Evaluation of a prophylactic transfusion program on obstetric outcomes in pregnant women with sickle cell disease: A single centre retrospective cohort study.

OBJECTIVE: To evaluate the effects of a prophylactic transfusion program (TP) on obstetric and perinatal outcomes in pregnant women with sickle cell disease (SCD). METHODS: This retrospective cohort study included all singleton pregnancies among women with SCD in a French university tertiary care center between 1 January 2004 and 31 December 2017. The TP group included patients selected according to the French guidelines who received regular red blood cell transfusions during pregnancy until delivery. The factors associated with TP indication [year of birth, SCD genotype, history of acute chest syndrome and delayed hemolysis transfusion reaction (DHTR) risk score] were taken into account in a propensity score. A composite obstetric adverse outcome was defined associating birth before 34 gestational weeks and/or pre-eclampsia and/or small for gestational age and/or abruption and/or stillbirth and/or maternal death and/or neonatal death. RESULTS: In total, 246 pregnancies in 173 patients were analyzed. Twenty-two pregnancies with a history of DHTR were excluded. A higher frequency of TP was found before 2013 [119/148 (80.4%) vs 38/76 (50%); p < 0.001]. Rates of preterm birth before 34 gestational weeks (5.6% vs 19.7%; p = 0.001), vaso-occlusive crisis (36.5% vs. 61.8%; p < 0.001), and acute chest syndrome (6.1% vs. 14.5%; p = 0.04) during pregnancy were decreased significantly in the TP group. Among the groups with and without composite obstetric adverse outcomes, the frequency of TP was 52.6% and 74.7%, respectively [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.09-1.02]. The multivariate analysis shows that the TP was associated with a significant reduction in the risk of composite obstetric adverse outcomes (OR 0.28, 95% CI 0.08-0.97; p = 0.04). CONCLUSION: A red blood cell TP may have an independent protective effect on maternal and perinatal adverse outcomes during pregnancy in women with SCD.

Antenatal screening of small for gestational age: Impact on obstetrical management and neonatal outcomes in case of trial of labor after 37 weeks.

OBJECTIVE: Antenatal screening of small fetuses for gestational age (SGA) is a public health challenge. The aim of this study is to assess the obstetrical management and the immediate neonatal outcomes, according to the antenatal screening of the SGA fetuses. METHODS: We performed a retrospective study in a French tertiary care hospital between January 1, 2016 and December 31, 2018. Women were eligible if they had a monofetal pregnancy with a fetus in head presentation and a trial of labor after 37 weeks. A fetus was considered SGA when the estimated fetal weight was less than the 10th percentile at the third trimester ultrasound. A newborn was considered hypotrophic when the birthweight was less than the 10th percentile. RESULTS: 8 153 newborns were included and 948 of the newborns were hypotrophic (308 were suspected for SGA, 640 were not suspected for SGA) and 7205 were eutrophic. Among the hypotrophic neonates, we observed no significant difference regarding the immediate neonatal outcomes between the two groups of fetuses suspected and not suspected for SGA. Among the fetuses not suspected for SGA, the rate of arterial umbilical cord pH below 7.10 was significantly higher in the hypotrophic newborns compared to the non hypotrophic newborns (4.7% vs 3.1%, p = 0.041). CONCLUSION: In our population, unsuspected fetal hypotrophy may be associated with an increased risk of neonatal acidosis. These results emphasize the benefit of improving prenatal screening to identify the SGA fetuses.

Impact of COVID-19 on surgical emergencies: nationwide analysis.

