Fetoscopic laser coagulation for twin-to-twin transfusion syndrome: a comparison of flexible 1.0/1.2 mm fetoscopes with curved sheaths of 2.7/3.3 mm2 vs. 2 mm fetoscopic lens technique with sheaths of 6.6/11.3 mm2.

OBJECTIVES: Fetoscopic laser coagulation of placental anastomoses is usually performed for a treatment of twin-to-twin transfusion syndrome (TTTS). A common complication of fetoscopic laser coagulation for TTTS is preterm preliminary rupture of fetal membranes (PPROM) aggravating the neonatal outcome significantly. However, use of an flexible 1 mm fetoscope with an curved sheath could reduce iatrogenic damage of the amniotic membrane and improve neonatal outcomes after laser treatment. The aim of this study was to compare neonatal outcomes using this flexible fetoscope with curved sheath vs. use of a standard lens technique. METHODS: Outcomes were retrospective analyzed after use of a standard lens fetoscope of 2 mm (sheath 6.63 mm2 or 11.27 mm2 for anterior placenta) and a flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2) in two German centers of fetal surgery, performed during 2006-2019. RESULTS: Neonatal outcome of 247 TTTS patients were analyzed including the rates of double and single fetal survival. The survival of at least one fetus was 97.2 % in the group with the ultrathin technique (n=154) compared to 88.3 % (n=93) in the group with the standard lens fetoscope (p=0.008). Survival of both fetuses was not different between groups (81.0 vs. 75.3 %). The procedure to delivery interval was significantly increased using the ultrathin fetoscope (89.1±35.0 d vs. 71.4±35.4 d, p=0.001) resulting in an increased gestational age at delivery by 11 days on average (231.9±28.1 d vs. 221.1±32.7 d, p=0.012). CONCLUSIONS: Fetal survival can be significantly increased following TTTS using flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2).

Treatment of Classic Mid-Trimester Preterm Premature Rupture of Membranes (PPROM) with Oligo/Anhydramnion between 22 and 26 Weeks of Gestation by Means of Continuous Amnioinfusion: Protocol of a Randomized Multicentric Prospective Controlled TRIAL and Review of the Literature.

BACKGROUND: The classic mid-trimester preterm premature rupture of membranes (PPROM) is defined as a rupture of the fetal membranes prior to 28 weeks of gestation (WG) with oligo/anhydramnion; it complicates approximately 0.4-0.7% of all pregnancies and is associated with very high neonatal mortality and morbidity. Antibiotics have limited success to prevent bacterial growth, chorioamnionitis and fetal inflammation. The repetitive amnioinfusion does not work because fluid is lost immediately after the intervention. The continuous amnioinfusion through the transabdominal port system or catheter in patients with classic PPROM shows promise by flushing out the bacteria and inflammatory components from the amniotic cavity, replacing amniotic fluid and thus prolonging the PPROM-to-delivery interval. OBJECTIVE: This multicenter trial aims to test the effect of continuous amnioinfusion on the neonatal survival without the typical major morbidities, such as severe bronchopulmonary dysplasia, intraventricular hemorrhage, cystic periventricular leukomalacia and necrotizing enterocolitis one year after the delivery. STUDY DESIGN: We plan to conduct a randomized multicenter trial with a two-arm parallel design. Randomization will be between 22/0 and 26/0 SSW. The control group: PPROM patients between 20/0 and 26/0 WG who will be treated with antibiotics and corticosteroids (from 22/0 SSW) in accordance with the guidelines of German Society of Obstetrics and Gynecology (standard PPROM therapy). In the interventional group, the standard PPROM therapy will be complemented with the Amnion Flush Method, with the amnioinfusion of Amnion Flush Solution through the intra-amnial catheter (up to 100 mL/h, 2400 mL/day). SUBJECTS: The study will include 68 patients with classic PPROM between 20/0 and 26/0 WG. TRIAL-REGISTRATION: ClinicalTrials.gov ID: NCT04696003. GERMAN CLINICAL TRIALS REGISTER: DRKS00024503, January 2021.

