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1.
Am J Obstet Gynecol MFM ; 6(4): 101209, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38536661

RESUMO

BACKGROUND: Trial of labor after cesarean after 2 cesarean deliveries is linked to a lower success rate of vaginal delivery and higher rates of adverse obstetrical outcomes than trial of labor after cesarean after 1 previous cesarean delivery. OBJECTIVE: This study aimed to investigate the factors associated with failed trial of labor after cesarean among women with 2 previous cesarean deliveries. STUDY DESIGN: This was a multicenter retrospective cohort study, which included all women with singleton pregnancies attempting trial of labor after cesarean after 2 previous cesarean deliveries between 2003 and 2021. This study compared labor, maternal, and neonatal characteristics between women with failed trial of labor after cesarean and those with successful trial of labor after cesarean. Univariate analysis was initially performed, followed by multivariable analysis (adjusted odds ratios with 95% confidence intervals). RESULTS: The study included a total of 1181 women attempting trial of labor after cesarean after 2 previous cesarean deliveries. Among these cases, vaginal birth after cesarean was achieved in 973 women (82.4%). Women with failed trial of labor after cesarean had higher rates of maternal and neonatal morbidities. Several factors were found to be associated with failed trial of labor after cesarean, including longer interpregnancy and interdelivery intervals, lower gravidity and parity, lower rates of previous successful vaginal delivery, smoking, earlier gestational age at delivery (38.3±2.1 vs 39.5±1.3 weeks), late preterm delivery (34-37 weeks of gestation), lower cervical dilation on admission, no use of epidural, and smaller neonatal birthweight. Our multivariable model revealed that late preterm delivery (adjusted odds ratio, 3.79; 95% confidence interval, 1.37-10.47) and cervical dilation on admission for labor <3 cm (adjusted odds ratio, 2.58; 95% confidence interval, 1.47-4.54) were associated with higher odds of failed trial of labor after cesarean. CONCLUSION: In the investigated population of women with 2 previous cesarean deliveries undergoing trial of labor after cesarean, admission at the late preterm period with a cervical dilation of <3 cm, which reflects the latent phase, may elevate the risk of failed trial of labor after cesarean and a repeated intrapartum cesarean delivery.


Assuntos
Prova de Trabalho de Parto , Nascimento Vaginal Após Cesárea , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Adulto , Nascimento Vaginal Após Cesárea/estatística & dados numéricos , Nascimento Vaginal Após Cesárea/métodos , Recém-Nascido , Paridade , Recesariana/estatística & dados numéricos , Recesariana/métodos , Fatores de Risco , Idade Gestacional , Cesárea/estatística & dados numéricos , Cesárea/métodos
2.
Am J Obstet Gynecol MFM ; 6(4): 101326, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38447679

RESUMO

BACKGROUND: An increased risk for preterm birth has been observed among individuals with a previous second stage cesarean delivery when compared with those with a previous vaginal delivery. One mechanism that may contribute to the increased risk for preterm birth following a second stage cesarean delivery is the increased risk for cervical injury because of extension of the uterine incision (hysterotomy) into the cervix. The contribution of hysterotomy extension to the rate of preterm birth in a subsequent pregnancy has not been investigated and may shed light on the mechanism underlying the observed relationship between the mode of delivery and subsequent preterm birth. OBJECTIVE: We aimed to quantify the association between unintended hysterotomy extension and preterm birth in a subsequent delivery. STUDY DESIGN: We performed a retrospective cohort study using electronic perinatal data collected from 2 university-affiliated obstetrical centers. The study included patients with a primary cesarean delivery of a term, singleton live birth and a subsequent singleton birth in the same catchment (2005-2021). The primary outcome was subsequent preterm birth <37 weeks' gestation; secondary outcomes included subsequent preterm birth at <34, <32, and <28 weeks' gestation. We assessed crude and adjusted associations between unintended hysterotomy extensions and subsequent preterm birth with log binomial regression models using rate ratios and 95% confidence intervals. Adjusted models included several characteristics of the primary cesarean delivery such as maternal age, length of active labor, indication for cesarean delivery, chorioamnionitis, and maternal comorbidity. RESULTS: A total 4797 patients met the study inclusion criteria. The overall rate of unintended hysterotomy extension in the primary cesarean delivery was 6.0% and the total rate of preterm birth in the subsequent pregnancy was 4.8%. Patients with an unintended hysterotomy extension were more likely to have a longer duration of active labor, chorioamnionitis, failed vacuum delivery attempt, second stage cesarean delivery, and persistent occiput posterior position of the fetal head in the primary cesarean delivery and higher rates of smoking in the subsequent pregnancy. Multivariable analyses that controlled for several confounders showed that a history of hysterotomy extension was not associated with a higher risk for preterm birth <37 weeks' gestation (adjusted rate ratio, 1.55; 95% confidence interval, 0.98-2.47), but it was associated with preterm birth <34 weeks' gestation (adjusted rate ratio, 2.49; 95% confidence interval, 1.06-5.42). CONCLUSION: Patients with a uterine incision extension have a 2.5 times higher rate of preterm birth <34 weeks' gestation when compared with patients who did not have this injury. This association was not observed for preterm birth <37 weeks' gestation. Future research should aim to replicate our analyses with incorporation of additional data to minimize the potential for residual confounding.


