Machine learning hypothesis-generation for patient stratification and target discovery in rare disease: our experience with Open Science in ALS.

Introduction: Advances in machine learning (ML) methodologies, combined with multidisciplinary collaborations across biological and physical sciences, has the potential to propel drug discovery and development. Open Science fosters this collaboration by releasing datasets and methods into the public space; however, further education and widespread acceptance and adoption of Open Science approaches are necessary to tackle the plethora of known disease states. Motivation: In addition to providing much needed insights into potential therapeutic protein targets, we also aim to demonstrate that small patient datasets have the potential to provide insights that usually require many samples (>5,000). There are many such datasets available and novel advancements in ML can provide valuable insights from these patient datasets. Problem statement: Using a public dataset made available by patient advocacy group AnswerALS and a multidisciplinary Open Science approach with a systems biology augmented ML technology, we aim to validate previously reported drug targets in ALS and provide novel insights about ALS subpopulations and potential drug targets using a unique combination of ML methods and graph theory. Methodology: We use NetraAI to generate hypotheses about specific patient subpopulations, which were then refined and validated through a combination of ML techniques, systems biology methods, and expert input. Results: We extracted 8 target classes, each comprising of several genes that shed light into ALS pathophysiology and represent new avenues for treatment. These target classes are broadly categorized as inflammation, epigenetic, heat shock, neuromuscular junction, autophagy, apoptosis, axonal transport, and excitotoxicity. These findings are not mutually exclusive, and instead represent a systematic view of ALS pathophysiology. Based on these findings, we suggest that simultaneous targeting of ALS has the potential to mitigate ALS progression, with the plausibility of maintaining and sustaining an improved quality of life (QoL) for ALS patients. Even further, we identified subpopulations based on disease onset. Conclusion: In the spirit of Open Science, this work aims to bridge the knowledge gap in ALS pathophysiology to aid in diagnostic, prognostic, and therapeutic strategies and pave the way for the development of personalized treatments tailored to the individual's needs.

Utilization of Point-of-Care Ultrasound in a Specialist Palliative Care Team Across Multiple Care Settings: A Retrospective Chart Review.

Background: Technological advancements have rapidly increased the use of point-of-care ultrasound (POCUS) across various medical disciplines, leading to real-time information for clinicians at the bed side. However, literature reveals scant evidence of POCUS use in palliative care. The objective of this study was to examine the use of POCUS in a specialist palliative care setting. Methods: A retrospective chart review was conducted from January 2018 to June 2019 in Brampton, Canada, to evaluate characteristics of patients for whom POCUS was utilized. Patients were identified through pre-existing logs and descriptive information was collected from electronic health records, including demographic information, life-limiting diagnosis, patient assessment location, diagnosis made with POCUS, and, if applicable, volume of fluid drained. Results: We identified 126 uses of POCUS in 89 unique patients. Sixty-two patients (69.7%) had a cancer diagnosis, with patients most commonly suffering from gastrointestinal, lung, and breast pathologies. Sixty-one POCUS cases (48.4%) were in the outpatient setting. Eighty-one POCUS cases (64.3%) revealed a diagnosis of ascites and 21 POCUS cases (16.7%) revealed a diagnosis of pleural effusion. Other diagnoses made with POCUS included bowel obstruction, pneumonia, and congestive heart failure. During the study period, 52 paracentesis and 7 thoracentesis procedures were performed using POCUS guidance. Conclusion: We identified multiple indications in our specialist palliative care setting where POCUS aided in diagnosis/management of patients in both inpatient and outpatient settings. Further studies can be conducted to identify the potential benefits in symptom burden, patient and caregiver satisfaction, and health care utilization in palliative care patients receiving POCUS.

Soluble T cell immunoglobulin and mucin-domain containing protein 3 in children hospitalized with pneumonia in resource-limited settings.

In a prospective cohort study of 77 children with severe pneumonia from two hospitals in Uganda, we assessed soluble T cell immunoglobulin and mucin-domain containing protein 3 (sTIM-3) levels at hospital admission and their association with pneumonia severity and subsequent mortality. sTIM-3 levels were positively correlated with the Respiratory Index of Severity in Children (RISC) (ρ = 0.35, p = 0.0017), sTIM-3 levels were higher in children who required transfer to a tertiary hospital (p = 0.014) and in fatal cases (p = 0.011). In summary, sTIM-3 is associated with disease severity and predictive of mortality in childhood pneumonia in resource-limited settings.

