High positive end-expiratory pressure ventilation mitigates the progression from unilateral pulmonary contusion to ARDS: An animal study.

BACKGROUND: Pulmonary contusion (PC) is common in severely traumatized patients and can lead to respiratory failure requiring mechanical ventilation (MV). Ventilator-induced lung injury (VILI) might aggravate lung damage. Despite underrepresentation of trauma patients in trials on lung-protective MV, results are extrapolated to these patients, potentially disregarding important pathophysiological differences. METHODS: Three MV protocols with different positive end-expiratory pressure (PEEP) levels: ARDSnetwork lower PEEP (ARDSnet-low), ARDSnetwork higher PEEP (ARDSnet-high), and open lung concept (OLC) were applied in swine for 24 hours following PC. Gas exchange, lung mechanics, quantitative computed tomography, and diffuse alveolar damage (DAD) score were analyzed. Results are given as median (interquartile range) at 24 hours. Statistical testing was performed using general linear models (group effect) over all measurement points and pairwise Mann-Whitney U tests for DAD. RESULTS: There were significant differences between groups: PEEP ( p < 0.0001) ARDSnet-low (8 [8-10] cmH 2 O), ARDSnet-high (12 [12-12] cmH 2 O), OLC (21 [20-22] cmH 2 O). The fraction of arterial partial pressure of oxygen and inspired oxygen fraction ( p = 0.0016) was lowest in ARDSnet-low (78 (73-111) mm Hg) compared with ARDSnet-high (375 (365-423) mm Hg) and OLC (499 (430-523) mm Hg). The end-expiratory lung volume (EELV) differed significantly ( p < 0.0001), with highest values in OLC (64% [60-70%]) and lowest in ARDSnet-low (34% [24-37%]). Costa's surrogate for mechanical power differed significantly ( p < 0.0001), with lowest values for ARDSnet-high (73 [58-76]) compared with OLC (105 [108-116]). Diffuse alveolar damage was lower in ARDSnet-high compared with ARDSnet-low (0.0007). CONCLUSION: Progression to ARDS, 24 hours after PC, was mitigated by OLC and ARDSnet-high. Both concepts restored EELV. ARDSnet-high had the lowest mechanical power surrogate and DAD. Our data suggest, that ARDSnet-high restored oxygenation and functional lung volume and reduced physiological and histological surrogates for VILI. ARDSnet-low generated unfavorable outcomes, such as loss of EELV, increased mechanical power and DAD after PC in swine. The high respiratory rate in the OLC may blunt favorable effects of lung recruitment.

Successful external cephalic version in a patient with uterus didelphys and fetal malpresentation.

Müllerian anomalies are congenital malformations of the female reproductive organs that occur when the müllerian ducts develop abnormally. Different types of müllerian anomalies have different pregnancy outcomes. Breech presentation is a common occurrence in pregnant women with uterus didelphys, and caesarean section is the traditional mode of delivery under such circumstances. Here, we present the case of a 29-year-old woman (gravida 2, para 1) with her fetus in a frank breech presentation. The patient had a known history of uterus didelphys and previous vaginal delivery. She elected to undergo external cephalic version (ECV) at 37 weeks with a trial of labour at 39 weeks as opposed to planned cesarean delivery. The version was successful, and the fetus was subsequently delivered vaginally without complications. This case demonstrates ECV as a possible option in women with uterus didelphys, provided the risks of the procedure are carefully weighed and individualised to each patient.

Correlation of lung collapse and gas exchange - a computer tomographic study in sheep and pigs with atelectasis in otherwise normal lungs.

