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1.
Sci Rep ; 14(1): 6564, 2024 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-38503816

RESUMEN

This study aimed to identify the risk factors for placenta accreta spectrum (PAS) in women who had at least one previous cesarean delivery and a placenta previa or low-lying. The PACCRETA prospective population-based study took place in 12 regional perinatal networks from 2013 through 2015. All women with one or more prior cesareans and a placenta previa or low lying were included. Placenta accreta spectrum (PAS) was diagnosed at delivery according to standardized clinical and histological criteria. Of the 520,114 deliveries, 396 fulfilled inclusion criteria; 108 were classified with PAS at delivery. Combining the number of prior cesareans and the placental location yielded a rate ranging from 5% for one prior cesarean combined with a posterior low-lying placenta to 63% for three or more prior cesareans combined with placenta previa. The factors independently associated with PAS disorders were BMI ≥ 30, previous uterine surgery, previous postpartum hemorrhage, a higher number of prior cesareans, and a placenta previa. Finally, in this high-risk population, the rate of PAS disorders varies greatly, not only with the number of prior cesareans but also with the exact placental location and some of the women's individual characteristics. Risk stratification is thus possible in this population.


Asunto(s)
Placenta Accreta , Placenta Previa , Embarazo , Femenino , Humanos , Placenta Previa/epidemiología , Placenta Previa/etiología , Placenta , Placenta Accreta/epidemiología , Placenta Accreta/etiología , Estudios Prospectivos , Cesárea/efectos adversos , Factores de Riesgo , Estudios Retrospectivos
2.
Soins ; 69(882): 37-40, 2024.
Artículo en Francés | MEDLINE | ID: mdl-38296419

RESUMEN

The context of the emergency department particularly exposes professionals to situations where the question of restraint arises. This article describes the indications and modalities of physical restraint. Physical restraint should be considered as a last resort, and requires systematic ethical questioning.


Asunto(s)
Servicio de Urgencia en Hospital , Restricción Física , Humanos
3.
Am J Obstet Gynecol ; 229(5): 542.e1-542.e14, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37209893

RESUMEN

BACKGROUND: Many questions remain about the appropriate use of intrauterine balloon devices in postpartum hemorrhage after vaginal delivery refractory to first-line uterotonics. Available data suggest that early use of intrauterine balloon tamponade might be beneficial. OBJECTIVE: This study aimed to compare the effect of intrauterine balloon tamponade used in combination with second-line uterotonics vs intrauterine balloon tamponade used after the failure of second-line uterotonic treatment on the rate of severe postpartum hemorrhage in women with postpartum hemorrhage after vaginal delivery refractory to first-line uterotonics. STUDY DESIGN: This multicenter, randomized, controlled, parallel-group, nonblinded trial was conducted at 18 hospitals and enrolled 403 women who had just given birth vaginally at 35 to 42 weeks of gestation. The inclusion criteria were a postpartum hemorrhage refractory to first-line uterotonics (oxytocin) and requiring a second-line uterotonic treatment with sulprostone (E1 prostaglandin). In the study group, the sulprostone infusion was combined with intrauterine tamponade by an ebb balloon performed within 15 minutes of randomization. In the control group, the sulprostone infusion was started alone within 15 minutes of randomization, and if bleeding persisted 30 minutes after the start of sulprostone infusion, intrauterine tamponade using the ebb balloon was performed. In both groups, if the bleeding persisted 30 minutes after the insertion of the balloon, an emergency radiological or surgical invasive procedure was performed. The primary outcome was the proportion of women who either received ≥3 units of packed red blood cells or had a calculated peripartum blood loss of >1000 mL. The prespecified secondary outcomes were the proportions of women who had a calculated blood loss of ≥1500 mL, any transfusion, an invasive procedure and women who were transferred to the intensive care unit. The analysis of the primary outcome with the triangular test was performed sequentially throughout the trial period. RESULTS: At the eighth interim analysis, the independent data monitoring committee concluded that the incidence of the primary outcome did not differ between the 2 groups and stopped inclusions. After 11 women were excluded because they met an exclusion criterion or withdrew their consent, 199 and 193 women remained in the study and control groups, respectively, for the intention-to-treat analysis. The women's baseline characteristics were similar in both groups. Peripartum hematocrit level change, which was needed for the calculation of the primary outcome, was missing for 4 women in the study group and 2 women in the control group. The primary outcome occurred in 131 of 195 women (67.2%) in the study group and 142 of 191 women (74.3%) in the control group (risk ratio, 0.90; 95% confidence interval, 0.79-1.03). The groups did not differ substantially for rates of calculated peripartum blood loss pf ≥1500 mL, any transfusion, invasive procedure, and admission to an intensive care unit. Endometritis occurred in 5 women (2.7%) in the study group and none in the control group (P=.06). CONCLUSION: The early use of intrauterine balloon tamponade did not reduce the incidence of severe postpartum hemorrhage compared with its use after the failure of second-line uterotonic treatment and before recourse to invasive procedures.