RELIEF: A Digital Health Tool for the Remote Self-Reporting of Symptoms in Patients with Cancer to Address Palliative Care Needs and Minimize Emergency Department Visits.

The lack of timely symptom reporting remains a barrier to effective symptom management and comfort for patients with cancer-related palliative care needs. Poor symptom management at home can lead to unwanted outcomes, such as emergency department visits and death in hospital. We developed and evaluated RELIEF, a remote symptom self-reporting app for community patients with palliative care needs. A pilot feasibility study was conducted at a large, community hospital in Ontario, Canada. Patients self-reported their symptoms each morning using validated clinical symptom measures and RELIEF would alert for worsening or severe symptoms. RELIEF alerts were monitored by palliative care nurses who would then contact patients to determine if appropriate clinical intervention could be initiated to avoid unnecessary emergency department visits. A total of 20 patients were recruited to use RELIEF for two months. Patients completed 80% of daily self-report assessments; 133 alerts were trigged, half of which required clinical intervention. No patient visited the emergency department for symptom management during the study. Clinical staff estimated five emergency department visits were avoided because of RELIEF-saving an estimated cost of over CAD 60,000. RELIEF is a feasible and acceptable method for the remote monitoring of patients with palliative care needs through regular symptom self-reporting.

Magnetic resonance imaging analysis of human skull diploic venous anatomy.

BACKGROUND: The skull diploic venous space (DVS) represents a potential route for cerebrospinal fluid (CSF) diversion and absorption in the treatment of hydrocephalus. The goal of this study was to carry out a detailed characterization of the drainage pattern of the DVS of the skull using high-resolution MRI, especially the diploic veins draining to the lacunae laterales (LLs) since the LLs constitute an important channel for the CSF to access the superior sagittal sinus and subsequently the systemic circulation. The objective was to identify those skull regions optimally suited for an intraosseous CSF diversion system. METHODS: High-resolution, T1-weighted MRI scans from 20 adult and 16 pediatric subjects were selected for analysis. Skulls were divided into four regions, that is, frontal, parietal, temporal, and occipital. On each scan, a trained observer counted all diploic veins in every skull region. Each diploic vein was also followed to determine its final drainage pathway (i.e., dural venous sinus, dural vein, LL, or indeterminate). RESULTS: In the adult age group, the frontal and occipital skull regions showed the highest number of diploic veins. However, the highest number of draining diploic veins connecting to the lacunae lateralis was found in the frontal and parietal skull region, just anterior and just posterior to the coronal suture. In the pediatric age group, the parietal skull region, just posterior to the coronal suture, showed the highest overall number of diploic veins and also the highest number of draining diploic veins connecting to the LL. CONCLUSION: This study suggested that diploic venous density across the skull varies with age, with more parietal diploic veins in the pediatric age range, and more occipital and frontal diploic veins in adults. If the DVS is ultimately used for CSF diversion, our anatomical data point to optimal sites for the insertion of specially designed intraosseous infusion devices for the treatment of hydrocephalus. Likely the optimal sites for CSF diversion would be the parietal region just posterior to the coronal suture in children, and in adults, frontal and/or parietal just anterior or just posterior to the coronal suture.

Myopenia and Reduced Subcutaneous Adiposity in Children With Liver Disease Are Associated With Adverse Outcomes.

BACKGROUND: Sarcopenia is defined as reduced skeletal muscle mass (SMM) or myopenia and altered muscle function and physical performance. It is unknown whether myopenia in children with end-stage liver disease (ESLD) adversely impacts clinical outcomes. We hypothesized that myopenia was prevalent in children with ESLD and related to suboptimal nutrition intake contributing to gross motor and growth delay, increased hospitalization, and medical complications. METHODS: This retrospective study evaluated abdominal imaging (computed tomography/magnetic resonance imaging) for SMM (total, psoas, paraspinal, abdominal wall muscle; cm2 /height2 ) and adipose tissue (total, visceral, subcutaneous adipose tissue [SAT], ) determinations at the third and fourth lumbar vertebrates during liver transplantation (LTx) assessment. ESLD children (n = 30) were age- and gender-matched to healthy controls (n = 24). Myopenia was defined as SMM index z score <-2 and low SAT was defined as SAT index z-score <-1.5. Anthropometric, biochemical, and clinical data (hospitalization, complications, growth, neurodevelopment, energy/protein intake) were collected at LTx assessment, LTx, and post LTx (first hospitalization, 6 months, 12 months). RESULTS: Four distinct body composition phenotypes in children with ESLD were found: (1) myopenia with low SAT (17%;5 of 30), (2) myopenia (3%;1 of 30), (3) low SAT (20%;6 of 30), (4) normal muscle mass and SAT (60%;18 of 30). Myopenia with low SAT was prevalent in older (>2 years), male children and was associated with gross motor delay, reduced energy intake, and increased hospitalization and infections (total/viral/fungal). CONCLUSIONS: Myopenia, accompanied by low SAT in children with ESLD, is associated with adverse clinical outcomes. Rehabilitation strategies aimed at combating myopenia in children are important.

