RESUMEN
Although the deleterious impact of chemotherapy regimen used to treat women of reproductive age with breast cancer on ovarian reserve has been extensively studied, hardly anything has been reported on the effect of these protocols on theca cell function and ovarian androgen secretion. The aim of this prospective multicentric cohort study was to describe serum levels of total testosterone and androstenedione during chemotherapy and 24-month follow-up in 250 patients <40 years treated for breast cancer. Mean basal levels of androstenedione and total testosterone at diagnosis were 1.68 ng/mL and 0.20 ng/mL respectively. No correlation with age was found. Serum levels of androstenedione and total testosterone rapidly decreased after chemotherapy completion, before slowly increasing and almost returning to basal levels in all patients during 2-year follow-up. In conclusion our study demonstrates a chemotherapy-induced alteration of ovarian thecal function, resulting in a significant decrease in serum androgen levels. This alteration of theca cell function adds to the well-known alteration of granulosa cell function, resulting in a global, but partly transient, ovarian failure in young women treated for breast cancer. These data bring new insight into ovarian physiology and emphasize the need for pre and post-treatment ovarian follow-up. Trial registration: ClinicalTrial.gov identifier NCT01114464.
Asunto(s)
Androstenodiona , Neoplasias de la Mama , Testosterona , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/sangre , Adulto , Androstenodiona/sangre , Estudios Prospectivos , Testosterona/sangre , Francia , Adulto Joven , Adolescente , Andrógenos/sangre , Antineoplásicos/uso terapéuticoRESUMEN
PURPOSE: Short-segment minimally invasive percutaneous spinal osteosynthesis has now become one of the treatments of choice to treat thoracolumbar fractures. The question of implant removal once the fracture has healed is still a matter of debate since this procedure can be associated with loss of sagittal correction. Therefore, we analyzed risk factors for kyphosis recurrence after spinal implants removal in patients treated with short-segment minimally invasive percutaneous spinal instrumentation for a thoracolumbar fracture. METHODS: A total of 32 patients who underwent implant removal in percutaneous osteosynthesis for post-traumatic thoracolumbar fracture were enrolled in our study. Patient's medical record, operative report and imaging examinations carried out at the trauma and during the follow-up were analyzed. RESULTS: Every patient experienced fracture union. Vertebral kyphotic angle (VKA) and Cobb angle (CA) improved significantly after stabilization surgery. VKA, CA, upper disk kyphotic angle (UDKA) and lower disk kyphotic angle (LDKA) significantly gradually decreased during follow-up. Traumatic disk injury (p: 0.001), younger age (p: 0.01), canal compromise (p: 0.04) and importance of surgical correction (p < 0.001) were significantly associated with kyphosis recurrence after implant removal. Anterior body augmentation did not affect loss of correction (CA and VKA) during the follow-up period (p: 0.57). CONCLUSION: Despite correction of the fracture after stabilization, we observed a progressive loss of correction over time appearing even before implant removal. Particular attention should be paid to post-traumatic disk damage or canal invasion, to young patients and to surgical overcorrection of the traumatic kyphosis.
