Coxsackievirus A16 (CV-A16) is the leading cause of hand-foot-mouth disease (HFMD), which usually presents as mild and self-limiting symptoms in young children. Rarely, CV-A16 has been reported to cause severe and fatal neurological complications but little is known about these complications. In the present study, 1-day and 7-day old mouse models of CV-A16 were developed using a clinical strain via subcutaneous inoculation. All infected mice exhibited clinical signs of infection, including reduced mobility, limb weakness and paralysis between 3 to 6 days post-infection. Pathologically, the main organs involved were the central nervous system (CNS), skeletal muscles and brown fat. In the CNS, viral antigens as demonstrated by immunohistochemistry, were localized mainly to neurons in the brain stem and spinal cord, suggesting that CV-A16 is neurotropic although inflammation is very mild. The skeletal muscles showed necrosis and myositis due to viral infection as evidenced by the dense viral antigens. Focal viral antigens were also detected in the brown fat. These preliminary pathological findings indicate that our mouse models can be further developed to be useful models for pathogenesis studies, and vaccine and anti-viral drug evaluation.

Coxsackievirus A16 (CV-A16) is the leading cause of hand-foot-mouth disease (HFMD), which usually presents as mild and self-limiting symptoms in young children. Rarely, CV-A16 has been reported to cause severe and fatal neurological complications but little is known about these complications. In the present study, 1-day and 7-day old mouse models of CV-A16 were developed using a clinical strain via subcutaneous inoculation. All infected mice exhibited clinical signs of infection, including reduced mobility, limb weakness and paralysis between 3 to 6 days post-infection. Pathologically, the main organs involved were the central nervous system (CNS), skeletal muscles and brown fat. In the CNS, viral antigens as demonstrated by immunohistochemistry, were localized mainly to neurons in the brain stem and spinal cord, suggesting that CV-A16 is neurotropic although inflammation is very mild. The skeletal muscles showed necrosis and myositis due to viral infection as evidenced by the dense viral antigens. Focal viral antigens were also detected in the brown fat. These preliminary pathological findings indicate that our mouse models can be further developed to be useful models for pathogenesis studies, and vaccine and anti-viral drug evaluation.
Coxsackievirus Infections

The Japanese encephalitis virus (JEV), a leading cause of encephalitis, exists as quasispecies in clinical isolates. Using a limiting dilution method combined with immunohistochemistry to detect viral antigens, 10 biological clones were isolated and purified from a clinical JEV isolate (CNS138/9) derived from an autopsy brain. These biological clones were tested for neurovirulence in SK-N-MC and NIE-115 neuronal cells, and a 2-week-old, footpad-infected, JE mouse model. Nine clones were found to be neurovirulent; one clone neuroattenuated. Although further studies are needed to determine genotypic differences, if any, in these clones, the limiting dilution purification and neurovirulence testing methods described herein should be useful for phenotypic studies of quasispecies of neurotropic viruses in general, and JEV and other flaviviruses in particular.

Many tertiary inflammatory bowel disease (IBD) centers recognize that a structured transition program is fundamental for an IBD unit. However, the path to ensuring a seamless transition for all stakeholders is often fraught with challenges. In this review, we go through current evidence, identify the requirementsof a successful transition program, and the barriers to seamless transfer. We also aim to shed light on differences in needs between the Western and Asian adolescent IBD populations. Majority of healthcare providers viewed having a structured transition program to be very important. The lack of a standard protocol led us to come up with a list of requirements ofa successful program. These include: multidisciplinary team meetings, alternating visits between the adultand pediatric clinics, proper documentation of records, and determining the ideal timing for transfer. The difficulties forthe Asian adolescent IBD population may be attributed to the reliance on parental support to make decisions regarding medicaltreatment. Lastly, there are various physician, patient and disease factors which are barriers to seamless transition. These includethe lack of proper documentation, and lack of patient self-efficacy. We also propose a standardized template for documentation of medical records for IBD patients.

INTRODUCTIONFetal imaging has improved with the development of faster magnetic resonance imaging (MRI) sequences, obviating the requirement for sedation. It is useful in characterising abnormality of the central nervous system in fetuses with abnormal or equivocal antenatal ultrasound findings. We reviewed all cases of fetal brain and spine MRI performed in our institution.

MATERIALS AND METHODSAll cases of fetal central nervous system MRI imaging from May 2006 to December 2008 were retrospectively reviewed, including fetal MRI, postnatal MRI and autopsy findings.