Daily monitoring of vaginal interleukin 6 as a predictor of intraamniotic inflammation after preterm premature rupture of membranes - a new method of sampling studied in a prospective multicenter trial.

OBJECTIVES: (A) To introduce a new technique for vaginal fluid sampling (biocompatible synthetic fiber sponge) and (B) evaluate the collected vaginal fluid interleukine-6 (IL-6vag)-concentration as a new diagnostic tool for daily monitoring of intrauterine inflammation after preterm premature rupture of membranes (PPROM). Secondary objectives were to compare the potential to predict an intrauterine inflammation with established inflammation parameters (e.g., maternal white blood cell count). METHODS: This prospective clinical case-control diagnostic accuracy multicenter study was performed with women after PPROM (gestational age 24.0/7 - 34.0/7 weeks). Sampling of vaginal fluid was performed once daily. IL-6vag was determined by electrochemiluminescence-immunoassay-kit. Neonatal outcome and placental histology results were used to retrospectively allocate the cohort into two subgroups: 1) inflammation and 2) no inflammation (controls). RESULTS: A total of 37 cases were included in the final analysis. (A): Measurement of IL-6 was successful in 86% of 172 vaginal fluid samples. (B): Median concentration of IL-6vag in the last vaginal fluid sample before delivery was significantly higher within the inflammation group (17,085 pg/mL) compared to the controls (1,888 pg/mL; p=0.01). By Youden's index an optimal cut-off for prediction an intrauterine inflammation was: 6,417 pg/mL. Two days before delivery, in contrast to all other parameters IL-6vag remained the only parameter with a sufficient AUC of 0.877, p<0.001, 95%CI [0.670-1.000]. CONCLUSIONS: This study established a new technique for vaginal fluid sampling, which permits assessment of IL-6vag concentration noninvasively in clinical daily routine monitoring.

Long tail balloon as a new approach for fetoscopic tracheal occlusion for a treatment of severe congenital diaphragmatic hernia.

Severe congenital diaphragmatic hernia (CDH) remains a significant challenge for neonatal specialists. In order to reduce complications during extraction of the surgical balloon after fetoscopic tracheal occlusion (FETO) CDH, we have developed a FETO with a 'long tail balloon' of 2.5 mL volume. Here we describe two successful uses of the device with observed/expected total fetal lung volume (o/e TFLV) of 15% and with o/e TFLV of 24% and 'liver up'. The o/e TFLV increased to 134% in first case and to 47% in second fetus. The balloon was successfully extracted at 34 weeks' gestation by pulling the long tail suture during second fetoscopy. In the second case the fetus pulled out the balloon from trachea itself by traction onto the balloon's long tail. Both neonates were operated on for their CDH with a good outcome. This work showed the feasibility of this long tail balloon for FETO to reduce the technical difficulty of the balloon extraction and the possibility that fetuses are able to extract the balloon by itself by pulling the balloons' long tail. Further development of long tail balloon for FETO could facilitate its extraction thereby reducing neonatal complications.

Successful Closure of Small Iatrogenic Chorioamniotic Membranes Defect After Fetoscopy with Laser: A Case Report.

Background: Fetoscopic laser coagulation of the placental anastomoses is the standard treatment for twin-to-twin transfusion syndrome (TTTS). Despite certain improvements in fetoscopic technique, every fourth fetoscopic procedure is still complicated by preterm premature rupture of membranes, leading to ascending infection, fetal demise, and/or preterm delivery. re-TTTS occurs after fetoscopy in 2­14% of cases, impairing the outcome. Case: A 26-year-old woman underwent laser coagulation of placental anastomoses because of stage III TTTS at 21/6 weeks of gestation. A microinvasive fetoscopic technique with 1-mm optic was used. Three weeks later, during a second fetoscopy because of re-TTTS, a defect of the chorioamniotic membranes of about 3 mm2 in area was visualized. This was without any signs of wound healing. We decided to perform laser coagulation with Nd:YAG laser of 10­30 W energy, moving from the wound's edge to the center until complete closure of the defect could be achieved. The patient gave birth at 34/0 weeks to 2 healthy female infants weighing 2,013 g and 1,712 g. Microscopic evaluation of chorioamniotic membranes found dystrophic calcification within the treated membranes; this had been covered by amniotic epithelium. Conclusion: Small iatrogenic amniotic membrane defects could be successfully treated by laser technique.