Asunto(s)
Fracturas Óseas , Cifosis , Fracturas de la Columna Vertebral , Humanos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/cirugía , Fracturas de la Columna Vertebral/complicaciones , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/cirugía , Vértebras Torácicas/lesiones , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Vértebras Lumbares/lesiones , Fracturas Óseas/complicaciones , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/métodos , Cifosis/diagnóstico por imagen , Cifosis/etiología , Cifosis/cirugía , Factores de Riesgo , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
Quantifying neutralising capacity of circulating SARS-COV-2 antibodies is critical in evaluating protective humoral immune responses generated post-infection/post-vaccination. Here we describe a novel medium-throughput flow cytometry-based micro-neutralisation test to evaluate Neutralising Antibody (NAb) responses against live SARS-CoV-2 Wild Type and Variants of Concern (VOC) in convalescent/vaccinated populations. Flow Cytometry-Based Micro-Neutralisation Test (Micro-NT) was performed in 96-well plates using clinical isolates WT-B, WT-B.1.177.18 and/or VOCs Beta and Omicron. Plasma samples (All Ireland Infectious Diseases (AIID) Cohort) were serially diluted (8 points, half-log) from 1:20 and pre-incubated with SARS-CoV-2 (1h, 37°C). Virus-plasma mixture were added onto Vero E6 or Vero E6/TMPRSS2 cells for 18h. Percentage infected cells was analysed by automated flow cytometry following trypsinisation, fixation and SARS-CoV-2 Nucleoprotein intracellular staining. Half-maximal Neutralisation Titres (NT50) were determined using non-linear regression. Our assay was compared to Plaque Reduction Neutralisation Test (PRNT) and validated against the First WHO International Standard for anti-SARS-CoV-2 immunoglobulin. Both Micro-NT and PRNT achieved comparable NT50 values. Further validation showed adequate correlation with PRNT using a panel of secondary standards of clinical convalescent and vaccinated plasma samples. We found the assay to be reproducible through measuring both repeatability and intermediate precision. Screening 190 convalescent samples and 11 COVID-19 naive controls (AIID cohort) we demonstrated that Micro-NT has broad dynamic range differentiating NT50s <1/20 to >1/5000. We could also characterise immune-escape VOC Beta and Omicron BA.5, achieving fold-reductions in neutralising capacity similar to those published. Our flow cytometry-based Micro-NT is a robust and reliable assay to quantify NAb titres, and has been selected as an endpoint in clinical trials.
Asunto(s)
COVID-19 , Vacunas , Humanos , Citometría de Flujo , SARS-CoV-2 , Pruebas de Neutralización , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
PURPOSE: To assess the viability and effectiveness of mono-segmental percutaneous screw fixation in the treatment of unstable type B thoracolumbar fracture due to ankylosing spondylitis. METHODS: We report here all 40 patients treated by mono-segmental screw fixation in this indication, between January 2018 and January 2022, with follow-up at 3 and 9 months. Study variables comprised operating time, length of stay, fusion, stabilization quality, and peri-operative morbidity and mortality. RESULTS: One patient showed early displacement of rods caused by technical error. None of the others showed secondary displacement of rods or screws. Mean age was 73 years (range 18-93), mean hospital stay 4.8 days (range 2-15), mean operative time 52minutes (range 26-95minutes) and mean estimated blood loss 40ml. There were 2 deaths caused by intensive care unit complications. All patients except those in intensive care were verticalized within 24hours after surgery. Parker score was unchanged for each patient before and after surgery and during follow-up. CONCLUSION: Mono-segmental percutaneous screw fixation in the treatment of unstable type B thoracolumbar fracture due to ankylosing spondylitis was safe and effective. This study showed that this surgery reduced length of hospital stay, operative time, blood loss and complications compared to open or extended percutaneous surgery, and allowed fast rehabilitation in this vulnerable population.
Asunto(s)
Tornillos Pediculares , Fracturas de la Columna Vertebral , Espondilitis Anquilosante , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Fracturas de la Columna Vertebral/cirugía , Fracturas de la Columna Vertebral/etiología , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/cirugía , Fijación Interna de Fracturas/efectos adversos , Tornillos Pediculares/efectos adversos , Vértebras Lumbares/cirugía , Vértebras Torácicas/cirugía , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
Programming is a powerful and ubiquitous problem-solving tool. Systems that can assist programmers or even generate programs themselves could make programming more productive and accessible. Recent transformer-based neural network models show impressive code generation abilities yet still perform poorly on more complex tasks requiring problem-solving skills, such as competitive programming problems. Here, we introduce AlphaCode, a system for code generation that achieved an average ranking in the top 54.3% in simulated evaluations on recent programming competitions on the Codeforces platform. AlphaCode solves problems by generating millions of diverse programs using specially trained transformer-based networks and then filtering and clustering those programs to a maximum of just 10 submissions. This result marks the first time an artificial intelligence system has performed competitively in programming competitions.
