Impact of pectus excavatum on pulmonary function and exercise capacity in patients treated with 3D custom-made silicone implants.

BACKGROUND: Pectus excavatum (PE) is the most common congenital chest wall deformity, whose cardiopulmonary consequences are controversial. PE surgery is in our experience usually performed for aesthetic reasons. OBJECTIVES: The aim of this study was to evaluate the impact of PE on respiratory function and exercise capacity in patients with PE before patient-specific silicone implant correction. METHODS: This monocentric prospective study conducted at Toulouse University Hospital included sixty patients scheduled for custom-made silicone implants correction. Respiratory function (pulmonary function tests (FPTs)) and exercise capacity (VO2 max) were measured before surgery. RESULTS: Before surgery, no (0/60) restrictive lung disease was detected, with a mean total lung capacity (TLC) of 98.5% of predicted value (IC 95%; 80.4-137). Median VO2 max (n=56) was normal (89% predicted), with no cardiac limitation. CONCLUSION: In this cohort, PE had no impact on respiratory function nor exercise capacity. In patients without cardiac or respiratory effects of PE, silicone implants should be considered the preferred approach as it adequately addressed patients' main complaint of low self-esteem.

The HERA (Hyper-response Risk Assessment) Delphi consensus for the management of hyper-responders in in vitro fertilization.

PURPOSE: To provide agreed-upon guidelines on the management of a hyper-responsive patient undergoing ovarian stimulation (OS) METHODS: A literature search was performed regarding the management of hyper-response to OS for assisted reproductive technology. A scientific committee consisting of 4 experts discussed, amended, and selected the final statements. A priori, it was decided that consensus would be reached when ≥66% of the participants agreed, and ≤3 rounds would be used to obtain this consensus. A total of 28/31 experts responded (selected for global coverage), anonymous to each other. RESULTS: A total of 26/28 statements reached consensus. The most relevant are summarized here. The target number of oocytes to be collected in a stimulation cycle for IVF in an anticipated hyper-responder is 15-19 (89.3% consensus). For a potential hyper-responder, it is preferable to achieve a hyper-response and freeze all than aim for a fresh transfer (71.4% consensus). GnRH agonists should be avoided for pituitary suppression in anticipated hyper-responders performing IVF (96.4% consensus). The preferred starting dose in the first IVF stimulation cycle of an anticipated hyper-responder of average weight is 150 IU/day (82.1% consensus). ICoasting in order to decrease the risk of OHSS should not be used (89.7% consensus). Metformin should be added before/during ovarian stimulation to anticipated hyper-responders only if the patient has PCOS and is insulin resistant (82.1% consensus). In the case of a hyper-response, a dopaminergic agent should be used only if hCG will be used as a trigger (including dual/double trigger) with or without a fresh transfer (67.9% consensus). After using a GnRH agonist trigger due to a perceived risk of OHSS, luteal phase rescue with hCG and an attempt of a fresh transfer is discouraged regardless of the number of oocytes collected (72.4% consensus). The choice of the FET protocol is not influenced by the fact that the patient is a hyper-responder (82.8% consensus). In the cases of freeze all due to OHSS risk, a FET cycle can be performed in the immediate first menstrual cycle (92.9% consensus). CONCLUSION: These guidelines for the management of hyper-response can be useful for tailoring patient care and for harmonizing future research.

The HERA (Hyper-response Risk Assessment) Delphi consensus definition of hyper-responders for in-vitro fertilization.

