Reedclemensen8846
Novel agents have made the management of chronic lymphocytic leukemia (CLL) more promising and personalized. However, long-term treatment is still warranted which may result in toxicity and resistance. Thus, new combination therapy may help achieve deeper remission and limited-duration therapy. Histone deacetylase inhibitors (HDACi) can affect many tumors by modulating key biological functions including autophagy. Studies have shown that some novel targeted agents including ibrutinib induce autophagy. This study aimed to explore the effect of oral HDAC inhibitor, chidamide, on CLL cells as well as the role of autophagy in this process. Here, we showed that autophagy flux in CLL cells was inhibited by chidamide via post-transcriptional modulation and chidamide had cytostatic and cytotoxic effects on CLL cells. Besides, the pro-survival role of autophagy in CLL cells was validated by using autophagy inhibitor and knocking down critical autophagy gene. Notably, a combination of chidamide and ibrutinib showed significant synergism and downregulated ibrutinib-induced autophagy. This work highlights the therapeutic potential of chidamide via its effect on autophagy, especially in combination with ibrutinib.
Health information about COVID-19 has been circulating in social networking sites, including unproven claims that smoking and alcohol drinking could protect against COVID-19. We examined if exposure to such claims was associated with changes in tobacco and alcohol consumption.
We conducted a population-based, landline and mobile phone survey of 1501 randomly sampled adults aged 18 years or older (47.5% male) in Hong Kong in April 2020. Respondents reported if they had ever seen claims that 'smoking/alcohol drinking can protect against COVID-19' from popular social networking platforms. Current tobacco and alcohol users reported if they had increased or reduced their consumption since the outbreak. Prevalence data were weighted by sex, age and education of the general adult population.
19.0% (95% CI 16.8% to 21.4%) of all respondents reported having seen claims that 'smoking/alcohol drinking can protect against COVID-19' from social networking sites. Multinomial logistic regression showed that exposure to the claims was significantly associated with increased tobacco use (OR 2.37, 95% CI 1.08 to 5.20) in current tobacco users (N=280) and increased alcohol use (OR 4.16, 95% CI 2.00 to 8.67) in current drinkers (N=722), adjusting for sex, age, education level, alcohol/tobacco use status, home isolation, anxiety and depressive symptoms, and survey method.
Our results first showed that exposure to health misinformation that smoking/alcohol drinking can protect against COVID-19 was associated with self-reported increases in tobacco and alcohol consumption in Chinese during the pandemic.
Our results first showed that exposure to health misinformation that smoking/alcohol drinking can protect against COVID-19 was associated with self-reported increases in tobacco and alcohol consumption in Chinese during the pandemic.
Patients with stroke-like symptoms may be underutilising emergency medical services and avoiding hospitalisation during the COVID-19 pandemic. DNA Repair inhibitor We investigated a decline in admissions for stroke and transient ischaemic attack (TIA) and emergency department (ED) stroke alert activations.
We retrospectively compiled total weekly hospital admissions for stroke and TIA between 31 December 2018 and 21 April 2019 versus 30 December 2019 and 19 April 2020 at five US tertiary academic comprehensive stroke centres in cities with early COVID-19 outbreaks in Boston, New York City, Providence and Seattle. We collected available data on ED stroke alerts, stroke severity using the National Institutes of Health Stroke Scale (NIHSS) and time from symptom onset to hospital arrival.
Compared with 31 December 2018 to 21 April 2019, a decline in stroke/TIA admissions and ED stroke alerts occurred during 30 December 2019 to 19 April 2020 (
trend <0.001 for each). The declines coincided with state stay-at-home recommendaers must continue to encourage patients with stroke to seek acute care during this crisis.
At these five large academic US hospitals, admissions for stroke and TIA declined during the COVID-19 pandemic. There was a trend for fewer ED stroke alerts at three of the five centres with available 2019 and 2020 data. Acute stroke therapies are time-sensitive, so decreased healthcare access or utilisation may lead to more disabling or fatal strokes, or more severe non-neurological complications related to stroke. Our findings underscore the indirect effects of this pandemic. Public health officials, hospital systems and healthcare providers must continue to encourage patients with stroke to seek acute care during this crisis.
Recent decision rules for the management of febrile infants support the identification of infants at higher risk of serious bacterial infections (SBIs) without the performance of routine lumbar puncture. We derive and validate a model to identify febrile infants ≤60 days of age at low risk for SBIs using supervised machine learning approaches.
We conducted a secondary analysis of a multicenter prospective study performed between December 2008 and May 2013 of febrile infants. Our outcome was SBI, (culture-positive urinary tract infection, bacteremia, and/or bacterial meningitis). We developed and validated 4 supervised learning models logistic regression, random forest, support vector machine, and a single-hidden layer neural network.
A total of 1470 patients were included (1014 >28 days old). One hundred thirty-eight (9.3%) had SBIs (122 urinary tract infections, 20 bacteremia, and 8 meningitis; 11 with concurrent SBIs). Using 4 features (urinalysis, white blood cell count, absolute neutrophil count,ations, and antibiotics while maintaining excellent sensitivity.
Children are at risk for multisystem inflammatory syndrome in children (MIS-C) after infection with severe acute respiratory syndrome coronavirus 2. Cardiovascular complications, including ventricular dysfunction and coronary dilation, are frequent, but there are limited data on arrhythmic complications.