RESUMEN
OBJECTIVE: Surgery is an effective treatment for drug-resistant temporal-lobe epilepsy (TLE), but is still underutilized for older patients because of a perceived higher rate of perioperative complications, cognitive decline and worse seizure outcome. METHODS: We retrospectively screened all patients operated on in our institution for drug-resistant TLE between 2007 and 2019. Data of patients aged ≥50 years versus <50 years at surgery were compared. The primary endpoint was freedom from disabling seizure (Engel I) at 2 years postoperatively. RESULTS: In patients aged ≥50 years (n=19), mean age at surgery was 54.9 years and mean disease duration was 36.6 years. At 2 years postoperatively, rates of Engel I seizure outcome were not significantly different between the two groups (73.9% in the <50 years group versus 94.4% in the ≥50 years group). Although surgical complications were significantly (47.4%) in the older patients, neurological deficit was permanent in only 5.3% of cases. At 1 year postoperatively, neuropsychological outcome did not significantly differ between the two groups. CONCLUSIONS: Patients aged ≥50 years had an excellent seizure outcome at 2 years postoperatively. Early postoperative complications were more frequent in patients aged ≥50 years but were mostly transient. Cognitive outcome was similar to that in younger patients. These findings strongly suggest that age ≥50 years should not be an exclusion criterion for resective epilepsy surgery in patients with drug-resistant TLE.
Asunto(s)
Epilepsia Refractaria , Epilepsia del Lóbulo Temporal , Epilepsia Refractaria/psicología , Epilepsia Refractaria/cirugía , Epilepsia del Lóbulo Temporal/cirugía , Humanos , Estudios Retrospectivos , Convulsiones/epidemiología , Convulsiones/cirugía , Lóbulo Temporal/cirugía , Resultado del TratamientoRESUMEN
Gastrointestinal symptoms are frequent in acute adrenal insufficiency. Although digestive symptoms can significantly reduce quality of life, they are rarely described in patients with treated chronic adrenal insufficiency (CAI). We aimed to characterize digestive symptoms in CAI patients. We used the section pertaining functional bowel disorders of the Rome IV questionnaire. A questionnaire was published on the website of the non-profit patient association "Adrenals" (NPPA of CAI patients) for five months. Information on demographics, characteristics of adrenal insufficiency, digestive symptoms and quality of life was collected. The relatives of CAI patients served as a control group. We analyzed responses of 33 control subjects and 119 patients (68 primary adrenal insufficiency (PAI), 30 secondary adrenal insufficiency (SAI) and 21 congenital adrenal hyperplasia (CAH)). Abdominal pain at least once a week over the past 3 months was reported by 40%, 47% and 33% of patients with PAI, SAI and CAH respectively versus 15% for the controls (p = 0.01). Symptoms were consistent with the Rome IV criteria for irritable bowel syndrome in 27%, 33% and 33% of patients respectively versus 6% for the controls (p < 0.0001). Quality of life was described as poor or very poor in 35%, 57% and 24% of patients respectively versus 5% for the controls (p < 0.0001). In conclusion, digestive symptoms are frequent and incapacitating in CAI patients and similar to symptoms of irritable bowel syndrome in 30% of CAI patients. Assessment and management of digestive symptoms should be considered a priority for physicians treating patients with CAI.
