Impact of direct acting antivirals (DAAs) on cardiovascular events in HCV cohort with pre-diabetes

Background and aimsBeyond type 2 diabetes, even a condition of prediabetes is associated with an increased cardiovascular (CV) risk, and HCV infection coexistence represents an exacerbating factor. CV prognosis improvement in prediabetes represents a challenge, due to the increasing prevalence of this metabolic condition worldwide. Hence, we aimed to prospectively assess how direct acting antivirals (DAAs) could affect major cardiovascular events (MACE) in a prediabetic HCV positive cohort.Methods and resultsIn this prospective multicenter study, we enrolled HCV patients with overt prediabetes. We compared a subgroup of patients treated with DAAs with untreated prediabetic controls. We recorded all CV events occurred during an overall median follow-up of 24 months (IQR 19–34). 770 HCV positive prediabetic patients were enrolled, 398 untreated controls and 372 DAAs treated patients. Overall, the CV events annual incidence was much higher among prediabetic treated patients (1.77 vs. 0.62, p < 0.001), and HCV clearance demonstrated to significantly reduce CV events (RR: 0.411, 95%CI 0.148–1.143; p < 0.001), with an estimated NNT for one additional patient to benefit of 52.1. Moreover, an independent association between a lower rate of CV events and HCV clearance after DAAs was observed (OR 4.67; 95%CI 0.44–53.95; p = 0.016).ConclusionsHCV eradication by DAAs allows a significant reduction of MACEs in the prediabetic population, and therefore represents a primary objective, regardless of the severity of liver disease and CV risk factors.     

Comparison between bioactive and immunoactive luteinizing hormone (LH) in ovariectomized streptozotocin-induced diabetic rats: response to LH-releasing hormone

The effect of streptozotocin-induced diabetes on circulating levels of immunoactive LH (I-LH) and bioactive LH (B-LH) was investigated. LH was measured in adult ovariectomized (OVX) rats before and after acute LHRH administration, with or without estradiol benzoate (Eb) treatment (10 micrograms, 48 and 24 h before experiments). I-LH and B-LH were measured in the same samples by RIA and the rat interstitial cell testosterone assay, respectively. OVX diabetic animals showed a significant reduction in both I-LH (63%) and B-LH (73%). Treatment with Eb induced a decrease in basal I-LH and B-LH levels in all experimental groups (50%). These values were normalized after insulin therapy. No alterations in the pituitary responsiveness to LHRH were detected when I-LH levels were determined. However, B-LH levels assayed after LHRH stimulation were significantly decreased in diabetic animals. Insulin treatment was unable to restore this response. The effect of Eb treatment on these parameters was also tested. In these conditions LHRH injections induced similar increases in serum I-LH and B-LH in both diabetic and control rats. These results indicate that, in diabetic OVX rats, basal and LHRH-induced LH has a reduced bioactivity, but this reduction is reversed by Eb treatment. This might indicate that the major defect lies in the ovary rather than at the pituitary level, supporting the notion of an important role of the steroid milieu on the B-LH modulation.     

Laser and brachytherapy in the palliation of adenocarcinoma of the oesophagus and cardia.

BACKGROUND: Palliation of malignant dysphagia is possible by a variety of methods although all have significant drawbacks. Laser therapy is an effective and safe treatment but has to be repeated at four to five weekly intervals to maintain palliation. A means of augmenting the benefits while reducing the need for repeat treatments would be highly beneficial to these patients. AIMS: To prospectively explore the safety and efficacy of intraluminal radiotherapy (brachytherapy) when used to augment laser recanalisation for malignant dysphagia. PATIENTS: Nineteen patients with dysphagia due to advanced adenocarcinoma of the oesophagus or cardia were recruited. METHODS: All patients received laser recanalisation until able to swallow a soft diet or better, before the application of a single dose of brachytherapy (10 Gy at 1 cm from the source). Patients were followed up and treated promptly by further endoscopic means in the event of their dysphagia worsening. RESULTS: Six patients (32%) required no further treatment until death at a median of 10 weeks (range 1-20 weeks). Further therapy was required at a median of 11 weeks (range 4-37 weeks) after brachytherapy for those 13 patients with recurrent dysphagia. Subsequent symptom control required endoscopic intervention at an average of once every nine weeks. There was no mortality associated with laser or brachytherapy. Median survival from initial treatment and including the one survivor was 36 weeks (range 5-132 weeks). CONCLUSIONS: Laser plus brachytherapy offers a safe and effective means of palliating malignant dysphagia due to adenocarcinoma, with a longer dysphagia free interval than historical controls treated with laser alone.