BACKGROUND: The COVID-19 pandemic has had a major impact on healthcare in many countries. This study assessed the effect of a nationwide lockdown in France on admissions for acute surgical conditions and the subsequent impact on postoperative mortality. METHODS: This was an observational analytical study, evaluating data from a national discharge database that collected all discharge reports from any hospital in France. All adult patients admitted through the emergency department and requiring a surgical treatment between 17 March and 11 May 2020, and the equivalent period in 2019 were included. The primary outcome was the change in number of hospital admissions for acute surgical conditions. Mortality was assessed in the matched population, and stratified by region. RESULTS: During the lockdown period, 57 589 consecutive patients were admitted for acute surgical conditions, representing a decrease of 20.9 per cent compared with the 2019 cohort. Significant differences between regions were observed: the decrease was 15.6, 17.2, and 26.8 per cent for low-, intermediate- and high-prevalence regions respectively. The mortality rate was 1.92 per cent during the lockdown period and 1.81 per cent in 2019. In high-prevalence zones, mortality was significantly increased (odds ratio 1.22, 95 per cent c.i. 1.06 to 1.40). CONCLUSION: A marked decrease in hospital admissions for surgical emergencies was observed during the lockdown period, with increased mortality in regions with a higher prevalence of COVID-19 infection. Health authorities should use these findings to preserve quality of care and deliver appropriate messages to the population.

Aspirin for the prevention of placenta-mediated complications in pregnant women with chronic hypertension.

Chronic hypertension affects 1-5% of women of childbearing age. During pregnancy, chronic hypertension is associated with an increased risk of vascular disease such as superimposed preeclampsia (PE), intrauterine growth retardation (IUGR), placental abruption, and preterm delivery. These serious and frequent pathologies, specific to pregnancy, carry a particularly high risk of maternal complications (HELLP syndrome, eclampsia, maternal death) and perinatal complications (perinatal death, neurological disorders). To date, there is no curative treatment of vascular complications of chronic hypertension during pregnancy. The only effective treatment, once the complications are established, is usually stopping the pregnancy and delivering the placenta. Some recommendations suggest the use of low dose aspirin in the prevention of these complications. Although the efficacy of low-dose aspirin is assumed in patients with previous preeclampsia, few studies have evaluated its efficacy in patients with chronic hypertension. Controlled prospective studies using very low doses of aspirin (less than 100 mg) and started after 15 weeks of gestation do not seem conclusive. The objective of this work is first to detail the complications of chronic hypertension during pregnancy, then to analyze the studies which evaluated the interest of low dose aspirin in prevention of the placental vascular complications of the pregnancy in patients with chronic hypertension. We also propose an update on the European and North American national recommendations for the prevention of preeclampsia by low dose aspirin in the high-risk population of patients with chronic hypertension. Finally we present the CHASAP (Chronic Hypertension and Acetyl Salicylic Acid in Pregnancy) trial (NCT04356326), a multicentric prospective randomized double-blind superiority trial, which will compare, in pregnant women with chronic hypertension, the efficacy of low dose aspirin (150 mg/day) with a placebo, in the prevention of maternal-fetal morbidity and mortality (preeclampsia, placental abruption, IUGR, perinatal death, maternal death, and preterm delivery).

Clinical and radiological outcomes of 40 cases of SLAC and SNAC wrist treated by four-corner arthrodesis with locking plate.

The treatment of scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC) wrist varies. No clear consensus exists on surgical indications. Scaphoid excision and four-corner arthrodesis with locking plate is one of preferred treatments for these lesions. The purpose of this study was to assess the clinical and radiological outcomes of locking plates for treating SNAC and SLAC wrist after a mean follow-up of 5 years and to compare these outcomes with the results reported in the literature. A retrospective study was conducted in two hospitals, involving 40 patients who underwent scaphoid excision and four-corner arthrodesis with locking plate between January 2006 and September 2016. All patients were reviewed as outpatients with clinical and radiographic measurements. At the last follow-up, the mean pain level on visual analog scale (VAS) was 2.5/10 [0-7] (SD: 1.7). Patients had a mean flexion of 46% and a mean extension of 46% compared to the contralateral side. An 18% gain was observed in grip strength. The mean postoperative QuickDASH score was 30 [0-57] (SD: 15.3). Seventy percent of patients were satisfied with the operation. Complete (all four joint interfaces) joint space fusion was achieved in 55% of patients. Only one patient (2.5%) had no joint fusion. The joint between the lunate and the capitate was fused in 38 patients (95%). Nine patients suffered complications; eight of them required surgical revision (20%). Four-corner arthrodesis with locking plate is a valuable surgical technique for treating SLAC and SNAC wrist because it preserve satisfactory range of motion and grip strength (64% compared to the non-operated side), maintains the height of the carpus and prevents the premature appearance of radiocarpal osteoarthritis, as long as the technical challenges of this procedure are mastered.