Assuntos
Cesárea , Histerotomia , Nascimento Prematuro , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Histerotomia/métodos , Histerotomia/efeitos adversos , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Adulto , Cesárea/estatística & dados numéricos , Cesárea/métodos , Cesárea/efeitos adversos , Idade Gestacional , Fatores de Risco , Colo do Útero/cirurgia
3.
Biomedicines ; 12(1)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38275417

RESUMO

Studying primordial events in cancer is pivotal for identifying predictive molecular indicators and for targeted intervention. While the involvement of G-protein-coupled receptors (GPCRs) in cancer is growing, GPCR-based therapies are yet rare. Here, we demonstrate the overexpression of protease-activated receptor 2 (PAR2), a GPCR member in the fallopian tubes (FTs) of high-risk BRCA carriers as compared to null in healthy tissues of FT. FTs, the origin of ovarian cancer, are known to express genes of serous tubal intraepithelial carcinoma (STICs), a precursor lesion of high-grade serous carcinoma (HGSC). PAR2 expression in FTs may serve as an early prediction sensor for ovarian cancer. We show now that knocking down Par2 inhibits ovarian cancer peritoneal dissemination in vivo, pointing to the central role of PAR2. Previously we identified pleckstrin homology (PH) binding domains within PAR1,2&4 as critical sites for cancer-growth. These motifs associate with PH-signal proteins via launching a discrete signaling network in cancer. Subsequently, we selected a compound from a library of backbone cyclic peptides generated toward the PAR PH binding motif, namely the lead compound, Pc(4-4). Pc(4-4) binds to the PAR PH binding domain and blocks the association of PH-signal proteins, such as Akt or Etk/Bmx with PAR2. It attenuates PAR2 oncogenic activity. The potent inhibitory function of Pc(4-4) is demonstrated via inhibition of ovarian cancer peritoneal spread in mice. While the detection of PAR2 may serve as a predictor for ovarian cancer, the novel Pc(4-4) compound may serve as a powerful medicament in STICs and ovarian cancer. This is the first demonstration of the involvement of PAR PH binding motif signaling in ovarian cancer and Pc(4-4) as a potential therapy treatment.

4.
PLoS One ; 18(7): e0288537, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37437055

RESUMO

Intrapartum fever (IF) accompanied by either maternal or foetal tachycardia, elevated WBC, or purulent discharge is classified as "suspected triple 1", the hallmark of intraamniotic infection (IAI). Poor specificity of the clinical diagnosis of IAI results, in retrospect, in the unnecessary treatment of most parturients and neonates. We studied the yield of specific acute phase reactants (APRs): procalcitonin, CRP, IL-6, in detecting bacterial IAI among parturients classified as "suspected triple 1" (cases) compared to afebrile parturients (controls). Procalcitonin, CRP, and IL-6 were all significantly elevated in the cases compared to the controls, yet this by itself was not sufficient for an additive effect in detecting a bacterial infection among parturients clinically diagnosed with "suspected triple 1", as demonstrated by the poor area under the receiver operating characteristic curve of all three APRs.


