Search

From 2014 to week 07/2020 the Centre for Health Protection in Hong Kong conducted screening for influenza C virus (ICV). A retrospective analysis of ICV detections to week 26/2019 revealed persistent low-level circulation with outbreaks occurring biennially in the winters of 2015 to 2016 and 2017 to 2018 (R. S. Daniels et al., J Virol 94:e01051-20, 2020, https://doi.org/10.1128/JVI.01051-20). Here, we report on an outbreak occurring in 2019 to 2020, reinforcing the observation of biennial seasonality in Hong Kong. All three outbreaks occurred in similar time frames, were subsequently dwarfed by seasonal epidemics of influenza types A and B, and were caused by similar proportions of C/Kanagawa/1/76 (K)-lineage and C/São Paulo/378/82 S1- and S2-sublineage viruses. Ongoing genetic drift was observed in all genes, with some evidence of amino acid substitution in the hemagglutinin-esterase-fusion (HEF) glycoprotein possibly associated with antigenic drift. A total of 61 ICV genomes covering the three outbreaks were analyzed for reassortment, and 9 different reassortant constellations were identified, 1 K-lineage, 4 S1-sublineage, and 4 S2-sublineage, with 6 of these being identified first in the 2019-1920 outbreak (2 S2-lineage and 4 S1-lineage). The roles that virus interference/enhancement, ICV persistent infection, genome evolution, and reassortment might play in the observed seasonality of ICV in Hong Kong are discussed. IMPORTANCE Influenza C virus (ICV) infection of humans is common, with the great majority of people being infected during childhood, though reinfection can occur throughout life. While infection normally results in "cold-like" symptoms, severe disease cases have been reported in recent years. However, knowledge of ICV is limited due to poor systematic surveillance and an inability to propagate the virus in large amounts in the laboratory. Following recent systematic surveillance in Hong Kong SAR, China, and direct ICV gene sequencing from clinical specimens, a 2-year cycle of disease outbreaks (epidemics) has been identified, with gene mixing playing a significant role in ICV evolution. Studies like those reported here are key to developing an understanding of the impact of influenza C virus infection in humans, notably where comorbidities exist and severe respiratory disease can develop.

In 2014, the Centre for Health Protection in Hong Kong introduced screening for influenza C virus (ICV) as part of its routine surveillance for infectious agents in specimens collected from patients presenting with symptoms of respiratory viral infection, including influenza-like illness (ILI). A retrospective analysis of ICV detections up to week 26 of 2019 revealed persistent low-level circulation, with two outbreaks having occurred in the winters of 2015 to 2016 and 2017 to 2018. These outbreaks occurred at the same time as, and were dwarfed by, seasonal epidemics of influenza types A and B. Gene sequencing studies on stored ICV-positive clinical specimens from the two outbreaks have shown that the hemagglutinin-esterase (HE) genes of the viruses fall into two of the six recognized genetic lineages (represented by C/Kanagawa/1/76 and C/São Paulo/378/82), with there being significant genetic drift compared to earlier circulating viruses within both lineages. The location of a number of encoded amino acid substitutions in hemagglutinin-esterase fusion (HEF) glycoproteins suggests that antigenic drift may also have occurred. Observations of ICV outbreaks in other countries, with some of the infections being associated with severe disease, indicates that ICV infection has the potential to have significant clinical and health care impacts in humans. IMPORTANCE Influenza C virus infection of humans is common, and reinfection can occur throughout life. While symptoms are generally mild, severe disease cases have been reported, but knowledge of the virus is limited, as little systematic surveillance for influenza C virus is conducted and the virus cannot be studied by classical virologic methods because it cannot be readily isolated in laboratories. A combination of systematic surveillance in Hong Kong SAR, China, and new gene sequencing methods has been used in this study to assess influenza C virus evolution and provides evidence for a 2-year cycle of disease outbreaks. The results of studies like that reported here are key to developing an understanding of the impact of influenza C virus infection in humans and how virus evolution might be associated with epidemics., (Copyright © 2020 Daniels et al.)

