Ten-year territory-wide trends in the utilisation and clinical outcomes of extracorporeal membrane oxygenation in Hong Kong.

INTRODUCTION: The utilisation of extracorporeal membrane oxygenation (ECMO) has been rapidly increasing in Hong Kong. This study examined 10-year trends in the utilisation and clinical outcomes of ECMO in Hong Kong. METHODS: We retrospectively reviewed the records of all adult patients receiving ECMO who were admitted to the intensive care units (ICUs) of public hospitals in Hong Kong between 2010 and 2019. Temporal trends across years were assessed using the Mann-Kendall test. Observed hospital mortality was compared with the Acute Physiology and Chronic Health Evaluation (APACHE) IV-predicted mortality. RESULTS: The annual number of patients receiving ECMO increased from 18 to 171 over 10 years. In total, 911 patients received ECMO during the study period: 297 (32.6%) received veno-arterial ECMO, 450 (49.4%) received veno-venous ECMO, and 164 (18.0%) received extracorporeal cardiopulmonary resuscitation. The annual number of patients aged ≥65 years increased from 0 to 47 (27.5%) [P for trend=0.001]. The median (interquartile range) Charlson Comorbidity Index increased from 1 (0-1) to 2 (1-3) [P for trend<0.001] while the median (interquartile range) APACHE IV score increased from 90 (57-112) to 105 (77-137) [P for trend=0.003]. The overall standardised mortality ratio comparing hospital mortality with APACHE IV-predicted mortality was 1.11 (95% confidence interval=1.01-1.22). Hospital and ICU length of stay both significantly decreased (P for trend=0.011 and <0.001, respectively). CONCLUSION: As ECMO utilisation increased in Hong Kong, patients put on ECMO were older, more critically ill, and had more co-morbidities. It is important to combine service expansion with adequate resource allocation and training to maintain quality of care.

A prospective study on serum citrate levels and clinical correlations in patients receiving regional citrate anticoagulation.

Background: Current ways to diagnose citrate accumulation (CA) in patients receiving regional citrate anticoagulation (RCA) continuous renal replacement therapy (CRRT) are confounded by various clinical factors. Serum citrate measurement emerges as a more direct way to diagnose CA, but its clinical utility and optimal cut-off values remain undefined. This study examined serum citrate kinetics and its diagnostic performance for CA in patients receiving RCA CRRT. Methods: A multicentre prospective study was carried out in two tertiary referral centre intensive care units in Hong Kong with serum citrate levels measured at baseline and 2, 6, 12, 24, 36, 48 and 72 h after initiation of RCA CRRT and their relationships with the development of CA. Results: Among the 133 patients analysed, 18 patients (13.5%) developed CA. The serum citrate levels at baseline and 2, 6 and 12 h after initiation of RCA CRRT in patients who had CA were significantly higher than the non-CA group (P < .001 for all). The CA group also had higher serum citrate levels than the non-CA group {median 0.93 mmol/L [interquartile range (IQR) 0.81-1.16) versus 0.37 mmol/L (IQR 0.26-0.57), P < .001}. Using a cut-off of 0.85 mmol/L, the serum citrate level had a sensitivity of 0.77 and a specificity 0.96 for the diagnosis of CA [area under the receiver operating characteristics curve (AUROC) 0.90, P < .001]. The 2-h and 6-h serum citrate levels had good discriminatory abilities for predicting subsequent development of CA (AUROC 0.86 and 0.83 for 2-h and 6-h citrate levels using cut-off values of 0.34 and 0.63 mmol/L, respectively; P < .001). Conclusion: Serum citrate levels were significantly higher in patients with CA compared with patients without CA. Serum citrate levels showed good performance in diagnosing and predicting the development of CA.

The utility of the radionuclide probe in parathyroidectomy for primary hyperparathyroidism.

INTRODUCTION Parathyroidectomy is the definitive treatment for primary hyperparathyroidism but the intraoperative identification of adenomas is challenging. The aim of this study was to evaluate the utility of a radionuclide probe (RNP) in addition to intraoperative parathyroid hormone ( IOPTH) measurement as an intraoperative diagnostic adjunct in patients undergoing parathyroidectomy for primary hyperparathyroidism. METHODS This was a retrospective cohort study of patients treated between 2004 and 2015 in a university affiliated teaching hospital. Patients were grouped into those with RNP use (RNP+) and those without (RNP-). The primary outcome measure was rate of operative failure, which included false positives. The diagnostic sensitivity and positive predictive value of both RNP and IOPTH were also evaluated. RESULTS A total of 298 patients were included in the study, 127 (42.6%) being in the RNP+ group and 171 (57.4%) in the RNP- group. The false positive rate for the RNP+ patients was 1.6% compared with 9.4% for RNP- patients (p=0.006, hazard ratio [HR]: 6.45). The rates of operative failure were 6.3% and 11.7% respectively (p=0.159, HR: 1.97). RNP use had a sensitivity of 92.0% and a positive predictive value of 98.3% compared with 78.6% and 95.2% respectively for IOPTH monitoring. CONCLUSIONS RNP use is associated with fewer false positives and reduced operative failure than IOPTH measurement. It also has a higher sensitivity and positive predictive value. RNP use is recommended in centres that have the required facilities.