Assuntos
Âmnio , Infecções Bacterianas , Febre , Interleucina-6 , Pró-Calcitonina , Humanos , Recém-Nascido , Proteínas de Fase Aguda , Febre/diagnóstico , Projetos Piloto , Feminino , Gravidez , Âmnio/microbiologia , Infecções Bacterianas/diagnóstico
5.
Diabetes Res Clin Pract ; 202: 110813, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37392938

RESUMO

AIM: To investigate whether women with twin gestation and one abnormal value on the diagnostic 3-hour oral glucose tolerance test (OGTT) are at an increased risk of adverse perinatal outcomes. METHODS: This was a retrospective multicenter study of women with twin gestation, comparing four groups: (1) normal 50-g screening, (2) normal 100-g 3-hour OGTT, (3) one abnormal value on the 3-hour OGTT, and (4) GDM. Multivariable logistic regressions adjusted for maternal age, gravidity, parity, previous CDs, fertility treatments, smoking, obesity and chorionicity were used. RESULTS: The study included 2,597 women with twin gestations, of which 79.7% had a normal screen, and 6.2% had one abnormal value on the OGTT. In adjusted analyses, women with one abnormal value were found to have higher rates of preterm delivery < 32 weeks, large for gestational age neonates, and composite neonatal morbidity of at least one fetus, however, similar maternal outcomes as those with a normal screen. CONCLUSION: Our study provides evidence that women with twin gestation and one abnormal value on the 3-hour OGTT are at an increased risk of unfavorable neonatal outcomes. This was confirmed by multivariable logistic regressions. Further research is needed to determine whether interventions such as nutritional counseling, blood glucose monitoring, and treatment with diet and medication would improve perinatal outcomes in this population.


Assuntos
Diabetes Gestacional , Gravidez , Recém-Nascido , Humanos , Feminino , Teste de Tolerância a Glucose , Diabetes Gestacional/epidemiologia , Glicemia , Automonitorização da Glicemia , Estudos Retrospectivos , Resultado da Gravidez
6.
J Minim Invasive Gynecol ; 30(6): 486-493, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36775053

RESUMO

STUDY OBJECTIVE: To establish a clinically relevant prediction score for the diagnosis of adnexal torsion (AT) in women who were operated on for suspected AT. DESIGN: A retrospective cohort study conducted between 2014 and 2021. SETTING: A large tertiary teaching medical center. PATIENTS: Women who underwent urgent laparoscopy for suspected AT. INTERVENTIONS: Analyses included univariate and multivariate models combined with the machine learning (ML) Random Forest model, which included all information available about the women and reported the accuracy of the model and the importance of each variable. Based on this model, we created a predictive score and evaluated its accuracy by receiver operating characteristic (ROC) curve. MEASUREMENTS AND MAIN RESULTS: A total of 503 women were included in our study, 244 (49%) of whom were diagnosed with AT during the surgery, and 44 (8.8%) cases of necrotic ovary were found. Based on the Random Forrest and multivariate models, the most important preoperative clinical predictive variables for AT were vomiting, left-side complaints, and concurrent pregnancy; cervical tenderness and urinary symptoms decreased the likelihood of surgically confirmed AT. The most important sonographic findings that predicted increased risk of surgically confirmed AT were ovarian edema and decreased vascular flow; in contrast, hemorrhagic corpus luteum decreased the likelihood of surgically confirmed AT. The accuracy of the Random Forest model was 71% for the training set and 68% for the testing set, and the area under the curve for the multivariate model was 0.75 (95% confidence interval [CI] 0.69-0.80). Based on these models, we created a predictive score with a total score that ranges from 4 to 12. The area under the curve for this score was 0.72 (95% CI 0.67-0.76), and the best cutoff for the final score was >5, with a sensitivity, specificity, positive predictive value, and negative predictive value of 64%, 73%, 70%, and 67%, respectively. CONCLUSION: Clinical characteristics and ultrasound findings may be incorporated into the emergency room workup of women with suspected AT. ML in this setting has no diagnostic/predictive advantage over the performance of logistic regression methods. Additional prospective studies are needed to confirm the accuracy of this model.


Assuntos
Doenças dos Anexos , Gravidez , Humanos , Feminino , Doenças dos Anexos/diagnóstico por imagem , Doenças dos Anexos/cirurgia , Torção Ovariana , Estudos Retrospectivos , Algoritmos , Aprendizado de Máquina
7.
Arch Gynecol Obstet ; 307(3): 739-746, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35488051