Background: Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir-ritonavir, and ribavirin for treating patients with COVID-19., Methods: This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688., Findings: Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3-7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5-11]) than the control group (12 days [8-15]; hazard ratio 4·37 [95% CI 1·86-10·24], p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir-ritonavir because of biochemical hepatitis. No patients died during the study., Interpretation: Early triple antiviral therapy was safe and superior to lopinavir-ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted., Funding: The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Over the last 10 years, there has been a major treatment revolution for early human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We aimed to explore the outcome of different neoadjuvant chemotherapy in a tertiary breast cancer centre with early HER2-positive breast cancer as well as factors associated with pathological complete response (pCR) and recurrence-free survival (RFS). The pattern of recurrence was also studied., Methods: This retrospective study analysed the outcome of neoadjuvant chemotherapy during the period 2005 to 2016 in a tertiary referral centre in Hong Kong. Patients were divided into three groups according to the neoadjuvant chemotherapy they received: chemotherapy only (Chemo), chemotherapy plus trastuzumab (Chemo-H) and chemotherapy plus double anti-HER2 therapy (Chemo-DH)., Results: There were 226 cases analysed during the study period. The rate of pCR was 5%, 26% and 60% in Chemo, Chemo-H and Chemo-DH groups, respectively (Chemo vs pooled Chemo-H/DH: p<0.0001; Chemo-H vs Chemo-DH: p<0.0001). This was accompanied by a trend of increased rate of breast conservation therapy in Chemo-DH cohort (p=0.046). Use of double anti-HER2 therapy, older age (>50 years) and hormone receptor negativity were associated with more pCR. pCR was associated with better RFS. Among those with recurrence, the proportion of patients with brain as the only site of recurrence increased remarkably with more efficacious anti-HER2 treatment (0% in Chemo, 8% in Chemo-H, 67% in Chemo-DH)., Conclusion: pCR remains an important predictive factor for improved RFS. In the era of dual anti-HER2 neoadjuvant therapy, brain-only recurrence poses a challenge to disease surveillance and treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: To quantify average angular measurements that define the soft tissue profiles of 12-year-old southern Chinese and to determine gender differences., Materials and Methods: A random population sample of 514 12-year-old children was recruited (about 10% of a Hong Kong Chinese birth cohort). Photographs were taken in natural head posture and 12 soft tissue landmarks were located on the photos to measure 12 angular measurements using ImageJ (V1.45s) for Windows. Approximately 10% of photographs were reanalyzed and method error was calculated. Angular norm values for the 12 parameters were determined and gender differences were assessed using 2 sample T-test with 95% confidence interval., Results: The response rate was 54.1% (278/514). Norm values for the 12 angular measurements were generated. The greatest variability was found for the nasolabial (Cm-Sn-Ls) and labiomental (Li-Sm-Pg) angles. Gender differences were found in 4 angular parameters: vertical nasal angle (N-Prn/TV) (p < 0.05), cervicomental angle (G-Pg/C-Me) (p < 0.001), facial convexity angle (G-Sn-Pg) (p < 0.01) and total facial convexity angle (G-Prn-Pg)(p < 0.01)., Conclusion: Norm values for 12 angular measurements among 12-year-old southern Chinese children were provided and some variability noted. Gender differences were apparent in several angular measurements. This study has implications in developing norm values for southern Chinese and for comparison with other ethnic groups.

Objectives: To evaluate nucleic acid testing of urine specimens against conventional Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) tests in genital swab specimens in a sexually transmitted infection (STI) clinic setting., Methods: Genital swab and urine samples were collected from attendees of public STI clinics in Hong Kong from May to June 2007. Swab specimens were subjected to on-site Gram stained microscopy and inoculation onto modified Thayer-Martin medium for NG culture before laboratory processing. CT PCR on genital swabs was performed by the Roche Cobas Amplicor test. Urine samples were tested for CT and NG by the Aptima Combo 2 (AC2) assay., Results: Data from 414 patients were analysed. The sensitivity and specificity of AC2 for NG were 100% (35/35) and 98.4% (373/379), respectively, with culture of genital swab specimens as standard. On-site microscopy provided timely results for empirical antimicrobial therapy, whereas culture yielded bacterial isolates for susceptibility testing and typing studies. Regarding CT, using Amplicor on genital swab specimens as reference, the sensitivity and specificity of AC2 were 98.7% (78/79) and 97.5% (313/321), respectively. Amplicor yielded uninterpretable results in 14 specimens due to PCR inhibitors., Conclusions: The current STI clinic and laboratory practices were practical and useful for clinical management, even though favourable results were obtained with the AC2 assay, which had streamlined laboratory workflow. The use of a molecular testing strategy may be cost-effective with microscopy and culture being targetted for patient groups with the highest expected yield of positive results.

Ninety-one ampicillin-resistant Shigella flexneri strains from Hong Kong and Shanghai were studied for production of beta-lactamases. TEM-1-like and OXA-1-like enzymes were identified in 21 and 79% of the strains, respectively, by isoelectric focusing (IEF). No difference in the pattern of beta-lactamase production was found between strains from Hong Kong and Shanghai. Four ribotypes were detected. Over 88% of OXA-producing strains had the same ribotype. All TEM-1-like strains harbored a plasmid which hybridized positively with the bla(TEM) probe. Total DNA from OXA-1-like strains failed to hybridize or only hybridized weakly with an OXA probe. The OXA resistance was not transferable. OXA-1-like enzymes exhibited substrate and inhibition profiles similar to that of OXA-1 and were shown to have a pI of 7.3 by further IEF using a narrow-range ampholine gel. The gene encoding the OXA-1-like enzyme from one isolate (CH-07) was cloned, sequenced, and found to differ from bla(OXA-1) at codon 131 (AGA-->GGA; Arg to Gly), resulting in the novel designation OXA-30. The predominance of OXA-type enzymes in ampicillin-resistant S. flexneri suggests host preference for specific beta-lactamases.

