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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

High throughput film dosimetry in homogeneous and heterogeneous media for a small animal irradiator.

PURPOSE: We have established a high-throughput Gafchromic film dosimetry protocol for narrow kilovoltage beams in homogeneous and heterogeneous media for small-animal radiotherapy applications. The kV beam characterization is based on extensive Gafchromic film dosimetry data acquired in homogeneous and heterogeneous media. An empirical model is used for parameterization of depth and off-axis dependence of measured data. METHODS: We have modified previously published methods of film dosimetry to suit the specific tasks of the study. Unlike film protocols used in previous studies, our protocol employs simultaneous multi-channel scanning and analysis of up to nine Gafchromic films per scan. A scanner and background correction were implemented to improve accuracy of the measurements. Measurements were taken in homogeneous and inhomogeneous phantoms at 220 kVp and a field size of 5 × 5 mm(2). The results were compared against Monte Carlo simulations. RESULTS: Dose differences caused by variations in background signal were effectively removed by the corrections applied. Measurements in homogeneous phantoms were used to empirically characterize beam data in homogeneous and heterogeneous media. Film measurements in inhomogeneous phantoms and their empirical parameterization differed by about 2%-3%. The model differed from MC by about 1% (water, lung) to 7% (bone). Good agreement was found for measured and modelled off-axis ratios. CONCLUSIONS: EBT2 films are a valuable tool for characterization of narrow kV beams, though care must be taken to eliminate disturbances caused by varying background signals. The usefulness of the empirical beam model in interpretation and parameterization of film data was demonstrated.

Clustering of gene expression data via normal mixture models.

There are two distinct but related clustering problems with microarray data. One problem concerns the clustering of the tissue samples (gene signatures) on the basis of the genes; the other concerns the clustering of the genes on the basis of the tissues (gene profiles). The clusters of tissues so obtained in the first problem can play a useful role in the discovery and understanding of new subclasses of diseases. The clusters of genes obtained in the second problem can be used to search for genetic pathways or groups of genes that might be regulated together. Also, in the first problem, we may wish first to summarize the information in the very large number of genes by clustering them into groups (of hyperspherical shape), which can be represented by some metagenes, such as the group sample means. We can then carry out the clustering of the tissues in terms of these metagenes. We focus here on mixtures of normals to provide a model-based clustering of tissue samples (gene signatures) and of gene profiles.

C-terminal binding protein-2 regulates response of epithelial ovarian cancer cells to histone deacetylase inhibitors.

Ovarian cancer survival rates have stagnated in the last 20 years despite the development of novel chemotherapeutic agents. Modulators of gene expression, such as histone deacetylase (HDAC) inhibitors, are among the new agents being used in clinical trials. Predictors of sensitivity to chemotherapy have remained elusive. In this study, we show that the expression of the transcriptional corepressor C-terminal binding protein-2 (CtBP2) is elevated in human ovarian tumors. Downregulation of CtBP2 expression in ovarian cancer cell lines using short-hairpin RNA strategy suppressed the growth rate and migration of the resultant cancer cells. The knockdown cell lines also showed upregulation of HDAC activity and increased sensitivity to selected HDAC inhibitors. Conversely, forced expression of wild-type CtBP2 in the knockdown cell lines reversed HDAC activity and partially rescued cellular sensitivity to the HDAC inhibitors. We propose that CtBP2 is an ovarian cancer oncogene that regulates gene expression program by modulating HDAC activity. CtBP2 expression may be a surrogate indicator of cellular sensitivity to HDAC inhibitors.

Evaluation of robustness of maximum likelihood cone-beam CT reconstruction with total variation regularization.

