Peptide Receptor Radionuclide Therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours

Peptide Receptor Radionuclide Therapy (PRRT) with radiolabelled somatostatin analogues is a promising treatment option for patients with inoperable or metastasised neuroendocrine tumours. Symptomatic improvement may occur with all of the various ¹¹¹In, ⁹⁰Y, or ¹⁷⁷Lu-labelled somatostatin analogues that have been used. Since tumour size reduction was seldom achieved with ¹¹¹Indium labelled somatostatin analogues, radiolabelled somatostatin analogues with beta-emitting isotopes like ⁹⁰Y and ¹⁷⁷Lu were developed. Reported anti-tumour effects of [⁹⁰Y-DOTA⁰,Tyr³]octreotide vary considerably between various studies: Tumour regression of 50% or more was achieved in 9 to 33% (mean 22%). With [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate treatments, tumour regression of 50% or more was achieved in 28% of patients and tumour regression of 25 to 50% in 19% of patients, stable disease was demonstrated in 35% and progressive disease in 18%. Predictive factors for tumour remission were high tumour uptake on somatostatin receptor scintigraphy and limited amount of liver metastases. The side-effects of PRRT are few and mostly mild, certainly when using renal protective agents: Serious side-effects like myelodysplastic syndrome or renal failure are rare. The median duration of the therapy response for [⁹⁰Y-DOTA⁰,Tyr³]octreotide and [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate is 30 months and more than 36 months respectively. Lastly, quality of life improves significantly after treatment with [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate. These data compare favourably with the limited number of alternative treatment approaches, like chemotherapy. If more widespread use of PRRT is possible, such therapy might become the therapy of first choice in patients with metastasised or inoperable gastroenteropancreatic neuroendocrine tumours. Also the role in somatostatin receptor expressing non-GEP tumours, like metastasised paraganglioma/pheochromocytoma and non-radioiodine-avid differentiated thyroid carcinoma might become more important.     

Development of classification models for early identification of persons at risk for persistent cognitive decline

Objective   To develop two classification models for use in primary care to aid early identification of persons at risk for persistent cognitive decline. Methods   Data were used from the Longitudinal Aging Study Amsterdam (LASA), an ongoing populationbased study. The study sample consisted of 2,021 non-demented men and women aged 58–88 years. Data on relevant predictors of persistent cognitive decline were collected at baseline. Results   The incidence of persistent cognitive decline after three years of follow-up was 4.0 %. In the first model, in which predictors already known or otherwise easily assessed (first set) were included, age was the strongest predictor of persistent cognitive decline, with an increased risk for persons > 75. In addition, having memory problems, low education, and a MMSE score of ≤ 24, resulted in a predictive value for persistent cognitive decline of 43.5 %. In the second classification model, in addition to the first set, predictors requiring additional measurement (e.g. markers determined in blood) were included in the analyses. Age was again the strongest predictor of persistent cognitive decline. In persons > 75 years, having a low total cholesterol level (< 5.0 mmol/L) and a MMSE score of ≤ 24 resulted in a predictive value of 30.0 %. Conclusions   Both models lead to a substantial increase of the predictive value for persistent cognitive decline, that is from 4.0 % to 43.5 % and 30.0 %, and may identify to a large extent a different subsample of persons who are at risk for persistent cognitive decline. The developed classification trees could be useful for case-finding of persons at risk for future persistent cognitive decline who are therefore at risk for dementia, in a feasible and cost-effective manner.     

Impact of repeated antral follicle counts on the prediction of poor ovarian response in women undergoing in vitro fertilization

OBJECTIVE: To study the value of a single antral follicle count and the additional value of repeated counts in different cycles for the prediction of poor ovarian response in IVF. DESIGN: Prospective. SETTING: Tertiary fertility center. PATIENT(S): One hundred twenty women undergoing their first IVF cycle. INTERVENTION(S): Measurement of the number of antral follicles on cycle day 3 in two spontaneous cycles.Ovarian response. RESULT(S): A single antral follicle count is clearly predictive of poor ovarian response and there is good agreement between repeated measurements in subsequent cycles (area under the receiver operating characteristic curve [ROC(AUC)]; cycle 1: 0.87, cycle 2: 0.85). In a logistic regression analysis, information obtained after the second cycle contributed significantly to the prediction of poor response by the antral follicle count of the first cycle. The predictive accuracy of the highest of two counts (ROC(AUC) 0.89) was slightly better than that of each single count. The predictive model with the highest count yielded slightly higher values of specificity and positive predictive value. Sensitivity, negative predictive value, and error rates were slightly lower. CONCLUSION(S): A single antral follicle count is a good predictor of poor ovarian response in IVF. Although the impact of a second antral follicle count on ovarian response predictions in IVF is statistically significant, clinical relevance is very limited. Repeating an antral follicle count in a subsequent cycle is not recommended.     

