Abstract A random population-based telephone survey ( n = 301) was conducted among the Hong Kong general population in July 2009. Past history of seasonal influenza vaccination (OR = 2.59–3.13) was ...associated with intention to take up A/H1N1 vaccination under three hypothetical scenarios (provided at <HK$100, HK$100–200 and >HK$200). Adjusting background variables, other significant factors were identified by stepwise models: perceived side effects (OR = 0.33), family members’ recommendations and friends’ acceptability toward the vaccine (OR = 2.80–4.74). In contrast to other studies on seasonal influenza and A/H1N1 vaccination, perceived susceptibility and perceived severity related to influenza A/H1N1 were non-significant. Cultural differences may therefore exist.
Author Affiliation: (1) Department of Anesthesiology and Pain Medicine, University of Alberta Hospital, Edmonton, AB, Canada (2) Department of Anesthesiology, University of Iowa, Iowa City, IA, USA ...(3) Department of Anesthesiology, Perioperative Medicine and Pain Medicine, Stanford University, Stanford, CA, USA (a) hip@ualberta.ca Article History: Registration Date: 01/06/2021 Received Date: 10/16/2020 Accepted Date: 12/28/2020 Online Date: 01/22/2021 Byline:
Purpose
Postamputation pain is challenging because of complex mechanisms involving a multitude of pain pathways and psychological factors. This patient population also tends to have extensive ...comorbidities with or without a background of chronic pain. Electrical neuromodulation such as peripheral nerve stimulation has gained traction in the realm of chronic pain. Recently, the off-label use of hybrid perineural nerve stimulation in combination with locoregional block via the stimulating nerve block catheter has been described in single-center case reports.
Clinical features
Herein, we present a case series of six patients from two different Canadian hospitals using such a hybrid technique in three different clinical scenarios. These scenarios were (1) local anesthetic dose minimization in the presence of multiple nerve block catheters, (2) analgesia augmentation when local anesthetic alone is insufficient, and (3) provision of an analgesic adjunct as part of a multimodal regimen. A stimulating sciatic nerve block catheter was inserted under ultrasound and nerve stimulation guidance for these cases. Patients tended to experience pain on the subsequent postoperative days whereby the off-label use of nerve stimulation successfully reduced their pain score and stabilized or decreased their opioid consumption or minimized the need to increase the local anesthetic dose when doing so could have precipitated local anesthetic toxicity.
Conclusion
Our case series supports the feasibility of using a combination of low-frequency perineural stimulation and local anesthetic infusion via a single perineural nerve block catheter to manage challenging postamputation pain.
Gastric cancer displays marked molecular heterogeneity with aggressive behavior and treatment resistance. Therefore, good in vitro models that encompass unique subtypes are urgently needed for ...precision medicine development. Here, we have established a primary gastric cancer organoid (GCO) biobank that comprises normal, dysplastic, cancer, and lymph node metastases (n = 63) from 34 patients, including detailed whole-exome and transcriptome analysis. The cohort encompasses most known molecular subtypes (including EBV, MSI, intestinal/CIN, and diffuse/GS, with CLDN18-ARHGAP6 or CTNND1-ARHGAP26 fusions or RHOA mutations), capturing regional heterogeneity and subclonal architecture, while their morphology, transcriptome, and genomic profiles remain closely similar to in vivo tumors, even after long-term culture. Large-scale drug screening revealed sensitivity to unexpected drugs that were recently approved or in clinical trials, including Napabucasin, Abemaciclib, and the ATR inhibitor VE-822. Overall, this new GCO biobank, with linked genomic data, provides a useful resource for studying both cancer cell biology and precision cancer therapy.
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•Living biobank includes 17 normal and 46 gastric cancer organoid lines•Organoid biobank encompasses most of the known molecular subtypes of gastric cancer•Organoids recapitulate the genomic and transcriptomic features of original tumors•High-throughput screen revealed potential target drugs for personalized therapy
Leung and colleagues established a biobank of patient-derived gastric cancer organoids that encompasses a diverse array of subtypes and maintained long-term similarity to the original tumors. They used the organoids to perform large-scale drug screening that identified potential target drugs and could guide patient drug selection.