Postoperative evaluation of chronic pain in patients with Mayer - Rokitansky - Küster - Hauser (MRKH) syndrome and uterine horn remnant: Experience of a tertiary referring gynaecological department.

INTRODUCTION: Patients with Mayer - Rokitansky - Küster - Hauser (MRKH) syndrome often experience chronic pelvic pain negatively impacting their life's quality. Our understanding of the factors involved in this symptom remains poor. The aim of our study was to further investigate the different components of this pelvic pain in patients with MRKH undergoing pelvic surgery. Our second objective was to assess the evolution of this pain in patients undergoing surgical removal of their uterine horn remnant. MATERIAL AND METHODS: We conducted a retrospective analysis of a cohort of patients treated in our tertiary referring gynaecological department. Patients included had a MRKH syndrome with at least one uterine horn remnant and all underwent at least one surgical procedure in our centre. Descriptive analysis of the main characteristics and of the management of these patients was conducted. Postoperative pain was evaluated using simple words and / or analgesic consumption evaluation. RESULTS: Between 1991 and 2013, twenty-one patients were included in our centre. Out of them, 20 (95 %) had chronic pelvic pain, mostly cyclic pain lasting 2-3 days. Fourteen patients had surgical removal of their uterine horns remnant and only 3 patients (21 %) had persistent pain at their postoperative visit. Surgical findings included peritoneal endometriosis in 8 patients (38 %) and other unexpected findings in 6. At pathological analysis, secretary endometrium in the uterine horn remnant was found in 11 patients (79 %). CONCLUSION: The origin of chronic pain in MRKH is combining several factors such as endometriosis or secretary endometrium. Surgical removal of uterine horn remnant improved most of our patients' pelvic chronic pain. Further studies should help improve our understanding of this specific entity.

Fertility and pregnancy outcomes in patients with bicorporeal uterus and blind hemivagina: 20 years of experience in a tertiary referral gynaecological department.

BACKGROUND: To evaluate fertility and pregnancy outcomes in patients with uterus bicorporeal and blind hemivagina. Our second objective was to investigate factors predicting fertility and pregnancy outcomes in those patients. MATERIAL AND METHODS: We conducted a retrospective analysis in a tertiary referring gynaecological department, in France. We included all patients with uterus bicorporeal and blind hemivagina who underwent at least one surgery in our centre. Initial characteristics of the patients included were extracted from their medical charts and patients were contacted to assess their fertility and pregnancies outcomes upon their consent to participate to the study. RESULTS: Between 1989 and 2010, 79 patients fulfilled inclusion criteria and were selected for analysis. Mean follow up of those patients was of 16.15 (QI 10-21) years. Forty-six patients (58.2%) returned the survey and among them, 21 (45.7%) were fertile, 8 (17.4%) were infertile and 17 (37%) never attempted to get pregnant following initial management. Forty-nine pregnancies were included to assess pregnancies outcomes: 11 (22.5%) early miscarriages, 1 (2.0%) extra-uterine pregnancy, 2 (4.1%) second semester miscarriages and 35 (71.4%) leaded to living birth. Nineteen (54.3%) deliveries occurred by caesarean section and 14 (40.0%) by vaginal delivery. Fifteen pregnancies (42.9%) were complicated. In univariate analysis, adhesiolysis performed at the time of initial surgery was the only factor associated with infertility (p=0.004). CONCLUSIONS: Fertility seems to be perfectly conserved in those patients and they do not have increased rate of adverse pregnancies outcomes.

Alterations in Cell Motility, Proliferation, and Metabolism in Novel Models of Acquired Temozolomide Resistant Glioblastoma.