RESULTSThirty-one fetuses were imaged with MRI for evaluation of the central nervous system of which 3 were specifically for spinal evaluation. On fetal MRI, there were 11 normal fetuses (2 with minor ventricular asymmetry), 4 fetuses with minor ventriculomegaly and 16 fetuses with significant abnormalities. Twenty-three fetuses were delivered and 8 were terminated. Fifteen of 23 babies underwent postnatal imaging, 21 had clinical follow-up and 2 were lost to clinical follow-up. Of the 11 fetuses reported as normal on fetal MRI, 3 had additional postnatal findings. A fetus with a megacisterna magna on fetal MRI was diagnosed with a posterior fossa arachnoid cyst on postnatal MRI. One, who had fetal MRI to assess suspected absent inferior cerebellar vermis, had intracranial calcifications from rubella infection. One was diagnosed with cerebro-occular-facio-skeletal (COFS) syndrome postnatally, 1 was lost to follow-up and the rest were discharged well. Seven out of 16 fetuses with significantly abnormal fetal MRI findings had confirmation of the findings on postnatal imaging. Postnatal MRI detected 2 cases of polymicrogyria which were not seen on fetal MRI. Autopsy was available in 1 abortus confirming intrauterine diagnosis of Dandy Walker malformation. A myelomeningocele was clinically obvious in 1 abortus.

CONCLUSIONFetal MRI is a good method of assessing brain and spine abnormalities in utero. However, disorders of neuronal migration remain a challenging diagnostic problem in fetal imaging.

Central Nervous System ; abnormalities ; Fetus ; Humans ; Infant, Newborn ; Magnetic Resonance Imaging ; Malformations of Cortical Development ; diagnosis ; epidemiology ; physiopathology ; Medical Audit ; Retrospective Studies ; Singapore ; epidemiology

INTRODUCTIONPre-hospital ambulance calls are not random events, but occur in patterns and trends that are related to movement patterns of people, as well as the geographical epidemiology of the population. This study describes the geographic-time epidemiology of ambulance calls in a large urban city and conducts a time demand analysis. This will facilitate a Systems Status Plan for the deployment of ambulances based on the most cost effective deployment strategy.

MATERIALS AND METHODSAn observational prospective study looking at the geographic-time epidemiology of all ambulance calls in Singapore. Locations of ambulance calls were spot mapped using Geographic Information Systems (GIS) technology. Ambulance response times were mapped and a demand analysis conducted by postal districts.

RESULTSBetween 1 January 2006 and 31 May 2006, 31,896 patients were enrolled into the study. Mean age of patients was 51.6 years (S.D. 23.0) with 60.0% male. Race distribution was 62.5% Chinese, 19.4% Malay, 12.9% Indian and 5.2% others. Trauma consisted 31.2% of calls and medical 68.8%. 9.7% of cases were priority 1 (most severe) and 70.1% priority 2 (moderate severity). Mean call receipt to arrival at scene was 8.0 min (S.D. 4.8). Call volumes in the day were almost twice those at night, with the most calls on Mondays. We found a definite geographical distribution pattern with heavier call volumes in the suburban town centres in the Eastern and Southern part of the country. We characterised the top 35 districts with the highest call volumes by time periods, which will form the basis for ambulance deployment plans.

CONCLUSIONWe found a definite geographical distribution pattern of ambulance calls. This study demonstrates the utility of GIS with despatch demand analysis and has implications for maximising the effectiveness of ambulance deployment.

Ambulances ; utilization ; Geographic Information Systems ; Singapore

BACKGROUND: Worldwide, approximately 2% of new cancers are of the brain. Five-year survival rates among brain cancer patients have been reported as a little over a third. Differences in clinical outcomes between brain tumor patients of different races remain poorly understood. METHODS: A retrospective chart review was performed on brain tumor resection patients≥18 years old. Demographics, treatment variables, and survival outcomes were collected. Primary outcomes were length of stay, recurrence rate, progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 452 patients were included in analysis. Females and males had nearly a 1:1 ratio (n=242 and n=220, respectively). Mean age was 54.8 years (SD: 14.5 range: 18–90). Females composed 69% (n=48) of Asian patients; males constituted 31% (n=22). Mean age of the Asian patients was 55.9 years (SD: 14.6 range: 26–89). Asian-only cohort tumor pathologies included glioblastoma (GBM) (n=14), high-grade glioma (n=7), low-grade glioma (n=4), meningioma (n=38), and metastases (n=7). Of the 185 meningioma patients, non-Asian patients comprised 79% of the group (n=146). Of the 65 GBM patients in total, non-Asian patients made up 89% of the GBM cohort (n=58). There were no statistically significant differences between these groups of both cohorts in recurrence (p=0.1580 and p=0.6294, respectively), PFS (p=0.9662 and p=0.4048, respectively), or OS (p=0.3711 and p=0.8183, respectively). CONCLUSION: Studies evaluating the survival between patients of different racial backgrounds against several tumor varieties are rare. Patients of certain racial backgrounds may need additional consideration when being attended to despite the same mutational composition as their counterparts. Repeated studies using national databases may yield more conclusive results.
Asian Continental Ancestry Group* ; Biomarkers ; Brain Neoplasms* ; Brain* ; Cohort Studies ; Continental Population Groups ; Demography ; Disease-Free Survival ; Female ; Glioblastoma ; Glioma ; Humans ; Length of Stay ; Male ; Meningioma ; Neoplasm Metastasis ; Pathology ; Recurrence ; Retrospective Studies ; Survival Rate

INTRODUCTIONThis study aims to study how the effect of the location of patient collapses from cardiac arrest, in the residential and non-residential areas within Singapore, relates to certain survival outcomes.

