[Efficacy and safety of oral misoprostol 25µg vs. vaginal dinoprostone in induction of labor at term]. / Efficacité et tolérance du misoprostol oral 25µg vs dinoprostone vaginale dans le déclenchement du travail à terme.

OBJECTIVE: To compare the efficacy and safety of oral misoprostol 25µg compared to vaginal dinoprostone in the induction of labor at term. METHODS: Analytic, retrospective study of patients induced at term by prostaglandins with an unfavorable cervix, over two consecutive periods from 01/01/2019 to 19/02/2020 and from 20/02/2020 to 07/04/2021, within a regional level III university hospital center. We compared the safety and the efficacy between the oral misoprostol Angusta® used since 20/02/2020 and the vaginal dinoprostone previously used in gel or diffuser. The primary endpoint was the rate of vaginal deliveries within 24h. Secondary endpoints were cesarean section rate, indications for cesarean section, uterine contractility abnormalities and neonatal outcomes. RESULTS: Our study found no difference in terms of efficacy with similar rates of vaginal deliveries within 24h (51.88% vs. 51.25%; P=0.87) and caesarean sections (misoprostol group: 19.42% vs. dinoprostone group: 16.62%; P=0.33). However, the tolerance criteria revealed in the dinoprostone group an increase in tachysystole (misoprostol group: 9.28% vs. dinoprostone group: 16.90%; P=0.003) and acidosis (arterial pH<7.10, misoprostol group: 3.83% vs. dinoprostone group: 9.29%; P=0.006). CONCLUSION: No difference in efficacy was found between the two induction techniques. Oral misoprostol 25µg seems to be better tolerated from a maternal and fetal point of view.

[Peripartum cardiomyopathy: A review of the literature]. / Cardiomyopathie du péripartum : une revue de la littérature.

Peripartum cardiomyopathy is a rare and unpredictable pregnancy-related pathology. Idiopathic cardiomyopathy is characterized by a heart failure secondary to left ventricular systolic dysfunction appearing towards the end of pregnancy or in the months following delivery with a non-specific clinic presentation. Through reviewing previous research, our critical literature review wishes to bring a concise and objective summarize for a better understanding of physiopathology, evocative symptoms and knowing of factors influencing prognosis in order to standardize peripartum management. The treatment remains mainly symptomatic but other promising treatments are still in development. In conclusion, early detection and treatment allow a better cardiac function recovery reducing cardiac transplantation.

[Interest of systematic shavings to reduce reoperation in breast-conserving surgery of breast cancer]. / Intérêt des recoupes systématiques pour éviter les réinterventions dans la chirurgie conservatrice du cancer du sein.

OBJECTIVE: The INCa and HAS have developed quality and safety indicators for care specific to breast cancer. Among these, in the conservative surgery of this cancer includes the reoperation rate: target˂10%, alert>20%. The main objective of our study was to evaluate whether the practice of systematic recuts still called "shaving" would meet the objectives of the indicators. METHODS: Observational, retrospective, single-center study over two years in a regional referral center. Two groups of patients were compared: one with "shaving" and one without (no shaving or oriented shaving). RESULTS: In total, 381 patients were operated on, including 48 (12.6%) with shaving and 333 (87.4%) without. Revision rates for damaged margins were 18.75% (9/48) in the shaving group which met the quality criterias vs. 23.7% (79/333) which did not satisfy them; P=0.4. Furthermore, the rate of discovery of occult sites on recuts was higher in the shaving group: 22.9% (11/48) vs. 9.9% (33/333); P=0.02. In the shaving group, 10.4% (5/48) of the patients were resected again for damaged margins for the initial cancer vs. 18.6% (62/333) in the group without shaving; P=0.23. CONCLUSION: Our study confirms the interest of performing "shaving" to meet the requirements of the INCa and HAS quality criteria. The absence of systematic cross-sectioning leads to the risk of not recognizing the existence of occult sites. However, the discovery of occult cancers does not significantly reduce the rate of repeat surgery.

Obstetrical and neonatal outcomes after successful external cephalic version relative to those after spontaneous cephalic presentations.

