Bacterial infections in patients with COVID-19: the impact of procalcitonin testing on antibiotics prescription in the real world.

BACKGROUND: Bacterial infections are not prevalent among patients hospitalized with COVID-19, while unnecessary prescription of antibiotics was commonly observed. This study aimed to determine the impact of procalcitonin testing on antibiotics prescription in the real-world setting. METHODS: We performed a territory-wide retrospective cohort study involving all laboratory-confirmed patients hospitalized in public hospitals in Hong Kong in 2020 with COVID-19. We determined the prevalence of bacterial co-infections (documented infections within 72 h of admission) and secondary bacterial infections (infections after 72 h of admission) and antibiotics consumption, and the correlation between procalcitonin testing and antibiotics prescription. RESULTS: The cohort included 8666 patients, with mean age 45.3 ± 19.9 years, 48.5% male, and comorbidities in 26.9%. Among 2688 patients with bacterial cultures performed, 147 (5.5%) had bacterial co-infections, and 222 (8.3%) had secondary bacterial infections. Antibiotics were prescribed for 2773 (32.0%) patients during the hospital admission. Procalcitonin tests were performed for 2543 (29.3%) patients. More patients with procalcitonin testing received antibiotics (65.9% vs. 17.9%, p < 0.001). Procalcitonin testing was associated with 5-fold increased risk of antibiotics prescription after adjusting for confounding variables. At hospital level, procalcitonin testing correlated with antibiotics prescription. Patients with procalcitonin level < 0.5 ng/mL had a lower probability of antibiotics initiation and shorter duration of antibiotics therapy. CONCLUSIONS: Procalcitonin testing was not associated with lower prescription of antibiotics. Patients with low procalcitonin level had lower antibiotics exposure, supporting the use of procalcitonin to exclude bacterial infections aiding early stopping of antibiotics among patients hospitalized with COVID-19.

Safety Profile and Clinical and Virological Outcomes of Nirmatrelvir-Ritonavir Treatment in Patients With Advanced Chronic Kidney Disease and Coronavirus Disease 2019.

BACKGROUND: Nirmatrelvir-ritonavir is currently not recommended in patients with an estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2. METHODS: To determine the safety profile and clinical and virological outcomes of nirmatrelvir-ritonavir use at a modified dosage in adults with chronic kidney disease (CKD), a prospective, single-arm, interventional trial recruited patients with eGFR <30 mL/minute/1.73 m2 and on dialysis. Primary outcomes included safety profile, adverse/serious adverse events, and events leading to drug discontinuation. Disease symptoms, virological outcomes by serial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral polymerase chain reaction (PCR) tests, rapid antigen tests, and virological and symptomatic rebound were also recorded. RESULTS: Fifty-nine (69.4%) of the 85 participants had stage 5 CKD and were on dialysis. Eighty (94.1%) completed the full treatment course; 9.4% and 5.9% had adverse and serious adverse events, and these were comparable between those with eGFR < or >30 mL/minute/1.73 m2. The viral load significantly decreased on days 5, 15, and 30 (P < .001 for all), and the reduction was consistent in the subgroup with eGFR <30 mL/minute/1.73 m2. Ten patients had virological rebound, which was transient and asymptomatic. CONCLUSIONS: Among patients with CKD, a modified dose of nirmatrelvir-ritonavir is a well-tolerated therapy in mild COVID-19 as it can effectively suppress the SARS-CoV-2 viral load with a favorable safety profile. Virological and symptomatic rebound, although transient with low infectivity, may occur after treatment. Nirmatrelvir-ritonavir should be considered for use in patients with CKD, including stage 5 CKD on dialysis. Clinical Trials Registration. Clinical Trials.gov; identifier: NCT05624840.

Incidence of hepatocellular carcinoma and mortality in chronic viral hepatitis in an Asian population with and without HIV infection.