Targeted Ablation of Periostin-Expressing Activated Fibroblasts Prevents Adverse Cardiac Remodeling in Mice.

RATIONALE: Activated cardiac fibroblasts (CF) are crucial players in the cardiac damage response; excess fibrosis, however, may result in myocardial stiffening and heart failure development. Inhibition of activated CF has been suggested as a therapeutic strategy in cardiac disease, but whether this truly improves cardiac function is unclear. OBJECTIVE: To study the effect of CF ablation on cardiac remodeling. METHODS AND RESULTS: We characterized subgroups of murine CF by single-cell expression analysis and identified periostin as the marker showing the highest correlation to an activated CF phenotype. We generated bacterial artificial chromosome-transgenic mice allowing tamoxifen-inducible Cre expression in periostin-positive cells as well as their diphtheria toxin-mediated ablation. In the healthy heart, periostin expression was restricted to valvular fibroblasts; ablation of this population did not affect cardiac function. After chronic angiotensin II exposure, ablation of activated CF resulted in significantly reduced cardiac fibrosis and improved cardiac function. After myocardial infarction, ablation of periostin-expressing CF resulted in reduced fibrosis without compromising scar stability, and cardiac function was significantly improved. Single-cell transcriptional analysis revealed reduced CF activation but increased expression of prohypertrophic factors in cardiac macrophages and cardiomyocytes, resulting in localized cardiomyocyte hypertrophy. CONCLUSIONS: Modulation of the activated CF population is a promising approach to prevent adverse cardiac remodeling in response to angiotensin II and after myocardial infarction.

Cross-clade immunogenicity and safety of an AS03A-adjuvanted prepandemic H5N1 influenza vaccine in Hong Kong.

OBJECTIVE: To present Hong Kong'Äìspecific data from a large Asian population (also involving Thailand, Singapore, and Taiwan) on safety and manufacturing consistency across four AS03(A)-adjuvanted H5N1 vaccine formulations in terms of immune response against the A/Vietnam/1194/2004 strain. Immunogenicity against the heterologous A/Indonesia/05/2005 strain was also assessed. NCT Number: 00449670. DESIGN: Prospective, observer-blind study. SETTING: Out-patient clinic of a tertiary hospital in Hong Kong. PARTICIPANTS: A total of 360 subjects aged 18 to 60 years were randomised into six groups to receive two doses (21 days apart) of the study vaccine. INTERVENTIONS: One of the four adjuvanted formulations (3.75 microgram H5N1 haemagglutinin [HA]+AS03(A)) of the vaccine (H5N1-AS03(A)) or one of the two non-adjuvanted (3.75 microgram H5N1 [HA]) formulations of the vaccine (H5N1-DIL). MAIN OUTCOME MEASURES: Blood samples collected before vaccination and 21 days after each vaccine dose were analysed using haemagglutination-inhibition and neutralisation assays. Solicited, unsolicited, and serious adverse events were recorded. RESULTS: Manufacturing consistency across all four vaccine formulations was demonstrated. After two doses, the AS03(A)-adjuvanted prepandemic influenza vaccine demonstrated high seroprotection rates against the A/Vietnam/1194/2004 strain (95.8%) and good immunogenicity against the heterologous A/Indonesia/05/2005 strain (45.7%), as compared to the non-adjuvanted vaccine (4.6% and 1.5%, respectively). The seroconversion rates induced by the adjuvanted formulations in terms of viral neutralising antibodies against the two strains were much higher than those induced by the non-adjuvanted formulations. There were no safety concerns for any of the adjuvanted vaccine formulations. CONCLUSIONS: The AS03(A)-adjuvanted H5N1 prepandemic influenza vaccine demonstrated good immunogenicity and an acceptable safety profile in Hong Kong.

Apoptotic and necrotic effects of tumour necrosis factor-alpha potentiated with hyperthermia on L929 and tumour necrosis factor-alpha-resistant L929.