PURPOSE: To provide an agreed upon definition of hyper-response for women undergoing ovarian stimulation (OS)? METHODS: A literature search was performed regarding hyper-response to ovarian stimulation for assisted reproductive technology. A scientific committee consisting of 5 experts discussed, amended, and selected the final statements in the questionnaire for the first round of the Delphi consensus. The questionnaire was distributed to 31 experts, 22 of whom responded (with representation selected for global coverage), each anonymous to the others. A priori, it was decided that consensus would be reached when ≥ 66% of the participants agreed and ≤ 3 rounds would be used to obtain this consensus. RESULTS: 17/18 statements reached consensus. The most relevant are summarized here. (I) Definition of a hyper-response: Collection of ≥ 15 oocytes is characterized as a hyper-response (72.7% agreement). OHSS is not relevant for the definition of hyper-response if the number of collected oocytes is above a threshold (≥ 15) (77.3% agreement). The most important factor in defining a hyper-response during stimulation is the number of follicles ≥ 10 mm in mean diameter (86.4% agreement). (II) Risk factors for hyper-response: AMH values (95.5% agreement), AFC (95.5% agreement), patient's age (77.3% agreement) but not ovarian volume (72.7% agreement). In a patient without previous ovarian stimulation, the most important risk factor for a hyper-response is the antral follicular count (AFC) (68.2% agreement). In a patient without previous ovarian stimulation, when AMH and AFC are discordant, one suggesting a hyper-response and the other not, AFC is the more reliable marker (68.2% agreement). The lowest serum AMH value that would place one at risk for a hyper-response is ≥ 2 ng/ml (14.3 pmol/L) (72.7% agreement). The lowest AFC that would place one at risk for a hyper-response is ≥ 18 (81.8% agreement). Women with polycystic ovarian syndrome (PCOS) as per Rotterdam criteria are at a higher risk of hyper-response than women without PCOS with equivalent follicle counts and gonadotropin doses during ovarian stimulation for IVF (86.4% agreement). No consensus was reached regarding the number of growing follicles ≥ 10 mm that would define a hyper-response. CONCLUSION: The definition of hyper-response and its risk factors can be useful for harmonizing research, improving understanding of the subject, and tailoring patient care.

[Congenital thoracic deformities and 3D custom-made implants. New classification based on a series of 789 treated cases]. / Malformations thoraciques congénitales et implants sur mesure 3D. Nouvelle classification basée sur une série de 789 cas traités.

The authors present a new study on 789 cases of congenital thoracic malformations including 638 pectus excavatum and 151 Poland syndromes, according to a new classification which completes Chin's one. All these malformations were treated with silicone elastomer implants. The contribution of computer-aided design and manufacturing (CAD/CAM) since 2008 is essential. The one-stage surgical protocol is precisely described. The results are impressive, permanent, for life, and complications are rare. The authors evoke a common vascular etiopathogenesis theory at the embryonic stage and question the heavy techniques of invasive remodeling that are most often unjustified.

The impact of embryo vitrification on placental histopathology features and perinatal outcome in singleton live births.

STUDY QUESTION: Does embryo vitrification affect placental histopathology pattern and perinatal outcome in singleton live births? SUMMARY ANSWER: Embryo vitrification has a significant effect on the placental histopathology pattern and is associated with a higher prevalence of dysfunctional labor. WHAT IS KNOWN ALREADY: Obstetrical and perinatal outcomes differ between live births resulting from fresh and frozen embryo transfers. The effect of embryo vitrification on the placental histopathology features associated with the development of perinatal complications remains unclear. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study evaluating data of all live births from one academic tertiary hospital resulting from IVF treatment with autologous oocytes during the period from 2009 to 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients had placentas sent for pathological evaluation irrelevant of maternal or fetal complications status. Placental, obstetric and perinatal outcomes of pregnancies resulting from hormone replacement vitrified embryo transfers were compared with those after fresh embryo transfers. A multivariate analysis was conducted to adjust the results for determinants potentially associated with the development of placental histopathology abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1014 singleton live births were included in the final analysis and were allocated to the group of pregnancies resulting from fresh (n = 660) and hormone replacement frozen (n = 354) embryo transfers. After the adjustment for confounding factors the frozen embryo transfers were found to be significantly associated with chorioamnionitis with maternal (odds ratio (OR) 2.0; 95% CI 1.2-3.3) and fetal response (OR 2.6; 95% CI 1.2-5.7), fetal vascular malperfusion (OR 3.9; 95% CI 1.4-9.2), furcate cord insertion (OR 2.3 95% CI 1.2-5.3), villitis of unknown etiology (OR 2.1; 95% CI 1.1-4.2), intervillous thrombi (OR 2.1; 95% CI 1.3-3.7), subchorionic thrombi (OR 3.4; 95% CI 1.6-7.0), as well as with failure of labor progress (OR 2.5; 95% CI 1.5-4.2). LIMITATIONS, REASONS FOR CAUTION: Since the live births resulted from frozen-thawed embryos included treatment cycles with previously failed embryo transfers, the factors over embryo vitrification may affect implantation and placental histopathology. WIDER IMPLICATIONS OF THE FINDINGS: The study results contribute to the understanding of the perinatal future of fresh and vitrified embryos. Our findings may have an implication for the clinical decision to perform fresh or frozen-thawed embryo transfer. STUDY FUNDING/COMPETING INTEREST(S): Authors have not received any funding to support this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Pregnancy outcomes in women with panhypopituitarism: a population-based study.

