Changes in the epidemiology and clinical manifestations of human immunodeficiency virus-associated tuberculosis in Hong Kong.

INTRODUCTION: Human immunodeficiency virus (HIV)-associated tuberculosis (TB) remains an important health challenge worldwide. Although TB prevalence has decreased in the general population, there is limited information regarding temporal trends in the incidence of HIV-associated TB in Hong Kong. There are also insufficient data regarding changes in clinical manifestation patterns among HIV-associated TB patients over time. This study aimed to describe temporal trends in the epidemiology and clinical manifestations of HIV-associated TB in Hong Kong. METHODS: We retrospectively reviewed data regarding HIV-associated TB patients that were reported to the TB-HIV Registry of the Department of Health during the period 2007 to 2020. Trends of TB as a primary acquired immunodeficiency syndrome (AIDS)-defining illness, as well as changes in demographic features and clinical manifestations of HIV-associated TB during this period were examined using Cochran-Armitage trend test. RESULTS: A decreasing trend was observed in the proportion of all reported cases of AIDS in which TB was a primary AIDS-defining illness during the study period. The proportions of female patients and patients with extrapulmonary involvement significantly increased, whereas the proportions of ever-smokers and patients with sputum smear positivity significantly decreased during the same period. A decreasing trend was observed in the proportion of patients with pulmonary TB in which the lower zone was the predominant site of lung parenchymal lesions. Among patients with a diagnosis of HIV infection before TB, an increasing trend was observed in the proportion of patients receiving antiretroviral therapy. CONCLUSION: Important temporal changes were observed in the epidemiology and clinical manifestations of HIV-associated TB. These results highlight the need for continued surveillance regarding the patterns of demographic features and clinical manifestations to inform policymakers when planning control strategies for HIV-associated TB.

Childhood Adversity, Resilience, and Mental Health: A Sequential Mixed-Methods Study of Chinese Young Adults.

Resilience is a key health protective factor for those with adverse childhood experiences (ACEs), but little research has explored how it manifests in early adulthood or across cultures. The purpose of this study was to generate a fuller understanding of resilience and its contribution to the relationships between mental health problems and ACEs among Chinese young adults in Hong Kong. Using a sequential explanatory mixed-methods design, 433 Chinese young adults aged 18 to 24 years were surveyed online to examine the relationships between ACEs, resilience, and mental health problems (depression, anxiety, maladjustment, and posttraumatic stress symptoms). Among them, 34 participants with ACEs were purposively selected and interviewed to explore cultural factors that influenced their resilience. Quantitative data were analyzed using multiple hierarchical regression analyses; qualitative data were analyzed using a qualitative descriptive approach. Higher cumulative ACE exposure was associated with higher severity of adjustment disorder and odds for screening positive for posttraumatic stress disorders, but not for symptoms of depression or anxiety. Resilience significantly contributed to explaining variances across all mental health outcomes over and beyond ACEs and in a protective fashion. Four themes emerged from qualitative interviews: (a) Privacy, emotional restraint, and "saving face"; (b) Conforming to preserve harmony; (c) A will to excel; and (d) Viewing adversity as a matter of luck. These findings suggest Chinese young adults' resilience was influenced by cultural norms of restraint, conformity, competition, and superstition. The present study provides a model for future studies using a mixed-methods design to deeply examine resilience among younger people exposed to early adversities within sociocultural, historical, or geographical contexts.

A distinctive epigenetic ageing profile in human granulosa cells.

