Outcomes of adolescents with acute lymphoblastic leukaemia.

INTRODUCTION: Compared with young children who have acute lymphoblastic leukaemia (ALL), adolescents with ALL have unfavourable disease profiles and worse survival. However, limited data are available regarding the characteristics and outcomes of adolescents with ALL who underwent treatment in clinical trials. The aim of this study was to investigate the causes of treatment failure in adolescents with ALL. METHODS: We retrospectively analysed the outcomes of 711 children with ALL, aged 1-18 years, who were enrolled in five clinical trials of paediatric ALL treatment between 1993 and 2015. RESULTS: Among the 711 children with ALL, 530 were young children (1-9 years at diagnosis) and 181 were adolescents (including 136 younger adolescents [10-14 years] and 45 older adolescents [15-18 years]). Compared with young children who had ALL, adolescents with ALL were less likely to have favourable genetic features and more likely to demonstrate poor early response to treatment. The 10-year overall survival and event-free survival rates were significantly lower among adolescents than among young children (77.9% vs 87.6%, P=0.0003; 69.7% vs 76.5%, P=0.0117). There were no significant differences in the 10-year cumulative incidence of relapse, but the 10-year cumulative incidence of treatment-related death (TRD) was significantly greater among adolescents (7.2%) than among young children (2.3%; P=0.002). Multivariable analysis showed that both younger and older adolescents (vs young children) had worse survival and greater incidence of TRD. CONCLUSION: Adolescents with ALL had worse survival because they experienced a greater incidence of TRD. There is a need to investigate optimal treatment adjustments and novel targeted agents to achieve better survival rates (without excessive toxicity) among adolescents with ALL.

Brain death in children: a retrospective review of patients at a paediatric intensive care unit.

PURPOSE: Among patients in paediatric intensive care units (PICUs), death is sometimes inevitable despite advances in treatment. Some PICU patients may have irreversible cessation of all brain function, which is considered as brain death (BD). This study investigated demographic and clinical differences between PICU patients with BD and those with cardiopulmonary death. METHODS: All children who died in the PICU at a university-affiliated trauma centre between October 2002 and October 2018 were included in this retrospective study. Demographics and clinical characteristics were compared between patients with BD and patients with cardiopulmonary death. RESULTS: Of the 2784 patients admitted to the PICU during the study period, 127 died (4.6%). Of these 127 deaths, 22 (17.3%) were BD and 105 were cardiopulmonary death. Length of PICU stay was shorter for patients with cardiopulmonary death than for patients with BD (2 vs 8.5 days, P=0.0042). The most common mechanisms of injury in patients with BD were hypoxic-ischaemic injury (40.9%), central nervous system infection (18.2%), and traumatic brain injury (13.6%). The combined proportion of accident and trauma-related injury was greater in patients with BD than in patients with cardiopulmonary death (27.3% vs 3.8%, P<0.001). Organ donation was approved by the families of four of the 22 patients with BD (18.2%) and was performed successfully in three of these four patients. CONCLUSIONS: These findings emphasise the importance of injury prevention in childhood, as well as the need for education of the public regarding acceptance of BD and support for organ donation.

Primary anorectal malignant melanoma: A clinical, radiology and pathology correlation.

INTRODUCTION: Primary gastrointestinal melanomas are mucosal malignancies that arise from melanocytes in the oropharynx, rectum, and anus. Anorectal malignant melanoma (ARMM) are exceedingly rare, accounting for less than 1% of all melanomas, 0.1% of all rectal malignancies and 4% of anal malignancies. Diagnosis is frequently delayed as these lesions are often mistaken for haemorrhoids. Histological evaluation with special immunohistochemical stains is often necessary for definitive diagnosis. Due to the aggressive nature, 61% of patients with ARMM would already have lymph node involvement or distant metastases, by the time of diagnosis. Prognosis is usually poor with 5-year survival rate of <20%. We report a case of metastatic ARMM in an elderly lady who presented with symptoms and signs mimicking a haemorrhoid. CASE REPORT: A 69-year-old lady presented with one year history of intermittent rectal bleed and an anorectal mass that was initially treated as haemorrhoid. Colonoscopy showed a hyperpigmented mass in the anorectal region which was confirmed as malignant melanoma on histopathological examination. Imaging with CT and MRI demonstrated locally advanced tumour with distant metastases to the liver and lung. Patient was referred for palliative management. CONCLUSION: ARMM is a rare malignancy and often presented with non-specific clinical signs. Diagnosis is frequently delayed without high index of suspicion. MRI pelvis is the imaging of choice to assess local extent of disease. Histologic evaluation with special immunohistochemical stains is often necessary for definitive diagnosis. Prognosis is poor despite surgical and chemotherapeutic interventions.