Serrated polyps (hyperplastic polyps, sessile or traditional serrated adenomas), which can arise in a sporadic or polyposis setting, predispose to colorectal cancer (CRC), especially those with ...microsatellite instability (MSI) due to MLH1 promoter methylation (MLH1
). We investigate genetic alterations in the serrated polyposis pathway.
We used a combination of exome sequencing and target gene Sanger sequencing to study serrated polyposis families, sporadic serrated polyps and CRCs, with validation by analysis of The Cancer Genome Atlas (TCGA) cohort, followed by organoid-based functional studies.
In one out of four serrated polyposis families, we identified a germline RNF43 mutation that displayed autosomal dominant cosegregation with the serrated polyposis phenotype, along with second-hit inactivation through loss of heterozygosity or somatic mutations in all serrated polyps (16), adenomas (5) and cancer (1) examined, as well as coincidental BRAF mutation in 62.5% of the serrated polyps. Concurrently, somatic RNF43 mutations were identified in 34% of sporadic sessile/traditional serrated adenomas, but 0% of hyperplastic polyps (p=0.013). Lastly, in MSI CRCs, we found significantly more frequent RNF43 mutations in the MLH1
(85%) versus MLH1
(33.3%) group (p<0.001). These findings were validated in the TCGA MSI CRCs (p=0.005), which further delineated a significant differential involvement of three Wnt pathway genes between these two groups (RNF43 in MLH1
; APC and CTNNB1 in MLH1
); and identified significant co-occurrence of BRAF and RNF43 mutations in the MSI (p<0.001), microsatellite stable (MSS) (p=0.002) and MLH1
MSI CRCs (p=0.042). Functionally, organoid culture of serrated adenoma or mouse colon with CRISPR-induced RNF43 mutations had reduced dependency on R-spondin1.
These results illustrate the importance of RNF43, along with BRAF mutation in the serrated neoplasia pathway (both the sporadic and familial forms), inform genetic diagnosis protocol and raise therapeutic opportunities through Wnt inhibition in different stages of evolution of serrated polyps.
This is the first study on prognostication in an entire cohort of laboratory-confirmed COVID-19 patients in the city of Hong Kong. Prognostic tool is essential in the contingency response for the ...next wave of outbreak. This study aims to develop prognostic models to predict COVID-19 patients' clinical outcome on day 1 and day 5 of hospital admission.
We did a retrospective analysis of a complete cohort of 1037 COVID-19 laboratory-confirmed patients in Hong Kong as of 30 April 2020, who were admitted to 16 public hospitals with their data sourced from an integrated electronic health records system. It covered demographic information, chronic disease(s) history, presenting symptoms as well as the worst clinical condition status, biomarkers' readings and Ct value of PCR tests on Day-1 and Day-5 of admission. The study subjects were randomly split into training and testing datasets in a 8:2 ratio. Extreme Gradient Boosting (XGBoost) model was used to classify the training data into three disease severity groups on Day-1 and Day-5.
The 1037 patients had a mean age of 37.8 (SD ± 17.8), 53.8% of them were male. They were grouped under three disease outcome: 4.8% critical/serious, 46.8% stable and 48.4% satisfactory. Under the full models, 30 indicators on Day-1 and Day-5 were used to predict the patients' disease outcome and achieved an accuracy rate of 92.3% and 99.5%. With a trade-off between practical application and predictive accuracy, the full models were reduced into simpler models with seven common specific predictors, including the worst clinical condition status (4-level), age group, and five biomarkers, namely, CRP, LDH, platelet, neutrophil/lymphocyte ratio and albumin/globulin ratio. Day-1 model's accuracy rate, macro-/micro-averaged sensitivity and specificity were 91.3%, 84.9%/91.3% and 96.0%/95.7% respectively, as compared to 94.2%, 95.9%/94.2% and 97.8%/97.1% under Day-5 model.
