Microstructural abnormalities found in uncinate fasciculus and superior cerebellar tracts in children with global developmental delay: a feasibility study.

AIM: To evaluate the microstructural abnormalities of the white matter tracts (WMT) using diffusion tensor imaging (DTI) in children with global developmental delay (GDD). MATERIALS AND METHODS: Sixteen children with GDD underwent magnetic resonance imaging (MRI) and cross-sectional DTI. Formal developmental assessment of all GDD patients was performed using the Mullen Scales of Early Learning. An automated processing pipeline for the WMT assessment was implemented. The DTI-derived metrics of the children with GDD were compared to healthy children with normal development (ND). RESULTS: Only two out of the 17 WMT demonstrated significant differences (p<0.05) in DTI parameters between the GDD and ND group. In the uncinate fasciculus (UF), the GDD group had lower mean values for fractional anisotropy (FA; 0.40 versus 0.44), higher values for mean diffusivity (0.96 versus 0.91×10-3 mm2/s) and radial diffusivity (0.75 versus 0.68×10-3 mm2/s) compared to the ND group. In the superior cerebellar peduncle (SCP), mean FA values were lower for the GDD group (0.38 versus 0.40). Normal myelination pattern of DTI parameters was deviated against age for GDD group for UF and SCP. CONCLUSION: The UF and SCP WMT showed microstructural changes suggestive of compromised white matter maturation in children with GDD. The DTI metrics have potential as imaging markers for inadequate white matter maturation in GDD children.

Impact of contusion injury on intramuscular emm1 group a streptococcus infection and lymphatic spread.

Invasive group A Streptococcus (iGAS) is frequently associated with emm1 isolates, with an attendant mortality of around 20%. Cases occasionally arise in previously healthy individuals with a history of upper respiratory tract infection, soft tissue contusion, and no obvious portal of entry. Using a new murine model of contusion, we determined the impact of contusion on iGAS bacterial burden and phenotype. Calibrated mild blunt contusion did not provide a focus for initiation or seeding of GAS that was detectable following systemic GAS bacteremia, but instead enhanced GAS migration to the local draining lymph node following GAS inoculation at the same time and site of contusion. Increased migration to lymph node was associated with emergence of mucoid bacteria, although was not specific to mucoid bacteria. In one study, mucoid colonies demonstrated a significant increase in capsular hyaluronan that was not linked to a covRS or rocA mutation, but to a deletion in the promoter of the capsule synthesis locus, hasABC, resulting in a strain with increased fitness for lymph node migration. In summary, in the mild contusion model used, we could not detect seeding of muscle by GAS. Contusion promoted bacterial transit to the local lymph node. The consequences of contusion-associated bacterial lymphatic migration may vary depending on the pathogen and virulence traits selected.

Echocardiographic and electrocardiographic presentations of patients with endomyocardial biopsy-proven cardiac amyloidosis.

OBJECTIVE: Cardiac amyloidosis is under diagnosed and its prevalence is unknown. This is a retrospective, nonrandomised, single centre study of patients with endomyocardial biopsy-proven cardiac amyloidosis focusing on their echocardiographic and electrocardiogram (ECG) presentations. This is the first case series in Malaysia on this subject. METHODS: We identified all of our endomyocardial biopsyproven cardiac amyloidosis patients from January 2010 to January 2018 and reviewed their medical records. All patients echocardiographic and ECG findings reviewed and analysed comparing to basic mean population value. RESULTS: In total there are 13 biopsy-proven cardiac amyloidosis patients. All of the biopsies shows light chain (AL) amyloid. Majority of the patients (8, 61.5%) is male, and most of our patients (8, 61.5%) is Chinese. All seven patients on whom we performed deformation imaging have apical sparing pattern on longitudinal strain echocardiogram. Mean ejection fraction is 49.3%, (SD=7.9). All patients have concentric left ventricular hypertrophy and right ventricular hypertrophy. Diastolic dysfunction was present in all of our patients with nine out of 13 patients (69.2%) having restrictive filling patterns (E/A ≥2.0 E/e' ≥15). On electrocardiogram, 12 (92%) patients have prolonged PR interval (median 200ms, IQR 76.50ms) and 9 (69.2%) patients have pseudoinfarct pattern. CONCLUSION: Echocardiography plays an important role in diagnosing cardiac amyloidosis. The findings of concentric left ventricular hypertrophy with preserved ejection fraction without increased in loading condition should alert the clinician towards its possibility. This is further supported by right ventricular hypertrophy and particularly longitudinal strain imaging showing apical sparing pattern.