BACKGROUND: Atelectasis can provoke pulmonary and non-pulmonary complications after general anaesthesia. Unfortunately, there is no instrument to estimate atelectasis and prompt changes of mechanical ventilation during general anaesthesia. Although arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt have both been suggested to correlate with atelectasis, studies yielded inconsistent results. Therefore, we investigated these correlations. METHODS: Shunt, PaO2 and atelectasis were measured in 11 sheep and 23 pigs with otherwise normal lungs. In pigs, contrasting measurements were available 12 hours after induction of acute respiratory distress syndrome (ARDS). Atelectasis was calculated by computed tomography relative to total lung mass (Mtotal). We logarithmically transformed PaO2 (lnPaO2) to linearize its relationships with shunt and atelectasis. Data are given as median (interquartile range). RESULTS: Mtotal was 768 (715-884) g in sheep and 543 (503-583) g in pigs. Atelectasis was 26 (16-47) % in sheep and 18 (13-23) % in pigs. PaO2 (FiO2 = 1.0) was 242 (106-414) mmHg in sheep and 480 (437-514) mmHg in pigs. Shunt was 39 (29-51) % in sheep and 15 (11-20) % in pigs. Atelectasis correlated closely with lnPaO2 (R2 = 0.78) and shunt (R2 = 0.79) in sheep (P-values<0.0001). The correlation of atelectasis with lnPaO2 (R2 = 0.63) and shunt (R2 = 0.34) was weaker in pigs, but R2 increased to 0.71 for lnPaO2 and 0.72 for shunt 12 hours after induction of ARDS. In both, sheep and pigs, changes in atelectasis correlated strongly with corresponding changes in lnPaO2 and shunt. DISCUSSION AND CONCLUSION: In lung-healthy sheep, atelectasis correlates closely with lnPaO2 and shunt, when blood gases are measured during ventilation with pure oxygen. In lung-healthy pigs, these correlations were significantly weaker, likely because pigs have stronger hypoxic pulmonary vasoconstriction (HPV) than sheep and humans. Nevertheless, correlations improved also in pigs after blunting of HPV during ARDS. In humans, the observed relationships may aid in assessing anaesthesia-related atelectasis.

Treatment of biliary tract cancer with NVP-AEW541: mechanisms of action and resistance.

AIM: To investigate in vitro treatment with NVP-AEW541, a small molecule inhibitor of insulin-like growth factor-1 receptor (IGF-1R), in biliary tract cancer (BTC), since this disease is associated with a poor prognosis due to wide resistance to chemotherapeutic agents and radiotherapy. METHODS: Cell growth inhibition by NVP-AEW541 was studied in vitro in 7 human BTC cell lines by automated cell counting. In addition, the anti-tumoral mechanism of NVP-AEW541 was studied by Western blotting, cell cycle analysis and reverse transcription-polymerase chain reaction (RT-PCR). Anti-tumoral drug effect in combination with gemcitabine, 5-fluorouracil (5-FU) and Polo-like kinase 1 inhibitor BI2536 was also studied. RESULTS: In vitro treatment with NVP-AEW541 suppressed growth in all human BTC cell lines, however response was lower in gallbladder cancer. Treatment with NVP-AEW541 was associated with dephosphorylation of IGF-1R and AKT. In contrast, phosphorylation of p42/p44 and Stat3 and expression of Bcl-xL were inconsistently downregulated. In addition, treated cells showed cell cycle arrest at the G1/S-checkpoint and an increase in sub-G1 peak. Moreover, IGF-1R and its ligands IGF-1 and IGF-2 were co-expressed in RT-PCR, suggesting an autocrine loop of tumor cell activation. Combined with gemcitabine, NVP-AEW541 exerted synergistic effects, particularly at low concentrations, while effects of combination with 5-FU or BI 2536 were only additive. CONCLUSION: Our findings suggest that NVP-AEW541 is active against BTC in vitro and potentiates the efficacy of gemcitabine.

Sublingual misoprostol for labor induction: a randomized clinical trial.

OBJECTIVE: To compare the effectiveness of 50 microg compared with 100 microg of repetitive misoprostol dosages administered sublingually for labor induction. METHODS: Two hundred twelve women who presented with an indication for cervical ripening and labor induction were randomly assigned to 50 microg or 100 microg of misoprostol tablets administered sublingually with double masking of treatment group dose allocation. The primary outcome was the interval from start of induction to vaginal delivery. RESULTS: Among the 203 evaluable participants, 102 were randomly assigned to the 50-microg group and 101 to the 100-microg group. The proportion of patients who delivered vaginally in less than 12 hours and less than 24 hours was significantly higher in the 100-microg group: 28% and 63% in the 100-microg group compared with 15% and 36% in the 50-microg group, respectively (P = .01 and P = .001). The incidence of tachysystole was significantly higher in the 100-microg group (P = .02). The incidence of hyperstimulation syndrome was higher in the 100-microg group, but not statistically significant (P = .46). With respect to the proportion of patients delivered after a single dose, mode of delivery, and perinatal outcome, no significant differences between treatment groups were observed. Regarding the need for oxytocin augmentation, 61% required augmentation in the 100-microg group compared with 81% in the 50-microg group (P = .002). CONCLUSION: One hundred micrograms of sublingual misoprostol is more effective than 50 microg of sublingual misoprostol, but is associated with a higher incidence of tachysystole and uterine hyperstimulation syndrome. LEVEL OF EVIDENCE: I.