[After the COVID crisis, what solutions for the future nursing home?] / Rapport 22-02. Après la crise COVID, quelles solutions pour l'EHPAD de demain ?

The ageing of the population induces situations of large vulnerability and dependence. Home care usually remains the best response to comply with the person's wish, the family's desire, and the civil society's interest. However, there are circumstances where patient management in a nursing home (EHPAD) is the only solution. The present pandemic of coronavirus COVID-19 has highlighted the issue of EHPAD and their limitations to provide high quality care. To analyze the current position of EHPAD into the care chain and to understand difficulties to their functioning, it seems essential to seek out accelerated changes in the EHPAD since their establishment in 1999 and then in the light of the current crisis, propose possible solutions with a positive view of the role which each EHPAD will have to ensure for future.

[Use of peak systolic velocity of the middle cerebral artery in the management of fetal anemia due to fetomaternal erythrocyte alloimmunization]. / Intérêt pratique du pic systolique de vélocité à l'artère cérébrale moyenne dans la prise en charge des anémies foetales par allo-immunisation érythrocytaire.

OBJECTIVE: To assess the peak systolic velocity in the middle cerebral artery (PSV-MCA) in the prediction of fetal anemia in case of severe red-cell alloimmunization. METHODS: A prospective study, from January 2003 to April 2006, of 47 consecutive pregnancies with severe alloimmunization. Fetal surveillance was based on titration and dosage of antibodies, ultrasound scans, and doppler for PSV-MCA measurement up to twice a week. A fetal blood sampling and in utero transfusion was performed in case of increase in PSV-MCA above 1.5 multiples of the median (MoM), and/or signs of hydrops on ultrasound. Severe fetal anemia was defined by fetal hemoglobin below 0.55MoM for gestational age. Analyses performed included the correlation between PSV-MCA and fetal hemoglobin, the value of PSV-MCA in the prediction of severe fetal anemia, and the determination of adequate threshold for intervention based on ROC curve analysis. RESULTS: Four hundred and eighty-five PSV-MCA were performed in 47 high-risk pregnancies, of which 125 were coupled with hemoglobin measurement by fetal blood sampling. There is a significant negative correlation between PSV-MCA and fetal hemoglobin (R2=0.6545 ; p<0.0001). Based on all prospective data, the negative predictive value of PSV-MCA was 97.8 %, sensitivity was 86.7 %, with a false positive rate of 12.2%. Area under the ROC curve was 0.85 (IC 95 %, 0.742-0.927 ; p<0.0001), suggesting an excellent value of this test. When switching the threshold for intervention from 1.5 to 1.6MoM, the positive predictive value increased, without decrease in sensitivity or negative predictive value. CONCLUSION: This study confirms the correlation between PSV-MCA and fetal hemoglobin. It allows a decrease of invasive procedures in the follow-up of pregnancies with severe red-cell alloimmunization.

IGFBP-1 inhibits EGF mitogenic activity in cultured endometrial stromal cells.

The properties of the insulin-like growth factor-binding proteins (IGFBP-1 to 6) are not limited to modulation of IGF actions. IGFBP-1, which shares an Arg-Gly-Asp (RGD) motif in its C-terminal domain, modulates cell motility by binding to integrin alpha5beta1. The cross-talks between integrins and growth factor receptor signalling pathways are extensively documented, particularly in the case of the epidermal growth factor receptor (EGFR). However, whether IGFBP-1 can modulate growth factor signalling through its interaction with integrin alpha5beta1 has not yet been studied. As EGF is involved in the decidualisation of endometrial stromal cells (ESCs) and as decidualised ESCs are a source of IGFBP-1, we investigated if IGFBP-1 can modulate EGF effects on ESCs. RGD- and IGF-independent inhibition of EGF mitogenic activity and EGFR signalling by IGFBP-1 were demonstrated in ESC primary cultures, A431, cells and in mouse fibroblasts lacking IGF receptors.

[Operative termination of pregnancy between 12 and 14 weeks' gestation: influence of the operator's experience]. / Particularités techniques de l'IVG instrumentale entre 12 et 14 semaines d'aménorrhée: influence de l'expérience de l'opérateur.

