Long-term outcomes of primary cystocele repair by transvaginal mesh surgery versus laparoscopic mesh sacropexy: extended follow up of the PROSPERE multicentre randomised trial.

OBJECTIVE: To compare the effectiveness and safety of laparoscopic sacropexy (LS) and transvaginal mesh (TVM) at 4 years. DESIGN: Extended follow up of a randomised trial. SETTING: Eleven centres. POPULATION: Women with cystocele stage ≥2 (pelvic organ prolapse quantification [POP-Q], aged 45-75 years without previous prolapse surgery. METHODS: Synthetic non-absorbable mesh placed in the vesicovaginal space and sutured to the promontory (LS) or maintained by arms through pelvic ligaments and/or muscles (TVM). MAIN OUTCOME MEASURES: Functional outcomes (pelvic floor distress inventory [PFDI-20] as primary outcome); anatomical assessment (POP-Q), composite outcome of success; re-interventions for complications. RESULTS: A total of 220 out of 262 randomised patients have been followed at 4 years. PFDI-20 significantly improved in both groups and was better (but below the minimal clinically important difference) after LS (mean difference -7.2 points; 95% CI -14.0 to -0.05; P = 0.029). The improvement in quality of life and the success rate (LS 70%, 61-81% versus TVM 71%, 62-81%; hazard ratio 0.92, 95% CI 0.55-1.54; P = 0.75) were similar. POP-Q measurements did not differ, except for point C (LS -57 mm versus TVM -48 mm, P = 0.0093). The grade III or higher complication rate was lower after LS (2%, 0-4.7%) than after TVM (8.7%, 3.4-13.7%; hazard ratio 4.6, 95% CI 1.007-21.0, P = 0.049)). CONCLUSIONS: Both techniques provided improvement and similar success rates. LS had a better benefit-harm balance with fewer re-interventions due to complications. TVM remains an option when LS is not feasible. TWEETABLE ABSTRACT: At 4 years, Laparoscopic Sacropexy (LS) had a better benefit-harm balance with fewer re-interventions due to complications than Trans-Vaginal Mesh (TVM).

The conventional protocol vs. a protocol including illumination with a fabric-based biophotonic device (the Phosistos protocol) in photodynamic therapy for actinic keratosis: a randomized, controlled, noninferiority clinical study.

BACKGROUND: Topical photodynamic therapy (PDT) using methyl aminolaevulinate is a noninvasive treatment option suitable to treat clinical and subclinical actinic keratosis (AK) over a large area (field cancerization). The most widely used, conventional protocol in Europe includes illumination with a red-light lamp. This illumination commonly causes pain, and patients often cannot complete the treatment. OBJECTIVES: The aims of this paper are twofold. The first aim is to introduce a novel protocol, the Phosistos protocol (P-PDT), which includes illumination with a fabric-based biophotonic device. The second and major aim is to assess the noninferiority, in terms of efficacy for PDT of AK, of P-PDT compared with the conventional protocol (C-PDT). METHODS: A randomized, controlled, multicentre, intraindividual clinical study was conducted. Forty-six patients with grade I-II AK of the forehead and scalp were treated with P-PDT on one area (280 AK lesions) and with C-PDT on the contralateral area (280 AK lesions). The primary end point was the lesion complete response (CR) rate at 3 months, with an absolute noninferiority margin of -10%. Secondary end points included pain scores, incidence of adverse effects and cosmetic outcome. RESULTS: Three months following treatment, the lesion CR rate of P-PDT was noninferior to that of C-PDT (79·3% vs. 80·7%, respectively; absolute difference -1·6%; one-sided 95% confidence interval -4·5% to infinity). The noninferiority of P-PDT to C-PDT in terms of the lesion CR rate remained at the 6-month follow-up (94·2% vs. 94·9%, respectively; absolute difference -0·6%; one-sided 95% confidence interval -2·7% to infinity). Moreover, the pain score at the end of illumination was significantly lower for P-PDT than for C-PDT (mean ± SD 0·3 ± 0·6 vs. 7·4 ± 2·3; P < 0·001). CONCLUSIONS: P-PDT is noninferior to C-PDT in terms of efficacy for treating AK of the forehead and scalp and resulted in much lower pain scores and fewer adverse effects. What's already known about this topic? Topical photodynamic therapy using methyl aminolaevulinate is effective for treating actinic keratosis. In Europe, the conventional protocol involves illumination with a red-light lamp. Unfortunately, pain is often experienced by patients undergoing this protocol. An alternative protocol that uses daylight illumination has recently been shown to be as effective as the conventional protocol while being nearly painless. However, this alternative protocol can be conducted only in suitable weather conditions. What does this study add? The Phosistos protocol is demonstrated to be as effective as the conventional protocol, nearly as painless as the daylight protocols and suitable year round for treatment of actinic keratosis.