Asunto(s)
Insuficiencia Suprarrenal , Síndrome del Colon Irritable , Adulto , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y CuestionariosRESUMEN
INTRODUCTION: This pilot study evaluated the imaging performance of pretargeted immunological positron emission tomography (immuno-PET) using an anti-carcinoembryonic antigen (CEA) recombinant bispecific monoclonal antibody (BsMAb), TF2 and the [68Ga]Ga-labelled HSG peptide, IMP288, in patients with metastatic colorectal carcinoma (CRC). PATIENTS AND METHODS: Patients requiring diagnostic workup of CRC metastases or in case of elevated CEA for surveillance were prospectively studied. They had to present with elevated CEA serum titre or positive CEA tumour staining by immunohistochemistry of a previous biopsy or surgical specimen. All patients underwent endoscopic ultrasound (EUS), chest-abdominal-pelvic computed tomography (CT), abdominal magnetic resonance imaging (MRI) and positron emission tomography using [18F]fluorodeoxyglucose (FDG-PET). For immuno-PET, patients received intravenously 120 nmol of TF2 followed 30 h later by 150 MBq of [68Ga]Ga-labelled IMP288, both I.V. The gold standard was histology and imaging after 6-month follow-up. RESULTS: Eleven patients were included. No adverse effects were reported after BsMAb and peptide injections. In a per-patient analysis, immuno-PET was positive in 9/11 patients. On a per-lesion analysis, 12 of 14 lesions were positive with immuno-PET. Median SUVmax, MTV and TLG were 7.65 [3.98-13.94, SD 3.37], 8.63 cm3 [1.98-46.64; SD 14.83] and 37.90 cm3 [8.07-127.5; SD 43.47] respectively for immuno-PET lesions. Based on a per-lesion analysis, the sensitivity, specificity, positive-predictive value and negative-predictive value were, respectively, 82%, 25%, 82% and 25% for the combination of EUS/CT/MRI; 76%, 67%, 87% and 33% for FDG-PET; and 88%, 100%, 100% and 67% for immuno-PET. Immuno-PET had an impact on management in 2 patients. CONCLUSION: This pilot study showed that pretargeted immuno-PET using anti-CEA/anti-IMP288 BsMAb and a [68Ga]Ga-labelled hapten was safe and feasible, with promising diagnostic performance. TRIAL REGISTRATION: ClinicalTrials.gov NCT02587247 Registered 27 October 2015.
Asunto(s)
Neoplasias Colorrectales , Radioisótopos de Galio , Anticuerpos Monoclonales , Antígeno Carcinoembrionario , Neoplasias Colorrectales/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Compuestos Heterocíclicos con 1 Anillo , Humanos , Oligopéptidos , Proyectos Piloto , Tomografía de Emisión de PositronesRESUMEN
OBJECTIVE: Serum AMH level has been shown to decrease in women treated for breast cancer in several studies. However, whether basal AMH status affects AMH dynamics during chemotherapy remains to be clarified. The objective of this study was to compare serum AMH dynamics in young women with either low, normal or high basal serum AMH level at diagnosis, during and after treatment with chemotherapy for breast cancer. STUDY DESIGN: In this secondary analysis of a prospective cohort study, serum AMH was measured during and after chemotherapy in 239 women of reproductive age diagnosed with breast cancer and treated with chemotherapy. The association between AMH dynamics throughout chemotherapy and during follow-up and basal AMH status, i.e. low AMH (<1 µg/l, <7 pmol/l), normal AMH (1-4.9 µg/l, 7-36 pmol/l) and high AMH (≥5 µg/l, >36 pmol/l), was evaluated. Menses occurrence was also recorded. RESULTS: A total of 21 women had low, 154 had normal and 64 had high basal AMH level. Serum AMH rapidly decreased during chemotherapy in all groups, and its variation during chemotherapy and follow-up was not significantly different between the 3 groups. CONCLUSION: No association was found between AMH variation during chemotherapy and follow-up, and basal AMH level at diagnosis. However, women with high basal AMH levels have significantly higher AMH levels throughout chemotherapy and follow-up than women with normal or low basal AMH levels at diagnosis.
