Hong Kong Society of Clinical Blood Management recommendations for implementation of patient blood management.

Patient blood management (PBM) is a patient-centred, multidisciplinary approach to optimise red cell mass, minimise blood loss, and manage tolerance to anaemia in an effort to improve patient outcomes. Well-implemented PBM improves patient outcomes and reduces demand for blood products. The multidisciplinary approach of PBM can often allow patients to avoid blood transfusions, which are associated with less favourable clinical outcomes. In Hong Kong, there has been increasing demand for blood in the ageing population, and there are simultaneous blood safety and donor issues that are adversely affecting the blood supply. To address these challenges, the Hong Kong Society of Clinical Blood Management recommends implementation of a PBM programme in Hong Kong, including strategies such as optimising red blood cell mass, improving anaemia management, minimising blood loss, and rationalising the use of blood and blood products.

Pseudoepitheliomatous keratotic and micaceous balanitis treated with topical 5-fluorouracil and liquid nitrogen.

Pseudoepitheliomatous keratotic and micaceous balanitis (PKMB) is an uncommon premalignant condition involving the glans penis. We report the case of an 86-year-old man who presented with phimosis and pain on retracting his foreskin. He had previously undergone circumcision, which revealed a hyperkeratotic plaque with thin mica-like scales involving his glans penis. Histology of the lesion showed hyperkeratosis, parakeratosis, epidermal acanthosis and papillomatosis with no evidence of dysplasia. Immunohistochemistry for human papillomavirus was negative. The patient was treated with topical 5-fluorouracil and liquid nitrogen with clinical improvement. He is now under long-term surveillance for verrucous carcinoma and squamous cell carcinoma.

Papular angiolymphoid hyperplasia and lymphoplasmacytic plaque: a clinical and histological spectrum.

Acral pseudolymphomatous angiokeratoma of children (APACHE) is a rare form of cutaneous pseudolymphoma characterized byangiomatous papules with a predilection for the acral regions of children. Classically, a dense dermal lymphocytic infiltrate composed of both T and B cells is seen in histological specimens, together with prominent vessels lined by plump endothelial cells. Increasing evidence suggests that this condition is neither necessarily acral, pseudolymphomatous, nor angiokeratomatous. It may not always be a pediatric disease. Therefore, the correctness of its nomenclature has been questioned. Herein, we report threecases whose clinical and histological features were consistent with the diagnosis of APACHE. To our knowledge, this is the first report of APACHE from Southeast Asia. We also discuss why we believe "APACHE" to be a misnomer and support "papular angiolymphoid hyperplasia" as a more accurate and encompassing term. In addition, we illustrate a case with significant overlapping features with lymphoplasmacytic plaque in children, suggesting that both entities may exist on a clinical andhistological spectrum.

A two-way clustering framework to identify disparities in multimorbidity patterns of mental and physical health conditions among Australians.

Multimorbidity is present in more than one quarter of the population in Australia, and its prevalence increases with age. Greater multimorbidity burden among individuals is always associated with poor health-related outcomes, including quality of life, health service utilization and mortality, among others. It is thus significant to identify the heterogeneity in multimorbidity patterns in the community and determine the impact of multimorbidity on individual health outcomes. In this paper, I propose a two-way clustering framework to identify clusters of most significant non-random comorbid health conditions and disparities in multimorbidity patterns among individuals. This framework can establish a clustering-based approach to determine the association between multimorbidity patterns and health-related outcomes and to calculate a multimorbidity score for each individual. The proposed method is illustrated using simulated data and a national survey data set of mental health and wellbeing in Australia.

Maternal pregravid body mass index and child hospital admissions in the first 5 years of life: results from an Australian birth cohort.

