17-Hydroxyprogesterone Caproate for the Prevention of Recurrent Preterm Birth – A Systematic Review and Meta-analysis Taking into Account the PROLONG Trial

Background Prior spontaneous preterm birth is a strong risk factor for the recurrence of spontaneous preterm birth in a subsequent pregnancy and has been evaluated in prevention studies using progesterone (natural progesterone administered orally or vaginally, and 17-hydroxyprogesterone caproate [17-OHPC]) as a selection criterion. Based on the findings of a randomized, placebo-controlled study, 17-OHPC was approved for use in 2011 by the Food and Drug Administration in the USA for the prevention of recurrent preterm birth. The approval was granted with qualification that a subsequent confirmatory study would need to be carried out, the results of which have just been published (PROLONG trial). Method A systematic literature search for the period from 1970 to April 2020 using the search terms “preterm birth” and “17-OHPC” or “progesterone” was carried out. Only randomized, placebo-controlled studies of women with singleton pregnancies who received 17-OHPC to prevent recurrent preterm birth were included in the subsequent meta-analysis. The relative risk and associated 95% confidence intervals were calculated. The heterogeneity between studies was evaluated with I ² statistics. Results In addition to the original study used for the approval and the PROLONG trial, only one other study was found which met the inclusion criteria (total number of patients: 2221). With considerable heterogeneity between the studies, particularly with respect to the risk factors for preterm birth, the comparison between 17-OHPC and placebo showed no significant reduction in preterm birth rates before 37, 35 and 32 weeks of gestation and no significant differences with regard to the prevalence of miscarriage before 20 weeks of gestation or fetal deaths (antepartum or intrapartum) after 20 weeks of gestation and neonatal morbidity. Conclusion Based on the currently available data, 17-OHPC cannot be recommended for the prevention of recurrent preterm birth. Further randomized, placebo-controlled studies with clearly defined, comparable risk factors are required to identify the group of pregnant women which could benefit from the use of 17-OHPC to prevent preterm birth. Key words: preterm birth, progesterone, 17α-hydroxyprogesterone caproate, prevention     

Outpatient Induction of Labor – Are Balloon Catheters an Appropriate Method?

As the number of labor inductions in high-income countries has steadily risen, hospital costs and the additional burden on obstetric staff have also increased. Outpatient induction of labor is therefore becoming increasingly important. It has been estimated that 20 – 50% of all pregnant women requiring induction would be eligible for outpatient induction. The use of balloon catheters in patients with an unripe cervix has been shown to be an effective and safe method of cervical priming. Balloon catheters are as effective as the vaginal administration of prostaglandin E ₂ or oral misoprostol. The advantage of using a balloon catheter is that it avoids uterine hyperstimulation and monitoring is less expensive. This makes balloon catheters a suitable option for outpatient cervical ripening. Admittedly, intravenous administration of oxytocin to induce or augment labor is required in approximately 75% of cases. Balloon catheters are not associated with a higher risk of maternal and neonatal infection compared to vaginal PGE ₂ . Low-risk pregnancies (e.g., post-term pregnancies, gestational diabetes) are suitable for outpatient cervical ripening with a balloon catheter. The data for high-risk pregnancies are still insufficient. The following conditions are recommended when considering an outpatient approach: strict selection of appropriate patients (singleton pregnancy, cephalic presentation, intact membranes), CTG monitoring for 20 – 40 minutes after balloon placement, the patient must be given detailed instructions about the indications for immediate readmission to hospital, and 24-hour phone access to the hospital must be ensured. According to reviewed studies, the balloon catheter remained in place between 12 hours (“overnight”) and 24 hours. The most common reason for readmission to hospital was expulsion of the balloon catheter. The advantages of outpatient versus inpatient induction of cervical ripening with a balloon catheter were the significantly shorter hospital stay, the lower costs, and higher patient satisfaction, with both procedures having been shown to be equally effective. Complication rates (e.g., vaginal bleeding, severe pain, uterine hyperstimulation syndrome) during the cervical ripening phase are low (0.3 – 1.5%); severe adverse outcomes (e.g., placental abruption) have not been reported. Compared to inpatient induction of labor using vaginal PGE ₂ , outpatient cervical ripening using a balloon catheter had a lower rate of deliveries/24 hours and a significantly higher need for oxytocin; however, hospital stay was significantly shorter, frequency of pain during the cervical ripening phase was significantly lower, and patientsʼ duration of sleep was longer. A randomized controlled study comparing outpatient cervical priming with a balloon catheter with outpatient or inpatient induction of labor with oral misoprostol would be of clinical interest. Key words: outpatient/inpatient induction of labor/cervical priming, balloon catheter, prostaglandins, efficacy, safety     

Is there a need for lumbar orthosis in mild compression fractures of the thoracolumbar spine?: A retrospective study comparing the radiographic results between early ambulation with and without lumbar orthosis

Compression fractures of the thoracolumbar spine are common in spinal trauma. Most patients are treated with early ambulation. Bracing is an option not always recommended by the treating team. There are no definite recommendations so far regarding the need for lumbar orthosis in this type of injury. The authors retrospectively compared two methods for treating patients with compression as great as 30%: early ambulation with and without lumbar orthosis. The results show that although demographic variables, type of injury, and cause of injury were similar between the groups, neither treatment emerged as superior. Thoracolumbar fractures with compression as much as 30% can be treated with early ambulation and no external support. Close clinical and radiographic follow-up is essential.     