Glioblastoma (GBM) is an aggressive and incurable tumor of the brain with limited treatment options. Current first-line standard of care is the DNA alkylating agent temozolomide (TMZ), but this treatment strategy adds only ~4 months to median survival due to the rapid development of resistance. While some mechanisms of TMZ resistance have been identified, they are not fully understood. There are few effective strategies to manage therapy resistant GBM, and we lack diverse preclinical models of acquired TMZ resistance in which to test therapeutic strategies on TMZ resistant GBM. In this study, we create and characterize two new GBM cell lines resistant to TMZ in vitro, based on the 8MGBA and 42MGBA cell lines. Analysis of the TMZ resistant (TMZres) variants in conjunction with their parental, sensitive cell lines shows that acquisition of TMZ resistance is accompanied by broad phenotypic changes, including increased proliferation, migration, chromosomal aberrations, and secretion of cytosolic lipids. Importantly, each TMZ resistant model captures a different facet of the "go" (8MGBA-TMZres) or "grow" (42MGBA-TMZres) hypothesis of GBM behavior. These in vitro model systems will be important additions to the available tools for investigators seeking to define molecular mechanisms of acquired TMZ resistance.

Prognostic value of local relapse for patients with endometrial cancer.

BACKGROUND: The objective of our study was to determine survival and prognostic factors associated with isolated local recurrence of endometrial cancer. METHODS: Data of 1229 patients with endometrial carcinoma treated between 2000 and 2012 were extracted from maintained databases of nine French University Hospitals as well as from the Senti-Endo trial. Patients with isolated central pelvic and vaginal recurrence were selected for further analysis. RESULTS: Two hundreds and twenty five patients recurred during the inclusion period, 20 with isolated central pelvic recurrence and 23 with vaginal recurrence. Patients without recurrence had initially significantly less lymphovascular space invasion (p = 0.01), less advanced diseases (>stage II) (p < 0.001) and more often low or intermediate risk tumours than patients with local recurrence. Local recurrence was statistically associated with better overall survival than non-local recurrence (p = 0.028) but dramatically decreased overall survival when compared to patients without any recurrence (p < 0.001). The site of recurrence, i.e. vaginal or central pelvic, was significantly associated with overall survival (p = 0.015). Patients without brachytherapy at initial management were more likely to have local recurrence of their disease when compared to those without recurrence (p = 0.03). None of the prognostics factors for survival in patients with local recurrence was statistically significant in multivariate analysis. CONCLUSIONS: Local recurrence is a key event in endometrial cancer evolution severely impacting overall survival. Better understanding of the factors associated with prolonged survival is mandatory to improve our management of these patients.

Influence of dentin thickness on intrapulpal temperature under simulated pulpal pressure during Nd:YAG laser irradiation.

The aim of this study was to evaluate the effects of dentin thickness and pulpal pressure simulation (PPS) on the variation of intrapulpal temperature (∆T) when submitted to an adhesive technique using laser irradiation. Sixty sound human molars were sectioned and randomly divided into two groups (n = 30): group 1-1 mm of dentin thickness; group 2-2 mm of dentin thickness. Each group was divided into two subgroups (n = 15): subgroup A-absence of PPS; subgroup P-presence of PPS (15 cm H2O), sequentially treated with the following: 37 % phosphoric acid, adhesive system (Adper Single Bond), irradiation with Nd:YAG laser (1064 nm, 10 Hz, 60 s) using 60, 80, and 100 mJ/pulse energy parameters and light-curing (10 s). The ∆T was evaluated during the laser irradiation with a digital thermometer. Data were analyzed by three-way ANOVA and Tukey tests (p < 0.05). Three-way ANOVA revealed no significant differences for dentin thickness (p = 0.6512) on ∆T. PPS significantly reduced ∆T (p = 0.0001). The laser energy parameters (p = 0.0027) indicated that 100 mJ presented with significantly greater ∆T when compared to the groups irradiated with 80 and 60 mJ. Dentin thickness did not affect ∆T. The presence of PPS reduced the mean temperature values. The Nd:YAG laser energy parameters had a negative influence on the variation of temperature in the absence of PPS. In the presence of PPS, there was no risk to the pulp, since this study obtained temperature increases below 5.5 °C for all energy parameters, showing the technical viability for in vivo conditions.

