The Omicron variant of COVID-19 and its association with croup in children: a single-centre study in Hong Kong.

INTRODUCTION: The fifth wave of the coronavirus disease 2019 (COVID-19) pandemic in Hong Kong was dominated by the Omicron variant, which may cause more upper airway involvement in children. This study was performed to identify any associations between the Omicron variant of COVID-19 and croup in children. METHODS: This retrospective study reviewed the electronic medical records of patients admitted to Tuen Mun Hospital in Hong Kong from 1 January 2018 to 31 March 2022 under the diagnostic code for croup (J05.0 in the International Classification of Diseases 10th Edition). Patients were categorised into three groups according to their admission periods, namely, non-COVID-19, COVID-19-pre-Omicron, and COVID-19-Omicron groups. Disease associations and severity were compared according to incidence, Westley Croup Score, length of hospital stay, medication use, respiratory support, and intensive care unit admissions. RESULTS: The COVID-19 incidence among patients with croup was significantly higher in the COVID-19-Omicron group than in the COVID-19-pre-Omicron group (90.0% vs 2.0%; P<0.001). Compared with patients in the COVID-19-pre-Omicron and non-COVID-19 groups, patients in the COVID-19-Omicron group also had a higher Westley score (moderate and severe disease in the COVID-19-Omicron group: 56.7%; COVID-19-pre-Omicron group: 22.0%, P=0.004; non-COVID-19 group: 24.8%, P<0.001), longer median hospital stay (COVID-19-Omicron group: 3.00 days; COVID-19-pre-Omicron group: 2.00 days, P<0.001; non-COVID-19 group: 2.00 days, P=0.034), and higher mean dexamethasone requirement (COVID-19-Omicron group: 0.78 mg/kg; COVID-19-pre-Omicron group: 0.49 mg/kg, P<0.001; non-COVID-19 group: 0.58 mg/kg, P=0.001). CONCLUSION: The Omicron variant of COVID-19 is associated with croup and can cause more severe disease in Hong Kong children.

Risks and impacts of thromboembolism in patients with pancreatic cancer.

INTRODUCTION: Patients with pancreatic cancer have a high risk of thromboembolism (TE), which may increase mortality. Most relevant studies have been conducted in Western populations. We investigated risk factors for TE in a predominantly Chinese population of patients with pancreatic cancer, along with effects of TE on overall survival. METHODS: This retrospective cohort study included patients diagnosed with exocrine pancreatic cancer in Prince of Wales Hospital in Hong Kong between 2010 and 2015. Data regarding patient demographics, World Health Organization performance status, stage, treatment, TE-related information, and time of death (if applicable) were retrieved from electronic medical records. Univariate and multivariable logistic regression analyses were performed to identify risk factors for TE. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: In total, 365 patients were included in the study. The overall incidence of TE (14.8%) was lower than in Western populations. In univariate logistic regression analysis, stage IV disease and non-head pancreatic cancer were significantly associated with TE (both P=0.01). Multivariable logistic regression analysis showed that stage IV disease was a significant risk factor (odds ratio=1.08, 95% confidence interval [CI]=1.00-1.17; P=0.046). Median overall survival did not significantly differ between patients with and without TE (4.88 months vs 7.80 months, hazard ratio=1.08, 95% CI=0.80-1.49; P=0.58) and between patients with TE who received anticoagulation treatment or not (5.63 months vs 4.77 months, hazard ratio=0.72, 95% CI=0.40-1.29; P=0.27). CONCLUSION: The incidence of TE was low in our Chinese cohort. Stage IV disease increased the risk of TE. Overall survival was not affected by TE or its treatment.

