Non-invasive prediction of massive transfusion during surgery using intraoperative hemodynamic monitoring data.

OBJECTIVE: Failure to receive prompt blood transfusion leads to severe complications if massive bleeding occurs during surgery. For the timely preparation of blood products, predicting the possibility of massive transfusion (MT) is essential to decrease morbidity and mortality. This study aimed to develop a model for predicting MT 10 min in advance using non-invasive bio-signal waveforms that change in real-time. METHODS: In this retrospective study, we developed a deep learning-based algorithm (DLA) to predict intraoperative MT within 10 min. MT was defined as the transfusion of 3 or more units of red blood cells within an hour. The datasets consisted of 18,135 patients who underwent surgery at Seoul National University Hospital (SNUH) for model development and internal validation and 621 patients who underwent surgery at the Boramae Medical Center (BMC) for external validation. We constructed the DLA by using features extracted from plethysmography (collected at 500 Hz) and hematocrit measured during surgery. RESULTS: Among 18,135 patients in SNUH and 621 patients in BMC, 265 patients (1.46%) and 14 patients (2.25%) received MT during surgery, respectively. The area under the receiver operating characteristic curve (AUROC) of DLA predicting intraoperative MT before 10 min was 0.962 (95% confidence interval [CI], 0.948-0.974) in internal validation and 0.922 (95% CI, 0.882-0.959) in external validation, respectively. CONCLUSION: The DLA can successfully predict intraoperative MT using non-invasive bio-signal waveforms.

STAT3-mediated IGF-2 secretion in the tumour microenvironment elicits innate resistance to anti-IGF-1R antibody.

Drug resistance is a major impediment in medical oncology. Recent studies have emphasized the importance of the tumour microenvironment (TME) to innate resistance, to molecularly targeted therapies. In this study, we investigate the role of TME in resistance to cixutumumab, an anti-IGF-1R monoclonal antibody that has shown limited clinical efficacy. We show that treatment with cixutumumab accelerates tumour infiltration of stromal cells and metastatic tumour growth, and decreases overall survival of mice. Cixutumumab treatment stimulates STAT3-dependent transcriptional upregulation of IGF-2 in cancer cells and recruitment of macrophages and fibroblasts via paracrine IGF-2/IGF-2R activation, resulting in the stroma-derived CXCL8 production, and thus angiogenic and metastatic environment. Silencing IGF-2 or STAT3 expression in cancer cells or IGF-2R or CXCL8 expression in stromal cells significantly inhibits the cancer-stroma communication and vascular endothelial cells' angiogenic activities. These findings suggest that blocking the STAT3/IGF-2/IGF-2R intercellular signalling loop may overcome the adverse consequences of anti-IGF-1R monoclonal antibody-based therapies.

The frequency and clinical significance of intra-amniotic inflammation in women with preterm uterine contractility but without cervical change: do the diagnostic criteria for preterm labor need to be changed?

OBJECTIVE: The objective of this study was to determine the frequency and clinical significance of intra-amniotic inflammation in patients with preterm increased uterine contractility with intact membranes but without cervical change. METHODS: Amniocentesis was performed in 132 patients with regular uterine contractions and intact membranes without cervical change. Amniotic fluid was cultured for bacteria and mycoplasmas and assayed for matrix metalloproteinase-8 (MMP-8). Intra-amniotic inflammation was defined as an elevated amniotic fluid MMP-8 concentration (>23 ng/mL). RESULTS: (1) Intra-amniotic inflammation was present in 12.1% (16/132); (2) Culture-proven intra-amniotic infection was diagnosed in 3% (4/132) of patients without demonstrable cervical change on admission or during the period of observation; and (3) Patients with intra-amniotic inflammation had significantly higher rates of preterm delivery and adverse outcomes, and shorter amniocentesis-to-delivery intervals than those without intra-amniotic inflammation (P < 0.05 for each). Adverse outcomes included chorioamnionitis, funisitis, and neonatal death. CONCLUSION: Intra-amniotic inflammation was present in 12% of patients with regular uterine contractions without cervical change, while culture-proven intra-amniotic infection was present in 3%. The presence of intra-amniotic inflammation was a significant risk factor for adverse neonatal outcomes. These observations question whether cervical changes should be required for the diagnosis of preterm labor, because patients without modifications in cervical status on admission or during a period of observation are at risk for adverse pregnancy outcomes.

