Improved HPLC method with automated pre-column sample derivatisation for serum pegylated L-asparaginase activity measurement in paediatric acute lymphoblastic leukaemia patients.

Therapeutic drug monitoring of pegylated L-asparaginase (ASNase) ensures the drug effectiveness in childhood acute lymphoblastic leukaemia (ALL) patients. The biological drug property with variable immunogenic host clearance, and the prescription of its generic formulation urge the need for a reliable assay to ensure an optimal treatment and improve outcome. This study aimed to optimise an existing isocratic reversed-phase high performance liquid chromatography (RP-HPLC) method with an automated pre-column sample derivatisation and injection program, and a computational algorithm for measuring serum pegylated ASNase activity in children with ALL. Nath et al.'s method in 2009 was adopted and modified using a pegylated ASNase. A set of Microsoft Excel macros was developed for the serum drug activity computation. An Agilent InfinityLab LC Series 1260 Infinity II Quaternary System with fluorescence detection was employed with an Agilent Poroshell 120 EC-C18 4.6×100 mm, 2.7 µm analytical column. System flow rate was optimised to 2.0 mL/min with 40×10-6/bar pump compressibility. The O-phthaldialdehyde (OPA) solution composition was optimised to 1 % o-phthaldialdehyde, 0.8 % 2-mercaptoethanol, 7.13 % methanol, and 1.81 % sodium tetraborate. The pre-column derivatisation program mixed 0.1 µL sample with 25 µL OPA solution before the automated injection. Method validation was according to the ICH guidelines. Total analysis time was 15 min, with L-aspartic acid eluted at 0.96 min and internal standard at 4.7 min. The calibration curves showed excellent linearity (R ≥0.9999). Interday precision for the drug activity at 0.1 IU/mL, 0.5 IU/mL, and 1 IU/mL were 4.15 %, 3.05 %, and 3.09 % (n = 6). Mean %error for the drug activity at 0.1 IU/mL, 0.5 IU/mL, and 1 IU/mL were 0.90±4.41 %, -1.37±3.04 %, and -3.03±3.02 % (n = 6). Limit of quantitation was 0.03 IU/mL. Majority of the patients' serum drug activity fell within the assay calibration range. Our improved method is automated, having shorter analysis time with a well-maintained separation resolution that enables a high-throughput analysis for application.

Roles of Baseline Intrinsic Capacity and its Subdomains on the Overall Efficacy of Multidomain Intervention in Promoting Healthy Aging among Community-Dwelling Older Adults: Analysis from a Nationwide Cluster-Randomized Controlled Trial.

BACKGROUND: Impaired intrinsic capacity (IC), which affects approximately 90% of older adults, is associated with a significantly heightened risk of frailty and cognitive decline. Existing evidence suggests that multidomain interventions have the potential to enhance cognitive performance and yield positive effects on physical frailty. OBJECTIVE: To examine roles of baseline IC and its subdomains on the efficacy of multidomain interventions in promoting healthy aging in older adults. DESIGN: a cluster-randomized controlled trial. SETTING AND PARTICIPANTS: 1,054 community-dwelling older adults from 40 community-based clusters across Taiwan. INTERVENTION: A 12-month pragmatic multidomain intervention of exercise, cognitive training, nutritional counseling and chronic condition management. MEASUREMENTS: Baseline IC was measured by 5 subdomains, including cognition (Montreal Cognitive Assessment, MoCA), sensory (visual and hearing impairment), vitality (handgrip strength or Mini-Nutritional Assessment-short form), psychological well-being (Geriatric Depression Scale-5), and locomotion (6m gait speed). Outcomes of interest were cognitive performance (MoCA scores) and physical frailty (CHS frailty score) over a follow-up period of 6 and 12 months. RESULTS: Of all participants (mean age:75.1±6.4 years, 68.6% female), about 90% participants had IC impairment at baseline (2.0±1.2 subdomains). After covariate adjustment using a generalized linear mixed model (GLMM), the multidomain intervention significantly prevented cognitive declines and physical frailty, particularly in those with IC impairment ≥ 3 subdomains (MoCA: coefficient: 1.909, 95% CI: 0.736 ~ 3.083; CHS frailty scores: coefficient = -0.405, 95% CI: -0.715 ~ -0.095). To assess the associations between baseline poor capacity in each IC subdomain and MoCA/CHS frailty scores over follow-up, a 3-way interaction terms (time*intervention*each poorer IC subdomains) were added to GLMM models. Significant improvements in MoCA scores were shown for participants with poorer baseline cognition (coefficient= 1.138, 95% CI: 0.080 ~ 2.195) and vitality domains (coefficient= 1.651, 95% CI: 0.541 ~ 2.760). The poor vitality domain also had a significant modulating effect on the reduction of CHS frailty score after the 6- and 12-month intervention period (6 months: coefficient= -0.311, 95% CI: -0.554 ~ -0.068; 12 months: coefficient= -0.257, 95% CI: -0.513 ~ -0.001). CONCLUSION AND IMPLICATIONS: A multidomain intervention in community-dwelling older adults improves cognitive decline and physical frailty, with its effectiveness influenced by baseline IC, highlighting the importance of personalized strategies for healthy aging.