Systematic rapid living review of the impact of the COVID-19 pandemic on cancer survivors: update to August 27, 2020.

BACKGROUND: The COVID-19 pandemic has resulted in drastic changes in the global healthcare delivery landscape and has had practical repercussions for cancer survivors. This systematic rapid living review has been undertaken to synthesise the available knowledge regarding the impact of the COVID-19 pandemic in a timely manner. This initial rapid review will present the findings of literature published up to August 27, 2020. DESIGN: A systematic search of PubMed, Scopus and Google Scholar databases was conducted to identify all articles, available in English language, regarding the impact of the COVID-19 pandemic on cancer survivors published between December 2019 and August 27, 2020. The search strategy employed the following search strings: "covid-19 OR coronavirus OR sars-cov-2" with "cancer survivors OR cancer survivorship". RESULTS: The database search yielded 1639 articles, of which 19 were included. Of the 19 selected articles, there were 12 expert opinion articles, two literature reviews, two prospective cohort studies, one retrospective cohort study, one descriptive study and one pooled meta-analysis that comment on the impact of the COVID-19 pandemic on the physical wellbeing (16 articles), psychosocial wellbeing (15 articles) and financial wellbeing of cancer survivors (3 articles). CONCLUSIONS: Limited definitive evidence exists regarding the impact of the COVID-19 pandemic on cancer survivors. Currently available literature provides preliminary indications of wide-ranging impacts of the pandemic on cancer survivors with respect to the requirement to adapt to new means of healthcare delivery as well as their physical, psychosocial and economic wellbeing. The pandemic has left survivors dealing with the consequences of rigorous cancer treatment in the context of new challenges related to social isolation, financial hardship and uncertainty with respect to their ongoing care. Additional rigorously designed research initiatives are required to elucidate the impact of the pandemic on cancer survivors.

Perceptions of palliative care in a South Asian community: findings from an observational study.

BACKGROUND: Patients often view "palliative care" (PC) as an approach that is synonymous with end-of-life and death, leading to shock and fear. Differing cultural and social norms and religious affiliations greatly determine perception of PC among diverse populations. METHODS: This prospective observational study aimed to explore perceptions of PC among South Asian community members at one Canadian site. Patients who identified themselves as being of South Asian origin were consented and enrolled at a PC Clinic at a community hospital in Brampton, Ontario serving a large South Asian population. Participants filled out an 18-question survey created for the study and responded to a semi-structured interview consisting of 8 questions that further probed their perceptions of PC. Survey responses and semi-structured interviews content were analyzed by four authors who reached consensus on key exploratory findings. RESULTS: Thirty-four participants of South Asian origin were recruited (61.8% males), and they were distributed by their age group as follows: [(30-49) - 18%; (50-64) - 21%; (65-79) - 41%; (≥ 80) - 21%]. Five main exploratory findings emerged: (i) differing attitudes towards talking about death; (ii) the key role of family in providing care; (iii) a significant lack of prior knowledge of PC; (iv) a common emphasis on the importance of alleviating suffering and pain to maintain comfort; and (v) that cultural values, faith, or spiritual belief do not pose a necessary challenge to acceptance of PC services. CONCLUSIONS: Observations from this study provide a source of reference to understand the key findings and variability in perceptions of palliative care in South Asian communities. Culturally competent interventions based on trends observed in this study could assist Palliative Physicians in delivering personalized care to South Asian populations.

Dysregulation of angiopoietin-Tie-2 axis in ugandan children hospitalized with pneumonia.

