Cardiovascular outcomes and hospitalizations in Asian patients receiving immune checkpoint inhibitors: a population-based study.

Immune checkpoint inhibitors (ICI) have known associations with cardiotoxicity. However, a representative quantification of the adverse cardiovascular events and cardiovascular attendances amongst Asian users of ICI has been lacking. This retrospective cohort study identified all ICI users in Hong Kong, China, between 2013-2021. All patients were followed up until the end of 2021 for the primary outcome of major adverse cardiovascular event (MACE; a composite of cardiovascular mortality, myocardial infarction, heart failure, and stroke). Patients with prior diagnosis of any component of MACE were excluded from all MACE analyses. In total, 4324 patients were analysed (2905 (67.2%) males; median age 63.5 years old (interquartile range 55.4-70.7 years old); median follow-up 1.0 year (interquartile range 0.4-2.3 years)), of whom 153 were excluded from MACE analyses due to prior events. MACE occurred in 116 (2.8%) with an incidence rate (IR) of 1.7 [95% confidence interval: 1.4, 2.0] events per 100 patient-years; IR was higher within the first year of follow-up (2.9 [2.3, 3.5] events per 100 patient-years). Cardiovascular hospitalization(s) occurred in 188 (4.4%) with 254 episodes (0.5% of all episodes) and 1555 days of hospitalization (1.3% of all hospitalized days), for whom the IR of cardiovascular hospitalization was 5.6 [4.6, 6.9] episodes per 100 person-years with 52.9 [39.8, 70.3] days' stay per 100 person-years. Amongst Asian users of ICI, MACE was uncommon, and a small proportion of hospitalizations was cardiovascular in nature. Most MACE and cardiovascular hospitalizations occurred during the first year after initiating ICI. [Abstract copyright: Copyright © 2022. Published by Elsevier Inc.

Cardiovascular outcomes and hospitalizations in Asian patients receiving immune checkpoint inhibitors: A population-based study

Immune checkpoint inhibitors (ICI) have known associations with cardiotoxicity. However, a representative quantification of the adverse cardiovascular events and cardiovascular attendances amongst Asian users of ICI has been lacking. This retrospective cohort study identified all ICI users in Hong Kong, China, between 2013 and 2021. All patients were followed up until the end of 2021 for the primary outcome of major adverse cardiovascular event (MACE; a composite of cardiovascular mortality, myocardial infarction, heart failure, and stroke). Patients with prior diagnosis of any component of MACE were excluded from all MACE analyses. In total, 4324 patients were analyzed (2905 (67.2%) males; median age 63.5 years old (interquartile range 55.4-70.7 years old); median follow-up 1.0 year (interquartile range 0.4-2.3 years)), of whom 153 were excluded from MACE analyses due to prior events. MACE occurred in 116 (2.8%) with an incidence rate (IR) of 1.7 [95% confidence interval: 1.4, 2.0] events per 100 patient-years; IR was higher within the first year of follow-up (2.9 [2.3, 3.5] events per 100 patient-years). Cardiovascular hospitalization(s) occurred in 188 (4.4%) with 254 episodes (0.5% of all episodes) and 1555 days of hospitalization (1.3% of all hospitalized days), for whom the IR of cardiovascular hospitalization was 5.6 [4.6, 6.9] episodes per 100 person-years with 52.9 [39.8, 70.3] days’ stay per 100 person-years. Amongst Asian users of ICI, MACE was uncommon, and a small proportion of hospitalizations were cardiovascular in nature. Most MACE and cardiovascular hospitalizations occurred during the first year after initiating ICI

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Successful Treatment of Lasiodiplodia theobromae Keratitis – Assessing the Role of Voriconazole

Purpose: The aim of this paper is to report the successful management of the first case of Lasiodiplodia theobromae keratitis in Hong Kong. Methods: We conducted a case report. Results: A 43-year-old Chinese male with a history of diabetes developed left eye keratitis after a trauma during tree felling. Fungal keratitis was diagnosed using a confocal microscope on day 1, and L. theobromae was confirmed from the culture. He was given oral voriconazole, topical natamycin, and topical and intracameral amphotericin B. The patient’s condition improved after the initial treatment. However, there was a slow progression to descemetocele formation and impending perforation due to corneal melting. Penetrating keratoplasty was performed at 8 weeks after presentation. Final visual recovery was good with no recurrence of infection. The cornea remained clear. Conclusions: We report the first case of L. theobromae keratitis in Hong Kong, and it is the only case so far that involved the use of oral voriconazole in the combination therapy. Early recognition with the aid of confocal microscopy allowed the early start of treatment. The use of newer antifungal voriconazole topically and orally combined with topical amphotericin B appeared to be useful in the eradication of the fungus and prevention of recurrence. Intracameral antifungals might have improved the clinical management

