Cangrelor is a relatively new antiplatelet drug that has been approved for use as an adjunct therapy to percutaneous coronary intervention (PCI) to decrease peri-procedural myocardial infarction ...(MI), coronary revascularization, and stent thrombosis. Cangrelor is an adenosine triphosphate analogue with a pharmacokinetic mechanism based on a reversible, dose-dependent inhibition adenosine diphosphate (ADP)-induced platelet aggregation. This drug has lately been in the spotlight as a possible bridge therapy for anti-platelet medication prior to cardiac and non-cardiac surgeries. Platelet function is usually restored within sixty minutes of cessation of therapy, thereby decreasing the risk of bleeding while providing adequate pre-procedural coverage to reduce ischemic events. This manuscript reviews the literature on cangrelor and summarizes its role as a peri-procedural bridge.Cangrelor is a relatively new antiplatelet drug that has been approved for use as an adjunct therapy to percutaneous coronary intervention (PCI) to decrease peri-procedural myocardial infarction (MI), coronary revascularization, and stent thrombosis. Cangrelor is an adenosine triphosphate analogue with a pharmacokinetic mechanism based on a reversible, dose-dependent inhibition adenosine diphosphate (ADP)-induced platelet aggregation. This drug has lately been in the spotlight as a possible bridge therapy for anti-platelet medication prior to cardiac and non-cardiac surgeries. Platelet function is usually restored within sixty minutes of cessation of therapy, thereby decreasing the risk of bleeding while providing adequate pre-procedural coverage to reduce ischemic events. This manuscript reviews the literature on cangrelor and summarizes its role as a peri-procedural bridge.
Hyperlipidemia is a metabolic abnormality in both young and aged populations across the world. Withaferin-A (WT) present in Withania somnifera (Indian ginseng) has been studied by many investigators ...for their therapeutic potentials. However, their effects on bile acid (BA) metabolism, that play a significant role in lipid homeostasis under hyperlipidemia has not been studied. This study explores the modulatory potential of WT on BA metabolism in young and aged hyperlipidemic rats. Hyperlipidemia was induced by feeding lard fat (35g/100g diet, HF) for 60 days. Withaferin-A (2.5 mg/kg diet) was fed to assess its effect on lipid metabolism and enterohepatic circulation of BA. In both models, compared to HF, WT had significantly (p < 0.05), decreased serum lipids, BA uptake, and HMG-CoA reductase activity, but increased hepatic Cyp7a1, decreased serum BA and increased fecal BA. WT re-regulated hyperlipidemia-induced aberrations in the intestinal uptake, hepatic synthesis, and cholesterol and BA metabolism in both models.
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•Withaferin-A (WT) modulate dyslipidemia-induced aberrations in the enterohepatic circulation of BA in young and aged rats.•WT showed favorable interaction with the Asbt indicating potential effect on bile acids absorption.•WT lowered the lipids by down-regulating bile acid absorption and its synthesis under dyslipidemia.
Abstract
Disclosure: S. Venugopal: None. S. Patel: None. Z. Wu: None. F. Galbiati: None. J. Oh: None. P. Manroa: None. E. Morariu: None. M. Stefanovic-Racic: None.