Prognostic implication of the neoadjuvant rectal score and other biomarkers of clinical outcome in Hong Kong Chinese patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy is a standard treatment for locally advanced rectal cancer, for which pathological complete response is typically used as a surrogate survival endpoint. Neoadjuvant rectal score is a new biomarker that has been shown to correlate with survival. The main objectives of this study were to investigate factors contributing to pathological complete response, to validate the prognostic significance of neoadjuvant rectal score, and to investigate factors associated with a lower neoadjuvant rectal score in a cohort of Hong Kong Chinese. METHODS: Data of patients with locally advanced rectal cancer who received neoadjuvant chemoradiotherapy from August 2006 to October 2018 were retrieved from hospital records and retrospectively analysed. RESULTS: Of 193 patients who had optimal response to neoadjuvant chemoradiotherapy and surgery, tumour down-staging was the only independent prognostic factor that predicted pathological complete response (P<0.0001). Neoadjuvant rectal score was associated with overall survival (hazard ratio [HR]=1.042, 95% confidence interval [CI]=1.021-1.064; P<0.0001), disease-free survival (HR=1.042, 95% CI=1.022-1.062; P<0.0001), locoregional recurrence-free survival (HR=1.070, 95% CI=1.039-1.102; P<0.0001) and distant recurrence-free survival (HR=1.034, 95% CI=1.012-1.056; P=0.002). Patients who had pathological complete response were associated with a lower neoadjuvant rectal score (P<0.0001), but pathological complete response was not associated with survival. For patients with intermediate neoadjuvant rectal scores, late recurrences beyond 72 months from diagnosis were observed. CONCLUSION: Neoadjuvant rectal score is an independent prognostic marker of survival and disease recurrence in a cohort of Hong Kong Chinese patients who received neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

Efficacy of postoperative oral metronidazole for haemorrhoidectomy pain: a randomized double-blind, placebo-controlled trial.

AIM: The aim of this work was to examine the efficacy of oral metronidazole in reducing posthaemorrhoidectomy pain versus placebo. METHOD: Forty patients were randomized to either metronidazole and standard care or placebo and standard care (21 metronidazole, 19 placebo) in a double-blinded, randomized controlled trial. The main outcome measure was posthaemorrhoidectomy pain scores over 21 days, measured on a 10-point Likert scale. RESULTS: There were no significant differences between groups with regards to age, gender, smoking status, self-reported general health or quality of life, haemorrhoid-related pain, haemorrhoid-related impact on quality of life, reported satisfaction with surgery, experience of surgery, median overall pain score or likelihood of recommending surgery to others. For reported median worst pain scores and defaecation-related pain, a trend to significance was identified between groups on days 16 and 18-21, with the metronidazole group reporting less pain. However, these differences were not significant when prespecified Bonferroni correction criteria were used. Using multilevel mixed effects modelling, the impact of time on median worst pain score was identified to be highly significant (P < 0.0001) whereas treatment allocation (placebo versus metronidazole) did not significantly affect the improvement in patients' reported pain (P = 0.8837). CONCLUSION: Our data do not support the hypothesis that postoperative metronidazole has a clinically meaningful effect on posthaemorrhoidectomy pain. This study adds to the previous literature, and implies that it should not be routinely used as an adjunct to analgesia.

Retraction Note: Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Integrating postradiotherapy plasma Epstein-Barr virus DNA and TNM stage for risk stratification of nasopharyngeal carcinoma to adjuvant therapy.

BACKGROUND: After curative radiotherapy (RT) or chemoradiation (CRT), there is no validated tool to accurately identify patients for adjuvant therapy in nasopharyngeal carcinoma (NPC). Post-RT circulating plasma Epstein-Barr virus (EBV) DNA can detect minimal residual disease and is associated with recurrence and survival independent of TNM (tumor-lymph node-metastasis) stage. We aimed to develop and validate a risk model for stratification of NPC patients after completion of RT/CRT to observation or adjuvant therapy. PATIENTS AND METHODS: The prospective multicenter 0502 EBV DNA screening cohort (Hong Kong NPC Study Group 0502 trial) enrolled from 2006 to 2015 (n = 745) was used for model development. For internal validation, we pooled independent patient cohorts from prospective clinical studies enrolled from 1997 to 2006 (n = 340). For external validation, we used retrospective cohort of NPC patients treated at Sun Yat-sen University Cancer Center from 2009 to 2012 (n = 837). Eligible patients had histologically confirmed NPC of Union for International Cancer Control (UICC) 7th Edition stage II-IVB who completed curative RT/CRT with or without neoadjuvant chemotherapy, had post-RT EBV DNA tested within 120 days after RT and received no adjuvant therapy. The primary end point was overall survival (OS). We used recursive-partitioning analysis (RPA) to classify patients into groups of low, intermediate, and high risk of death. RESULTS: Combining post-RT EBV DNA level (0, 1-49, 50-499, and ≥500 copies/ml) and TNM stage (II, III, IVAB), RPA model classified patients into low-, intermediate-, and high-risk groups with 5-year OS of 89.4%, 78.5% and 37.2%, respectively. The RPA low-risk group had comparable OS to TNM stage II (5-year OS 88.5%) but identified more patients (64.8% versus stage II 28.1%) that could potentially be spared adjuvant therapy toxicity. The RPA model (c-index 0.712) showed better risk discrimination than either the TNM stage (0.604) or post-RT EBV DNA alone (0.675) with improved calibration and consistence. These results were validated in both internal and external cohorts. CONCLUSION: Combining post-RT EBV DNA and TNM stage improved risk stratification in NPC.