STUDY QUESTION: Does women's age affect the DNA methylation (DNAm) profile differently in mural granulosa cells (MGCs) from other somatic cells? SUMMARY ANSWER: Accumulation of epimutations by age and a higher number of age-related differentially methylated regions (DMR) in MGCs were found compared to leukocytes from the same woman, suggesting that the MGCs have a distinctive epigenetic profile. WHAT IS KNOWN ALREADY: The mechanisms underlying the decline in women's fertility from the mid-30s remain to be fully elucidated. The DNAm age of many healthy tissues changes predictably with and follows chronological age, but DNAm age in some reproductive tissues has been shown to depart from chronological age (older: endometrium; younger: cumulus cells, spermatozoa). STUDY DESIGN, SIZE, DURATION: This study is a multicenter cohort study based on retrospective analysis of prospectively collected data and material derived from healthy women undergoing IVF or ICSI treatment following ovarian stimulation with antagonist protocol. One hundred and nineteen women were included from September 2016 to June 2018 from four clinics in Denmark and Sweden. PARTICIPANTS/MATERIALS, SETTING, METHODS: Blood samples were obtained from 118 healthy women with varying ovarian reserve status. MGCs were collected from 63 of the 119 women by isolation from pooled follicles immediately after oocyte retrieval. DNA from leukocytes and MGCs was extracted and analysed with a genome-wide methylation array. Data from the methylation array were processed using the ENmix package. Subsequently, DNAm age was calculated using established and tailored age predictors and DMRs were analysed with the DMRcate package. MAIN RESULTS AND ROLE OF CHANCE: Using established age predictors, DNAm age in MGCs was found to be considerable younger and constant (average: 2.7 years) compared to chronological age (average: 33.9 years). A Granulosa Cell clock able to predict the age of both MGCs (average: 32.4 years) and leukocytes (average: 38.8 years) was successfully developed. MGCs differed from leukocytes in having a higher number of epimutations (P = 0.003) but predicted telomere lengths unaffected by age (Pearson's correlation coefficient = -0.1, P = 0.47). DMRs associated with age (age-DMRs) were identified in MGCs (n = 335) and in leukocytes (n = 1) with a significant enrichment in MGCs for genes involved in RNA processing (45 genes, P = 3.96 × 10-08) and gene expression (152 genes, P = 2.3 × 10-06). The top age-DMRs included the metastable epiallele VTRNA2-1, the DNAm regulator ZFP57 and the anti-Müllerian hormone (AMH) gene. The apparent discordance between different epigenetic measures of age in MGCs suggests that they reflect difference stages in the MGC life cycle. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: No gene expression data were available to associate with the epigenetic findings. The MGCs are collected during ovarian stimulation, which may influence DNAm; however, no correlation between FSH dose and number of epimutations was found. WIDER IMPLICATIONS OF THE FINDINGS: Our findings underline that the somatic compartment of the follicle follows a different methylation trajectory with age than other somatic cells. The higher number of epimutations and age-DMRs in MGCs suggest that their function is affected by age. STUDY FUNDING/COMPETING INTEREST(S): This project is part of ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS, the Danish National Research Foundation and the European Research Council. The authors declare no conflict of interest.

Knowledge and Perceptions of Child Protection and Mandatory Reporting: A Survey of Nurses in Hong Kong.

In the absence of a mandatory reporting (MR) structure, it is unclear how nurses perceive or exercise their role in child protection. This study examined knowledge and perceptions of child protection and MR among nurses working in Hong Kong. This cross-sectional web-based survey used the Child Abuse Report Intention Scale to measure nurses' child protection knowledge and attitudes, and their perceived norms, control, and intention to report suspected maltreatment. Nurses also indicated if they support MR and to provide an explanation for their preference. Quantitative data were described and analyzed using bivariate and regression analyses. Open-ended responses were analyzed using directed content analysis. A convenient sample of 91 nurses working in Hong Kong completed the survey. The majority (86%) were female with a mean of 9.5 years of nursing experience; their mean knowledge score was 6.64 out of 13 (range 2-10). Compared with other maltreatment types, sexual abuse was perceived to be most severe and most likely to be reported. Perceived severity and attitudes toward child maltreatment was significantly associated with nurses' intention to report. Over half (58%) supported MR; those against MR expressed concerns about lack of support from management. Although nurses working in Hong Kong still hold polarized views about MR, findings point to the importance of creating a supportive reporting culture, and designing training programs that focus on changing perceptions about child protection in order to improve their tendency to report.

Patterns of exposure to adverse childhood experiences and their associations with mental health: a survey of 1346 university students in East Asia.

INTRODUCTION: Adverse childhood experiences (ACEs) constitute a significant global mental health burden. Prior studies typically investigated the impact of ACEs on mental health using a cumulative risk approach; most ACEs studies were also conducted in Western settings. PURPOSE: This study aimed to examine ACEs using a pattern-based approach and assess their associations with mental health outcomes by early adulthood in East Asia. METHODS: The present study included measures of exposure to 13 categories of ACEs, depression, anxiety, maladjustment, and posttraumatic stress in a sample of 1346 university students from Hong Kong, China, Taiwan, and Japan. RESULTS: Latent class analysis indicated three distinct patterns of ACE exposure: Class 1: Low ACEs (76.0%); Class 2: Household Violence (20.6%); and Class 3: Household Dysfunction (3.4%). Those representing Class 3 had significantly more ACEs compared with those in Classes 1 or 2. Controlling for age and sex, those in Class 2 reported significantly higher depression and maladjustment symptoms compared with those in Class 1; both Classes 2 and 3 had significantly higher anxiety symptoms and odds for meeting diagnostic criteria for posttraumatic stress disorders compared with those in Class 1. CONCLUSIONS: Study findings suggest that young adults' mental health, at least under certain contexts, is more closely linked with the nature and pattern of ACE co-occurrence, rather than the number of ACEs.