RESEARCH QUESTION: What are the consequences of panhypopituitarism on pregnancy outcomes? DESIGN: Retrospective population-based study using data from the Healthcare Cost and Utilization Project - Nationwide Inpatient Sample (HCUP-NIS). A dataset was created of all deliveries between 2004 and 2014 inclusive. Within this group, all deliveries to women who had a diagnosis of panhypopituitarism during pregnancy were identified as part of the study group (n = 120), and the remaining deliveries comprised the reference group (n = 8,732,641). A multivariate logistic regression analysis, controlling for confounding effects, was conducted to explore associations between panhypopituitarism and pregnancy complications, delivery and neonatal outcomes. RESULTS: No significant differences were found in the risk of developing gestational hypertension, gestational diabetes mellitus, placental abruption, or preterm delivery delivering a small for gestational age neonate, or in the mode of delivery. There was a higher risk of developing maternal infection (odds ratio [OR] 3.14, 95% confidence interval [CI] 1.46-6.74) and congenital anomalies (OR 6.97, 95% CI 2.57-18.95); however, due to the small number of cases these results should be interpreted with caution. CONCLUSIONS: Pregnancy outcomes of women with panhypopituitarism are comparable to those of the general population. Further studies are needed to assess the risk of congenital anomalies and maternal infection in pregnant women with panhypopituitarism.

EUS-guided biliary drainage with electrocautery-enhanced lumen-apposing metal stent placement should replace PTBD after ERCP failure in patients with distal tumoral biliary obstruction: a large real-life study.

AIMS: In cases of malignant distal biliary obstruction, ERCP is the preferred technique for bile duct drainage. In case of failure, the alternative techniques are percutaneous transhepatic biliary drainage (PTBD) and more recently endoscopic ultrasound-guided biliary drainage. A new type of stent called the electrocautery-enhanced lumen-apposing metal stent (EC-LAMS) has been developed to enable the performance of biliary-enteric anastomosis under EUS-guidance in a single step, without prior bile duct puncture or the need for a guidewire. The aim of our study was to compare the real-life efficacies of PTBD and EUS-BD with the EC-LAMS for cases of ERCP failure in patients with malignant biliary obstruction. METHODS: We performed a monocentric retrospective study comparing PTBD and EUS-BD with the use of electrocautery-enhanced lumen-apposing metal stent in the context of a malignant distal biliary obstruction after ERCP failure. RESULTS: 95 patients were included (50 in EUS-BD group and 45 in PTBD group). The main etiology of malignant obstruction was adenocarcinoma of the head of pancreas (85%). There was a significant difference in favor of endoscopic ultrasound-guided biliary drainage using electrocautery-enhanced lumen-apposing metal stent for the following criteria: clinical success: 89.3% vs. 45.5%; p < 0.0001; procedure-related adverse event rate: 2.12% vs. 22.7%; p = 0.003; duration of post-drainage hospitalization: 3.5 vs. 8.2 days; p < 0.0001, overall survival (median survival): 118.2 vs. 42 days; p = 0.012, overall cost of the strategy per patient: 5098 vs. 9363 euros; p < 0.001. CONCLUSION: Our results are in favor of EUS-BD using electrocautery-enhanced lumen-apposing metal stent in case of ERCP failure for a distal tumor biliary obstruction. Operators performing ERCP for distal tumor biliary obstruction must learn this backup procedure because of its superiority over percutaneous transhepatic biliary drainage in terms of clinical success, safety, cost, and overall survival.