Abnormal Response of the Proliferation and Differentiation of Growth Plate Chondrocytes to Melatonin in Adolescent Idiopathic Scoliosis

Abnormalities in the melatonin signaling pathway and the involvement of melatonin receptor MT2 have been reported in patients with adolescent idiopathic scoliosis (AIS). Whether these abnormalities were involved in the systemic abnormal skeletal growth in AIS during the peripubertal period remain unknown. In this cross-sectional case-control study, growth plate chondrocytes (GPCs) were cultured from twenty AIS and ten normal control subjects. Although the MT2 receptor was identified in GPCs from both AIS and controls, its mRNA expression was significantly lower in AIS patients than the controls. GPCs were cultured in the presence of either the vehicle or various concentrations of melatonin, with or without the selective MT2 melatonin receptor antagonist 4-P-PDOT (10 µM). Then the cell viability and the mRNA expression of collagen type X (COLX) and alkaline phosphatase (ALP) were assessed by MTT and qPCR, respectively. In the control GPCs, melatonin at the concentrations of 1, 100 nM and 10 µM significantly reduced the population of viable cells, and the mRNA level of COLX and ALP compared to the vehicle. Similar changes were not observed in the presence of 4-P-PDOT. Further, neither proliferation nor differentiation of GPCs from AIS patients was affected by the melatonin treatment. These findings support the presence of a functional abnormality of the melatonin signaling pathway in AIS GPCs, which might be associated with the abnormal endochondral ossification in AIS patients

Functional outcome after head injury: Comparison of 12-45 year old male and female hormonally active patients

Objectives: Head injury is the leading cause of death in patients with major trauma, but little is known of post-trauma rehabilitation morbidity in Hong Kong. The purpose of this study was to identify factors affecting functional outcome in hormonally active patients 6 months after head injury. Methods: Secondary analysis of the trauma registry database with data collected prospectively at two trauma centres between January 2001 and December 2007. Demographic and trauma data for patients aged 12–45 years with a head Abbreviated Injury Score ≥3 were analysed. The Glasgow outcome scale (GOS) was used for assessment and was assessed 6 months after head injury. The primary outcome measure was a composite poor outcome, namely “dead, vegetative and severely disabled” measured using the GOS. Results: Of 698 patients included in the study (mean age 29 years; range 12–45 years; 75.8% male), 581 (83.2%) had a good outcome, and 117 (16.8%) met the primary outcome measure, namely a poor outcome, including 88 (12.6%) patients who died. 453 (64.9%) patients had an injury severity score (ISS) of 16–40, and 102 (14.6%) patients had an ISS > 40. 220 (31.5%) patients underwent head injury related operation. The mean length of stay in the intensive care unit (ICU) was 3.9 days. Univariate analysis showed that high ISS, Emergency Department (ED) systolic blood pressure (SBP) > 160 mm Hg or 24/min, low ED Glasgow Coma Score (GCS), trauma call activation, head related operation and ICU admission were related to poor outcome. Multivariate analysis showed that high ISS, low or high ED SBP and low ED GCS were related to poor functional outcome. Conclusion: This study showed that ISS, ED SBP and ED GCS were related to poor functional outcome. Gender showed no statistically significant relationship with functional outcome

A prospective study of variations in conventional semen parameters among local andrology laboratories

Introduction: Wide variations in semen parameters exist among different andrology laboratories. This study sought to determine the inter- and intra-technician variations in conventional semen parameters among local andrology laboratories. Methods: Pooled semen samples were prepared and sent in two batches to participating andrology laboratories. One technician who routinely performed semen analysis in the participating laboratories was asked to analyze the study samples. The inter-technician and intra-technician coefficients of variation (CVs) were calculated. Information on the qualification and training of the participating technicians, the workload of the centers, their techniques and participation in external quality assurance programs were collected and correlated with the CVs. Results: Eleven andrology laboratories participated in the study. The inter-technician CVs ranged from 14.3% to 44.1% for concentration, 13.8% to 26.2% for progressive motility, and 38.8% to 95.3% for morphology. Andrology laboratories which participated in external quality assurance programs had lower inter-technician CVs for concentration (P = 0.004) and progressive motility (P = 0.002), but not for morphology (P = 0.232). Technicians with more experience or higher workload did not demonstrate lower intra-technician CVs. Conclusion: There were considerable inter- and intra- technician variations in the assessment of sperm concentration, progressive motility and morphology among local andrology laboratories, independent of the workload and experience of the technicians. Participation in external quality assurance programs reduced inter-technician variations in sperm concentration and progressive motility but not morphology