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.

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.

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.

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.

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.

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.

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.

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.

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.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing-like attacks in a pediatric patient found to have a pontine capillary telangiectasia and developmental venous anomaly: A case report exploring the root of the problem.

Introduction Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)-like attacks are rarely reported in the pediatric population and may remain undiagnosed and under-investigated as a result. Case presentation We present a case of a 15-year-old male with intermittent, episodic, right-sided brief headaches most in keeping with SUNCT, initially diagnosed as paroxysmal hemicrania, but with no response to indomethacin. The pain was likewise not responsive to typical migraine treatments or steroids. Management and outcome Contrast-enhanced magnetic resonance imaging demonstrated a right pontine capillary telangiectasia with an associated developmental venous anomaly that was adjacent to the root of the right trigeminal nerve. Differential diagnosis included first division trigeminal neuralgia with autonomic features. The patient's pain was partially alleviated by oxygen administration and responded well to carbamazepine; he remained pain free on carbamazepine a year later. Conclusion This case highlights the diagnostic dilemma of differentiating SUNCT from trigeminal neuralgia with autonomic features, both of which are rare diagnoses in pediatric patients, and the importance of appropriate neuroimaging to rule out secondary causes in patients presenting with trigeminal autonomic cephalalgias, recognizing that abnormalities identified on neuroimaging, such as vessels adjacent to the trigeminal nerve, may not be causative findings.

Reported distress in patients living with advanced cancer: changes pre-post interdisciplinary palliative rehabilitation.

PURPOSE: Patients are living extended life with advanced cancer making it chronic rather than imminently terminal. Literature on the experience of living with advanced cancer is emerging, indicating ongoing polysymptomatic burden, lack of information, burnout (patients and caregivers), and emotional concerns, all of which contribute to emotional distress. The interdisciplinary Ottawa Palliative Rehabilitation Program (PRP) offers a scarce clinical resource for this population. The current research aimed to explore changes in self-reported distress for patients who completed the PRP, from baseline to program completion. METHODS: A secondary analysis of self-report and clinical measures was performed for 180 patients who completed the PRP. Measures included the Distress Thermometer and the Problem checklists. Descriptive statistics described the sample, paired-sample t tests examined changes in Distress Thermometer scores from baseline to PRP completion, and McNemar's tests revealed whether the most commonly endorsed checklist items changed by PRP completion. RESULTS: Participants (n = 180) had advanced heterogeneous cancers (mean age = 62.18, 49.4% male). From baseline to completion, significant reported changes included decreases in endorsement of clinical distress (from 55.6 to 38.9%; p < 0.001) and decreases in 7/10 of the most commonly endorsed checklist problems (p values ranging from 0.016 to <0.001). CONCLUSIONS: A number of endorsed checklist problems significantly decreased, as did overall self-reported distress. Compared to the existing literature that does not show improvements, our finding begins to support that palliative rehabilitation may benefit patient levels of distress by improving function and quality of life. Psychotherapy, anesthesia, and additional intervention for cognitive difficulties may further benefit patients.

Safety of gadobutrol in more than 1,000 pediatric patients: subanalysis of the GARDIAN study, a global multicenter prospective non-interventional study.

BACKGROUND: Gadobutrol is a gadolinium-based contrast agent, uniquely formulated at 1.0 mmol/ml. Although there is extensive safety evidence on the use of gadobutrol in adults, few studies have addressed the safety and tolerability of gadobutrol in pediatric patients. OBJECTIVE: This subanalysis of data from the GARDIAN study evaluated the safety and use of gadobutrol in pediatric patients (age <18 years). MATERIALS AND METHODS: The GARDIAN study was a large phase IV non-interventional prospective multicenter post-authorization safety study performed in Europe, Asia, North America and Africa. A total of 23,708 patients were included who were scheduled to undergo cranial or spinal MRI, liver or kidney MRI, or MR angiography with gadobutrol enhancement. The primary study endpoint was the overall incidence of adverse drug reactions (ADRs) and serious adverse events (SAEs) following gadobutrol administration. RESULTS: The GARDIAN study included 1,142 children (age <18 years) who received gadobutrol at a mean dose of 0.13 (range 0.04-0.50) mmol/kg body weight. Gadobutrol was well tolerated in these children, with low rates of ADRs (0.5%) and no SAEs, consistent with results in adults enrolled in the GARDIAN study. Rates of adverse events and ADRs were unrelated to pediatric age or gadobutrol weight-adjusted dose. There were no symptoms suggestive of nephrogenic systemic fibrosis. Investigators rated the contrast quality of gadobutrol-enhanced images as good or excellent in 97.8% of pediatric patients, similar to the main study population. CONCLUSION: Gadobutrol is very well tolerated and provides excellent contrast quality at the recommended weight-adjusted dose in children (age <18 years), similar to the profile in adults.