Asunto(s)
Hormona Antimülleriana , Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Estudios Prospectivos , ReproducciónRESUMEN
Measles virus (MeV), like all viruses of the order Mononegavirales, utilizes a complex consisting of genomic RNA, nucleoprotein, the RNA-dependent RNA polymerase, and a polymerase cofactor, the phosphoprotein (P), for transcription and replication. We previously showed that a recombinant MeV that does not express another viral protein, C, has severe transcription and replication deficiencies, including a steeper transcription gradient than the parental virus and generation of defective interfering RNA. This virus is attenuated in vitro and in vivo However, how the C protein operates and whether it is a component of the replication complex remained unclear. Here, we show that C associates with the ribonucleocapsid and forms a complex that can be purified by immunoprecipitation or ultracentrifugation. In the presence of detergent, the C protein is retained on purified ribonucleocapsids less efficiently than the P protein and the polymerase. The C protein is recruited to the ribonucleocapsid through its interaction with the P protein, as shown by immunofluorescence microscopy of cells expressing different combinations of viral proteins and by split luciferase complementation assays. Forty amino-terminal C protein residues are dispensable for the interaction with P, and the carboxyl-terminal half of P is sufficient for the interaction with C. Thus, the C protein, rather than being an "accessory" protein as qualified in textbooks so far, is a ribonucleocapsid-associated protein that interacts with P, thereby increasing replication accuracy and processivity of the polymerase complex.IMPORTANCE Replication of negative-strand RNA viruses relies on two components: a helical ribonucleocapsid and an RNA-dependent RNA polymerase composed of a catalytic subunit, the L protein, and a cofactor, the P protein. We show that the measles virus (MeV) C protein is an additional component of the replication complex. We provide evidence that the C protein is recruited to the ribonucleocapsid by the P protein and map the interacting segments of both C and P proteins. We conclude that the primary function of MeV C is to improve polymerase processivity and accuracy, rather than uniquely to antagonize the type I interferon response. Since most viruses of the Paramyxoviridae family express C proteins, their primary function may be conserved.
Asunto(s)
Virus del Sarampión/metabolismo , Nucleoproteínas/genética , Proteínas no Estructurales Virales/metabolismo , Proteínas Virales/genética , Animales , Proteínas Portadoras , Línea Celular , Chlorocebus aethiops , Células HEK293 , Células HeLa , Humanos , Sarampión/virología , Virus del Sarampión/genética , Proteínas de la Nucleocápside , Nucleoproteínas/metabolismo , Fosfoproteínas/metabolismo , Unión Proteica , ARN Polimerasa Dependiente del ARN/metabolismo , Células Vero , Proteínas no Estructurales Virales/fisiología , Proteínas Virales/metabolismo , Activación Viral/genética , Replicación Viral/genéticaRESUMEN
We report the attitudes and practices of health care workers involved in the disclosure process to adolescents living with HIV (ALHIV) in a network including West and Central African French-speaking countries, and the experiences of young living with HIV (YLHIV). During a three-day workshop in Abidjan, Côte d'Ivoire, caregivers (doctors, psychologists, social workers) from 19 pediatric HIV treatment sites shared their practices and difficulties, and four YPLHIV their own disclosure experience. Thirty five participants from eight West/Central African countries (Benin, Burkina Faso, Ivory Coast, Cameroon, Mali, Democratic Republic of Congo, Senegal, Togo) contributed: 14 doctors, eight psychologists, six counselors, three social workers. The experience of the centers was variable, but the age at disclosure was late: 34% of 1296 adolescents between 10 and 12 years of age knew their status. The median age at disclosure was 13 years (range: 11-15 years). The practice of the disclosure was often complex, because of multiple factors (fear of the parents of the breaking of the secrecy, lack of communication between professionals). The individual disclosure was the main practice. Four centers practiced HIV disclosure in group sessions to facilitate mirror support, and one used peer-to-peer support. YPLHIV have advocated for an earlier disclosure, from 10 years. In West and Central Africa, the process of HIV disclosure remains complex for parents and caregivers, and occurs too late. The development of a good practice guideline for HIV disclosing adapted to socio-cultural contexts should help to improve this process.