The effects of smoking on pregnancy risks in women with polycystic ovary syndrome: a population-based study.

STUDY QUESTION: Is there is an association between smoking and pregnancy complications in pregnant women with polycystic ovarian syndrome (PCOS)? SUMMARY ANSWER: There is an increased risk of developing gestational diabetes mellitus (GDM) among women with PCOS who smoke. WHAT IS KNOWN ALREADY: Smokers are at increased risk of developing Type 2 Diabetes Mellitus (DM). Given the common pathophysiology and shared risk factors between type 2 DM and GDM, we sought to assess whether an association between smoking and the development of GDM exists. STUDY DESIGN, SIZE, DURATION: This is a retrospective population-based study utilizing data from the HCUP-NIS over 11 years from 2004 to 2014. Pregnant women with PCOS who did smoke were compared to pregnant women with PCOS who did not smoke. A second comparison was made between pregnant smokers with and without PCOS. Of the 443 590 women who smoked during pregnancy and the 14 882 women with PCOS, 631 women were both smokers and diagnosed with PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: The Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) is the largest inpatient sample database in the USA and is composed of hospital inpatient stays submitted by hospitals throughout the entire country. Each year, the database provides information relating to 7 million inpatient stays, including patient characteristics, diagnosis and procedures. The data are representative of ∼20% of admissions to US hospitals across 48 states and the District of Columbia. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in the risks of preterm delivery (aOR1.2; CI 0.8-1.9), placental abruption (aOR1.1; CI 0.4-3.2), pregnancy induced hypertension (aOR1.0; CI 0.7-1.5), rate of operative vaginal delivery (aOR1.5; CI 0.9-2.5) and rates of cesarean section (C/S) (aOR1.0; CI 0.7-1.3) between smoking and non-smoking women with PCOS. A significant association between smoking and GDM was observed in women with PCOS (aOR1.5; CI1.01-2.1). LIMITATIONS, REASONS FOR CAUTION: The limitations of our study are its retrospective nature and the fact that it relies on an administrative database. Data regarding smoking and PCOS diagnosis could be skewed due to patients' underreporting, lack of documentation and documentation differences. WIDER IMPLICATIONS OF THE FINDINGS: The public health implications of confirming smoking as a risk for GDM among women with PCOS are many. This can lead to earlier screening in pregnancy of smokers for GDM. Earlier initiation of interventions could decrease fetal complications and possibly have an impact on the life and long-term health of the offspring. Future studies are needed in order to assess whether smoking cessation during pregnancy decreases the risk of GDM in that gestation. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used. The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

[Update on precursors of vulvar carcinoma]. / Lésions vulvaires précancéreuses : mise au point.

