Journal of Thrombosis and Thrombolysis - The decision by pulmonary embolism response teams (PERTs) to utilize anticoagulation (AC) with or without systemic thrombolysis (ST) or catheter-directed... 相似文献
The ABCD semaglutide audit was designed to capture the routine clinical outcomes of people commenced on semaglutide in the UK. Previous work showed differential reductions in HbA1c and weight dependent on previous glucagon-like peptide-1 receptor agonist (GLP-1RA) exposure. The analysis, in this research letter, shows that decreases in HbA1c and weight associated with semaglutide occur irrespective of previous GLP-1RA use. However, HbA1c reductions were less if switched from dulaglutide or liraglutide and weight changes were attenuated if switched from dulaglutide or exenatide, potentially suggesting differing potencies between GLP-1RAs. Dedicated studies with head-to-head comparisons are needed to confirm these findings. 相似文献
One of the primary mechanisms of tumor cell immune evasion is the loss of antigenicity, which arises due to lack of immunogenic tumor antigens as well as dysregulation of the antigen processing machinery. In a screen for small-molecule compounds from herbal medicine that potentiate T cell–mediated cytotoxicity, we identified atractylenolide I (ATT-I), which substantially promotes tumor antigen presentation of both human and mouse colorectal cancer (CRC) cells and thereby enhances the cytotoxic response of CD8+ T cells. Cellular thermal shift assay (CETSA) with multiplexed quantitative mass spectrometry identified the proteasome 26S subunit non–ATPase 4 (PSMD4), an essential component of the immunoproteasome complex, as a primary target protein of ATT-I. Binding of ATT-I with PSMD4 augments the antigen-processing activity of immunoproteasome, leading to enhanced MHC-I–mediated antigen presentation on cancer cells. In syngeneic mouse CRC models and human patient–derived CRC organoid models, ATT-I treatment promotes the cytotoxicity of CD8+ T cells and thus profoundly enhances the efficacy of immune checkpoint blockade therapy. Collectively, we show here that targeting the function of immunoproteasome with ATT-I promotes tumor antigen presentation and empowers T cell cytotoxicity, thus elevating the tumor response to immunotherapy. 相似文献
To set up the minimal conditions necessary to ensure that the social and familial network of the patient is preserved during the hospital stay for allogeneic hematopoïetic stem cell transplantation.
Material and methods
A national survey was conducted to increase knowledge about the conditions of hospital stay of adult and pediatric stem cell recipients. Then a multidisciplinary panel of health workers including doctors and nurses met to establish recommendations for maintaining the social and familial relationships optimally during the HSCT procedure.
Results
Practices and policies are very heterogeneous among the transplant centers. No consensus has been established and the literature data are scarce. The panel has thus established a list of recommendations to maintain optimal relationships between the patient and his relatives and friends during the hospital stay. The objective is to ensure a better acceptation of the isolation conditions and to facilitate the return home after D30.
Conclusion
Since there is no established scientific background for drastic isolation conditions, a multi-disciplinary approach in relationship with patients associations should allow softening of the procedures without impairing the quality of care. 相似文献
Novel biorenewable copolymer thermosets are successfully synthesized by the ring‐opening metathesis polymerization (ROMP) of norbornenyl‐functionalized castor oil (NCO) and norbornenyl‐functionalized castor oil alcohol (NCA) with controlled amounts of 0.8 and 1.8 norbornene rings per fatty acid chain, respectively. The NCO and NCA monomers are mixed in different concentrations and simultaneously polymerized via ROMP using Grubbs catalyst. Broadband dielectric relaxation spectroscopy (BDRS) is used to investigate the molecular dynamics of the fully cured copolymer thermosets over a wide range of frequencies (5 × 10?2 to 0.5 × 107 Hz) at different constant temperatures (?70 to 125 °C). Four phenomena, namely α‐, β‐, and γ‐relaxation processes and ionic conductivity are observed for all the measured samples.
Marine organisms have been considered an interesting target for the discovery of different classes of secondary natural products with wide-ranging biological activities. Sponges which belong to the order Dictyoceratida are distinctly classified into 5 families: Dysideidae, Irciniidae, Spongiidae, Thorectidae, and Verticilliitidae. In this review, compounds isolated from Dictyoceratida sponges were discussed with their biological potential within the period 2013 to December 2019. Moreover, analysis of the physicochemical properties of these marine natural products was investigated and the results showed that 78% of the compounds have oral bioavailability potential. This review highlights sponges of the order Dictyoceratida as exciting source for discovery of new drug leads.Marine organisms have been considered an interesting target for the discovery of different classes of secondary natural products with wide-ranging biological activities.相似文献
Central nervous system (CNS) involvement in hepatitis C virus (HCV) infection has different facets such as anxiety, depression, cognitive impairment and vasculitis. We were interested in detecting subclinical CNS involvement in chronic HCV infected subjects with and without systemic vasculitis.