OBJECTIVES: To examine the association of maternal pregravid body mass index (BMI) and child offspring, all-cause hospitalisations in the first 5 years of life. METHODS: Prospective birth cohort study. From 2006 to 2011, 2779 pregnant women (2807 children) were enrolled in the Environments for Healthy Living: Griffith birth cohort study in South-East Queensland, Australia. Hospital delivery record and self-report baseline survey of maternal, household and demographic factors during pregnancy were linked to the Queensland Hospital Admitted Patients Data Collection from 1 November 2006 to 30 June 2012, for child admissions. Maternal pregravid BMI was classified as underweight (<18.5 kg m(-)(2)), normal weight (18.5-24.9 kg m(-)(2)), overweight (25.0-29.9 kg m(-)(2)) or obese (⩾30 kg m(-)(2)). Main outcomes were the total number of child hospital admissions and ICD-10-AM diagnostic groupings in the first 5 years of life. Negative binomial regression models were calculated, adjusting for follow-up duration, demographic and health factors. The cohort comprised 8397.9 person years (PYs) follow-up. RESULTS: Children of mothers who were classified as obese had an increased risk of all-cause hospital admissions in the first 5 years of life than the children of mothers with a normal BMI (adjusted rate ratio (RR) =1.48, 95% confidence interval 1.10-1.98). Conditions of the nervous system, infections, metabolic conditions, perinatal conditions, injuries and respiratory conditions were excessive, in both absolute and relative terms, for children of obese mothers, with RRs ranging from 1.3-4.0 (PYs adjusted). Children of mothers who were underweight were 1.8 times more likely to sustain an injury or poisoning than children of normal-weight mothers (PYs adjusted). CONCLUSION: RESULTS suggest that if the intergenerational impact of maternal obesity (and similarly issues related to underweight) could be addressed, a significant reduction in child health care use, costs and public health burden would be likely.

Imprinting in the schizophrenia candidate gene GABRB2 encoding GABA(A) receptor ß(2) subunit.

Schizophrenia is a complex genetic disorder, the inheritance pattern of which is likely complicated by epigenetic factors yet to be elucidated. In this study, transmission disequilibrium tests with family trios yielded significant differences between paternal and maternal transmissions of the disease-associated single-nucleotide polymorphism (SNP) rs6556547 and its haplotypes. The minor allele (T) of rs6556547 was paternally undertransmitted to male schizophrenic offsprings, and this parent-of-origin effect strongly suggested that GABRB2 is imprinted. 'Flipping' of allelic expression in heterozygotes of SNP rs2229944 (C/T) in GABRB2 or rs2290732 (G/A) in the neighboring GABRA1 was compatible with imprinting effects on gene expression. Clustering analysis of GABRB2 mRNA expressions suggested that imprinting brought about the observed two-tiered distribution of expression levels in controls with heterozygous genotype at the disease-associated SNP rs1816071 (A/G). The deficit of upper-tiered expressions accounted for the lowered expression levels in the schizophrenic heterozygotes. The occurrence of a two-tiered distribution furnished support for imprinting, and also pointed to the necessity of differentiating between two kinds of heterozygotes of different parental origins in disease association studies on GABRB2. Bisulfite sequencing revealed hypermethylation in the neighborhood of SNP rs1816071, and methylation differences between controls and schizophrenia patients. Notably, the two schizophrenia-associated SNPs rs6556547 and rs1816071 overlapped with a CpG dinucleotide, thereby opening the possibility that CpG methylation status of these sites could have an impact on the risk of schizophrenia. Thus multiple lines of evidence pointed to the occurrence of imprinting in the GABRB2 gene and its possible role in the development of schizophrenia.

Amicrobial pustulosis associated with autoimmune disease in a patient with Sjögren syndrome and IgA nephropathy.

Amicrobial pustulosis associated with autoimmune disease (APAD) is a rare clinical condition, characterized by relapsing pustular eruption, affecting mainly the skin folds. Almost all previously described cases were young women with varying underlying autoimmune diseases. We report a 36-year-old woman with the interesting triad of APAD, Sjögren syndrome and IgA nephropathy. Her rashes responded to oral prednisolone and cyclophosphamide.

Natural history and predictors for progression of mild childhood obstructive sleep apnoea.