Vulvar carcinomas represent 4% of all gynaecological cancers with 838 new cases in France in 2018. The precursor lesions of vulvar carcinomas are differentiated vulvar intraepithelial lesion (dVIN) in a context of lichen sclerosus and vulvar high-grade squamous intraepithelial lesion (HSIL) link to human papillomavirus (HPV) infection. Three typical clinical forms of HSIL are described: the Bowenoid papulosis, the Bowen's disease and the confluent VIN. Histopathology cannot differentiate effectively these two types of lesions. P16 and P53 immunostaining are valuable tools to respectively assess HPV infection and divide different types of dVIN. However, P53 immunostaining is still lacking sensibility to detect dVIN. First line therapies are medical treatment excluding the cases with a doubt of invasion. The gold standard treatment for dVIN and vulvar HSIL are respectively topical corticosteroids and imiquimod. Primary prevention for vulvar HSIL and dVIN are respectively HPV vaccination and early treatment of lichen sclerosus. Destructive therapy can be used in case of medical treatment failure such as CO2 laser, cryotherapy, dynamic phototherapy. Surgical indications should be carefully assessed between the risk of recurrence, the spread of the lesions, the aesthetic and functional aspect. Surgical procedures consist in either superficial vulvectomy or radical vulvectomy with or without flap reconstruction. Recurrence rate after surgery is around 20%.

[The pectus excavatum: Secondary surgery with implants]. / Le pectus excavatum : chirurgie secondaire par implants.

The pectus excavatum affects about one in 500 people. It is the most common malformation of the thorax. Several surgical or medical techniques have been proposed. Some are followed by complications or insufficient results. Secondary surgery with a deep customized 3D implant, may be an elegant and effective solution; it allows to obtain a good aesthetic result expected by patients in the absence of any respiratory or cardiovascular functional context.

Relationship between surrogate estimates and direct measurement of insulin resistance in women with polycystic ovary syndrome.

PURPOSE: To evaluate the relationship between surrogate estimates of insulin resistance and a direct measurement of insulin-mediated glucose uptake women with and without PCOS. METHODS: Retrospective cohort study of 75 PCOS and 118 controls. Fasting plasma glucose and insulin concentrations, insulin resistance as determined by the insulin suppression test, calculation of multiple surrogate estimates of insulin resistance, total and free testosterone concentrations, and correlations between the direct measure and surrogate estimates of insulin resistance were evaluated. RESULT(S): Surrogate markers of insulin resistance were correlated to a variable, but statistically significant degree with the direct measure of insulin resistance in control population and the women with PCOS. There was no correlation between the surrogate estimates of insulin resistance and total or free plasma testosterone concentrations. CONCLUSION(S): The surrogate estimates of insulin resistance evaluated were significantly related to a direct measure of insulin resistance, and this was true of both the control population and women with PCOS. The magnitude of the relationship between the surrogate estimates and the direct measurement was comparable and not significantly altered by androgen levels. Fasting plasma insulin concentration seems to be at least as accurate as any other surrogate estimate, and is by far the simplest.

[Twenty years later A story of intra-thoracic textiloma]. / Vingt ans après Histoire d'un textilome intra-thoracique.

INTRODUCTION: Intrathoracic textiloma is a rare complication possibly leading to misdiagnosis. It could present as haemoptysis, lung abscess, pseudo-tumour or a chronic cough. CASE REPORT: A 65-year-old patient with a history of multiple cardiac problems and needing long-term anticoagulation, complained since 2007 of recurrent haemoptysis of increasing abundance, the etiological investigation of which was negative. A thoracic CT-scan revealed a lesion in the lingula in contact with the pericardial plates of an implanted automatic defibrillator dating from 1989. In 2016, after two failures of arterial embolization, a diagnostic and therapeutic surgical exploration was undertaken on this patient who was a high operative risk. A segmental resection revealed an intra-pulmonary textiloma on pathological examination. CONCLUSION: The diagnosis of intrathoracic textiloma remains rare and its late presentation is non specific. Radiological imaging with a CT-scan and/or MRI could lead to the diagnosis. Surgery remains the reference treatment for the diagnosis and cure of intrathoracic textiloma with pathological examination, essential for confirmation. A means of prevention has to be developed because swab count is not totally reliable.