Hepatitis B Vaccination in Patients Receiving Oral Antiviral Therapy Without Hepatitis B Immunoglobulin After Liver Transplant.

Our study aimed to determine if a double-dose pre-S containing hepatitis B virus (HBV) vaccination (Sci-B-Vac) could elicit an adequate and sustainable immune response in HBV patients who developed spontaneous hepatitis B surface antibody (anti-HBs) response after liver transplant. PATIENTS AND METHODS: All patients who received transplants for HBV-related disease for >1 year with normal graft function and hepatitis B surface antigen seronegativity were evaluated. They received a 40-µg HBV vaccine if they were responders in our previous vaccine trial, if anti-HBs was positive for >1 year after liver transplant (LT), or if a peak anti-HBs at any time point after LT was >100 mIU/mL. Primary endpoint was the development of anti-HBs ≥ 10 mIU/mL from previous negative value or a 1-log increase from baseline. RESULTS: A total of 86 patients were recruited; 5 were responders from a previous trial; 45 patients had detectable anti-HBs >1 year after LT, and 36 patients had an anti-HBs >100 mIU/mL. All (5/5, 100%) previous responders responded to booster vaccination. For the remaining 81 patients, 10 of 81 (12.3%) responded. CONCLUSION: All previous responders responded to booster vaccination, implying durability and memory of HBV immune response, which is an important prerequisite for definitive host immunity for HBV. In patients who had spontaneous anti-HBs production after LT, a single vaccination can induce response in 12.3% of patients.

Changing Paradigm in the Surgical Management of Hepatocellular Carcinoma With Salvage Transplantation.

OBJECTIVE: The objective of this study was to compare the long-term outcomes of primary and salvage liver transplantation for patients with hepatocellular carcinoma (HCC). METHOD: This was a 10-year retrospective analysis in a tertiary referral center. RESULTS: There were 184 patients recruited (primary liver transplantation [pLT]:salvage liver transplantation [sLT], 143:41). The median follow-up time was 79 months. Operation time was shorter in the pLT group than the sLT group (661 ± 164 minutes vs 754 ± 206 minutes; P = .01) and the blood loss was 3749 mL and 3545 mL for pLT and sLT, respectively (P = .735). The reoperation rate was 5.6% and 4.9%, respectively (P = 1.0). The 5-year overall and disease-free survival rates from the time of transplantation for pLT and sLT were 84.1% versus 70.2% (P = .01) and 82.2% versus 65.8% (P = .01), respectively. The 5-year overall survival rate from the time of primary treatment for sLT was 80.3% (P = .1). Subgroup analysis of sLT showed that young age (50 vs 56 year old; P = .004) was the only factor associated with poor overall survival. Young age (P = .004) and microvascular permeation (P = .008) in the recurrent tumor were associated with HCC recurrence. Young age stands out to be the only independent factor associated with HCC recurrence. CONCLUSION: sLT is the treatment of choice for patients with recurrent HCC in regions of graft shortage.

Randomized clinical trial of hepatic resection versus radiofrequency ablation for early-stage hepatocellular carcinoma.

BACKGROUND: Hepatic resection and radiofrequency ablation (RFA) are treatment options for early-stage hepatocellular carcinoma (HCC). Whether tumour recurrence and long-term survival favour either treatment has not been established. This randomized trial aimed to test the hypothesis that RFA is superior to hepatic resection in terms of lower tumour recurrence rate and better long-term survival. METHODS: Patients with early-stage HCC (solitary tumour no larger than 5 cm; or no more than 3 tumours, each 3 cm or smaller) were randomized into hepatic resection and RFA groups. Demographic and clinical characteristics, and short- and long-term outcome measures were compared between groups. Primary and secondary outcome measures were overall tumour recurrence and survival respectively. RESULTS: Clinicopathological data were similar in the two groups, which each contained 109 patients. The RFA group had a shorter treatment duration, less blood loss and shorter hospital stay than the resection group. Mortality and morbidity rates were similar in the two groups. The overall tumour recurrence rate was similar in the resection and RFA groups (71·3 versus 81·7 per cent respectively). The 1-, 3-, 5- and 10-year overall survival rates were 94·5, 80·6, 66·5 and 47·6 per cent respectively in the resection group, compared with 95·4, 82·3, 66·4 and 41·8 per cent in the RFA group (P = 0·531). Corresponding disease-free survival rates were 74·1, 50·9, 41·5 and 31·9 per cent in the resection group, and 70·6, 46·6, 33·6 and 18·6 per cent in the RFA group (P = 0·072). CONCLUSION: RFA for early-stage HCC is not superior to hepatic resection, in terms of tumour recurrence, overall survival and disease-free survival. Registration number: HKUCTR-10 (http://www.hkuctr.com).

