Long-term treatment-related morbidity in differentiated thyroid cancer: a systematic review of the literature

Background: Differentiated thyroid cancer (DTC) occurs in relatively young patients and is associated with a good prognosis and long survival. The management of this disease involves thyroidectomy, radioiodine therapy, and long-term thyroid-stimulating hormone suppression therapy (THST). The long-term effects of the treatment and the interaction between subclinical hyperthyroidism and long-term hypoparathyroidism are poorly understood. This review sought to examine the available evidence. Methods: A PubMed search was carried out using the search terms “Thyroid Neoplasms” AND (“Thyroxine” OR “Hypocalcemia” OR “Thyrotropin”). Original English language articles published in the last 30 years studying the morbidity from thyroid-stimulating hormone (TSH) suppression and hypoparathyroidism following a surgery for DTC were retrieved and reviewed by 2 authors. Results: Of the 3,000 results, 66 papers including 4,517 patients were selected for the present study. Studies reported on a range of skeletal (included in 34 studies, 1,647 patients), cardiovascular (17 studies, 957 patients), psychological (10 studies, 663 patients), and other outcomes (10 studies, 1,348 patients). Nine of 26 studies on patients who underwent THST showed a reduction in bone density, and 13 of 23 studies showed an increase in bone turnover markers. Skeletal effects were more marked in postmenopausal women. There was no evidence of increased fracture risk, and only little data were available on hypoparathyroidism. Four of five studies showed an increased left ventricular mass index on echocardiography, and one study showed a higher prevalence of atrial fibrillation (AF). There was little difference in basic physiological parameters and limited literature regarding symptoms or significant events. Six studies showed associations between long-term TSH suppression and impaired quality of life. Impaired glucose metabolism and prothrombotic states were also found in DTC patients. Conclusion: There is limited literature regarding long-term DTC treatment-related morbidity, particularly regarding the effects of long-term hypocalcemia. Most studies have focused on surrogate markers and not on clinical outcomes. A large prospective study on defined clinical outcomes would help characterize the morbidity of treatment and stimulate research on tailoring treatment strategies

The role of platelet P2Y12 receptors in inflammation

Inflammation is a complex pathophysiological process underlying many clinical conditions. Platelets contribute to the thrombo-inflammatory response. Platelet P2Y12 receptors amplify platelet activation, potentiating platelet aggregation, degranulation and shape change. The contents of platelet alpha granules, in particular, act directly on leucocytes, including mediating platelet–leucocyte aggregation and activation via platelet P-selectin. Much evidence for the role of platelet P2Y12 receptors in inflammation comes from studies using antagonists of these receptors, such as the thienopyridines clopidogrel and prasugrel, and the cyclopentyltriazolopyrimidine ticagrelor, in animal and human experimental models. These suggest that antagonism of P2Y12 receptors decreases markers of inflammation with some evidence that this reduces incidence of adverse clinical sequelae during inflammatory conditions. Interpretation is complicated by pleiotropic effects such as those of the thienopyridines on circulating leucocyte numbers and of ticagrelor on adenosine reuptake. The available evidence suggests that P2Y12 receptors are prominent mediators of inflammation and P2Y12 receptor antagonism as a potentially powerful strategy in a broad range of inflammatory conditions

Ticagrelor : clinical development and future potential

Platelets participate centrally in atherothrombosis, resulting in vessel occlusion and ischaemia. Consequently, optimisation of antiplatelet regimens has the potential to further reduce the residual burden of morbidity and mortality associated with atherosclerosis. Ticagrelor is a potent oral platelet P2Y12 receptor antagonist that (1) inhibits a central amplification pathway of platelet activation directly as well as via an active metabolite, (2) has a rapid onset and offset of antiplatelet action that remains consistent in the circulation during twice-daily administration and is amenable to reversal, (3) has inverse agonist properties, and (4) demonstrates pleiotropic effects that contribute to anti-thrombotic, anti-inflammatory and vasodilatory properties. These advantageous characteristics of ticagrelor have translated to beneficial clinical outcomes in patients with acute coronary syndromes or ischaemic stroke, during prolonged maintenance therapy in specific high-risk populations, and following percutaneous coronary intervention but not definitively following coronary artery bypass graft surgery or in peripheral artery disease patients. Novel innovative strategies aim to reduce the risk of bleeding during dual antiplatelet therapy via shortening the duration of treatment and replacing the standard-of-care with ticagrelor monotherapy. In cases where aspirin is an essential component in secondary prevention, dose modification when combined with ticagrelor may hypothetically provide desirable clinical outcomes following appropriate clinical assessment as predicted by pharmacological studies. Overall, the future management of acute coronary syndromes could potentially involve the dichotomisation of antithrombotic therapies, whereby only those with high-risk of ischaemia, without a high-risk of bleeding, receive ticagrelor plus very-low-dose aspirin, while ticagrelor monotherapy is administered to the remaining majority

Treatment inequity in antiplatelet therapy for ischaemic heart disease in patients with advanced chronic kidney disease: releasing the evidence vacuum

