Thomsonterrell4415

Purpose of review Primary headaches are less common and differ in presentation in older versus younger individuals. Secondary headaches become more common among older patients. Recent findings Diagnosis and management of headaches in those > 65 years are discussed. Migraine and tension-type headaches are rarely new onset in this age group and should be a diagnosis of exclusion. In older individuals, migraine is more likely to be bilateral with less sensory sensitivities. Migraine aura may present without headache; careful assessment is needed to exclude stroke. Diphenyleneiodonium Other primary headaches discussed include cough, hypnic, and other headaches. link2 Secondary causes discussed include giant cell arteritis, trigeminal post-herpetic neuropathy, sleep apnea, cardiac cephalgia, cervicogenic pain, vascular etiologies, medications, and burning-mouth syndrome. In older individuals, primary headaches are diagnoses of exclusion, and treatment is affected by comorbidities and polypharmacy. Secondary headaches are a major consideration requiring appropriate workup. Many treatments can safely be offered regardless of age.We tested the hypothesis that adjunctive thrombolysis at time of primary percutaneous coronary intervention (PCI) may affect favourably the long-term outcome of patients with ST elevation myocardial infarction (STEMI). To this end, we undertook a substudy of the DISSOLUTION (Delivery of thrombolytIcs before thrombectomy in patientS with ST-segment elevatiOn myocardiaL infarction Undergoing primary percuTaneous coronary interventION) trial. A total of 95 patients were randomized to local delivery of urokinase (n = 48) or placebo (n = 47). After PCI, a greater proportion of patients receiving urokinase had an improvement in myocardial perfusion, as indicated by a significantly higher final Thrombolysis in myocardial infarction (TIMI) grade 3, myocardial blush grade, and 60-min ST-segment resolution > 70%, as well as lower corrected TIMI frame count. At 1-year echocardiography, urokinase-treated patients exhibited significantly lower LV dimension, as well as higher LV ejection fraction and wall motion score index as compared with placebo-treated patients. At 5 years, major acute cardiovascular events (MACEs) were significantly less common in the urokinase group (P = 0.023), mainly due to a lower occurrence of hospitalisation for heart failure (P = 0.038). Multivariate analysis showed that factors independently associated with 5-year occurrence of MACEs were LV remodelling at 1-year echocardiography (P = 0.0001), 1-year LV ejection fraction (P = 0.0001), TIMI grade flow 0-2 (P = 0.0019), and age at time of PCI (P = 0.0173). In conclusion, low-dose intracoronary urokinase during primary PCI is associated with a more favourable 5-year outcome of patients with STEMI.As the degree of luminal narrowing increases, shear stress increases, and high shear stress is known to activate platelets. However, the relationship between the degree of luminal narrowing and the composition of thrombus in patients with plaque erosion has not been studied. A total of 148 patients with plaque erosion and thrombus detected by optical coherence tomography were divided into tertiles based on the minimum lumen area (MLA) at the culprit lesion. Thrombus was categorized as platelet-rich or fibrin-rich. Among 148 patients, 50 (34%) were in the mild stenosis group, 49 (33%) were in the moderate stenosis group, and 49 (33%) were in the severe stenosis group. The composition of thrombus was significantly different among the 3 groups (prevalence of platelet-rich thrombus was 60% in the mild stenosis group; 78% in the moderate stenosis group; and 84% in the severe stenosis group; P = 0.021). The pattern of fibrin-rich thrombus showed the opposite 40%, 22%, and 16%, respectively. In the multivariate analysis, current smoking was independently associated with fibrin-rich thrombus (odds ratio [OR] 2.364 [95% CI 1.004-5.567], P = 0.049). This study demonstrated that platelet-rich thrombus was the predominant type of thrombus in plaque erosion. The prevalence of fibrin-rich thrombus was highest in the mild stenosis group.Pemigatinib (PEMAZYRE™), a small molecule inhibitor of fibroblast growth factor receptor (FGFR) 1, FGFR2 and FGFR3, received accelerated approval in April 2020 in the USA for the treatment of adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma and a FGFR2 fusion or other rearrangement, as detected by a US FDA-approved test. Developed by Incyte Corporation, it is the first targeted treatment for cholangiocarcinoma in the USA. The recommended dosage of pemigatinib is 13.5 mg once daily, administered orally with or without food, on days 1-14 of a 21-day cycle until disease progression or unacceptable toxicity. Pemigatinib received orphan designation for the treatment of myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2 in August 2019 in the USA. A regulatory assessment for pemigatinib as a treatment for adults with locally advanced or metastatic cholangiocarcinoma and a FGFR2 fusion or rearrangement that is relapsed or refractory after ≥ 1 line of systemic therapy is underway in the EU. Pemigatinib is also undergoing clinical development in various countries worldwide for use in several other FGFR-driven malignancies (e.g. solid tumour, urothelial carcinoma). This article summarizes the milestones in the development of pemigatinib leading to this first approval for the treatment of adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma and a FGFR2 fusion or other rearrangement, as detected by a US FDA-approved test.Background Acute myocardial infarction (AMI) is usually caused by rupture of an atherosclerotic plaque leading to thrombotic