Should ALPPS be Used for Liver Resection in Intermediate-Stage HCC?

BACKGROUND: Extended liver resections in patients with hepatocellular carcinoma (HCC) are problematic due to hepatitis, fibrosis, and cirrhosis. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) has been promoted as a novel method to induce hypertrophy for patients with extensive colorectal liver metastases, but outcomes in HCC have not been well investigated. METHODS: All patients registered in the international ALPPS Registry ( www.alpps.org ) from 2010 to 2015 were studied. Hypertrophy of the future liver remnant, perioperative morbidity and mortality, age, overall survival, and other parameters were compared between patients with HCC and patients with colorectal liver metastases (CRLM). RESULTS: The study compared 35 patients with HCC and 225 patients with CRLM. The majority of patients undergoing ALPPS for HCC fall into the intermediate-stage category of the Barcelona clinic algorithm. In this study, hypertrophy was rapid and extensive for the HCC patients, albeit lower than for the CRLM patients (47 vs. 76 %; p < 0.002). Hypertrophy showed a linear negative correlation with the degrees of fibrosis. The 90-day mortality for ALPPS used to treat HCC was almost fivefold higher than for CRLM (31 vs. 7 %; p < 0.001). Multivariate analysis showed that patients older than 61 years had a significantly reduced overall survival (p < 0.004). CONCLUSION: The ALPPS approach induces a considerable hypertrophic response in HCC patients and allows resection of intermediate-stage HCC, albeit at the cost of a 31 % perioperative mortality rate. The use of ALPPS for HCC remains prohibitive for most patients and should be performed only for a highly selected patient population younger than 60 years with low-grade fibrosis.

Prognostic factors associated with clear cell sarcoma in 14 Chinese patients.

PURPOSE. To identify prognostic factors associated with clear cell sarcomas in 14 Chinese patients. METHODS. Medical records of 7 men and 7 women (mean age, 36 years) with histologically confirmed clear cell sarcoma of tendons and aponeuroses were reviewed. Patient demographics, tumour characteristics, and treatment modalities were retrieved. Prognostic factors associated with favourable 5-year survival were determined. RESULTS. The most affected sites were the thigh (n=5) and the foot (n=4); the mean time from symptom onset to diagnosis was 9.5 months. The tumour stage at diagnosis was IIA in 8 patients, IIB in 2, and III in 4. The mean tumour size was 4.5 cm in diameter. One patient was lost to follow-up. For the remaining 13 patients, the mean time to disease-related mortality was 2.5 years. Nine patients had distant metastases; the most common sites were lungs and pleura (n=7), followed by distant lymph nodes (n=4), bone (n=2), pericardium (n=2), and brain (n=1). All patients underwent surgical excision. Three women and one man (mean age, 27 years) attained 5-year disease-free survival. All had stage IIA tumours at diagnosis. Their mean tumour size was 1.75 cm in diameter, which was significantly smaller than that of all patients (4.5 cm). Tumour size of ≤ 2.5 cm in diameter (p=0.004) and stage IIA tumour at diagnosis (p=0.04) were significant prognostic factors for 5-year survival. CONCLUSION. Tumour size of ≤ 2.5 cm and early stage tumour are associated with 5-year disease-free survival. Early detection is crucial for the prognosis of clear cell sarcomas.

Natural killer T cell defects in multiple myeloma and the impact of lenalidomide therapy.