BACKGROUND: It is uncertain whether people with HIV infection have a higher incidence of hepatocellular carcinoma (HCC) than the general population. AIMS: To compare the incidence of HCC between people infected with HBV and/or HCV with and without HIV METHODS: We performed a retrospective population-based cohort study, involving people with HBV and/or HCV infection from 2001 to 2018. The primary endpoint was incidence of HCC; secondary endpoint was all-cause mortality. We performed Cox proportional hazard regression models to estimate the hazard ratios (HR) of HIV for the primary and secondary endpoints. RESULTS: We identified 1374 people infected with HIV and 39,908 people without HIV with HBV and/or HCV infection. Among those with HIV, 654 (47.6%) had HBV, 649 (47.2%) HCV and 71 (5.2%) HBV-HCV-co-infection; they were younger, and had a higher prevalence of HCV and a lower prevalence of cirrhosis. The incidence rate estimates of HCC were, respectively, 1.5 (95% CI: 0.8-2.5) and 7.6 (95% CI 7.3-8.0) per 1000 person-years for those with and without HIV infection. Using multivariate Cox proportional hazard regression models, among people with HBV, HIV was associated with lower risk of HCC (adjusted HR: 0.376, 95% CI: 0.201-0.704, p = 0.01) and death (adjusted HR: 0.692, 95% CI: 0.552-0.867, p = 0.007). Risks of HCC were similar for HCV and HBV-HCV co-infection for people with and without HIV. CONCLUSIONS: Among individuals with HBV infection, the Incidence of HCC was lower in those with HIV. For HCV infection, incidence of HCC was similar between those with and without HIV.

Erythrocytosis and thrombotic events in kidney transplant recipients prescribed a sodium glucose cotransport-2 inhibitor.

INTRODUCTION: The safety and efficacy of sodium glucose cotransport-2 inhibitors (SGLT2i) in kidney transplant recipients remains uncertain. Transplant recipients may be at risk of thrombosis because of post-transplant erythrocytosis and SGLT2i are associated with an increase in hematocrit. METHODS: We determined SGLT2i use, the change in hematocrit and incidence of thrombotic events in kidney transplant recipients in 1700 prevalent patients in our center. RESULTS: Among the 42 patients treated with SGLT2i, the mean pre-transplant hematocrit was 31%, and none of the patients had a hematocrit ≥50%. The mean percent change in hematocrit measured at an average of 53 days after initiation of an SGLT2i was 11% and four patients (10%) had a hematocrit ≥ 50%. The mean hematocrit measured 3 months after treatment was 42% and two patients (5%) had a hematocrit ≥50%. One patient had a cerebellar stroke 14 months post-SGLT2i initiation when the hemoglobin was 173 grams/liter, and the hematocrit was 52%. CONCLUSIONS: All patients had a sustained increase in hematocrit 3 months after SGLT2i treatment. Hematocrit ≥50% occurred in 10%, and one patient had a thrombotic event that may or may not have been related to an increase in hematocrit. Clinicians may consider monitoring for erythrocytosis after starting and SGLT2i in kidney transplant recipients.

Use of sodium-glucose co-transporter 2 inhibitors in solid organ transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus: A systematic review.

INTRODUCTION: Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitors have demonstrated kidney, cardiovascular and mortality benefits in the general population; however, the evidence is limited in solid organ transplant recipients. The aim of this systematic review was to evaluate the current efficacy and safety data of SGLT2 inhibitors in adult kidney, heart, lung, and liver transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus. METHOD: We searched MEDLINE, MEDLINE Epub, CENTRAL, CDSR, EMBASE, CINAHL, and sources of unpublished literature. All primary interventional and observational studies on SGLT2 inhibitors in transplant recipients were included. Clinical outcomes included mortality, cardiovascular and kidney events, and adverse events such as graft rejection. Surrogate markers including hemoglobin A1c (HbA1c) and weight reduction were also evaluated. RESULTS: Of the 17 studies that were included in this systematic review, there were 15 studies on kidney transplant recipients (n = 2417 patients) and two studies on heart transplant recipients (n = 122 patients). There was only one randomized controlled trial which evaluated 49 kidney transplant patients over 24 weeks. Overall, studies were heterogeneous in study design, sample size, duration of diabetes, time to SGLT2 inhibitor initiation post-transplantation (ranging from 0.88 to 11 years post kidney transplant; five to 5.7 years post heart transplant) and follow-up (ranging from 0.4 to 5.25 years in kidney transplant patients; 0.75 to one year in heart transplant patients). Only one retrospective study evaluated mortality as a part of a composite outcome in kidney transplant patients; however, study limitations restrict generalizability of results. Overall, studies could not confirm clinical cardiovascular and kidney benefits in the transplant population. Findings suggested that SGLT2 inhibitors may improve glycemic control; however, they are associated with urinary tract infection. Diabetic ketoacidosis and acute kidney injury also occurred in these studies, with precipitating factors such as infection and acute heart failure exacerbation. CONCLUSIONS: While SGLT2 inhibitors are promising agents with expanding indications in the non-transplant population, these agents may not be suitable for all solid organ transplant recipients, and close monitoring (e.g. for urinary tract infections) and patient education (e.g. sick day management) are essential if these agents are initiated. Evidence is based on short-term findings and suggests an association with hemoglobin A1c reduction and increased adverse events. Further long-term randomized controlled trials are needed to evaluate the effect of SGLT2 inhibitors on clinically important outcomes, including mortality reduction, in solid organ transplant recipients.

