A prospective study of incidence and outcome of acute kidney injury among hospitalised patients in Malaysia (My-AKI).

INTRODUCTION: The incidence of acute kidney injury (AKI) among hospitalised patients has not been well studied in Malaysia. MATERIALS AND METHODS: We conducted a prospective, multicentre study in seven hospitals in West Malaysia. All the adults admitted in March 2017 fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI were included. RESULTS: Of the 34,204 patients screened, 2,457 developed AKI (7.18%), 13.1% of which occurred in intensive care unit (ICU). There were 60.2% males with a mean age of 57.8 (±17.5) years. The most common comorbidities were hypertension (55.0%), diabetes (46.6%), ischaemic heart disease (15.1%) and chronic kidney disease (12.0%). The commonest causes of AKI were sepsis (41.7%), pre-renal (24.2%) and cardiorenal syndrome (10.8%). Nephrotoxin exposure was reported in 31%. At diagnosis, the proportion of AKI stages 1, 2 and 3 were 79.1%, 9.7%, 11.2%, respectively. Referral to nephrologists was reported in 16.5%. Dialysis was required in 176 (7.2%) patients and 55.6% were performed in the ICU. Acidosis (46.2%), uraemia (31.6%) and electrolyte disturbance (11.1%) were the commonest indications. Continuous renal replacement therapy (CRRT) was required in 14%. The average length of hospital stay was 9.5 days. In-hospital mortality was 16.4%. Among survivors, full and partial renal recovery was seen in 74.7% and 16.4% respectively while 8.9% failed to recover. After a mean follow-up of 13.7 months, 593 (30.2%) of survivors died and 38 (1.9%) initiated chronic dialysis. Mortality was highest among those with malignancies (Hazard Ratio, HR 2.14), chronic liver disease (HR 2.13), neurological disease (HR 1.56) and cardiovascular disease (HR 1.17). CONCLUSION: AKI is common in hospitalised patients and is with associated high mortality during and after hospitalisation.

Detection, molecular characterization, and antibiogram of multi-drug resistant and methicillin-resistant Staphylococcus aureus (MRSA) isolated from pets and pet owners in Malaysia.

BACKGROUND: The emergence of multidrug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Staphylococcus aureus (MDRSA) in animals and humans with continuous contact are a great zoonotic concern. AIMS: This cross-sectional study was performed to investigate the carriage rate, genotypic characteristics, and to determine the antibiogram of S. aureus isolated from pets and pet owners in Malaysia. METHODS: Nasal and oral swab samples from 40 cats, 30 dogs, and 70 pet owners were collected through convenient sampling. Presumptive colonies on mannitol salt agar were subjected to biochemical identification. S. aureus and MRSA were confirmed by PCR detection of nuc and mecA genes, respectively. Molecular profiles for antimicrobial resistance and virulence genes in S. aureus were also determined. The antibiogram was carried out via Kirby-Bauer test using 18 antibiotics. RESULTS: 17.5% of cats, 20% of dogs, and 27% of pet owners were S. aureus positive. MRSA was also detected in dogs, and pet owners. S. aureus isolates displayed high resistance against penicillin (72.7%), and amoxicillin/clavulanate (66.7%). 39.4% of S. aureus isolates showed multidrug-resistance traits, phenotypically. Molecular characterization of S. aureus revealed the presence of mecA, tetk, tetL, ermA, ermB, ermC, msrA, scn, chp, sak, sep, and sea genes. CONCLUSION: This study showed the emergence of MRSA and MDRSA in pets and pet owners in Malaysia. The antibiogram findings showed resistance of S. aureus to multiple antibiotics. Furthermore, molecular analysis of immune evasion cluster (IEC) strongly suggests the spread of animal-adapted S. aureus lineages among pets and pet owners.

Effect of Intracanal Medicaments on the Bond Strength of Bioceramic Root Filling Materials to Oval Canals.