Treatment of cutaneous angiosarcoma of the scalp and face in Chinese patients: local experience at a regional hospital in Hong Kong.

INTRODUCTION: Angiosarcoma is a rare aggressive sarcoma that occurs mostly in the skin of the head and neck in the elderly population. The optimal management is dubious and most studies are from Caucasian populations. We aimed to examine the treatment and outcome of this disease in Chinese patients. METHODS: Data of patients with histopathologically verified cutaneous angiosarcoma of the head and neck during December 1997 to September 2016 were retrieved from our hospital cancer registry. The demographic data, clinicopathological information, modality of treatment, and outcomes were reviewed. RESULTS: During the study period, 17 Chinese patients were treated. Their median age was 81 years. The tumours were present in the scalp only (n=11), face only (n=4), or both scalp and face (n=2). Only two patients had distant metastases. The modalities of treatment were surgery (n=6), surgery and adjuvant radiotherapy (n=1), palliative radiotherapy (n=5), or palliative chemotherapy (n=3). The remaining two patients refused any treatment initially. Of the seven patients treated surgically, there were four local and two regional recurrences. The median time to relapse was 7.5 months. Overall, 16 patients had died; causes of death were disease-related in 12 whereas four other patients died of inter-current illnesses. One patient was still living with the disease. The median overall survival was 11.1 months and the longest overall survival was 42 months. CONCLUSION: The outcome of angiosarcoma in our series is poor. A high index of suspicion is mandatory for prompt diagnosis. Adjuvant radiotherapy is recommended following surgery. The benefit and role of systemic treatment in various combinations with surgery or radiotherapy require further study.

Fatal spontaneous rupture of splenic artery aneurysm in third trimester pregnancy.

INTRODUCTION: Unforeseen emergency in late pregnancy can be catastrophic and cause unexpected maternal and foetal demise. Moreover, lack of awareness and failure of prompt treatment raise mortality rate. Such fatalities warrant a forensic autopsy as it may raise redundant medico-legal concerns. CASE REPORT: We report a case that revealed significant intra-abdominal haemorrhage at autopsy. The source of haemorrhage was at the spleen hilum and histology established rupture of splenic artery aneurysm. There was no associated obstetric cause found. CONCLUSION: Knowledge of spontaneous rupture of splenic artery aneurysm in late pregnancy is essential for monitoring maternal and foetal, morbidity and mortality. However, in the eventuality of death a comprehensive forensic autopsy is the only investigation to recognise such calamity and clear clinical confusion.

In-vivo imaging of grey and white matter neuroinflammation in Alzheimer's disease: a positron emission tomography study with a novel radioligand, [18F]-FEPPA.

Our primary aim was to compare neuroinflammation in cognitively intact control subjects and patients with Alzheimer's disease (AD) by using positron emission tomography (PET) with translocator protein 18 kDa (TSPO)-specific radioligand [(18)F]-FEPPA. [(18)F]-FEPPA PET scans were acquired on a high-resolution research tomograph in 21 patients with AD (47- 81 years) and 21 control subjects (49-82 years). They were analyzed by using a 2-tissue compartment model with arterial plasma input function. Differences in neuroinflammation, indexed as [(18)F]-FEPPA binding were compared, adjusting for differences in binding affinity class as determined by a single polymorphism in the TSPO gene (rs6971). In grey matter areas, [(18)F]-FEPPA was significantly higher in AD compared with healthy control subjects. Large increases were seen in the hippocampus, prefrontal, temporal, parietal and occipital cortex (average Cohen's d= 0.89). Voxel-based analyses confirmed significant clusters of neuroinflammation in the frontal, temporal and parietal cortex in patients with AD. In white matter, [(18)F]-FEPPA binding was elevated in the posterior limb of the internal capsule, and the cingulum bundle. Higher neuroinflammation in the parietal cortex (r= -0.7, P= 0.005), and posterior limb of the internal capsule (r= -0.8, P=0.001) was associated with poorer visuospatial function. In addition, a higher [(18)F]-FEPPA binding in the posterior limb of the internal capsule was associated with a greater impairment in language ability (r= -0.7, P=0.004). Elevated neuroinflammation can be detected in AD patients throughout the brain grey and white matter by using [(18)F]-FEPPA PET. Our results also suggest that neuroinflammation is associated with some cognitive deficits.