Patients and methods
Nineteen patients (15 females and 4 males) with chronic HCV infection (mean age 46.5?±?7 and mean duration since diagnosis of HCV infection 4.7?±?4?years, including 6 (32%) Child-Pugh class A cirrhotic patients) and 30 age, sex and education matched healthy control subjects were studied. Thirteen patients had associated vasculitis. Patients and control subjects were assessed using the block design and comprehension subtests of Wechsler Bellevue Adult Intelligence Scale, Wechsler Memory scale (WMS), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI). Brain HMPAO Single Photon Emission Computed Tomography (SPECT) was performed for HCV patients.
Results
Patients with HCV had lower scores on the block design test compared to control subjects (8.37?±?1.89 versus 10.37?±?1.47, p?<?0.001), lower total WMS scores (43.15?±?10.49 versus 60.27?±?8.08, p?<?0.001) and higher anxiety and depression scores (16.94?±?10.46 and 37.17?±?10.38 versus 10.3?±?4.67 and 28.9?±?5.99, p?=?0.004 and 0.001, respectively). Total WMS were lower in HCV patients with vasculitis compared to those without vasculitis (39.14?±?9.3 versus 51.17?±?8.3, p?=?0.019) while the block design and comprehension tests, BAI and BDI were not significantly different between both groups. The block design and comprehension tests, WMS, BAI and BDI were not significantly different between cirrhotic and non-cirrhotic patients. Seven patients had different patterns of cerebral hypoperfusion on SPECT, and all of them had associated vasculitis. Abnormal SPECT was associated with lower total WMS scores (35.87?±?10.8 versus 46.79?±?8.6 in those with normal SPECT, p?=?0.049).
Conclusions
Vasculitis may contribute to the development of neuropsychiatric involvement in HCV patients. 相似文献
Hypertension is twice as common in patients with diabetes compared to those without diabetes. It accounts for up to 75% of cardiovascular disease risk leading to the substantial increase in morbidity and mortality. Control of blood pressure in people with diabetes has been shown in randomized controlled trials to decrease cardiovascular risk and improve outcome especially in preventing stroke. A target blood pressure goal of <130/80 mm Hg is currently recommended for patients with diabetes. However, less than 1/3 of these patients achieve such a goal. This is in part due to the inherent difficulty in controlling blood pressure in these patients where hypertension is usually associated with increased salt sensitivity, volume expansion and isolated systolic hypertension. Therefore, patients with diabetes usually require multiple medications for optimal blood pressure control. Calcium channel antagonists have been shown in large clinical trials to be both safe and effective in controlling blood pressure in diabetic patients and will continue to play a major role in the management of hypertension in this population, particularly in the combination therapy that these patients usually require. 相似文献
The magnitude of the risk of severe hypoglycemia associated with sulfonylureas as the initial treatment for type 2 diabetes in the real-world setting is unknown. We assessed the risk of severe hypoglycemia associated with initiating monotherapy with sulfonylurea compared with metformin for the treatment of type 2 diabetes.
Methods
By using the UK Clinical Practice Research Datalink and Hospital Episode Statistics linked to the Office for National Statistics, we identified a cohort of patients with type 2 diabetes who initiated sulfonylureas or metformin monotherapy between April 1, 1998, and December 31, 2012, with follow-up until December 31, 2013. Sulfonylurea users were matched one-to-one to metformin users by high-dimensional propensity scores. Hazard ratios (HRs) and 95% confidence intervals (CIs) of severe hypoglycemia, defined as requiring hospitalization, were estimated using Cox proportional hazards models comparing sulfonylureas with metformin monotherapy.
Results
The study cohort consisted of 14,012 initiators of sulfonylureas matched to 14,012 initiators of metformin. The mean treated follow-up time was 1.41 (standard deviation, 1.84) years. Use of sulfonylurea was associated with an elevated incidence of severe hypoglycemia compared with metformin as the initiating monotherapy for type 2 diabetes (incidence rate, 2.4/1000 person-years; 95% CI, 1.90-2.90; HR, 4.53; 95% CI, 2.76-7.45).
Conclusions
Sulfonylureas, when prescribed as the initiating monotherapy for the treatment of type 2 diabetes, is associated with a 4.5-fold increase in the risk of severe hypoglycemia. Given the negative consequences of this outcome, clinicians should consider alternative hypoglycemic agents when metformin is not tolerated or contraindicated. 相似文献