A case of successfully managed pregnancy in a patient with complex cyanotic congenital heart disease.

Medical advances have increased survival of patients with congenital heart disease. However, cardiac disease in pregnancy carries significant maternal and fetal risks, posing enormous challenges to obstetricians. Cyanotic congenital heart disease is associated with maternal complications such as arrhythmias, thromboembolic events and death. Fetal complications include small for gestational age, miscarriage and prematurity. Cyanotic congenital heart disease patients who continue their pregnancies require holistic multidisciplinary team care with early and coordinated planning for delivery. Management of such patients include early counseling regarding pregnancy-associated risks, close monitoring of their cardiac function and regular scanning for fetal assessment. Choice of anesthesia for these patients requires meticulous planning to achieve a favorable balance between systemic and pulmonary vascular resistance, ensuring minimal change in right-to-left shunting. We report a case of a successfully managed pregnancy in a patient with complex congenital heart disease and a single ventricle of left ventricle morphology.

An exploration of the applicability of the refined disease risk index and its integration with other independent risk factors for individualized prognostication.

The refined disease risk index (DRI) is a powerful prognostic model based solely on the disease type and stage for predicting survival outcomes of various hematological malignancies after allogeneic transplant. Here, we analyzed our series of 690 patients transplanted over the past 15 years, and showed that besides overall survival (OS), the refined DRI is also able to segregate event-free survival and relapse mortality in our cohort of largely Southeast Asian patients with a long and complete follow-up. Stratification by refined DRI remains statistically significant even when broken down by specific diseases each with a smaller number of patients, as well as for a small subset of patients younger than 18 years old, providing a robust model for prognostication. Multivariable analysis shows that refined DRI, age, year of transplant and donor type are independent risk factors for OS. We further demonstrated here that prognostication for a given patient with a specific disease can be made more discriminating by integrating independent risk factors such as age and donor type with the refined DRI. The future development of prognostic system incorporating the refined DRI with patient- and transplant-related risk factors will provide a more precise estimate of transplant outcome.

Repeated failed non-invasive prenatal testing in a woman with immune thrombocytopenia and antiphospholipid syndrome: lessons learnt.

We present a case of a 37-year-old Chinese woman (gravida 4 para 0) with a history of immune thrombocytopenia and type IIb antiphospholipid syndrome. She was started on 100 mg of aspirin, 20 mg of prednisolone and 20 mg of subcutaneous low-molecular-weight heparin daily for her fourth pregnancy. She opted for non-invasive prenatal testing for aneuploidy screening but had failed results three times consecutively from insufficient fetal cfDNA initially or high variance in cfDNA counts on redraws. She declined invasive karyotyping. Her pregnancy was complicated by severe pre-eclampsia and fetal growth restriction at 19+6 weeks of gestation and was terminated. Subsequent fetal karyotyping revealed a normal karyotype of 46XY with no apparent abnormalities.

A national common massive transfusion protocol (MTP) is a feasible and advantageous option for centralized blood services and hospitals.