The objective of this paper is to evaluate an iterative maximum likelihood (ML) cone-beam computed tomography (CBCT) reconstruction with total variation (TV) regularization with respect to the robustness of the algorithm due to data inconsistencies. Three different and (for clinical application) typical classes of errors are considered for simulated phantom and measured projection data: quantum noise, defect detector pixels and projection matrix errors. To quantify those errors we apply error measures like mean square error, signal-to-noise ratio, contrast-to-noise ratio and streak indicator. These measures are derived from linear signal theory and generalized and applied for nonlinear signal reconstruction. For quality check, we focus on resolution and CT-number linearity based on a Catphan phantom. All comparisons are made versus the clinical standard, the filtered backprojection algorithm (FBP). In our results, we confirm and substantially extend previous results on iterative reconstruction such as massive undersampling of the number of projections. Errors of projection matrix parameters of up to 1° projection angle deviations are still in the tolerance level. Single defect pixels exhibit ring artifacts for each method. However using defect pixel compensation, allows up to 40% of defect pixels for passing the standard clinical quality check. Further, the iterative algorithm is extraordinarily robust in the low photon regime (down to 0.05 mAs) when compared to FPB, allowing for extremely low-dose image acquisitions, a substantial issue when considering daily CBCT imaging for position correction in radiotherapy. We conclude that the ML method studied herein is robust under clinical quality assurance conditions. Consequently, low-dose regime imaging, especially for daily patient localization in radiation therapy is possible without change of the current hardware of the imaging system.

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.

SU-E-T-163: Thin-Film Organic Photocell (OPV) Properties in MV and KV Beams for Dosimetry Applications.

PURPOSE: To characterize dosimetric properties of low-cost thin film organic-based photovoltaic (OPV) cells to kV and MV x-ray beams for their usage as large area dosimeter for QA and patient safety monitoring device. METHODS: A series of thin film OPV cells of various areas and thicknesses were irradiated with MV beams to evaluate the stability and reproducibility of their response, linearity and sensitivity to absorbed dose. The OPV response to x-rays of various linac energies were also characterized. Furthermore the practical (clinical) sensitivity of the cells was determined using IMRT sweeping gap test generated with various gap sizes. To evaluate their potential usage in the development of low cost kV imaging device, the OPV cells were irradiated with kV beam (60-120 kVp) from a fluoroscopy unit. Photocell response to the absorbed dose was characterized as a function of the organic thin film thickness and size, beam energy and exposure for kV beams as well. In addition, photocell response was determined with and without thin plastic scintillator. RESULTS: Response of the OPV cells to the absorbed dose from kV and MV beams are stable and reproducible. The photocell response was linearly proportional to the size and about slightly decreasing with the thickness of the organic thin film, which agrees with the general performance of the photocells in visible light. The photocell response increases as a linear function of absorbed dose and x-ray energy. The sweeping gap tests performed showed that OPV cells have sufficient practical sensitivity to measured MV x-ray delivery with gap size as small as 1 mm. CONCLUSIONS: With proper calibration, the OPV cells could be used for online radiation dose measurement for quality assurance and patient safety purposes. Their response to kV beam show promising potential in development of low cost kV radiation detection devices.

A mixed treatment comparison of the short-term efficacy of biologic disease modifying anti-rheumatic drugs in established rheumatoid arthritis.

BACKGROUND: The short-term efficacy of biological disease modifying anti-rheumatic drugs (bDMARDs) for the treatment of established moderate to severe rheumatoid arthritis (RA) has been demonstrated by various randomized placebo or active treatment controlled trials. However, there is a lack of direct comparison of these agents. SCOPE: To compare the short-term efficacy of nine bDMARDs - abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab and tocilizumab - in patients with established RA. FINDINGS: A systematic review was conducted to obtain all available efficacy data for each included bDMARD. Medline, EMBASE, and Cochrane clinical trials were searched for trials in patients with RA. Twenty-seven trials were retrieved from a systematic literature search and included in the meta-analysis. Mixed treatment comparison (MTC) techniques were used to perform indirect comparisons. Analyses were conducted to estimate the odds ratio of an ACR20, ACR50, and ACR70 response at approximately six months if treated with a bDMARD compared with placebo or methotrexate. Between-drug comparisons were also made. The analyses were performed including recommended doses only (as per the product information). All drugs except anakinra and golimumab demonstrated a statistically significant advantage compared to control treatment for ACR20 responses. The between-drug comparisons revealed a statistically significant advantage for certolizumab compared to most bDMARDs for ACR20, ACR50 and ACR70 response and for etanercept versus adalimumab and anakinra for ACR20 and ACR50 response, as well as a statistically significant advantage for tocilizumab versus anakinra for ACR50 response. CONCLUSION: The analyses, using MTC of efficacy of nine bDMARDs suggest that treatment with anakinra is inferior to other bDMARDs and that etanercept and certolizumab may be more effective than other bDMARDs. There are some limitations of our analyses due to MTC assumptions, variations in trial design and the fact that only ACR outcomes at six months were included.