Histo-blood group antigens and rotavirus vaccine virus shedding in Australian infants.

Rotavirus vaccine performance varies between high and low income countries. One possible explanation is inherited histo-blood group antigens (HBGAs) the expression of which differs between populations. HBGAs are polymorphic glycans on mucosal surfaces. Their presence indicates the secretor phenotype, while their absence identifies a non-secretor status. HBGAs can act as rotavirus receptors and might influence live-attenuated rotavirus vaccine virus replication and shedding. Studies in low and middle income countries of the human rotavirus vaccine Rotarix (RV1), suggest HBGA secretor phenotype is important for vaccine immunogenicity. We investigated in a high income country the association between HBGA phenotype (secretor and Lewis) and the bovine-human reassortment vaccine RotaTeq (RV5) vaccine shedding in the stools of infants following each vaccine dose. Eighty-two infants from an Australian birth cohort provided saliva and weekly stool samples after RV5 vaccination doses. Lewis and secretor HBGA phenotyping was identified from saliva samples and confirmed by genotyping. Vaccine virus strains were detected by real-time polymerase chain reaction assays. No significant association between secretor status and vaccine virus shedding was identified. The proportion of infants who shed rotavirus following the first RV5 dose for secretor and non-secretor infants was 57/64 (89%) and 17/18 (94%), respectively, decreasing to 24/64 (33%) and 9/18 (50%) after the second dose and 26/64 (42%) and 8/18 (44%) following the third vaccine dose, respectively. Similarly, no significant differences were observed in vaccine virus shedding by Lewis, or combined Lewis and secretor status, after each vaccine dose. We found HBGAs were not associated with RV5 vaccine virus shedding in Australian infants.

Seven-year excess mortality, functional outcome and health status after trauma in Hong Kong.

PURPOSE: The purpose was to investigate long-term health impacts of trauma and the aim was to describe the functional outcome and health status up to 7 years after trauma. METHODS: We conducted a prospective, multi-centre cohort study of adult trauma patients admitted to three regional trauma centres with moderate or major trauma (ISS ≥ 9) in Hong Kong (HK). Patients were followed up at regular time points (1, 6 months and 1, 2, 3, 4, 5, 6, and 7 years) by telephone using extended Glasgow Outcome Scale (GOSE) and the Short-Form 36 (SF36). Observed annual mortality rate was compared with the expected mortality rate estimated using the HK population cohort. Linear mixed model (LMM) analyses examined the changes in SF36 with subgroups of age ≥ 65 years, ISS > 15, and GOSE ≥ 5 over time. RESULTS: At 7 years, 115 patients had died and 48% (138/285) of the survivors responded. The annual mortality rate (AMR) of the trauma cohort was consistently higher than the expected mortality rate from the general population. Forty-one percent of respondents had upper good recovery (GOSE = 8) at 7 years. Seven-year mean PCS and MCS were 45.06 and 52.06, respectively. LMM showed PCS improved over time in patients aged < 65 years and with baseline GOSE ≥ 5, and the MCS improved over time with baseline GOSE ≥ 5. Higher mortality rate, limited functional recovery and worse physical health status persisted up to 7 years post-injury. CONCLUSION: Long-term mortality and morbidity should be monitored for Asian trauma centre patients to understand the impact of trauma beyond hospital discharge.

Patient-reported outcome measures for life participation in peritoneal dialysis: a systematic review.