The frequency of meconium-stained amniotic fluid increases as a function of the duration of labor.

OBJECTIVE: The purpose of this study was to determine whether there is a relationship between the frequency of meconium-stained amniotic fluid (MSAF) and the duration of labor in term singleton gestation. METHODS: The clinical characteristics of women who delivered term singleton live newborns between 2001 and 2006 were examined. The cases involving neonates with major congenital anomalies were excluded. RESULTS: (1) The frequency of MSAF in term pregnancies was 18.4% (806/4376); (2) MSAF was found in only 2.8% (28/1008) of women who delivered by elective cesarean, but in 23.1% (778/3368) of women who delivered after the onset of labor (p < 0.001); (3) The longer the duration of labor (first stage, second stage, or total), the higher the frequency of MSAF (p < 0.001 for each); this remained significant after adjusting for other confounding variables such as parity, duration of rupture of membranes, gestational age at delivery, and mode of delivery (p < 0.001 for each). CONCLUSION: MSAF was found in only 2.8% (28/1008) of women who delivered before the onset of labor, but in 23.1% (778/3368) of women who delivered after the onset of labor. The longer the duration of labor, the higher the risk of MSAF in term singleton gestation.

Clinical significance of oligohydramnios in patients with preterm labor and intact membranes.

OBJECTIVE: To determine the frequency and clinical significance of oligohydramnios in patients with preterm labor and intact membranes. STUDY DESIGN: An amniotic fluid index (AFI) was determined before amniocentesis (<24 h) in 272 patients with preterm labor and intact membranes (<35 weeks of gestation). Amniotic fluid (AF) was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and assayed for matrix metalloproteinase-8 (MMP-8). Non-parametric statistical techniques and survival analysis were used. RESULTS: 1) The overall prevalence of oligohydramnios (AFI of ≤5 cm) in patients with preterm labor and intact membranes was 2.6% (7/272); 2) patients with oligohydramnios had a higher frequency of AF infection and/or inflammation than those without oligohydramnios [85.7% (6/7) vs. 32.8% (87/265); P<0.01]; 3) patients with oligohydramnios had a higher median AF MMP-8 concentration than those without oligohydramnios [median 664.2 (range 16.6-3424.7) ng/mL vs. median 2.3 (range <0.3-6142.6) ng/mL; P<0.01]; 4) women with preterm labor and oligohydramnios had a shorter interval to delivery than those without oligohydramnios [median 18 h (range 0-74 h) vs. median 311 h (range 0-3228 h); P<0.01], and this difference remained significant after adjusting for gestational age and the presence or absence of AF infection/inflammation. CONCLUSION: Patients with preterm labor and oligohydramnios are at increased risk for impending preterm delivery and intra-amniotic inflammation and, therefore, may benefit from careful surveillance.

The frequency and risk factors of funisitis and histologic chorioamnionitis in pregnant women at term who delivered after the spontaneous onset of labor.

OBJECTIVE: To examine the frequency and risk factors of funisitis and histologic chorioamnionitis in the placentas of term pregnant women who delivered after the spontaneous onset of labor. METHODS: The frequency of funisitis and histologic chorioamnionitis was examined in consecutive pregnant women at term with singleton pregnancies who delivered after the spontaneous onset of labor. Nonparametric statistics were used for data analysis. RESULTS: (1) The frequency of funisitis and histologic chorioamnionitis was 6.7% (88/1316) and 23.6% (310/1316), respectively; (2) Patients with funisitis had significantly higher rates of nulliparity, regional analgesia, operative vaginal delivery, longer duration of labor and rupture of membranes (ROM), and higher gestational age and birthweight than those without funisitis (p < 0.05 for each); (3) Patients with histologic chorioamnionitis had significantly higher rates of nulliparity, oxytocin augmentation, regional analgesia, cesarean section or operative vaginal delivery, longer duration of labor and ROM, and higher gestational age and birthweight than those without histologic chorioamnionitis (p < 0.05 for each); (4) Multiple logistic regression analysis indicated that the longer the duration of labor, the higher the risk of funisitis, and that nulliparity and the duration of labor significantly increased the odds of histologic chorioamnionitis (p < 0.05 for each). CONCLUSION: The longer the duration of labor, the higher the risk of funisitis and histologic chorioamnionitis in pregnant women at term who delivered after the spontaneous onset of labor.