[Predictive and prognostic factors of preeclampsia: Interest of PlGF and sFLT-1]. / Facteurs prédictifs et pronostiques de la prééclampsie : intérêt du dosage du PlGF et du sFLT-1.

Preeclampsia is characterized by the association of hypertension and a de novo proteinuria in the second half of pregnancy. Currently, obstetrical teams do not have any tool to detect during the first trimester of pregnancy, in low risk population, the patients likely to develop early and severe preeclampsia. On the other hand, there is no diagnostic/prognostic tool in case of strong suspicion of preeclampsia. The Placental Growth Factor (PIGF) and soluble receptor of the Vascular Endothelial Growth Factor (sFlt-1) are respectively two molecules pro- and anti-angiogenic released mainly by the placenta during pregnancy. Numerous experimental and clinical results suggest that an imbalance of pro/anti-angiogenic factors is involved in the pathophysiology of preeclampsia. We selected and analyzed the main studies that have evaluated the predictive, diagnostic and prognostic value of these two biomarkers for preeclampsia.

Enamel surface alterations after repeated conditioning with HCl.

BACKGROUND: The aim of this study was to investigate the influence of etching time with 15% hydrochloric acid (HCl) on the enamel surface destruction by studying the resulting roughness and erosion depth. METHODS: The vestibular surfaces of 12 extracted, caries free human incisors were divided into four quadrants, and each quadrant was etched with 15% HCl for different numbers of etching cycles (1×2, 2×2, 3×2 and 4×2 min). Surface roughness and erosion depth were measured quantitatively with optical profilometry, and the surface morphology was imaged with scanning electron microscopy (SEM). RESULTS: After two minutes of 15% HCl application a median enamel substance loss of 34.02 µm was observed. Lengthening of etching time (2×2, 3×2 and 4×2 min) resulted in significantly increase in erosion depth to each additionally, between 13.28 -15.16 µm (p < 0.05) ending up in a total median enamel surface loss of 77 µm. Regarding surface roughness no significant (p > 0.05) difference was found between unetched enamel and the etched enamel surfaces. CONCLUSION: Repeated 15% HCl conditioning of the enamel surface increases the depth of the etched surface erosion. However, the total erosion depth is rather shallow and therefore negligible.

Comparability, diagnostic validity and completeness of Nigerian cancer registries.

BACKGROUND: Like many countries in Africa, Nigeria is improving the quality and coverage of its cancer surveillance. This work is essential to address this growing category of chronic diseases, but is made difficult by economic, geographic and other challenges. PURPOSE: To evaluate the completeness, comparability and diagnostic validity of Nigeria's cancer registries. METHODS: Completeness was measured using children's age-specific incidence (ASI) and an established metric based on a modified Poisson distribution with regional comparisons. We used a registry questionnaire as well as percentages of death-certificate-only cases, morphologically verified cases, and case registration errors to examine comparability and diagnostic validity. RESULTS: Among the children's results, we found that over half of all cancers were non-Hodgkin lymphoma. There was also evidence of incompleteness. Considering the regional completeness comparisons, we found potential evidence of cancer-specific general incompleteness as well as what appears to be incompleteness due to inability to diagnose specific cancers. We found that registration was generally comparable, with some exceptions. Since autopsies are not common across Nigeria, coding for both them and death-certificate-only cases was also rare. With one exception, registries in our study had high rates of morphological verification of female breast, cervical and prostate cancers. CONCLUSIONS: Nigeria's registration procedures were generally comparable to each other and to international standards, and we found high rates of morphological verification, suggesting high diagnostic validity. There was, however, evidence of incompleteness.

[Operative technique: The clitoral transposition]. / Technique opératoire: la transposition clitoridienne.