OBJECTIVE: Pneumonia is the leading cause of death in children under 5, with the highest burden in resource-limited countries. Endothelial activation occurs in pneumonia and can be assessed using quantitative levels of biomarkers angiopoietin (Ang)-1 and Ang-2. We examined admission levels of Ang-1 and Ang-2 in pediatric pneumonia and their association with disease severity and outcome. METHODS: Prospective cohort study of children with hypoxemic pneumonia admitted to two hospitals in Uganda. Clinical, radiographic, and microbiologic characteristics were measured at admission. Disease severity was assessed using the Respiratory Index of Severity in Children (RISC). Plasma levels of Ang-1 and Ang-2 were quantified by enzyme-linked immunosorbent assay. Vital signs, oxygen supplementation, and mortality were assessed prospectively. RESULTS: We included 65 patients (43% female) with median age 19 months (IQR 8-24). Admission Ang-2/Ang-1 ratio directly correlated with RISC (ρ = 0.32, p = 0.008) and lactate level (ρ = 0.48, p < 0.001). Ang-2/Ang-1 ratio was higher in pneumococcal pneumonia than viral RTI (0.19 [IQR: 0.076-0.54] vs. 0.078 [IQR: 0.027-0.11]; p = 0.03). Elevated Ang-2/Ang-1 ratio (>0.084) was associated with prolonged tachypnea (HR 0.50 (95%CI 0.29-0.87), p = 0.02), fever (HR 0.56 (95%CI 0.33 to 0.96), p = 0.02), longer duration of oxygen therapy (HR 0.59 (95%CI 0.35-0.99), p = 0.04), and hospital stay (HR 0.43 (95%CI 0.25-0.74), p = 0.001). The Ang-2/Ang-1 ratio at admission was higher in fatal cases relative to survivors (0.36 [IQR: 0.17-0.58] vs. 0.077 [IQR: 0.025-0.19]; p = 0.05) CONCLUSION: Endothelial activation in hypoxemic pediatric pneumonia, reflected by high plasma Ang-2/Ang-1 ratio, is associated with disease severity, prolonged recovery time, and mortality.

Magnetic Apposition across the Epiglottis: Radiographic and Operative Correlation of a Rare Hypopharyngeal Foreign Body.

Background and Aim. Rare-earth magnet ingestions are a subset of foreign body ingestions and can result in significant morbidity secondary to pressure necrosis. These magnets are best visualized radiographically, typically located in the gastrointestinal tract. However, unusual locations of magnetic adherence may include the hypopharynx along the epiglottis, where only 2 previous cases have been reported. Clinicians should be aware of the potential dangers of rare-earth magnet ingestion and consider atypical locations of attachment in the appropriate clinical setting. Case Presentation. We present an interesting case of a fourteen-year-old female patient who presents with witnessed ingestion of multiple rare-earth magnets. Soft-tissue neck radiographs demonstrate two adjacent rounded radiopaque densities in the hypopharynx. Intraoperative images confirmed the radiographic findings and identified two magnetic balls stuck along the dorsal and ventral aspect of the epiglottis without evidence of pressure necrosis. CONCLUSION: This is the first published case of magnetic foreign body adherence to the epiglottis in the Radiology literature. Awareness and recognition of the unique radiographic findings of this rare entity can help clinicians streamline timely management.

Deficits in Muscle Strength and Physical Performance Influence Physical Activity in Sarcopenic Children After Liver Transplantation.

Sarcopenia is a muscle disease characterized by reduced skeletal muscle mass (SMM), muscle strength, and physical performance. Reduced SMM has been identified in children after liver transplantation (LT), but no information related to muscle strength/physical performance or lifestyle factors contributing to sarcopenia is available. We hypothesized that sarcopenia, as determined by measures of SMM, muscle strength, and physical performance, is highly prevalent in children after LT and is related to poor diet quality (DQ) and physical inactivity. A cross-sectional study in post-LT children (n = 22) and age-matched healthy controls (n = 47) between the ages of 6 and 18 years examining body composition (dual energy X-ray absorptiometry and multiple skinfold), measures of muscle strength (handgrip, sit-to-stand, and push-ups), physical performance (6-minute walk test and stair climb test), diet (3-day food intake), and physical activity (accelerometer) was conducted. Low muscle strength/physical performance and SMM (SMM z scores ≤-1.5) were defined by values 2 standard deviations below the mean values for age- and sex-matched controls. Sarcopenia occurred in 36% of children who underwent LT, and they had significantly lower scores for muscle strength (sit-to-stand and push-up tests) and physical performance (stair climb test) than controls (P < 0.05). Deficits in physical performance in children with sarcopenia were predominantly revealed by longer stair climbing times (P = 0.03), with no differences in other muscle tests. Low SMM, muscle strength, and physical performance were associated with a lower amount of time spent in fairly and very active physical activity, but no associations with DQ were found. Sarcopenia is highly prevalent in children after LT and is related to lower moderate-to-vigorous physical activity. Development of effective rehabilitation strategies to treat sarcopenia are needed in post-LT children.