RESUMO

PURPOSE: Prolonged cesarean operative time (OT) is a well-established proxy for post-operative maternal complications. We aimed to study whether prolonged OT may serve as a proxy for maternal complications in the subsequent cesarean delivery. METHODS: A retrospective cohort study of women who underwent cesarean delivery between 2005 and 2019. Parturients who had two subsequent cesarean deliveries were included and those with Placenta Accreta Syndrome (PAS) were excluded. Prolonged operative time was defined as the duration of cesarean delivery above 60 min. Univariate analyses were followed by multivariate analysis (adjusted Odds Ratio (aORs); [95% Confidence Interval]). RESULTS: A total of 5163 women met the inclusion and exclusion criteria of which 360 (7%) had prolonged operative time. Prolonged operative time of a cesarean section in the index pregnancy was significantly associated in the subsequent cesarean delivery with the following: Prolonged operative time, intra-operative blood loss > 1000 ml, postpartum hemorrhage, blood products transfusion, injuries to the urinary system in the subsequent delivery, and hysterectomy. Multivariate analysis revealed that prolonged OT in the index delivery was associated with composite adverse maternal outcome (aOR 1.46 [1.09-1.95]; P = 0.01) and blood products transfusion (aOR 2.93 [1.90-4.52]; P < 0.01) in the subsequent delivery. CONCLUSION: Prolonged operative may serve as a proxy for adverse maternal outcomes, mostly blood products transfusion, in the subsequent cesarean delivery among women undergoing repeat cesarean delivery.


Assuntos
Cesárea , Hemorragia Pós-Parto , Gravidez , Feminino , Humanos , Cesárea/efeitos adversos , Estudos Retrospectivos , Duração da Cirurgia , Hemorragia Pós-Parto/etiologia , Complicações Pós-Operatórias/etiologia
8.
Eur J Obstet Gynecol Reprod Biol ; 269: 55-61, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34968875

RESUMO

OBJECTIVE: To estimate the frequency of post cesarean paralytic ileus and to identify associated risk factors and outcomes. STUDY DESIGN: A retrospective cohort study of woman who underwent cesarean delivery between 2005 and 2019. All parturients who had cesarean delivery were stratified and compared according to whether or not they were diagnosed with a paralytic ileus. Women were excluded if they had an intestinal injury or repair during the cesarean or if they suffered from a post cesarean mechanical bowel obstruction diagnosed during re-laparotomy. Basic demographics, obstetric history, current delivery characteristics, re-suturing indications and outcomes were obtained and analyzed. Univariate analyses were followed by a multivariate analysis (adjusted Odds Ratio (aORs) ; [95% Confidence Interval]). RESULTS: A total of 23,486 women met the inclusion and exclusion criteria of which 135 (0.6%) were diagnosed with paralytic ileus whilst 23,347 (99.4%) did not and served as the control group. Multivariate analysis revealed that an estimated intra-operative blood loss ≥ 1000 ml was the most significant risk factor for post cesarean paralytic ileus (aOR 2.27 (1.18-4.36)), followed by multifetal gestation (aOR 2.08 (1.24-3.51)), corporeal uterine incision (aOR 1.97 (1.07-3.63)), use of topical hemostatic agents (aOR 1.78 (1.19-2.66)) and increasing maternal age (aOR 1.78 (1.19-2.66)). Regarding maternal outcomes, post cesarean paralytic ileus was associated with higher rates of postpartum hemorrhage (44.4% vs. 13.4%, p < 0.01), transfusion of blood products (23.7% vs. 3.9%, p < 0.01), post-cesarean exploratory laparotomy (4.4% vs. 0.1%, p < 0.01) and prolonged hospital stay (32.6% vs. 5.2%, p < 0.01). CONCLUSION: In our population, whilst post cesarean paralytic ileus is infrequent, when it occurs it is associated with increased short-term maternal morbidity.


Assuntos
Cesárea , Íleus , Cesárea/efeitos adversos , Feminino , Humanos , Íleus/epidemiologia , Íleus/etiologia , Incidência , Gravidez , Estudos Retrospectivos , Fatores de Risco
9.
Surg Endosc ; 36(1): 544-549, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33527207

RESUMO

BACKGROUND: The impact on pregnancy of laparoscopy for acute appendicitis is well documented. However, with an accurate pre-operative diagnosis being more challenging in pregnant patients, the incidence of a negative appendectomy (NA) is higher in this cohort. The aim of this study was to evaluate the maternal and neonatal implications of a NA during pregnancy. METHODS: A single center retrospective study between 2004 and 2019 was performed. Pregnant women who underwent laparoscopic appendectomy for suspected appendicitis were identified from which those who had a pathologically normal appendix were selected. The maternal and neonatal outcome of this group were compared with a matched control group of pregnant women who underwent diagnostic laparoscopy for a presumed ovarian torsion in whom no further surgical intervention was performed. Multivariate regression analysis was performed to explore factors that gestational size. RESULTS: Of the 225 pregnant women who underwent laparoscopy appendectomy, a NA was performed in 33 (14.7%). These were compared with 50 pregnant women in the diagnostic laparoscopy group. The former was characterized by higher rate of nulliparity and later gestational age at the time of the surgery (17.8 ± 7.5 vs 11.3 ± 6.3, p < 0.001). Whilst the rate of maternal complications during pregnancy were similar between the groups, NA was associated with significantly lower neonatal birthweights (2733.9 ± 731.1 vs 3200.7 ± 458.5 g, p = 0.002) and a significantly higher risk of small for gestational age (SGA) infants (OR 5.6, 95% CI 1.02-30.9). CONCLUSIONS: Performing a NA during pregnancy is an indicator for perioperative counseling and antenatal follow up.