AIMS: The natural history of mild childhood obstructive sleep apnoea (OSA) was examined and factors associated with disease progression were identified. METHODS: Subjects were recruited from an epidemiological study which examined the prevalence of OSA in Chinese children aged 6-13 years. The first 56 consecutive children identified with mild OSA (apnoea-hypopnoea index 1-5) were invited for a repeat assessment 2 years after the diagnosis. RESULTS: 45 children participated in the follow-up study, in 13 of whom (29%) the OSA was found to have worsened. Compared with those in whom OSA had not worsened, the worsened OSA group had a greater increase in waist circumference, a higher prevalence of large tonsils (occupying > or =50% of the airway) at both baseline and follow-up, and a higher prevalence of habitual snoring at both baseline and follow-up. The presence of large tonsils had a positive predictive value of 53% and a negative predictive value of 83% for worsening OSA over a 2-year period. Multivariate linear regression analysis showed that the change in obstructive apnoea-hypopnoea index was associated with age at baseline (beta (SE) = -0.92 (0.34), p = 0.009), gender (male = 1; female = 0) (beta (SE) = 4.69 (1.29), p<0.001), presence of large tonsils at baseline (beta (SE) = 4.36 (1.24), p = 0.001), change in waist circumference (beta (SE) = 0.30 (0.09), p = 0.002) and persistently large tonsils (beta (SE) = 5.69 (1.36), p<0.001) over the 2-year period. CONCLUSIONS: Mild OSA in the majority of children does not resolve spontaneously. Subjects with tonsillar hypertrophy, especially boys, should be closely monitored to allow early detection of worsening OSA. Weight control should be stressed in the management of childhood OSA.

Cardiac remodelling and dysfunction in children with obstructive sleep apnoea: a community based study.

BACKGROUND: Childhood obstructive sleep apnoea (OSA) is suggested to be associated with cardiac structural abnormalities and dysfunction but existing evidence is limited and the treatment effect on echocardiographic outcome remains controversial. OBJECTIVE: To examine the presence of subclinical cardiac abnormalities in childhood OSA and the effects of treatment on cardiac changes. METHODS: Polysomnography (PSG) and echocardiographic examinations were performed in 101 children aged between 6 and 13 years who were invited from a community based questionnaire survey. They were classified into a reference group (apnoea-hypopnoea index (AHI) <1, n = 35), mild OSA group (AHI 1-5, n = 39) and moderate to severe group (AHI >5, n = 27) based on the PSG results. Treatments, including adenotonsillectomy or nasal steroids, were offered to the mild and moderate to severe OSA groups. RESULTS: The moderate to severe OSA group had greater right ventricular (RV) systolic volume index (RVSVI), lower RV ejection fraction (RVEF) and higher RV myocardial performance index (RVMPI) than the reference group. They also had more significant left ventricular (LV) diastolic dysfunction and remodelling with larger interventricular septal thickness index (IVSI) and relative wall thickness than those with lower AHI values. The moderate to severe OSA group had an increased risk of abnormal LV geometry compared with the reference group (odds ratio 4.21 (95% CI 1.35 to 13.12)). Log transformed AHI was associated with RVSVI (p = 0.0002), RVEF (p = 0.0001) and RVMPI (p<0.0001), independent of the effect of obesity. Improvement in RVMPI, IVSI and E/e' were observed in those with a significant reduction in AHI (>50%) comparing 6 month with baseline data. CONCLUSIONS: OSA is an independent risk factor for subclinical RV and LV dysfunction, and improvement in AHI is associated with reversibility of these abnormalities.

Prurigo pigmentosa: a report of two cases that responded to minocycline.

Prurigo pigmentosa (PP) is an unusual pruriginous dermatosis of unknown aetiology and is often misdiagnosed. We report two people (a 16-year-old Chinese boy and a 21-year-old Chinese woman), who presented with clinicopathological features consistent with PP. Both patients were successfully treated with minocycline. Better knowledge of this disease will lead to early recognition and appropriate treatment.

Placing the tip of the endotracheal tube at the carina and passing the endobronchial blocker through the Murphy eye may reduce the risk of blocker retrograde dislodgement during one-lung anaesthesia in small children.

