[HPV testing in the screening and follow-up of patients with cervical high-grade squamous intraepithelial lesions]. / Le test HPV dans le dépistage et le suivi des patientes présentant une lésion histologique de haut grade du col utérin.

OBJECTIVES: To evaluate the value of high-risk HPV (HR HPV) testing in screening and post-treatment follow-up of high-grade squamous intraepithelial cervical lesions (HSIL). METHODS: A systematic review of the literature from 2000 to 2019 was conducted including the following keywords: "human papilloma virus", "HPV testing", "cervical squamous intraepithelial lesion", "cervical cancer". RESULT: Numerous recent randomized studies and meta-analyzes have concordant results in favor of HR HPV superiority over cervical smear in the screening and post-treatment monitoring of HSIL. In screening, the sensitivity of the HR HPV tests is 63% to 98% whereas that of the cervical smear is only 38% to 65% for the detection of HSIL+ (HSIL and invasive cancers). A negative HR HPV test is associated with less than 5% risk of LIEHG+at 6 years. In addition, after removal of a LIEHG, HR HPV tests have a sensitivity>90% and specificity>80% to predict treatment failure. After surgicale exision, a negative HR HPV test is associated with a risk of failure<2% (negative predictive value of 98%), and 12-25% if it is positive. CONCLUSIONS: HR HPV tests are effective, allowing early detection of LIEHG+ identification of low-risk women in case of negative test, and a prediction of the risk of failure after treatment.

[For which patients could we consider de-escalation in the management of ductal carcinomas in situ?] / Pour quelles patientes peut-on envisager une désescalade dans la prise en charge des carcinomes canalaires in situ ?

Ductal carcinomas in situ (DCIS) of the breast account for 85% to 90% of breast cancer in situ. Current recommendations for the management of DCIS in France are based on surgical excision of the lesions, lumpectomy in healthy margins (margins of excision≥2mm) or mastectomy in case of extensive lesions. Radiation therapy is recommended after conservative surgical treatment. However, it seems relevant for some patients to discuss the benefit of a therapeutic de-escalation. Indeed, it has been reported that radiotherapy has no major impact on overall survival and that its interest could be discussed in the low-risk situations of invasive recurrence for which surgery alone could be sufficient, subject to sufficient margins. These questions call for the precise definition of low risk populations and to clarify the importance of taking into account decision support tools and new molecular markers. The place of scores like that of the University of Southern California - Van Nuys, and that of genomic tests such as the Oncotype test© DX DCIS (DCIS score) need to be specified. The expected results of several prospective studies could go in the direction of a significant therapeutic de-escalation for the management of DCIS in the years to come. In the meantime, however, it is advisable to remain cautious and the inclusion of patients in clinical trials should be favored.

[Fertility-sparing management of endometrial cancer and atypical hyperplasia]. / Traitement conservateur des hyperplasies atypiques et cancers de l'endomètre et préservation de la fertilité.

The fertility sparing management of endometrial cancer and atypical hyperplasia concern women in childbearing age with stage 1, grade 1, endometrioid adenocarcinoma confined to endometrium or atypical hyperplasia (simple or complex). These pathologies affecting more frequently postmenopausal women, the number of people involved is relatively low. The main risk factor is hyperestrogenism and these patients often present a history of infertility with a desire for pregnancy. The recommendations for this conservative management are scarce and unclear. The national observatory in the gynecology and obstetrics department of Bichat hospital gives expert advice to help doctors and patients concerned. We present a type of conservative management based on the expertise of the national observatory. Rigorous pre-therapeutic assessment must first be made to avoid missing a more advanced lesion. Hormone therapy is then started to obtain complete remission. In case of remission, fast achieving pregnancy is advised, and the use of assisted reproductive therapy is possible if necessary. Monitoring by hysteroscopy and histological examination is essential during the treatment. Hysterectomy is the last time the conservative management. It is motivated by the risk of recurrence and progression. The probability of remission after conservative treatment is estimated at 78.0 % at 12 months, the probability of recurrence at 29.2 % at 24 months, and the risk of progression at 15 % (stage 1A with myometrial invasion or more on the hysterectomy specimen). In terms of fertility, 32 % of women get at least one pregnancy.