Deep neuromuscular blockade improves surgical conditions during low-pressure pneumoperitoneum laparoscopic donor nephrectomy.

BACKGROUND: Evidence indicates that low-pressure pneumoperitoneum (PNP) reduces postoperative pain and analgesic consumption. A lower insufflation pressure may hamper visibility and working space. The aim of the study is to investigate whether deep neuromuscular blockade (NMB) improves surgical conditions during low-pressure PNP. METHODS: This study was a blinded randomized controlled multicenter trial. 34 kidney donors scheduled for laparoscopic donor nephrectomy randomly received low-pressure PNP (6 mmHg) with either deep (PTC 1-5) or moderate NMB (TOF 0-1). In case of insufficient surgical conditions, the insufflation pressure was increased stepwise. Surgical conditions were rated by the Leiden-Surgical Rating Scale (L-SRS) ranging from 1 (extremely poor) to 5 (optimal). RESULTS: Mean surgical conditions were significantly better for patients allocated to a deep NMB (SRS 4.5 versus 4.0; p < 0.01). The final insufflation pressure was 7.7 mmHg in patients with deep NMB as compared to 9.1 mmHg with moderate NMB (p = 0.19). The cumulative opiate consumption during the first 48 h was significantly lower in patients receiving deep NMB, while postoperative pain scores were similar. In four patients allocated to a moderate NMB, a significant intraoperative complication occurred, and in two of these patients a conversion to an open procedure was required. CONCLUSIONS: Our data show that deep NMB facilitates the use of low-pressure PNP during laparoscopic donor nephrectomy by improving the quality of the surgical field. The relatively high incidence of intraoperative complications indicates that the use of low pressure with moderate NMB may compromise safety during LDN. Clinicaltrials.gov identifier: NCT 02602964.

Hepatocellular differentiation status is characterized by distinct subnuclear localization and form of the chanzyme TRPM7.

The channel-kinase TRPM7 is important for the survival, proliferation, and differentiation, of many cell types. Both plasma membrane channel activity and kinase function are implicated in these roles. Channel activity is greater in less differentiated hepatoma cells compared with non-dividing, terminally differentiated adult hepatocytes, suggesting differences in protein expression and/or localization. We used electrophysiological and immunofluorescence approaches to establish whether hepatocellular differentiation is associated with altered TRPM7 expression. Mean outward current decreased by 44% in WIF-B hepatoma cells incubated with the established hepatic differentiating factors oncostatin M/dexamethasone for 1-8 days. Pre-incubation with pyridone 6, a pan-JAK inhibitor, blocked the current reduction. An antibody targeted to the C-terminus of TRPM7 labelled the cytoplasm in WIF-B cells and intact rat liver. Significant label also localized to the nuclear envelope (NE), with relatively more detected in adult hepatocytes compared with WIF-B cells. Hepatoma cells also exhibited nucleoplasmic labelling with intense signal in the nucleolus. The endogenous labelling pattern closely resembles that of HEK293T cells heterologously expressing a TRPM7 kinase construct containing a putative nucleolar localization sequence. These results suggest that TRPM7 form and distribution between the plasma membrane and nucleus, rather than expression, is altered in parallel with differentiation status in rat hepatic cells.