Assuntos
Apendicite , Laparoscopia , Complicações na Gravidez , Apendicectomia/efeitos adversos , Apendicite/diagnóstico , Apendicite/etiologia , Apendicite/cirurgia , Feminino , Humanos , Lactente , Recém-Nascido , Laparoscopia/efeitos adversos , Gravidez , Complicações na Gravidez/cirurgia , Resultado da Gravidez , Estudos Retrospectivos
10.
Int J Gynaecol Obstet ; 153(3): 457-461, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33599285

RESUMO

OBJECTIVE: We aimed to assess the rates of overall diagnosis of ectopic pregnancy (EP), treatment modality and associated complications during the COVID-19 pandemic compared to the exact time period in the previous year (pre-COVID-19). METHODS: A retrospective cohort study was conducted at a single referral regional center (Shaare Zedek Medical Center, Jerusalem, Israel). Prevalence of the diagnosis of EP, treatment modality and associated complications during the COVID-19 lockdown period in the state of Israel (March 10-May 12, 2020) was compared to patients receiving the same diagnosis during the parallel timeframe in the previous year (2019). RESULTS: Overall there were 29 and 43 cases of EP during the COVID-19 and pre COVID-19 epoch, respectively. COVID-19 period patients presented to the emergency room with significantly higher ß-human chorionic gonadotrophin level; median of 1364 versus 633 IU, P = 0.001. The rate of ruptured EP was; 20.7% versus 4.3% P = 0.031, and surgical approach; 55.2% versus 27.9%, P = 0.001. Significantly higher median volume of blood loss; median volume 852 versus 300 ml, P = 0.042 were observed in patients during the COVID-19 epoch. CONCLUSION: The COVID-19 pandemic led to delayed presentation of patients with EP, and the requirement of subsequent emergency surgical management and excessive blood loss. Special attention should be given to the decline in routine medical care during the pandemic.


Assuntos
Gravidez Ectópica/diagnóstico , Gravidez Ectópica/epidemiologia , Gravidez Ectópica/terapia , Adulto , COVID-19/epidemiologia , Gonadotropina Coriônica Humana Subunidade beta/sangue , Estudos de Coortes , Diagnóstico Tardio , Emergências , Feminino , Humanos , Israel/epidemiologia , Gravidez , Gravidez Ectópica/cirurgia , Estudos Retrospectivos , Ruptura Espontânea/epidemiologia , Ruptura Espontânea/cirurgia , SARS-CoV-2
11.
J Crit Care ; 63: 8-14, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549910

RESUMO

PURPOSE: To describe shock severity, physiological stabilization and organ failure in healthy women admitted to the intensive care unit (ICU) after major peripartum hemorrhage (PPH). MATERIALS AND METHODS: Retrospective, descriptive, single center study. RESULTS: Twenty-nine women median age 33 years (interquartile range [IQR] 30-36) and gravidity 5 pregnancies (IQR 3-9) were studied. One woman died. The median maternal admission hematocrit was 28.8 (IQR 25.7-32.4). Median transfusion rates were nine units of packed red blood cells (IQR 7-12.25), eight fresh frozen plasma (IQR 6-12), 17 platelets (IQR 10-22) and 15 cryoprecipitate (IQR 9.75-20). Blood pressure dropped significantly in the six hours following ICU admission. Nonetheless, lactate decreased from 3.23 mmol/L to 1.54 mmol/L within 24 h of ICU admission, renal and pulmonary function were unaffected and coagulopathy was never observed. Two-thirds of the women underwent hysterectomy. One-third underwent repeated surgery. The median length of ICU stay was <48 h and that of mechanical ventilation was <24 h. Increased transfusion rates correlated with lengthier ICU admission (p ≤ 0.01 regardless of blood product). CONCLUSIONS: Ongoing hemorrhage in women with severe PPH manifests subtly and often requires active intervention. Hemorrhage control is required to achieve physiological stabilization and minimize organ damage.