Nous rapportons les attitudes et pratiques des soignants en Afrique francophone concernant l'annonce du statut VIH aux adolescents, et les témoignages de jeunes vivant avec le VIH (jvVIH). Lors d'un atelier de trois jours à Abidjan, Côte d'Ivoire, en novembre 2016, les soignants (médecins, psychologues, travailleurs sociaux) de 19 sites de prise en charge pédiatrique du VIH ont partagé leurs pratiques et difficultés et 4 jvVIH leur vécu de l'annonce. Au total, 35 participants de 8 pays d'Afrique de l'Ouest/centrale (Bénin, Burkina Faso, Côte d'Ivoire, Cameroun, Mali, République démocratique du Congo, Sénégal, Togo) ont contribué : 14 médecins, 8 psychologues, 6 conseillers, 3 travailleurs sociaux. L'expérience des centres était variable, mais l'âge à l'annonce restait tardif : 34 % des 1 296 adolescents âgés entre 10 et 12 ans connaissaient leur statut. L'âge médian à l'annonce était de 13 ans (étendue : 11-15 ans). La pratique de l'annonce s'avérait complexe, en raison de multiples facteurs (crainte des parents de la rupture du secret, manque de communication entre professionnels). L'annonce individuelle était la pratique majoritairement adoptée. Quatre centres pratiquaient une annonce en séances de groupe pour faciliter le soutien en miroir, et un avait recours à l'appui de pairs-adolescents. Les jvVIH ont plaidé pour une annonce plus précoce, dès 10 ans. En Afrique de l'Ouest/centrale francophone, le processus de l'annonce reste complexe pour parents et soignants, et l'annonce trop tardive. L'élaboration d'un guide de bonnes pratiques de l'annonce du VIH, adapté aux contextes socio-culturels devrait permettre d'améliorer ce processus.
Asunto(s)
Actitud del Personal de Salud , Revelación/normas , Infecciones por VIH/psicología , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud/psicología , Adolescente , África Central , África Occidental , Niño , HumanosRESUMEN
Hepatitis E Virus (HEV) genome encodes three proteins including the ORF2 capsid protein. Recently, we demonstrated that HEV produces three different forms of ORF2: (i) the ORF2i form (infectious ORF2) which is the component of infectious particles, (ii) the secreted ORF2g (glycosylated ORF2) and ORF2c (cleaved ORF2) forms that are not associated with infectious particles, but are the major antigens in HEV-infected patient sera. The ORF2 protein sequence contains three highly conserved potential N-glycosylation sites (N1, N2 and N3). The status and biological relevance of ORF2 N-glycosylation in HEV lifecycle remain to be elucidated. Here, we generated and extensively characterized a series of ORF2 mutants in which the three N-glycosylation sites were mutated individually or in combination. We demonstrated that the ORF2g/c protein is N-glycosylated on N1 and N3 sites but not on the N2 site. We showed that N-glycosylation of ORF2 protein does not play any role in replication and assembly of infectious HEV particles. We found that glycosylated ORF2g/c forms are very stable proteins which are targeted by patient antibodies. We also demonstrated that the ORF2i protein is translocated into the nucleus of infected cells. Hence, our study led to new insights into the molecular mechanisms of ORF2 expression.