[Mediating effect of hemoglobin and hematocrit on the association between alcohol consumption and blood pressure among middle-aged and elderly male residents in Guangzhou].

Objective: To explore the mediating effect of hemoglobin (Hb) and hematocrit (HCT) on the association between alcohol consumption and blood pressure, and provide evidence for the prevention and control of alcohol-attributed hypertension. Methods: 1 091 male (age >50 years old) participants with drinking habit were selected from the Guangzhou biobank cohort study (GBCS). Mediation analysis was used to evaluate the mediating effect of Hb and HCT on the association of alcohol consumption (unit/day) with systolic blood pressure (SBP), diastolic blood pressure(DBP), pulse pressure(PP) and mean arterial pressure (MAP). Results: After adjusting for age, body mass index, education level, personal annual income, smoking, occupation and physical activity, the associations of alcohol consumption with SBP, DBP, PP and MAP were partly mediated by Hb, the proportion of mediating effect was 11.8% (95%CI 4.8%-24.7%), 15.3% (95%CI 6.5%-32.0%), 8.4% (95%CI 2.2%-22.5%) and 13.5% (95%CI 5.9%-27.5%), respectively. The associations of alcohol consumption with SBP, DBP, and MAP were also partly mediated by HCT, the proportion of mediating effect was 6.3% (95%CI 1.0%-16.0%), 8.7% (95%CI 1.4%-21.4%), and 7.5% (95%CI 1.0%-18.6%), respectively. Conclusion: There is a significant mediating effect of Hb and HCT on the association between alcohol consumption and blood pressure. Besides efforts on alcohol control, the potential effects of alcohol-induced increase on Hb and HCT, which might also increase the blood pressure, need to be considered to achieve optimal monitoring and prevention of alcohol-related hypertension.

Managing malignant pleural effusion with an indwelling pleural catheter: factors associated with spontaneous pleurodesis.

INTRODUCTION: Malignant pleural effusion can be recurrent despite active anti-cancer treatment. Significant malignant pleural effusion leads to debilitating dyspnoea and worsening quality of life in patients with advanced cancer. An indwelling pleural catheter offers a novel means to manage recurrent malignant pleural effusion and may remove the need for repeated thoracocentesis. Spontaneous pleurodesis is another unique advantage of indwelling pleural catheter placement but the factors associated with its occurrence are not clearly established. The aims of this study were to explore the safety of an indwelling pleural catheter in the management of symptomatic recurrent malignant pleural effusion, and to identify the factors associated with spontaneous pleurodesis. METHODS: This case series with internal comparisons was conducted in the Division of Respiratory Medicine, Department of Medicine, Queen Mary Hospital, Hong Kong. All patients who underwent insertion of an indwelling pleural catheter from the initiation of such service from January 2010 to December 2014 were included for data analysis. Patients were monitored until December 2014, with the last catheter inserted in July 2014. RESULTS: Between 2010 and 2014, a total of 23 indwelling pleural catheters were inserted in 22 consecutive patients with malignant pleural effusion, including 15 (65.2%) cases with malignant pleural effusion as a result of metastatic lung cancer. Ten (43.5%) cases achieved minimal output according to defined criteria, in five of whom the pleural catheter was removed without subsequent re-accumulation of effusion (ie spontaneous pleurodesis). Factors associated with minimal output were the absence of trapped lung (P=0.036), shorter time from first appearance of malignant pleural effusion to catheter insertion (P=0.017), and longer time from catheter insertion till patient's death or end of study (P=0.007). CONCLUSIONS: An indwelling pleural catheter provides a safe means to manage symptomatic malignant pleural effusion. Potential clinical factors associated with minimal output were identified along with the occurrence of spontaneous pleurodesis, which is a unique advantage offered by indwelling pleural catheter.

Clinical outcome of neoadjuvant chemoradiation in locally advanced rectal cancer at a tertiary hospital.