Assuntos
Unidades de Terapia Intensiva , Período Periparto , Adulto , Feminino , Hemorragia , Hospitalização , Humanos , Gravidez , Estudos Retrospectivos
12.
Taiwan J Obstet Gynecol ; 60(1): 70-77, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33495012

RESUMO

OBJECTIVE: Inflammatory bowel diseases (IBD) are a group of pathologies associated with an increased rate of abortions, premature deliveries, cesarean sections and other morbidity during the peripartum period. The objective of this retrospective study was to investigate the anesthetic management for delivery of women with IBD. MATERIAL AND METHODS: The records of patients with IBD, who delivered at our Center, were obtained for data which included anesthetic and obstetric management as well as neonatal outcome. Five subgroups were defined based on mode of delivery, presence or absence of epidural in normal vaginal delivery (NVD) and urgency of cesarean section, each of which was compared with control groups of healthy parturients in the same period. Additionally, the rate of cesarean sections and the use of epidural analgesia for NVD were compared with the general obstetric population of our center in the same period. RESULTS: 107 patients with IBD who delivered at our center were studied. The rates of cesarean sections and emergency cesarean sections were significantly higher compared to the general population. However, the rate of instrumental delivery and of epidural analgesia use for NVD were similar. Among those who underwent cesarean sections, no significant differences were found in anesthesia type, surgery duration, number of complications, type of monitoring or postoperative management compared to the control group. CONCLUSION: Peripartum anesthetic management of patients with IBD does not differ significantly from that of parturients without it. Anesthesiologists can plan their anesthesia in a similar way as they do in healthy parturients.


Assuntos
Anestesia Obstétrica/métodos , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Parto Obstétrico/estatística & dados numéricos , Complicações na Gravidez/terapia , Adulto , Estudos de Casos e Controles , Cesárea/estatística & dados numéricos , Parto Obstétrico/métodos , Feminino , Humanos , Período Periparto , Gravidez , Complicações na Gravidez/etiologia , Estudos Retrospectivos
14.
FASEB J ; 34(12): 15701-15717, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33136328

RESUMO

While the involvement of protease-activated receptors (PARs) in the physiological regulation of human placenta development, as in tumor biology, is recognized, the molecular pathway is unknown. We evaluated the impact of PAR1 and PAR2 function in cytotrophoblast (CTB) proliferation and invasion in a system of extravillous trophoblast (EVT) organ culture and in human cell-lines. Activation of PAR1 - and PAR2 -induced EVT invasion and proliferation, while the shRNA silencing of low-density lipoprotein receptor-related protein 5/6 (LRP5/6) inhibited these processes. PAR1 and PAR2 effectively induce ß-catenin stabilization in a manner similar to that shown for the canonical ß-catenin stabilization pathway yet independent of Wnts. Immunoprecipitation analyses and protein-protein docking demonstrated the co-association between either PAR1 or PAR2 with LRP5/6 forming an axis of PAR-LRP5/6-Axin. Noticeably, in PAR1 -PAR2 heterodimers a dominant role is assigned to PAR2 over PAR1 as shown by inhibition of PAR1 -induced ß-catenin levels, and Dvl nuclear localization. This inhibition takes place either by shRNA silenced hPar2 or in the presence of a TrPAR2 devoid its cytoplasmic tail. Indeed, TrPAR2 cannot form the PAR1 -PAR2 complex, obstructing thereby the flow of signals downstream. Elucidation of the mechanism of PAR-induced invasion contributes to therapeutic options highlighting key partners in the process.


Assuntos
Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Placenta/metabolismo , Receptor PAR-1/metabolismo , Receptor PAR-2/metabolismo , Linhagem Celular , Células Cultivadas , Citoplasma/metabolismo , Feminino , Células HEK293 , Humanos , Placentação/fisiologia , Gravidez , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/fisiologia , Trofoblastos/metabolismo , beta Catenina/metabolismo
15.
Arch Gynecol Obstet ; 302(6): 1413-1419, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32889559