OBJECTIVE: External cephalic version (ECV) is a procedure during which the fetus is rotated from breech or transversal to cephalic presentation. Our aim was to assess the outcomes of successful ECV in terms of obstetrical and immediate neonatal outcomes relative spontaneous cephalic presentation. METHODS: We performed a retrospective single-center observational study from January 2007 to December 2017. All included participants benefited from trial of labor with delivery of the fetus in cephalic presentation. They were divided into two groups depending on whether an ECV had been successfully performed or cephalic presentation was spontaneous. RESULTS: The cephalic presentation after ECV and spontaneous cephalic groups comprised 55 and 244 patients, respectively. The two groups differed significantly in terms of the proportion of induced labor (20 [36.4 %] and 56 [22.9 %], p = 0.04), use of oxytocin during labor (31 [56.4 %] and 100 [49.9 %], p = 0.04), duration of labor (342 ± 183 min and 279 ± 140 min, p = 0.008), spontaneous delivery (38 [69.1 %] and 199 [81.5 %], p = 0.04), intrapartum cesarean section (9 [16.4 %] and 16 [6.6 %], p = 0.02), occiput-posterior variety at birth (20 [36.4 %] and 56 [22.9 %], p = 0.04), and brace umbilical positioning at birth (3 [5.4 %] and 2 [0.8 %], p = 0.04), respectively. There were no significant intergroup differences in terms of APGAR score, cord arterial pH/lactates, or reanimation/intensive care admission. CONCLUSION: A successful ECV does not seem to guaranty an identical labor progress and obstetrical outcome as spontaneous cephalic presentations. Immediate neonatal state, on the other hand, seems unaffected by a history of ECV.

[Contribution of array CGH in the management of fetal nuchal translucency]. / L'apport de l'ACPA dans la prise en charge des hyperclartés nucales.

OBJECTIVES: Increased nuchal translucency and cystic hygroma have a neonatal prognosis, when the karyotype is normal, which depends on the findings during the medical follow-up. Array comparative genomic hybridization (aCGH) has been systematically included in this follow-up by prenatal diagnosis teams. There are no guidelines and little information on the advantages of carrying out this test systematically. The aim of our study is to evaluate the contribution of the aCGH in the medical follow-up. METHODS: Fifty-one patients were included during 18 months and followed till the end of their pregnancy in prenatal diagnosis centers in Brest and Amiens. Inclusion criterion was a nuchal translucency above 3,5mm on the first trimester ultrasound. A fetal DNA ChromoQuant and aCGH analysis on chorionic villi sampling, and an ultrasound at 18 weeks of gestation were performed during the follow-up. RESULTS: The aCGH was decisive in only 2 cases. The ultrasound at 18 weeks gestation seemed to be more sensible in the detection of an abnormality. When the aCGH relieved an abnormality, the ultrasound permitted already to detect the presence of a deformity. In 10 cases, the aCGH could not be interpreted on the chorionic villi sampling. In 9 cases, an amniocentesis was performed in order to obtain this result. CONCLUSION: Given the results of this study, the aCGH was rarely determinant or decisive on the realization of a therapeutic abortion. These elements make us reflect on the necessity of maintaining this test before 14 weeks of gestation or propose it as a second-line test after the ultrasound shows signs at 18weeks of gestation.

Management of breech and twin labor during registrarship: A two-year prospective, observational study.

INTRODUCTION: Breech presentation and twin pregnancy are regarded as stressful situations for medical staff. This stress is often associated with an increased likelihood of intervention during labor - especially when the on-shift obstetrician lacks experience. MATERIAL AND METHODS: We performed a 2-year prospective, observational study of cesarean section (CSDs) and assisted vaginal (AVDs) deliveries in a tertiary maternity unit for attempted vaginal deliveries of breech presentations and twin pregnancies. The obstetric management decisions taken by a group of four registrars were compared with those taken by a group of 11 experienced obstetricians. Changes over time in practice were also monitored. RESULTS: Registrars managed 66 and 52 breech presentations and twin pregnancies respectively (30 and 27 in the experienced group). Groups' neonatal outcomes were similar. There were no intergroup differences in proportions of CSDs for either breech presentations (25 [37.5%] vs. 15 [50%] in the registrar and experienced groups, respectively; P=0.26) or twin pregnancies (11 [21.1%] vs. 6 [22.2%], respectively; P=0.91) or in proportion of AVDs for twin pregnancies (41 [78.8%] vs. 21 [77.8%], respectively; P=0.91). Proportions of CSDs for breech presentation and AVDs for twin pregnancies did not change over time in either group. However, proportion of CSDs for twin pregnancies increased over time in the registrar group (P=0.004). DISCUSSION: Well-trained registrars appeared to have acquired the skills required to safely manage an obstetric ward; this pleads to maintain clinical practice during residency to preserve low CSD and AVD rates.