BACKGROUND: Patients receiving peritoneal dialysis (PD) endure an ongoing regimen of daily fluid exchanges and are at risk of potentially life-threatening complications and debilitating symptoms that can limit their ability to participate in life activities. The aim of the study was to identify the characteristics, content and psychometric properties of measures for life participation used in research in PD. METHODS: We searched MEDLINE, Embase, PsychInfo, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Central Register of Controlled Trials from inception to May 2020 for all studies that reported life participation in patients on PD. The characteristics, dimensions of life participation and psychometric properties of these measures were extracted and analyzed. RESULTS: Of the 301 studies included, 17 (6%) were randomized studies and 284 (94%) were nonrandomized studies. Forty-two different measures were used to assess life participation. Of these, 23 (55%) were used in only one study. Fifteen (36%) measures were specifically designed to assess life participation, while 27 (64%) measures assessed broader constructs, such as quality of life, but included questions on life participation. The 36-Item Short Form Health Survey and Kidney Disease Quality of Life Short Form were the most frequently used measures [122 (41%) and 86 (29%) studies, respectively]. Eight (19%) measures had validation data to support their use in patients on PD. CONCLUSIONS: The many measures currently used to assess life participation in patients receiving PD vary in their characteristics, content and validation. Further work to pilot and validate potential measures is required to establish a core patient-reported outcome measure to assess life participation in patients receiving PD.

Direct Oral Anticoagulant Use in Chronic Kidney Disease and Dialysis Patients With Venous Thromboembolism: A Systematic Review of Thrombosis and Bleeding Outcomes.

OBJECTIVE: To evaluate how treatment with DOACs for VTE affects thrombosis and bleeding outcomes compared to warfarin in CKD and dialysis patients. DATA SOURCES: A literature search was conducted for studies evaluating VTE and bleeding outcomes with DOAC use in CKD and dialysis patients. Searches conducted through EMBASE, MEDLINE/PubMed, Scopus, and Cochrane Central Register of Controlled Trials, from inception to September 22, 2020. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials, cohort studies, and case series with ≥10 patients included. DATA SYNTHESIS: From 7286 studies, nine studies met inclusion criteria. There was no significant difference between DOACs (dabigatran, rivaroxaban, apixaban) and warfarin for reducing recurrent VTE and bleeding events in moderate CKD patients. The risk of overall major bleeding increased when the degree of kidney impairment increased. There was no significant difference between apixaban and warfarin for VTE outcomes in dialysis patients. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: There continues to be a controversial debate whether it may be more beneficial to use DOACs versus warfarin in CKD/dialysis patients with venous thromboembolism (VTE). The risk vs benefit of using DOACs in the CKD/ESKD population should continue to be evaluated for each individual patient. CONCLUSION: Apixaban may be used cautiously as an alternative in acute VTE treatment in severe CKD patients. Insufficient evidence is available to suggest the use of dabigatran and rivaroxaban in this patient population. The benefit of using DOACs in this population for VTE treatment should be weighed against the potential bleeding risk in patients with CKD.

Dissociable effects of subthalamic nucleus deep brain stimulation surgery and acute stimulation on verbal fluency in Parkinson's disease.

OBJECT: Verbal fluency (VF) is the cognitive test which shows the most consistent and persistent post-operative decline after subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD). However, the reasons are not completely understood, and the debate has focused on two hypotheses: a surgical effect or an acute STN-DBS effect. METHODS: We recruited 3 PD samples: (1) a group assessed before and after STN-DBS surgery (2) a group assessed On vs. Off STN-DBS and (3) an unoperated PD control group. All groups performed letter, category and switching category VF tasks. The total number of correct words generated were noted and measures of clustering and switching were also obtained. RESULTS: We found a significant effect of STN-DBS surgery on all VF tasks which was associated with a post-operative decline in the total number of words generated, and a reduction of phonemic switching during the letter and category VF tasks, and a reduction of semantic clustering for category VF. By contrast to the effects of surgery, acute On vs. Off stimulation did not influence the number of words generated on any of the VF tasks. Acute stimulation only produced two effects on the category VF task: increased semantic cluster size and decreased number of semantic switches when STN-DBS was switched On. CONCLUSIONS: This study differentiates between the effects of STN-DBS surgery and acute stimulation on VF performance. Our findings indicate that the STN-DBS effect on VF are a surgical and not an acute STN stimulation effect.

Social Decision Making in Autistic Adolescents: The Role of Theory of Mind, Executive Functioning and Emotion Regulation.