Introduction: Fournier’s gangrene ...(FG) is a rare, necrotizing fasciitis of the external genitalia with high mortality up to 30% that is more prevalent in males, diabetes, HIV, and immunocompromised states. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been linked with FG. Interestingly, multiple studies have found no significantly increased risk of FG with SGLT2i use. However, these studies have very large confidence intervals due to the rarity of the observed event. Methods: A retrospective study between 3/1/2013-6/12/2020 was performed at four different tertiary hospitals within the University of Pittsburgh Medical Center (UPMC) system to compare the severity and outcome of FG between type 2 diabetes patients who were treated with SGLT2is, metformin, and insulin prior to admission. Results: 202 patients were admitted for FG (8 on SGLT2is, 80 on Metformin, and 88 on insulin). Baseline characteristics such as age, sex, and HbA1c were generally similar. Duration of diabetes was longer in subjects on insulin vs not on insulin (p<0.001). Creatinine(Cr) on admission was lower in SGLT2i vs not on SGLT2i (p=0.056) and metformin vs not on metformin (p=0.037), but was higher in the insulin vs non-insulin group (p=0.004). The SGLT2i group had a shorter hospital stay (p=0.045), a lower rate of ICU admission (p=0.0093), and a trend toward a shorter ICU stay than the non-SGLT2i group (p=0.053). In the metformin group, the cases of amputation were lower compared to the non-metformin group (p=0.026). In the insulin group, there was a trend toward a longer hospital stay (p=0.057) and ICU stay (p=0.052) vs the non-insulin group. Conclusion: The use of SGLT2i does not appear to worsen the clinical course or outcome of FG and may actually improve it based on our data showing decreased ICU admissions and length of stay. Metformin usage may dampen the severity of FG by significantly decreasing cases of amputation. Noteworthy is that Cr was lower in the SGLT2i and metformin groups. Further analysis of baseline characteristics such as renal function, HbA1c, and duration of diabetes will determine whether they may affect the severity of FG.
Presentation: Thursday, June 15, 2023
Immortalized liver cell lines and primary hepatocytes are currently used as in vitro models for hepatotoxic drug screening. However, a decline in the viability and functionality of hepatocytes with ...time is an important limitation of these culture models. Advancements in tissue engineering techniques have allowed us to overcome this challenge by designing suitable scaffolds for maintaining viable and functional primary hepatocytes for a longer period of time in culture. In the current study, we fabricated liver-specific nanofiber scaffolds with polylactic acid (PLA) along with a decellularized liver extracellular matrix (LEM) by the electrospinning technique. The fabricated hybrid PLA-LEM scaffolds were more hydrophilic and had better swelling properties than the PLA scaffolds. The hybrid scaffolds had a pore size of 38 ± 8 μm and supported primary rat hepatocyte cultures for 10 days. Increased viability (2-fold increase in the number of live cells) and functionality (5-fold increase in albumin secretion) were observed in primary hepatocytes cultured on the PLA-LEM scaffolds as compared to those on conventional collagen-coated plates on day 10 of culture. A significant increase in CYP1A2 enzyme activity was observed in hepatocytes cultured on PLA-LEM hybrid scaffolds in comparison to those on collagen upon induction with phenobarbital. Drugs like acetaminophen and rifampicin showed the highest toxicity in hepatocytes cultured on hybrid scaffolds. Also, the lethal dose of these drugs in rodents was accurately predicted as 1.6 g/kg and 594 mg/kg, respectively, from the corresponding IC50 values obtained from drug-treated hepatocytes on hybrid scaffolds. Thus, the fabricated liver-specific electrospun scaffolds maintained primary hepatocyte viability and functionality for an extended period in culture and served as an effective ex vivo drug screening platform to predict an accurate in vivo drug-induced hepatotoxicity.
Introduction: Dental caries is highly prevalent among children and persists to be a significant public health problem worldwide. Aim: The aim of this study is to assess the prevalence of dental ...caries and treatment needs of 12- and 15-year-old schoolchildren of Bhopal district and to compare the dental caries levels and treatment needs of government schoolchildren of urban and rural areas of Bhopal district. Materials and Methods: A cross-sectional study was conducted among 12- and 15-year-old urban and rural school-going children of Bhopal district. A total of 1100 schoolchildren were screened using a multistage sampling procedure. The children were examined according to the dentition status and treatment needs, WHO (modified) oral health assessment. Student's t-test was used for continuous variables and Chi-square test used for categorical data and P < 0.05 was considered statistically significant. Results: The prevalence of dental caries at the age of 12 years was 33.5% and 26.5% at the age of 15 years. Dental caries was higher in urban schools as compared to rural schools. The maximum need was for one-surface restoration. Conclusion: The prevalence of dental caries at both the age groups was low. This suggested a need of dental health education program including proper oral hygiene instruction which helps children to improve positive dental attitude and behavior.