The impact of using electrical impedance spectroscopy (ZedScan) on the performance of colposcopy in diagnosing high grade squamous lesions of the cervix.

OBJECTIVES: To determine the efficacy of colposcopy plus ZedScan, which measures changes in tissue electrical impedance, for detecting intraepithelial high-grade lesions compared to colposcopy alone. METHODS: A prospective study conducted at a university hospital colposcopy clinic. Patients referred following abnormal cervical cytology or colposcopic follow up were examined by colposcopy plus ZedScan to assess the cervix. The results of ZedScan directed and colposcopically directed biopsies were compared. RESULTS: Ninety-one patients were included in this study. The median age was 33 years. Eighty (88%) were referred with abnormal cytology; LSIL 45%, ASCUS 27%, ACS-H 8%, HSIL 7%, AGC 1% and 12% follow-up postconisation or colposcopic follow up. Colposcopy alone detected 18 high-grade lesions with 64 women undergoing biopsy with a total of 115 biopsies being taken with a sensitivity of 60% and NPV estimated at 81.7%. ZedScan with colposcopy increased the detection of high-grade lesions by 47.3%, identifying 27 high-grade lesions and one case of invasive cancer. Sensitivity was 93.1% and NPV estimated at 91.3%. A combination of normal colposcopy practice and ZedScan had a sensitivity and NPV of 100%. CONCLUSION: ZedScan used in conjunction with the colposcopy improves sensitivity in detecting high-grade lesions at the expense of a moderate increase in the number of biopsies.

Impact of anaesthesia mode on evaluation of LEEP specimen dimensions.

OBJECTIVES: To study the influence of anaesthesia (local by cervical block vs. general or spinal anaesthesia) on height and volume of resection specimens in case of conization treatment for cervical intraepithelial neoplasia (CIN). METHODS: Prospective observational study of all patients who underwent a first treatment by loop electrosurgical excision procedure (LEEP) for CIN. Height of fresh resection specimens was first measured by the operator and then by the pathologist after formaldehyde fixation. Volume of fresh specimens was measured in a measuring cylinder by fluid displacement. RESULTS: One hundred patients were included and 35% of LEEP were performed under local anaesthesia. There was a significant difference in height of specimens depending on anaesthesia mode: after fixation, the average height was 11.2mm in the general or spinal anaesthesia group vs. 8.8mm in the local anaesthesia group (P=0.002). There was also a difference in terms of volume depending on anaesthesia mode: 1.6mL in local anaesthesia group vs. 2.3mm in general and spinal anaesthesia group (P=0.01). CONCLUSIONS: Anaesthesia mode has an impact on height and volume of LEEP specimens. In our experience, local anaesthesia could reduce LEEP specimen height.

Preservation of Malassezia pachydermatis using skimmed milk as cryoprotective agent.

This study evaluated the effect of skimmed milk as a cryoprotectant for the maintenance and long-term preservation of 70 Malassezia pachydermatis strains. An initial suspension of each strain was prepared in sterile distilled water with skimmed milk. The most effective method was cryopreservation that ensured 100% viability for 2years.

[Indications of primary cesarean deliveries in a regional teaching hospital and reasonable strategies for reducing them]. / Indications des premières césariennes dans un centre hospitalo-universitaire régional et stratégies raisonnables pour les diminuer.