Photodynamic therapy for actinic keratosis of the forehead and scalp: a randomized, controlled, phase II clinical study evaluating the noninferiority of a new protocol involving irradiation with a light-emitting, fabric-based device (the Flexitheralight protocol) compared with the conventional protocol involving irradiation with the Aktilite CL 128 lamp.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK), particularly for patients with large areas of field cancerization. Among the approved protocols in Europe, the most widely used requires irradiation with the Aktilite CL 128 lamp. However, pain during irradiation and the suboptimal adaptability of the lamp relative to the treatment area are two limiting factors of this protocol. To overcome these limits, a new protocol (referred to as the Flexitheralight protocol) involving irradiation with a light-emitting, fabric-based device was developed. OBJECTIVES: This paper aims to assess the noninferiority, in terms of PDT efficacy for treating AK, of the Flexitheralight protocol compared with the conventional protocol, which requires irradiation with the Aktilite CL 128 lamp. METHODS: A monocentric, randomized, controlled, phase II clinical study was performed. Twenty-five patients with grade I-II AKs of the forehead and scalp were treated with methyl aminolaevulinate PDT in two symmetrical areas. One area was treated with the conventional protocol (n = 154 AKs), whereas the other area was treated with the Flexitheralight protocol (n = 156 AKs). The primary end-point was the lesion complete response (CR) rate at 3 months (an absolute noninferiority margin of -10% was used). The secondary end-points included patient-reported pain at the end of the irradiation. RESULTS: At 3 months, the lesion CR rate with the Flexitheralight protocol was noninferior to that obtained with the conventional protocol (66·0% vs. 59·1%, respectively; absolute difference, 6·9%; 95% confidence interval -0·6% to 14·5%). Patient-reported pain was significantly lower with the Flexitheralight protocol than with the conventional protocol (mean ± SD: 0·4 ± 0·6 vs. 5·0 ± 2·6; P < 0·0001). CONCLUSIONS: The Flexitheralight protocol is noninferior in terms of efficacy and superior in terms of tolerability to the conventional protocol for treating AKs of the forehead and scalp.

Better early outcome with enteral rather than parenteral nutrition in children undergoing MAC allo-SCT.

There is no consensus on the type of nutritional support to introduce in children undergoing allogeneic stem cell transplantation (allo-SCT) after myeloablative conditioning (MAC). This retrospective, multicenter, observational study compared the early administration of enteral nutrition (EN group, n = 97) versus parenteral nutrition (PN group, n = 97) in such patients with matching for important covariates. The primary endpoint was the study of day 100 overall mortality. The early outcome at day 100 was better in EN group regarding mortality rate (1% vs. 13%; p = 0.0127), non relapse mortality (1% vs. 7%; p = 0.066), acute GVHD grades II-IV (37% vs. 54%; p = 0.0127), III-IV (18% vs. 34%; p = 0.0333) and its gut localization (16% vs. 32%; p = 0.0136). Platelet engraftment was better in EN group than in PN group for the threshold of 20 G/L (97% vs. 80% p < 0.0001) and 50 G/L (92% vs. 78%, p < 0.0001). The length of stay was shorter in EN group (28 vs. 52 days, p < 0.0001). There were no differences between the two groups regarding the polynuclear neutrophil engraftment, infection rate or mucositis occurrence. These results suggest that, in children undergoing MAC allo-SCT, PN should be reserved to the only cases when up-front EN is insufficient or impossible to perform.

Polycystic ovarian morphology and the diagnosis of polycystic ovary syndrome: redefining threshold levels for follicle count and serum anti-Müllerian hormone using cluster analysis.

STUDY QUESTION: Can cluster analysis be used to differentiate between normo-ovulatory women with normal ovaries and normo-ovulatory women with polycystic ovarian morphology (PCOM) in a non-subjective manner? SUMMARY ANSWER: Cluster analysis can be used to accurately and non-subjectively differentiate between normo-ovulatory women with normal ovaries and normo-ovulatory women with PCOM. WHAT IS KNOWN ALREADY: Currently, PCOM is diagnosed using a fixed threshold level, i.e. 12 or more follicles per ovary, and is one of the diagnostic criteria of polycystic ovary syndrome (PCOS). However, PCOM is also encountered in normo-ovulatory women, suggesting that it could just represent a normal variant. On the other hand, recent studies have shown subtle endocrine abnormalities in women with isolated PCOM that resemble those found in women with PCOS. Because of the strong correlation between anti-Müllerian hormone (AMH) and follicle number, a high serum AMH level has been proposed as a surrogate marker for PCOM and could, therefore, be integrated in the diagnostic classifications for PCOS. STUDY DESIGN, SIZE, DURATION: This was a retrospective observational cohort study. Original cohorts had been recruited for previous studies between 1998 and 2010. Two hundred ninety-seven regularly cycling women and 700 women with PCOS were eligible for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cluster analysis was performed in 297 regularly cycling women. After exclusion of 'PCOM' clusters, each 'non-PCOM' cluster (young, n = 118 and old, n = 100) was included in the construction of a receiver operating characteristics curve to test the diagnostic performance of follicle number per ovary (FNPO) and serum AMH in discriminating similarly aged full-blown PCOS patients (n = 411 and 237, respectively) from normal regularly cycling non-PCOM women. MAIN RESULTS AND ROLE OF CHANCE: The optimal number of clusters was four; age was the most important classifying variable, followed by the FNPO and serum AMH. Two distinct clusters of normo-ovulatory women with PCOM were isolated and differed solely by age, i.e. 'young' and 'old'. Both 'PCOM' clusters had their similarly aged counterpart of 'non-PCOM' clusters. Likewise, two clusters comprised women younger than 30 years, with (n = 28, 'PCOM regularly cycling women') or without (n = 118, 'normal regularly cycling women') features of PCOM (increased FNPO and/or serum AMH). The two other clusters in older women could be labelled 'normal regularly cycling women' or 'PCOM regularly cycling women' (n = 100 and 51, respectively). The prevalence of PCOM was significantly greater in old than in young regularly cycling women controls. In the young population, after exclusion of the 'PCOM regularly cycling women', the diagnostic performance of AMH, expressed by area under the curve (AUC) (AUC = 0.903; CI (0.876-0.930)) to differentiate PCOS women from normal regularly cycling women was similar to that using the FNPO (AUC = 0.915, CI (0.891-0.940)) (P = 0.25), confirming results from earlier studies. In the old population, the diagnostic performance of AMH was greater than that of FNPO (AUCs = 0.948 (0.927-0.970) vs 0.874 (0.836-0.912), respectively, P = 0.00035). Cut-off levels of AMH and antral follicle count distinguishing regularly cycling non-PCOM women from PCOS women were higher in young women than in older women. LIMITATIONS, REASONS FOR CAUTION: Data of normal women were obtained from earlier studies, aiming to measure normal endocrine values. Apparently, the strong effect of age in cluster analysis revealed a dichotomy in the age distribution among the cohort of regularly cycling women included. This was involuntary since in none of the original studies, eligibility was limited by age and there was considerable overlap in age ranges of the cohorts. Transvaginal ultrasound was performed using a 6.5-8 mHz probe and our data confirm that this threshold level for FNPO is still valid if using such probe frequencies, although the use of devices with a maximum frequency lower than 8 mHz has become obsolete. Obviously, newer ultrasound scanner using higher transducer frequency will facilitate the detection of more follicles. WIDER IMPLICATIONS OF THE FINDINGS: Our data support the use of AMH as a surrogate for ultrasound to define PCOM, which is one of the three items of the Rotterdam classification. They also show that age should be taken into account to define the optimal threshold. The fact that the prevalence of PCOM was increased in the older regularly cycling women, may be due to 'attenuated' PCOS, a phenomenon that has been described in ageing women with PCOS. These women might have had anovulatory cycles in the past and have become ovulatory with increasing age, and were, therefore, eligible for this study. However, since most women included at older age have had spontaneous pregnancies in the past, PCOM at older age may be associated with a subclinical form of PCOS, which may also be present in young regularly cycling women. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. J.S.E.L. has received grants and support from Ferring, MSD, Organon, Merck-Serono, Schering Plough and Serono during recruitment and analysis of data for this study. S.L.F., A.D. and D.D. do not have any conflict of interest.

Impact of Wilms' tumor 1 expression on outcome of patients undergoing allogeneic stem cell transplantation for AML.

The monitoring of the minimal residual disease by Wilms' tumor 1 expression (MRDWT1) is a standardized test, which can be used in over 80% of patients with AML. To investigate the prognostic value of MRDWT1 in patients undergoing allogeneic stem cell transplantation (allo-SCT) for AML, MRDWT1 was monitored 3 months after transplantation in 139 patients. MRDWT1 positivity did not lead to any therapeutic intervention. Median follow-up was 39.3 (6.4-99.8) months. Patients with positive MRDWT1 at 3 months experienced more often post-transplant relapse (27/30, 90%) than those with negative MRDWT1 (16/109, 14.7%) (P<0.0001). Similarly, a shorter 3-year event-free survival (EFS) was observed in MRDWT1-positive patients (10% vs 72.3% in MRDWT1-negative patients, P<0.0001). The correlation between relapse and MRDWT1 was stronger in blood than in bone marrow samples. Multivariate analysis confirmed the detrimental role of 3-month positive MRDWT1 for relapse (hazard ratio (HR): 15.42; 95% confidence interval (CI): 7.53-31.59; P<0.0001) and EFS (HR: 10.71; 95% CI: 5.41-21.21; P<0.0001). Interestingly, 3-month chimerism was less predictive of relapse than positive MRDWT1. In conclusion, our results demonstrate the usefulness of peripheral blood MRDWT1 monitoring in identifying very high-risk patients, who could benefit from an early preemptive treatment, and those who do not need such an intervention.

Validation of a French patient-reported outcome measure for patello-femoral disorders: The Lille Patello-Femoral Score.

BACKGROUND: The diagnosis of patello-femoral instability (PFI) relies chiefly on the patient's clinical findings. Nevertheless, few clinical scores specifically designed to evaluate the patello-femoral joint are available. The Lille scoring system is a 12-item self-questionnaire yielding a score from 0 to 100 that is used in France but has not been validated. We therefore conducted a validation study in a population of younger patients with PFI. HYPOTHESIS: The Lille scoring system meets validation criteria for patient-reported outcome measures (PROMs). MATERIAL AND METHOD: A retrospective study done in two centres identified 136 patients with objective (n=109) or potential (n=27) PFI. Before and after surgery, the Lille score was determined by all patients and the Kujala score in 61 patients. The Lille score was also determined by 30 controls free of patello-femoral disorders to allow an evaluation of discrimination between PFI and other knee disorders in individuals of similar age. RESULTS: The response rate was 100%, indicating that the Lille questionnaire was easy to complete. Consistency was established: (a) the global score showed no floor or ceiling effect (in no questionnaires were over 85% of items given the highest or lowest possible score), and saturation occurred neither for the global score nor for the item sub-scores (fewer than 85% of patients had the lowest or highest possible score); (b) a single redundancy was found, between the items 'pain' and 'locking', for which the correlation coefficient was≥0.7 (P<0.0001). Discriminating performance was assessed by comparing the mean Lille score values in the controls (67.8±9.2) and patients (38.1±10.4); the difference was significant (P<0.05) and the estimated effect size was>0.8, indicating strong discrimination by the Lille scoring system. Item uniformity, with all items measuring the same phenomenon, was established by the Cronbach alpha coefficient value>0.7. External consistency between the Lille and Kujala scoring systems was confirmed in the 61 patients for whom both scores were available (Pearson correlation coefficient, 0.5). Sensitivity to change was established by the>0.8 effect size of surgical treatment. DISCUSSION: The Lille scoring system deserves to be used routinely in clinical practice as a patient-reported outcome measure. A prospective study will assess intra-observer reproducibility and sensitivity to change in patients treated non-operatively. Although confined to retrospective data, this study based on methods designed to assess PROMs establishes the validity of the Lille scoring system and supports its use in PFI. LEVEL OF EVIDENCE: III, case-control design.

Epidemiology of patients with MSSA versus MRSA infections of orthopedic implants: Retrospective study of 115 patients.

Factors that predict the occurrence of a surgical site infection due to methicillin-resistant Staphylococcus aureus (MRSA) are not well known; however this information could be used to modify the recommended antimicrobial prophylaxis. We carried out a retrospective study of S. aureus infections on orthopedic implants to determine: (1) whether epidemiological factors can be identified that predict a MRSA infection, (2) the impact of these factors as evidenced by the odds ratio (OR). HYPOTHESIS: Risk factors for a MRSA infection can be identified from a cohort of patients with S. aureus infections. MATERIALS AND METHODS: We identified 244 patients who experienced a S. aureus surgical site infection (SSI) in 2011-2012 documented by intraoperative sample collection. Of these 244 patients, those who had a previous SSI (n=44), those with a SSI but no orthopedic implant (n=80) or those who had the infection more than 1-year after the initial surgery (n=5) were excluded. This resulted in 115 patients (53 arthroplasty, 62 bone fixation) being analyzed for this study. There were 24 MRSA infections and 91 MSSA infections. The following factors were evaluated in bivariate and multifactorial analysis: age, sex, type of device (prosthesis/bone fixation), predisposition (diabetes, obesity, kidney failure), and environmental factors (hospitalization in intensive care unit within past 5 years, nursing home stay). RESULTS: Two factors were correlated with the occurrence of MRSA infections. (1) Nursing home patients had a higher rate of MRSA infections (67% vs. 18%, P=0.017) with an OR of 8.42 (95% CI: 1.06-66.43). (2) Patients who had undergone bone fixation had a lower rate of MRSA infections than patients who had undergone arthroplasty (13% vs. 30%, P=0.023), OR 0.11 (95% CI: 0.02-0.56). Although the sample size was too small to be statistically significant, all of the patients with kidney failure (n=4) had a MRSA infection. DISCUSSION: Since these MRSA infection risk factors are easy to identify, the antimicrobial prophylaxis could be adapted in these specific patient groups.

Statistical controversies in clinical research: should schedules of tumor size assessments be changed?

BACKGROUND: Time to progression (TTP) is often used as a primary end point in phase II clinical trials. Since the actual date of nadir and progression is never known, most calculated TTP are overestimated. This study evaluates the imprecision on the estimate of TTP under two hypothetical tumor kinetic settings and various assessment schedules. DESIGN: A two-component tumor growth model was used to account for treatment effect assuming exponential decay for tumor shrinkage and linear growth for progression. Evolution of tumor burden (TB) was modelized according to two scenarios using either a cytotoxic or a cytostatic agent and several assessment schedules. TB, nadir, progression and TTP were simulated for each visit schedule. RESULTS: For cytotoxic agents, our model predicted response at 1.5 weeks, a TB at nadir of 40.2 mm (starting from 100 mm) occurring at 6.7 weeks and true progression at 11.2 weeks with a TB of 48.2 mm. For cytostatic agents, our model predicted no response, a TB at nadir of 77 mm occurring at 9.2 weeks and true progression at 19.4 weeks with a TB of 92 mm. Depending on the assessment schedule, estimated TTP was increased from 0.8 to 36.8 weeks and from 0.6 to 28.6 weeks when compared with the true TTP and varied from 5.2% to 298% and from 1.66 to 109.58% when compared with the true TB at progression for cytotoxic and cytostatic agents, respectively. Our model further shows that for cytotoxic agents, evaluation of TB every 6 weeks is optimal to capture the true nadir, the time to nadir, the true progression and the true TTP, whereas for cytostatic agents, this evaluation is optimal every 10 weeks. CONCLUSIONS: Our results emphasize the importance to estimate the effects of tested drugs on tumor shrinkage before design any phase II clinical trials to choose optimal TB evaluation's timing.

Postpartum haemorrhage related early increase in D-dimers is inhibited by tranexamic acid: haemostasis parameters of a randomized controlled open labelled trial.

BACKGROUND: Beneficial effects of tranexamic acid (TA) have been established in surgery and trauma. In ongoing postpartum haemorrhage (PPH), a moderate reduction of blood loss was observed in a previously published randomized controlled trial. Analysis of haemostasis parameters obtained from samples collected as part of this study are presented. METHODS: Women with PPH >800 ml after vaginal delivery were assigned to receive either TA (4 g over 1 h, then 1 g per h over six h) (TA) or not (H). A non-haemorrhagic group (NH), <800 ml blood loss, was included as postpartum reference. At four time-points (enrolment, +30 min, +2 h, +6 h), haemostasis was assessed. Haemostasis assays were performed blinded to group allocation. Data were expressed as median [interquartiles] and compared with non-parametric tests. RESULTS: In H compared with NH group, D-dimers increase (3730 ng ml(-1) [2468-8493] vs 2649 [2667-4375]; P=0.0001) and fibrinogen and factor II decrease were observed at enrolment and became maximal 2 h later. When comparing TA to H patients, the increase in Plasmin-Antiplasmin-complexes at +30 min (486 ng ml(-1) [340-1116] vs 674 [548-1640]; P=0.03) and D-dimers at +2 h (3888 ng ml(-1) [2688-6172] vs 7495 [4400-15772]; P=0.0001) was blunted. TA had no effect on fibrinogen decrease. CONCLUSIONS: This study provides biological evidence of an early increase in D-dimers and plasmin-antiplasmin complexes associated with active post-partum haemorrhage and its attenuation by the early use of a clinically effective high dose of TA, opening the perspective of dose ranging studies to determinate the optimal dose and timing in this setting. CLINICAL TRIAL REGISTRATION: ISRCTN09968140.

Multicentre study of neoadjuvant chemotherapy for stage I and II oesophageal cancer.

BACKGROUND: The benefit of neoadjuvant chemotherapy (NCT) for early-stage oesophageal cancer is unknown. The aim of this study was to assess whether NCT improves the outcome of patients with stage I or II disease. METHODS: Data were collected from 30 European centres from 2000 to 2010. Patients who received NCT for stage I or II oesophageal cancer were compared with patients who underwent primary surgery with regard to postoperative morbidity, mortality, and overall and disease-free survival. Propensity score matching was used to adjust for differences in baseline characteristics. RESULTS: Of 1173 patients recruited (181 NCT, 992 primary surgery), 651 (55·5 per cent) had clinical stage I disease and 522 (44·5 per cent) had stage II disease. Comparisons of the NCT and primary surgery groups in the matched population (181 patients in each group) revealed in-hospital mortality rates of 4·4 and 5·5 per cent respectively (P = 0·660), R0 resection rates of 91·7 and 86·7 per cent (P = 0·338), 5-year overall survival rates of 47·7 and 38·6 per cent (hazard ratio (HR) 0·68, 95 per cent c.i. 0·49 to 0·93; P = 0·016), and 5-year disease-free survival rates of 44·9 and 36·1 per cent (HR 0·68, 0·50 to 0·93; P = 0·017). CONCLUSION: NCT was associated with better overall and disease-free survival in patients with stage I or II oesophageal cancer, without increasing postoperative morbidity.

The phenotypic diversity in per-follicle anti-Müllerian hormone production in polycystic ovary syndrome.

STUDY QUESTION: Is intrinsic dysregulation of granulosa cells (GC) and consequent increases in the per-follicle production of anti-Müllerian hormone (AMH), correlated with the phenotypic presentation of women with polycystic ovaries? SUMMARY ANSWER: Involvement of intrinsic GC dysregulation in oligo-anovulation associated with polycystic ovary syndrome (PCOS) is likely because among women with PCOS, those with oligo-amenorrhea have higher per-follicle AMH production than those who ovulate normally, irrespective of their androgen and/or metabolic status. WHAT IS KNOWN ALREADY: Women with PCOS have higher serum AMH level than non-PCOS women due to an increased follicle number and excessive AMH production per follicle, the latter reflecting a putative GC dysfunction that may vary between PCOS phenotypes. STUDY DESIGN, SIZE, DURATION: This is a retrospective analysis of data collected from 1021 women undergoing infertility evaluation from March 2011 to October 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included women with polycystic ovarian morphology (PCOM) who met the Rotterdam criteria for PCOS (n = 272), women with PCOM only (n = 168) and controls (n = 581). MAIN RESULTS AND THE ROLE OF CHANCE: We used serum AMH to antral follicle count (AFC) ratio (AMH/AFC) as a marker of per-follicle AMH production and checked whether this ratio was associated with the PCOS phenotype and to the menstrual, androgen and metabolic status in women with PCOS, women with PCOM only and in controls. AMH/AFC was significantly higher in oligo-amenorrheic women with PCOS than in eumenorrheic women with PCOS or PCOM (P < 0.001) but also in the latter group compared with controls (P < 0.001) regardless of androgen status. Stepwise discriminant analysis yielded a significant score for the menstrual status with a discriminant power of 26.5% (P < 0.001). This score included AFC, AMH/AFC, waist circumference and LH with partial R(2) of 0.172, 0.042, 0.024 and 0.023, respectively. LIMITATIONS, REASONS FOR CAUTION: The AMH to AFC ratio as a surrogate marker for average AMH may be subject to error because follicles below the sensitivity limit of the ultrasonography used may also contribute to serum AMH concentration and secondly, AFC can be subjective. WIDER IMPLICATIONS OF THE FINDINGS: The higher AMH/AFC in women with PCOM only than in controls suggests that isolated PCOM may represent a PCOS-like phenotype in which an inherent dysfunction of GC exists but is too mild to affect the ovulatory process. STUDY FUNDING/COMPETING INTERESTS: No funding was obtained for this study. There are no conflicts of interest to be declared. TRIAL REGISTRATION NUMBER: Non-applicable.

Long-term outcomes of primary constrained condylar knee arthroplasty.

BACKGROUND: Although constrained condylar knee (CCK) inserts are widely used for total knee arthroplasty (TKA), their long-term outcomes remain unclear. We sought to evaluate patients with at least 10 years' follow-up after CCK TKA to identify potential adverse events (osteolysis, loosening, constraint-mechanism failure), assess functional outcomes with special emphasis on range of motion, and determine prosthesis survival. HYPOTHESIS: Increasing constraint by implantation of a CCK insert does not increase the long-term frequencies of osteolysis or mechanical loosening. MATERIAL AND METHODS: We studied 43 knees after Legacy(®) CCK TKA. The indication was severe deformity (n=20), pre-operative laxity (n=6), or failure to achieve intra-operative balancing (n=17). There were 41 patients with a mean age of 66 years (21-88). A history of one or more surgical procedures was noted for 27 (63%) knees. Outcome measures were the Hospital for Special Surgery (HSS) knee score, Knee Society Score (KSS), and change in the hip-knee-ankle (HKA) angle. Prosthesis survival was assessed using revision surgery for any reason or for reasons other than infection as the censoring criterion. RESULTS: Complications other than venous thrombosis occurred in 16% of patients, including 3 who required revision surgery (septic loosening, n=2; and major instability in a patient with ipsilateral hip arthrodesis). No cases of osteolysis or aseptic loosening were recorded. Mean follow-up was 12.7 years (range, 10-14). At last follow-up, the HSS score had improved from 53 (26-83) pre-operatively to 80 (55-93), the KSS knee component from 42 (16-77) to 90 (77-99), and the KSS function component from 31 (0-80) to 61 (10-90) (P<0.001). Mean range of flexion increased from 109° (50°-140°) to 112° (90°-130°) (P=0.12). The HKA angle changed from 182°±15.5° (150°-210°) to 179.5°±2.5° (174°-184°) (P=0.5). The 11-year prosthesis survival rate was 88.5% (95% confidence interval, 0.69-0.94) overall and 97.7% (0.76-0.99) after excluding the cases of infection. DISCUSSION: Long-term functional gains after CCK TKA were similar to those reported after standard posterior-stabilised TKA, with no cases of constraint-mechanism failure or osteolysis. The complication rate was higher, with decreased survival compared to standard TKA, but the knee deformities and/or instability were particularly severe and two-thirds of knees had a history of one or more surgical procedures.

[Indoor tanning: motivations and beliefs among users and non-users in the population of Lille (Northern France)]. / Cabines de bronzage : étude des motivations et croyances des utilisateurs et non-utilisateurs dans la population lilloise.

BACKGROUND: Uncontrolled use of tanning beds is a major public health problem. The role of UV in skin carcinogenesis has in fact been clearly demonstrated. AIMS: The main purpose of the study was to assess the motivations and beliefs of the population concerning the use of indoor tanning. The secondary objectives were to compare the knowledge of users and non-users and to screen for addiction criteria among users. PATIENTS AND METHODS: This was a transversal descriptive study conducted between April and June 2013 in Lille town center. The motivations of the participants were determined using a multiple-choice questionnaire. A Likert scale was used to assess beliefs and an m-CAGE questionnaire was used to screen for addiction. RESULTS: Of the 200 respondents, 30% (n=60) had used tanning beds in a non-medical setting. The median age of first use was 23 years (15-59). 11.7% of respondents had started before the authorised age of 18 years. "To prepare the skin for exposure to the sun" was the main reason given (68.3%) for use of tanning beds. The population was aware that use of such apparatus favours onset of skin cancer and ageing of the skin. Users were more convinced than non-users that UV cabins "prepare the skin for exposure to the sun" (75% vs. 49.6%, P=0.0009) and that they "favour skin cancer" (56.9% against 36.2%, P=0.0444). Addictive behaviour was detected in 3.3% (2/60) of users. CONCLUSION: Users are aware of the carcinogenic risk of UV cabins but expose themselves to such risk, as they believe it prepares their skin for sun exposure.

Pelvic endometriosis in women under 25: a specific management?

AIM: The aim of this study was to describe the characteristics of women under 25 years with pelvic endometriosis and assess their potential for recurrence and fertility after surgery. METHODS: In a comparative retrospective study, 108 patients aged less than 25 years who underwent surgery for pelvic endometriosis were included: 49 in the DIE group (deep infiltrating endometriosis) and 59 in the SE group (superficial endometriosis). The main outcome measures were complications, recurrence and fertility. This study received the favorable opinion of the CEROG No 2012-GYN-04-02. RESULTS: The diagnosis was made at 21.6 ± 2.8 years, mainly considering clinical signs (78.4%), and on average 4.3 ± 3.7 years after the onset of symptoms; 16.1% of patients had to be reoperated (N.=5/31) due to a recurrence of their endometriosis. There were more recurrent pain (50% vs. 21.7%, P=0.005) and endometriosis (35.7 vs. 19.6%, P=0.08) in the DIE group. 75% (N.=33/44) patients desired pregnancy after surgery and 50% of them became pregnant, with one third thanks to assisted reproductive technology. CONCLUSION: In young women, endometriosis is often more severe. The early treatment does not improve the rate of recurrence and fertility, but can reduce pain and thus improve the quality of life.

Light microscopy morphological characteristics of the sperm flagellum may be related to axonemal abnormalities.

Although electron microscopy provides a detailed analysis of ultrastructural abnormalities, this technique is not available in all laboratories. We sought to determine whether certain characteristics of the flagellum as assessed by light microscopy were related to axonemal abnormalities. Forty-one patients with an absence of outer dynein arms (type I), a lack of a central complex (type III) and an absence of peripheral doublets (type IV) were studied. Sperm morphology was scored according to David's modified classification. Flagella with an irregular thickness were classified as being of normal length, short or broken. There were correlations between missing outer dynein arms and abnormal, short or coiled flagellum. Type III patients showed the highest flagellar defects (a short (P = 0.0027) or an absent flagellum (P = 0.011)). Just over 68% of the irregular flagella were short in Type III patients, whereas this value was only 34.5% in type I and 26.4% in type IV (P = 0.002). There was a negative correlation between misassembly and spermatozoa of irregular flagella (r = -0.79; P = 0.019). It is concluded that light microscopy analysis of flagellum abnormalities may help provide a correct diagnosis, identify sperm abnormalities with fertility potentials and outcomes in assisted reproduction technologies and assess the genetic risk.

Using cluster analysis to identify a homogeneous subpopulation of women with polycystic ovarian morphology in a population of non-hyperandrogenic women with regular menstrual cycles.

STUDY QUESTION: Can cluster analysis can be used to identify a homogeneous subpopulation of women with polycystic ovarian morphology (PCOM) within a very large population of control women in a non-subjective way? SUMMARY ANSWER: Identification and exclusion of the cluster corresponding to women with PCOM from controls improved the diagnostic power of serum anti-Müllerian hormone (AMH) level and follicle number per ovary (FNPO) in discriminating between women with or without polycystic ovary syndrome (PCOS). WHAT IS KNOWN ALREADY: There is disagreement as to whether women with PCOM should be excluded from the control population when establishing FNPO and AMH diagnostic thresholds for the definition of PCOS and how to identify such women. It has been demonstrated that cluster analysis can detect women with PCOM within the control population through a set of classifying variables among which the most relevant was AMH. The adequacy of this approach has not been confirmed in other clinical settings. STUDY DESIGN, SIZE, DURATION: This was a retrospective study using clinical and laboratory data derived from the computerized database. The data were collected from March 2011 to May 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included 893 patients referred for routine infertility evaluation and treatment. The patients were divided into three groups: (i) the control group (n = 621) included women with regular menstrual cycles and no signs of hyperandrogenism (HA), (ii) the full-blown PCOS group (n = 95) consisted of women who were diagnosed as having PCOS based on the presence of both HA and oligo/amenorrhoea (OA), (iii) the mild PCOS group included women with only two items of the Rotterdam classification, i.e. PCOM at ultrasonography according to the FNPO threshold of 12 or more and either OA (n = 110) or HA (n = 67). MAIN RESULTS AND THE ROLE OF CHANCE: After exclusion of women with PCOM from the controls, the AMH threshold of 28 pmol/l with specificity 97.5% and sensitivity 84.2% [area under the curve (AUC) 0.948 (95% confidence interval (CI) 0.915-0.982)] and FNPO threshold of 12 with specificity 92.5% and sensitivity 83.2% [AUC 0.940 (95% CI 0.909-0.971)] for identifying PCOS were derived from the receiver operating characteristic curve analysis. The AMH threshold of 28 pmol/l had the same specificity for discriminating the mild and the full-blown PCOS phenotypes from controls. LIMITATIONS, REASONS FOR CAUTION: There was no selection bias other than being evaluated for infertility treatment, however, this could also be considered as a limitation of the study as these women may not necessarily be a representative sample of the general population. The study demonstrated that serum AMH has intrinsically a very high potency to detect women with PCOM within a control group. However, the AMH threshold is specific for this method and clinical setting. WIDER IMPLICATIONS OF THE FINDINGS: AMH threshold value for the definition of PCOM is method specific and cannot be universally applied. This study confirmed the results of previous studies that cluster analysis can identify women with PCOM within the very large control population without using a predefined diagnostic threshold for FNPO, and that AMH can detect women with PCOM with a high specificity. The exclusion of PCOM women from the controls by using a cluster analysis should be considered when establishing reference intervals and decision threshold values for various parameters used to characterize PCOS. STUDY FUNDING/COMPETING INTERESTS: The authors have no funding/competing interest(s) to declare.