Social decision making is often challenging for autistic individuals. Twenty autistic adolescents made decisions in the socially interactive context of a one-shot ultimatum game, and performance was compared to a large matched typical reference sample. Theory of mind, executive functioning and emotion regulation were measured via direct assessments, self- and parent report. Relative to the reference sample, autistic adolescents proposed fewer fair offers, and this was associated with poorer theory of mind. Autistic adolescents responded similarly to the reference sample when making decisions about offers proposed to them, however they did not appear to down regulate their negative emotion in response to unfair treatment in the same way. Atypical processes may underpin even apparently typical decisions made by autistic adolescents.

Trauma team activation criteria and outcomes of geriatric trauma: 10 year single centre cohort study.

BACKGROUND: With the aging population, the number of older patients with multiple injuries is increasing. The aim of this study was to understand the patterns and outcomes of older patients admitted to a major trauma centre in Hong Kong from 2006 to 2015, and investigate the performance of the trauma team activation (TTA) criteria for these elderly patients. METHODS: This was a retrospective cohort study from a university hospital major trauma centre in Hong Kong from 2006 to 2015. Patients aged 55 or above who entered the trauma registry were included. Patients were divided into those aged 55-70, and above 70. To test the performance of the TTA criteria, we defined injured patients with severe outcomes as those having any of the following: death within 30 days; the need for surgery; or the need for intensive care unit (ICU) care. RESULTS: 2218 patients were included over the 10 year period. The 30-day mortality was 7.5% for aged 55-70 and 17.7% for those aged above 70. The sensitivity of TTA criteria for identifying severe outcomes for those aged 55 or above was 35.6%, with 91.6% specificity. The under-triage rate was 59% for age 55-70, and 69.1% for those aged above 70. CONCLUSION: There is a need to consider alternative TTA criteria for our geriatric trauma population, and to more clearly define the process and standards of care in Hong Kong.

Ribavirin-induced anaemia reduced tacrolimus level in a hepatitis C patient receiving haemodialysis.

A 37-year-old man with hepatitis C virus (HCV) genotype 3A developed renal failure. In 2007, the patient received a renal transplant and started receiving tacrolimus (Tac); the transplant subsequently failed. In April 2015, the patient restarted haemodialysis and in May initiated sofosbuvir 400 mg and ribavirin 400 mg daily. Baseline Tac level was 6.6 ng/mL and haemoglobin (Hb) was 10.3 g/dL. The patient then left the country for vacation and Hb was found to be dramatically low at 3.7 g/dL on return on 5 August. Ribavirin was put on hold, while darbepoetin dose was increased. On 23 August, Tac level was found undetectable; hence, dosage was increased. Hb eventually bounced back to >10 g/dL in October and Tac to 7.2 ng/mL; ribavirin was restarted at 200 mg three times weekly. HCV RNA level was undetectable at 3 months and remained undetectable 12 weeks after therapy finished.

Brief Report: Progression of Atherosclerosis in HIV-Infected Individuals-Prospective Data From an Asian Cohort.

BACKGROUND: The magnitude and risk factors of progression of atherosclerosis in Asian HIV-infected individuals were unknown. This study aimed to evaluate: (1) the rate of progression of atherosclerosis in HIV-infected individuals, and (2) metabolic and inflammatory parameters that may predict atherosclerosis progression in HIV-infected individuals in an Asian cohort. SETTING: A prospective, longitudinal study was performed among adults attending an HIV Metabolic clinic in Hong Kong. METHODS: Carotid intima media thickness (cIMT) was measured at baseline and 24 months. Body composition, metabolic, and inflammatory biomarkers [including homeostasis model assessment of insulin resistance, LDL (low-density lipoprotein) cholesterol particle size, high-sensitive C reactive protein, adiponectin] associated with cIMT change were analyzed; their predictive performances were estimated using receiver operating characteristic analyses. RESULTS: Sixty-one HIV-infected individuals (mean ± SD age 49.8 ± 11.4 years, 89% men, 97% Chinese, diabetes 39%, hypertension 30%, and dyslipidemia 85%) were recruited. Annual rate of change of cIMT was +0.0075 (0.0000-0.0163) mm/yr, and 19% developed new plaque at 24 months. Two patients died during the study period, 1 because of sudden cardiac death. Using receiver operating characteristic analyses, combination of lower limb fat percentage, LDL cholesterol subclass pattern B, and lower adiponectin level, but not Framingham score, predicted greater cIMT progression in HIV-infected individuals. CONCLUSIONS: Asian HIV-infected individuals had atherosclerosis progression. Limb fat percentage, LDL cholesterol particle size, and adiponectin level may identify at-risk Asian HIV-infected individuals for early intervention.