OBJECTIVES: To review the clinical outcome of locally advanced rectal cancer treated with neoadjuvant chemoradiation followed by definitive surgery with or without adjuvant chemotherapy and to elucidate the prognostic factors for treatment outcome. METHODS: This historical cohort study was conducted at a tertiary public hospital in Hong Kong. All patients who had undergone neoadjuvant chemoradiation for locally advanced rectal cancer in our department from November 2005 to October 2014 were recruited. Local recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival of patients were documented. RESULTS: A total of 135 patients who had received neoadjuvant chemoradiation during the study period were reviewed. There were 130 patients who had completed neoadjuvant chemoradiation and surgery. The median follow-up time was 35.1 months. The 3- and 5-year local recurrence-free survival, distant metastasis-free survival, disease-free survival, as well as overall survival rates were 91.8% and 86.7%, 73.9% and 72.1%, 70.1% and 64.6%, as well as 86.5% and 68.4%, respectively. The rate of pathological complete response was 13.8%. The T and N downstaging rate was 49.2% and 63.1%, respectively. The rate of conversion from threatened circumferential resection margin to clearance of margin was 90.6%. Of the 42 cases that were initially deemed to require abdominal perineal resection, 15 (35.7%) were converted to sphincter-sparing surgery. CONCLUSIONS: The treatment outcome of neoadjuvant chemoradiation for locally advanced rectal cancer was comparable with overseas data in terms of local control rate and overall survival. This strategy may increase the chance of achieving a clear surgical margin by downstaging the tumour, especially in patients who presented with threatened circumferential margin.

Chronic inflammatory demyelinating polyradiculoneuropathy: A new animal model for new therapeutic targets.

Animal models are fundamental to advance knowledge of disease pathogenesis and to test/develop new therapeutic strategies. Most of the current knowledge about the pathogenic mechanisms underpinning autoimmune demyelination processes implicating autoantigens has been obtained using the Experimental Autoimmune Neuritis (EAN) animal model. The most widely used EAN model is obtained by active immunization of Lewis rats using a peptide, P0 (180-199), issuing from the major peripheral nervous system myelin protein. But this model mimics only the classical monophasic acute form of demyelinating polyradiculoneuropathy, i.e. Guillain-Barré syndrome (GBS). We developed a new model by immunizing Lewis rats using the same immunodominant neuritogenic peptide P0 (180-199) but this time with its S-palmitoyl derivative, S-palm P0 (180-199). All of the animals immunized with the S-palm P0 (180-199) peptide developed a chronic relapsing-remitting form of the disease corresponding to the electrophysiological criteria of demyelination (slow sensory nerve conduction velocity, prolonged motor nerve latency, partial motor nerve conduction blocks) with axon degeneration. These findings were confirmed by immunohistopathology study and thus, appear to mimic human chronic inflammatory demyelinating polyradiculopathy (CIDP). This new model opens up new avenues of research for testing new anti-inflammatory and neuroprotective therapeutic strategies.

[Effectiveness of bupropion and counseling for smoking cessation].

OBJECTIVE: To evaluate the effectiveness of bupropion for smoking cessation among Chinese smokers at a smoking cessation clinic. METHODS: A prospective observational study was conducted in a hospital located in Beijing during 2008 and from 28 to 31 October 2014. A total of 287 smokers (265 men and 22 women) were assessed using data from structured questionnaires at baseline and were followed up at 1 and 6 months. Trained physician counselors provided free brief education and individual counseling sessions for all participants at the first visit. A total 131 participants were prescribed bupropion in addition to counseling. The counseling plus bupropion group was compared with the group who underwent counseling without bupropion. Outcomes were self-reported 7-day point prevalence abstinence rates at 1- and 6-month follow-up and continuous abstinence rates at 6-month follow-up. Smoking reduction rates at 1 and 6 months were also measured. RESULTS: By intention-to-treat analysis, the 7-day point prevalence abstinence rate of the bupropion group at 1 and 6 months was higher than for the counseling-only group: at 1-month follow-up, 26.0% (34/131) vs. 15.4% (24/156), with OR (95% CI) 1.93(1.07-3.46); these rates at 6-month follow-up were 27.8% (35/131) vs. 15.4% (24/156), with OR (95% CI) 2.01(1.12-3.59). The 1-month continuous abstinence rate at 6 months was higher in the bupropion group: 26.0% (34/131) vs. 14.7% (23/156), with OR (95%CI) 2.03(1.12-3.66). Participants in the bupropion group also had a higher smoking reduction rate at 1 month than those in the counseling-only group: 55.0% (72/131) vs. 38.5% (60/156), with OR (95%CI) 1.95 (1.22-3.13). CONCLUSION: Prescription of bupropion at this smoking cessation clinic was effective in doubling the quitting rates and smoking reduction rates among Chinese smokers.

