hazard ratio 2.65; 95% confidence interval 1.44–4.89; p = 0.002), according to multivariate analysis. During the follow-up period, 16 (11.6%) patients experienced endocrine/exocrine dysfunction and 32 (23.2%) patients developed de novo pancreatic calcifications/stones. No pancreatic cancer occurred in any patients.

Conclusions

Type 1 AIP has common relapses, and patients with OOI, especially OOI of the proximal bile duct, appear to be at increased risk for relapse. Long-term sequelae, including pancreatic insufficiency and pancreatic calcifications/stones, are common in patients with relapse. To reduce the relapse, longer maintenance treatment may be needed especially for patients at high risk for relapse.

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Manipulation and mobilization for treating chronic low back pain: a systematic review and meta-analysis

Mobilization and manipulation therapies are widely used to benefit patients with chronic low back pain. However, questions remain about their efficacy, dosing, safety, as well as how these approaches compare to other therapies.

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Complex signatures of natural selection at GYPA

Abstract

The human MN blood group antigens are isoforms of glycophorin A (GPA) encoded by the gene, GYPA, and are the most abundant erythrocyte sialoglycoproteins. The distribution of MN antigens has been widely studied in human populations yet the evolutionary and/or demographic factors affecting population variation remain elusive. While the primary function of GPA is yet to be discovered, it serves as the major binding site for the 175-kD erythrocyte-binding antigen (EB-175) of the malarial parasite, Plasmodium falciparum, a major selective pressure in recent human history. More specifically, exon two of GYPA encodes the receptor-binding ligand to which P. falciparum binds. Accordingly, there has been keen interest in understanding what impact, if any, natural selection has had on the distribution of variation in GYPA and exon two in particular. To this end, we resequenced GYPA in individuals sampled from both P. falciparum endemic (sub-Saharan Africa and South India) and non-endemic (Europe and East Asia) regions of the world. Observed patterns of variation suggest that GYPA has been subject to balancing selection in populations living in malaria endemic areas and in Europeans, but no such evidence was found in samples from East Asia, Oceania, and the Americas. These results are consistent with malaria acting as a selective pressure on GYPA, but also suggest that another selective force has resulted in a similar pattern of variation in Europeans. Accordingly, GYPA has perhaps a more complex evolutionary history, wherein on a global scale, spatially varying selective pressures have governed its natural history.

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The role of hypoxia-inducible factors in carotid body (patho) physiology

Abstract

Hypoxia-inducible factors mediate adaptive responses to reduced O₂ availability. In patients with obstructive sleep apnea, repeated episodes of hypoxemia and reoxygenation (intermittent hypoxia) are sensed by the carotid body (CB). The ensuing CB chemosensory reflex activates the sympathetic nervous system and increased secretion of catecholamines by the adrenal medulla, resulting in hypertension and breathing abnormalities. In the CB, intermittent hypoxia induces the formation of reactive oxygen species (ROS) and increased intracellular Ca²⁺ levels, which drive increased expression of hypoxia-inducible factor 1α (HIF-1α) and a decrease in the levels of HIF-2α.  Intermittent hypoxia increases HIF-1α-dependent expression of Nox2, encoding the pro-oxidant enzyme NADPH oxidase 2, and decreased HIF-2α-dependent expression of Sod2, encoding the anti-oxidant enzyme superoxide dismutase 2. These changes in gene expression drive persistently elevated ROS levels in the CB, brainstem, and adrenal medulla that are required for the development of hypertension and breathing abnormalities. The ROS generated by dysregulated HIF activity in the CB results in oxidation and inhibition of heme oxygenase 2, and the resulting reduction in the levels of carbon monoxide lead to increased hydrogen sulfide production, triggering glomus cell depolarization. Thus, the pathophysiology of obstructive sleep apnea involves the dysregulation of O₂-regulated transcription factors, gasotransmitters, and sympathetic outflow that affects blood pressure and breathing.

This article is protected by copyright. All rights reserved

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Sympatholysis: the more we learn, the less we know

Abstract

During exercise, blood is redistributed to meet the metabolic demands of the working skeletal muscle and to regulate core temperature and systemic haemodynamics, primarily mean arterial pressure.

