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BACKGROUND: Intrauterine balloon tamponade is an effective treatment for postpartum hemorrhage when first-line treatments fail. The optimal duration of intrauterine balloon tamponade for management of postpartum hemorrhage is unclear. OBJECTIVE: The objective of the study was to determine whether intrauterine balloon tamponade removal >12 hours of duration is associated with postpartum hemorrhage-related clinical outcomes. STUDY DESIGN: This was a retrospective cohort study of women with postpartum hemorrhage from 2007 through 2014 who underwent intrauterine balloon tamponade. We excluded failures of intrauterine balloon tamponade (intrauterine balloon expulsion with duration <2 hours or if hysterectomy was required prior to planned intrauterine balloon removal). Patients who underwent intrauterine balloon tamponade for 2-12 hours were compared with those who underwent intrauterine balloon tamponade for >12 hours. Examined postpartum hemorrhage-related clinical outcomes included estimated blood loss after intrauterine balloon tamponade placement, blood product transfusion, use of adjuvant measures to control postpartum hemorrhage after intrauterine balloon tamponade (either uterine artery embolization or hysterectomy), and maternal intensive care unit admission. Secondary outcomes examined included postpartum fever and hospital length of stay. Multivariable logistic regression models were used to control for confounding variables. RESULTS: Of 274 eligible women, 206 (75%) underwent intrauterine balloon tamponade for >12 hours and 68 (25%) underwent intrauterine balloon tamponade for 2-12 hours. The median estimated blood loss after intrauterine balloon tamponade placement (190 vs 143 mL, P = .116) as well as the frequencies of blood product transfusion (62.1% vs 51.5%, P = .120), transfusion of ≥4 U of packed red blood cells (17.0% vs 14.7%, P = .659), uterine artery embolization (15.1% vs 16.2%, P = .823), hysterectomy (0.0% vs 1.5%, P = .248), and intensive care unit admission (8.7% vs 7.4%, P = .721), was not statistically different between the groups, and this lack of association persisted in multivariable regressions. Intrauterine balloon tamponade duration >12 hours was associated with a higher frequency of postpartum fever (27% vs 15%, P = .047) and a longer mean hospital length of stay (3.7 vs 3.1 days, P = .002). After adjusting for variables that differed statistically between groups, the difference in length of stay associated with intrauterine balloon tamponade duration was no longer present, but the association between intrauterine balloon tamponade duration >12 hours and postpartum fever persisted (odds ratio, 2.33, 95% confidence interval, 1.07-5.11). Including chorioamnionitis as an independent variable in a post hoc multivariable analysis diminished the association between intrauterine balloon tamponade >12 hours and postpartum fever (adjusted odds ratio, 2.04, 95% confidence interval, 0.92-4.53). CONCLUSION: There are no significant differences in postpartum hemorrhage-related outcomes associated with intrauterine balloon tamponade duration >12 hours compared with removal 2-12 hours. If ongoing hemorrhage has abated, it is reasonable to consider the removal of an intrauterine balloon by 12 hours after its initial placement.
Assuntos
Oclusão com Balão , Hemorragia Pós-Parto/terapia , Embolização da Artéria Uterina/métodos , Adulto , Estudos de Coortes , Feminino , Humanos , Histerectomia , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
Assuntos
Doenças Placentárias , Hemorragia Pós-Parto/etiologia , Hemorragia Pós-Parto/terapia , Tamponamento com Balão Uterino , Inércia Uterina , Adulto , Transfusão de Eritrócitos , Fator VIII/uso terapêutico , Feminino , Fibrinogênio/uso terapêutico , Humanos , Histerectomia , Unidades de Terapia Intensiva , Admissão do Paciente , Doenças Placentárias/terapia , Plasma , Gravidez , Retratamento , Estudos Retrospectivos , Falha de Tratamento , Embolização da Artéria Uterina , Inércia Uterina/terapiaRESUMO
INTRODUCTION & OBJECTIVE: Ovarian and testicular torsion are comparable surgical emergencies that may result in organ loss and, as such, have high litigious potential. We sought to describe the relative frequency and outcome of malpractice litigation between cases of ovarian and testicular torsion. METHODS: Searches were completed in the Westlaw Jury Verdicts & Settlements and Lexis Cases databases using the following search terms: "(ovarian or ovary)/5 torsion" and "(testicular or testicle)/5 torsion". Cases were excluded if they were not directly related to torsion or were not malpractice claims. Cases were reviewed for year, jurisdiction, age of plaintiff, verdict, appeal status, contention, damages, and alleged time delay to appropriate care. RESULTS: The legal databases contained 155 malpractice cases related to testicular torsion and 4 cases related to ovarian torsion. Two of three ovarian torsion cases and 52% of testicular torsion cases with available rulings were in favor of the defense. The median age of plaintiffs in testicular torsion cases was 14, and 75% were minors. Median delay in care for testicular cases was 3 days, and median damages awarded to plaintiffs was $250,000 ($12,000-8.5 million). No data regarding age, delay in care, or damages were available for ovarian torsion cases. CONCLUSIONS: Among malpractice cases related to gonadal torsion, testicular torsion is vastly overrepresented despite literature demonstrating longer delays in care and greater likelihood of gonadal loss in ovarian torsion during the study period. LEVEL OF EVIDENCE: IV.