Anti-inflammatory effects of adjunctive macrolide treatment in adults hospitalized with influenza: A randomized controlled trial.

INTRODUCTION: - Macrolides can ameliorate inflammation in respiratory diseases, providing clinical benefits. Data in influenza is lacking. METHOD: - A randomized, open-label, multicenter trial among adults hospitalized for laboratory-confirmed influenza was conducted. Study treatments of oseltamivir and azithromycin (500 mg/day), or oseltamivir alone, both for 5 days, were allocated at 1:1 ratio. The primary outcome was plasma cytokine/chemokine concentration change over time (Day 0-10); secondary outcomes were viral load and symptom score changes. Generalized Estimating Equation (GEE) models were used to analyze longitudinal data. RESULTS: - Fifty patients were randomized to the oseltamivir-azithromycin or oseltamivir groups, with comparable baseline characteristics (age, 57 ± 18 years; A/H3N2, 70%), complications (72%), and viral load. Pro-inflammatory cytokines IL-6 (GEE: ß -0.037, 95%CI-0.067,-0.007, P = 0.016; reduction from baseline -83.4% vs -59.5%), CXCL8/IL-8 (ß -0.018, 95%CI-0.037,0.000, P = 0.056; -80.5% vs -58.0%), IL-17 (ß -0.064, 95%CI-0.117,-0.012, P = 0.015; -74.0% vs -34.3%), CXCL9/MIG (ß -0.010, 95%CI-0.020,0.000, P = 0.043; -71.3% vs -56.0%), sTNFR-1, IL-18, and CRP declined faster in the oseltamivir-azithromycin group. There was a trend toward faster symptom resolution (ß -0.463, 95%CI-1.297,0.371). Viral RNA decline (P = 0.777) and culture-negativity rates were unaffected. Additional ex vivo studies confirmed reduced induction of IL-6 (P = 0.017) and CXCL8/IL-8 (P = 0.005) with azithromycin. CONCLUSION: - We found significant anti-inflammatory effects with adjunctive macrolide treatment in adults with severe influenza infections. Virus control was unimpaired. Clinical benefits of a macrolide-containing regimen deserve further study. [ClinicalTrials.gov NCT01779570].

Older Adults, Falls, and Skin Integrity.

GENERAL PURPOSE: To provide an overview of the assessment and management of risk factors for falls in older adults. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant should be better able to:1. Outline the components of an evidence-based falls assessment and identify risk factors for falls.2. Specify strategies to reduce falls in older adults, especially as related to maintaining skin integrity. ABSTRACT: Older adult patients may present to skin and wound care clinicians with skin injuries as a result of falls. In addition, chronic wounds associated with the patient's conditions may also increase his/her falls risk. Hence, appropriate assessment and management of the risk of falls in older adult patients are key elements of patient-centered care.

Surgical options for Chinese patients with early invasive breast cancer: Data from the Hong Kong Breast Cancer Registry.

BACKGROUND: Breast conserving surgery (BCS) is preferred for suitable candidates, while mastectomy (MTX) with reconstruction (MTX + R) is considered a better option for patients requiring MTX. In Hong Kong, the rates of BCS and breast reconstruction are relatively low. This paper aims to study the surgical options and their predictors among Hong Kong breast cancer patients. METHODS: Data is retrieved from the Hong Kong Breast Cancer Registry (HKBCR) from 2007 to 2013. A total of 4519 Stage I-II breast cancer patients who had surgical treatments were included in this retrospective study. RESULTS: Our multivariate logistic regression shows that people who were younger (age < 40 years: OR, 1.5; 95% CI, 1.1-2.1; p = 0.010), more educated (undergraduate/postgraduate: OR, 2.8; 95% CI, 1.7-4.4; p < 0.0001), never married (OR, 1.5; 95% CI, 1.1-1.9; p = 0.002), had regular mammography screening (OR, 1.5; 95% CI, 1.3-1.8; p < 0.0001), had screen-detected cancers (OR, 1.3; 95% CI, 1.0-1.6; p = 0.031), and who underwent surgery at a private medical service facility (OR, 1.8; 95% CI, 1.6-2.2; p < 0.0001) were more likely to receive BCS. In addition, people who were younger (age < 40 years: OR, 15.9; 95% CI, 6.5-39.2; p < 0.0001), more educated (undergraduate/postgraduate: OR, 26.8; 95% CI, 3.6-201.4; p = 0.001), had regular mammography screening (OR, 1.6; 95% CI, 1.1-2.3; p = 0.008), had screen-detected cancers (OR, 2.1; 95% CI, 1.4-3.3; p = 0.001), and had smaller tumor (≤ 2.0 cm: OR, 0.39; 95% CI, 0.20-0.76; p = 0.005) were more likely to have reconstruction after MTX. CONCLUSION: Chinese patients have lower BCS and breast reconstruction rate. Besides cultural difference, patient-related factors such as age, education, marital status, mammography screening, the use of private medical facilities, and clinical characteristics including smaller tumor size and peripherally located tumor were significant predictors for type of surgical treatments in Chinese women with early breast cancer.