A Review of L-Asparaginase Hypersensitivity in Paediatric Acute Lymphoblastic Leukaemia Patients with Regard to the Measurement of Anti-Asparaginase Antibodies and Their Genetic Predisposition.

L-asparaginase is effective as part of the first line childhood acute lymphoblastic leukaemia (ALL) treatment regimen but suffers the risk of antibody production causing immune-mediated sequelae. This article aimed to describe the clinical implication of L-asparaginase hypersensitivity and review the types of antibodies and genetic polymorphisms contributing to it. Clinical or subclinical L-asparaginase hypersensitivity may lead to suboptimum therapeutic effect and jeopardise the clinical outcome in ALL children. Anti-asparaginase antibodies immunoglobulin (Ig)G, IgM and IgE were identified in the L-asparaginase hypersensitivities. Enzyme-linked immunosorbent assay (ELISA) is commonly used to quantify the IgG and IgM levels. The role of IgE in mediating L-asparaginase hypersensitivity is contradictory. Moreover, the presence of antibodies may not necessarily correlate inversely with the L-asparaginase efficacies in some studies. Patients with specific genetic variants have been shown to be more susceptible to clinical hypersensitivity of L-asparaginase. With the advance of technology, gene polymorphisms have been identified among Caucasians using whole-genome or exon sequencing, but the evidence is scanty among Asians. There is lack of pre-clinical study models that could help in understanding the pathophysiological pathway co-relating the gene expression and anti-asparaginase antibody formation. In conclusion, future research studies are required to fill the current gap in understanding the immune mediated reactions towards L-asparaginase upon its administration and its potential impact to the disease outcome.

Validation and use of the Second Victim Experience and Support Tool questionnaire: a scoping review.

OBJECTIVES: Patient safety incidents can impact not only patients and families but also healthcare providers, who may experience negative emotions and symptoms, such as anxiety, guilt, stress, and loss of confidence. To identify and support these "second victims," a screening tool called the Second Victim Experience and Support Tool (SVEST) has been developed. This scoping review aims to map our current knowledge of the SVEST in terms of its scope of use, validation and limitations. STUDY DESIGN: Scoping review. METHODS: In accordance with the framework outlined by Arksey and O'Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews, we conducted a literature search in MEDLINE, CINAHL, Cochrane Library, SCOPUS, Embase and PsycINFO databases from database inception up till 1 March 2023. RESULTS: A total of 31 studies were reviewed. The SVEST has been cross-culturally adapted from English into other languages. The SVEST has been successfully used in different contexts and with various healthcare professionals, including doctors, nurses, allied health professionals, midwives and pharmacists. The tool has been used to assess the impact of second victim experiences and the effectiveness of support interventions in addressing the phenomenon. Validity assessment of translated versions of SVEST in the reviewed studies revealed good content validity in most cases, although some studies did not report clear values for scale-level Content Validity Index. On the whole, SVEST is generally a reliable and valid tool, although further refinements and modifications may improve its validity and reliability. CONCLUSIONS: The review highlights the significance of SVEST as a crucial resource for healthcare providers and organisations that prioritise well-being and safety in health care. It also underscores the importance of recognising the needs of second victims and offering them appropriate interventions to manage the aftermath of adverse events.

Long-Term Mortality Risk in Older Adults with Sarcopenia: An 11-Year Prospective Cohort Study Comparing AWGS 2014 and AWGS 2019 Guidelines for Enhanced Clinical Utility and Accurate Risk Prediction.