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Imperícia , Torção do Cordão Espermático , Masculino , Feminino , Humanos , Torção do Cordão Espermático/cirurgia , Torção Ovariana , Bases de Dados FactuaisRESUMO
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.
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Complexo 1 de Proteínas Adaptadoras/metabolismo , Subunidades beta do Complexo de Proteínas Adaptadoras/metabolismo , Polaridade Celular/fisiologia , Endossomos/metabolismo , Células Epiteliais/metabolismo , Proteínas SNARE/metabolismo , Proteína 3 Associada à Membrana da Vesícula/metabolismo , Complexo 1 de Proteínas Adaptadoras/genética , Subunidades beta do Complexo de Proteínas Adaptadoras/genética , Animais , Linhagem Celular , Membrana Celular/metabolismo , Polaridade Celular/efeitos dos fármacos , Cães , Células Epiteliais/citologia , Humanos , Fusão de Membrana/efeitos dos fármacos , Fusão de Membrana/fisiologia , Metaloendopeptidases/farmacologia , Transporte Proteico/efeitos dos fármacos , Transporte Proteico/fisiologia , Proteínas Qa-SNARE/genética , Proteínas Qa-SNARE/metabolismo , Receptores de LDL/metabolismo , Proteínas SNARE/genética , Toxina Tetânica/farmacologia , Proteína 3 Associada à Membrana da Vesícula/genéticaRESUMO
The human bladder contains bacteria, even in the absence of infection. Interest in studying these bacteria and their association with bladder conditions is increasing. However, the chosen experimental method can limit the resolution of the taxonomy that can be assigned to the bacteria found in the bladder. 16S rRNA amplicon sequencing is commonly used to identify bacteria in urinary specimens, but it is typically restricted to genus-level identification. Our primary aim here was to determine if accurate species-level identification of bladder bacteria is possible using 16S rRNA amplicon sequencing. We evaluated the ability of different classification schemes, each consisting of combinations of a reference database, a 16S rRNA gene variable region, and a taxonomic classification algorithm to correctly classify bladder bacteria. We show that species-level identification is possible and that the reference database chosen is the most important component, followed by the 16S variable region sequenced. IMPORTANCE Accurate species-level identification from culture-independent techniques is of importance for microbial niches that are less well characterized, such as that of the bladder. 16S rRNA amplicon sequencing, a common culture-independent way to identify bacteria, is often critiqued for lacking species-level resolution. Here, we extensively evaluate classification schemes for species-level bacterial annotation of 16S amplicon data from bladder bacteria. Our results show that the proper choice of taxonomic database and variable region of the 16S rRNA gene sequence makes species level identification possible. We also show that this improvement can be achieved through the more careful application of existing methods and resources. Species-level information may deepen our understanding of associations between bacteria in the bladder and bladder conditions such as lower urinary tract symptoms and urinary tract infections.
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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.
Assuntos
Subunidades mu do Complexo de Proteínas Adaptadoras/metabolismo , Polaridade Celular , Endocitose , Endossomos/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Subunidades mu do Complexo de Proteínas Adaptadoras/química , Sequência de Aminoácidos , Aminoácidos/metabolismo , Animais , Linhagem Celular , Técnicas de Silenciamento de Genes , Proteínas de Fluorescência Verde/metabolismo , Humanos , Camundongos , Dados de Sequência Molecular , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Transporte Proteico , Receptores da Transferrina/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , SuínosRESUMO
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.