BACKGROUND: A common national MTP was jointly implemented in 2011 by the national blood service (Blood Services Group) and seven participating acute hospitals to provide rapid access to transfusion support for massively haemorrhaging patients treated in all acute care hospitals. METHODS: Through a systematic clinical workflow, blood components are transfused in a ratio of 1:1:1 (pRBC: whole blood-derived platelets: FFP), together with cryoprecipitate for fibrinogen replacement. The composition of components for the MTP is fixed, although operational aspects of the MTP can be adapted by individual hospitals to suit local hospital workflow. The MTP could be activated in support of any patient with critical bleeding and at risk of massive transfusion, including trauma and non-trauma general medical, surgical and obstetric patients. RESULTS: There were 434 activations of the MTP from October 2011 to October 2013. Thirty-nine per cent were for trauma patients, and 30% were for surgical patients with heavy intra-operative bleeding, with 25% and 6% for patients with gastrointestinal bleeding and peri-partum haemorrhage, respectively. Several hospitals reported reduction in mean time between request and arrival of blood. Mean transfusion ratio achieved was one red cell unit: 0·8 FFP units: 0·8 whole blood-derived platelet units: 0·4 units of cryoprecipitate. Although cryoprecipitate usage more than doubled after introduction of MTP, there was no significant rise in overall red cells, platelet and FFP usage following implementation. CONCLUSION: This successful collaboration shows that shared transfusion protocols are feasible and potentially advantageous for hospitals sharing a central blood provider.

Motion corrected LV quantification based on 3D modelling for improved functional assessment in cardiac MRI.

Cine MRI is a clinical reference standard for the quantitative assessment of cardiac function, but reproducibility is confounded by motion artefacts. We explore the feasibility of a motion corrected 3D left ventricle (LV) quantification method, incorporating multislice image registration into the 3D model reconstruction, to improve reproducibility of 3D LV functional quantification. Multi-breath-hold short-axis and radial long-axis images were acquired from 10 patients and 10 healthy subjects. The proposed framework reduced misalignment between slices to subpixel accuracy (2.88 to 1.21 mm), and improved interstudy reproducibility for 5 important clinical functional measures, i.e. end-diastolic volume, end-systolic volume, ejection fraction, myocardial mass and 3D-sphericity index, as reflected in a reduction in the sample size required to detect statistically significant cardiac changes: a reduction of 21-66%. Our investigation on the optimum registration parameters, including both cardiac time frames and number of long-axis (LA) slices, suggested that a single time frame is adequate for motion correction whereas integrating more LA slices can improve registration and model reconstruction accuracy for improved functional quantification especially on datasets with severe motion artefacts.

Glaucoma severity affects diffusion tensor imaging (DTI) parameters of the optic nerve and optic radiation.

OBJECTIVES: To evaluate whether MR diffusion tensor imaging (DTI) of the optic nerve and optic radiation in glaucoma patients provides parameters to discriminate between mild and severe glaucoma and to determine whether DTI derived indices correlate with retinal nerve fibre layer (RNFL) thickness. METHODS: 3-Tesla DTI was performed on 90 subjects (30 normal, 30 mild glaucoma and 30 severe glaucoma subjects) and the FA and MD of the optic nerve and optic radiation were measured. The categorisation into mild and severe glaucoma was done using the Hodapp-Parrish-Anderson (HPA) classification. RNFL thickness was also assessed on all subjects using OCT. Receiver operating characteristic (ROC) analysis and Spearman's correlation coefficient was carried out. RESULTS: FA and MD values in the optic nerve and optic radiation decreased and increased respectively as the disease progressed. FA at the optic nerve had the highest sensitivity (87%) and specificity (80%). FA values displayed the strongest correlation with RNFL thickness in the optic nerve (r=0.684, p ≤ 0.001) while MD at the optic radiation showed the weakest correlation with RNFL thickness (r=-0.360, p ≤ 0.001). CONCLUSIONS: The high sensitivity and specificity of DTI-derived FA values in the optic nerve and the strong correlation between DTI-FA and RNFL thickness suggest that these parameters could serve as indicators of disease severity.

Improved diagnostic accuracy in differentiating malignant and benign lesions using single-voxel proton MRS of the breast at 3 T MRI.