Malignant presternal goitre.

Goitres usually enlarge and descend caudad into the substernal space and are not palpable. We report on a patient whose goitre spread downward but anterior to the sternum. The thyroid mass was subsequently removed and was proven to be a papillary thyroid carcinoma. The mechanism by which a presternal goitre develops is probably due to invasion and erosion of the strap muscles and the cervical linea alba. The clinical implication of this presentation is complete extirpation of the presternal goitre with a cuff of the strap muscles.

Right-sided pyriform sinus fistula in an adult.

Pyriform sinus fistula is important despite its rarity, as it can induce a recurrent neck abscess. Most of the reported cases occur in children and the majority affect only the left side. We report a patient with a pyriform sinus fistula of the right neck in an adult, which was successfully treated by surgery. The aetiology of this entity is also discussed herein.

An integrated framework of mobile crowd estimation for the 2019, July 1st rally in Hong Kong.

Traditional approach of mobile crowd estimation involves counting a group of individuals at a specific place, manually, in real-time. It is a laborious exercise that can be physically and mentally demanding. In Hong Kong, a large rally can last more than six hours, making the manual count method susceptible to human errors. While crowd counting using object detection and tracking has been well-established in computer vision, such application has remained relatively small scale within a controlled indoor setting (e.g. counting people at fixed gateways in a mall). No attempt to date has applied the automatic crowd counting method to count hundreds of thousands of people along an open stretch of rally route within the complex urban outdoor landscape. This research proposed an integrated approach that combines the capture-recapture method in statistics and a Convolutional Neural Network (CNN) method in computer vision to count the mobile crowd. The research teams implemented the integrative approach and counted 276,970 people with a 95% confidence interval of 263,663 to 290,276 in the 2019, July 1st Rally in Hong Kong. This work counted the attendance of a large-scale rally as a proof of concept to fill in a gap in the empirical studies. The intellectual merits and research findings shed useful insights to improve mobile population estimation and leverage alternative data sources to support related scientific applications.

Differentiation of patient-specific void urine-derived human induced pluripotent stem cells to fibroblasts and skeletal muscle myocytes.

Cell-based therapy is a major focus for treatment of stress urinary incontinence (SUI). However, derivation of primary cells requires tissue biopsies, which often have adverse effects on patients. A recent study used human induced pluripotent stem cells (iPSC)-derived smooth muscle myocytes for urethral sphincter regeneration in rats. Here, we establish a workflow using iPSC-derived fibroblasts and skeletal myocytes for urethral tissue regeneration: (1) Cells from voided urine of women were reprogrammed into iPSC. (2) The iPSC line U1 and hESC line H9 (control) were differentiated into fibroblasts expressing FSP1, TE7, vinculin, vimentin, αSMA, fibronectin and paxillin. (3) Myogenic differentiation of U1 and H9 was induced by small molecule CHIR99021 and confirmed by protein expression of myogenic factors PAX7, MYOD, MYOG, and MF20. Striated muscle cells enriched by FACS expressed NCAM1, TITIN, DESMIN, TNNT3. (4) Human iPSC-derived fibroblasts and myocytes were engrafted into the periurethral region of RNU rats. Injected cells were labelled with ferric nanoparticles and traced by Prussian Blue stain, human-specific nuclear protein KU80, and human anti-mitochondria antibody. This workflow allows the scalable derivation, culture, and in vivo tracing of patient-specific fibroblasts and myocytes, which can be assessed in rat SUI models to regenerate urethral damages and restore continence.

Different types of visual cells in the photoreceptor layer of the retinae of the treeshrew (Tupaia belangeri chinensis) as revealed by scanning microscopy.