Background: Medical personnel are expected to parse through scores of reports each day, covering the medical history of their patients. This reading task is crucial to the effectiveness of the ...healthcare provided. However, it has been noticed that doctors often have to spend a lot of time going through these documents, in order to get a concise gist of the most medically relevant details. This could even affect the amount of time left for doctor-patient interaction. It is in this scenario, that the potential usefulness of an automatic clinical report summarization tool becomes apparent. Such a system would save a lot of effort for the doctor, and make a lot of time available for quality patient-doctor interaction. The focus of this paper is on extractive summarization.Method: Due to its vast pre-training, BERT (Bidirectional Encoder Representations from Transformers) is one of the most knowledgeable NLP (Natural Language Processing) models currently available- making it one of the best choices for a task like summarization. BERTSUM is the BERT version fine-tuned for summarization, BERTSUMEXT being the extractive summarization variant. The BERTSUMEXT architecture has previously been used to create a model that has been extensively pre-trained on the CNN/DailyMail dataset of news articles and corresponding summaries. It was noticed through testing that this pre-trained version of BERTSUMEXT does not perform very well on clinical reports and therefore needs to be improved to be employed in a clinical report summarization system. The method adopted here is to further train the BERTSUMEXT model using different training strategies on a clinical report summarization dataset and assess the performance improvement. The idea is to expand BERTSUMEXT's knowledge to give it a 'medical edge' that it lacks.Results: The training strategy that modifies the parameter values of the extractive summarization layers of the BERTSUMEXT architecture shows a clear improvement on all nine parameters of the ROUGE (Recall Oriented Understudy for Gisting Evalution) automatic evaluation metric and the human evaluation paradigm. The ROUGE metric evaluates summary quality by measuring the overlap between the reference gold summary and the candidate summary generated by the model. The Human Evaluation Paradigm is a method where we obtain a professional doctor's opinion on the summary quality produced by the model.
Importance: Non-contrast head CT scan is the current standard for initial imaging of patients with head trauma or stroke symptoms. Objective: To develop and validate a set of deep learning algorithms ...for automated detection of following key findings from non-contrast head CT scans: intracranial hemorrhage (ICH) and its types, intraparenchymal (IPH), intraventricular (IVH), subdural (SDH), extradural (EDH) and subarachnoid (SAH) hemorrhages, calvarial fractures, midline shift and mass effect. Design and Settings: We retrospectively collected a dataset containing 313,318 head CT scans along with their clinical reports from various centers. A part of this dataset (Qure25k dataset) was used to validate and the rest to develop algorithms. Additionally, a dataset (CQ500 dataset) was collected from different centers in two batches B1 & B2 to clinically validate the algorithms. Main Outcomes and Measures: Original clinical radiology report and consensus of three independent radiologists were considered as gold standard for Qure25k and CQ500 datasets respectively. Area under receiver operating characteristics curve (AUC) for each finding was primarily used to evaluate the algorithms. Results: Qure25k dataset contained 21,095 scans (mean age 43.31; 42.87% female) while batches B1 and B2 of CQ500 dataset consisted of 214 (mean age 43.40; 43.92% female) and 277 (mean age 51.70; 30.31% female) scans respectively. On Qure25k dataset, the algorithms achieved AUCs of 0.9194, 0.8977, 0.9559, 0.9161, 0.9288 and 0.9044 for detecting ICH, IPH, IVH, SDH, EDH and SAH respectively. AUCs for the same on CQ500 dataset were 0.9419, 0.9544, 0.9310, 0.9521, 0.9731 and 0.9574 respectively. For detecting calvarial fractures, midline shift and mass effect, AUCs on Qure25k dataset were 0.9244, 0.9276 and 0.8583 respectively, while AUCs on CQ500 dataset were 0.9624, 0.9697 and 0.9216 respectively.
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