The effect of intraumbilical fetal nutrition via a subcutaneously implanted port system on amino acid concentration by severe IUGR human fetuses.

OBJECTIVE: To determine if intrauterine intraumbilical supplementation with amino acids (AA) and glucose can improve neonatal outcome of severe growth restricted human fetuses (IUGR). METHODS: Prospective pilot study of intrauterine treatment of severe IUGR fetuses [n=14, 27 weeks of gestation (range 23-31)] with cerebroplacental ratio <1, with long-term intraumbilical AA and glucose supplementation (10% of feto-placental blood volume/day) using a perinatal port system alone (n=5) or combined with hyperbaric oxygenation (n=1, HBO) vs. control group (n=8). RESULTS: The duration of continuous intraumbilical AA/glucose supplementation was 11 (6-13) days. Daily intravascular fetal nutrition significantly prolonged the brain sparing to delivery interval by 24 (14-33) days vs. 5.6 (2-12) days in controls. Fetal nutrition reduced blood flow resistance in the placental circulation but did not affect the Doppler profile of cerebral arteries. Higher weight gain of 113.5 (36-539) g was observed following supplementation compared to 33.3 (8-98) g in the control group (P<0.05). In spite of this, fetuses below 28 weeks of gestation did not sufficiently benefit from infused commercial AA. We found a reduced fetal plasma concentration of the essential AA histidine, threonine, lysine and arginine, and non-essential AA taurine, in severe IUGR fetuses in both groups. Long-term supplementation with a commercial AA formula led to a slight, but not significant, reduction of histidine, threonine, lysine, arginine, asparagine and glutamine. However, the concentration of tryptophan and glutamic acid slightly increased. HBO can be combined with AA supplementation via a port system. In one case, the port system was also successfully used for fetal blood transfusion. CONCLUSIONS: Intravascular treatment of IUGR with fetal nutrition can prolong pregnancy with severe placental insufficiency and brain sparing for many weeks. However, rather than normalizing AA concentrations, an enhanced AA imbalance was observed in IUGR fetuses following supplementation. These deviations in AA concentrations prevent the recommendation for use of commercial AA solutions for prenatal treatment of extreme preterm IUGR fetuses.

Incremental value of copeptin in suspected acute myocardial infarction very early after symptom onset.

BACKGROUND: Patients presenting very early after chest pain onset may provide a diagnostic challenge even when using a high-sensitivity cardiac troponin (hs-cTnT). We hypothesized that in these patients the incremental value of copeptin in the early diagnosis of acute myocardial infarction (AMI) may be substantial. METHODS: We aimed to investigate the incremental value of copeptin in a pre-specified subgroup analysis of patients presenting with suspected AMI to the emergency department within 2 hours of symptom onset in a multicenter study. Copeptin was measured in a blinded fashion. Two independent cardiologists adjudicated the final diagnosis using all available clinical informations, including high-sensitivity cardiac troponin T (hs-cTnT). RESULTS: Overall, 2000 patients were enrolled, of whom 519 (26%) arrived within 2 hours of symptom onset. Of these, 102 patients (20%) had an AMI. The additional use of copeptin did not increase diagnostic accuracy as quantified by the area under the receiver-operating characteristic curve (AUC) of hs-cTnT (0.87 (95% confidence interval (CI): 0.83-0.90) for hs-cTnT alone to 0.86 (95% CI: 0.82-0.90) for the combination; p = NS). Copeptin (using 9 pmol/L as a cut-off) increased the negative predictive value (NPV) of hs-cTnT (using 14 ng/L as a cut-off) alone from 93% (95% CI: 90-95%) to 96% (95% CI: 93-98%). The NPV for the combination of hs-cTnT and copeptin was lower in patients arriving in the first 2 hours than in those arriving after 2 hours: 96% (95% CI: 93-98%) versus 99% (95% CI: 99-100%), respectively. CONCLUSIONS: The additional use of copeptin on top of hs-cTnT seems to lead to a small increase in NPV, but no increase in AUC. Routine use of copeptin in early presenters does not seem warranted.