OBJECTIVE: To assess the feasibility of operative termination of pregnancy between 12 and 14 weeks of gestation and the role of the operator's experience in physicians previously unfamiliar to this technique. MATERIALS AND METHODS: A prospective study of 251 operative terminations of pregnancy, from July 1st, 2001 to January 31st, 2002, and from May 1st, 2002 to October 31st, 2002, in order to assess the role of operator's experience. 104 terminations between 12 and 14 weeks were compared to 147 terminations at earlier gestational ages. All patients received cervical ripening with 400 mcg oral misoprostol 3-4 hours before operation performed under general anesthesia. Evaluation criteria were: duration of operation, need for use of forceps, and complications: uterine perforation, cervical laceration, bleeding > 500 ml and need for blood transfusion. RESULTS: There was no difference in the rate of operative complications between terminations before and after 12 weeks. The duration of operation was slightly longer after 12 weeks than before (12.9 +/- 6.7 min versus 11.1 +/- 2.8 min.; p < 0.05). Forceps use was 0.7% before 12 weeks, 20% between 12 and 13 weeks, and 59% between 13 and 14 weeks (p < 0.01). There was no difference in the complication rate or in the need for forceps according to the operator's experience. The perceived difficulty in cervical dilatation was higher in early experience than in experimented operators (19.6% versus 5.2%; p < 0.05). CONCLUSION: Operative termination of pregnancy is technically feasible beyond 12 weeks without dramatic increase in operative complications. Technical skill can be acquired in a short time interval.

[Smoking and ectopic pregnancy: is there a causal relationship?]. / Tabac et grossesse extra-utérine: y a-t-il un lien de causalité?

Tobacco smoking is often studied as a risk factor in epidemiology. The impact on fertility and pregnancy is significant. At conception, maternal smoking may have an effect on the occurrence of ectopic pregnancy. Experimental studies on hamsters show interactions between tobacco and the oviduct. These interactions may explain the role of tobacco in ectopic pregnancy. Eleven case-control studies compared smoking in two groups of women: a cases group with ectopic pregnancy, and a control group. Ten of them found a relationship between tobacco smoking and ectopic pregnancy (increased relative risk). Considering this results, we must encourage women to reduce or better to stop smoking.

[Surgical site infections after cesarean section: results of a five-year prospective surveillance]. / Infections de site opératoire chez les patientes césarisées: bilan de 5 années de surveillance.

AIMS: To determine the incidence of surgical site infections and to identify risk factors for infections. METHOD: A prospective study of surgical site infections (SSI) after cesarean section was carried out from September 1997 to September 1998 (pilot study) and from January 2000 to August 2003, using the methodology of the American National Nosocomial Infection Surveillance System. Follow up of women was performed by midwives until discharge and during the post-natal visit. Suspected surgical site infections were confirmed by surgeons and infection control practitioners. The microbiological file of each patient was edited 30 days after cesarean section. Risk factors were analyzed using a logistic regression model. RESULTS: During the pilot study, infection rate was estimated at 3.2%. At multivariate analysis, factors independently associated with an increased risk of SSI were ASA score > 1, performance of cesarean section in a room not dedicated to this activity, and use of an open urine drainage system. During the following years (2000-2003), infection rates progressively decreased to reach 1.9% in 2003. Infections included superficial wound infections (involving skin and subcutaneous tissue) (47%), deep wound infections (involving deep and soft tissue (fascia and muscle) (20%) and organ/space infections (i.e. endometritis, pelvic abscess) (33%). Infections occurred after patient discharge in 47.5% of cases and diagnosis was based only on clinical findings in 30% of cases. Infected patients were hospitalized longer (median: 6 days) than non infected patients. CONCLUSION: Prospective surveillance of SSI led to better awareness of infectious problems among health care workers, to identification of risk factors and evaluation of health procedures. Surveillance contributed to a decrease in nosocomial infections.

Antiphospholipid syndrome and second- or third-trimester fetal death: follow-up in the next pregnancy.