MATERIALS AND METHODSA retrospective cohort study of data were done from the Cardiac Arrest and Resuscitation Epidemiology (CARE) project. Out-of- hospital cardiac arrest (OHCA) data from October 2001 to October 2004 (CARE) were used. All patients with OHCA as confirmed by the absence of a pulse, unresponsiveness and apnoea were included. All events had occurred in Singapore. Analysis was performed and expressed in terms of the odds ratio (OR) and the corresponding 95% confidence interval (CI).

RESULTSA total of 2375 cases were used for this analysis. Outcomes for OHCA in residential areas were poorer than in non-residential areas-1638 (68.9%) patients collapsed in residential areas, and 14 (0.9%) survived to discharge. This was significantly less than the 2.7% of patients who survived after collapsing in a non-residential area (OR 0.31 [0.16 - 0.62]). Multivariate logistic regression analysis showed that location alone had no independent effect on survival (adjusted OR 1.13 [0.32 - 4.05]); instead, underlying factors such as bystander CPR (OR 3.67 [1.13 - 11.97]) and initial shockable rhythms (OR 6.78 [1.95 - 23.53]) gave rise to better outcomes.

CONCLUSIONEfforts to improve survival from OHCA in residential areas should include increasing CPR by family members, and reducing ambulance response times.

Adult ; Aged ; Aged, 80 and over ; Ambulances ; Cardiopulmonary Resuscitation ; statistics & numerical data ; Cohort Studies ; Emergency Medical Services ; statistics & numerical data ; Female ; Geography ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Out-of-Hospital Cardiac Arrest ; mortality ; Residence Characteristics ; statistics & numerical data ; Retrospective Studies ; Singapore ; epidemiology ; Time-to-Treatment ; statistics & numerical data ; Treatment Outcome

Synchronous primary tumors of the urothelium and prostate are a diagnostic challenge among pathologists. Differentiating carcinomas of urothelial and prostatic origin requires careful assessment of histomorphology coupled with ancillary studies such as immunohistochemistry stains (IHC) to support the diagnosis. We report two cases of adult patients who underwent transurethral resection of the prostate (TURP), with two distinct morphologies noted on routine H&E sections. After a panel of immunohistochemical stains (HMWCK, CK5/6, CK7, CK20, GATA-3, p63, NKX3.1, and PSA), both cases were signed out as papillary urothelial carcinoma and prostatic acinar adenocarcinoma. Correlation of histomorphology with an IHC panel consisting of cytokeratins (CK5/6, CK7, CK20), a urothelial marker (GATA-3), and at least two prostatic markers (PSA, NKX3.1) is recommended in such cases.

INTRODUCTION: The role of the laboratory during the COVID-19 pandemic is not limited to just diagnosis of the disease, but also in clinical decision-making, by providing information on relevant laboratory biomarkers. Clinicians also use Ct value to guide patient management. There are limited studies available locally regarding the significance of Ct value and pertinent laboratory biomarkers in COVID-19 patients. This study aimed to assess the aforementioned laboratory data, along with the clinicopathologic characteristics of affected patients, and determined if this information may be useful for robust clinical decision-makin METHODOLOGY: In this retrospective analytic study, we identified 325 out of 1,049 adult Filipino inpatients diagnosed with COVID-19 and analyzed their Ct values and pertinent laboratory biomarkers such as neutrophil and lymphocyte count, platelet count, LDH, ferritin, procalcitonin, CRP, AST/SGOT, ALT/SGPT, PT/ INR, and D-dimer, and correlated them with the severity of the disease. RESULTS: Two hundred twenty (67.7%) patients had non-severe disease, while 105 (32.3%) had severe disease. Lower Ct values of ORF1ab (median = 26.4) and N (median = 24.8) genes were seen in the severe group compared to the non-severe group and were found to be significant (p<0.001). Laboratory markers (neutrophil, platelet counts, LDH, ferritin, procalcitonin, CRP, AST, PT/INR, and D-dimer) were associated with severe COVID-19. On the other hand, ALT was not associated with severe disease. CONCLUSION The laboratory biomarkers together with Ct value and overall clinical picture may provide valuable information to physicians for more robust clinical decision-making.
COVID-19 ; laboratory biomarkers ; SARS-CoV-2 ; RT-PCR