[Treatment of below the knee lesions: Broadening the limits of vascular surgery]. / Traitement de l'artérite jambière : les frontières de la chirurgie vasculaire sont repoussées.

One third of patients with critical limb ischemia (CLI) has below the knee lesions and requires a restoration of direct blood flow into the foot. However, many of these patients are ineligible for open surgery. The primary goals thus become pain relief and limb salvage over patency. The angiosome concept helps determine the target artery to treat in priority. The endovascular approach has decreased morbidity and mortality rates compared to distal bypass surgery; while subintimal retrograde, trans-collateral and loop techniques push the limits of open surgery by reopening the plantar arch, thereby improving run-off. Early restenosis phenomena after angioplasty have been improved by the use of - limus drug eluting balloons and balloon expandable stents in case of flow limiting dissection or recoil with increased limb salvage rates. Moreover, drug-eluting stents have been proposed, and allow a reduction in reintervention and in-stent restenosis rates in short lesions; however, results on amputation rates or survival are limited. Vessel preparation is a key to overcoming some current limitations, including atherectomy, which increases technical success rates and reduces restenosis rates, especially in calcified lesions, chronic total occlusions and restenosis. These advanced techniques in distal endovascular revascularization have revolutionized limb salvage and support the interest of an endovascular first approach in CLI treatment.

[French validation of the Frustration Discomfort Scale]. / Validation française de l'échelle de frustration et d'inconfort (Frustration Discomfort Scale).

BACKGROUND: Rational emotive behavior therapy originally considered the concept of frustration intolerance in relation to different beliefs or cognitive patterns. Psychological disorders or, to some extent, certain affects such as frustration could result from irrational beliefs. Initially regarded as a unidimensional construct, recent literature considers those irrational beliefs as a multidimensional construct; such is the case for the phenomenon of frustration. In order to measure frustration intolerance, Harrington (2005) developed and validated the Frustration Discomfort Scale. The scale includes four dimensions of beliefs: emotional intolerance includes beliefs according to which emotional distress is intolerable and must be controlled or avoided as soon as possible. The intolerance of discomfort or demand for comfort is the second dimension based on beliefs that life should be peaceful and comfortable and that any inconvenience, effort or hassle should be avoided. The third dimension is entitlement, which includes beliefs about personal goals, such as merit, fairness, respect and gratification, and that others must not frustrate those non-negotiable desires. The fourth dimension is achievement, which reflects demands for high expectations or standards. METHODS: The aim of this study was to translate and validate in a French population the Frustration and Discomfort Scale developed by Harrington (2005), assess its psychometric properties, highlight the four factors structure of the scale, and examine the relationships between this concept and both emotion regulation and perceived stress. We translated the Frustration Discomfort Scale from English to French and back from French to English in order to ensure good quality of translation. We then submitted the scale to 289 students (239 females and 50 males) from the University of Savoy in addition to the Cognitive Emotional Regulation Questionnaire and the Perceived Stress Scale. RESULTS: The results showed satisfactory psychometric qualities. After removing five items from the original scale, the internal consistency appeared satisfactory for both the full scale (α=0.86), and the four sub-dimensions, with alphas ranging from 0.64 to 0.71. Although these values are lower than those from the original tool (Harrington, 2005), they are very close to the validation data in other languages (Ozer et al., 2012). Interestingly, the FDS score was related to the Perceived Stress Scale and non-adaptive emotion regulation factor but not to the adaptive emotion regulation factor. However, the factorial analyses do not unambiguously support the original four factors structure proposed by Harrington (2005). CONCLUSION: Reliability as well as convergent and divergent validity indicate that the French version of the Frustration Discomfort Scale is a relevant measure of frustration intolerance. However, divergent validity has not been completely demonstrated. The validation data is more congruent with a one-dimensional factor structure than with the original four-dimensional structure. Frustration intolerance could therefore be understood as a unitary concept.

[Social inequalities in maternal health]. / Inégalités sociales de santé maternelle.