AIM: This study aimed to evaluate the effect of the prior application of intracanal medicaments on the bond strength of OrthoMTA (mineral trioxide aggregate) and iRoot SP to the root dentin. MATERIALS AND METHODS: Thirty single-rooted mandibular premolars were standardized and prepared using ProTaper rotary files. The specimens were divided into a control group and two experimental groups receiving Diapex and Odontopaste medicament, either filled with iRoot SP or OrthoMTA, for 1 week. Each root was sectioned transversally, and the push-out bond strength and failure modes were evaluated. The data were analyzed using Kruskal Wallis and Mann-Whitney U post hoc test. RESULTS: There was no significant difference between the bond strength of iRoot SP and OrthoMTA without medicaments and with the prior placement of Diapex (p value > 0.05). However, iRoot SP showed significantly higher bond strength with the prior placement of Odontopaste (p value < 0.05). Also, there was no association between bond strength of OrthoMTA with or without intracanal medicament (p value > 0.05) and between failure mode and root filling materials (p value > 0.05). The prominent failure mode for all groups was cohesive. CONCLUSION: Prior application of Diapex has no effect on the bond strength of iRoot SP and OrthoMTA. However, Odontopaste improved the bond strength of iRoot SP. CLINICAL SIGNIFICANCE: Dislodgment resistance of root canal filling from root dentin could be an indicator of the durability and prognosis of endodontic treated teeth.

Photodynamic therapy for the prevention and treatment of actinic keratosis/squamous cell carcinoma in solid organ transplant recipients: a systematic review and meta-analysis.

Solid organ transplant recipients (sOTR) are at an increased risk of developing cutaneous cancers, especially squamous cell carcinoma (SCC). Photodynamic therapy (PDT) for the prevention and treatment of actinic keratosis (AK)/SCC in sOTR is increasingly prescribed given the increase in solid organ transplantations performed worldwide. PDT has added advantages of superior cosmetic outcomes and good safety profile compared to conventional surgical methods and other topical therapies. We aim to evaluate the role of PDT in the prevention and treatment of AK/SCC in sOTRs. The Cochrane Library, PubMed and EMBASE database were searched. Articles reporting PDT outcomes amongst sOTR with or without AK/SCC at baseline were selected. We classified the studies into two categories: (i) PDT as prevention measure and (ii) treatment of AK/SCC in sOTR. Primary outcome for the prevention category was 3-year incidence of AK/SCC and complete response (CR) of lesions after PDT exposure in the treatment category. Secondary outcomes were cosmesis and adverse reaction in both categories. Pooled results were expressed as risk difference (RD) with corresponding 95% confidence interval (95% CI). Twelve out of 641 articles met our eligibility criteria, out of which four RCTs reported the preventive effect of AK/SCC and another five RCTs reported the treatment effect of PDT in sOTR. One RCT did not report absolute number of lesions at baseline/end of study for results to be pooled in the quantitative analysis. The remaining three studies were cohort studies reporting treatment and preventive effect of PDT in sOTR. PDT group had a lower incidence as a preventive measure with pooled RD of 0.14 (95% CI 0.08-0.19). The CR in PDT was higher in the treatment group with a pooled RD of 0.77 (95% CI 0.6-0.94) and 0.50 (95% CI 0.22-0.79) in predivided lesional areas and number of lesions, respectively. In conclusion, PDT is efficacious for prevention and treatment of AK/SCC in sOTRs.

Spontaneous Thyroid Haemorrhage: A Cause of Upper Airway Obstruction.

BACKGROUND: Spontaneous thyroid haemorrhage is a very rare condition that is potentially life-threatening. We report an unusual case of spontaneous thyroid haemorrhage leading to airway compromise requiring urgent intervention. We highlight key clinical findings and management steps with comparison to similar cases in the literature. CASE SUMMARY: An adult male presented with sudden anterior neck swelling and bruises on his neck and chest with hoarseness and dysphagia. Clinical assessment and CT scan revealed a thyroid haemorrhage with laryngopharyngeal, neck and chest haematoma. He was intubated for airway protection and given intravenous steroids and antibiotics. He was extubated well after 3 days. CONCLUSION: Careful prompt management of the patient's airway is of vital importance as worsening haematoma can lead to rapid airway compromise. Acute physicians should be aware of the clinical signs of thyroid haemorrhage, as this rare condition may present to the acute medical take.

Acute necrotising encephalopathy of childhood: A review of two cases.