occlusion of a coronary artery. Cardiovascular disease has recently emerged as the leading cause of death during hajj. Our aim is to demonstrate the AMI pilgrim's related disparities and comparing them to non-pilgrim patients. Result Out of 3044 of patients presented with AMI from January 2016 to August 2019, 1008 (33%) were pilgrims. They were older in age (P less then 0.001) and showed significantly lower rates cardiovascular risk factors (P less then 0.001 for DM, smoking, and obesity). Pilgrims were also less likely to receive thrombolytic therapy (P less then 0.001), show lower rate of late AMI presentation (P less then 0.001), develop more LV dysfunction post AMI (P less then 0.001), and have critical CAD anatomy in their coronary angiography (P less then 0.001 for MVD and = 0.02 for LM disease) compared to non-pilgrim AMI patients. Despite AMI pilgrims recorded higher rate of primary percutaneous coronary intervention (PPCI) procedures, they still showed poor hospital outcomes (P less then 0.001, 0.004, less then 0.001, 0.05, and 0.001, respectively for pulmonary edema, cardiogenic shock, mechanical ventilation, cardiac arrest, and in-hospital mortality, respectively). Being a pilgrim and presence of significant left ventricular systolic dysfunction, post AMI was the two independent predictors of mortality among our studied patients (P = 0.005 and 0.001, respectively). Conclusion Although AMI pilgrims had less cardiovascular risk factors and they were early revascularized, they showed higher rates of post myocardial infarction complication and poor hospital outcomes. Implementation of pre-hajj screening, awareness and education programs, and primary and secondary preventive measures should be taken in to consideration to improve AMI pilgrim's outcome.Accurate measurement of sedentary time and physical activity (PA) is essential to establish their relationships with rheumatoid arthritis (RA) outcomes. Study objectives were to (1) validate the GT3X+ and activPAL3μ™, and develop RA-specific accelerometer (count-based) cut-points for measuring sedentary time, light-intensity PA and moderate-intensity PA (laboratory-validation); (2) determine the accuracy of the RA-specific (vs. non-RA) cut-points, for estimating free-living sedentary time in RA (field-validation). Laboratory-validation RA patients (n = 22) were fitted with a GT3X+, activPAL3μ™ and indirect calorimeter. Whilst being video-recorded, participants undertook 11 activities, comprising sedentary, light-intensity and moderate-intensity behaviours. Criterion standards for devices were indirect calorimetry (GT3X+) and direct observation (activPAL3μ™). Field-validation RA patients (n = 100) wore a GT3X+ and activPAL3μ™ for 7 days. link3 The criterion standard for sedentary time cut-points (RA-specific vs. nonRA cut-points.Treatment recommendations of early rheumatoid arthritis (RA) suggest differential management of patients on the basis of prognostic factors. In this study we aimed to investigate the relationship between autoantibodies against a novel citrullinated fibrinogen peptide (anti-CFP), smoking status, clinical activity and therapeutic response in Cuban patients with early RA, receiving treatment with methotrexate in comparison to rheumatoid factor (RF), anti-cyclic citrullinated peptide of second generation (anti-CCP2) and anti-mutated citrullinated vimentin (anti-MCV). A 6-month prospective observational study was performed in 60 early RA patients at baseline and 6 months after receiving methotrexate. Baseline and outcome measures included disease activity score of 28 joints (DAS 28), simplified disease activity index (SDAI), anti-CFP antibodies, RF, anti-CCP2 and anti-MCV. Therapeutic response was determined using 20/50/70 American College of Rheumatology (ACR) response rates. DAS28 (p less then 0.0001), SDAI (p less then 0.0001) as well as titres of anti-CFP (p = 0.0481), anti-CCP2 (p = 0.0082), RF IgM (p = 0.0187) and RF IgA (p = 0.0252) decreased under therapy. Multivariate analyses showed association of final anti-CFP values with sex and smoking status (p = 0.0296). It is of note that anti-CFP antibodies were one of predictors for DAS 28 (p = 0.0072) SDAI (p less then 0.0001) and ACR response (p = 0.0003) in multivariate models. Anti-CFP antibodies decrease in correspondence with clinical improvement after 6-month therapy and are associated with sex and smoking status. Moreover, baseline anti-CFP antibodies, using in combination with sex, smoking status and autoantibodies (anti-CCP2, anti-MCV or RF) seems to have clinical relevance for predicting clinical activity and therapeutic response.This study aimed to establish an in vitro model for lipid synthesis in primary bovine mammary epithelial cells (pbMECs) extracted from milk and cultured on Transwell permeable supports (TW culture). The suitability of these cells as a functional model for lactation was assessed by measuring κ-casein (CSN3) and diacylglycerol acyl transferase 1 (DGAT1) gene expression, the presence of intracellular lipid droplets, and the concentration of triacylglycerol in the cell lysates. The functionality of the milk-derived pbMECs cultured under lactogenic conditions, with and without oleic acid supplementation, was evaluated by comparing the cells grown on Transwell supports to cells grown on an extracellular matrix (ECM) gel (3D culture) or a plastic surface (2D culture). Furthermore, the functionality of milk-derived cells was compared to pbMECs obtained from bovine mammary tissue. Here, we show that in both tissue and milk-derived pbMECs, 3D culture offered the most suitable in vitro environment and led to increased levels of CSN3 and DGAT1 gene expression along with increased intracellular triacylglycerol content.