OBJECTIVES: To discern the diagnostic accuracy between the updated diagnostic consensus of the Asian Working Group for Sarcopenia (AWGS) in 2019 (AWGS 2019) and the previous AWGS 2014 guidelines. DESIGN: A prospective population-based cohort study. SETTING AND PARTICIPANTS: The study included 731 older community-dwelling adults aged ≥ 65 years who participated in face-to-face interviews and were followed up for 11-year mortality until 31 Mar 2022. MEASUREMENTS: We utilized a handgrip strength dynamometer to measure participants' muscle strength, while their walking speed was determined by a timed 6-meter walk test at their usual pace. Additionally, muscle mass was measured using dual-energy X-ray absorptiometry scanning. Sarcopenia was defined as the presence of low muscle mass in combination with weakness and/or slowness both by AWGS 2014 and 2019 criteria. RESULTS: The present study followed 731 participants (mean age 73.4 ± 5.4 years, men predominant 52.8%) over a period of 11 years, yielding 5927 person-years and 159 deaths. Prevalence of sarcopenia defined by AWGS 2019 and 2014 criteria were 8.5% and 6.8%, respectively. Sarcopenia defined by AWGS 2019 (HR 1.62, 95% CI 1.04-2.54, p=0.034) but not AWGS 2014 was significantly associated with mortality in community-living older adults after adjusting for potential confounders such as age, sex, education, drinking, disease burden and serum level of testosterone. The study also found that the AWGS 2019 criteria had a better model fitness than AWGS 2014 criteria in predicting mortality. CONCLUSION: AWGS 2019 criteria outperformed AWGS 2014 in identifying sarcopenia risk and predicting mortality. Screening for sarcopenia in older adults may improve health outcomes by identifying those at increased mortality risk.

Synchronous Primary Parosteal Osteosarcoma and Primary Mediastinal Germ Cell Tumour with Atypical Mycobacterial Infection - A Rare Phenomenon: A Case Report.

Mediastinal germ cell tumours are a rare group of extragonadal germ cell tumours with less than 5% prevalence of all germ cell tumours. Primary mediastinal germ cell tumours themselves account for 16-36% of the extragonadal germ cell tumours. Along the spectrum of osteosarcoma, parosteal osteosarcoma is a well-differentiated surface osteosarcoma with a prevalence of 4% of all osteosarcoma. As such synchronous primary parosteal osteosarcoma and primary mediastinal germ cell tumour are exceedingly rare. This leads to complexity in determining the most appropriate chemotherapy for two different types of tumours and its potential side effects of reduced immunity leading to potential secondary infection. Here we report a case of a 16-year-old boy who presented with synchronous primary osteosarcoma and primary mediastinal germ cell tumour, complicated with atypical mycobacterial infection post-operatively. Additionally, we discuss our choice of chemotherapy and the management of the atypical mycobacterial infection.

Foetal haemoglobin inducers for reducing blood transfusion in non-transfusion-dependent beta-thalassaemias.