Mycobacterium chimaera Encephalitis Following Cardiac Surgery: A New Syndrome.

We report the cases of 3 patients with fatal, disseminated Mycobacterium chimaera infections following cardiac surgeries. Progressive neurocognitive decline and death were explained by active granulomatous encephalitis, with widespread involvement of other organs. This syndrome is clinically elusive and, thus, may have caused deaths in prior reported series.

Effects of a Cancer Survivorship Clinic-preliminary results.

PURPOSE: Initial investigation of the impact of a Cancer Survivorship Clinic following its introduction in February 2017. METHODS: A systematic chart review of 176 patients enrolled in the Cancer Survivorship Clinic (CSC) who completed a minimum of one follow-up visit after the initial baseline visit. This was assessed using three screening tools: distress thermometer (DT), Canadian Problem Checklist (CPC), and Edmonton Symptom Assessment Scale (ESAS). Descriptive statistics and t tests were utilized to assess the impact of the CSC. RESULTS: Distress thermometer: Statistically significant decline in scores from the baseline visit to the follow-up visit among the study population (p < 0.05). There was a significant decline in score among high-risk patients with an initial DT≥4 (p < 0.0001). Canadian Problem Checklist: Based on the initial baseline visit, the top five reported causes of distress among the study population include pain, anxiety, fatigue, tingling in hands and feet, sleep. Edmonton Symptom Assessment Scale: Statistically significant decline in reported pain, tiredness, nausea, depression, anxiety, drowsiness, and shortness of breath scores (p < 0.05). CONCLUSIONS: Overall, patients had a significant reduction in distress from the baseline visit to the follow-up visit. High-risk patients experienced a more significant reduction in distress. Reduction in patient distress was independent of the number of visits to the clinic. Reported symptom severity for pain, tiredness, depression, anxiety, drowsiness, and shortness of breath also declined significantly following clinic intervention. Further qualitative studies required to establish the clinical significance of study findings. IMPLICATIONS FOR CANCER SURVIVORS: Continued active clinical support and education for cancer survivors should be considered a potentially essential element in the cancer treatment trajectory to address patient well-being and distress.

The effect of ginger (Zingiber officinale Roscoe) in patients with advanced cancer.

BACKGROUND: Anorexia-cachexia syndrome (ACS) is a complex condition in advanced cancer patients, defined by disproportionate loss of skeletal muscle mass, and a lack or loss of appetite. This condition greatly lowers the quality of life and limits the treatment options. ACS is commonly associated with gastrointestinal symptoms such as nausea and vomiting. Ginger has been successful in treating these symptoms but has not yet been tested on patients with advanced cancer. Electrogastrography is a technology that allows the direct recording of the gastric myoelectrical activity (GMA). PURPOSE: The aim of this study is to (1) determine the effects of ginger on the GMA in these patients, (2) evaluate the subjective symptoms using 3 validated scales, and (3) correlate the level of inflammatory factors and ghrelin in this patient population. METHODS: Patients with ACS and advanced cancer were recruited from the Palliative Rehabilitation outpatient program at Elisabeth Bruyère Hospital. Patients were instructed to take a daily capsule of 1650 mg of ginger for 14 days and outcome measures were recorded at pre- and post-intervention, which included a blood test for analysis of CRP, albumin and ghrelin levels, 3 self-administered surveys (DSSI, PG-SGA, ESAS), patient-reported symptoms, and an EGG diagnosis. RESULTS: Fifteen patients with a median age of 58 and varying cancer diagnoses were enrolled. EGG diagnosis showed that 9 of the 15 patients had a direct improvement in their GMA, and all patients showed improvement in reported symptoms, most notably nausea, dysmotility- and reflux-like symptoms. There was no correlation found for ginger administration and inflammatory factors. CONCLUSION: These findings suggest that ginger may improve GMA as measured by EGG and may have a notable effect on symptom improvement.

