Noninvasive induction of angiogenesis in tissues by external suction: sequential optimization for use in reconstructive surgery.

In reconstructive surgery, tissues are routinely transferred to repair a defect caused by trauma, cancer, chronic diseases, or congenital malformations; surgical transfer intrinsically impairs metabolic supply to tissues placing a risk of ischemia-related complications such as necrosis, impaired healing, or infection. Pre-surgical induction of angiogenesis in tissues (preconditioning) can limit postsurgical ischemic complications and improve outcomes, but very few preconditioning strategies have successfully been translated to clinical practice due to the invasiveness of most proposed approaches, their suboptimal effects, and their challenging regulatory approval. We optimized a method that adopts noninvasive external suction to precondition tissues through the induction of hypoxia-mediated angiogenesis. Using a sequential approach in a rodent model, we determined the parameters of application (frequency, suction levels, duration, and interfaces) that fine-tune the balance of enhanced angiogenesis, attenuation of hypoxic tissue damage, and length of treatment. The optimized repeated short-intermittent applications of intermediate suction induced a 1.7-fold increase in tissue vascular density after only 5 days of treatment (p < 0.05); foam interfaces showed the same effectiveness and caused less complications. In a second separate experiment, our model showed that the optimized technique significantly improves survival of transferred tissues. Here we demonstrate that noninvasive external suction can successfully, safely, and promptly enhance vascularity of soft tissues: these translational principles can help design effective preconditioning strategies, transform best clinical practice in surgery, and improve patient outcomes.

A randomised controlled double-blind clinical trial of 17-hydroxyprogesterone caproate for the prevention of preterm birth in twin gestation (PROGESTWIN): evidence for reduced neonatal morbidity.

OBJECTIVE: To determine whether 17 alpha-hydroxyprogesterone caproate (17OHPC) prolongs gestation beyond 37 weeks of gestation (primary outcome) and reduces neonatal morbidity (secondary outcome) in twin pregnancy. DESIGN: Randomised controlled double-blind clinical trial. SETTING: Tertiary-care university medical centre. POPULATION: Unselected women with twin pregnancies. METHODS: Participants received weekly injections of 250 mg 17OHPC (n = 194) or placebo (n = 94), from 16-20 to 36 weeks of gestation. Randomisation was performed using the permuted-block randomisation method. Data were analysed on an intention-to-treat basis. MAIN OUTCOME MEASURE: Preterm birth (PTB) rate before 37 weeks of gestation. RESULTS: There were no significant differences in the average gestational age at delivery, or in the rates of PTB before 37, 32, and 28 weeks of gestation, between the two groups. The proportion of very-low-birthweight neonates (<1500 g) was significantly lower in the 17OHPC group (7.6%) compared with placebo (14.3%) (relative risk, RR 0.5; 95% confidence interval, 95% CI 0.3-0.9; P = 0.01). Progestogen-treated neonates had a significantly lower composite neonatal morbidity (19.1%) compared with placebo (30.9%) (odds ratio, OR 0.53; 95% CI 0.31-0.90; P = 0.02), with significantly lower odds for respiratory distress syndrome (14.4 versus 23.4%; OR 0.55; 95% CI 0.31-0.98; P = 0.04), retinopathy of prematurity (1.1 versus 4.6%; OR 0.21; 95% CI 0.05-0.96; P = 0.04), and culture-confirmed sepsis (3.4 versus 12.8%; OR 0.24; 95% CI 0.10-0.57; P = 0.00). CONCLUSIONS: Intramuscular 17OHPC therapy did not reduce PTB before 37 weeks of gestation in unselected twin pregnancies. Nonetheless, 17OHPC significantly reduced neonatal morbidity parameters and increased birthweight.

The effect of maternal fasting during Ramadan on preterm delivery: a prospective cohort study.

OBJECTIVE: To determine the effect of fasting during the month of Ramadan on the rate of preterm delivery (PTD). DESIGN: A prospective cohort study of women with singleton pregnancies who elected to fast and matched controls. SETTING: Four medical centres in Beirut, Lebanon. POPULATION: Women presenting for prenatal care (20-34 weeks of gestation) during the month of Ramadan, September 2008. METHODS: Data were collected prospectively. The frequency of PTD was evaluated in relation to the duration of fasting and the stage of gestation at the time of fasting. MAIN OUTCOME MEASURES: The primary endpoint was the percentage of pregnant women who had PTD, defined as delivery before 37 completed weeks of gestation. RESULTS: A total of 468 women were approached, of whom 402 were included in the study. There were no differences in smoking history and employment. There was no difference in the proportion of women who had PTD at <37 weeks (10.4% versus 10.4%) or PTD at <32 weeks (1.5% versus 0.5%) in the Ramadan-fasted group and the controls, respectively. The PTD rate was also similar in those who fasted before or during the third trimester. The mean birthweight was lower (3094 ± 467 g versus 3202 ± 473 g, P = 0.024) and the rate of ketosis and ketonuria was higher in the Ramadan-fasted women. On multivariate stepwise logistic regression analysis, fasting was not associated with an increased risk of PTD (odds ratio 0.72; 95% confidence interval 0.34-1.54; P = 0.397). The only factor that had a significant effect on the PTD rate was body mass index (odds ratio 0.43; 95% confidence interval 0.20-0.93; P = 0.033). CONCLUSIONS: Fasting during the month of Ramadan does not seem to increase the baseline risk of preterm delivery in pregnant women regardless of the gestational age during which this practice is observed.

Mesigyna once-a-month combined injectable contraceptive: experience in Latin America.

A phase III clinical study was carried out among 534 fertile Latin American women to evaluate cycle control, side effects, and contraceptive efficacy of a once-a-month combined injectable, Mesigyna, consisting of 50 mg norethisterone enanthate and 5 mg estradiol valerate. The pregnancy rate at 1 year was 0 per 100 woman-years for a total experience of 4688 woman-months. The overall discontinuation rate at one year was 17.9%. Discontinuation rate for bleeding problems was 5.1%. The Colombian women had a significant increase (p <0.001) in bleeding problems compared to other countries. The discontinuation rate for amenorrhea was 1.1%. There were no significant differences between the groups regarding discontinuation for other medical or non-medical reasons. Mean weight gain after one year of use was 1.02 kg. Mesigyna is an appropiate once-a-month injectable contraceptive for Latin American women since it is highly effective and its perception of normal menstrual bleeding is of importance in the Latin American population.