Seven living-related liver transplants (LRLT) and two reduced-size liver transplants (RSLT) were performed on eight children who suffered from end-stage liver disease, having previously undergone one to three abdominal operations. Their ages at initial transplantation ranged from 8 months to 11 years (mean 35 months, median 12 months). Excluding the two older children aged 7 and 11 years, respectively, the rest of the children weighed 6 to 9.5 kg (mean 7.3 kg) at the time of the initial transplantation. Seven left lateral segments (S2 + 3) and two left lobes (S2 + 3 + 4) were used; of these the smallest graft had a graft-to-recipient body weight ratio of 0.9%. The volunteer living donors were four mothers, two fathers and one sister who were selected after medical and psychiatric evaluations, and their suitability was confirmed by hematological, biochemical, and radiological criteria. During a follow-up period of 3 to 30 months, all eight children are alive and well with normal liver function, one of them having undergone a retransplant LRLT because of hepatitis of undetermined etiology following a RSLT 1.5 years earlier. All seven donors had an uneventful postoperative course and were discharged on day 4 to 7 postoperatively. They have all resumed normal day-to-day activities. There were no complications in the donor group. A variety of complications occurred in the recipients, all of which were overcome. Operating microscope was used to perform all the arterial anastomoses using microvascular techniques. This method has proven to be a major factor in preventing arterial thrombosis even with the smallest of arterial anastomosis where a 1.5-mm diameter recipient artery was anastomosed to a 2.5-mm diameter donor hepatic artery.

We analyzed data from 1233 Chinese patients of a wide age range who received patient-controlled analgesia (PCA) intravenous morphine for postoperative pain relief, during the period of January 1992 to May 1995. The analgesic regimen was standardized as follows: PCA bolus 1 to 1.5 mg; lock-out interval 5 minutes; one-hour maximum dose 0.075 to 0.1 mg.kg-1 and background infusion 0 or 0.5 mg.h-1. Most patients underwent major surgery that was broadly subclassified according to the anatomical area involved. The median verbal numerical rating scales of pain (0 to 10) at rest and while coughing for the first, second and third 24 hours were 3.0/5.0, 1.5/4.0 and 0/3.0 respectively and the corresponding demand to delivery ratios were 2.8 +/- 2.9, 2.6 +/- 2.4 and 2.4 +/- 2.6. The overall morphine consumptions in 1004 of these Chinese patients were 27.5 +/- 16.8, 17.8 +/- 16.1 and 18.1 +/- 21.0 micrograms.kg-1.h-1 during the first 16, 17 to 41 and 42 to 66 postoperative hours respectively. These figures were the same as for Caucasian patients managed in the same institution. Morphine consumption was significant higher following thoracic, upper abdominal and spinal surgery. Also it was higher in patients younger than 65 years, males, cigarette smokers and those with ASA physical status I or II. The commonest side-effects were nausea (34.5%) and vomiting (18.2%). Bradypnoea and oxygen desaturation occurred in 0.5% and 1.6% respectively. All cases were promptly detected and managed with no adverse outcomes. Most patients were satisfied (76.7% ranked "good") with their postoperative analgesia. The commonest reasons for dissatisfaction were inadequate pain relief, nausea and reluctance to self-control analgesic administration. It is concluded that PCA with intravenous morphine is effective and safe as a routine postoperative technique for Chinese surgical patients.

More than 60% of cancer patients suffers from unbearable pain, especially towards their terminal stages. Anaesthesiologists are involved in cancer pain management because of their expertise in analgesic pharmacology and neurolytic procedures. This manuscript reported on the experience of treating cancer pain in Chinese patient in Hong Kong with reference to current literature in other parts of the world. One hundred and sixty two Chinese patients were referred from other specialists to the Department of Anaesthesiology, Queen Mary Hospital for further management because of their cancer pain control were considered difficult. Upon referral, the mean visual analogue scale of pain (VAS) was 5.8 +/- 2.7. The pain caused insomnia (66.7%) and appetite loss (45%) as well. By far most (80%) patients' pain were successively controlled with oral systemic analgesics. These were prescribed in form of a combination of NSAID (72.2%), potent opioids (76.5%) and co-analgesics (21.6%). In our series, the mean oral morphine (MS Continus) requirements was 96.0 +/- 68.3 mg on discharge. Frequent nausea and constipation persisted in 16.0% and 8.0% respectively despite active treatment with anti-emetics and laxatives. Twenty eight neurolytic blocks was performed in 22 (13.6%) patients. Good pain relief was achieved in 78.6%. Overall speaking most patients (90.7%) were able to achieve adequate analgesia before death.