Asunto(s)
Oclusión con Balón , Hemorragia Posparto , Taponamiento Uterino con Balón , Embarazo , Femenino , Humanos , Hemorragia Posparto/etiología , Parto Obstétrico/efectos adversos , Parto Obstétrico/métodos , Oxitocina , Taponamiento Uterino con Balón/efectos adversos
5.
Am J Obstet Gynecol ; 226(6): 839.e1-839.e24, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34914894

RESUMEN

BACKGROUND: Placenta accreta spectrum is a life-threatening condition that has increased dramatically in recent decades along with cesarean rates worldwide. Cesarean hysterectomy is widely practiced in women with placenta accreta spectrum; however, the maternal outcomes after cesarean hysterectomy have not been thoroughly compared with the maternal outcomes after alternative approaches, such as conservative management. OBJECTIVE: This study aimed to compare the severe maternal outcomes between women with placenta accreta spectrum treated with cesarean hysterectomy and those treated with conservative management (leaving the placenta in situ). STUDY DESIGN: From a source population of 520,114 deliveries in 176 hospitals (PACCRETA study), we designed an observational cohort of women with placenta accreta spectrum who had either a cesarean hysterectomy or a conservative management (the placenta left in situ) during cesarean delivery. Clinicians prospectively identified women meeting the inclusion criteria and included them at delivery. Data collection started only after the women had received information and agreed to participate in the study in the immediate postpartum period. The primary outcome was the transfusion of >4 units of packed red blood cells within 6 months after delivery. Secondary outcomes were other maternal complications within 6 months. We used propensity score weighting to account for potential indication bias. RESULTS: Here, 86 women had conservative management and 62 women had cesarean hysterectomy for placenta accreta spectrum during cesarean delivery. The primary outcome occurred in 14 of 86 women in the conservative management group (16.3%) and 36 of 61 (59.0%) in the cesarean hysterectomy group (risk ratio in propensity score weighted model, 0.29; 95% confidence interval, 0.19-0.45). The rates of hysterectomy, total estimated blood loss exceeding 3000 mL, any blood product transfusion, adjacent organ injury, and nonpostpartum hemorrhage-related severe maternal morbidity were lower with conservative management than with cesarean hysterectomy (all adjusted, P≤.02); but, the rates of arterial embolization, endometritis, and readmission within 6 months of discharge were higher with conservative management than with cesarean hysterectomy. CONCLUSION: Among women with placenta accreta spectrum who underwent cesarean delivery, conservative management was associated with a lower risk of transfusion of >4 units of packed red blood cells within 6 months than cesarean hysterectomy.


Asunto(s)
Placenta Accreta , Cesárea , Tratamiento Conservador , Femenino , Humanos , Histerectomía , Placenta Accreta/epidemiología , Placenta Accreta/cirugía , Embarazo , Estudios Prospectivos , Estudios Retrospectivos
6.
JCI Insight ; 7(1)2022 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-34793337

RESUMEN

The biosynthetic routes leading to de novo nicotinamide adenine dinucleotide (NAD+) production are involved in acute kidney injury (AKI), with a critical role for quinolinate phosphoribosyl transferase (QPRT), a bottleneck enzyme of de novo NAD+ biosynthesis. The molecular mechanisms determining reduced QPRT in AKI, and the role of impaired NAD+ biosynthesis in the progression to chronic kidney disease (CKD), are unknown. We demonstrate that a high urinary quinolinate-to-tryptophan ratio, an indirect indicator of impaired QPRT activity and reduced de novo NAD+ biosynthesis in the kidney, is a clinically applicable early marker of AKI after cardiac surgery and is predictive of progression to CKD in kidney transplant recipients. We also provide evidence that the endoplasmic reticulum (ER) stress response may impair de novo NAD+ biosynthesis by repressing QPRT transcription. In conclusion, NAD+ biosynthesis impairment is an early event in AKI embedded with the ER stress response, and persistent reduction of QPRT expression is associated with AKI to CKD progression. This finding may lead to identification of noninvasive metabolic biomarkers of kidney injury with prognostic and therapeutic implications.