Doppler ultrasound values after liver transplantation in children and their association with graft outcomes: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Liver graft and patient survival in children have improved substantially over the years; nevertheless, graft-related complications persist as the most important risk factor for mortality and graft loss. Doppler ultrasound evaluation is routinely used after liver transplantation; however, there is no consensus defining normal values, timing or frequency of Doppler ultrasound postoperative evaluation. Identification of patients who require an intervention or change in postoperative management is therefore challenging. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis to appraise and synthesise evidence describing Doppler ultrasound measurements and their association with graft complications in children who have received a liver transplant. We will search multiple databases: Ovid Medline, Embase, Wiley Cochrane Library, Web of Science-Science Citation Index Expanded, trial registry records and meeting abstracts using a combination of subject headings and keywords for liver transplantation, Doppler ultrasound and paediatric patients. All identified titles and abstracts of studies will be assessed for potential relevance. Selected studies will be retrieved and subjected to a second phase of screening, both selection phases will be done in duplicate by two independent reviewers, and discrepancies will be documented and resolved by a third reviewer. Data extraction will be done independently by two reviewers using a standardised data extraction form. Quality of evidence and risk of bias will be assessed, synthesised and pooled for meta-analysis if possible. We will perform a subgroup analysis if enough data are available. ETHICS AND DISSEMINATION: Strategies to disseminate our review include presenting in liver transplant review sessions, publishing in high-impact peer-reviewed medical journals, and presenting at national and international paediatric radiology and liver transplant meetings, conference presentations, events, courses and plain-language summaries. This knowledge will allow easier identification of patients with a higher risk of developing graft-related complications and could potentially improve patient and graft outcomes. We wish to disseminate our results to discover potential areas for future research and drive improved future practices and policies. Our target audience includes researchers, institutions, healthcare professionals, health system decision-makers, policy-makers and research funders community. TRIAL REGISTRATION NUMBER: CRD42019119986.

Biomarkers of Systemic Inflammation in Ugandan Infants and Children Hospitalized With Respiratory Syncytial Virus Infection.

BACKGROUND: Optimizing outcomes in respiratory syncytial virus (RSV) pneumonia requires accurate diagnosis and determination of severity that, in resource-limited settings, is often based on clinical assessment alone. We describe host inflammatory biomarkers and clinical outcomes among children hospitalized with RSV lower respiratory tract infection (LRTI) in Uganda and controls with rhinovirus and pneumococcal pneumonia. METHODS: 58 children hospitalized with LRTI were included. We compared 37 patients with RSV, 10 control patients with rhinovirus and 11 control patients with suspected pneumococcal pneumonia. RESULTS: Patients in the RSV group had significantly lower levels of C-reactive protein (CRP) and chitinase-3-like protein 1 (CHI3L1) than the pneumococcal pneumonia group (P < 0.05 for both). Among children with RSV, higher admission levels of CRP predicted prolonged time to resolution of tachypnea, tachycardia and fever. Higher levels of CHI3L1 were associated with higher composite clinical severity scores and predicted prolonged time to resolution of tachypnea and tachycardia, time to wean oxygen and time to sit. Higher levels of lipocalin-2 (LCN2) predicted prolonged time to resolution of tachypnea, tachycardia and time to feed. Higher admission levels of all 3 biomarkers were predictive of a higher total volume of oxygen administered during hospitalization (P < 0.05 for all comparisons). Of note, CHI3L1 and LCN2 appeared to predict clinical outcomes more accurately than CRP, the inflammatory biomarker most widely used in clinical practice. CONCLUSIONS: Our findings suggest that CHI3L1 and LCN2 may be clinically informative biomarkers in childhood RSV LRTI in low-resource settings.

Sarcopenia in Chronic Liver Disease: Impact on Outcomes.

