Risk of Seizure Aggravation after COVID-19 Vaccinations in Patients with Epilepsy.

Although Coronavirus disease 2019 (COVID-19) vaccinations are generally recommended for persons with epilepsy (PwE), a significant vaccination gap remains due to patient concerns over the risk of post-vaccination seizure aggravation (PVSA). In this single-centre, retrospective cohort study, we aimed to determine the early (7-day) and delayed (30-day) risk of PVSA, and to identify clinical predictors of PVSA among PwE. Adult epilepsy patients aged ≥18 years without a history of COVID-19 infection were recruited from a specialty epilepsy clinic in early 2022. Demographic, epilepsy characteristics, and vaccination data were extracted from a centralized electronic patient record. Seizure frequency before and after vaccination, vaccination-related adverse effects, and reasons for or against vaccination were obtained by a structured questionnaire. A total of 786 PwEs were included, of which 27.0% were drug-resistant. At the time of recruitment, 74.6% had at least 1 dose of the COVID-19 vaccine. Subjects with higher seizure frequency (p < 0.0005), on more anti-seizure medications (p = 0.004), or had drug-resistant epilepsy (p = 0.001) were less likely to be vaccinated. No significant increase in seizure frequency was observed in the early (7 days) and delayed phases (30 days) after vaccination in our cohort. On the contrary, there was an overall significant reduction in seizure frequency 30 days after vaccination (1.31 vs. 1.89, t = 3.436; p = 0.001). This difference was seen in both types of vaccine (BNT162b2 and CoronaVac) and drug-resistant epilepsy, but just missed significance for the second dose (1.13 vs. 1.87, t = 1.921; p = 0.055). Only 5.3% had PVSA after either dose of vaccine. Higher pre-vaccination seizure frequency of ≥1 per week (OR 3.01, 95% CI 1.05-8.62; p = 0.04) and drug-resistant status (OR 3.32, 95% CI 1.45-249 7.61; p = 0.005) were predictive of PVSA. Meanwhile, seizure freedom for 3 months before vaccination was independently associated with a lower risk of PVSA (OR 0.11, 95% CI 0.04-0.28; p < 0.0005). This may guide epilepsy treatment strategies to achieve better seizure control for at least 3 months prior to vaccination. As COVID-19 shifts to an endemic phase, this study provides important data demonstrating the overall safety of COVID-19 vaccinations among PwE. Identification of high-risk patients with subsequent individualized approaches in treatment and monitoring strategies may alleviate vaccination hesitancy among PwE.

Association between time to surgery and hospital mortality in patients with community-acquired limb necrotizing fasciitis: an 11-year multicenter retrospective cohort analysis.

BACKGROUND: Necrotizing fasciitis (NF) is a rare but potentially life-threatening soft tissue infection. The objective of this study was to assess the association between timely surgery within 6 h and hospital mortality in patients with limb NF, and to describe the trends in patients with NF, time to surgery and standardized mortality ratio (SMR) over 11 years. METHODS: This was a multicenter, retrospective cohort study of all intensive care unit patients who had emergency surgery within 24 h of hospitalization for limb NF between April 1, 2008 and March 31, 2019 in Hong Kong. Timely surgery was defined as the first surgical treatment within 6 h of initial hospitalization. Appropriate antibiotics were achieved if the patient was given antibiotic(s) for all documented pathogens prior to or on day of culture results. The primary outcome was hospital mortality. RESULTS: There were 495 patients (median age 62 years, 349 (70.5%) males) with limb NF treated by surgery within 24 h of hospitalization over the 11 years. Appropriate antibiotic(s) were used in 392 (79.2%) patients. There were 181 (36.5%) deaths. Timely surgery was not associated with hospital mortality (Relative Risk 0.89, 95% CI: 0.73 to 1.07) but admission year, advanced age, higher severity of illness, comorbidities, renal replacement therapy, vasopressor use, and type of surgery were significant predictors in the multivariable model. There was an upward trend in NF diagnosis (1.9 cases/year, 95% CI: 0.7 to 3.1; P < 0.01; R2 = 0.60) but there was no downward trend in median time to surgery (-0.2 h/year, 95% CI: -0.4 to 0.1; P = 0.16) or SMR (-0.02/year, 95% CI: -0.06 to 0.01; P = 0.22; R2 = 0.16). CONCLUSIONS: Among patients operated within 24 h, very early surgery within 6-12 h was not associated with survival. Increasing limb NF cases were reported each year but mortality remained high despite a high rate of appropriate antibiotic use and timely surgical intervention.

Characteristics and outcomes of patients admitted to adult intensive care units in Hong Kong: a population retrospective cohort study from 2008 to 2018.