BACKGROUND: Non-transfusion-dependent ß-thalassaemia (NTDßT) is a subset of inherited haemoglobin disorders characterised by reduced production of the ß-globin chain of haemoglobin leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it may be required to prevent complications of chronic anaemia, such as impaired growth and hypercoagulability. People with NTDßT also experience iron overload due to increased iron absorption from food sources which becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin (HbF) level have been found to require fewer blood transfusions, thus leading to the emergence of treatments that could increase its level. HbF inducers stimulate HbF production without altering any gene structures. Evidence for the possible benefits and harms of these inducers is important for making an informed decision on their use. OBJECTIVES: To compare the effectiveness and safety of the following for reducing blood transfusion for people with NTDßT: 1. HbF inducers versus usual care or placebo; 2. single HbF inducer with another HbF inducer, and single dose with another dose; and 3. combination of HbF inducers versus usual care or placebo, or single HbF inducer. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 21 August 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs comparing single HbF inducer with placebo or usual care, with another single HbF inducer or with a combination of HbF inducers; or comparing different doses of the same HbF inducer. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were blood transfusion and haemoglobin levels. Our secondary outcomes were HbF levels, the long-term sequelae of NTDßT, quality of life and adverse events. MAIN RESULTS: We included seven RCTs involving 291 people with NTDßT, aged two to 49 years, from five countries. We reported 10 comparisons using eight different HbF inducers (four pharmacological and four natural): three RCTs compared a single HbF inducer to placebo and seven to another HbF inducer. The duration of the intervention lasted from 56 days to six months. Most studies did not adequately report the randomisation procedures or whether and how blinding was achieved. HbF inducer against placebo or usual care Three HbF inducers, HQK-1001, Radix Astragali or a 3-in-1 combined natural preparation (CNP), were compared with a placebo. None of the comparisons reported the frequency of blood transfusion. We are uncertain whether Radix Astragali and CNP increase haemoglobin at three months (mean difference (MD) 1.33 g/dL, 95% confidence interval (CI) 0.54 to 2.11; 1 study, 2 interventions, 35 participants; very low-certainty evidence). We are uncertain whether Radix Astragali and CNP have any effect on HbF (MD 12%, 95% CI -0.74% to 24.75%; 1 study, 2 interventions, 35 participants; very low-certainty evidence). Only medians on haemoglobin and HbF levels were reported for HQK-1001. Adverse effects reported for HQK-1001 were nausea, vomiting, dizziness and suprapubic pain. There were no prespecified adverse effects for Radix Astragali and CNP. HbF inducer versus another HbF inducer Four studies compared a single inducer with another over three to six months. Comparisons included hydroxyurea versus resveratrol, hydroxyurea versus thalidomide, hydroxyurea versus decitabine and Radix Astragali versus CNP. No study reported our prespecified outcomes on blood transfusion. Haemoglobin and HbF were reported for the comparison Radix Astragali versus CNP, but we are uncertain whether there were any differences (1 study, 24 participants; low-certainty evidence). Different doses of the same HbF inducer Two studies compared two different types of HbF inducers at different doses over two to six months. Comparisons included hydroxyurea 20 mg/kg/day versus 10 mg/kg/day and HQK-1001 10 mg/kg/day, 20 mg/kg/day, 30 mg/kg/day and 40 mg/kg/day. Blood transfusion, as prespecified, was not reported. In one study (61 participants) we are uncertain whether the lower levels of both haemoglobin and HbF at 24 weeks were due to the higher dose of hydroxyurea (haemoglobin: MD -2.39 g/dL, 95% CI -2.80 to -1.98; very low-certainty evidence; HbF: MD -10.20%, 95% CI -16.28% to -4.12%; very low-certainty evidence). The study of the four different doses of HQK-1001 did not report results for either haemoglobin or HbF. We are not certain if major adverse effects may be more common with higher hydroxyurea doses (neutropenia: risk ratio (RR) 9.93, 95% CI 1.34 to 73.97; thrombocytopenia: RR 3.68, 95% CI 1.12 to 12.07; very low-certainty evidence). Taking HQK-1001 20 mg/kg/day may result in the fewest adverse effects. A combination of HbF inducers versus a single HbF inducer Two studies compared three combinations of two inducers with a single inducer over six months: hydroxyurea plus resveratrol versus resveratrol or hydroxyurea alone, and hydroxyurea plus l-carnitine versus hydroxyurea alone. Blood transfusion was not reported. Hydroxyurea plus resveratrol may reduce haemoglobin compared with either resveratrol or hydroxyurea alone (MD -0.74 g/dL, 95% CI -1.45 to -0.03; 1 study, 54 participants; low-certainty evidence). We are not certain whether the gastrointestinal disturbances, headache and malaise more commonly reported with hydroxyurea plus resveratrol than resveratrol alone were due to the interventions. We are uncertain whether hydroxyurea plus l-carnitine compared with hydroxyurea alone may increase mean haemoglobin, and reduce pulmonary hypertension (1 study, 60 participants; very low-certainty evidence). Adverse events were reported but not in the intervention group. None of the comparisons reported the outcome of HbF. AUTHORS' CONCLUSIONS: We are uncertain whether any of the eight HbF inducers in this review have a beneficial effect on people with NTDßT. For each of these HbF inducers, we found only one or at the most two small studies. There is no information on whether any of these HbF inducers have an effect on our primary outcome, blood transfusion. For the second primary outcome, haemoglobin, there may be small differences between intervention groups, but these may not be clinically meaningful and are of low- to very low-certainty evidence. Data on adverse effects and optimal doses are limited. Five studies are awaiting classification, but none are ongoing.

Case report: Kaposi hemangioendothelioma of the right upper limb with the Kasabach-Merritt phenomenon: A potentially lethal diagnostic challenge.