Asunto(s)
Lesión Renal Aguda/metabolismo , Estrés del Retículo Endoplásmico/fisiología , Riñón/metabolismo , NAD/biosíntesis , Animales , Línea Celular , Masculino , Ratones , Ratones Endogámicos C57BL , Pentosiltransferasa/metabolismo , Ácido Quinolínico/orina , Triptófano/orina
7.
JAMA ; 326(21): 2141-2149, 2021 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-34874418

RESUMEN

Importance: Uncontrolled studies suggest that pulmonary embolism (PE) can be safely ruled out using the YEARS rule, a diagnostic strategy that uses varying D-dimer thresholds. Objective: To prospectively validate the safety of a strategy that combines the YEARS rule with the pulmonary embolism rule-out criteria (PERC) rule and an age-adjusted D-dimer threshold. Design, Settings, and Participants: A cluster-randomized, crossover, noninferiority trial in 18 emergency departments (EDs) in France and Spain. Patients (N = 1414) who had a low clinical risk of PE not excluded by the PERC rule or a subjective clinical intermediate risk of PE were included from October 2019 to June 2020, and followed up until October 2020. Interventions: Each center was randomized for the sequence of intervention periods. In the intervention period (726 patients), PE was excluded without chest imaging in patients with no YEARS criteria and a D-dimer level less than 1000 ng/mL and in patients with 1 or more YEARS criteria and a D-dimer level less than the age-adjusted threshold (500 ng/mL if age <50 years or age in years × 10 in patients ≥50 years). In the control period (688 patients), PE was excluded without chest imaging if the D-dimer level was less than the age-adjusted threshold. Main Outcomes and Measures: The primary end point was venous thromboembolism (VTE) at 3 months. The noninferiority margin was set at 1.35%. There were 8 secondary end points, including chest imaging, ED length of stay, hospital admission, nonindicated anticoagulation treatment, all-cause death, and all-cause readmission at 3 months. Results: Of the 1414 included patients (mean age, 55 years; 58% female), 1217 (86%) were analyzed in the per-protocol analysis. PE was diagnosed in the ED in 100 patients (7.1%). At 3 months, VTE was diagnosed in 1 patient in the intervention group (0.15% [95% CI, 0.0% to 0.86%]) vs 5 patients in the control group (0.80% [95% CI, 0.26% to 1.86%]) (adjusted difference, -0.64% [1-sided 97.5% CI, -∞ to 0.21%], within the noninferiority margin). Of the 6 analyzed secondary end points, only 2 showed a statistically significant difference in the intervention group compared with the control group: chest imaging (30.4% vs 40.0%; adjusted difference, -8.7% [95% CI, -13.8% to -3.5%]) and ED median length of stay (6 hours [IQR, 4 to 8 hours] vs 6 hours [IQR, 5 to 9 hours]; adjusted difference, -1.6 hours [95% CI, -2.3 to -0.9]). Conclusions and Relevance: Among ED patients with suspected PE, the use of the YEARS rule combined with the age-adjusted D-dimer threshold in PERC-positive patients, compared with a conventional diagnostic strategy, did not result in an inferior rate of thromboembolic events. Trial Registration: ClinicalTrials.gov Identifier: NCT04032769.