This article is protected by copyright. All rights reserved

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Benign and malignant tumors in Rubinstein–Taybi syndrome

Rubinstein–Taybi syndrome (RSTS) is a multiple congenital anomalies syndrome associated with mutations in CREBBP (70%) and EP300 (5–10%). Previous reports have suggested an increased incidence of specific benign and possibly also malignant tumors. We identified all known individuals diagnosed with RSTS in the Netherlands until 2015 (n = 87) and studied the incidence and character of neoplastic tumors in relation to their CREBBP/EP300 alterations. The population–based Dutch RSTS data are compared to similar data of the Dutch general population and to an overview of case reports and series of all RSTS individuals with tumors reported in the literature to date. Using the Nationwide Network and Registry of Histopathology and Cytopathology in the Netherlands (PALGA Foundation), 35 benign and malignant tumors were observed in 26/87 individuals. Meningiomas and pilomatricomas were the most frequent benign tumors and their incidence was significantly elevated in comparison to the general Dutch population. Five malignant tumors were observed in four persons with RSTS (medulloblastoma; diffuse large-cell B-cell lymphoma; breast cancer; non-small cell lung carcinoma; colon carcinoma). No clear genotype–phenotype correlation became evident. The Dutch population-based data and reported case studies underscore the increased incidence of meningiomas and pilomatricomas in individuals with RSTS. There is no supporting evidence for an increased risk for malignant tumors in individuals with RSTS, however, due to the small numbers this risk may not be fully dismissed.

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Clinical features, BTD gene mutations, and their functional studies of eight symptomatic patients with biotinidase deficiency from Southern China

Biotinidase (BTD) deficiency is a rare autosomal recessive metabolic disease, which develops neurological and cutaneous symptoms because of the impaired biotin recycling. Pathogenic mutations on BTD gene cause BTD deficiency. Clinical features and mutation analysis of Chinese children with BTD deficiency were rarely described. Herein, for the first time, we reported the clinical features, BTD gene mutations and their functional studies of eight symptomatic children with BTD deficiency from southern China. Fatigue, hypotonia, proximal muscular weakness, hearing deficits, rash and respiratory problems are common clinical phenotype of our patients. Seizures are observed only in patients with profound BTD deficiency. Five novel mutations were detected, among which c.637delC (H213TfsTer51) was found in 50% of our patients and might be considered as a common mutation. In vitro studies confirmed three mild mutations c.1368A>C (Q456H), c.1613G>A (R538H), and c.644T>A (L215H) which retained 10–30% of wild type enzyme activity, and six severe mutations c.235C>T (R79C), c.1271G>C (C424S), c.1412G>A (C471Y), c.637delC (H213TfsTer51), c.395T>G (M132W), c.464T>C (L155P), and c.1493dupT (L498FfsTer13) which retained <10% of wild type enzyme activity. c.1330G>C (D444H) decreased the protein expression but not activity of BTD enzyme, and H213TfsTer51 was structurally damaging while L498FfsTer13 was functionally damaging. These results will be helpful in establishing the definitive diagnosis of BTD deficiency at the gene level, offering appropriate genetic counseling, and providing clues to structure/function relationships of the enzyme.

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Ultrasound-guided lumbar plexus block in children and adolescents using a transverse lumbar paravertebral sonogram: Initial experience

Summary

Background

The clinical reliability and reproducibility of ultrasound-guided lumbar plexus blocks is not established in pediatric populations. We present the results of a combined nerve stimulation ultrasound-guided lumbar plexus block using the vertebral body, transverse process, and psoas muscle as landmarks on a transverse lumbar paravertebral sonogram with mid-axillary transducer placement, "shamrock method," in children and adolescents.

Aims

Our primary objective was to determine the rate of achieving sensory changes in the lumbar plexus distribution. Secondary outcomes were performance time, reliability of echo-landmarks, measures of patient comfort, and complications.

Methods

We reviewed prospectively collected quality assurance data and electronic medical records of 21 patients having major orthopedic surgery with lumbar plexus block catheter for postoperative analgesia.

Results

Twenty-one patients were studied with mean age and weight (SD, range) of 13.6 years (3.8, 6-18) and 49.3 kg (18.6, 19.2-87.6). Surgical procedures included periacetabular osteotomy, pelvic osteotomy, and proximal femoral osteotomy. Mean volume of 0.5 mL/kg (0.05) 0.2% ropivacaine produced thermal sensory changes to femoral and lateral femoral cutaneous nerves in 20/21 (95% CI 0.76 to >0.99) and 19/21 (95% CI 0.70-0.99) patients. Identification of transverse process (TP), vertebral body (VB), and psoas muscle (PM): 21/21 (95% CI 0.86-1.0). Average block performance time was 9:08 minutes (2:09, 2-13). Average opioid consumption (SD) in operating room, postanesthesia care unit, 0-12 and 12-24-hour periods were 0.17 mg/kg (0.08), 0.08 mg/kg (0.06), 0.06 mg/kg (0.06), and 0.06 mg/kg (0.05). Median pain score by severity category in postanesthesia care unit: (0-3) 66.7%, (4-6) 28.5%, (>7) 4.8%; 0-12 hours: (0-3) 76.2%, (4-6) 19.0%, (>7) 4.8%; 12-24 hours: (0-3) 57.2%, (4-6) 42.8%, (>7) 0%. No complications were recorded.