Malnutrition is a common complication in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT). Malnutrition and sarcopenia overlap in etiology and outcomes, with sarcopenia being defined as reduced skeletal muscle mass and muscle function. The purpose of this review was to identify the prevalence of sarcopenia with and without obesity in adults and children with ESLD and to assess the methodological considerations in sarcopenia diagnosis and the association of sarcopenia with pre- and post-LT outcomes. A total of 38 articles (35 adult and 3 pediatric articles) retrieved from PubMed or Web of Science databases were included. In adults, the prevalence rates of pre-LT sarcopenia, pre-LT sarcopenic obesity (SO), post-LT sarcopenia, and post-LT SO were 14%-78%, 2%-42%, 30%-100%, and 88%, respectively. Only 2 adult studies assessed muscle function in patients diagnosed with sarcopenia. The presence of pre-LT sarcopenia is associated with higher wait-list mortality, greater postoperative mortality, higher infection risk and postoperative complications, longer intensive care unit (ICU) stay, and ventilator dependency. The emerging pediatric data suggest that sarcopenia is prevalent in pre- and post-LT periods. In 1 pediatric study, sarcopenia was associated with poor growth, longer perioperative length of stay (total/ICU) and ventilator dependency, and increased rehospitalization in children after LT. In conclusion, there is a high prevalence of sarcopenia in adults and children with ESLD. Sarcopenia is associated with adverse clinical outcomes. The present review is limited by heterogeneity in the definition of sarcopenia and in the methodological approaches in assessing sarcopenia. Future studies are needed to standardize the sarcopenia diagnosis and muscle function assessment, particularly in the pediatric population, to enable early identification and treatment of sarcopenia in adults and children with ESLD.

Multiple Administrations of Gadobutrol in the Pediatric Brain: No Change in T1 Signal at MRI.

Purpose To determine whether multiple doses of gadobutrol increase the T1 signal intensity in the brains of children. Materials and Methods This retrospective imaging study evaluated 91 children (median age, 5.4 years; age range, 0-17 years) with brain tumors who underwent five or more MR brain examinations at a single institution. A subgroup of 46 patients received five or more administrations of gadobutrol (0.1 mmol/kg) and underwent follow-up MRI. T1 signal intensity in the globus pallidus and dentate nucleus was measured at the first to sixth unenhanced MR brain examination in these children. Globus pallidus-to-corpus callosum and dentate nucleus-to-corpus callosum signal intensity ratios were analyzed by linear mixed-effect analysis. Subgroup analysis was performed for six children who underwent 14 or more administrations of gadobutrol. Results The globus pallidus-to-corpus callosum ratio increased with patient age (absolute change, 0.0052 per year; 95% confidence interval: 0.0033, 0.0071; P < .0001). There was no change in the dentate nucleus-to-corpus callosum ratio with age (P = .30). Among 46 children who received five or more doses of gadobutrol (median dose, 11 mL; range, 3.9-31 mL), there was no change in signal intensity ratio of the globus pallidus (P = .17) or dentate nucleus (P = .44). Among six children who underwent more than 14 administrations of gadobutrol (median dose, 64 mL; range, 40-91 mL) there was no change in signal intensity ratio of the globus pallidus (P = .15) or dentate nucleus (P = .50). Conclusion No increase in T1-weighted signal intensity ratio was observed in the globus pallidus or dentate nucleus after the administration of at least five doses of gadobutrol. © RSNA, 2018 Online supplemental material is available for this article.

Towards the elimination of paediatric tuberculosis in high-income, immigrant-receiving countries: a 25-year conventional and molecular epidemiological case study.

The epidemiology of tuberculosis (TB) in high-income countries is increasingly dictated by immigration. The influence of this trend on paediatric TB and TB elimination are not well defined. We undertook a 25-year conventional and molecular epidemiologic study of paediatric TB in Alberta, one of four major immigrant-receiving provinces in Canada. All isolates of Mycobacterium tuberculosis were DNA fingerprinted using standard methodology. Between 1990 and 2014, 176 children aged 0-14 years were diagnosed with TB. Foreign-born children or Canadian-born children of foreign-born parents accounted for an increasingly large proportion of total cases during the study period (from 32.1% to 89.5%). Of the 78 culture-positive cases, 35 (44.9%) had a putative source case identified by conventional epidemiology, with 34 (97.1%) having a concordant molecular profile. Of the remaining 43 culture-positive cases, molecular profiling identified spatially and temporally related sources in six cases (14.0%). These six children, along with four other children whose source cases were discovered through reverse-contact tracing, had a high morbidity and mortality. The increasing burden of paediatric TB in both foreign-born children and Canadian-born children of foreign-born parents calls for more timely diagnosis of source cases and more targeted screening for latent TB infection.