OBJECTIVES: To characterize the indications of primary cesarean sections and discuss the various possibilities to reduce them. MATERIALS AND METHODS: Retrospective study, carried out over a period of 1 year in a university hospital having a level 3 perinatal activity, including the 499 primary cesarean sections of 2013. Two groups were defined by parity: nulliparous patients (group 1) and multiparous patients who had never previously been delivered by cesarean section (group 2). We have assessed the indication of every primary cesarean section and health status of newborns in each group. RESULTS: Groups 1 and 2 respectively included 369 and 130 patients. The cesarean section rate in 2013 was 24.7% with a primary cesarean section rate of 17%. Seventy-four percent of the primary caesarean deliveries were performed on nulliparous women and 26% on multiparous (P<0.001). Sixty-three percent of the primary caesarean deliveries were performed on nulliparous women with a singleton fetus in cephalic presentation. The most common indications for primary cesarean delivery were non-reassuring fetal heart rate tracing (47.1%), failure to progress (24.8%) for which nulliparous women were more involved (29% vs. 13%, P<0.001) and fetal malpresentation (9.6%). CONCLUSION: Further analysis of fetal heart rate during labor, a larger use of second line means to evaluate the fetal status during labor, using 6cm as the cut off for active labor, and encouraging vaginal operative delivery constitute the best way to decrease the primary cesarean section rate.

[Usefulness of a rapid intrapartum real-time PCR assay in comparison with the group B Streptococcus culture screening at the end of pregnancy in pregnant women]. / Intérêt d'un test de PCR en temps réel en intrapartum en comparaison à la culture de fin de grossesse pour le dépistage du streptocoque du groupe B chez la femme enceinte.

OBJECTIVES: The objectives were to evaluate and compare the diagnostic accuracy of a rapid real-time PCR assay at the onset of labor with those of the current antenatal culture-based test at 34-38 weeks gestation for group B Streptococcus (GBS) screening. MATERIALS AND METHODS: A prospective study including all pregnant women admitted for delivery after a 34-week gestation period was conducted in October 2012 at the Grenoble University Hospital Centre. A first culture-based GBS screening test was performed between 34 and 38 weeks of gestation followed by a second screening test at the onset of labor, using a real-time PCR Assay and a culture-based method (gold standard) in order to calculate the diagnostic accuracy. RESULTS: One hundred an fifty-seven patients were enrolled. The sensitivity was 94.4% (95% CI, 72.7-99.9%) with intrapartum PCR assay and 50% (95% CI, 26-74%) with antepartum culture. Prevalence of GBS colonization was 7.6% with the antepartum culture method, 11.5% with intrapartum culture and 16.6% by using PCR-test. CONCLUSION: Intrapartum PCR shows a much higher sensitivity compared to the antepartum culture-based screening mainly due to variations in GBS colonization and could allow us to target patients requiring intrapartum antibiotic prophylaxis more effectively.

[Management of postpartum ovarian vein thrombosis. The experience of Amiens university hospital]. / Prise en charge de la thrombose veineuse ovarienne du post-partum. L'expérience du CHU d'Amiens.

OBJECTIVES: Postpartum ovarian vein thrombophlebitis is an uncommon complication that may threaten mothers' lives. The extension of thrombosis in the inferior vena cava causes a pulmonary embolisme risk and requires urgent care. The main objective of this study was, from a series of patients, to determine the clinical and paraclincal signs to suggest the diagnosis of postpartum ovarian vein thrombosis. Secondary objectives were to assess the location and extent of thrombosis and the therapeutic management of this disease at the University Hospital of Amiens. METHODS: A retrospective study was performed in the Obstetrics and Gynecology department of Amiens University Hospital between January 2011 and May 2015. Were included in this study all patients for whom the diagnosis of postpartum ovarian thrombophlebitis was confirmed by computed tomography. RESULTS: Thirteen patients had postpartum thrombosis of the ovarian vein. The incidence of this disease in our series was 0.13%. The average age of patients was 30 years. The median onset of symptoms was located on the 4th day; in 92% of cases, they appeared within 10 days after delivery. The clinical picture was not specific and the main symptoms were fever (46.1%) and abdominal pain (53.8%). Biologically inflammatory syndrome was commonly found with elevated leukocytes and CRP. Bacteriological samples were in most cases negative. Sixty-nine percent of lesions concerned the right ovarian vein; 23% had renal extension, 53.8% had inferior vena cava extension and 23% got complicated with pulmonary embolism. No maternal deaths were reported. One hundred percent of patients received anticoagulation at curative dose, the mean duration of which was 6 months. In all, 84.6% of patients received in combination antibiotic therapy with oral and parenteral initially broad spectrum. CONCLUSION: Ovarian postpartum thrombosis is a rare complication that must be evoked and sought, especially in front of a non-septic febrile abdominal pain syndrome in postpartum.

[Introducing a daily obstetric audit: A solution to reduce the cesarean section rate?]. / L'introduction d'un audit obstétrical quotidien: une solution pour diminuer le taux de césarienne ?