OBJECTIVE: To evaluate the efficacy of a uniform management protocol in antiphospholipid-antibody-positive obstetric patients with at least one second- or third-trimester intra-uterine fetal death. STUDY DESIGN: A prospective study of 33 successive pregnancies in antiphospholipid-antibody-positive patients, diagnosed after an intra-uterine fetal death. The management included treatment by a combination of aspirin and low-molecular-weight heparin, and a close follow-up with at least clinical examination, ultrasonography, uterine, and umbilical artery Doppler monthly from the first trimester. In the absence of any anomaly, delivery was induced between 37 and 38 weeks' gestation. RESULTS: In this high risk population, seven recurrences of vascular pathology occurred: five cases of mild, isolated fetal growth retardation and one of preeclampsia associated with fetal growth retardation requiring preterm delivery. Eight patients were delivered before 37 weeks. No recurrence of second- or third-trimester fetal death was observed. Uterine artery Doppler was informative as early as the first trimester (12-15 weeks): a bilateral notch was associated with a lower birthweight (2626+/-688 g versus 3178+/-353 g, respectively, p = 0.01), despite similar gestational age. The negative predictive value of uterine Doppler was more than 92% at 12-15 weeks' gestation and remained high throughout pregnancy. CONCLUSION: Although intra-uterine fetal death is considered at high risk of recurrence in case of antiphospholipid syndrome (APS), a uniform management protocol including aspirin and heparin and close obstetrical follow-up led to a favorable outcome in most cases.

[Operable stage IB and II cancer of the uterine neck: retrospective comparison between preoperative utero-vaginal curietherapy and initial surgery followed by radiotherapy]. / Cancer du col utérin stades IB et II opérable: comparaison rétrospective entre curiethérapie utérovaginale préopératoire et chirurgie première suivies d'une radiothérapie.

PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable stages IB and II cervical carcinomas. PATIENTS AND METHODS: Between May 1972 and January 1994, 414 patients (pts) with cervical carcinoma staged according to the 1995 FIGO staging system underwent radical hysterectomy with (n = 380) or without (n = 34) bilateral pelvic lymph node dissection. Lateral ovarian transposition to preserve ovarian function was performed on 12 pts. The methods of radiation therapy (RT) were not randomised and depended on the usual practices of the surgical teams. Group I: 168 pts received postoperative RT (64 pts received vaginal brachytherapy alone [mean total dose (MD): 50 Gy], 93 pts had external beam pelvis RT (EBPRT) [MD: 45 Gy over 5 weeks] followed by vaginal brachytherapy [MD: 20 Gy], and 11 pts had EBPRT alone [MD: 50 Gy over 6 weeks]. Group II: 246 pts received preoperative utero-vaginal brachytherapy [MD: 65 Gy], and 32 of theses 246 pts also received postoperative EBPRT [MD: 45 Gy over 5 weeks] delivered to the parametric and the pelvic lymph nodes with a midline pelvic shield. The mean follow-up was 106 months. RESULTS: The 10-year disease-free survival (DFS) rate was 80%. From 75 recurrences, 35 were isolated locoregional. Multivariate analysis showed that independent factors decreasing the probability of DFS were: both exo and endocervical tumour site (p = 0.047), lymph-vascular space invasion (p = 0.041), age < or = 51 yr (p = 0.013), 1995 FIGO staging system (stage IB1 vs stage IIA, p = 0.004, stage IB1 vs stage IB2, p = 0.0009, and stage IB1 vs stage IIB with 1/3 proximal parametrical infiltration, p = 0.00002), and histological pelvic involved lymph nodes (p = 0.00009). Methods of adjuvant RT did not influence the probability of DFS (group I vs group II, p = 0.10). The postoperative complication rate was 10.2% in group I and 8.9% in group II (p = 0.7) but the postoperative urethral complication rate necessitating surgical intervention with reimplantation was lower in group I than in group II (0.6% vs 2.3%, respectively, p = 0.03). The 10-year rate for grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 10.4%. EPRT significantly increased the 10-year rate for grade 3 and 4 late radiation complications (yes vs no: 22% vs 7%, respectively, p = 0.0002). CONCLUSION: In our series, the methods of adjuvant RT (primary surgery vs preoperative uterovaginal brachytherapy) do not seem to influence the prognosis of the stage IB, IIA, and IIB (with 1/3 proximal parametrical involvement only) cervical carcinomas. The postoperative EPRT applied according to histopathological risk factors after surgical treatment increases the risk of late radiation complications.