Asunto(s)
Virus de la Hepatitis E/patogenicidad , Proteínas Virales/química , Proteínas Virales/metabolismo , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/metabolismo , Anticuerpos Antivirales/química , Anticuerpos Antivirales/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/virología , Glicosilación , Virus de la Hepatitis E/genética , Virus de la Hepatitis E/fisiología , Interacciones Huésped-Patógeno , Humanos , Mutación , Señales de Clasificación de Proteína , Estabilidad Proteica , Proteínas Virales/genética , Proteínas Virales/inmunologíaRESUMEN
OBJECTIVES: Despite its simple definition, preeclampsia can have variable and atypical clinical presentations, an unpredictable course, and potential adverse maternal and fetal outcomes. No single test currently predicts risk or prognosis adequately. Scientific advances suggest that an angiogenic imbalance is involved in its pathophysiology. The objective of this study was to investigate the use of sFlt-1, PlGF, and their ratio in predicting preeclampsia. MATERIALS AND METHODS: In a single-center prospective observational study, we measured the angiogenic markers sFlt-1 and PlGF and calculated the sFlt-1/PlGF ratio in patients at risk of preeclampsia at 20 to 37 weeks of gestation. The main outcomes were the occurrence of preeclampsia and the interval before its onset. RESULTS: Of the 67 at risk patients included, 8 (12%) developed preeclampsia. For a sFlt-1/PlGF ratio ≥85, the specificity was 93%. The ratio was significantly higher (ratio=104±30) in women with an onset time less than 5 weeks than in those with later preeclampsia (ratio=10±2), P<0.001. CONCLUSION: In a high-risk population, angiogenic markers appear to be an interesting aid in predicting the onset of preeclampsia with high specificity and in estimating time to onset. However, due to small number of cases of PE, more studies are needed before recommendations to use these markers in daily practice.
Asunto(s)
Factor de Crecimiento Placentario/sangre , Preeclampsia/sangre , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Adulto , Femenino , Edad Gestacional , Humanos , Embarazo , Pronóstico , Estudios Prospectivos , RiesgoRESUMEN
PURPOSE: The goal of this prospective study was to analyze the potential of S100B protein as a negative predictive marker for intracranial hemorrhage (ICH) after mild head trauma (MHT) in patient under antithrombotic medication. METHODS: Patients under antithrombotic medication who had MHT were consecutively included in this study. S100B blood levels were determined from samples drawn within 6hours after injury and were analyzed with the results of head CT performed within the 24hours after injury. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of S100B levels for the detection of ICH, with a cut-off set at 0.105µg/L, were calculated. RESULTS: A total of 308 patients (151 men and 157 women) with a mean age of 79.1±10.5years (SD) were included in the analysis. CT was positive for the presence of ICH in 33 patients (10.7%; 95% CI: 7.5-14.7%). In the study population, S100B showed a sensitivity of 84.8% (95%CI: 68.1-94.9%), a specificity of 30.2% (95% CI: 24.8-36.0%), a NPV of 94.3% (95% CI: 87.2-98.1%), and a PPV of 12.7% (95% CI: 8.6-17.9%) for the diagnosis of ICH. CONCLUSION: The results of this study suggest that a S100B serum level<0.105µg/L has a high NPV for ICH after mild head trauma in patients under antithrombotic medication.
RESUMEN
The novel HLA-B*41:50 allele differs from HLA-B*41:01:01 by a single nucleotide substitution at codon 116.