AIM: To investigate the diagnostic accuracy of single-voxel proton magnetic resonance spectroscopy (SV (1)H MRS) by quantifying total choline-containing compounds (tCho) in differentiating malignant from benign lesions, and subsequently, to analyse the relationship of tCho levels in malignant breast lesions with their histopathological subtypes. MATERIALS AND METHODS: A prospective study of SV 1H MRS was performed following dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in 61 women using a 3 T MR system. All lesions (n = 57) were analysed for characteristics of morphology, contrast-enhancement kinetics, and tCho peak heights at SV (1)H MRS that were two-times above baseline. Subsequently, the tCho in selected lesions (n = 32) was quantified by calculating the area under the curve, and a tCho concentration equal to or greater than the cut-off value was considered to represent malignancy. The relationship between tCho in invasive ductal carcinomas (IDCs) and their Bloom & Richardson grading of malignancy was assessed. RESULTS: Fifty-two patients (57 lesions; 42 malignant and 15 benign) were analysed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), of predicting malignancy were 100, 73.3, 91.3, and 100%, respectively, using DCE-MRI and 95.2, 93.3, 97.6, and 87.5%, respectively, using SV (1)H MRS. The tCho cut-off for receiver operating characteristic (ROC) curve was 0.33 mmol/l. The relationship between tCho levels in malignant breast lesions with their histopathological subtypes was not statistically significant (p = 0.3). CONCLUSION: Good correlation between tCho peaks and malignancy, enables SV (1)H MRS to be used as a clinically applicable, simple, yet non-invasive tool for improved specificity and diagnostic accuracy in detecting breast cancer.

Awareness of and attitudes toward congenital cytomegalovirus infection among pregnant women in Singapore.

OBJECTIVE: To assess the level of awareness of congenital cytomegalovirus (CMV) infection and attitudes toward prenatal CMV serologic testing among pregnant women. METHODS: A questionnaire was distributed to pregnant women who attended a specialist outpatient clinic at Singapore General Hospital, Singapore, between September and December 2010. RESULTS: Among 200 respondents, 40 (20.0%) were aware of CMV. Healthcare workers were more likely to be aware of CMV (odds ratio 6.91, confidence interval 2.14-22.30; P=0.001). Most respondents found it "very" or "somewhat" easy to adhere to standard guidelines for primary prevention of CMV. Among the respondents, 62.0% (124/200) would like to be given the option of prenatal CMV screening and 72.0% (144/200) were keen to be screened. On multivariate analysis, respondents who were keen to undergo serologic screening for CMV were not more likely to consider invasive testing or termination of pregnancy should the test results demonstrate primary maternal CMV infection. CONCLUSION: Pregnant women who were keen to undergo CMV testing demonstrated attitudes toward invasive testing and termination of pregnancy that were not significantly different from those of women who would refuse testing. Patient choice and expectations should be considered in the implementation of preventive measures against congenital CMV.

Quantification of diffusion tensor imaging in normal white matter maturation of early childhood using an automated processing pipeline.

OBJECTIVES: The degree and status of white matter myelination can be sensitively monitored using diffusion tensor imaging (DTI). This study looks at the measurement of fractional anistropy (FA) and mean diffusivity (MD) using an automated ROI with an existing DTI atlas. METHODS: Anatomical MRI and structural DTI were performed cross-sectionally on 26 normal children (newborn to 48 months old), using 1.5-T MRI. The automated processing pipeline was implemented to convert diffusion-weighted images into the NIfTI format. DTI-TK software was used to register the processed images to the ICBM DTI-81 atlas, while AFNI software was used for automated atlas-based volumes of interest (VOIs) and statistical value extraction. RESULTS: DTI exhibited consistent grey-white matter contrast. Triphasic temporal variation of the FA and MD values was noted, with FA increasing and MD decreasing rapidly early in the first 12 months. The second phase lasted 12-24 months during which the rate of FA and MD changes was reduced. After 24 months, the FA and MD values plateaued. CONCLUSION: DTI is a superior technique to conventional MR imaging in depicting WM maturation. The use of the automated processing pipeline provides a reliable environment for quantitative analysis of high-throughput DTI data. KEY POINTS: Diffusion tensor imaging outperforms conventional MRI in depicting white matter maturation. • DTI will become an important clinical tool for diagnosing paediatric neurological diseases. • DTI appears especially helpful for developmental abnormalities, tumours and white matter disease. • An automated processing pipeline assists quantitative analysis of high throughput DTI data.