HMGB1/RAGE Signaling and Pro-Inflammatory Cytokine Responses in Non-HIV Adults with Active Pulmonary Tuberculosis.

BACKGROUND: We aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1) / Receptor-for-Advanced-Glycation-End-products (RAGE) signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB). METHODS: A prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80); age-and-sex matched asymptomatic individuals (tested for latent TB) were used for comparison (n = 45). Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA) of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients' PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan) for cytokine induction ex vivo. RESULTS: In active PTB, plasma IL-8/CXCL8 [median(IQR), 6.0(3.6-15.1) vs 3.6(3.6-3.6) pg/ml, P<0.001] and IL-6 were elevated, which significantly correlated with mycobacterial load, extent of lung consolidation (rs +0.509, P<0.001), severity-score (rs +0.317, P = 0.004), and fever and hospitalization durations (rs +0.407, P<0.001). IL-18 and sTNFR1 also increased. Plasma IL-8/CXCL8 (adjusted OR 1.12, 95%CI 1.02-1.23 per unit increase, P = 0.021) and HMGB1 (adjusted OR 1.42 per unit increase, 95%CI 1.08-1.87, P = 0.012) concentrations were independent predictors for respiratory failure, as well as for ICU admission/death. Gene expression of HMGB1, RAGE, and inflammasome-NALP3 were upregulated (1.2-2.8 fold). Transmembrane-RAGE was increased, whereas the decoy soluble-RAGE was significantly depleted. RAGE and HMGB1 gene expressions positively correlated with cytokine levels (IL-8/CXCL8, IL-6, sTNFR1) and clinico-/radiographical severity (e.g. extent of consolidation rs +0.240, P = 0.034). Ex vivo, recombinant-HMGB1 potentiated cytokine release (e.g. TNF-α) when combined with lipoarabinomannan. CONCLUSION: In patients with active PTB, HMGB1/RAGE signaling and pro-inflammatory cytokines may play important roles in pathogenesis and disease manifestations. Our clinico-immunological data can provide basis for the development of new strategies for disease monitoring, management and control.

High morbidity and mortality of Clostridium difficile infection and its associations with ribotype 002 in Hong Kong.

OBJECTIVES: We aim to study the disease burden, risk factors and severity of Clostridium difficile infection (CDI) in Hong Kong. METHODS: We conducted a prospective, case-control study in three acute-care hospitals in Hong Kong. Adult inpatients who developed CDI diarrhoea confirmed by PCR (n = 139) were compared with the non-CDI controls (n = 114). Ribotyping of isolates and antimicrobial susceptibility testing were performed. RESULTS: The estimated crude annual incidence of CDI was 23-33/100,000 population, and 133-207/100,000 population among those aged ≥65 years. The mean age of CDI patients was 71.5. Nursing home care, recent hospitalization, antibiotics exposure (adjusted OR 3.0, 95% CI 1.3-7.1) and proton-pump inhibitors use (adjusted OR 2.2, 95% CI 1.2-3.9) were risk factors. Severe CDI occurred in 41.7%. Overall mortality was 16.5% (among severe CDI, 26.5%). The commonest ribotypes were 002 (22.8%), 014 (14.1%), 012 and 046; ribotype 027 was absent. Ribotype 002 was associated with fluoroquinolone resistance and higher mortality (47.6% vs. 12.7%; adjusted HR 2.8, 95% CI 1.1-7.0). CONCLUSIONS: Our findings show high morbidity and mortality of CDI in the older adults, and identify ribotype 002 as a possible virulent strain causing serious infections in this cohort.