Hong Kong domestic health spending: financial years 1989/90 to 2011/12.

This report presents the latest estimates of Hong Kong domestic health spending for financial years 1989/90 to 2011/12, cross-stratified and categorized by financing source, provider, and function. Total expenditure on health (TEH) was HK$101 985 million in financial year 2011/12, which represents an increase of HK$8580 million or 9.2% over the preceding year. TEH grew faster relative to gross domestic product (GDP) leading to a rise in TEH as a percentage of GDP from 5.1% in 2010/11 to 5.2% in 2011/12. During the period 1989/90 to 2011/12, total health spending per capita (at constant 2012 prices) grew at an average annual rate of 4.8%, which was faster than the average annual growth rate of per capita GDP by 1.8 percentage points. In 2011/12, public and private expenditure on health increased by 8.3% and 10.0% when compared with 2010/11, reaching HK$49,262 million and HK$52,723 million respectively. Consequently, public share of total health expenditure dropped slightly from 48.7% to 48.3% over the year. Of private spending, the most important source of health financing was out-of-pocket payments by households (34.9% of TEH), followed by employer-provided group medical benefits (7.5%) and private insurance (7.4%). It is worth noting that private insurance will likely take over employers as the second largest private payer if the insurance market continues to expand at the current rate. Of the HK$101,985 million total health expenditure in 2011/12, current expenditure comprised HK$96,572 million (94.7%), whereas HK$5413 million (5.3%) was for capital expenses (ie investment in medical facilities). Analysed by health care function, services of curative care accounted for the largest share of total health spending (65.2%), which was made up of ambulatory services (33.6%), in-patient curative care (26.9%), day patient hospital services (4.1%), and home care (0.5%). Notwithstanding its small share, the total spending for day patient hospital services shows an increasing trend over the period 1989/90 to 2011/12, likely as a result of policy directives to shift the emphasis from in-patient to day patient care. Hospitals accounted for an increasing share of total spending, from 28.2% in 1989/90 to 46.8% in 2002/03 and then dropped slightly to 42% to 44% during the period 2005/06 to 2011/12, which was primarily driven by reduced expenditure of Hospital Authority. As a result of the epidemics which are of public health importance (eg avian flu, SARS, swine flu) and the expansion of private health insurance market in the last two decades, spending on provision and administration of public health programmes, and general health administration and insurance accounted for increasing, though less significant, shares of total health spending over the period. Without taking into account capital expenses (ie investment in medical facilities), public current expenditure on health amounted to HK$45,321 million (46.9% of total current expenditure) in 2011/12 with the remaining HK$51,251 million made up of private sources of funds. Public current expenditure was mostly incurred at hospitals (74.1%), whereas private current expenditure was mostly incurred at providers of ambulatory health care (51.2%). Although both public and private spending were mostly expended on personal health care services and goods (91.1% of total current spending), the distributional patterns among functional categories differed. Public expenditure was targeted at in-patient care (47.3%) and substantially less on out-patient care (27.4%). In comparison, private spending was mostly concentrated on out-patient care (42.7%), whereas in-patient care (24.7%) and medical goods outside the patient care setting (19.9%) comprised the majority of the remaining share. Compared to the Organisation for Economic Co-operation and Development countries, Hong Kong has devoted a relatively low percentage of GDP to health care in the last decade. As a share of total spending, public funding (either general government revenue or social security funds) was also lower than those in most economies with comparable economic development and public revenue collection base. Nonetheless, Hong Kong health care system achieved service quality and health outcome that fared well by global standards, indicating cost efficiency and effectiveness.