Attitudes of oncologists towards palliative care and the Edmonton Symptom Assessment System (ESAS) at an Ontario cancer center in Canada.

BACKGROUND: Cancer Care Ontario promotes the Edmonton Symptom Assessment System (ESAS) for standardized systematic screening and assessment of symptoms across cancer centers in Ontario, Canada. Attitudes of medical oncologists (MOs), radiation oncologists (ROs), and general practitioners in oncology (GPOs) toward palliative care, and the ESAS were surveyed in Ottawa. METHODS: A four-part questionnaire was developed, drawing on items from similar studies. RESULTS: Forty respondents (17 MOs, 16 ROs, and 7 GPOs) were interviewed. Attitudes to palliative care: regarding coordination of care across the illness trajectory including end of life by MOs, all ROs disagreed while 71.4 % of GPOs and 41.2 % of MOs agreed that this was the MO's role. Most respondents supported palliative care alongside concurrent anti-tumor therapies (82.4 % MOs, 62.5 % ROs, and 100 % GPOs). Attitudes to ESAS: respondents agreed that the ESAS enhances care and assessment of symptom severity. ROs felt that reviewing the ESAS histogram was less useful than did MOs (42.9 versus 76.5 %, respectively); 56.3 % of ROs and 88.2 % of MOs agreed that the ESAS is useful for follow-up (p < 0.08); 64.7 % of MOs, 88.3 % of GPOs, and 6.3 % of ROs agreed with ESAS completion at every visit (p < 0.00). Frequency of use of the ESAS: 62.5 % of respondents reported inspecting the ESAS "most of the time or always," while 17.5 % reported "never" or "rarely." CONCLUSIONS: MOs and GPOs appear more positive than ROs toward regular use of ESAS. There is discordance between what is perceived to be a useful beneficial instrument versus actual use of the instrument in daily practice. The reasons for this gap need to be better understood in future studies.

Postnatal Diagnosis of a Baby With Multiple Rare Congenital Anomalies Including Syngnathia, Brain Dysmorphism, and Skin Pigmentation.

Syngnathia is a rare congenital disorder of jaw fusion with a paucity of literature from developed countries. We present a case of an infant noted to have multiple anomalies at birth including syngnathia, microcephaly with a variant of brain abnormality between holoprosencephaly and syntelencephaly, optic nerve hypoplasia, ear canal anomalies, hemi-vertebrae, and suspected hypomelanosis of Ito. To our knowledge, this patient with syngnathia and multiple anomalies is the first to be reported, but whether they are a coincidence, a pathogenetic association, or a new syndrome remains unknown. This case is discussed with a brief review of the literature.

Doppler ultrasound velocities and resistive indexes immediately after pediatric liver transplantation: normal ranges and predictors of failure.

OBJECTIVE: We sought to determine the ranges of Doppler ultrasound findings immediately after pediatric liver transplantation that are associated with successful outcomes or postoperative complications. MATERIALS AND METHODS: This study included consecutive children who underwent Doppler ultrasound less than 48 hours after liver transplantation from 2001 to 2011. Operative reports and clinical outcome data were recorded. We had 110 patients (54% girls) with mean age at transplantation of 2.9 years (median, 1.3 years; range, 0-14 years) and a median follow-up interval of 3.5 years. Two pediatric radiologists reviewed ultrasound images in consensus. We computed descriptive statistics, interindex correlations, and analysis of variance. RESULTS: Twenty-four of 110 patients had a vascular complication, most commonly hepatic arterial thrombosis (seven patients). Compared with published adult normal values, normal pediatric Doppler parameters at postoperative day 1 trended toward higher normal velocities and resistive indexes (up to 0.95). Absent or low-velocity common hepatic artery flow less than 50 cm/s or a common hepatic artery resistive index less than 0.50 were significantly associated with hepatic artery thrombosis, whereas absent or low-velocity portal venous flow less than 30 cm/s or low-velocity hepatic venous flow less than 25 cm/s were significantly associated with vascular complications and a monotonic hepatic venous waveform was significantly associated with venous complications. CONCLUSION: Flow in a pediatric liver on the first day after transplantation is normally hyperdynamic, especially in the youngest transplant recipients, and, as a result, low velocities or resistive indexes are particularly concerning for complications. The pediatric-specific ranges of expected posttransplantation Doppler ultrasound findings presented in this article should assist in identifying normal variation and potentially life-threatening complications.