Kaposi hemangioendothelioma (KHE) is a rare vascular neoplasm that presents usually within the first year of life. Because of its rarity and complexity, there is often a delay in diagnosis. KHE could be associated with a life-threatening consumptive coagulopathy named the Kasabach-Merritt phenomenon (KMP). Here, we present the case of a 2-month-old girl who presented with progressive redness and swelling of her right upper limb over 6 weeks. Multiple health practitioners misdiagnosed her condition as an insect bite, cellulitis, and necrotizing fasciitis and gave treatment accordingly, which proved futile. A full blood count revealed bicytopenia of anemia and thrombocytopenia, a normal coagulation cascade, low fibrinogen, and raised D-Dimer levels. The imaging was suggestive of a high-flow vascular tumor likely to be a KHE. Subsequently, she was started on single-agent oral sirolimus with a dose increment to achieve satisfactory therapeutic levels and was treated for 1 year. She successfully completed the treatment regimen and had only transient hypertriglyceridemia, which resolved upon the completion of treatment. Currently, she is in remission 3 years after treatment. Keeping her case as an example, we would like to highlight the potentially lethal misdiagnosis of KHE with KMP, the importance of an early diagnosis of this condition, and the successful treatment outcome with single-agent sirolimus.

Isolated Infiltrative Optic Neuropathy in an Acute Lymphoblastic Leukemia Relapse.

Optic nerve infiltration as the first sign of isolated central nervous system relapse of acute lymphoblastic leukemia (ALL) is rare. A seven-year-old girl with standard-risk B-cell ALL who was in remission presented with sudden onset of left eye pain and loss of vision. Examination revealed no perception to light in the left eye with positive relative afferent pupillary defect. The optic disc was hyperemic and swollen with total obscuration of the disc margin associated with central retinal artery and vein occlusion. Magnetic resonance imaging of the brain and optic nerve showed left intraorbital optic nerve thickening associated with perineural enhancement and intraconal fat involvement. Lumbar puncture revealed leukemic infiltration with blast cells after a week of eye symptoms, while bone marrow aspiration was negative for malignant cells. A diagnosis of left leukemic optic nerve infiltration with central retinal artery and vein occlusion was made. A high index of suspicion with repeat cerebrospinal fluid sampling is crucial to confirm the diagnosis as vitreous biopsy may fail to reveal infiltrative cells.

Magnetic resonance imaging T2* of the pancreas value using an online software tool and correlate with T2* value of myocardium and liver among patients with transfusion-dependent thalassemia major.

Objective: Patients with thalassemia major do require lifetime blood transfusions that eventually result in iron accumulation in different organs. We described the usefulness of using magnetic resonance imaging (MRI) T2*imaging values for the evaluation of pancreatic iron load in these patients, and we correlated it with MRI T2* haemosiderosis of the myocardium and liver that has been recognized as a non-invasive assessment of iron overload among patients with thalassemia major. Materials and methods: We conducted a cross-sectional study on 39 patients with thalassemia major in one of the tertiary university hospitals for a 1-year period. Demographic data were collected from the patient's history. MRI T2* of the pancreas, liver, and heart were executed on all patients in the same setting. Objective values of iron overload in these organs were obtained using the MRI post-processing software from online software. Results: A total of 32 (82.1%) patients had pancreatic iron overload including 2 patients (5.1%) with severe iron overload and 15 patients (38.5%) with moderate and mild iron overload, respectively. Nine patients (23.1%) had myocardial iron overload, which included 3 patients (7.7%) who had severe cardiac haemosiderosis. Notably, 37 patients (94.9%) had liver iron overload, which included 15 patients (38.5%) who had severe liver haemosiderosis. There was a moderate positive correlation between the relaxation time of the pancreas and heart haemosiderosis (r = 0.504, P < 0.001). No significant correlation was found between the relaxation time of the pancreas with the liver and the heart with the liver. Conclusion: Pancreatic haemosiderosis precedes cardiac haemosiderosis, which establishes a basis for initiating earlier iron chelation therapy to patients with thalassemia major.

Feasibility of modified-TEP technique for large inguinoscrotal and large femoral hernia and its advantages.

PURPOSE: To describe the feasibility of modified-TEP technique in reducing dead space in large inguinoscrotal and large femoral hernia to prevent seroma, reduce recurrence and complications. METHODS: This is a case series of patients who have completed a minimum of 9 months follow-up after undergoing elective endo-laparoscopic inguinal hernia repair with modified-TEP technique for large inguinoscrotal and large femoral hernia in a single institution from June to October 2020. RESULTS: 14 large inguinoscrotal hernia and 4 large femoral hernia were repaired using the modified-TEP technique in 15 patients. These patients reported minimal pain after surgery. There were no reported seroma, complications or recurrences up to 9 months follow-up period. CONCLUSION: Modified-TEP technique for large inguinoscrotal and large femoral hernia has shown good outcomes and patients reported minimum levels of pain. In experienced hands, it is safe, feasible and effective in reducing seroma formation and hernia recurrence.