Asunto(s)
Productos de Degradación de Fibrina-Fibrinógeno/análisis , Embolia Pulmonar/diagnóstico , Tromboembolia Venosa/diagnóstico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Causas de Muerte , Intervalos de Confianza , Estudios Cruzados , Servicio de Urgencia en Hospital , Femenino , Francia , Hospitalización/estadística & datos numéricos , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Readmisión del Paciente/estadística & datos numéricos , Estudios Prospectivos , Embolia Pulmonar/sangre , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/mortalidad , Reproducibilidad de los Resultados , España , Tromboembolia Venosa/sangre , Adulto Joven
8.
BMJ Case Rep ; 14(6)2021 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-34088694

RESUMEN

Patients with COVID-19 may be asymptomatic or present with extrarespiratory symptoms, such as liver injury. It has been reported that 22.5%-46.2% of patients have moderate elevation of liver enzymes. To our knowledge, acute hepatitis has never been described as an isolated symptom of COVID-19 in a previously healthy patient. We report the case of a 53-year-old patient with COVID-19 whose first clinical presentation was acute icteric hepatitis, several days before the development of others symptoms. During the pandemic, we suggest that patients with acute hepatitis be considered as COVID-19 suspects, tested and isolated.


Asunto(s)
COVID-19 , Hepatitis , Ictericia , Enfermedad Aguda , Hepatitis/diagnóstico , Humanos , Persona de Mediana Edad , SARS-CoV-2
9.
Front Med (Lausanne) ; 7: 584036, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33195335

RESUMEN

Background: The coronavirus infectious disease-2019 (COVID-19) pandemic has led to an unprecedented shortage of healthcare resources, primarily personal protective equipment like surgical masks, and N95/filtering face piece type 2 (FFP2) respirators. Objective: Reuse of surgical masks and N95/FFP2 respirators may circumvent the supply chain constraints and thus overcome mass shortage. Methods, design, setting, and measurement: Herein, we tested the effects of dry- and moist-air controlled heating treatment on structure and chemical integrity, decontamination yield, and filtration performance of surgical masks and FFP2 respirators. Results: We found that treatment in a climate chamber at 70°C during 1 h with 75% humidity rate was adequate for enabling substantial decontamination of both respiratory viruses, oropharyngeal bacteria, and model animal coronaviuses, while maintaining a satisfying filtering capacity. Limitations: Further studies are now required to confirm the feasibility of the whole process during routine practice. Conclusion: Our findings provide compelling evidence for the recycling of pre-used surgical masks and N95/FFP2 respirators in case of imminent mass shortfall.

10.
J Mol Biol ; 432(13): 3802-3819, 2020 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-32371046

RESUMEN

Hepatitis B virus (HBV) core protein (HBc) is essential to the formation of the HBV capsid. HBc contains two domains: the N-terminal domain corresponding to residues 1-140 essential to form the icosahedral shell and the C-terminal domain corresponding to a basic and phosphorylated peptide, and required for DNA replication. The role of these two domains for HBV capsid assembly was essentially studied in vitro with HBc purified from mammalian or non-mammalian cell lysates, but their respective role in living cells remains to be clarified. We therefore investigated the assembly of the HBV capsid in Huh7 cells by combining fluorescence lifetime imaging microscopy/Förster's resonance energy transfer, fluorescence correlation spectroscopy and transmission electron microscopy approaches. We found that wild-type HBc forms oligomers early after transfection and at a sub-micromolar concentration. These oligomers are homogeneously diffused throughout the cell. We quantified a stoichiometry ranging from ~170 to ~230 HBc proteins per oligomer, consistent with the visualization of eGFP-containingHBV capsid shaped as native capsid particles by transmission electron microscopy. In contrast, no assembly was observed when HBc-N-terminal domain was expressed. This highlights the essential role of the C-terminal domain to form capsid in mammalian cells. Deletion of either the third helix or of the 124-135 residues of HBc had a dramatic impact on the assembly of the HBV capsid, inducing the formation of mis-assembled oligomers and monomers, respectively. This study shows that our approach using fluorescent derivatives of HBc is an innovative method to investigate HBV capsid formation.