Complex primary percutaneous coronary intervention with ultrathin-strut biodegradable versus thin-strut durable polymer drug-eluting stents in patients with ST-segment elevation myocardial infarction: A subgroup analysis from the BIOSTEMI randomized trial

Background

Ultrathin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) are superior to thin-strut durable polymer everolimus-eluting stents (DP-EES) with respect to target lesion failure (TLF) at 2 years among patients with ST-segment elevation myocardial infarction (STEMI). We sought to determine the impact of primary percutaneous coronary intervention (pPCI) complexity on long-term clinical outcomes with BP-SES versus DP-EES in STEMI patients.

Methods

We performed a post hoc subgroup analysis from the BIOSTEMI (NCT02579031) randomized trial, which included individual data from 407 STEMI patients enrolled in the BIOSCIENCE trial (NCT01443104). STEMI patients were randomly assigned to treatment with ultrathin-strut BP-SES or thin-strut DP-EES, and further categorized into those undergoing complex versus noncomplex pPCI. Complex pPCI was defined by the presence of ≥1 of the following criteria: 3 vessel treatment, ≥3 stents implanted, ≥3 lesions treated, bifurcation lesion with ≥2 stents implanted, total stent length ≥60 mm, and/or chronic total occlusion treatment. The primary endpoint was TLF, a composite of cardiac death, target-vessel myocardial reinfarction, or clinically indicated target lesion revascularization, within 2 years.

Results

Among a total of 1707 STEMI patients, 421 (24.7%) underwent complex pPCI. Baseline characteristics were similar between groups. At 2 years, TLF occurred in 14 patients (7.1%) treated with BP-SES and 25 patients (11.6%) treated with DP-EES (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.32–1.19; p = 0.15) in the complex pPCI group, and in 28 patients (4.4%) treated with BP-SES and 49 patients (8.2%) treated with DP-EES (HR: 0.54; 95% CI: 0.34–0.86; p = 0.008; p for interaction = 0.74) in the noncomplex pPCI group. Individual TLF components and stent thrombosis rates did not significantly differ between groups.

Conclusion

In a post hoc subgroup analysis from the BIOSTEMI randomized trial, ultrathin-strut BP-SES were superior to thin-strut DP-EES with respect to TLF at 2 years among STEMI patients undergoing both complex and noncomplex pPCI.     

Effect of phosphodiesterase-5 inhibition on SystEmic Right VEntricular size and function. A multicentre,double-blind,randomized, placebo-controlled trial: SERVE

Aims

In adults with congenital heart disease and systemic right ventricles, progressive right ventricular systolic dysfunction is common and is associated with adverse outcomes. Our aim was to assess the impact of the phosphodiesterase-5-inhibitor tadalafil on right ventricular systolic function.

Methods and results

This was a double-blind, randomized, placebo-controlled, multicentre superiority trial (NCT03049540) involving 100 adults with systemic right ventricles (33 women, mean age: 40.7 ± 10.7 years), comparing tadalafil 20 mg once daily versus placebo (1:1 ratio). The primary endpoint was the change in right ventricular end-systolic volume after 3 years of therapy. Secondary endpoints were changes in right ventricular ejection fraction, exercise capacity and N-terminal pro-B-type natriuretic peptide concentration. Primary endpoint assessment by intention to treat analysis at 3 years of follow-up was possible in 83 patients (42 patients in the tadalafil group and 41 patients in the placebo group). No significant changes over time in right ventricular end-systolic volumes were observed in the tadalafil and the placebo group, and no significant differences between treatment groups (3.4 ml, 95% confidence interval −4.3 to 11.0, p = 0.39). No significant changes over time were observed for the pre-specified secondary endpoints for the entire study population, without differences between the tadalafil and the placebo group.

Conclusions

In this trial in adults with systemic right ventricles, right ventricular systolic function, exercise capacity and neuro-hormonal activation remained stable over a 3-year follow-up period. No significant treatment effect of tadalafil was observed. Further research is needed to find effective treatment for improvement of ventricular function in adults with systemic right ventricles.