The causes of multiple myeloma (MM) remain obscure and there are few known risk factors; however, natural killer T (NKT) cell abnormalities have been reported in patients with MM, and therapeutic targeting of NKT cells is promoted as a potential treatment. We characterized NKT cell defects in treated and untreated patients with MM and determined the impact of lenalidomide therapy on the NKT cell pool. Lenalidomide is an immunomodulatory drug with co-stimulatory effects on NKT cells in vitro and is an approved treatment for MM, although its mode of action in that context is not well defined. We find that patients with relapsed/progressive MM had a marked deficiency in NKT cell numbers. In contrast, newly diagnosed patients had relatively normal NKT cell frequency and function prior to treatment, although a specific NKT cell deficiency emerged after high-dose melphalan and autologous stem cell transplantation (ASCT) regimen. This also impacted NK cells and conventional T cells, but the recovery of NKT cells was considerably delayed, resulting in a prolonged, treatment-induced NKT cell deficit. Longitudinal analysis of individual patients revealed that lenalidomide therapy had no in-vivo impact on NKT cell numbers or cytokine production, either as induction therapy, or as maintenance therapy following ASCT, indicating that its clinical benefits in this setting are independent of NKT cell modulation.

Non-occupational post-exposure prophylaxis for HIV at St Michael's Hospital, Toronto: a retrospective review of patient eligibility and clinical outcomes.

Stringent eligibility criteria, drug costs and antiretroviral toxicities are challenges in delivering HIV non-occupational post-exposure prophylaxis (nPEP). We reviewed patients' nPEP eligibility and clinical outcomes at St Michael's Hospital, Toronto, Canada to identify opportunities for improvement. Of 241 patients, 59%, 36% and 6% presented for high- (receptive anal/vaginal, blood), medium- (insertive anal/vaginal) and low-risk (oral) sexual exposures, respectively, and nearly all (93%) presented within 72 hours. Of 205 patients given nPEP, 20 were known to have discontinued nPEP prematurely: three due to costs but none due to toxicities. Two HIV seroconversions occurred in patients with suspected ongoing potential exposures. Five asymptomatic syphilis diagnoses were made among 71 tested. Only 39% and 19% of nPEP patients returned to our institution for follow-up at 3-4 and six months, respectively. Our findings underscore the feasibility and importance of nPEP programmes to HIV and sexually transmitted infection control, while identifying opportunities for improvement.

Chylous leakage post mastectomy and axillary clearance: clinical aspect, causes and review of literature.

Chylous leakage after mastectomy & axillary clearance is a rare complication. The incidence is less than 0.5%. Anatomical variations in the termination of thoracic duct can occur, rendering it susceptible to injury during axillary dissection. Most chyle leaks in the axilla are managed through conservative measures. Surgical intervention is required in high output chylous leaks. We encountered a case of chylous leak post mastectomy with axillary clearance, which was successfully treated conservatively.

Ex-vivo analysis of human natural killer T cells demonstrates heterogeneity between tissues and within established CD4(+) and CD4(-) subsets.

Our understanding of human type 1 natural killer T (NKT) cells has been heavily dependent on studies of cells from peripheral blood. These have identified two functionally distinct subsets defined by expression of CD4, although it is widely believed that this underestimates the true number of subsets. Two recent studies supporting this view have provided more detail about diversity of the human NKT cells, but relied on analysis of NKT cells from human blood that had been expanded in vitro prior to analysis. In this study we extend those findings by assessing the heterogeneity of CD4(+) and CD4(-) human NKT cell subsets from peripheral blood, cord blood, thymus and spleen without prior expansion ex vivo, and identifying for the first time cytokines expressed by human NKT cells from spleen and thymus. Our comparative analysis reveals highly heterogeneous expression of surface antigens by CD4(+) and CD4(-) NKT cell subsets and identifies several antigens whose differential expression correlates with the cytokine response. Collectively, our findings reveal that the common classification of NKT cells into CD4(+) and CD4(-) subsets fails to reflect the diversity of this lineage, and that more studies are needed to establish the functional significance of the antigen expression patterns and tissue residency of human NKT cells.

Examining the adverse effects of limb position on pattern recognition based myoelectric control.

Pattern recognition of myoelectric signals for the control of prosthetic devices has been widely reported and debated. A large portion of the literature focuses on offline classification accuracy of pre-recorded signals. Historically, however, there has been a semantic gap between research findings and a clinically viable implementation. Recently, renewed focus on prosthetics research has pushed the field to provide more clinically relevant outcomes. One way to work towards this goal is to examine the differences between research and clinical results. The constrained nature in which offline training and test data is often collected compared to the dynamic nature of prosthetic use is just one example. In this work, we demonstrate that variations in limb position after training can have a substantial impact on the robustness of myoelectric pattern recognition.