Female sexual mutilations result in an important physical and mental suffering. A large number of women have been affected and require a global management, including surgical clitoral transposition. This surgical technique is allowing a rapid improvement of clinical symptoms. In this article, we will describe the indications and operative technique of the clitoral transposition.

Cell growth density modulates cancer cell vascular invasion via Hippo pathway activity and CXCR2 signaling.

Metastasis of cancer cells involves multiple steps, including their dissociation from the primary tumor and invasion through the endothelial cell barrier to enter the circulation and finding their way to distant organ sites where they extravasate and establish metastatic lesions. Deficient contact inhibition is a hallmark of invasive cancer cells, yet surprisingly the vascular invasiveness of commonly studied cancer cell lines is regulated by the density at which cells are propagated in culture. Cells grown at high density were less effective at invading an endothelial monolayer than cells grown at low density. This phenotypic difference was also observed in a zebrafish model of vascular invasion of cancer cells after injection into the yolk sac and extravasation of cancer cells into tissues from the vasculature. The vascular invasive phenotypes were reversible. A kinome-wide RNA interference screen was used to identify drivers of vascular invasion by panning small hairpin RNA (shRNA) library-transduced noninvasive cancer cell populations on endothelial monolayers. The selection of invasive subpopulations showed enrichment of shRNAs targeting the large tumor suppressor 1 (LATS1) kinase that inhibits the activity of the transcriptional coactivator yes-associated protein (YAP) in the Hippo pathway. Depletion of LATS1 from noninvasive cancer cells restored the invasive phenotype. Complementary to this, inhibition or depletion of YAP inhibited invasion in vitro and in vivo. The vascular invasive phenotype was associated with a YAP-dependent upregulation of the cytokines IL6, IL8 and C-X-C motif ligand 1, 2 and 3. Antibody blockade of cytokine receptors inhibited invasion and confirmed that they are rate-limiting drivers that promote cancer cell vascular invasiveness and could provide therapeutic targets.

Association of marital status and colorectal cancer screening participation in the USA.

AIM: In the USA, for both men and women, colorectal cancer (CRC) ranks third in incidence and second in mortality. Despite evidence that it decreases mortality, CRC screening in the USA remains under-utilized. Some European studies have suggested that marital status affects participation in CRC screening, but the effect of marital status on CRC screening participation in the USA is unknown. In this study, the aim was to compare CRC screening participation rates among married and unmarried couples, separated, widowed, never married and divorced adults living in the USA. METHOD: This was a retrospective data analysis of the 2010 Behavioural Risk Factor Surveillance System survey. The population studied included 239,300 participants, aged 50-75 years, who completed the 2010 survey. Logistic regression analysis was conducted to assess the association between adherence with CRC screening guidelines and marital status while accounting for survey stratum/weight and covariates. RESULTS: Individuals who were divorced or separated, never married or widowed had decreased odds of adherence with CRC screening guidelines compared with individuals who were married and unmarried couples. CONCLUSION: In this study, individuals living in the USA who were married and unmarried couples had increased odds of undergoing CRC screening compared to individuals in other marital status groups. Public health interventions are needed to promote CRC screening participation in these other groups.

Hypercalcaemia secondary to hypervitaminosis a in a patient with chronic renal failure.

Vitamin A toxicity is a well-described medical condition with a multitude of potential presenting signs and symptoms. It can be divided into acute and chronic toxicity. Serum vitamin A concentrations are raised in chronic renal failure even with ingestion of less than the usual toxic doses. Hypercalcaemia can occasionally be associated with high levels of vitamin A but it is rare. In this report, we describe a 67- year old female patient with chronic kidney disease who was taking vitamin A supplements for approximately 10 years. The patient had worsening of her chronic kidney disease over the last years and developed chronic hypercalcaemia. Her vitamin A level was elevated with a daily intake of 7000 IU. The vitamin A supplement was stopped. A few months later, vitamin A level diminished substantially and serum calcium levels returned to normal.