BACKGROUND: Globally, mortality rates of patients admitted to the intensive care unit (ICU) have decreased over the last two decades. However, evaluations of the temporal trends in the characteristics and outcomes of ICU patients in Asia are limited. The objective of this study was to describe the characteristics and risk adjusted outcomes of all patients admitted to publicly funded ICUs in Hong Kong over a 11-year period. The secondary objective was to validate the predictive performance of Acute Physiology And Chronic Health Evaluation (APACHE) IV for ICU patients in Hong Kong. METHODS: This was an 11-year population-based retrospective study of all patients admitted to adult general (mixed medical-surgical) intensive care units in Hong Kong public hospitals. ICU patients were identified from a population electronic health record database. Prospectively collected APACHE IV data and clinical outcomes were analysed. RESULTS: From 1 April 2008 to 31 March 2019, there were a total of 133,858 adult ICU admissions in Hong Kong public hospitals. During this time, annual ICU admissions increased from 11,267 to 14,068, whilst hospital mortality decreased from 19.7 to 14.3%. The APACHE IV standard mortality ratio (SMR) decreased from 0.81 to 0.65 during the same period. Linear regression demonstrated that APACHE IV SMR changed by - 0.15 (95% CI - 0.18 to - 0.11) per year (Pearson's R = - 0.951, p < 0.001). Observed median ICU length of stay was shorter than that predicted by APACHE IV (1.98 vs. 4.77, p < 0.001). C-statistic for APACHE IV to predict hospital mortality was 0.889 (95% CI 0.887 to 0.891) whilst calibration was limited (Hosmer-Lemeshow test p < 0.001). CONCLUSIONS: Despite relatively modest per capita health expenditure, and a small number of ICU beds per population, Hong Kong consistently provides a high-quality and efficient ICU service. Number of adult ICU admissions has increased, whilst adjusted mortality has decreased over the last decade. Although APACHE IV had good discrimination for hospital mortality, it overestimated hospital mortality of critically ill patients in Hong Kong.

Biomarker responses in oysters Crassostrea hongkongensis in relation to metal contamination patterns in the Pearl River Estuary, southern China.

The Pearl River Estuary (PRE) is the third largest estuary in China, where estuarine organisms are under metal stress at various biological levels. Based on the metal concentrations measured in oyster Crassostrea hongkongensis, we documented a change in dominance of metal contamination from Cd, Cr, Cu, Ni and Zn to Ag, Cd, Cu and Zn. In general, metal concentrations were higher in upstream stations and displayed a clear up-downstream gradient. Compared to the historical values, we noted the reductions in Cd, Cr and Ni concentrations, and the changing inputs due to evolving industrial activities were responsible for shaping the metal contamination profile in the PRE region. Along with metal concentrations, a suite of biomarkers was analyzed. Among the metals measured in the oyster tissues, Ag, Cd, Cu, Ni and Zn showed the strongest associations with pro-oxidant and oxidative stress responses (superoxide dismutase, lipid peroxidation and lysosomal membrane destabilization) and detoxification responses (glutathione and metallothionein), suggesting that the present metal contamination still exerts significant amount of stress in biota in the PRE. Metal contamination in estuaries in China is still severe compared to other countries, therefore continuous efforts should be taken to monitor the changing metal profiles with necessary control and remediation measures.

A lipidomic approach to understand copper resilience in oyster Crassostrea hongkongensis.

Copper (Cu) can cause oxidative stress and inflammatory responses, and there is arising evidence between Cu toxicity and lipid disturbance. In this study, we examined the relationships between Cu exposure and lipid metabolism in an estuarine oyster (Crassostrea hongkongensis) and aimed to understand the effects and resilience strategies of Cu on oyster metabolism. We exposed the oysters to waterborne Cu (10 and 50 µg/L) and measured the physiological changes (condition index and clearance rate), lipid accumulation and lipid peroxidation in the oysters. We found more altered lipid responses in oysters exposed to a lower Cu concentration (10 µg/L), and speculated that oysters exposed to 50 µg/L may upregulate the defenses. We further evaluated the changes in lipidome profiling of the Cu-exposed oysters in aspects of membrane dynamics, lipid signaling and energy metabolism. We documented the phospholipid remodeling as well as quick modulation in inflammatory responses and extensive vesicle formation for subcellular compartmentalization and autophagosome formation, as well as the possible impacts on mitochondrial bioenergetics in the Cu-exposed oysters. The lipidomics approach provided a comprehensive lipid profile of possible alteration by Cu exposure. In combination with other omics approaches, it may be possible to elucidate the pathways and mechanisms in stress acclimation and resilience associated between Cu contamination and lipid metabolism.

Seasonal and spatial variations of biomarker responses of rock oysters in a coastal environment influenced by large estuary input.

The present study assessed the spatial and temporal variations and the potential influences of the Pearl River discharge on trace metal bioaccumulation and biomarker responses in Hong Kong coastal waters. A suite of biomarkers including antioxidant defense, oxidative stress, metal detoxification, cellular response, neurotoxicity, and energy reserve were quantified in the rock oyster Saccostrea cucullata over spatial scale across the east and west of Hong Kong. We documented the elevated Cd, Cu and Zn concentrations in all western stations in the fall season, as a result of time-integrated accumulation during the peak discharge of the Pearl River Estuary (PRE) in summer. Lipid peroxidation and total glutathione corresponded well with the overall metal gradient and showed significant correlation with the tissue Cu bioaccumulation. The eastern station (Clear Water Bay) also exhibited high Cd and Cu concentrations with increased oxidative stress responses. In the spring, metal bioaccumulation in the oysters was reduced due to the weakened influence of PRE, with correspondingly less obvious biomarker responses. Our coupling measurements of biomarkers and tissue metal concentrations for the first time revealed that the large PRE could have latent and seasonal biological effects on the Hong Kong coastal biota. Sensitive biomarkers such as lipid peroxidation and glutathione responses might be good candidates for detecting the early biological responses in such sub-lethal contaminated environments.