Asunto(s)
Alelos , Antígenos HLA-B/genética , Francia , HumanosRESUMEN
AIM: Women of reproductive age with breast cancer generally receive gonadotoxic chemotherapy. Fertility issues are of great concern for them. However, little is known on ovarian damage during chemotherapy and its evolution during long-term follow-up. The aim of this study was to provide a detailed description of serum anti-Müllerian hormone (AMH) evolution during chemotherapy and 24-month follow-up. METHODS: This prospective cohort study was conducted in 250 patients, aged 18-39 years, diagnosed with breast cancer and treated with adjuvant/neoadjuvant chemotherapy. Each patient underwent blood AMH measurement at each chemotherapy cycle, and at 6, 12 and 24 months after chemotherapy. Menses occurrence was also recorded. RESULTS: Mean basal AMH level was 4.19 ± 4.84 ng/mL, and was negatively correlated with age. Serum AMH level rapidly decreased in all patients after each chemotherapy cycle to undetectable levels in most of them, and slowly increased in 45% of the patients during the 24-month follow-up. AMH decrease was significantly associated with age and basal AMH level, but not with cyclophosphamide dose and tamoxifen use. The prevalence of chemotherapy-related amenorrhoea was 92.4% at the end of chemotherapy; women with amenorrhoea being significantly older and having lower basal AMH than women who resumed menses. CONCLUSIONS: Our study confirms rapid and deep ovarian reserve alteration in young women receiving chemotherapy for breast cancer, and shows moderate AMH recovery in some patients. Although AMH cannot alone predict fertility potential, these new data emphasise the need for post-treatment ovarian insufficiency follow-up, strongly support the use of fertility preservation strategies and may provide new tools for improved counselling.
Asunto(s)
Hormona Antimülleriana/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adolescente , Distribución por Edad , Neoplasias de la Mama/sangre , Ciclofosfamida/administración & dosificación , Femenino , Humanos , Ciclo Menstrual/fisiología , Embarazo , Complicaciones Neoplásicas del Embarazo/sangre , Complicaciones Neoplásicas del Embarazo/tratamiento farmacológico , Estudios Prospectivos , Tamoxifeno/administración & dosificación , Adulto JovenRESUMEN
The novel HLA-B*15:416 allele differs from HLA-B*15:01:01:01 by a single nucleotide substitution at codon 114.
Asunto(s)
Alelos , Exones , Antígeno HLA-B15/genética , Polimorfismo de Nucleótido Simple , Donantes de Tejidos , Sustitución de Aminoácidos , Secuencia de Bases , Trasplante de Médula Ósea , Codón/química , Expresión Génica , Genotipo , Antígeno HLA-B15/inmunología , Trasplante de Células Madre Hematopoyéticas , Prueba de Histocompatibilidad , Humanos , Reacción en Cadena de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Long-term consequences of cancer treatments in young women, and especially fertility issues, are gaining attention as survival rates increase. Breast cancer is the most frequent malignancy in women of reproductive age. AIM: The purpose of this review is to describe serum anti-müllerian hormone (AMH) level at diagnosis and its evolution during and after chemotherapy in women of reproductive age treated for breast cancer. Second, the impact of taxanes on AMH, the association between AMH and amenorrhea, and the comparison of AMH with other hormonal markers of ovarian reserve were studied. METHODS: A systematic PubMed search was conducted on all articles, published up to April 2016 and related to AMH in women suffering from breast cancer using the following key words: AMH, müllerian-inhibiting substance, ovarian reserve, ovarian function, breast cancer, gonadotoxicity, ovarian toxicity, amenorrhea, chemotherapy, and menopause. RESULTS: AMH levels rapidly fall down to undetectable levels in most women during chemotherapy and generally persist at very low levels in most women after the treatment. Taxanes seem to impact negatively ovarian function, but data on ovarian reserve are scarce. AMH is a predictor of the occurrence of chemotherapy-related amenorrhea and is the most relevant hormonal marker of ovarian reserve. CONCLUSION: Serum AMH is a relevant tool for ovarian reserve assessment and follow-up during treatment in premenopausal women with breast cancer. Further large prospective studies are necessary to determine its predictive interest for post-treatment residual fertility, and eventually use it in fertility preservation counseling before treatment initiation.
Asunto(s)
Hormona Antimülleriana/metabolismo , Antineoplásicos/administración & dosificación , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Taxoides/efectos adversos , Adulto , Amenorrea/inducido químicamente , Femenino , Humanos , Persona de Mediana Edad , Ovario/efectos de los fármacos , Ovario/fisiología , Adulto JovenRESUMEN
The novel HLA-B*08:163 allele differs from HLA-B*08:01:01:01 by a single nucleotide substitution at codon 105.