Management of recurrent implantation failure by gonadotropin-releasing hormone agonist and aromatase inhibitor suppression, in women without evidence of endometriosis.

Endometriosis is common among those with infertility, although many cases go undiagnosed. This study was performed to determine whether empiric treatment with two months of depo-leuprolide 3.75 mg monthly (dep-GnRH-ag) and letrozole 5 mg daily improves pregnancy outcomes in patients with at least two unexplained failed embryo transfers (ETs) but without a previous diagnosis of endometriosis. A retrospective cohort study was performed with subjects who failed at least two good quality ET. The study excluded women with a known history of endometriosis or ovarian cysts (possible endometriomas). Subjects (N = 38) were treated with dep-GnRH-ag and letrozole pre-cycle. Matched women (N = 37) who did not receive either pretreatment served as a control group. Data were compared by non-paired T-tests and multivariate logistic regression to control for confounding effects. Demographic data, hormonal profiles, and ovarian reserve parameters were similar between the two groups. The treated group had failed more embryo transfers (3.5 ± 1.7 vs. 2.0 ± 1.3, p = .01) than the controls. When adjusting for the number of MII oocytes collected, number of blastocysts developed and number of blastocysts transferred, there were more pregnancies (24/38 vs. 11/37, p = .02) and ongoing pregnancies (18/38 vs. 9/37, p = .03) in the treated group. Patients with multiple unexplained failed ET may have undiagnosed endometriosis and may benefit from pretreatment with dep-GnRH-ag and letrozole. These results would benefit from being subjected to a randomized prospective study.

Optogenetic dissection of Rac1 and Cdc42 gradient shaping.

During cell migration, Rho GTPases spontaneously form spatial gradients that define the front and back of cells. At the front, active Cdc42 forms a steep gradient whereas active Rac1 forms a more extended pattern peaking a few microns away. What are the mechanisms shaping these gradients, and what is the functional role of the shape of these gradients? Here we report, using a combination of optogenetics and micropatterning, that Cdc42 and Rac1 gradients are set by spatial patterns of activators and deactivators and not directly by transport mechanisms. Cdc42 simply follows the distribution of Guanine nucleotide Exchange Factors, whereas Rac1 shaping requires the activity of a GTPase-Activating Protein, ß2-chimaerin, which is sharply localized at the tip of the cell through feedbacks from Cdc42 and Rac1. Functionally, the spatial extent of Rho GTPases gradients governs cell migration, a sharp Cdc42 gradient maximizes directionality while an extended Rac1 gradient controls the speed.

New Simplified Screening Method for Postprandial Hypotension in Older People.

BACKGROUND: Postprandial hypotension (PPH) is an important disorder in the older people that remain underdiagnosed. The reference PPH diagnostic method is too demanding, because blood pressure (BP) needs to be measured 8 times in 2 hours. OBJECTIVES: Our primary objective was to define a new simplified PPH diagnostic method and to evaluate its performances. DESIGN: We conducted a cross-sectional study. SETTING: Two geriatric rehabilitation units in France. PARTICIPANTS: 104 patients (70 women, 34 men) with high risk of PPH were included. MEASUREMENTS: BP was measured twice before the midday meal in seated position at the table, and every 15 minutes for 90 minutes after the end of the meal. Receiver Operating Characteristic curves were plotted for each postprandial BP measure to determine the best postprandial measure in terms of sensitivity and specificity. The optimal diagnostic threshold was calculated with Youden's index according to BP difference before and after the meal. RESULTS: A new simplified diagnostic method is proposed: a decrease of at least 10 mmHg systolic BP between BP measures before the meal and 75 minutes after the end of the meal. This new method had a sensitivity of 82% (95%CI 66 - 92) and a specificity of 91% (95%CI 81 - 97). CONCLUSION: This new diagnostic method is fast, efficient and suitable for everyday use. It could improve PPH diagnosis in older people. Larger studies are needed to validate it.