PURPOSE: The cytotoxic effect of the combination treatment of TNF-alpha and hyperthermia on L929 and TNF-alpha-resistant L929 (rL929) cells was investigated. MATERIALS AND METHODS: L929 cells were treated with TNF-alpha (5 ng/mL), heating at 43 degrees C or the combination of TNF-alpha and heating. The cells were harvested at different time within the 24-hour period. The viability and the type of cell death of the harvested cells were examined. RESULTS: When L929 cells were treated with a combination of TNF-alpha and heating the cells died quickly and apoptosis increased to an overwhelming extent, especially in the group pre-treated with TNF-alpha for 1 h prior to heating. Although rL929 cells were resistant to TNF-alpha alone, the cells became sensitive to TNF-alpha treatment when combined with heating. Similar to the L929 cell, the cells also died rapidly and exhibited apoptosis to a higher extent. Using an Annexin-V-FITC kit and flow cytometer, we found that both necrosis and apoptosis occurred. Agarose gel electrophoresis of DNA extracted from treated cells showed that the DNA fragments were multiples of approximately 200 bp. Furthermore, by studying the kinetics of cell death and apoptosis, we found that the loss of cell membrane integrity preceded the DNA fragmentation in both L929 and rL929 cells. CONCLUSION: The results suggested that hyperthermia may enhance the necrotic and apoptotic effects of TNF-alpha on some tumour cells and overcome the resistance of some tumour cells to TNF-alpha.

A prospective study on the effect of rapid aneuploidy testing (amnio-PCR) on anxiety levels and quality of life measures in women and their partners with positive Down screening result.

OBJECTIVES: To examine the effect of rapid aneuploidy testing by amnio-PCR on anxiety levels and quality of life measures in women and their partners with positive Down screening result. METHODS: In the original design, screen-positive women were to be randomized to have amnio-PCR or not. Of the first 60 women approached to join the study between April 2004 and April 2005, 4 declined amniocentesis, 14 agreed to be randomized, while the other 42 (75%) chose to pay for the amnio-PCR themselves (3 excluded: 2 because of Down syndrome and 1 dropout). The study was thus performed as a prospective observational study on the remaining 39 women of the last group. The longitudinal profile of the state-anxiety and quality of life domain scores for this cohort were studied using the Spielberger State-Trait Anxiety Inventory and WHO Quality of Life Measure--abbreviated version (Hong Kong) Questionnaire at 5 time points: (1) before amniocentesis, (2) 2 days after amniocentesis when amnio-PCR report was disclosed, (3) 3 weeks after amniocentesis when karyotyping report was disclosed, (4) 30-32 weeks' gestation, (5) 6 weeks after delivery. RESULTS: In the final cohort of 39 women and 27 partners, a significant reduction in their state-anxiety scores was found when they received the normal amnio-PCR report. On the other hand, there was no significant change in their quality of life domain scores. CONCLUSIONS: There is a demand from women and their partners who had a positive Down screening result for rapid aneuploidy testing (amnio-PCR) which can effectively alleviate their anxiety. A rapid aneuploidy test should be made available to women in a Down screening programme.

Fetal methylmercury exposure as measured by cord blood mercury concentrations in a mother-infant cohort in Hong Kong.

This study was designed to examine newborn infants in Hong Kong prenatally exposed to levels of methylmercury considered to increase risk of neurotoxic effects and to examine subject characteristics that modify the degree of prenatal mercury exposure. Mercury concentrations in 1057 sets of maternal and cord blood samples and 96 randomly selected maternal hair samples were measured. Subject characteristics were measured or collected by questionnaire. Of the 1057 cord blood samples collected only 21.6% had mercury concentrations less than 29 nmol/L (5.8 micro g/L). Median maternal hair mercury concentration was 1.7 ppm. The geometric mean cord to maternal blood mercury ratio was 1.79 to 1. Increasing maternal fish consumption and maternal age were found to be associated with increased cord blood mercury concentrations. Marine fish consumption increased cord blood mercury concentrations more than freshwater fish (5.09%/kg vs 2.86%/kg). Female babies, maternal alcohol consumption and increasing maternal height were associated with decreased cord blood mercury concentrations. Pregnant women in Hong Kong consume large amounts of fish and as a result, most of their offspring have been prenatally exposed to moderately high levels of mercury. In this population, pregnant women should choose freshwater over marine fish and limit fish consumption.

The effects on maternal anxiety of two-dimensional versus two- plus three-/four-dimensional ultrasound in pregnancies at risk of fetal abnormalities: A randomized study.