Asunto(s)
Virus de la Hepatitis B/genética , Hepatitis B/genética , Proteínas del Núcleo Viral/genética , Ensamble de Virus/genética , Cápside/metabolismo , Replicación del ADN , Hepatitis B/virología , Virus de la Hepatitis B/patogenicidad , Humanos , Dominios Proteicos/genética , ARN Viral/genética , Replicación Viral/genética
12.
J Virol ; 94(6)2020 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-31896595

RESUMEN

Most people are asymptomatic carriers of the BK polyomavirus (BKPyV), but the mechanisms of persistence and immune evasion remain poorly understood. Furthermore, BKPyV is responsible for nephropathies in kidney transplant recipients. Unfortunately, the sole therapeutic option is to modulate immunosuppression, which increases the risk of transplant rejection. Using iodixanol density gradients, we observed that Vero and renal proximal tubular epithelial infected cells release two populations of infectious particles, one of which cosediments with extracellular vesicles (EVs). Electron microscopy confirmed that a single vesicle could traffic tens of viral particles. In contrast to naked virions, the EV-associated particles (eBKPyVs) were not able to agglutinate red blood cells and did not use cell surface sialylated glycans as an attachment factor, demonstrating that different entry pathways were involved for each type of infectious particle. However, we also observed that naked BKPyV and eBKPyV were equally sensitive to neutralization by the serum of a seropositive patient or commercially available polyvalent immunoglobulin preparations, which occurred at a postattachment step, after endocytosis. In conclusion, our work shows a new mechanism that likely plays a critical role during the primary infection and in the persistence, but also the reactivation, of BKPyV.IMPORTANCE Reactivation of BKPyV is responsible for nephropathies in kidney transplant recipients, which frequently lead to graft loss. The mechanisms of persistence and immune evasion used by this virus remain poorly understood, and a therapeutic option for transplant patients is still lacking. Here, we show that BKPyV can be released into EVs, enabling viral particles to infect cells using an alternative entry pathway. This provides a new view of BKPyV pathogenesis. Even though we did not find any decreased sensitivity to neutralizing antibodies when comparing EV-associated particles and naked virions, our study also raises important questions about developing prevention strategies based on the induction or administration of neutralizing antibodies. Deciphering this new release pathway could enable the identification of therapeutic targets to prevent BKPyV nephropathies. It could also lead to a better understanding of the pathophysiology of other polyomaviruses that are associated with human diseases.


Asunto(s)
Virus BK/metabolismo , Vesículas Extracelulares/metabolismo , Infecciones por Polyomavirus/transmisión , Animales , Virus BK/genética , Virus BK/patogenicidad , Chlorocebus aethiops , Vesículas Extracelulares/genética , Vesículas Extracelulares/virología , Infecciones por Polyomavirus/genética , Infecciones por Polyomavirus/metabolismo , Células Vero
13.
Eur J Emerg Med ; 26(6): 458-461, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31609876

RESUMEN

BACKGROUNDS: Paramount to guide the diagnostic strategy, the prevalence of pulmonary embolism in patients with syncope and no other symptoms is uncertain. We aimed to assess the pulmonary embolism prevalence in patients that present to the emergency department (ED) with syncope and no chest pain nor dyspnea. METHODS: Multicenter prospective cohort study in seven EDs in France. Adult patients who presented to the ED with syncope (transient loss of consciousness) were included. Patients with chest pain or dyspnea were excluded. Included patients underwent formal work-up for pulmonary embolism, including D-dimer testing and further imaging if positive. Cases of pulmonary embolism were adjudicated by two independent expert radiologists with the review of imaging studies. Secondary objectives included the pulmonary embolism prevalence in the subgroup of patients with cancer, in patients with negative Pulmonary Embolism Rule Out criteria (PERC) score, and according to the clinical probability assessed either by Wells or revised Geneva score. RESULTS: We analyzed 411 patients, in whom 128 (31%) underwent a computed tomographic pulmonary angiogram and 9 (2%) a ventilation-perfusion scan. A pulmonary embolism was confirmed in nine patients (prevalence of 2.2%, 95% confidence interval, 1.1-4.3%), including one subsegmental pulmonary embolism. This prevalence was of 18% (3-52%) in patients with cancer and 0.7% (0.1-4%) in PERC negative patients. CONCLUSION: In our sample of patients with isolated syncope, the prevalence of pulmonary embolism was 2.2%. This value is not sufficiently low to negate the requirement for a formal work up in the ED, even in the absence of chest pain or dyspnea. However, the large confidence interval precludes any strong conclusion.


Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Embolia Pulmonar/diagnóstico , Síncope/etiología , Adulto , Anciano , Anciano de 80 o más Años , Angiografía por Tomografía Computarizada , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Pulmón/irrigación sanguínea , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Embolia Pulmonar/complicaciones , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/epidemiología
14.
Ann Emerg Med ; 74(4): 580-591, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30982631

RESUMEN

STUDY OBJECTIVE: Efforts to reduce unnecessary and unnecessarily long antibiotic treatment for community-acquired pneumonia have been attempted through use of procalcitonin and through guidelines based on serial clinical assessment. Our aim is to compare guideline-based clinical assessment- and procalcitonin algorithm-guided antibiotic use among patients with community-acquired pneumonia. METHODS: We performed a pragmatic, randomized, multicenter trial from November 2012 to April 2015 at 12 French hospitals. We included emergency department (ED) patients older than 18 years with community-acquired pneumonia. Patients were randomly assigned to either the procalcitonin-guided or clinical assessment group. In accordance with past studies, we hypothesized that serial clinical assessment would be superior to procalcitonin-guided care. The primary outcome was antibiotic duration, and secondary outcomes included rates of antibiotic duration less than or equal to 5 days, and clinical success and combined serious adverse outcomes at 30 days in the intention-to-treat population. RESULTS: Of 370 eligible patients, 285 (77%) were randomly assigned to either clinical assessment- (n=143) or procalcitonin-guided care (n=142). Median age was 67 years (range 18 to 93 years) and 40% of patients were deemed to have Pneumonia Severity Index class IV or V. Procalcitonin algorithm adherence was 76%. Antibiotic duration was not significantly different between clinical assessment- and procalcitonin-guided groups (median 9 versus 10 days, respectively). Clinical success rate was 92% in each group and serious adverse outcome rates were similar (15% versus 20%, respectively). CONCLUSION: Guideline-based serial clinical assessment did not reduce antibiotic exposure compared with procalcitonin-guided care among ED patients with community-acquired pneumonia. The strategies were similar in terms of duration of antibiotic use and clinical outcomes.


Asunto(s)
Combinación Amoxicilina-Clavulanato de Potasio/administración & dosificación , Antibacterianos/administración & dosificación , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Neumonía Bacteriana/tratamiento farmacológico , Polipéptido alfa Relacionado con Calcitonina/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Esquema de Medicación , Femenino , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Resultado del Tratamiento , Procedimientos Innecesarios , Adulto Joven
15.
Nat Commun ; 10(1): 465, 2019 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-30692527

RESUMEN

Alzheimer's disease (AD) is a heterogeneous disorder with multiple etiologies. Harnessing the immune system by blocking the programmed cell death receptor (PD)-1 pathway in an amyloid beta mouse model was shown to evoke a sequence of immune responses that lead to disease modification. Here, blocking PD-L1, a PD-1 ligand, was found to have similar efficacy to that of PD-1 blocking in disease modification, in both animal models of AD and of tauopathy. Targeting PD-L1 in a tau-driven disease model resulted in increased immunomodulatory monocyte-derived macrophages within the brain parenchyma. Single cell RNA-seq revealed that the homing macrophages expressed unique scavenger molecules including macrophage scavenger receptor 1 (MSR1), which was shown here to be required for the effect of PD-L1 blockade in disease modification. Overall, our results demonstrate that immune checkpoint blockade targeting the PD-1/PD-L1 pathway leads to modification of common factors that go awry in AD and dementia, and thus can potentially provide an immunotherapy to help combat these diseases.


Asunto(s)
Antígeno B7-H1/metabolismo , Disfunción Cognitiva/metabolismo , Macrófagos/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Tauopatías/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Animales , Anticuerpos Bloqueadores/farmacología , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Encéfalo/inmunología , Encéfalo/metabolismo , Disfunción Cognitiva/genética , Modelos Animales de Enfermedad , Humanos , Macrófagos/inmunología , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos , Ratones Transgénicos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Tauopatías/genética
16.
Rev Med Virol ; 29(1): e2019, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30411832