Both Day-1 and Day-5 models can accurately predict the disease severity. Relevant clinical management could be planned according to the predicted patients' outcome. The model is transformed into a simple online calculator to provide convenient clinical reference tools at the point of care, with an aim to inform clinical decision on triage and step-down care.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sporadic early-onset colorectal cancer (EOCRC) has bad prognosis, yet is poorly represented by cell line models. We examine the key mutational and transcriptomic alterations in an organoid biobank ...enriched in EOCRCs.
We established paired cancer (n=32) and normal organoids (n=18) from 20 patients enriched in microsatellite-stable EOCRC. Exome and transcriptome analysis was performed.
We observed a striking diversity of molecular phenotypes, including
fusions. Transcriptionally,
fusion organoids resembled normal colon organoids and were distinct from
mutant organoids, with high
and low
expression. Single cell transcriptome analysis confirmed the similarity between
fusion organoids and normal organoids, with a propensity for maturation on Wnt withdrawal, whereas the
mutant organoids were locked in progenitor stages. CRISPR/Cas9 engineered mutation of
in normal human colon organoids led to upregulation of PTK7 protein and suppression of
, but less so with an engineered
mutation. The frequent co-occurrence of
fusions with
or
mutation was confirmed in TCGA database searches.
mutation was found in organoid from a leukaemia survivor with a novel mutational signature; and organoids with POLE proofreading mutation displayed ultramutation. The cancer organoid genomes were stable over long culture periods, while normal human colon organoids tended to be subject to clonal dominance over time.
These organoid models enriched in EOCRCs with linked genomic data fill a gap in existing CRC models and reveal distinct genetic profiles and novel pathway cooperativity.
To understand different aspects of community responses related to severe acute respiratory syndrome (SARS), 2 population-based, random telephone surveys were conducted in June 2003 and January 2004 ...in Hong Kong. More than 70% of respondents would avoid visiting hospitals or mainland China to avoid contracting SARS. Most respondents believed that SARS could be transmitted through droplets, fomites, sewage, and animals. More than 90% believed that public health measures were efficacious means of prevention; 40.4% believed that SARS would resurge in Hong Kong; and approximately equals 70% would then wear masks in public places. High percentages of respondents felt helpless, horrified, and apprehensive because of SARS. Approximately 16% showed signs of posttraumatic symptoms, and approximately equals 40% perceived increased stress in family or work settings. The general public in Hong Kong has been very vigilant about SARS but needs to be more psychologically prepared to face a resurgence of the epidemic.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We aimed to evaluate and characterize the scale and relationships of emergency department (ED) visits and excess mortality associated with the early phase of the COVID-19 pandemic in the territory of ...Hong Kong.
We conducted a territory-wide, retrospective cohort study to compare ED visits and the related impact of the COVID-19 pandemic on mortality. All ED visits at 18 public acute hospitals in Hong Kong between January 1 and August 31 of 2019 (n=1,426,259) and 2020 (n=1,035,562) were included. The primary outcome was all-cause mortality in the 28 days following an ED visit. The secondary outcomes were weekly number of ED visits and diagnosis-specific mortality.
ED visits decreased by 27.4%, from 1,426,259 in 2019 to 1,035,562 in 2020. Overall period mortality increased from 28,686 (2.0%) in 2019 to 29,737 (2.9%) in 2020. The adjusted odds ratio for 28-day, all-cause mortality in the pandemic period of 2020 relative to 2019 was 1.26 (95% confidence interval 1.24 to 1.28). Both sexes, age more than 45 years, all triage categories, all social classes, all ED visit periods, epilepsy (odds ratio 1.58, 95% confidence interval 1.20 to 2.07), lower respiratory tract infection, and airway disease had higher adjusted ORs for all-cause mortality.
A significant reduction in ED visits in the first 8 months of the COVID-19 pandemic was associated with an increase in deaths certified in the ED. The government must make provisions to encourage patients with alarming symptoms, mental health conditions, and comorbidities to seek timely emergency care, regardless of the pandemic.
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