Case Report: The Use of Intravenous SMOFlipid Infusion to Treat Severe Asparaginase-Induced Hypertriglyceridemia in Two Pediatric Acute Lymphoblastic Leukemia Patients.

Asparaginase-induced hypertriglyceridemia can have a spectrum of clinical presentations, from being asymptomatic to having life-threatening thrombosis or hyperviscosity syndrome. At present, there is no recommendation on routine lipid monitoring during asparaginase-containing treatment phase, nor a standardized guideline on its management. Two cases are presented here to illustrate the effects of concurrent infection on asparaginase-induced hypertriglyceridemia in patients with high-risk ALL and the use of SMOFlipid infusion as a treatment option in an acute situation.

Siriraj I Gγ(Aγδß)0-thalassaemia causing severe thalassaemia intermedia in compound heterozygous state with IVS1-1(G→T) mutation.

The Siriraj I Gγ(Aγδß)0-thalassaemia is a novel mutation involving a 118kb deletion of the ß-globin gene cluster. It was first reported in 2012 in two unrelated families from the southern part of Thailand. The carriers in the heterozygous state are clinically asymptomatic. Nonetheless, its complex interaction with other ß-thalassaemia could give rise to different clinical phenotypes, ranging from mild thalassaemia intermedia to thalassaemia major. We report here a case of a six-year-old Malay boy, presented with pallor, growth failure and hepatosplenomegaly. His haemoglobin at presentation was 9.2g/dL with a mean cell haemoglobin of 22.6pg and a mean cell volume of 69.9fl. His peripheral blood smear showed features of thalassaemia intermedia. Haemoglobin (Hb) analysis revealed markedly raised Hb F (83%), normal HbA2 levels and absent HbA. Deoxyribonucleic acid (DNA) analysis showed compound heterozygous IVS1-1 (G→T) ß-globin gene mutation and Siriraj I Gγ(Aγδß)0-deletion (genotype ßIVS1-1/ ß Siriraj I deletion). Both his father and elder sister are carriers of Siriraj I Gγ(Aγδß)0-thalassaemia while his mother carries IVS1-1 (G→T) gene mutation. Clinically, the patient is transfusion dependent on six weekly regime. To the best of our knowledge, this is the first reported case in Malaysia involving unique Siriraj I Gγ(Aγδß)0-thalassaemia and IVS1-1 (G→T) in a compound heterozygous state. In summary, detection of Siriraj I Gγ(Aγδß)0-thalassaemia is essential as this deletion can lead to severe disease upon interaction with a ß-thalassemia point mutation as demonstrated in our case. The establishment of effective carrier screening and genetic counselling is important to prevent its adverse consequences.

Primary extragonadal vaginal yolk sac tumour: A case report.

INTRODUCTION: Yolk sac tumour (YST) or endodermal sinus tumour is rare and typically seen in gonads. CASE REPORT: We described a case of extragonadal vaginal YST in a one year and seven months old girl who presented with vaginal discharge and bleeding, and discuss its differential diagnosis and potential pitfalls in immunohistochemistry. She was found to have a suprapubic mass on examination. The serum alpha fetoprotein was 11919.4 ng/mL. Computed tomography of the pelvis revealed a large 6.4 cm heterogenous pelvic mass. Colposcopic examination of the pelvis showed a fungating vaginal mass that was subsequently confirmed as a yolk sac tumour. Immunohistochemically, the malignant cells were positive toward CKAE1/AE3, AFP and glypican-3, as well as CD117. DISCUSSION: Solid pattern extragonadal vaginal YST may morphologically resemble dysgerminoma that is also CD117 positive, while the glandular pattern YST may have clear cytoplasm and is positive for cytokeratin; hence, may resemble clear cell carcinoma. Being mindful of these potential diagnostic caveats is necessary to prevent misdiagnosis.

Correlation between MRI characteristics of medulloblastoma with histopathological subtypes and 2-year survival.