Although medical literature on social inequalities in perinatal health is qualitatively heterogeneous, it is quantitatively important and reveals the existence of a social gradient in terms of perinatal risk. However, published data regarding maternal health, if also qualitatively heterogeneous, are relatively less numerous. Nevertheless, it appears that social inequalities also exist concerning severe maternal morbidity as well as maternal mortality. Analyses are still insufficient to understand the mechanisms involved and explain how the various dimensions of the women social condition interact with maternal health indicators. Inadequate prenatal care and suboptimal obstetric care may be intermediary factors, as they are related to both social status and maternal outcomes, in terms of maternal morbidity, its worsening or progression, and maternal mortality.

[Coronary artery spasm during dobutamine stress echocardiography: prevalence, clinical and echocardiographic characteristics and prognosis]. / Spasme coronaire et échographie de stress à la dobutamine : prévalence, profil clinique et échocardiographique et aspects évolutifs.

OBJECTIVES: To assess the prevalence of coronary artery spasm during dobutamine stress chocardiography (DSE), to describe clinical and echocardiographic characteristics and prognosis. PATIENTS AND METHODS: We evaluated all the patients with known or suspected coronary artery disease (CAD) referred to our echocardiography laboratory for dobutamine stress test between January 2004 and June 2012, (10013 exams). Those with abnormal DSE underwent coronary angiograms with a systematic methylergometrine intracoronary injection in case of absence of significant coronary stenosis or spontaneous occlusive coronary spasm. Patients who had spontaneous occlusive coronary spasm or positive methylergometrine test but no significant stenoses were included. RESULTS: One thousand and four patients had abnormal DSE, 78 (7.7%) fulfilled the inclusion criteria. There were 57 males and 21 females, mean age was 57.9 years, 37 patients had a known history of CAD. Twenty-four patients had a spasm on the left anterior artery (31%), 37 on the right coronary artery (47%) and 17 on the circumflex (22%). There was a good correlation between spastic arteries and dobutamine induced wall motion abnormalities territories. No complications occurred during the exams or during the provocation test. After 46 months mean follow up; one case of myocardial infarction with normal coronary arteries was noted and six patients experienced recurrent angina responding to treatment intensification. CONCLUSION: Coronary artery spasm during DSE but is a rare and under-diagnosed finding; it has, though, to be recognized as it may partly explain some erroneously labelled "false positive" exams. Methylergometrine provocation test should be performed in such a situation to establish the diagnosis. Prognosis appears favourable.

Exon deletion in the non-catalytic domain of eIF2Bepsilon due to a splice site mutation leads to infantile forms of CACH/VWM with severe decrease of eIF2B GEF activity.

The CACH/VWM syndrome is an autosomal recessive leukodystrophy characterized by a broad spectrum of clinical presentations and by diffuse cavitary degeneration of the white matter on MRI. Mutations responsible for this disorder are missense or frameshift mutations occurring in the five genes (EIF2B1-5) that encode the translation eukaryotic initiation factor eIF2B. We found that a patient with infantile CACH/VWM carries a mutation in the acceptor splice site of EIF2B5 exon 6. In lymphoblastoid cells of the patient, we detected an abnormal EIF2B5 transcript in which exon 6 was absent, however, the predicted protein product lacking part of the non-catalytic domain encoded by exon 6 was not detected. The eIF2B GEF activity was severely decreased. These data support the importance of the non-catalytic domain of the eIF2Bepsilon subunit in the eIF2B complex formation and activity.

Feeding micronized and extruded flaxseed to dairy cows: effects on blood parameters and milk fatty acid composition.