RESUMO

PURPOSE: To investigate the association of maternal and perinatal outcomes with the surgical diagnosis of adnexal torsion in a retrospective cohort of women operated for suspected torsion during pregnancy. STUDY DESIGN: This is a multicenter retrospective study and telephone questionnaire of urgent laparoscopies that occurred during pregnancy for suspected torsion between 2004 and 2019 in three tertiary medical centers. Pregnancy outcomes of women with the surgical diagnosis were compared with those whose laparoscopy was negative for adnexal torsion. Multivariable regression modeling was applied to control for possible confounders ((adjusted odds ratios (aOR) ± 95% confidence intervals (CI)]. RESULTS: The study cohort included 186 women. Adnexal torsion was surgically found in 129/186 (69.4%) cases. The torsion group was characterized by higher rate of nulliparity, fertility treatments and multiple gestations as well as lower rates of previous cesarean delivery. Live birth was reported for 171 (91.9%) pregnancies, and the miscarriage rate was significantly higher in the non-torsion group. Women with torsion were more likely to be hospitalizes due to preterm labor; however, rates of preterm delivery were comparable between the groups (10.8% vs. 10.9%, p = 0.99). Logistic regression analysis had demonstrated that the performance of laparoscopy prior to 8 weeks of gestation was the only independent factor associated with miscarriage (8.23, 2.01-33.67). CONCLUSION: Pregnancy outcomes following the diagnosis of adnexal torsion throughout gestation were overall favorable. Laparoscopic procedure during early stages of pregnancy was associated with higher rates of miscarriage, regardless of the surgical diagnosis of adnexal torsion.


Assuntos
Doenças dos Anexos/cirurgia , Laparoscopia , Torção Ovariana/cirurgia , Doenças dos Anexos/diagnóstico , Adulto , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Trabalho de Parto Prematuro/epidemiologia , Torção Ovariana/diagnóstico , Gravidez , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , Anormalidade Torcional
16.
Arch Gynecol Obstet ; 302(1): 101-108, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32415470

RESUMO

PURPOSE: We aimed to evaluate the effect of an absorbable adhesion barrier (oxidized regenerated cellulose) for the prevention of peritoneal adhesions in women undergoing repeat cesarean delivery (CD). METHODS: This is a retrospective, single center study that included all women who underwent two consecutive CDs, 2011-2018. Women in whom an absorbable adhesion barrier (oxidized regenerated cellulose) was placed at the time of the initial CD (index CD) were compared to women in whom no such barrier was placed. The association between absorbable adhesion barrier placement at index CD and the presence of intraperitoneal adhesions at subsequent CD was assessed. Factors evaluated included intraperitoneal adhesion severity, time from skin incision to newborn delivery and total duration of surgery. RESULTS: We identified 2125 women that met the inclusion criteria. They were divided into two groups; those in whom an absorbable adhesion barrier was placed at index CD and those in whom no such absorbable barrier was placed. 161 (7.6%) had an absorbable adhesion barrier placed at index CD. At the time of index CD, the rate of intra-peritoneal adhesions was 34.8% in the absorbable adhesion barrier group vs 26.5% in the group without the absorbable adhesion barrier (p = 0.02). At the time of subsequent CD, the rate of intraperitoneal adhesions was 39.8% in the absorbable adhesion barrier group vs 46% in the group without the absorbable adhesion barrier (p = 0.13). Notably, the use of an absorbable adhesion barrier lowered the mean increase in adhesions rate 0.05 ± 0.55 vs 0.20 ± 0.55 (p < 0.01). Absorbable adhesion barrier placement at index CD was found to be independently associated with a lower rate of intraperitoneal adhesions at subsequent CD, aOR 0.67 (0.47-0.96). Overall, absorbable adhesion barrier placement at index CD was associated with a shorter mean duration of subsequent surgery (min), 37.7 ± 18.9 vs. 42.7 ± 27.1 (p = 0.02). CONCLUSION: Absorbable adhesion barrier placement is associated with reduction in intraperitoneal adhesions and duration of surgery in subsequent CD.


Assuntos
Cesárea/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Aderências Teciduais/cirurgia , Adulto , Feminino , Humanos , Incidência , Gravidez , Estudos Retrospectivos
17.
Rom J Anaesth Intensive Care ; 27(1): 11-14, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34056118

RESUMO

OBJECTIVE: Maternal heart disease is one of the major causes for mortality among parturients. In our study, we surveyed 220 patients with different valvular disorders who gave birth in our medical center in the years 2012-2018. The aim of this study was to characterize various valvular pathologies and compare the results of different anesthetic approaches. METHODS: In this retrospective study, the computerized system and file archive were searched for maternal valvular pathologies according to the International Classification of Diseases, Ninth Revision (ICD-9). The women included in the study were defined as American Society of Anesthesiology (ASA)-II or more, who suffer from valvular heart disease. RESULTS: The most common pathology was mitral valve regurgitation (57.73% of all cardiac patients). Most women were defined as having mild insufficiency, and 82.68% had normal vaginal delivery. In 17.3% of patients who had cesarean section, the main type of anesthesia was neuraxial anesthesia (95.45%). The second most common pathology was tricuspid valve regurgitation (22.73%). Most patients (78%) had normal vaginal delivery, and epidural analgesia was used in 64.1%. A minority of cardiac patients in our study were patients with stenotic heart diseases, such as aortic stenosis, mitral stenosis and pulmonic stenosis (8.18%, 4.55%, and 1.36%, respectively). No complications were observed in the peripartum period. CONCLUSION: The use of regional anesthesia is recommended for all valvular pathologies without exception, as we observed no cases in which the severity of cardiac condition had not allowed the use of various types of regional anesthesia, for surgery or vaginal delivery.