Use of gemcitabine with multi-stage surgical resection as successful second-line treatment of metastatic pancreatoblastoma.

Pancreatoblastoma is a rare pediatric pancreatic malignancy. It confers a worse prognosis if there is metastatic or unresectable disease. We report a case of a 12-year-old boy who presented with pancreatoblastoma of the head of the pancreas with multiple intrahepatic metastases. We successfully treated him using aggressive chemotherapy, multi-stage surgery, and gemcitabine chemotherapy, which has not been described as treatment for pancreatoblastoma. Rare childhood malignancies such as pancreatoblastoma require a coordinated, multidisciplinary approach and frequent reassessment of therapeutic interventions. Complete surgical resection is important for cure and may require complex, aggressive, multiple-stage surgical procedures with concurrent or novel chemotherapy.

How specific is the MRI appearance of supratentorial atypical teratoid rhabdoid tumors?

BACKGROUND: Supratentorial atypical teratoid rhabdoid tumor (ATRT) in many cases has a distinctive appearance on post-gadolinium MRI. OBJECTIVE: We sought to determine whether this is a unique appearance allowing ATRT to be distinguished accurately from other types of pediatric supratentorial tumors. MATERIALS AND METHODS: Retrospective review of all available preoperative MRI of pediatric supratentorial tumors at two tertiary children's hospitals, and systematic literature review of case series and reports describing the MRI imaging appearances of supratentorial ATRT. RESULTS: We had 61 supratentorial tumors, including 32 gliomas, 6 ATRT, 8 ependymomas, 6 gangliogliomas, 2 pilomyxoid astrocytomas, 3 primitive neuro-ectodermal tumors, 2 choroid plexus papillomas, and 2 meningiomas. ATRT presented in significantly younger patients than astrocytomas (mean age 2.6 years vs. 9.9 years, P < 0.05). The visual pattern of a thick, wavy (irregular) heterogeneously enhancing wall around a cystic center was seen in 5/6 (83%) ATRTs and only 3/55 (5.4%) other tumors (P < 0.0001), for specificity of 95%, sensitivity of 83%, positive predictive value of 63% and a negative predictive value of 95%. CONCLUSION: A supratentorial tumor with a thick, wavy (irregular) heterogeneously enhancing wall surrounding a central cystic region is suggestive of ATRT in the appropriate clinical setting, especially in a child of preschool age.

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.

Gastrointestinal symptoms, electrogastrography, inflammatory markers, and PG-SGA in patients with advanced cancer.

OBJECTIVES: Electrogastrography (EGG) is a technique used to record gastric myoelectrical activity (GMA). Our aim is to investigate the (1) prevalent patterns of GMA, (2) most frequent gastrointestinal (GI) symptoms reported on the Dyspepsia Symptom Severity Index (DSSI), and (3) EGG diagnosis and correlations with GI symptoms, ghrelin, and inflammatory markers. METHODS: An EGG was performed 10 min preprandial and 30 min postprandial after ingestion of 500 ml water. EGG measurements were recorded by electrodes positioned externally on the abdominal wall. C-reactive protein (CRP), ghrelin, and albumin were included at baseline. RESULT: There were 53 patients enrolled, with a median age of 60 years (range, 18-82 years) and EGG diagnoses of mixed dysrhythmia (n = 25), tachygastria (n = 15), bradygastria (n = 6), gastric outlet obstruction (n = 1), and normal (n = 6). Forty-seven patients with an abnormal EGG had high median CRP, low median albumin, and high median ghrelin levels when compared to 6 patients with a normal EGG, with CRP [12 (8-22) vs. 6 (5-8)]; albumin [35 (26-40) vs. 38.5 (34-42)]; ghrelin [4 (2-10) vs. 2.5 (2-9)]. According to the DSSI, the most frequent dysmotility-like symptoms were (1) frequent burping and belching [73.6%], (2) bloating [60.4%], (3) feeling full after meals [69.8%], (4) inability to finish normal-sized meal [66%], (5) abdominal distention [51%], and (6) nausea after meals [50.9%]. The most frequent reflux- and ulcer-like symptoms were (1) regurgitation of bitter fluid [43.4%] and abdominal pain before meals [39.6%]. The most frequent nutrition impact symptoms as recorded on the Patient-Generated Subjective Global Assessment in patients with an abnormal EGG diagnosis were no appetite or did not feel like eating, nausea, vomiting, and feeling full quickly. CONCLUSIONS: Abnormal EGG diagnosis, ghrelin, albumin, and CRP levels are found in the majority of patients with advanced cancer. Further studies are needed to better understand the correlation of these abnormal serum levels and their interaction with the pathogenesis of abnormal electrogastrographic rhythms.