Four lactating Holstein cows fitted with ruminal and duodenal cannulas were used in a 4 x 4 Latin square design to determine the effects of feeding micronized and extruded flaxseed on milk composition and blood profile in late lactation. Four diets were formulated: a control (C) diet with no flaxseed, a raw flaxseed (RF) diet, a micronized flaxseed (MF) diet, and an extruded flaxseed (EF) diet. Flaxseed diets contained 12.6% flax-seed (dry matter basis). Experimental periods consisted of 21 d of diet adaptation and 7 d of data collection. Feeding flaxseed reduced milk yield and energy-corrected milk by 1.8 and 1.4 kg/d, respectively. Yields of milk protein and casein were also lower for cows fed flaxseed diets than for those fed the C diet. Milk yield (1.6 kg/d) and milk fat percentage (0.4 percentage unit) were lower for cows fed EF than those fed MF. Plasma cholesterol and nonesterified fatty acid concentrations were higher for cows fed flaxseed diets relative to those fed the C diet. Flaxseed supplementation decreased plasma concentrations of medium-chain (MCFA) and saturated (SFA) fatty acids and increased concentrations of long-chain (LCFA) and monounsaturated fatty acids. Feeding flaxseed reduced the concentrations of short-chain fatty acids (SCFA), MCFA, and SFA in milk fat. Consequently, concentrations of LCFA and unsaturated fatty acids were higher for cows fed flaxseed diets than for those fed the C diet. Flaxseed supplementation increased average concentrations of C(18:3) and conjugated linoleic acid by 152 and 68%, respectively. Micronization increased C(18:3) level, and extrusion reduced concentrations of SCFA and SFA in milk. It was concluded that feeding raw or heated flaxseed to dairy cows alters blood and milk fatty acid composition. Feeding extruded flaxseed relative to raw or micronized flaxseed had negative effects on milk yield and milk composition.

Effects of feeding micronized and extruded flaxseed on ruminal fermentation and nutrient utilization by dairy cows.

Four lactating Holstein cows with ruminal and duo-denal cannulas were used in a 4 x 4 latin square design to determine the effects of feeding heat-treated flaxseed on ruminal fermentation and site and extent of nutrient utilization. Four diets were formulated: a control diet with no flaxseed, a raw flaxseed diet (RF), a micronized flaxseed diet (MF), and an extruded flaxseed diet (EF). Flaxseed diets contained 12.6% flaxseed (dry matter [DM] basis). Ruminal pH, NH3 N, and total concentration of volatile fatty acids were not affected by dietary treatments. However, feeding flaxseed decreased the molar proportion of acetate and increased that of propionate. Flaxseed supplementation had no effect on ruminal digestion of DM, organic matter (OM), neutral detergent fiber (NDF), crude protein (CP), fatty acids (FA), and gross energy. However, ruminal digestion of acid detergent fiber (ADF) was lower for cows fed the flaxseed diets than for cows fed the control diet. Feeding flaxseed tended to increase post-ruminal and total tract digestibilities of DM, OM, NDF, and gross energy. Feeding heat-treated flaxseed diets relative to RF had no effect on ruminal, post-ruminal, and total tract nutrient digestibilities. Cows fed EF had higher ruminal and lower post-ruminal digestibilities of DM, OM, ADF, CP, and FA than cows fed MF. However, total tract digestibilities were similar for the 2 heat treatments. It was concluded that flaxseed supplementation improved total tract nutrient utilization with no adverse effects on ruminal fermentation. Extrusion failed to protect flaxseed from ruminal digestion. However, micronization can be used to increase the ruminal undegraded protein value of flaxseed.

Effects of extrusion of flaxseed on ruminal and postruminal nutrient digestibilities.

A study was conducted to determine the effects of extrusion on ruminal, post-ruminal and whole tract digestibility of flaxseed. Extrusion was performed at 155 degrees C with a residence time of 43 s. Two non-lactating Holstein cows fitted with ruminal and duodenal cannulas were used in a randomized complete block design. Results showed that extruded flaxseed had higher (P < 0.05) in situ soluble and lower (P < 0.05) slowly degradable DM and CP fractions than unheated flaxseed. Extrusion increased (P < 0.05) ruminal DM and CP degradability of flaxseed by 7 and 13%, respectively. Ruminal undegraded DM, CP and NDF were all lower (P < 0.05) for extruded flaxseed than for unheated flaxseed. Extrusion increased (P < 0.05) ruminal degradability and reduced (P < 0.05) post-ruminal availability of most amino acids of flaxseed. Whole tract digestibility of DM, CP, NDF and amino acids were higher (P < 0.05) for extruded than for unheated flaxseed. It was concluded that extrusion under the conditions used in the present experiment increases ruminal and whole tract nutrient degradabilities of flaxseed and therefore was ineffective in increasing the post-ruminal supply of amino acids from flaxseed.