OBJECTIVE: To evaluate the impact of a medical audit assessing the accuracy of caesarean indications on the final caesarean section rate of an obstetrics department. MATERIAL AND METHOD: Comparative observational study conducted in a regional university teaching hospital on the two first quadrimester periods of 2013. During the first quadrimester, there was no cesarean section audit introduced for the daily reports meetings, while an audit was introduced during the second quadrimester. The caesarean rate and the instrumental delivery rate on both quadrimesters were compared. RESULTS: In the first quadrimester period, there were 248 caesarean sections for 947 deliveries (26.2%), while in the second quadrimester period, there were 246 for 1033 deliveries (23.8%), P=0.014. The emergency caesarean rate decreased from 19.6 to 16.7%, P=0.02 in the second quadrimester period while the instrumental delivery rate increased from 14.4 to 17.2%, P=0.0004. Mothers and children's health was not modified between the two periods. CONCLUSION: In our experience, the introduction of a daily obstetric audit of the caesarean indications is effective to decrease the emergency caesarean section rate and it encourages us to be active in the first like in the second part of the labor.

Endocrine gland-derived endothelial growth factor (EG-VEGF) is a potential novel regulator of human parturition.

EG-VEGF is an angiogenic factor that we identified as a new placental growth factor during human pregnancy. EG-VEGF is also expressed in the mouse fetal membrane (FM) by the end of gestation, suggesting a local role for this protein in the mechanism of parturition. However, injection of EG-VEGF to gravid mice did not induce labor, suggesting a different role for EG-VEGF in parturition. Here, we searched for its role in the FM in relation to human parturition. Human pregnant sera and total FM, chorion, and amnion were collected during the second and third trimesters from preterm no labor, term no labor, and term labor patients. Primary human chorion trophoblast and FM explants cultures were also used. We demonstrate that circulating EG-VEGF increased toward term and significantly decreased at the time of labor. EG-VEGF production was higher in the FM compared to placentas matched for gestational age. Within the FM, the chorion was the main source of EG-VEGF. EG-VEGF receptors, PROKR1 and PROKR2, were differentially expressed within the FM with increased expression toward term and an abrupt decrease with the onset of labor. In chorion trophoblast and FM explants collected from nonlaboring patients, EG-VEGF decreased metalloproteinase-2 and -9 activities and increased PGDH (prostaglandin-metabolizing enzyme) expression. Altogether these data demonstrate that EG-VEGF is a new cytokine that acts locally to ensure FM protection in late pregnancy. Its fine contribution to the initiation of human labor is exhibited by the abrupt decrease in its levels as well as a reduction in its receptors.

Noninvasive and quantitative assessment of in vivo fetomaternal interface angiogenesis using RGD-based fluorescence.

Angiogenesis is a key process for proper placental development and for the success of pregnancy. Although numerous in vitro methods have been developed for the assessment of this process, relatively few reliable in vivo methods are available to evaluate this activity throughout gestation. Here we report an in vivo technique that specifically measures placental neovascularization. The technique is based on the measurement of a fluorescent alpha v beta 3 (αvß3) integrin-targeting molecule called Angiolone-Alexa-Fluor 700. The αvß3 integrin is highly expressed by endothelial cells during the neovascularization and by trophoblast cells during their invasion of the maternal decidua. Angiolone was injected to gravid mice at 6.5 and 11.5 days post coitus (dpc). The fluorescence was analyzed one day later at 7.5 and 12.5 dpc, respectively. We demonstrated that (i) Angiolone targets αvß3 protein in the placenta with a strong specificity, (ii) this technique is quantitative as the measurement was correlated to the increase of the placental size observed with increasing gestational age, and (iii) information on the outcome is possible, as abnormal placentation could be detected early on during gestation. In conclusion, we report the validation of a new noninvasive and quantitative method to assess the placental angiogenic activity, in vivo.

[The urinary bladder is an uncommon site of metastasis from breast cancer]. / La vessie : un site rare de métastase de cancer du sein.

Bladder metastasis of breast origin are rare. Lobular carcinoma is the most frequent histological subtype of the primary tumor. This secondary location can be the only one or can be associated with other locations. The prognosis is poor. The period between primary breast tumor and the development of bladder metastasis is variable. Herein is reported the case of a 68-year-old woman presenting with irritative disorders. Urological examination was performed and made the diagnosis. When having a history of breast cancer, the occurrence of urinary symptoms require radiographics and a cystoscopy.