OBJECTIVES: The objective of this study is to describe the imaging features of medulloblastoma (MB) and correlate the MR characteristics with the different histological subtype of MB with 2-year survival. MATERIALS AND METHODS: This is a retrospective descriptive study. A total of 29 patients diagnosed with MB from January 2005 to December 2015 were included in this study. The MRI brain and spine studies of these patients were retrieved and reviewed by a pediatric radiologist and a neuroradiologist independently, both blinded from the histological type of the MB. The HPE slides were also retrieved and reviewed by a pathologist. RESULTS: 80% of desmoplastic MB showed the presence of intracranial leptomeningeal seeding and 57.1% of anaplastic MB showed the presence of necrosis. The presence of intracranial leptomeningeal seeding (P = 0.002) and necrosis (P = 0.019) was predictive of the histological subtypes. There is a significant correlation between the enhancement pattern and the 2-year outcome (P = 0.03) with 6 out of 8 patients whose tumors showed minimal enhancement having disease progression within 2 years. A significant correlation was also seen between the presence of necrosis with a poorer outcome (P = 0.03) and between the HPE subtype and 2-year outcome (P = 0.03) with anaplastic MB having the poorest prognosis. CONCLUSION: MR imaging features of intracranial leptomeningeal seeding and the presence of necrosis were correlated with a specific histologic subtype of MB. The enhancement pattern as well as necrosis correlated with 2-year poorer outcome of the disease.

Development and Validation of a Tool to Screen for Cognitive Frailty among Community-Dwelling Elders.

OBJECTIVES: Reciprocal age-related impairments in physical and cognitive functioning have been termed 'cognitive frailty', which is associated with adverse health outcomes and is a potential target for preventing or delaying the onset of disability in older people. However, cognitive frailty as currently defined is challenging to diagnose. To facilitate earlier diagnosis and intervention, we conducted this study to develop and validate a simple evidence-based instrument to identify community-dwelling elders at risk of cognitive frailty. DESIGN: Retrospective analyses of data from the I-Lan Longitudinal Aging Study (ILAS) to develop a prediction model, and from the Longitudinal Aging Study of Taipei (LAST) for external validation. SETTING: Community-dwelling adults from Taipei City, New Taipei City and Yilan (I-Lan) County, Taiwan. PARTICIPANTS: 1271 community residents ≥65 years old, without impaired global cognition or dependency for activities of daily living/instrumental activities of daily living. MEASUREMENTS: Demographic characteristics, anthropometric measurements, medical history, Mini-Mental State Examination, Montreal Cognitive Assessment, Functional Autonomy Measuring System, Functional Assessment Staging Test, Center for Epidemiologic Studies Depression Scale, handgrip strength, 6-metre walk speed. METHODS: Baseline characteristics of groups with/without cognitive frailty were analyzed and factors differing significantly in univariate analysis input to binary logistic regression to develop a cognitive frailty risk (CFR) score. RESULTS: The prevalence of cognitive frailty was 15.8% overall; ILAS 21.4%, LAST 8.4%. Predictors of CFR comprised: age ≥75 years; female sex; waist circumference ≥90 cm (male), ≥80 cm (female); calf circumference <33 cm (male), <32 cm (female); memory deficits; and diabetes mellitus. CFR ≥5/14 had sensitivity of 70%, specificity of 60%, and predictive accuracy of 72%. CONCLUSIONS: A CFR score based on simple history-taking and anthropometric measurements integrates age, sex, cardiometabolic risk, memory deficits, sarcopenia, and nutrition, with validated predictive accuracy, and could be performed easily in community settings to identify seniors with cognitive frailty for appropriate interventions.

A clinical prediction model for hospitalized COPD exacerbations based on "treatable traits".