RESUMEN

Transmission electron microscopy (TEM) is the only imaging technique allowing the direct visualization of viruses, due to its nanometer-scale resolution. Between the 1960s and 1990s, TEM contributed to the discovery of many types of viruses and served as a diagnostic tool for identifying viruses directly in biological samples, either in suspension or in sections of tissues or mammalian cells grown in vitro in contact with clinical samples. The diagnosis of viral infections improved considerably during the 1990s, with the advent of highly sensitive techniques, such as enzyme-linked immunosorbent assay (ELISA) and PCR, rendering TEM obsolete for this purpose. However, the last 20 years have demonstrated the utility of this technique in particular situations, due to its "catch-all" nature, making diagnosis possible through visualization of the virus, without the need of prior assumptions about the infectious agent sought. Thus, in several major outbreaks in which molecular techniques failed to identify the infectious agent, TEM provided the answer. TEM is also still occasionally used in routine diagnosis to characterize infections not diagnosed by molecular assays. It is also used to check the microbiological safety of biological products. Many biopharmaceuticals are produced in animal cells that might contain little-known, difficult-to-detect viruses. In this context, the "catch-all" properties of TEM make it possible to document the presence of viruses or virus-like particles in these products.


Asunto(s)
Contención de Riesgos Biológicos/métodos , Pruebas Diagnósticas de Rutina/métodos , Microscopía Electrónica de Transmisión/métodos , Virión/ultraestructura , Virosis/diagnóstico , Virus/aislamiento & purificación , Animales , Transmisión de Enfermedad Infecciosa/prevención & control , Humanos , Tecnología Farmacéutica/métodos , Virus/ultraestructura
17.
JAMA ; 319(6): 559-566, 2018 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-29450523

RESUMEN

Importance: The safety of the pulmonary embolism rule-out criteria (PERC), an 8-item block of clinical criteria aimed at ruling out pulmonary embolism (PE), has not been assessed in a randomized clinical trial. Objective: To prospectively validate the safety of a PERC-based strategy to rule out PE. Design, Setting, and Patients: A crossover cluster-randomized clinical noninferiority trial in 14 emergency departments in France. Patients with a low gestalt clinical probability of PE were included from August 2015 to September 2016, and followed up until December 2016. Interventions: Each center was randomized for the sequence of intervention periods. In the PERC period, the diagnosis of PE was excluded with no further testing if all 8 items of the PERC rule were negative. Main Outcomes and Measures: The primary end point was the occurrence of a thromboembolic event during the 3-month follow-up period that was not initially diagnosed. The noninferiority margin was set at 1.5%. Secondary end points included the rate of computed tomographic pulmonary angiography (CTPA), median length of stay in the emergency department, and rate of hospital admission. Results: Among 1916 patients who were cluster-randomized (mean age 44 years, 980 [51%] women), 962 were assigned to the PERC group and 954 were assigned to the control group. A total of 1749 patients completed the trial. A PE was diagnosed at initial presentation in 26 patients in the control group (2.7%) vs 14 (1.5%) in the PERC group (difference, 1.3% [95% CI, -0.1% to 2.7%]; P = .052). One PE (0.1%) was diagnosed during follow-up in the PERC group vs none in the control group (difference, 0.1% [95% CI, -∞ to 0.8%]). The proportion of patients undergoing CTPA in the PERC group vs control group was 13% vs 23% (difference, -10% [95% CI, -13% to -6%]; P < .001). In the PERC group, rates were significantly reduced for the median length of emergency department stay (mean reduction, 36 minutes [95% CI, 4 to 68]) and hospital admission (difference, 3.3% [95% CI, 0.1% to 6.6%]). Conclusions and Relevance: Among very low-risk patients with suspected PE, randomization to a PERC strategy vs conventional strategy did not result in an inferior rate of thromboembolic events over 3 months. These findings support the safety of PERC for very low-risk patients presenting to the emergency department. Trial Registration: clinicaltrials.gov Identifier: NCT02375919.


Asunto(s)
Protocolos Clínicos , Técnicas de Apoyo para la Decisión , Servicio de Urgencia en Hospital , Embolia Pulmonar/diagnóstico , Adulto , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Riesgo , Tromboembolia/epidemiología
18.
Urol Int ; 101(4): 478-480, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29050000

RESUMEN

Varicocele is one of the causes of male infertility. Treatment aims to improve the chance of conception despite lasting controversies about benefits of varicocele repair on fertility. Many techniques have been described for varicocele management including the antegrade scrotal sclerotherapy (ASS). Interestingly, ASS is often presented as a safe, easy, and cost-effective procedure with low recurrence and complication rates. However, we report the first case of spinal cord paralysis following ASS probably due to embolization of venous anastomoses between left spermatic and ascending lumbar veins, which were undetected at preoperative phlebography. Based on this case and recent literature, we raise questions about the safety of ASS and try to figure out what would be the best way to improve the detectability of potential harmful anastomoses at preoperative phlebography.