Incremental value of heart-type fatty acid-binding protein in suspected acute myocardial infarction early after symptom onset.

BACKGROUND: The early diagnosis of acute myocardial infarction (AMI) very soon after symptom onset remains a major clinical challenge, even when using high-sensitivity cardiac troponin (hs-cTnT). METHODS AND RESULTS: We investigated the incremental value of heart-type fatty acid-binding protein (hFABP) in a pre-specified subgroup analysis of patients presenting with suspected AMI within 1 h of symptom onset to the emergency department (ED) in a multicentre study. HFABP was measured in a blinded fashion. Two independent cardiologists using all available clinical information, including hs-cTnT, adjudicated the final diagnosis. Overall, 1411 patients were enrolled, of whom 105 patients presented within 1 h of symptom onset. Of these, 34 patients (32.4%) had AMI. The diagnostic accuracy as quantified by the area under the receiver-operating characteristics curve (AUC) of hFABP was high (0.84 (95% CI 0.74-0.94)). However, the additional use of hFABP only marginally increased the diagnostic accuracy of hs-cTnT (AUC 0.88 (95% CI 0.81-0.94) for hs-cTnT alone to 0.90 (95% CI 0.83-0.98) for the combination; p=ns). After the exclusion of 18 AMI patients with ST-segment elevation, similar results were obtained. Among the 16 AMI patients without ST-segment elevation, six had normal hs-cTnT at presentation. Of these, hFABP was elevated in two (33.3%) patients. CONCLUSIONS: hFABP does not seem to significantly improve the early diagnostic accuracy of hs-cTnT in the important subgroup of patients with suspected AMI presenting to the ED very early after symptom onset.

Improvement of cardiac function with device-based diaphragmatic stimulation in chronic heart failure patients: the randomized, open-label, crossover Epiphrenic II Pilot Trial.

AIMS: Device-based pacing-induced diaphragmatic stimulation (PIDS) may have therapeutic potential for chronic heart failure (HF) patients. We studied the effects of PIDS on cardiac function and functional outcomes. METHODS AND RESULTS: In 24 chronic HF patients with CRT, an additional electrode was attached to the left diaphragm. Randomized into two groups, patients received the following PIDS modes for 3 weeks in a different sequence: (i) PIDS off (control group); (ii) PIDS 0 ms mode (PIDS simultaneously with ventricular CRT pulse); or (iii) PIDS optimized mode (PIDS with optimized delay to ventricular CRT pulse). For PIDS optimization, acoustic cardiography was used. Effects of each PIDS mode on dyspnoea, power during exercise testing, and LVEF were assessed. Dyspnoea improved with the PIDS 0 ms mode (P = 0.057) and the PIDS optimized mode (P = 0.034) as compared with the control group. Maximal power increased from median 100.5 W in the control group to 104.0 W in the PIDS 0 ms mode (P = 0.092) and 109.5 W in the PIDS optimized mode (P = 0.022). Median LVEF was 33.5% in the control group, 33.0% in the PIDS 0 ms mode, and 37.0% in the PIDS optimized mode (P = 0.763 and P = 0.009 as compared with the control group, respectively). PIDS was asymptomatic in all patients. CONCLUSION: PIDS improves dyspnoea, working capacity, and LVEF in chronic HF patients over a 3 week period in addition to CRT. This pilot study demonstrates proof of principle of an innovative technology which should be confirmed in a larger sample. TRIAL REGISTRATION: NCT00769678.

Usefulness of aspiration of pulmonary emboli and prolonged local thrombolysis to treat pulmonary embolism.