[Which prostheses to use in mesh sacrocolpopexy? Experimental and clinical study]. / Promontofixation : quelles prothèses choisir ? Étude expérimentale et clinique.

BACKGROUND: Sacrocolpopexy is the standard surgical treatment of genital prolapse of the upper vaginal wall. Nowadays, the laparotomy approach is progressively supplanted by the laparoscopic procedure for the same anatomical results. About sacrocolpopexy, to date it still remains details of the technique, which differ with surgical teams maintaining controversy. Among them, the choice of the meshes certainly creates debate. OBJECTIVES: To state the basic physicochemical principles which are necessary for surgeons to select the most suitable prosthetic material to obtain the most beneficial anatomic and functional outcomes for patients. MATERIAL AND METHODS: The concepts of prosthetic biocompatibility, strength, shrinkage, deformation and elasticity are discussed. They are illustrated by experimental animal references and also human clinical references. RESULTS: Macroporous polypropylene and polyester prostheses (pore size>1 mm) are properly integrated. Collagen prosthetic coating improves tissue integration. Absorbable and nonabsorbable ultralight prostheses expose patients to a high risk of recurrence. Multifilament polyester wide pore-side prostheses have less retraction and are more flexible than monofilament polypropylene prostheses. DISCUSSION AND CONCLUSION: The prosthetic cut-off weight below which the mesh does not offer any guarantee of strength is not precisely known. Moreover, the benefit of weight reduction is not proved. Currently, heavy weight multifilament polyester prostheses with wide pore size, more than 1mm, appear to be the most appropriate meshes for sacrocolpopexy without vaginal incision.

[Pyelovenous fistula revealed by repeated thromboembolic events after emergency peripartum hysterectomy]. / Fistule pyéloveineuse révélée par des accidents thromboemboliques après hystérectomie d'hémostase.

We report the case of a 51-year old woman presenting pyelovenous fistula revealed by recurrent and serious thromboembolic events after ureteral ligation during emergency peripartum hysterectomy. Imaging reported a complete left ureteral obstruction, a fistula between the upper calix and the left renal vein and a renal function preserved. Uretero-vesical reimplantation was performed. The patient was well doing after 12 months. The authors wonder if pyelovenous fistula is responsible for prothrombotic state and maintaining renal function.

[Interstitial pregnancy: experience at Rouen's hospital]. / Grossesses interstitielles : traitement chirurgical, fertilité et devenir obstétrical. L'expérience rouennaise.

OBJECTIVE: Presenting our experience concerning interstitial pregnancies (IP) surgical management and to evaluate our patients' subsequent long-term fertility. PATIENTS AND METHOD: Twenty patients underwent surgical treatment of IP in our department over 15 years. In this retrospective study, we present symptoms that led to diagnosis, treatments, fertility and obstetrical outcome. RESULTS: Mean gestational age at diagnosis was 8SA, with a median BHCG rate of 7411 IU/L, and a patient mean age of 30 years. Ninety percent of patients had at least one risk factor for ectopic pregnancy. Pain or bleeding were the most common symptoms at admission, 4 patients were admitted in an hypovolemic shock status. Location of the interstitial ectopic pregnancy was discovered during surgery in 45 % of cases. Six patients had a large hemoperitoneum bigger than 1L, 5 patients had an IP of uterine stump after salpingectomy for a previous ectopic pregnancy. The most used surgical technique was in 60 % of cases the excision by Endo GIA stapling(®) with salpingectomy. Regarding fertility, 12 patients wished pregnancy in the aftermath of the intervention, 10 had at least one pregnancy, among them there is an ectopic contralateral ampullary pregnancy, and a contralateral recurrence of interstitial pregnancy. Four patients were delivered by cesarean section and 4 patients were delivered vaginally, some several times. No uterine rupture occured. DISCUSSION AND CONCLUSION: Interstitial pregnancy is a rare ectopic pregnancy. Its diagnosis is difficult and may involve maternal life-threatening and fertility. In subsequent pregnancies, the clinician has to be careful concerning the risks of interstitial pregnancy recurrence and uterine rupture.