19.
Eur J Obstet Gynecol Reprod Biol ; 237: 139-144, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31039488

RESUMO

BACKGROUND: Adherent and invasive placenta, termed Placenta Creta Spectrum (PCS), is associated with increased maternal morbidity and mortality. Incidence and risk factors for Placenta Creta are on the rise and call to optimize the obstetric care for this condition. OBJECTIVES: We sought to compare maternal and neonatal outcomes between a ProActive Peripartum Multidisciplinary Approach (PAMA) as compared to the urgent management of the Placenta Creta Spectrum patients. STUDY DESIGN: We conducted a single-center prospective observational study between 2005-2016. PCS patients registered with the implementation of a PAMA protocol 2014-2016 epoch(E2) were compared with the pre-PAMA 2005-2013 epoch(E1), managed by urgent team recruitment. The PAMA protocol is grounded on a continuum of care; A. Antenatal: PCS risk assessment based on clinical history and imaging, surgical, anesthesia, urological consults and designation of a dedicated team to be present at planned surgery; B. Delivery: planned at 34-35 weeks, massive transfusion protocol activation, insertion of ureteral catheters, vertical uterine incision, placement of vessel loops on the iliac vessels, avoidance of active placenta delivery, followed by the decision of hysterectomy or uterine repair; C. Post-operative care: intensive care admission. We evaluated maternal and neonatal outcomes. RESULTS: During the study period 158,438 deliveries were registered in our institution; we identified a total of 72 PCS cases (0.05%): 50(69.4%) in E1 and 22 (30.6%) in E2. Patient characteristics were comparable among epochs. Significantly, patients in E2 vs. E1 had fewer events of massive blood transfusion 36.0% vs. 13.6%, p = 0.05; were transfused less RBC units: median 4 vs. 1.5, p = 0.012, had no transfusion-related respiratory complications and hemorrhage control re-laparotomies. Hysterectomy and hollow visceral injury rates were comparable (72% vs. 63.7%, 26% vs. 22%; respectively). The hysterectomy pathology assessment was available for the majority of the cases in both epochs; percreta diagnosis rate significantly increased in E2. The neonatal outcome was similar among the epochs. CONCLUSIONS: Institution of a PAMA protocol for PCS resulted in eliminating the urgent deliveries and in reducing the associated significant hemorrhagic related maternal morbidity, with no increase in the rate of hysterectomy or adverse neonatal outcome.


Assuntos
Parto Obstétrico , Equipe de Assistência ao Paciente , Placenta Acreta/terapia , Resultado da Gravidez , Adulto , Cesárea , Feminino , Humanos , Histerectomia , Período Periparto , Placenta Acreta/cirurgia , Gravidez , Estudos Prospectivos
20.
Am J Gastroenterol ; 114(7): 1172-1175, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30920987

RESUMO

OBJECTIVES: Despite encouraging data gathered in inflammatory bowel diseases (IBD) patients, Vedolizumabs' (VDZ) safety profile in pregnancy is not established. DESIGN: Data of 330 consecutive pregnancies with IBD was prospectively collected. RESULTS: Women with IBD were treated with: VDZ (n = 24), anti-tumor necrosis factors (n = 82) or conventional therapy (n = 224). Gravidity and parity were similar among the 3 groups. The VDZ group was comprised mostly of Crohn's disease patients who were all not naïve to biological treatment. They had significantly higher conception rates during active disease (P < 0.05), with fewer flares during pregnancy. DISCUSSION: Although further study is needed, VDZ appears of low risk during pregnancy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Segurança do Paciente , Resultado da Gravidez , Fator de Necrose Tumoral alfa/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos de Coortes , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Humanos , Recém-Nascido , Doenças Inflamatórias Intestinais/diagnóstico , Gravidez , Gravidez de Alto Risco , Prognóstico , Estudos Prospectivos , Medição de Risco
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