We present nine cases of one-lung anaesthesia in small children and infants in which a novel technique was used to reduce the risk of endobronchial blocker retrograde dislodgement. The technique involved threading the stem of the blocker through the Murphy eye of the endotracheal tube (ETT) and deliberately passing the tip of the ETT all the way to the carina. The tip of the ETT blocked any retrograde movement of the blocker.

A mixture model with random-effects components for clustering correlated gene-expression profiles.

MOTIVATION: The clustering of gene profiles across some experimental conditions of interest contributes significantly to the elucidation of unknown gene function, the validation of gene discoveries and the interpretation of biological processes. However, this clustering problem is not straightforward as the profiles of the genes are not all independently distributed and the expression levels may have been obtained from an experimental design involving replicated arrays. Ignoring the dependence between the gene profiles and the structure of the replicated data can result in important sources of variability in the experiments being overlooked in the analysis, with the consequent possibility of misleading inferences being made. We propose a random-effects model that provides a unified approach to the clustering of genes with correlated expression levels measured in a wide variety of experimental situations. Our model is an extension of the normal mixture model to account for the correlations between the gene profiles and to enable covariate information to be incorporated into the clustering process. Hence the model is applicable to longitudinal studies with or without replication, for example, time-course experiments by using time as a covariate, and to cross-sectional experiments by using categorical covariates to represent the different experimental classes. RESULTS: We show that our random-effects model can be fitted by maximum likelihood via the EM algorithm for which the E(expectation)and M(maximization) steps can be implemented in closed form. Hence our model can be fitted deterministically without the need for time-consuming Monte Carlo approximations. The effectiveness of our model-based procedure for the clustering of correlated gene profiles is demonstrated on three real datasets, representing typical microarray experimental designs, covering time-course, repeated-measurement and cross-sectional data. In these examples, relevant clusters of the genes are obtained, which are supported by existing gene-function annotation. A synthetic dataset is considered too. AVAILABILITY: A Fortran program blue called EMMIX-WIRE (EM-based MIXture analysis WIth Random Effects) is available on request from the corresponding author.

Clustering.

Clustering techniques are used to arrange genes in some natural way, that is, to organize genes into groups or clusters with similar behavior across relevant tissue samples (or cell lines). These techniques can also be applied to tissues rather than genes. Methods such as hierarchical agglomerative clustering, k-means clustering, the self-organizing map, and model-based methods have been used. Here we focus on mixtures of normals to provide a model-based clustering of tissue samples (gene signatures) and of gene profiles, including time-course gene expression data.

The role of the extracellular matrix in primary myelofibrosis.

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm that arises from clonal proliferation of hematopoietic stem cells and leads to progressive bone marrow (BM) fibrosis. While cellular mutations involved in the development of PMF have been heavily investigated, noteworthy is the important role the extracellular matrix (ECM) plays in the progression of BM fibrosis. This review surveys ECM proteins contributors of PMF, and highlights how better understanding of the control of the ECM within the BM niche may lead to combined therapeutic options in PMF.

Conservative management of postoperative chylous fistula with octreotide and peripheral total parenteral nutrition.

Postoperative chylous fistula after neck dissection is an uncommon complication associated with significant patient morbidity. Octreotide acetate is a somatostatin analogue established in the treatment of chylothorax; however, its utility in the management of cervical chylous fistulae has not been fully evaluated. The investigators hypothesized that chylous fistula can be managed by a combination of octreotide and peripheral total parenteral nutrition (TPN). A retrospective review of cases compiled at our institution from 2009 to 2015 was conducted. Ten patients, all men, were identified as having a postoperative chylous fistula after a neck dissection. All patients were treated with peripheral TPN and intravenous octreotide. Mean age of the patients was 63.0 years (range 49 to 82). Five (50.0%) had a neck dissection for the management of metastatic nasopharyngeal carcinoma and had previous neck irradiation. In 8 (80%) patients, chylous fistula occurred in the left neck. Seven (70.0%) of the leaks occurred within the first 2 postoperative days. Eight (80%) leaks were controlled using TPN and octreotide, with 2 (20%) patients requiring surgical intervention. No factors were significant in the successful conservative management of chylous fistulae. One patient with a chylous fistula of 1,800 ml/day was managed successfully without surgical intervention. The results of this case series suggest that chylous fistulae may be managed conservatively with octreotide and TPN. However, long-term evaluation is needed to define if and when surgical intervention is required for control.