Acute necrotising encephalopathy of childhood (ANEC) is an uncommon disease with characteristic clinical and imaging findings. We present two cases of ANEC secondary to Respiratory Syncytial Virus (RSV) and mycoplasma infections. An eight-month-old boy presented with features of gastroenteritis but soon developed multiple episodes of seizures. Blood and CSF cultures were negative but nasopharyngeal aspirate immunofluorescence was positive for RSV. A nine-year-old girl presented with abnormal behaviour following two days of prodromal symptoms. Her serological markers implicated mycoplasma (IgM titre 1: 640). CT brain of both patients showed bilateral symmetrical thalamic hypodensities, while MRI revealed more extensive white matter involvements.

Robotic navigation to subcortical neural tissue for intracellular electrophysiology in vivo.

In vivo studies of neurophysiology using the whole cell patch-clamp technique enable exquisite access to both intracellular dynamics and cytosol of cells in the living brain but are underrepresented in deep subcortical nuclei because of fouling of the sensitive electrode tip. We have developed an autonomous method to navigate electrodes around obstacles such as blood vessels after identifying them as a source of contamination during regional pipette localization (RPL) in vivo. In mice, robotic navigation prevented fouling of the electrode tip, increasing RPL success probability 3 mm below the pial surface to 82% (n = 72/88) over traditional, linear localization (25%, n = 24/95), and resulted in high-quality thalamic whole cell recordings with average access resistance (32.0 MΩ) and resting membrane potential (-62.9 mV) similar to cortical recordings in isoflurane-anesthetized mice. Whole cell yield improved from 1% (n = 1/95) to 10% (n = 9/88) when robotic navigation was used during RPL. This method opens the door to whole cell studies in deep subcortical nuclei, including multimodal cell typing and studies of long-range circuits.NEW & NOTEWORTHY This work represents an automated method for accessing subcortical neural tissue for intracellular electrophysiology in vivo. We have implemented a novel algorithm to detect obstructions during regional pipette localization and move around them while minimizing lateral displacement within brain tissue. This approach leverages computer control of pressure, manipulator position, and impedance measurements to create a closed-loop platform for pipette navigation in vivo. This technique enables whole cell patching studies to be performed throughout the living brain.

Diverse and novel RHD variants in Australian blood donors with a weak D phenotype: implication for transfusion management.

BACKGROUND AND OBJECTIVES: Variant RHD genes associated with the weak D phenotype can result in complete or partial D-epitope expression on the red cell. This study examines the genetic classification in Australian blood donors with a weak D phenotype and correlates RHD variants associated with the weak D phenotype against D-epitope profile. MATERIALS AND METHODS: Following automated and manual serology, blood samples from donors reported as 'weak D' (n = 100) were RHD genotyped by a commercial SNP-typing platform and Sanger sequencing. Two commercial anti-D antibody kits were used for extended serological testing for D-epitope profiles. RESULTS: Three samples had wild-type RHD exonic sequences, and 97 samples had RHD variants. RHD*weak D type 1, RHD*weak D type 2 or RHD*weak D type 3 was detected in 75 donors. The remaining 22 samples exhibited 17 different RHD variants. One donor exhibited a novel RHD*c.939+3A>C lacking one D-epitope. Weak D types 1·1, 5, 15, 17 and 90 showed a partial D-epitope profile. CONCLUSION: The array of RHD variants detected in this study indicated diversity in the Australian donor population that needs to be accommodated for in future genotyping strategies.

Severe descending necrotizing mediastinitis: vacuum-assisted dressing did wonder.

Descending necrotizing mediastinitis (DNM) is a rapidly progressive disease from the spread of cervical infection. Transcervical and transthoracic drainage was the recognized traditional surgical approach to achieve adequate clearance of infection. Non-invasive vacuum-assisted dressing is a new technique where applied negative pressure can help remove infective fluid and to promote wound healing. A 60-year-old man presented with odynophagia, fever and anterior neck swelling for 2 weeks. He was diagnosed to have anterior neck abscess and underwent surgical drainage. However, it did not respond well, but progressed to involve superior and inferior mediastinum. Vacuum-assisted dressing was applied for total of 2 weeks and the patient recovered without going through usual traditional transthoracic drainage. Vacuum drainage is a simple, safe and non-invasive method of managing DNM, in well selected group with small abscess cavity without airway obstruction and septicemia. This potential technique can lead to paradigm shift in treating life-threatening DNM.