Ministry of health clinical practice guidelines: clinical blood transfusion.

The Health Sciences Authority (HSA) and the Ministry of Health (MOH) publish clinical practice guidelines on Clinical Blood Transfusion to provide doctors and patients in Singapore with evidence-based guidance for blood transfusion. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the HSA-MOH clinical practice guidelines on Clinical Blood Transfusion, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov.sg/mohcorp/publications.aspx?id=25700). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Severe septic-shock like reaction to co-trimoxazole in an HIV-positive man.

Adverse drug reactions occur at a greater frequency in HIV-infected individuals. A 38-year-old Eritrean man was treated with outpatient co-trimoxazole for confirmed Pneumocystis jirovecii pneumonia, but was switched to clindamycin and primaquine due to nausea and vomiting. Following development of methaemaglobinaemia, he was recommenced on prophylactic co-trimoxazole. He was later found moribund with features resembling septic shock and required invasive respiratory support. The diagnosis of a rare, but severe reaction to co-trimoxazole did not become apparent until he was rechallenged with prophylactic co-trimoxazole after recovery from his initial severe reaction. In an era of polypharmacy and an increasing availability of novel drugs, this case is a timely reminder to clinicians of the ongoing need for pharmacovigilance, especially in HIV-infected individuals who may have unusual presentations of an adverse drug reaction.

Molar pregnancy with false negative urine hCG: the hook effect.

Urine pregnancy tests are widely used in emergency departments as the first screening test for patients of reproductive age presenting with gynaecological problems in order to rule out pregnancy. Conditions such as complete molar pregnancy, which produces large amounts of beta human chorionic gonadotropin (beta-hCG), may cause a false negative result due to an oversaturation of the assay system, known as the "hook effect". We report a case where the exclusion of pregnancy by urine testing led to the initial misdiagnosis of a molar pregnancy as a degenerative fibroid. Physicians need to be reminded of the possibility of false negative results with this commonly used test. Negative or inconclusive results in patients with a high suspicion of pregnancy should be further evaluated by serum quantification of beta-hCG and appropriate sample dilution.

Obstetric outcomes in women with end-stage renal disease on chronic dialysis: a review.

Pregnancies in women on chronic dialysis for end-stage renal disease are high risk, but outcomes appear to have improved with increasing experience and advances in dialysis care. This paper reviews the existing data on outcomes in such pregnancies to enable evidence-based preconception counselling and anticipation of antenatal complications.

B-Lynch suture for the treatment of uterine atony.

INTRODUCTION: Over 125,000 women die of postpartum haemorrhage (PPH) each year, with the commonest cause being uterine atony (75-90 percent). Failing conservative management, hysterectomy is usually the final resort. In 1997, Christopher B-Lynch devised an innovative technique to treat uterine atony, and it has been widely used around the world since its original report. However, there are hardly any reports of this technique being utilised in East Asian countries, including Singapore. Our study reviews the cases in which the B-Lynch suture was used to treat uterine atony, and the clinical outcomes of these cases. METHODS: A retrospective study of data of all women who delivered between May 2004 and June 2007 was collected from the department's database, to identify patients who had undergone the B-Lynch procedure. Primary PPH is defined as a blood loss of more than 500 ml at or within 24 hours of delivery. RESULTS: There were a total of 5,470 deliveries during this period, with primary PPH occurring in 100 cases. The B-Lynch procedure was performed in seven women, avoiding the need for a hysterectomy in five cases. CONCLUSION: Our series of cases treated with the B-Lynch procedure showed that it is an effective method of containing PPH. It has the advantage of being applied easily and rapidly, and should be taught to all trainees and registrars in obstetrics. It should be attempted when conservative management of PPH fails and before any radical surgery is considered.