Update on the safety and efficacy of teriparatide in the treatment of osteoporosis

Following the completion of the Fracture Prevention Trial, teriparatide was approved by the United States Food and Drug Administration and the European Medicine Agency as the first therapeutic anabolic agent for the treatment of postmenopausal women with severe osteoporosis. It subsequently received additional approval for the treatment of osteoporosis in men, and for the treatment of osteoporosis associated with glucocorticoid therapy in men and women at risk of fracture. In this review, we summarize the most important data concerning PTH 1-34 therapy before 2016 in the treatment of osteoporosis, and report some outstanding results published in the last 2 years. New data on safety will also discussed, together with the state of art of nonclassical utilization. Finally, in view of the recent approval of biosimilars, possible future landscapes are discussed

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Java SAM Typed Closures: A Sound and Complete Type Inference System for Nominal Types

The last proposal for Java closures, as emerged in JSR 000335, is mainly innovative in: (1)Use of nominal types, SAM types, for closures; (2) Introduction of target types and compatibility for a contextual typing of closures; (3) Need for a type inference that reconstructs the omitted type annotations of closures and closure arguments. The paper provides a sound and complete type system, with nominal types, for such a type inference and discusses role and formalization of targeting and of compatibility in the designed inference process

[Surgical anatomy of the pancreas with special reference to arterial and venous vascularization of the corporeo-caudal segment]

Thrombosis accounts for 10-20% of the complications that follow human pancreas transplants. The extent to which this is determined by the vascularisation of the transplanted caudocorporeal segment is uncertain. An account is given of the literature data on the surgical anatomy of the pancreas as a whole and a detailed examination is made of the vascularisation of its left segment. Most workers feel that the arterial axis is sufficient to ensure an optimum vascular support. It has been shown, however, that in 25% of cases that branches issuing from the right-hand system (hepatic, superior mesenteric and colic arteries) and insufficiently anastomosed with the splenic artery are also of importance. This suggests that: a preoperative study should be made of the vascular system of the transplant; a double anastomosis should be created between the donor splenic and pancreatic arteries and the host vessels; particular care should be taken to prevent damage to vessels of fundamental importance to the nutrition of the pancreas when the transplant is removed