Catheter-based treatment of pulmonary embolism (PE) has been demonstrated to be successful in case reports and small series. The investigators report the results of a novel, pharmacomechanical approach with prolonged infusion of urokinase in the occluded pulmonary arteries (PAs). Manual aspiration of thrombus using guide catheters was followed by introduction of thrombolysis catheters and a local bolus of urokinase. The lysis catheters were left in place, and repeat PA cine angiography and right-sided cardiac catheterization was performed 3 days later. A total of 63 patients (mean age 60 ± 15 years) were treated over 8 years: 17 patients (27%) had massive and 46 patients (73%) submassive PE. The mean PA pressure was 35 ± 10 mm Hg, and 54% had central bilateral PE. Five patients died, 1 before, 1 during, and 3 after the intervention. Nine patients (14%) had major bleeds (hemoglobin decrease >30 g/L), but in none of these patients was bleeding the reason for fatal outcome. After 3.3 ± 1.0 days, 49 of 58 living patients (84%) were restudied. In 29 (59%), there was a reduction of thrombotic burden by >90%, and in 14 (29%), the reduction was 50% to 90%. Mean PA pressure was reduced from 33 ± 8 to 21 ± 7 mm Hg (p <0.001), and this was not dependent on a reduction of thrombus. In conclusion, manual aspiration and application of prolonged thrombolysis is feasible and safe. Improvement of PA pressures is impressive and there is no correlation between morphologic disappearance of thrombus and normalization of PA pressures.

Associations of reactive hyperemia index and intravascular ultrasound-assessed coronary plaque morphology in patients with coronary artery disease.

Although reactive hyperemia index (RHI) predicts future coronary events, associations with intravascular ultrasound (IVUS)-assessed coronary plaque structure have not been reported. This study therefore investigated associations between RHI and IVUS-assessed coronary plaques. In 362 patients RHI was measured by noninvasive peripheral arterial tonometry and coronary plaque components (fibrous, fibrofatty, necrotic core, and dense calcium) were identified by IVUS in 594 vessel segments of the left anterior descending, circumflex, and/or right coronary arteries. RHI values <1.67 were considered abnormal. Analysis of variance was used to detect independent associations between RHI and plaque composition. Patients with an abnormal RHI had greater plaque burden (41% vs 39% in patients with normal RHI, p = 0.047). Compared to patients with normal RHI, plaque of patients with abnormal RHI had more necrotic core (21% vs 17%, p <0.001) and dense calcium (19% vs 15%, p <0.001) and less fibrous (49% vs 54%, p <0.001) and fibrofatty (11% vs 14%, p = 0.002) tissue. After adjustment for age, gender, cardiovascular risk factors, and drug therapy, abnormal RHI remained significantly associated with fibrous (F ratio 14.79, p <0.001), fibrofatty (F ratio 5.66, p = 0.018), necrotic core (F ratio 14.47, p <0.001), and dense calcium (F ratio 10.80, p = 0.001) volumes. In conclusion, coronary artery plaques of patients with abnormal RHI had a larger proportion of necrotic core and dense calcium. The association of an abnormal RHI with a plaque structure that is more prone to rupture may explain why these patients exhibit a greater risk of coronary events.

Inflammatory myopathy and severe rhabdomyolysis induced by leuprolide acetate therapy for prostate cancer: a case report.

INTRODUCTION: Leuprolide acetate is a synthetic analog of gonadotropin-releasing hormone used for the treatment of prostate cancer. Its side effects are hot flashes, nausea, and fatigue. We report a case of a patient with proximal inflammatory myopathy accompanied by severe rhabdomyolysis and renal failure following the second application of leuprolide acetate. Drug withdrawal and steroid therapy resulted in remission within six weeks of the diagnosis. To the best of our knowledge, our case report describes the second case of leuprolide acetate-induced inflammatory myopathy and the first case of severe leuprolide acetate-induced rhabdomyolysis and renal failure in the literature. CASE PRESENTATION: A 64-year-old Swiss Caucasian man was admitted to the hospital because of progressive proximal muscle weakness, dyspnea, and oliguria. He had been treated twice with leuprolide acetate in monthly doses. We performed a muscle biopsy, which excluded other causes of myopathy. The patient's renal failure and rhabdomyolysis were treated with rehydration and steroid therapy. CONCLUSION: The aim of our case report is to highlight the rare but severe side effects associated with leuprolide acetate therapy used to treat patients with inflammatory myopathy: severe rhabdomyolysis and renal failure.