Genomes of coral dinoflagellate symbionts highlight evolutionary adaptations conducive to a symbiotic lifestyle.

Despite half a century of research, the biology of dinoflagellates remains enigmatic: they defy many functional and genetic traits attributed to typical eukaryotic cells. Genomic approaches to study dinoflagellates are often stymied due to their large, multi-gigabase genomes. Members of the genus Symbiodinium are photosynthetic endosymbionts of stony corals that provide the foundation of coral reef ecosystems. Their smaller genome sizes provide an opportunity to interrogate evolution and functionality of dinoflagellate genomes and endosymbiosis. We sequenced the genome of the ancestral Symbiodinium microadriaticum and compared it to the genomes of the more derived Symbiodinium minutum and Symbiodinium kawagutii and eukaryote model systems as well as transcriptomes from other dinoflagellates. Comparative analyses of genome and transcriptome protein sets show that all dinoflagellates, not only Symbiodinium, possess significantly more transmembrane transporters involved in the exchange of amino acids, lipids, and glycerol than other eukaryotes. Importantly, we find that only Symbiodinium harbor an extensive transporter repertoire associated with the provisioning of carbon and nitrogen. Analyses of these transporters show species-specific expansions, which provides a genomic basis to explain differential compatibilities to an array of hosts and environments, and highlights the putative importance of gene duplications as an evolutionary mechanism in dinoflagellates and Symbiodinium.

Duffy blood group phenotype-genotype correlations using high-resolution melting analysis PCR and microarray reveal complex cases including a new null FY*A allele: the role for sequencing in genotyping algorithms.

BACKGROUND AND OBJECTIVES: Duffy blood group phenotypes can be predicted by genotyping for single nucleotide polymorphisms (SNPs) responsible for the Fy(a) /Fy(b) polymorphism, for weak Fy(b) antigen, and for the red cell null Fy(a-b-) phenotype. This study correlates Duffy phenotype predictions with serotyping to assess the most reliable procedure for typing. MATERIALS AND METHODS: Samples, n = 155 (135 donors and 20 patients), were genotyped by high-resolution melt PCR and by microarray. Samples were in three serology groups: 1) Duffy patterns expected n = 79, 2) weak and equivocal Fy(b) patterns n = 29 and 3) Fy(a-b-) n = 47 (one with anti-Fy3 antibody). RESULTS: Discrepancies were observed for five samples. For two, SNP genotyping predicted weak Fy(b) expression discrepant with Fy(b-) (Group 1 and 3). For three, SNP genotyping predicted Fy(a) , discrepant with Fy(a-b-) (Group 3). DNA sequencing identified silencing mutations in these FY*A alleles. One was a novel FY*A 719delG. One, the sample with the anti-Fy3, was homozygous for a 14-bp deletion (FY*01N.02); a true null. CONCLUSION: Both the high-resolution melting analysis and SNP microarray assays were concordant and showed genotyping, as well as phenotyping, is essential to ensure 100% accuracy for Duffy blood group assignments. Sequencing is important to resolve phenotype/genotype conflicts which here identified alleles, one novel, that carry silencing mutations. The risk of alloimmunisation may be dependent on this zygosity status.

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.

Management experience of subglottic stenosis by endoscopic bougie dilatation with mitomycin C and review of literature: case series.