Background: Assessing risk of future exacerbations is an important component in COPD management. History of exacerbation is a strong and independent predictor of future exacerbations, and the criterion of ≥2 nonhospitalized or ≥1 hospitalized exacerbation is often used to identify high-risk patients in whom therapy should be intensified. However, other factors or "treatable traits" also contribute to risk of exacerbation. Objective: The objective of the study was to develop and externally validate a novel clinical prediction model for risk of hospitalized COPD exacerbations based on both exacerbation history and treatable traits. Patients and methods: A total of 237 patients from the COPD Registry of Changi General Hospital, Singapore, aged 75±9 years and with mean post-bronchodilator FEV1 60%±20% predicted, formed the derivation cohort. Hospitalized exacerbation rate was modeled using zero-inflated negative binomial regression. Calibration was assessed by graphically comparing the agreement between predicted and observed annual hospitalized exacerbation rates. Predictive (discriminative) accuracy of the model for identifying high-risk patients (defined as experiencing ≥1 hospitalized exacerbations) was assessed with area under the curve (AUC) and receiver operating characteristics analyses, and compared to other existing risk indices. We externally validated the prediction model using a multicenter dataset comprising 419 COPD patients. Results: The final model included hospitalized exacerbation rate in the previous year, history of acute invasive/noninvasive ventilation, coronary artery disease, bronchiectasis, and sputum nontuberculous mycobacteria isolation. There was excellent agreement between predicted and observed annual hospitalized exacerbation rates. AUC was 0.789 indicating good discriminative accuracy, and was significantly higher than the AUC of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) risk assessment criterion (history of ≥1 hospitalized exacerbation in the previous year) and the age, dyspnea, and obstruction index. When applied to the independent multicenter validation cohort, the model was well-calibrated and discrimination was good. Conclusion: We have derived and externally validated a novel risk prediction model for COPD hospitalizations which outperforms several other risk indices. Our model incorporates several treatable traits which can be targeted for intervention to reduce risk of future hospitalized exacerbations.

Early Surgery Is Feasible for a Very Large Congenital Infantile Fibrosarcoma Associated With Life Threatening Coagulopathy: A Case Report and Literature Review.

Background: Congenital infantile fibrosarcoma (CIF) is a rare malignant soft tissue tumor that predominantly occurs in children under 1 year of age. CIF is frequently misdiagnosed with other conditions like hemangioma of infancy, infantile fibromatosis, or kaposiform hemangioendothelioma. Disseminated intravascular coagulopathy (DIVC) is rarely reported to be associated with CIF. Case presentation: We describe an infant who presented with a large mass over the right arm. She was initially treated conservatively as hemangioma but was later confirmed by tissue histopathological examination to have CIF as the mass rapidly increased in size. She developed massive intra-tumoral bleed with DIVC whilst receiving neoadjuvant chemotherapy requiring multiple blood products transfusion. An urgent near-total resection of the tumor was performed in view of life threatening bleeding despite multiple blood transfusions. Post-operatively, she received further adjuvant chemotherapy. Subsequently, she remained in complete remission 32 months off-treatment and has full function of the affected limb. Conclusions: CIF is an important condition to be considered in infant who has large mass over the extremity. DIVC could be associated with large CIF and when it occurs can be life-threatening. Whenever feasible early surgery should be performed in very young patients with large CIF to prevent mortality from bleeding.

Effect of Body Weight, Waist Circumference and Their Changes on Mortality: a 10-Year Population-based Study.

OBJECTIVES: To investigate the effect of body weight, waist circumference and their changes on all-cause and cardiovascular mortality. DESIGN: A nationwide population-based cohort study. PARTICIPANTS: 627 community-dwelling older adults. MEASUREMENTS: Participants were interviewed for demographic and anthropometric data collected. Blood were drawn for testing biochemistry data. Central obesity was defined as waist circumference is greater than 80 cm for women and 90 cm for men. Obesity, overweight, normal and underweight were defined as BMI ≥27 kg/m2 , ≥24 kg/m2 ,18.5-24 kg/m2 and < 18.5 kg/m2. Cox proportion hazard model was used to explore the impact of body weight and its change on mortality. RESULTS: The distribution of weight changes and mortality was right skewed, but U-shape of waist change for all-cause mortality was observed. Compared to normal BMI at baseline, the association between underweight (HR: 1.7, 95% CI: 0.7-4.0), overweight (HR:0.7, 95% CI:0.4-1.2) and obesity (HR:1.3,95% CI:0.8-2.3) showed insignificantly associated with all-cause mortality. The HR of those weight loss >5% (HR: 1.7, 95% CI: 1.1-2.8) and waist decrease >5% (HR: 1.7, 95% CI: 1.0-2.8) were higher than those of stable weight/waist +/- 5% over a 6-year period. Compared to those stable weight/waist, the mortality risk was similar in those of weight gain or waist increase (HR 0.7,95%CI: 0.4-1.5 and HR:0.9, 95%CI:0.4-1.6). CONCLUSION: Weight loss and waist decrease were significantly associated with long-term mortality risk, a life-course approach for body weight management is needed to pursuit the most optimal health benefits for the middle-aged and older adults.