Chronic kidney disease (CKD) is a global health problem and an independent risk factor for cardiovascular morbidity and mortality. Despite evidence-based therapies significantly improving cardiovascular mortality outcomes in the general population and those with non-dialysis-dependent CKD, this risk reduction has not translated to patients with end-stage kidney disease (ESKD). Absent from all major antiplatelet trials, this has led to insufficient safety data for P2Y12 inhibitor prescriptions and treatment inequity in this subpopulation. This review article presents an overview of the progression of research in understanding antiplatelet therapy for ischaemic heart disease in patients with advanced CKD (defined as eGFR <30 mL/min/1.73 m2). Beyond trial recruitment strategies, new approaches should focus on registry documentation by CKD stage, risk stratification with biomarkers associated with inflammation and haemorrhage and building a knowledge base on optimal duration of dual and single antiplatelet therapies

Prevention of stroke in patients with chronic coronary syndromes or peripheral arterial disease

Stroke is a common and devastating condition caused by atherothrombosis, thromboembolism, or haemorrhage. Patients with chronic coronary syndromes (CCS) or peripheral artery disease (PAD) are at increased risk of stroke because of shared pathophysiological mechanisms and risk-factor profiles. A range of pharmacological and non-pharmacological strategies can help to reduce stroke risk in these groups. Antithrombotic therapy reduces the risk of major adverse cardiovascular events, including ischaemic stroke, but increases the incidence of haemorrhagic stroke. Nevertheless, the net clinical benefits mean antithrombotic therapy is recommended in those with CCS or symptomatic PAD. Whilst single antiplatelet therapy is recommended as chronic treatment, dual antiplatelet therapy should be considered for those with CCS with prior myocardial infarction at high ischaemic but low bleeding risk. Similarly, dual antithrombotic therapy with aspirin and very-low-dose rivaroxaban is an alternative in CCS, as well as in symptomatic PAD. Full-dose anticoagulation should always be considered in those with CCS/PAD and atrial fibrillation. Unless ischaemic risk is particularly high, antiplatelet therapy should not generally be added to full-dose anticoagulation. Optimization of blood pressure, low-density lipoprotein levels, glycaemic control, and lifestyle characteristics may also reduce stroke risk. Overall, a multifaceted approach is essential to best prevent stroke in patients with CCS/PAD

Prolonged enoxaparin therapy compared with standard-of-care antithrombotic therapy in opiate-treated patients undergoing primary percutaneous coronary intervention

A novel enoxaparin regimen consisting of intra-arterial bolus (0.75 mg/kg) followed by intravenous infusion (0.75 mg/kg/6 hours) has been developed as a possible solution to the delayed absorption of oral P2Y12 inhibitors in opiate-treated ST-elevation myocardial infarction (STEMI) patients undergoing primary angioplasty. We aimed to study the feasibility of this regimen as an alternative to standard-of-care treatment (SOC) with unfractionated heparin ± glycoprotein IIb/IIIa antagonist (GPI). One hundred opiate-treated patients presenting with STEMI and accepted for primary angioplasty were randomized (1:1) to either enoxaparin or SOC. Fifty patients were allocated enoxaparin (median age 61, 40% females) and 49 allocated SOC (median age 62, 22% females). One developed stroke before angiography and was withdrawn. One SOC patient had a gastrointestinal bleed resulting in 1 g drop in hemoglobin and early cessation of GPI infusion. Two enoxaparin patients had transient minor bleeding: one transient gingival bleed and one episode of coffee ground vomit with no hemoglobin drop or hemodynamic instability. Two SOC and no enoxaparin group patients had acute stent thrombosis. These preliminary data support further study of this novel 6-hour enoxaparin regimen in opiate-treated PPCI patients

Computed tomography chest imaging offers no advantage over chest X-ray in the initial assessment of gestational trophoblastic neoplasia

Background The International Federation of Gynaecology and Obstetrics (FIGO) score identifies gestational trophoblastic neoplasia (GTN) patients as low- or high-risk of single-agent chemotherapy resistance (SACR). Computed tomography (CT) has greater sensitivity than chest X-ray (CXR) in detecting pulmonary metastases, but effects upon outcomes remain unclear. Methods Five hundred and eighty-nine patients underwent both CXR and CT during GTN assessment. Treatment decisions were CXR based. The number of metastases, risk scores, and risk category using CXR versus CT were compared. CT-derived chest assessment was evaluated as impact upon treatment decision compared to patient outcome, incidence of SACR, time-to-normal human chorionic gonadotrophin hormone (TNhCG), and primary chemotherapy resistance (PCR). Results Metastasis detection (p < 0.0001) and FIGO score (p = 0.001) were higher using CT versus CXR. CT would have increased FIGO score in 188 (31.9%), with 43 re-classified from low- to high-risk, of whom 23 (53.5%) received curative single-agent chemotherapy. SACR was higher when score (p = 0.044) or risk group (p < 0.0001) changed. Metastases on CXR (p = 0.019) but not CT (p = 0.088) lengthened TNhCG. Logistic regression analysis found no difference between CXR (area under the curve (AUC) = 0.63) versus CT (AUC = 0.64) in predicting PCR. Conclusions CT chest would improve the prediction of SACR, but does not influence overall treatment outcome, TNhCG, or prediction of PCR. Lower radiation doses and cost mean ongoing CXR-based assessment is recommended