OBJECTIVE: To test the hypothesis that the use of two-dimensional (2D) ultrasonography with three-dimensional/four-dimensional (3D/4D) ultrasonography can reduce anxiety to a greater extent in women at risk of having a fetus with congenital abnormalities than the use of 2D ultrasonography alone. METHODS: A total of 124 women attending the prenatal diagnostic clinic of a teaching hospital were randomized into the intervention group (2D ultrasonography followed by 3D/4D ultrasonography) or control group (2D ultrasonography alone). The primary outcome was maternal anxiety levels, which were assessed by the Spielberger state-trait anxiety inventory. We measured the anxiety levels in all women at the first visit, at around 18 weeks' gestation (immediately after ultrasound examinations) and at 28 weeks' gestation. RESULTS: A short-term reduction of the state-anxiety score (by around 2 points) from the first visit to after ultrasound examinations was observed in both the intervention group and the control group. Unexpectedly, a small increase in the state-anxiety score from the first visit to 28 weeks' gestation was observed in the intervention group but not in the control group, though there was no significant difference in the changes between the two groups. Repeated measures ANOVA (analysis of variance) also showed that there was no significant interaction effect between groups and time of assessment on the state-anxiety scores (F = 1.072 and P = 0.344). About 80% of women reported a better understanding that their baby was normal after viewing 3D rather than 2D images. CONCLUSION: This randomized study indicates that the addition of 3D/4D ultrasound does not cause a significant reduction in maternal anxiety in pregnancies at risk of fetal abnormalities compared with conventional 2D ultrasound alone.

Splenic rupture in a premature neonate.

Splenic injuries are very rare in neonates. We report a case of splenic injury in a premature neonate, highlighting the importance of a high-index suspicion in early recognition of this rare but potentially fatal intra-abdominal injury. We also review the literature on possible aetiologies and mechanism of splenic injury, as well as its management. This is the first reported case of a very low-birth-weight neonate with splenic rupture who survived with intact neurology.

Three-dimensional extended imaging: a new display modality for three-dimensional ultrasound examination.

OBJECTIVE: To describe Three-Dimensional eXtended Imaging (3DXI) as a new display modality for three-dimensional (3D) ultrasound examination of the fetus. METHODS: The spine, palate, heart and brain were evaluated using 3D ultrasound examination at a mean gestational age of 22 weeks in 35, 31, 32 and 31 fetuses, respectively. The volume data captured were analyzed using the conventional orthogonal display mode (ODM), as well as the 3DXI, which includes the Multi-Slice View (MSV) mode and the Oblique View (OBV) mode. The MSV mode allows simultaneous display of multiple sequential parallel planes while the OBV mode allows examination of a non-standard straight or curved plane. RESULTS: The MSV mode allowed a simultaneous display of multiple sequential parallel planes of the fetal structures, but we found some uncertainty if an isolated image in one of the multi-slice images represented the exact level of a fetal structure. The MSV mode was advantageous in one of the six cases of facial cleft by allowing the simultaneous display of bilateral clefts that were located in two different axial planes. The multi-slice images were helpful in making the diagnosis in one case of holoprosencephaly. The OBV mode allowed examination of the coronal plane across the curvature of the spine, and the 'in-plane' view of the interventricular septum in a non-gated study. CONCLUSION: The 3DXI can display the volume data in a different manner from that which usually results from the use of more conventional ODM, and provide additional information over conventional two-dimensional sonography.

Unexpected intrauterine death following resolution of hydrops fetalis after betamethasone treatment in a fetus with a large cystic adenomatoid malformation of the lung.

Without intervention, the development of hydrops fetalis secondary to cystic adenomatoid malformation of the lung (CAML) implies a 100% mortality rate. Conversely, four CAML cases with in-utero resolution of hydrops fetalis after prenatal betamethasone therapy with good clinical outcome have been reported in the literature. The mechanism is speculated to be the effect of corticosteroid in improving lung maturation. Here we present another CAML case with resolution of hydrops fetalis after prenatal betamethasone therapy but which was followed by later intrauterine death. We speculate that the resolution of the CAML lesion itself may be more important in determining the clinical outcome than the resolution of hydrops. The association between prenatal betamethasone therapy and resolution of hydrops may be related to a different mechanism other than improvement of lung maturation.

