Is There an Association Between Indication for Intrauterine Balloon Tamponade and Balloon Failure?

Objective Determine whether the indication for intrauterine balloon tamponade (IUBT) is associated with failure rates. Study Design Cohort study of women who underwent IUBT for postpartum hemorrhage (PPH) from 2007 to 2014. The indication was categorized as uterine atony or placental-site bleeding. Primary outcome was IUBT failure, defined as the need for uterine artery embolization or hysterectomy. Secondary outcomes were estimated blood loss (EBL) after balloon placement, transfusion of red blood cells (RBC), transfusion of fresh frozen plasma (FFP) and/or cryoprecipitate, and intensive care unit (ICU) admission. Results 306 women underwent IUBT: 241 (78.8%) for uterine atony and 65 (21.2%) for placental site bleeding. Overall, 67 (21.9%) women experienced IUBT failure. The frequency of failure was similar in those with uterine atony compared with those with placental-site bleeding (21.2 vs 24.6%, p = 0.55). This finding persisted after adjusting for potential confounders (aOR, 0.97; 95% CI, 0.48-1.99). Median EBL after balloon placement (190 [interquartile range, 93-375] vs 195 [interquartile range, 103-500] mL, p = 0.46), and frequencies of RBC transfusion (62.7 vs 66.2%, p = 0.60), FFP and/or cryoprecipitate transfusion (25.3 vs 33.8%, p = 0.17), and ICU admission (12.4 vs 16.9%, p = 0.35) were also similar. Conclusion IUBT was similarly effective for managing PPH from uterine atony or placental-site bleeding.

Phosphatidylinositol 3,4,5-trisphosphate localization in recycling endosomes is necessary for AP-1B-dependent sorting in polarized epithelial cells.

Polarized epithelial cells coexpress two almost identical AP-1 clathrin adaptor complexes: the ubiquitously expressed AP-1A and the epithelial cell-specific AP-1B. The only difference between the two complexes is the incorporation of the respective medium subunits micro1A or micro1B, which are responsible for the different functions of AP-1A and AP-1B in TGN to endosome or endosome to basolateral membrane targeting, respectively. Here we demonstrate that the C-terminus of micro1B is important for AP-1B recruitment onto recycling endosomes. We define a patch of three amino acid residues in micro1B that are necessary for recruitment of AP-1B onto recycling endosomes containing phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P(3)]. We found this lipid enriched in recycling endosomes of epithelial cells only when AP-1B is expressed. Interfering with PI(3,4,5)P(3) formation leads to displacement of AP-1B from recycling endosomes and missorting of AP-1B-dependent cargo to the apical plasma membrane. In conclusion, PI(3,4,5)P(3) formation in recycling endosomes is essential for AP-1B function.

Rab13 regulates membrane trafficking between TGN and recycling endosomes in polarized epithelial cells.

To maintain polarity, epithelial cells continuously sort transmembrane proteins to the apical or basolateral membrane domains during biosynthetic delivery or after internalization. During biosynthetic delivery, some cargo proteins move from the trans-Golgi network (TGN) into recycling endosomes (RE) before being delivered to the plasma membrane. However, proteins that regulate this transport step remained elusive. In this study, we show that Rab13 partially colocalizes with TGN38 at the TGN and transferrin receptors in RE. Knockdown of Rab13 with short hairpin RNA in human bronchial epithelial cells or overexpression of dominant-active or dominant-negative alleles of Rab13 in Madin-Darby canine kidney cells disrupts TGN38/46 localization at the TGN. Moreover, overexpression of Rab13 mutant alleles inhibits surface arrival of proteins that move through RE during biosynthetic delivery (vesicular stomatitis virus glycoprotein [VSVG], A-VSVG, and LDLR-CT27). Importantly, proteins using a direct route from the TGN to the plasma membrane are not affected. Thus, Rab13 appears to regulate membrane trafficking between TGN and RE.

v-SNARE cellubrevin is required for basolateral sorting of AP-1B-dependent cargo in polarized epithelial cells.

The epithelial cell-specific adaptor complex AP-1B is crucial for correct delivery of many transmembrane proteins from recycling endosomes to the basolateral plasma membrane. Subsequently, membrane fusion is dependent on the formation of complexes between SNARE proteins located at the target membrane and on transport vesicles. Although the t-SNARE syntaxin 4 has been localized to the basolateral membrane, the v-SNARE operative in the AP-1B pathway remained unknown. We show that the ubiquitously expressed v-SNARE cellubrevin localizes to the basolateral membrane and to recycling endosomes, where it colocalizes with AP-1B. Furthermore, we demonstrate that cellubrevin coimmunoprecipitates preferentially with syntaxin 4, implicating this v-SNARE in basolateral fusion events. Cleavage of cellubrevin with tetanus neurotoxin (TeNT) results in scattering of AP-1B localization and missorting of AP-1B-dependent cargos, such as transferrin receptor and a truncated low-density lipoprotein receptor, LDLR-CT27. These data suggest that cellubrevin and AP-1B cooperate in basolateral membrane trafficking.