Percutaneous transluminal myocardial revascularisation: current status and future perspectives

Percutaneous transluminal myocardial revascularisation presently appears to be a potential palliative treatment for coronary artery disease, neither controlled with drugs nor amenable to available coronary revascularisation techniques. Ongoing trials will provide answer to short and long term efficacy. Recent developments using angiogenic growth factors appear very promising, and the role of growth factors as an adjunct to percutaneous transmyocardial revascularisation with laser remains to be seen.     

Risk assessment in COVID‐19: Prognostic importance of cardiovascular parameters

BackgroundCardiovascular risk factors and comorbidities are highly prevalent among COVID‐19 patients and are associated with worse outcomes.HypothesisWe therefore investigated if established cardiovascular risk assessment models could efficiently predict adverse outcomes in COVID‐19. Furthermore, we aimed to generate novel risk scores including various cardiovascular parameters for prediction of short‐ and midterm outcomes in COVID‐19.MethodsWe included 441 consecutive patients diagnosed with SARS‐CoV‐2 infection. Patients were followed‐up for 30 days after the hospital admission for all‐cause mortality (ACM), venous/arterial thromboembolism, and mechanical ventilation. We further followed up the patients for post‐COVID‐19 syndrome for 6 months and occurrence of myocarditis, heart failure, acute coronary syndrome (ACS), and rhythm events in a 12‐month follow‐up. Discrimination performance of DAPT, GRACE 2.0, PARIS‐CTE, PREDICT‐STABLE, CHA2‐DS2‐VASc, HAS‐BLED, PARIS‐MB, PRECISE‐DAPT scores for selected endpoints was evaluated by ROC‐analysis.ResultsOut of established risk assessment models, GRACE 2.0 score performed best in predicting combined endpoint and ACM. Risk assessment models including age, cardiovascular risk factors, echocardiographic parameters, and biomarkers, were generated and could successfully predict the combined endpoint, ACM, venous/arterial thromboembolism, need for mechanical ventilation, myocarditis, ACS, heart failure, and rhythm events. Prediction of post‐COVID‐19 syndrome was poor.ConclusionRisk assessment models including age, laboratory parameters, cardiovascular risk factors, and echocardiographic parameters showed good discrimination performance for adverse short‐ and midterm outcomes in COVID‐19 and outweighed discrimination performance of established cardiovascular risk assessment models.     

Proliferative responses in the placenta after endotoxin exposure in preterm fetal sheep

OBJECTIVES: Antenatal infections are associated with an increased risk of perinatal morbidity and mortality. Systemic application of endotoxins to the fetus results in an increase in placental vascular resistance and chronic reduction in umbilical blood flow. We studied morphological alterations of the placenta in response to fetal inflammation in the preterm sheep. STUDY DESIGN: Therefore, 14 fetal sheep were chronically instrumented at a mean gestational age of 107+/-1 days (term is 147 days). Four days after surgery fetuses received 100 ng lipopolysaccharide (LPS; n=8) or saline (control; n=6) intravenously. Fetal heart rate and arterial blood pressure were monitored continuously while blood gases and acid-base balance were measured at time points 0, +1, +3, +6, +12, +24, +48 and +72 h. Three days after LPS application placental cotyledons were analyzed by immunohistochemistry and morphometry. Different primary antibodies like AE 1 and AE 3 against cytokeratins were used. Secondary antibodies were visualized with 3-amino-9-ethylcarbazole (AEC) or using the Vectastain kit (Vector Laboratories, Burlingame, CA). Double staining was carried out first by utilizing Vectastain kit (black), followed by AEC staining (red). Counterstaining was performed with haematoxylin. RESULTS: Fetal tachycardia and hypertension were induced transiently during the first 12h after LPS application. Fetuses suffered from mild hypoxaemia while acidemia was absent. Morphometry revealed a non-significant shift in the relation of maternal and fetal placental compartments towards the maternal parts in response to LPS treatment. Endotoxin induced an increased proliferation in both compartments of the placenta with a 3.2-fold increase on the maternal and a 1.8-fold increase on the fetal side. CONCLUSIONS: Systemic endotoxin exposure of the preterm fetal sheep leads to a change in the gross organization of the placenta and changes in the proliferation patterns in both placental compartments. These rearrangements inside the placenta may disturb its organ function and subsequently lead to fetal morbidity associated with the fetal inflammatory response syndrome and chronic placental dysfunction, respectively.     

Thromboembolic diseases in pregnancy

In pregnancy, thromboembolic complications are six times more frequent than in nonpregnant women. Maternal age, idiopathic or secondary thrombosis in the patients history, the mode of delivery, bed rest and / or obesity as well as the thrombophilic defects are considerable factors for an increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE). Compared to unfractionated heparins (UFHs) prophylactic treatment relies mainly on low molecular weight heparins (LMWHs) which safety is now well established in pregnant women. In view of their multiple side effects oral anticoagulants such as cumarine or aspirin are contraindicated or of subordinate importance. The procedures to exclude DVT follow the usual diagnostic algorithms considering maximum radiation protection in case of further apparative diagnostics. Although there are reported good experiences with LMWHs in the treatment of DVT, UFHs are still the preferred drugs in this clinical condition. Insufficient heparin treatment or impending postthrombotic complications may be reasons for additional therapies like thrombolysis or operative thrombectomy.