Lung pathology of fatal severe acute respiratory syndrome.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a novel infectious disease with global impact. A virus from the family Coronaviridae has been identified as the cause, but the pathogenesis is still unclear. METHODS: Post-mortem tissue samples from six patients who died from SARS in February and March, 2003, and an open lung biopsy from one of these patients were studied by histology and virology. Only one full autopsy was done. Evidence of infection with the SARS-associated coronavirus (SARS-CoV) and human metapneumovirus was sought by reverse-transcriptase PCR and serology. Pathological samples were examined by light and electron microscopy and immunohistochemistry. FINDINGS: All six patients had serological evidence of recent infection with SARS-CoV. Diffuse alveolar damage was common but not universal. Morphological changes identified were bronchial epithelial denudation, loss of cilia, and squamous metaplasia. Secondary bacterial pneumonia was present in one case. A giant-cell infiltrate was seen in four patients, with a pronounced increase in macrophages in the alveoli and the interstitium of the lung. Haemophagocytosis was present in two patients. The alveolar pneumocytes also showed cytomegaly with granular amphophilic cytoplasm. The patient for whom full autopsy was done had atrophy of the white pulp of the spleen. Electron microscopy revealed viral particles in the cytoplasm of epithelial cells corresponding to coronavirus. INTERPRETATION: SARS is associated with epithelial-cell proliferation and an increase in macrophages in the lung. The presence of haemophagocytosis supports the contention that cytokine dysregulation may account, at least partly, for the severity of the clinical disease. The case definition of SARS should acknowledge the range of lung pathology associated with this disease.

A comparison of two regimens of intravaginal misoprostol for termination of second trimester pregnancy: a randomized comparative trial.

A prospective randomized trial was conducted in 148 women to compare the efficacy of two regimens of vaginal misoprostol for termination of second trimester pregnancy. Women aged 16-40 years requesting termination of second trimester pregnancy were randomized into two groups. Women in group 1 were given vaginal misoprostol 400 microg every 3 h for a maximum of five doses in 24 h. Women in group 2 were given vaginal misoprostol 400 microg every 6 h for a maximum of three doses in 24 h. If women did not abort in 24 h, the same regimen was repeated. The median induction-abortion interval in group 1 (15.2 h) was significantly shorter (P < 0.01) than that in the group 2 (19.0 h). The percentage of women who achieved successful abortion within 48 h in group 1 (90.5%) was also significantly higher (P < 0.02) than that in group 2 (75.7%). The incidence of fever was more common in group 1 (P = 0.01). It is concluded that the regimen of vaginal misoprostol 400 microg every 3 h with maximum of five doses in 24 h was more effective than the regimen of misoprostol every 6 h in termination of second trimester pregnancy.

A common Hpa I RFLP of apolipoprotein C-I increases gene transcription and exhibits an ethnically distinct pattern of linkage disequilibrium with the alleles of apolipoprotein E.

Apolipoprotein (apo) C-I is a constituent of triglyceride-rich lipoproteins (TGRL) that interferes with their hepatic clearance. Functional polymorphism in the apoC-I gene has not been established. We determined that an Hpa I site variably present at -317 relative to the apoC-I gene is produced by a 4-bp CGTT insertion. The apoC-I Hpa I alleles showed an ethnically distinct pattern of linkage disequilibrium with the alleles of the adjacent apoE gene. The frequency of apoC-I Hpa I-positive (H2) with apoE varepsilon2 was 0. 98, without significant ethnic difference. In contrast, the frequency of H2 with apoE epsilon4 was 0.85 in European-Americans but only 0.55 in African-Americans (P < 0.001). The frequency of H2 with apoE epsilon3 was 0.02 in European-Americans and 0.08 in African-Americans (P < 0.001). African-American apoE epsilon3/epsilon3 carriers of apoC-I H2 had 19% lower fasting triglyceride levels than H1 homozygotes (P = 0.03) along with 18% higher HDL-cholesterol levels (P = 0.02). ApoB levels were 21% lower (P = 0.002). H2-allelic reporter-gene constructions showed 50% higher expression in transient transfection studies. We localized the source of this difference in expression to the CGTT insertion itself. Deletion studies of the H1 allele showed a negative transcriptional effect of the polymorphic region. An H1 oligodeoxynucleotide showed specific binding of a hepatoma-cell nuclear protein not evident with an H2 oligodeoxynucleotide. The H2 sequence may decrease the binding of a negatively acting transcription factor, leading to overexpression of apoC-I. This may produce a functional effect on lipoprotein levels but confirmation is needed in other populations.

Joint processing of hartmann sensor and conventional image measurements to estimate large aberrations: theory and experimental results.

We report experimental results for what we believe to be a new technique for estimating aberrations that extends the strength of an aberration that may be sensed with Hartmann sensor technology by means of an algorithm that processes both a Hartmann sensor image and a conventional image formed with the same aberration. We find that the theory and the experiment match well within the experimental error and that strong defocus aberrations can be accurately sensed with this technique.