[Endometrial adenocarcinoma treated with combined radiotherapy and surgery: 437 cases]. / Adénocarcinome de l'endomètre traité par association radiochirurgicale: à propos de 437 cas.

PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. PATIENTS AND METHODS: Between November 1971 and October 1992, 437 patients (pts) with endometrial carcinoma, staged according to the 1988 FIGO staging system, underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy without (n = 140) or with (n = 297) pelvic lymph node dissection. The chronology of RT was not randomized and depended on the usual practices of the surgical teams. Group I: 79 pts received preoperative uterovaginal brachytherapy (mean total dose [MD]: 57 Gy). Group II: 358 pts received postoperative RT (196 pts received vaginal brachytherapy alone [MD: 50 Gy], 158 pts had external beam pelvis RT [EPRT] [MD: 46 Gy over 5 weeks] followed by vaginal brachytherapy [MD: 17 Gy], and 4 pts had EPRT alone [MD: 46 Gy over 5 weeks]). The mean follow-up was 128 months. RESULTS: The 10-year disease-free survival rate was 86%. From 57 recurrences, 12 were isolated locoregionally. Multivariate analysis showed that independent factors decreasing the probability of disease-free survival were: histologic type (clear cell carcinoma, p = 0.038), largest histologic tumor diameter > 3 cm (p = 0.015), histologic grade (p = 0.008), myometrial invasion > 1/2 (p = 0.0055), and 1988 FIGO staging system (p = 9.10(-8)). In group II, the addition of EPRT did not seem to improve locoregional control. The postoperative complication rate was 7%. The independent factors increasing the risk of postoperative complications were FIGO stage (p = 0.02) and pelvic lymph node dissection (p = 0.011). The 10-year rate for grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 3.1%. EPRT independently increased the 10-year rate for grade 3 and 4 late radiation complications (R.R.: 5.6, p = 0.0096). CONCLUSION: EPRT increases the risk of late radiation complications. After surgical and histopathologic staging with pelvic lymph node dissection, in a subgroup of intermediate risk patients (stage IA grade 3, IB-C and II), postoperative vaginal brachytherapy alone is probably sufficient to obtain a good therapeutic index. Results for patients with stage III tumor are not satisfactory.

Palliative care with pregnant women.

When a pregnant woman has been declared dead because of brain death or cerebral death and a permanent vegetative state, the life and wellbeing of her fetus become a matter of crucial consideration. The possible options are an immediate caesarean section, continuation of efforts to maintain the organ functions of the woman to allow her fetus to mature, or discontinuation of the woman's somatic organ support. The decisions depend on the viability of the fetus, the probable health status of the fetus, any wish expressed by the mother and the commitment of her next of kin. Maintaining the pregnancy in order for the fetus to become more mature requires counselling of the woman's partner or family members. Immediate recourse of caesarean section should be withheld if the fetus is too immature or has a probable poor health status. Terminally ill pregnant women may require treatments which are potentially harmful to their fetus. Medical abortion early in pregnancy or premature delivery later in pregnancy are the usually recommended options. When the fetus is viable although extremely premature, delivery should not be imposed on a woman concerned with the risk of leaving a possibly handicapped child after her death.

Adenocarcinoma of the endometrium treated with combined irradiation and surgery: study of 437 patients.

PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. METHODS AND MATERIALS: Between November 1971 and October 1992, 437 patients (pts) with endometrial carcinoma, staged according to the 1988 FIGO staging system (225 Stage IB, 107 Stage IC, 4 Stage IIA, 35 Stage IIB, 30 Stage IIIA, 6 Stage IIIB, and 30 Stage IIIC), underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy without (n = 140) or with (n = 297) pelvic lymph node dissection. The chronology of adjuvant RT was not randomized and depended on the usual practices of the surgical teams. Seventy-nine pts (Group I) received preoperative low-dose-rate uterovaginal brachytherapy (mean dose [MD]: 57 Gy). Three hundred fifty-eight pts (Group II) received postoperative RT. One hundred ninety-six pts received low-dose-rate vaginal brachytherapy alone (MD: 50 Gy). One hundred fifty-eight pts had external beam pelvic RT (MD: 46 Gy) followed by low-dose-rate vaginal brachytherapy (MD: 17 Gy). Four pts had external beam pelvic RT alone (MD: 47 Gy). The mean follow-up from the beginning of treatment was 128 months. RESULTS: The 10-year disease-free survival rate was 86%. From 57 recurrences, only 12 were isolated locoregional recurrences. The independent factors decreasing the probability of disease-free survival were as follows: histologic type (clear-cell carcinoma, p = 0.038), largest histologic tumor diameter >3 cm (p = 0.015), histologic grade (p = 0.008), myometrial invasion > 1/2 (p = 0.005), and 1988 FIGO staging system (p = 9.10(-8)). In Group II, the addition of external beam pelvic RT did not seem to independently improve vaginal or pelvic control. The postoperative complication rate was 7%. The independent factors increasing the risk of postoperative complications were stage FIGO (p = 0.02) and pelvic lymph node dissection (p = 0.011). The 10-year rate for Grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 3.1%. External beam pelvic RT independently increased the rate for Grade 3 and 4 late complication (RR: 5.6, p = 0.0096). CONCLUSION: Postoperative external beam pelvic RT increases the risk of late radiation complications. After surgical and histopathologic staging with pelvic lymph node dissection, in subgroup of "intermediate-risk" patients (Stage IA Grade 3, IB-C and II), postoperative vaginal brachytherapy alone is probably sufficient to obtain a good therapeutic index. Results for patients with Stage III tumor are not satisfactory.

Factor V Leiden and G20210A prothrombin mutations are risk factors for very early recurrent miscarriage.

OBJECTIVE: To determine whether there is an association between early recurrent miscarriage (before 10 weeks of pregnancy) and Factor V Leiden and G20210A prothrombin mutations. DESIGN: A prospective study. SETTING: Department of Gynaecology and Obstetrics, Saint Antoine Hospital, Paris, France. POPULATION: Two groups of women: those with early unexplained recurrent miscarriage before 10 weeks of pregnancy (n = 260) and control healthy women without a previous history of thromboembolism (n = 240). METHODS: Screening for defects in the protein C anticoagulant pathway was performed using the anticoagulant response to agkistrodon confortrix venom (ACV test). Protein C and Factor V Leiden mutation testing was performed for each low ACV level. Each sample was tested for the G20210A prothrombin mutation. RESULTS: Factor V Leiden and G20210A mutations were found to be associated with early recurrent spontaneous miscarriage before 10 weeks of pregnancy, the odds ratios being 2.4 (95% CI 1-5) and 2.7 (95% CI 1-7), respectively. Similar results were found whether or not women had had a previous live birth. CONCLUSIONS: Early recurrent miscarriage before 10 weeks of pregnancy is significantly associated with Factor V or G20210A prothrombin mutations. These results indicate a possible role for anticoagulant prevention in these early miscarriages.

IFN-gamma induces apoptosis in mouse embryonic stem cells, a putative mechanism of its embryotoxicity.

It has been reported that interferon (IFN)-gamma should inhibit in vitro mouse embryo growth by direct cell toxicity. However, the mechanism involved has not been clearly established. In the present study, this question was addressed using the embryonic stem (ES) cell model. It was found that IFN-gamma, induces a dose-dependent apoptosis in ES cells, as assessed by trypan-blue staining, by Annexin-V labeling and DNA analysis, Moreover, IFN-gamma treatment cooperates with Fas-mediated apoptosis, a phenomenon that has been recently reported. As Bcl-2 oncoprotein functions as a death repressor molecule in an evolutionarily conserved cell death pathway, its expression was analyzed by flow cytometry. It was demonstrated that Bcl-2 is expressed in ES cells. When compared to untreated ES cells, IFN-gamma-treated, apoptotic cells expressed a lower Bcl-2 level and a normal level of Fas, whereas surviving cells expressed a normal level of Bcl-2 but a lower Fas expression. Altogether, these data suggest that IFN-gamma may influence early mouse embryo development by promoting apoptosis, which may constitute a novel mechanism of IFN-gamma embryotoxicity.