BACKGROUND: The retinae of treeshrew have never been evaluated by scanning electron microscopic studies. MATERIALS AND METHODS: This work described the visual cells in the photoreceptor layer of the retinae of treeshrew (Tupaia belangeri chinensis) living on the high plateau of Yunnan, China, via scanning electron microscopy. RESULTS: Results indicated five morphologically different types of cones, two of which contain oil droplets in their inner segments. To our knowledge, no prior studies have reported oil droplets in the visual cells of higher mammals, only in lower vertebrate and primitive mammals. In addition, this study revealed one type of degenerative visual cell without outer segments. CONCLUSIONS: The findings signal the needs for additional studies to understand the physiological functions and phylogenetic relationships of the diversity of visual cells in this group of mammal.

A case of semantic variant primary progressive aphasia with severe insular atrophy.

Insular degeneration has been linked to symptoms of frontotemporal dementia (FTD). Presented in this case is a patient exhibiting semantic variant primary progressive aphasia, behavioral disturbance. Upon autopsy, he was found to have severe insular atrophy. In addition, selective serotonin reuptake inhibitors were ineffective in reducing symptoms of obsessive-compulsive behaviors or emotional blunting. This case suggests that Seeley et al.'s (2007 , Alzheimer Disease & Associated Disorders, 21, S50) hypothesis that von Economo neurons and fork cell-rich brain regions, particularly in the insula, are targeted in additional subtypes of FTD beyond the behavioral variant.

BDNF and DARPP-32 genes are not risk factors for schizophrenia in the Malay population.

A number of studies have pointed to the association of BDNF (brain-derived neurotrophic factor) and DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) with schizophrenia. The purpose of this study was to determine whether these two genes are involved in the pathogenesis of schizophrenia in the Malay population. Two single nucleotide polymorphisms Val66Met of BDNF, -2036C>G and g.1238delG of DARPP-32 were genotyped in the Malay population in 200 patients with schizophrenia and 256 healthy controls. Analysis of allele and genotype frequencies in these two groups revealed no significant association of BDNF or DARPP-32 polymorphisms with schizophrenia in Malays. This is the first such association study in the Malay population.

Visual rating versus volumetry to detect frontotemporal dementia.

BACKGROUND/AIMS: Automated, volumetrically defined atrophy in the left anterior cingulate (LAC) and anterior temporal regions (LAT) on MRI can be used to distinguish most patients with frontotemporal dementia (FTD) from controls. FTD and Alzheimer's disease (AD) can differ in the degree of anterior temporal atrophy. We explored whether clinicians can visually detect this atrophy pattern and whether they can use it to classify the 2 groups of dementia patients with the same accuracy. METHODS: Four neurologists rated atrophy in the LAC and LAT regions on MRI slices from 21 FTD, 21 controls, and 14 AD participants. Inter-rater reliability and diagnostic accuracy were assessed. RESULTS: All 4 raters agreed on the presence of clinically significant atrophy, and their atrophy scoring correlated with the volumes, but without translation into high inter-rater diagnostic agreement. CONCLUSIONS: Volumetric analyses are difficult to translate into routine clinical practice.

Evaluation of thermal comfort conditions in a classroom with three ventilation methods.

UNLABELLED: Thermal sensation is studied experimentally under mixing ventilation, displacement ventilation, and stratum ventilation in an environmental chamber. Forty-eight subjects participated in all tests under the same boundary conditions but different ventilation methods in the classroom. Thermal comfort analysis was carried out according to the designated supply airflow rate, room temperature, and relative humidity for the three ventilation methods. The thermal neutral temperature under stratum ventilation is approximately 2.5 °C higher than that under mixing ventilation and 2.0 °C higher than that under displacement ventilation. This result indicates that stratum ventilation could provide satisfactory thermal comfort level to rooms of temperature up to 27 °C. The energy saving attributable to less ventilation load alone is around 12% compared with mixing ventilation and 9% compared with displacement ventilation. PRACTICAL IMPLICATIONS: The confirmation of the significantly elevated thermal neutral temperature can have a number of implications for both thermal comfort in an air-conditioned room and energy consumption of the associate air-conditioning system. With respect to the former, it provides scientific basis for the feasibility of elevated room temperatures, and with respect to the latter, it reveals considerable potentials for energy saving.