Asunto(s)
Escleroterapia , Cordón Espermático/anatomía & histología , Traumatismos de la Médula Espinal/complicaciones , Varicocele/cirugía , Anastomosis Quirúrgica , Análisis Costo-Beneficio , Humanos , Masculino , Flebografía , Prevalencia , Recurrencia , Escroto , Cordón Espermático/diagnóstico por imagen , Médula Espinal , Venas/anatomía & histología , Venas/diagnóstico por imagen , Adulto Joven
19.
Scand J Trauma Resusc Emerg Med ; 25(1): 78, 2017 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-28807040

RESUMEN

BACKGROUND: Upper gastrointestinal bleeding (UGB) is common in emergency departments (EDs) and can be caused by many eso-gastro-duodenal lesions. Most available epidemiological data and data on the management of UGB comes from specialized departments (intensive care units or gastroenterology departments), but little is known from the ED perspective. We aimed to determine the distribution of symptoms revealing UGB in EDs and the hemorrhagic lesions identified by endoscopy. We also describe the characteristics of patients consulting for UGB, UGB management in the ED and patients outcomes. METHOD: This was a prospective, observational, multicenter study covering 4 consecutive days in November 2013. Participating EDs were part of the Initiatives de Recherche aux Urgences network coordinated by the French Society of Emergency Medicine. All patients with suspected UGB in these EDs were included. RESULTS: In total, 110 EDs participated, including 194 patients with suspected UGB (median age 66 years [Q1-Q3: 51-81]). Overall, 104 patients (54%) had hematemesis and 75 (39%) melena. Endoscopy revealed lesions in 121 patients, mainly gastroduodenal ulcer or ulcerations (41%) or bleeding lesions due to portal hypertension (20%). The final diagnosis of UGB was reversed by endoscopy in only 3% of cases. Overall, 67 patients (35%) had at least one severity sign. Twenty-one patients died (11%); 40 (21%) were hospitalized in intensive care units and 126 (65%) in medicine departments; 28 (14%) were outpatients. Mortality was higher among patients with clinical and biological severity signs. CONCLUSION: Most of the UGB cases in EDs are revealed by hematemesis. The emergency physician diagnosis of UGB is rarely challenged by the endoscopic findings.


Asunto(s)
Servicio de Urgencia en Hospital , Endoscopía , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Francia , Hemorragia Gastrointestinal/terapia , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Evaluación de Síntomas
20.
Am J Public Health ; 106(5): 893-8, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26985613

RESUMEN

OBJECTIVES: To determine whether homeless patients experience suboptimal care in the emergency department (ED) by the provision of fewer health care resources. METHODS: We conducted a prospective multicenter cohort study in 30 EDs in France. During 72 hours in March 2015, all homeless patients that visited the participating EDs were included in the study. The primary health care service measure was the order by the physician of a diagnostic investigation or provision of a treatment in the ED. Secondary measures of health care services included ED waiting time, number and type of investigations per patient, treatment in the ED, and discharge disposition. RESULTS: A total of 254 homeless patients and 254 nonhomeless patients were included. After excluding homeless patients that attended the ED for the sole purpose of housing, we analyzed 214 homeless and 214 nonhomeless. We found no significant difference between the 2 groups in terms of health care resource consumption, and for our secondary endpoints. CONCLUSIONS: We did not find significant differences in the level of medical care delivered in French EDs to homeless patients compared with matched nonhomeless patients.


Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Servicio de Urgencia en Hospital/normas , Personas con Mala Vivienda/estadística & datos numéricos , Calidad de la Atención de Salud/estadística & datos numéricos , Adulto , Anciano , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Alta del Paciente/estadística & datos numéricos , Estudios Prospectivos , Indicadores de Calidad de la Atención de Salud , Índice de Severidad de la Enfermedad , Listas de Espera
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