Pushing the limits of CMOS optical parametric amplifiers with USRN:Si7N3 above the two-photon absorption edge.

CMOS platforms operating at the telecommunications wavelength either reside within the highly dissipative two-photon regime in silicon-based optical devices, or possess small nonlinearities. Bandgap engineering of non-stoichiometric silicon nitride using state-of-the-art fabrication techniques has led to our development of USRN (ultra-silicon-rich nitride) in the form of Si7N3, that possesses a high Kerr nonlinearity (2.8 × 10-13 cm2 W-1), an order of magnitude larger than that in stoichiometric silicon nitride. Here we experimentally demonstrate high-gain optical parametric amplification using USRN, which is compositionally tailored such that the 1,550 nm wavelength resides above the two-photon absorption edge, while still possessing large nonlinearities. Optical parametric gain of 42.5 dB, as well as cascaded four-wave mixing with gain down to the third idler is observed and attributed to the high photon efficiency achieved through operating above the two-photon absorption edge, representing one of the largest optical parametric gains to date on a CMOS platform.

A randomized controlled trial of 2 protocols for weaning cardiac surgical patients receiving adaptive support ventilation.

PURPOSE: This study aims to compare the effectiveness of weaning with adaptive support ventilation (ASV) incorporating progressively reduced or constant target minute ventilation in the protocol in postoperative care after cardiac surgery. MATERIAL AND METHODS: A randomized controlled unblinded study of 52 patients after elective coronary artery bypass surgery was carried out to determine whether a protocol incorporating a decremental target minute ventilation (DTMV) results in more rapid weaning of patients ventilated in ASV mode compared to a protocol incorporating a constant target minute ventilation. RESULTS: Median duration of mechanical ventilation (145 vs 309 minutes; P = .001) and intubation (225 vs 423 minutes; P = .005) were significantly shorter in the DTMV group. There was no difference in adverse effects (42% vs 46%) or mortality (0% vs 0%) between the 2 groups. CONCLUSIONS: Use of a DTMV protocol for postoperative ventilation of cardiac surgical patients in ASV mode results in a shorter duration of ventilation and intubation without evidence of increased risk of adverse effects.

Local anaesthetic toxicity after bilateral thoracic paravertebral block in patients undergoing coronary artery bypass surgery.

We conducted a small pilot observational study of the effects of bilateral thoracic paravertebral block (BTPB) as an adjunct to perioperative analgesia in coronary artery bypass surgery patients. The initial ropivacaine dose prior to induction of general anaesthesia was 3 mg/kg, which was followed at the end of the surgery by infusion of ropivacaine 0.25% 0.1 ml/kg/hour on each side (e.g. total 35 mg/hour for a 70 kg person). The BTPB did not eliminate the need for supplemental opioids after CABG in the eight patients studied. Moreover, in spite of boluses that were within the manufacturer's recommendation for epidural and major nerve blocks, and an infusion rate that was only slightly higher than what appeared to be safe for epidural infusion, potentially toxic total plasma ropivacaine concentrations were common. We also could not exclude the possibility that the high ropivacaine concentrations were contributing to postoperative mental state changes in the postoperative period. Also, one patient developed local anaesthetic toxicity after the bilateral paravertebral dose. As a result, the study was terminated early after four days. The question of whether paravertebral block confers benefits in cardiac surgery remains unanswered. However, we believe that the bolus dosage and the injection rate we used for BTPB were both too high, and caution other clinicians against the use of these doses. Future studies on the use of BTPB in cardiac surgery patients should include reduced ropivacaine doses injected over longer periods.