Retrospective cohort study of children and young adults aged ≤21 years admitted with MIS-C. Demographic characteristics, electrocardiogram (ECG) and echocardiogram findings, and hospital course were described.
Among 25 patients admitted with MIS-C (60% male; median age 9.7 [interquartile range 2.7-15.0] years), ECG anomalies were found in 14 (56%). First-degree atrioventricular block (AVB) was seen in 5 (20%) patients a median of 6 (interquartile range 5-8) days after onset of fever and progressed to second- or third-degree AVB in 4 patients. No patient required intervention for AVB. All patients with AVB were admitted to the ICU (before onset of AVB) and had ventricular dysfunction on echocardiograms. required in patients with evidence of first-degree AVB because of risk of progression to high-grade AVB.
Wheat flour exposure in bakers can elicit respiratory and skin symptoms. Scarce data are available on the prevalence of such conditions in bakers. We investigated the prevalence of work-related rhinitis, asthma-like symptoms and dermatitis in bakers according to job task and type of allergens involved.
Of the 229 traditional bakeries in Verona area who were invited to participate in a cross-sectional survey, 211 (92%) accepted; 727 employees in these bakeries answered a modified version of a questionnaire on job tasks; allergen exposure within the bakery; and work-related nasal, asthma-like and skin symptoms during 2010-2014. Determinants of work-related nasal, asthma-like or skin disorders were separately evaluated using different logistic models.
The prevalence of work-related nasal and asthma-like symptoms was, respectively, 15.1% and 4.2% in bakery shop assistants, increasing to 25.7% and 9.5% in bakers using only wheat flour, and further to 31.8% and 13.6% in bakers using flour and additives, and then to 34.1% and 18.2% in bakers using flour with additives and multigrain (p<0.001). The risk of work-related asthma-like symptoms was more than doubled in bakers using additives without or with multigrain than in shop assistants (OR 2.3, 95% CI 1.0 to 5.5 and OR 3.4, 95% CI 1.1 to 10.8, respectively). Making bread with additives alone or with multigrain significantly increased the risk of work-related nasal symptoms in shop assistants, while the risk of skin symptoms was not significantly affected.
Bakers using additives alone or with multigrain are at a high risk of experiencing nasal and asthma-like symptoms.
Bakers using additives alone or with multigrain are at a high risk of experiencing nasal and asthma-like symptoms.
Ambient air pollution is associated with ischaemic stroke incidence. However, most of the previous studies used stroke-related hospital admission rather than stroke onset itself. This study aimed to evaluate the relationship between ambient air pollutant exposures and acute ischaemic stroke based on the timing of symptom onset.
A time-stratified, case-crossover analysis was performed among 520 patients who had ischaemic stroke admitted to the Second Hospital of Tianjin Medical University (Tianjin, China) between 1 April 2018 and 31 March 2019 (365 days). Daily air pollutant concentrations of particulate matter with aerodynamic diameter 2.5 µm, particulate matter with aerodynamic diameter 10 µm (PM10), sulfur dioxide, nitrogen dioxide, carbon monoxide and ozone were obtained from fixed-site monitoring stations. We used conditional logistic regression to estimate OR and 95% CI corresponding to an increase in IQR of each air pollutant after adjusting for the effects of temperature and relative humidity.
Overall, a higher risk of ischaemic stroke was found between April and September. During this period PM10 was associated with an increased risk of ischaemic stroke (1-day lag OR=1.49, 95% CI 1.09 to 2.02; 3-day mean OR=1.58, 95% CI 1.09 to 2.29) among patients between 34 and 70 years old. Positive associations were also observed between PM10 (1-day lag OR=1.51, 95% CI 1.10 to 2.07; 3-day mean OR=1.57, 95% CI 1.08 to 2.29), ozone (1-day lag OR=1.83, 95% CI 1.16 to 2.87; 3-day mean OR=1.90, 95% CI 1.06 to 3.42) and ischaemic stroke occurrence among those with hyperlipidaemia.
Our results suggest that air pollution is associated with a higher risk of ischaemic stroke in younger people or people with hyperlipidemia. These findings still need to be further investigated.
Our results suggest that air pollution is associated with a higher risk of ischaemic stroke in younger people or people with hyperlipidemia. These findings still need to be further investigated.
Moderately raised serum bilirubin levels are associated with lower rates of lung cancer, particularly among smokers. It is not known whether these relationships reflect antioxidant properties or residual confounding.
This study aimed to investigate potential causal relationships between serum total bilirubin and lung cancer incidence using one-sample Mendelian randomisation (MR) and UK Biobank.
We instrumented serum total bilirubin level using two variants (rs887829 and rs4149056) that together explain ~40% of population-level variability and are linked to mild hereditary hyperbilirubinaemia. Lung cancer events occurring after recruitment were identified from national cancer registries. Observational and genetically instrumented incidence rate ratios (IRRs) and rate differences per 10 000 person-years (PYs) by smoking status were estimated.
We included 377 294 participants (median bilirubin 8.1 μmol/L (IQR 6.4-10.4)) and 2002 lung cancer events in the MR analysis. Each 5 μmol/L increase in observed bilirubin levels was associated with 1.