The aim of the study was to examine and analyze the epidemiology and outcome of treatment for paediatric acquired subglottic stenosis treated with endoscopic bougie dilatation and topical mitomycin C. There were 15 patients identified from 2008 until 2013. All of them had acquired subglottic stenosis due to history of intubation. Majority of the patients had grade III stenosis, with the total of seven. Three patients had grade IV; three were grade II and two were grade I. All of the patients with severe stenosis (grade III and IV) needed tracheostomy while only one in mild stenosis group (grade I and II) required it for prolonged ventilation rather than obstruction due to subglottic stenosis. All of them underwent direct laryngoscopy under general anesthesia followed by endoscopic dilatation with bougie and topical mitomycin C 0.4 mg/ml for 5 min. Aim of success in our study was decannulation of tracheostomy or absence of symptoms at exertion. We achieved 6 (60 %) successful decannulation out of 10 patients with tracheostomy (excluded the patient with tracheostomy in grade I stenosis due to prolonged ventilation). As for those without tracheostomy, 3 (75 %) out of 4 patients were asymptomatic even at exertion. Average number of dilatation was 3.1 times, with mean duration of 28 min. No complications were reported in our series. One patient with grade I stenosis passed away due to severe pneumonia unrelated to the stenosis or dilatation, and she did not have any dilatation before she passed away. Multiple related risk factors were identified such as intubation, prematurity, movement of endotracheal tube, respiratory infection, traumatic intubation and gastroesophageal reflux disease. Experience of open surgical method was very limited in our centre in Sabah in East Malaysia. Endoscopic technique plays an important role in treatment of subglottic stenosis with adjunct like mitomycin C possibly booster the successful rate.

A novel FY*A allele with the 265T and 298A SNPs formerly associated exclusively with the FY*B allele and weak Fy(b) antigen expression: implication for genotyping interpretative algorithms.

BACKGROUND AND OBJECTIVES: An Australian Caucasian blood donor consistently presented a serology profile for the Duffy blood group as Fy(a+b+) with Fy(a) antigen expression weaker than other examples of Fy(a+b+) red cells. Molecular typing studies were performed to investigate the reason for the observed serology profile. MATERIAL AND METHODS: Blood group genotyping was performed using a commercial SNP microarray platform. Sanger sequencing was performed using primer sets to amplify across exons 1 and 2 of the FY gene and using allele-specific primers. RESULTS: The propositus was genotyped as FY*A/B, FY*X heterozygote that predicted the Fy(a+b+(w) ) phenotype. Sequencing identified the 265T and 298A variants on the FY*A allele. This link between FY*A allele and 265T was confirmed by allele-specific PCR. CONCLUSION: The reduced Fy(a) antigen reactivity is attributed to a FY*A allele-carrying 265T and 298A variants previously defined in combination only with the FY*B allele and associated with weak Fy(b) antigen expression. This novel allele should be considered in genotyping interpretative algorithms for generating a predicted phenotype.

Public and Private Hospitals in Kuala Lumpur and Selangor, Malaysia: How Do They Fare in Terms of Accessibility for the Physically Disabled?

Public and private hospitals in Kuala Lumpur and Selangor were evaluated in terms of their accessibility for the physically disabled. The research hypotheses for this study included the following: (1) Both types of hospitals are accessible for the physically disabled as measured by specifi c criteria but (2) the degree of accessibility is higher in the case of private hospitals as compared to public hospitals. A total of 23 private hospitals and 11 public hospitals in Kuala Lumpur and Selangor were invited to participate in the study. The 5 private hospitals and 5 public hospitals that agreed were evaluated for adequacy of facilities for the physically-disabled. For this purpose, 13 specifi c criteria were assessed and scored for each hospital. These criteria were also grouped into 5 categories, namely, parking, toilet, door and lift, corridor and ramp. Scores were compared between each hospital and then aggregated and compared for private hospitals versus public hospitals. It was found that none of the 5 private hospitals and 5 public hospitals studied satisfi ed 100% of the criteria evaluated. Looking at each hospital individually, the overall scores range from 32% to 92% for the criteria set. Only 4 of the 10 hospitals in our sample achieved overall scores of 80% or higher in terms of the evaluation criteria we used. With the exception of availability of ramps where public hospitals scored slightly higher ,for most of the individual criterion, private hospitals scored higher than public hospitals. Looking at each criterion across all hospitals, the scores range from 59.2% (adequacy of parking) to 85% (adequacy of corridors). The median score obtained by private hospitals and by public hospitals for all 13 criteria were analysed for any difference. The difference between private hospitals and public hospitals is not statistically signifi cant (Mann-Whitney U = 6.5, p-value = 0.099). There is no signifi cant difference between Kuala Lumpur/Selangor private and public hospitals in terms of accessibility for physically disabled people. However, some hospitals are more accessible for the physically disabled than other hospitals. These fi ndings indicate that there is room for improvement.