Conclusion

Ultrasound guidance using lateral imaging of transverse process, vertebral body, and psoas muscle allows practitioners to reach the nerves of the lumbar plexus and achieve sensory block in pediatric patients with a high success rate.

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Correction to: Beta2-Agonist Doping Control and Optical Isomer Challenges

Abstract

Page 1789, table 1, 'Carmoterol' row: The cell entry in the 'Stereochemistry' column, which previously read.

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Is Platelet-Rich Plasma (PRP) Effective in the Treatment of Acute Muscle Injuries? A Systematic Review and Meta-Analysis

Abstract

Background

Muscle lesions account for one-third of sport-related injuries, thus representing a substantial problem for both players and their teams. The use of platelet-rich plasma (PRP) injections is rapidly growing in clinical practice, prompted by an unmet clinical need with a large commercial market. However, after early reports of positive preliminary experience, higher quality studies recently questioned the real benefit provided by PRP injections to promote muscle healing and return to sport.

Objective

To evaluate the effect of platelet-rich plasma (PRP) injections on outcomes following acute muscle injuries.

Design

Meta-analysis of randomized, controlled trials (RCTs), Level I.

Data sources

PubMed (MEDLINE), Cochrane (CENTRAL), Web of Science, clinicaltrials.gov, who.int, isrctn.com, greylit.org, opengrey.eu.

Eligibility criteria

RCTs investigating the effect of PRP for the treatment of acute muscle injuries against at least one control group including patients treated with placebo injection or physical therapy. The outcomes evaluated were time to return to sport, re-injuries, complications, pain, muscle strength, range of motion (ROM)/flexibility, muscle function, and imaging.

Results

Six studies, involving 374 patients, were included in the meta-analysis. The time to return to sport evaluated in all six studies was significantly shorter in patients treated with PRP (mean difference = − 7.17 days). However, if only the double-blind studies (n = 2) or studies including only hamstring injuries (n = 3) were considered, non-significant differences were found. Re-injuries (relative risk = − 0.03) and complications (relative risk = 0.01) were also similar between the two groups (p > 0.05), nor were any substantial differences found regarding pain, muscle strength, ROM/flexibility, muscle function, and imaging. The performance bias was high risk due to the lack of patient blinding in four studies. The quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was therefore low or very low.

Conclusions

The promising biological rationale, the positive preclinical findings, and the successful early clinical experience of PRP injections are not confirmed by the recent high-level RCTs. Therefore any benefit in terms of pain, function, return to sport, and recurrence using PRP injections for the treatment of acute muscle injuries is not supported. Due to the bias in the studies, the heterogeneity of the findings, and the limited sample size, the evidence should be considered to be of low or very low quality.

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Beyond Cut-points: Accelerometer Metrics that Capture the Physical Activity Profile

AbstractPurposeCommonly used physical activity metrics tell us little about the intensity distribution across the activity profile. The purpose of this paper is to introduce a metric, the intensity gradient, which can be used in combination with average acceleration (overall activity level) to fully describe the activity profile.Methods1669 adolescent girls (sample 1) and 295 adults with type 2 diabetes (sample 2) wore a GENEActiv accelerometer on their non-dominant wrist for up to 7-days. Body mass index and percent body fat were assessed in both samples and physical function (grip strength, Short Physical Performance Battery, sit-to-stand repetitions) in sample 2. Physical activity metrics were: average acceleration (AccelAV); the intensity gradient (IntensityGRAD from the log-log regression line: 25 mg intensity bins (x)/time accumulated in each bin (y)); total moderate-to-vigorous physical activity (MVPA); and bouted MVPA (sample 2 only).ResultsCorrelations between AccelAV and the IntensityGRAD (r=0.39-0.51) were similar to correlations between AccelAV and bouted MVPA (r=0.48), and substantially lower than between AccelAV and total MVPA (r>0.93). The IntensityGRAD was negatively associated with body fatness in sample 1 (p0.93). The IntensityGRAD was negatively associated with body fatness in sample 1 (p

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