Using apheresis to remove a serum protein called soluble Fms-like tyrosine kinase-1 (Sflt-1) may help pregnant women with severe preeclampsia safely delay delivery, according to a pilot study.

‘Based on recent advances in the understanding of this condition, we and others are developing treatments for preeclampsia to allow women to safely prolong their pregnancy if they are suffering from very preterm preeclampsia,’ first author Ravi Thadhani, MD, MPH, from Massachusetts General Hospital in Boston, said in a press release.

Symptoms of preeclampsia include high blood pressure and proteinuria. The condition affects between 3% and 8% of pregnancies worldwide and can be harmful or even fatal to both the mother and newborn. Because of limited understanding about its underlying mechanisms, no cure exists other than delivery, which can be problematic if preeclampsia develops very early in pregnancy, the authors note.

In the open pilot study, Dr Thadhani and colleagues tested the safety and efficacy of removing sFlt-1 from the blood of pregnant women with very preterm preeclampsia. The serum protein sFLT-1 acts as a receptor for vascular endothelial growth factor. By inhibiting vascular endothelial growth factor activity, sFTL-1 modifies blood vessel growth. Women with preeclampsia often have elevated sFTL-1 levels.

Using apheresis, researchers removed the blood from 11 pregnant women and passed it through a negatively charged dextran sulfate column to bind and remove the positively charged sFLT-1. Participants were aged 20 to 38 years and were between 23 to 32 weeks of gestation. Inclusion criteria included systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher, new-onset protein/creatinine ratio higher than 0.30 g/g, and sFLT-1/placental growth factor ratio higher than 85.

Apheresis resulted in an 18% (range, 7% – 28%) reduction in mean sFLT-1 levels, as well as reductions of 44% in protein/creatinine ratios.

Pregnancy continued 8 days after admission (range, 2 – 11 days) in six women treated once with apheresis, and 12 days (range, 7 – 19 days) in five women treated multiple times. In comparison, delivery occurred after 3 days (range, 0 – 14 days) in untreated women with preeclampsia (n = 22) and women who delivered preterm for other reasons (n = 22); the control participants, who had been treated contemporaneously, were matched to the treated women for several factors, including gestational age at delivery.

Although antihypertensive treatments were withheld the morning of the apheresis treatment, the most common adverse effect of apheresis was transient hypotension, which was treated with saline hydration and decreasing blood flow through the column. Hypotension was not severe enough to cause any of the women to stop treatments. No significant changes in foetal heart monitoring occurred during apheresis.

Babies born to apheresis-treated women needed fewer days of supplemental oxygen than babies born to untreated women. However, neonatal test results, total days in the neonatal ICU, and days spent in the hospital did not differ between the groups.

‘Our pilot study suggested we can safely prolong pregnancy when we target removal of sFlt-1 in women with severe preterm preeclampsia, and we hope this is confirmed in randomized trials,’ Dr Thadhani. MedScape

Data from the ILUMIEN II trial found that guidance from optimal coherence tomography (OCT) was associated with comparable stent expansion as guidance from intravascular ultrasound (IVUS) in patients undergoing percutaneous coronary intervention (PCI). Coronary stents must be optimally deployed with full lesion coverage and complete stent expansion to optimize outcomes. Less than full expansion can result in stent thrombosis or restenosis. Previous studies have found that the strongest predictor of stent thrombosis and restenosis is the minimum stent area (MSA) achieved after PCI.
Advanced imaging techniques, such as IVUS and OCT, help cardiologists to measure, place, and expand the stent with optimal precision. By achieving greater stent luminal dimensions, IVUS-guidance has been associated with improved event-free survival compared to angiographic guidance alone. Compared to IVUS, OCT has superior resolution but does not penetrate as deeply into the arterial wall. Consequently it has limitations in assessing the true diameter of the native artery. It is unknown whether stent expansion, a surrogate of clinical outcomes, is as great with OCTguidance as with IVUS-guidance.
ILUMIEN II was a prospectively planned, retrospective comparison of OCT-guidance in ILUMIEN I and IVUS-guidance in ADAPT-DES. The overall study population initially included a total of 940 patients (one lesion randomly chosen per patient; 354 from ILUMIEN I and 586 from ADAPTDES). Aft er 1:1 propensity matching, 286 patients/lesions from each group were analyzed (n=572).Both the OCT and IVUS analyses were performed by the CRF Clinical Trials Center.
The primary endpoint was post-PCI stent expansion (%) defined as the minimum stent area (MSA) divided by the mean reference lumen area as assessed by OCT in ILUMIEN I and by IVUS in ADAPT-DES. The secondary endpoints were the following IVUS and OCT core lab measures:
Mean stent expansion (defined as stent volume/stent length divided by the mean reference lumen area);
Prevalence of major edge dissection (≥3 mm in length); Prevalence of major stent malapposition (malapposition distance/luminal diameter ≥20%). The secondary endpoint using angiographic core lab measures (independent of technique) was post-PCI mean lumen diameter (MLD), percent diameter stenosis, and acute gain.
The post-PCI stent expansion was 72.8% [63.3, 81.3] in the OCT-guided group compared to 70.6% [62.3, 78.8] in the IVUSguided group (p=0.29). Similar rates of major stent edge dissection (2.4% vs. 1.0%, p=0.29) and major stent malapposition (1.4% vs. 0.7%, p=0.69) occurred in both groups.

Researchers from North Carolina State University, Institut Langevin and Paris-Descartes University have conducted a proof-of-concept study that raises the possibility of using ultrasound techniques to detect cervical stiffness changes that indicate an increased risk of preterm labour in pregnant women. While additional work needs to be done, it may ultimately give doctors a new tool for determining when to provide treatment that can prevent preterm birth.
Premature births can mean low birth-weights and other medical problems for newborns, but there are steps that doctors can take to reduce the chances of premature birth if early warning signs are detected. One of those early symptoms is a softening of the cervix. Traditionally, this stiffness is assessed by manually palpating the cervix.

Penn Medicine has performed more than 1,200 Transcatheter Aortic Valve Replacements (TAVR) on patients with severe aortic stenosis. At the Transcatheter Cardiac Therapeutics conference in San Francisco, Howard C. Herrmann, MD, the John Winthrop Bryfogle Professor of Cardiovascular Diseasesand director of Penn Medicine

At a median follow-up of 10.9 years, an EORTC study has shown that irradiation of regional nodes in patients with stage I, II, or III breast cancer has a marginal effect on overall survival, the primary endpoint (at 10 years, overall survival was 82.3 % for regional irradiation versus 80.7% for no regional irradiation, (HR=0.87 (95%CI: 0.76, 1.00), p=0.06). The results also showed that disease-free survival, distant-disease-free survival, and breast cancer mortality were significantly improved. Side effects were very limited, although very long-term toxicity of radiation remains unknown.

The phase III EORTC 22922-10925 trial was conducted to evaluate what effect regional node irradiation, i.e., irradiation of the internal mammary and medial supraclavicular lymph nodes, would add to whole breast or chest wall irradiation following surgery in patients with stage I, II, and III breast cancer.

Prof Philip Poortmans of the Radboud university medical center, Nijmegen, The Netherlands says: