Refracture following vertebral fragility fracture when bone fragility is not recognized: summarizing findings from comparator arms of randomized clinical trials.

PURPOSE: Since vertebral fragility fractures (VFFs) might increase the risk of subsequent fractures, we evaluated the incidence rate and the refracture risk of subsequent vertebral and non-vertebral fragility fractures (nVFFs) in untreated patients with a previous VFF. METHODS: We systematically searched PubMed, Embase, and Cochrane Library up to February 2022 for randomized clinical trials (RCTs) that analyzed the occurrence of subsequent fractures in untreated patients with prior VFFs. Two authors independently extracted data and appraised the risk of bias in the selected studies. Primary outcomes were subsequent VFFs, while secondary outcomes were further nVFFs. The outcome of refracture within ≥ 2 years after the index fracture was measured as (i) rate, expressed per 100 person-years (PYs), and (ii) risk, expressed in percentage. RESULTS: Forty RCTs met our inclusion criteria, ranging from medium to high quality. Among untreated patients with prior VFFs, the rate of subsequent VFFs and nVFFs was 12 [95% confidence interval (CI) 9-16] and 6 (95% CI 5-8%) per 100 PYs, respectively. The higher the number of previous VFFs, the higher the incidence. Moreover, the risk of VFFs and nVFFs increased within 2 (16.6% and 8%) and 4 years (35.1% and 17.4%) based on the index VFF. CONCLUSION: The highest risk of subsequent VFFs or nVFFs was already detected within 2 years following the initial VFF. Thus, prompt interventions should be designed to improve the detection and treatment of VFFs, aiming to reduce the risk of future FFs and properly implement secondary preventive measures.

The integrated structure of care: evidence for the efficacy of models of clinical governance in the prevention of fragility fractures after recent sentinel fracture after the age of 50 years.

Randomized clinical trials and observational studies on the implementation of clinical governance models, in patients who had experienced a fragility fracture, were examined. Literature was systematically reviewed and summarized by a panel of experts who formulated recommendations for the Italian guideline. PURPOSE: After experiencing a fracture, several strategies may be adopted to reduce the risk of recurrent fragility fractures and associated morbidity and mortality. Clinical governance models, such as the fracture liaison service (FLS), have been introduced for the identification, treatment, and monitoring of patients with secondary fragility fractures. A systematic review was conducted to evaluate the association between multidisciplinary care systems and several outcomes in patients with a fragility fracture in the context of the development of the Italian Guidelines. METHODS: PubMed, Embase, and the Cochrane Library were investigated up to December 2020 to update the search of the Scottish Intercollegiate Guidelines Network. Randomized clinical trials (RCTs) and observational studies that analyzed clinical governance models in patients who had experienced a fragility fracture were eligible. Three authors independently extracted data and appraised the risk of bias in the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Effect sizes were pooled in a meta-analysis using random-effects models. Primary outcomes were bone mineral density values, antiosteoporotic therapy initiation, adherence to antiosteoporotic medications, subsequent fracture, and mortality risk, while secondary outcomes were quality of life and physical performance. RESULTS: Fifteen RCTs and 62 observational studies, ranging from very low to low quality for bone mineral density values, antiosteoporotic initiation, adherence to antiosteoporotic medications, subsequent fracture, mortality, met our inclusion criteria. The implementation of clinical governance models compared to their pre-implementation or standard care/non-attenders significantly improved BMD testing rate, and increased the number of patients who initiated antiosteoporotic therapy and enhanced their adherence to the medications. Moreover, the treatment by clinical governance model respect to standard care/non-attenders significantly reduced the risk of subsequent fracture and mortality. The integrated structure of care enhanced the quality of life and physical function among patients with fragility fractures. CONCLUSIONS: Based on our findings, clinicians should promote the management of patients experiencing a fragility fracture through structured and integrated models of care. The task force has formulated appropriate recommendations on the implementation of multidisciplinary care systems in patients with, or at risk of, fragility fractures.

A systematic review on the performance of fracture risk assessment tools: FRAX, DeFRA, FRA-HS.

PURPOSE: Preventing fragility fractures by treating osteoporosis may reduce disability and mortality worldwide. Algorithms combining clinical risk factors with bone mineral density have been developed to better estimate fracture risk and possible treatment thresholds. This systematic review supported panel members of the Italian Fragility Fracture Guidelines in recommending the use of best-performant tool. The clinical performance of the three most used fracture risk assessment tools (DeFRA, FRAX, and FRA-HS) was assessed in at-risk patients. METHODS: PubMed, Embase, and Cochrane Library were searched till December 2020 for studies investigating risk assessment tools for predicting major osteoporotic or hip fractures in patients with osteoporosis or fragility fractures. Sensitivity (Sn), specificity (Sp), and areas under the curve (AUCs) were evaluated for all tools at different thresholds. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2; certainty of evidence (CoE) was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Forty-three articles were considered (40, 1, and 2 for FRAX, FRA-HS, and DeFRA, respectively), with the CoE ranging from very low to high quality. A reduction of Sn and increase of Sp for major osteoporotic fractures were observed among women and the entire population with cut-off augmentation. No significant differences were found on comparing FRAX to DeFRA in women (AUC 59-88% vs. 74%) and diabetics (AUC 73% vs. 89%). FRAX demonstrated non-significantly better discriminatory power than FRA-HS among men. CONCLUSION: The task force formulated appropriate recommendations on the use of any fracture risk assessment tools in patients with or at risk of fragility fractures, since no statistically significant differences emerged across different prediction tools.

A large observational data study supporting the PROsPeR score classification in poor ovarian responders according to live birth outcome.

STUDY QUESTION: Can the Poor Responder Outcome Prediction (PROsPeR) score identify live birth outcomes in subpopulations of patients with poor ovarian response (POR) defined according to the ESHRE Bologna criteria (female age, anti-Müllerian hormone (AMH), number of oocytes retrieved during the previous cycle (PNO) after treatment with originator recombinant human follitropin alfa? SUMMARY ANSWER: The PROsPeR score discriminated the probability of live birth in patients with POR using observational data with fair discrimination (AUC ≅ 70%) and calibration, and the AUC losing less than 5% precision compared with a model developed using the observational data. WHAT IS KNOWN ALREADY: Although scoring systems for the likelihood of live birth after ART have been developed, their accuracy may be insufficient, as they have generally been developed in the general population with infertility and were not validated for patients with POR. The PROsPeR score was developed using data from the follitropin alfa (GONAL-f; Merck KGaA, Darmstadt, Germany) arm of the Efficacy and Safety of Pergoveris in Assisted Reproductive Technology (ESPART) randomized controlled trial (RCT) and classifies women with POR as mild, moderate or severe, based upon three variables: female age, serum AMH level and number of oocytes retrieved during the previous cycle (PNO). STUDY DESIGN, SIZE, DURATION: The external validation of the PROsPeR score was completed using data derived from eight different centres in France. In addition, the follitropin alfa data from the ESPART RCT, originally used to develop the PROsPeR score, were used as reference cohort. The external validation of the PROsPeR score l was assessed using AUC. A predetermined non-inferiority limit of 0.10 compared with a reference sample and calibration (Hosmer-Lemeshow test) were the two conditions required for evaluation. PARTICIPANTS/MATERIALS, SETTING, METHODS: The observational cohort included data from 8085 ART treatment cycles performed with follitropin alfa in patients with POR defined according to the ESHRE Bologna criteria (17.6% of the initial data set). The ESPART cohort included 477 ART treatment cycles with ovarian stimulation performed with follitropin alfa in patients with POR. MAIN RESULTS AND THE ROLE OF CHANCE: The external validation of the PROsPeR score to identify subpopulations of women with POR with different live birth outcomes was shown in the observational cohort (AUC = 0.688; 95% CI: 0.662, 0.714) compared with the ESPART cohort (AUC = 0.695; 95% CI: 0.623, 0.767). The AUC difference was -0.0074 (95% CI: -0.083, 0.0689). This provided evidence, with 97.5% one-sided confidence, that there was a maximum estimated loss of 8.4% in discrimination between the observational cohort and the ESPART cohort, which was below the predetermined margin of 10%. The Hosmer-Lemeshow test did not reject the calibration when comparing observed and predicted data (Hosmer-Lemeshow test = 1.266688; P = 0.260). LIMITATIONS, REASONS FOR CAUTION: The study was based on secondary use of data that had not been collected specifically for the analysis reported here and the number of characteristics used to classify women with POR was limited to the available data. The data were from a limited number of ART centres in a single country, which may present a bias risk; however, baseline patient data were similar to other POR studies. WIDER IMPLICATIONS OF THE FINDINGS: This evaluation of the PROsPeR score using observational data supports the notion that the likelihood of live birth may be calculated with reasonable precision using three readily available pieces of data (female age, serum AMH and PNO). The PROsPeR score has potential to be used to discriminate expected probability of live birth according to the degree of POR (mild, moderate, severe) after treatment with follitropin alfa, enabling comparison of performance at one centre over time and the comparison between centres. STUDY FUNDING/COMPETING INTEREST(S): This analysis was funded by Merck KGaA, Darmstadt, Germany. P.L. received grants from Merck KGaA, outside of the submitted work. N.M. reports grants, personal fees and non-financial support from Merck KGaA outside the submitted work. T.D.H. is Vice President and Head of Global Medical Affairs Fertility, Research and Development at Merck KGaA, Darmstadt, Germany. P.A. has received personal fees from Merck KGaA, Darmstadt, Germany, outside the submitted work. C.R. has received grants and personal fees from Gedeon Richter and Merck Serono S.A.S., France, an affiliate of Merck KGaA, Darmstadt, Germany, outside the submitted work. P.S. reports congress support from Merck Serono S.A.S., France (an affiliate of Merck KGaA, Darmstadt, Germany), Gedeon Richter, TEVA and MDS outside the submitted work. C.A., J.P., G.P. and R.W. declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Antigenic profile, prevalence, and clinical significance of antiphospholipid antibodies in women referred for in vitro fertilization.

The aim of this prospective study was to assess the prevalence of antiphospholipid antibodies (aPL) in women who had undergone in vitro fertilization (IVF) and the relationship between aPL and IVF outcome. A total of 101 infertile women with at least three unsuccessful IVF attempts were consecutively included in this study. Samples were collected in the follicular phase of a spontaneous ovarian cycle 2 months after the last ovulation induction treatment. Age-matched healthy fertile women (n = 160) were included as controls. All were evaluated for the presence of lupus anticoagulant (LA), antibodies (IgG, IgA, IgM) to cardiolipin (aCL), beta2-glycoprotein I (abeta2GPI), and phosphatidylethanolamine (aPE). Out of the 101 infertile women, 40 were persistently positive for aPL, showing a prevalence significantly higher than in controls (39.6% versus 5%, P < 0.0001). Among aPL, aPE were found with a significantly higher prevalence compared with LA, aCL, and aP2GPI (67.5% versus 0%, 15%, and 40%, respectively). Interestingly, aPE were found in 70% of the cases in the absence of the other aPL. The predominant isotype of aPL was IgA, in particular for abeta2GPI. Finally, no significant association was found between the presence of aPL and IVF outcome. This prospective study shows aPE as the most prevalent aPL in infertile women and IgA as more common than IgG and IgM. However, our results do not support an association between aPL and IVF outcome.

[Ovarian cryopreservation: clinical and ethical problems arisen further to study on cases of ovarian cryopreservation]. / Cryoconservation ovarienne: problèmes cliniques et éthiques. A propos d'une série de cas d'autoconservation de tissu ovarien.

OBJECTIVE: An early ovarian failure and sterility, on patients often still young, may result from some of the anticancerous treatments. Ovarian cryopreservation is a research way for fertility restoration on patients who will have gonadotoxic treatment. The aim of our work was to study the cases of ovarian tissue preserved in our Department, enabling us to assess the clinical and ethical problems of this technique. PATIENTS AND METHODS: A retrospective study was conducted from January 2001 onwards up to October 2005, on 14 patients, whose ovarian cortex was frozen our the University Fertility Center (Hôpital de la Conception, Marseille, France). RESULTS: In our study, the patients' average age was 17+/-5.5 and the median was 14 years [13-24]. Eight patients were under 18 (11+/-3-years-old). The cryopreservation indications were especially haematological (N = 9). More than half of the patients (N = 8) had undergone a gonadotoxic treatment before ovarian cryopreservation. DISCUSSION AND CONCLUSION: Ovarian cryopreservation is still a recent technology in reproductive medicine. The future of ovarian tissue after thawing, with its different techniques of autograft, is still not consensual. Experimental research remains essential to improve the freezing protocols and ovarian transplant in human medicine.

[Conservative treatment of placenta accreta]. / Placenta accreta: place du traitement conservateur.

OBJECTIVE: Examination of modalities and results of conservative treatment of placenta accreta. MATERIAL AND METHOD: Ten-year hospital records were reviewed, with analysis of patients who had diagnosis of placenta accreta associated with conservative treatment. RESULTS: During the study period, 21259 deliveries were registered, with an incidence of placenta accreta of 1 per 1 000 deliveries (n=23). Conservative treatment was applied in 13 patients. All of them had factors commonly associated with placenta accreta: prior cesarean sections (7/13), prior curettage or endouterine surgery (11/13), placenta praevia (11/13). Antenatal diagnosis was performed in only 64% of the cases (n=7). In our conservative strategy, placenta accreta was always left in situ, with an associated treatment in most of cases (n=10): Bilateral hypogastric artery ligation (n=7), medical treatment with methotrexate (n=5), uterine artery embolization (n=2). There was no case of maternal mortality. Conservative treatment was successful in 11 patients. It failed in 2 cases: hysterectomy was performed in one case for life-threatening hemorrhage, and in the other case for post-embolization uterine necrosis. The morbidity described was blood transfusion (n=7), endometritis (n=1), and one late hemorrhage with expelling necrotic tissue. Afterwards, 2 women became pregnant: one miscarriage and one normal term delivery. CONCLUSION: Conservative treatment of placenta accreta appears to be a efficient way to preserve fertility. Antepartum diagnosis should be improved among patients with a high risk of placenta accreta in order to optimize conservative strategy.

[Uterine receptivity and embryo implantation. The use of transvaginal scan and Doppler study in its evaluation in ART]. / Réceptivité utérine et implantation embryonnaire: apport de l'échographie et du Doppler dans son évaluation en fécondation in vitro.

Embryo implantation is a multifactorial event. Biochemical factors are implicated in the quality of the endometrium and in its vascularization. The non-invasive vaginal scan studies the endometrial morphology whereas color and power Doppler studies its vascularity. Through an analysis of the literature, we point out the interest of those techniques in ART.

[Metastatic thyroid tumors from adenocarcinoma of the colon: clinical and anatomo-pathological contribution]. / Tumore metastatico della tiroide da adenocarcinoma del colon: contributo clinico e anatomo-patologico.

We report herein the case of a 43 year-old man who was operated 1998 of left colectomy and hepatic resection for colic adenocarcinoma metastasized in the liver. He suffers of multinodular goiter from some years; was admitted to our hospital with a 2-month history of enlargement of goiter and appearance of a new nodule. Physical and imaging examinations disclosed a new nodules in the thyroid. Was operated of total thyroidectomia and lymphoadenectomia cervical in the December 2002. Hystologic examinations revealed adenocarcinoma which was consistent with a diagnosis of metastases from the primary colon adenocarcinoma to the thyroid. The rarity, diagnosis, and prognosis of thyroid metastasis from colon carcinoma are discussed.

Pregnancies after ICSI using sperm with abnormal head-tail junction from two brothers: case report.

We report ICSI pregnancies in two couples with a history of long standing primary infertility in which the sperm of the male partner were either acephalic or had abnormal head-midpiece attachments. The two couples, in which the men are brothers, underwent ICSI. Sperm were analysed by transmission electron microscopy and immunocytochemistry with an anti-MPM2 monoclonal antibody. The first couple underwent two ICSI cycles, each consisting of the injection of two mature oocytes and the transfer of two embryos. A successful pregnancy occurred after the second transfer and led to the birth to a healthy girl. The second couple underwent three ICSI cycles, each consisting of the injection of 18 oocytes and the transfer of two embryos; the last of these led to a triple ongoing pregnancy which included two identical twins. Caesarean section led to the birth of three fetal-growth restricted children. This case report demonstrates that ongoing pregnancies can be achieved in cases of abnormal development of the head-neck attachment. The genetic origin of this syndrome is generally accepted, but the phenotypic heterogeneity observed by light and electron microscopy among published cases suggests that there are a variety of genetic causes of this syndrome.

Thyroid metastases from colon cancer case report in a long term survivor.

Colon cancer usually has an hematogenous spread to liver and lung: rarely, or in the case of most advanced disease, also brain and bone can be involved. Thyroid metastasis is generally thought to be infrequent, breast and kidney cancer being the most frequent causes. Herein we present the case of a man affected by liver metastasis from colon cancer, who developed unusual metastasis to thyroid.

[MRI and in utero ventriculomegaly]. / IRM et ventriculomégalie in utero.

Ventriculomegaly constitutes the major indication of fetal brain MRI. MRI is therefore of utmost importance to look for a cause through the depiction of criteria of malformations and through the definition of criteria of destructive lesions. Malformations and destructive lesions are the most common causes of ventricular dilatation. Some challenging points are worth mentioning in term of mechanism with the challenge of hydrocephalus (in term of increased in intracranial pressure) and of isolated ventriculomegaly. The image itself is also challenging since a similar image may be of different origin. In term of natural history of fetal brain injury an irregular, nodular aspect of the ventricular wall and/or the germinal matrix is often the only pathologic MRI finding that is known to be of clastic origin. In term of prognosis the challenge is represented by the isolated mild ventriculomegaly, the literature being quite confusing. The purpose of this review paper is to highlight the underlying mechanisms and pathophysiology of ventricular dilatation based on results from the literature as well as from personal experience.

[Beta-thalassemia and pregnancy. Apropos of 2 cases]. / Bêta-thalassémie majeure et grossesse. A propos de deux cas.

Homozygous beta-thalassemia is a severe, transfusion dependent anaemia that also causes infertility. Preimplantation genetic diagnosis is possible. Very few pregnancies are reported among such patients. They have a very high obstetrical risk and a pluridisciplinary follow is necessary.

Effects of cannabinoids on prefrontal neuronal responses to ventral tegmental area stimulation.

Cannabinoids activate the firing of mesoprefrontocortical dopamine neurons and release dopamine in the prefrontal cortex. This study was undertaken with the aim of clarifying the interaction between cannabinoids and mesocortical system in the prefrontal cortex. The effect of Delta9-tetrahydrocannabinol (Delta9-THC) and the synthetic CB1 agonist WIN55,212-2 (WIN) was studied by extracellular single unit recordings, in chloral hydrate anaesthetised rats, on the spontaneous activity of pyramidal neurons and on the inhibition produced on these neurons by the electrical stimulation of the ventral tegmental area (VTA). Intravenously administered Delta9-THC and WIN (1.0 and 0.5 mg/kg, respectively), increased the firing rate of pyramidal neurons projecting to the VTA. VTA stimulation produced a phasic inhibition (167 +/- 6 ms) in 79% of prefrontal cortex pyramidal neurons. Delta9-THC and WIN reverted this inhibition in 73% and 100% of the neurons tested, respectively. The subsequent administration of the selective CB1 antagonist SR141716A (1 mg/kg) readily suppressed the effects of both cannabinoids and restored the inhibitory response to VTA stimulation. Moreover, when administered alone, SR141716A prolonged the inhibition in 55.6% of the neurons tested. The results indicate that stimulation of CB1 receptors by cannabinoids results in an enhanced excitability of prefrontal cortex pyramidal neurons as indexed by the suppression of the inhibitory effect of VTA stimulation and by the increase in firing rate of antidromically identified neurons projecting to the VTA. Furthermore, our results support the view that endogenous cannabinoids exert a negative control on dopamine activity in the prefrontal cortex. This study may be relevant in helping to understand the influence of cannabinoids on cognitive processes mediated by the prefrontal cortex.

A new supported reagent for the photochemical generation of radicals in solution.

A new polymer-supported radical source was developed by loading an N-hydroxy thiazole 2(3)-thione on a Wang resin. This new supported reagent can be employed for a solid-phase version of the Hunsdiecker reaction or to liberate free alkoxy radicals, in a variant of the "catch and release" technique, under very mild conditions (irradiation with a discharge lamp) and simplifying the purification procedure.

Hysteroscopic metroplasty for septate uterus and repetitive abortions: reproductive outcome.

OBJECTIVES: The aim of this study is to assess fertility outcome and obstetrical prognosis of 63 patients after hysteroscopic section of uterine septa. MATERIALS AND METHODS: This is a retrospective study about 63 patients consulting for septate uterus and repeated pregnancy loss or abnormal fetal presentation between January 1988 and December 1996 in La Conception hospital in Marseille. Septal lysis was performed with microscissors or resectoscope. Statistical analysis was performed using the CHI2-test. RESULTS: The anatomical result was considered satisfactory in 57.1% of cases. Forty-five pregnancies were obtained, two after an IVF-program in 56 patients. Twenty-eight living children were born: twenty-six at term. Twenty patients delivered normally. Two women are still pregnant. Obstetrical prognosis of these patients is statistically improved by the treatment (P=0.001). CONCLUSION: Obstetrical prognosis of patients presenting repeated pregnancy loss and septate uterus is statistically improved by hysteroscopic metroplasty.

[Decubitus lesions in patients referred to acute and post-acute home nursing care for the elderly in Genova]. / Le lesioni da decubito nella popolazione afferente al nucleo operativo assistenza anziani e RSA post-acuti della USL 3 "Genovese".

The Elderly Services of USL 3 "Genovese" together with the team for Continuing Education designed and implemented a survey on the elderly clients referred to the home care and nursing home services. The aim of the study was to describe the frequency, distribution and severity of pressure ulcers. The data were collected during a period of seven months: from 1st November 1997 to 31st May 1998. One thousand seven hundred and twenty nine clients were observed; 705 (41%) had single or multiple pressure ulcers. Patients with multiple pressure ulcers accounted for 42% of the total. The sacrum was the most affected site (43% of the patients with a single ulcer and 33% with multiple ulcers). Patients with severe pressure ulcers (stages 3 degrees and 4 degrees NPUAP classification) accounted for 42% of the total. Pressure sores were observed in 15% of "at no risk" patients and in 40% of those at low risk (Norton Scale score). The study highlighted a lack of documentation (90% patients) on treatments performed in the hospital and prescribed at discharge for the pressure sores. These findings reflects possibly the fact that this aspect of care is unduly disregarded by nursing personnel, and that a goal-oriented retraining, underlining also the need of appropriate documentation, is warranted.