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1.
Nature ; 609(7926): 282-286, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36071189

RESUMEN

The recent discoveries of two-dimensional (2D) magnets1-6 and their stacking into van der Waals structures7-11 have expanded the horizon of 2D phenomena. One exciting application is to exploit coherent magnons12 as energy-efficient information carriers in spintronics and magnonics13,14 or as interconnects in hybrid quantum systems15-17. A particular opportunity arises when a 2D magnet is also a semiconductor, as reported recently for CrSBr (refs. 18-20) and NiPS3 (refs. 21-23) that feature both tightly bound excitons with a large oscillator strength and potentially long-lived coherent magnons owing to the bandgap and spatial confinement. Although magnons and excitons are energetically mismatched by orders of magnitude, their coupling can lead to efficient optical access to spin information. Here we report strong magnon-exciton coupling in the 2D A-type antiferromagnetic semiconductor CrSBr. Coherent magnons launched by above-gap excitation modulate the exciton energies. Time-resolved exciton sensing reveals magnons that can coherently travel beyond seven micrometres, with a coherence time of above five nanoseconds. We observe these exciton-coupled coherent magnons in both even and odd numbers of layers, with and without compensated magnetization, down to the bilayer limit. Given the versatility of van der Waals heterostructures, these coherent 2D magnons may be a basis for optically accessible spintronics, magnonics and quantum interconnects.

2.
Nat Immunol ; 15(12): 1143-51, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25344724

RESUMEN

Activated CD8(+) T cells choose between terminal effector cell (TEC) or memory precursor cell (MPC) fates. We found that the signaling receptor Notch controls this 'choice'. Notch promoted the differentiation of immediately protective TECs and was correspondingly required for the clearance of acute infection with influenza virus. Notch activated a major portion of the TEC-specific gene-expression program and suppressed the MPC-specific program. Expression of Notch was induced on naive CD8(+) T cells by inflammatory mediators and interleukin 2 (IL-2) via pathways dependent on the metabolic checkpoint kinase mTOR and the transcription factor T-bet. These pathways were subsequently amplified downstream of Notch, creating a positive feedback loop. Notch thus functions as a central hub where information from different sources converges to match effector T cell differentiation to the demands of an infection.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Diferenciación Celular/inmunología , Receptores Notch/inmunología , Subgrupos de Linfocitos T/inmunología , Inmunidad Adaptativa/inmunología , Traslado Adoptivo , Animales , Linfocitos T CD8-positivos/citología , Separación Celular , Citometría de Flujo , Virus de la Influenza A , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Infecciones por Orthomyxoviridae/inmunología , Reacción en Cadena en Tiempo Real de la Polimerasa , Subgrupos de Linfocitos T/citología , Transcriptoma , Transducción Genética
3.
Cancer ; 129(7): 981-985, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36585394

RESUMEN

In the year 2021, there were three new Food and Drug Administration approvals for all leukemia types: asciminib (Scemblix) for chronic myeloid leukemia, brexucabtagene autoleucel (Tecartus) for relapsed/refractory B-cell acute lymphocytic leukemia, and asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze) for acute lymphocytic leukemia. This is down from 2017-2018 when eight new therapies were approved for acute myeloid leukemia alone. However, this decrease from prior years does not imply that little progress was made in our understanding or treatment of leukemias in 2021. Asciminib and brexucabtagene autoleucel, in particular, are representative of major developing trends. Asciminib, a targeted therapy, is only one of many drugs in development that are products of a bedside-to-bench approach fueled by new sequencing and other genetic technologies that have greatly increased our understanding of the biology behind hematologic diseases. Brexucabtagene autoleucel, an adoptive cell therapy, is the newest of several similar treatments for B cell-associated neoplasms, and it is representative of a massive push to develop novel immunotherapies for a broad range of hematologic malignancies. This commentary reviews the development of asciminib and brexucabtagene autoleucel and describes other major advances in the associated fields of targeted therapy and immunotherapy for leukemias.


Asunto(s)
Neoplasias Hematológicas , Leucemia Linfocítica Crónica de Células B , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Linfocitos T , Neoplasias Hematológicas/terapia , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Inmunoterapia Adoptiva
4.
Haematologica ; 108(10): 2616-2625, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37051756

RESUMEN

Venetoclax+azacitidine is the standard of care for newly-diagnosed patients with acute myeloid leukemia (AML) for whom intensive chemotherapy is inappropriate. Efforts to optimize this regimen are necessary. We designed a clinical trial to investigate two hypotheses: i) higher doses of venetoclax are tolerable and more effective, and ii) azacitidine can be discontinued after deep remissions. Forty-two newly diagnosed AML patients were enrolled in the investigator-initiated High Dose Discontinuation Azacitidine+Venetoclax (HiDDAV) Study (clinicaltrials gov. Identifier: NCT03466294). Patients received one to three "induction" cycles of venetoclax 600 mg daily with azacitidine. Responders received MRD-positive or MRDnegative "maintenance" arms: azacitidine with 400 mg venetoclax or 400 mg venetoclax alone, respectively. The toxicity profile of HiDDAV was similar to 400 mg venetoclax. The overall response rate was 66.7%; the duration of response (DOR), event-free survival (EFS) and overall survival were 12.9, 7.8 and 9.8 months, respectively. The MRD negativity rate was 64.3% by flow cytometry and 25.0% when also measured by droplet digital polymerase chain recation. MRD-negative patients by flow cytometry had improved DOR and EFS; more stringent measures of MRD negativity were not associated with improved OS, DOR or EFS. Using MRD to guide azacitidine discontinuation did not lead to improved DOR, EFS or OS compared to patients who discontinued azacitidine without MRD guidance. Within the context of this study design, venetoclax doses >400 mg with azacitidine were well tolerated but not associated with discernible clinical improvement, and MRD may not assist in recommendations to discontinue azacitidine. Other strategies to optimize, and for some patients, de-intensify, venetoclax+azacitidine regimens are needed.


Asunto(s)
Azacitidina , Leucemia Mieloide Aguda , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Neoplasia Residual/tratamiento farmacológico
5.
Nano Lett ; 22(15): 6091-6097, 2022 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-35877983

RESUMEN

Skyrmion racetrack memories are highly attractive for next-generation data storage technologies. Skyrmions are noncollinear spin textures stabilized by chiral interactions. To achieve a fast-operating memory device, it is critical to move skyrmions at high speeds. The skyrmion dynamics induced by spin-orbit torques (SOTs) in the commonly studied ferromagnetic films is hindered by strong pinning effects and a large skyrmion Hall effect causing deflection of the skyrmion toward the racetrack edge, which can lead to information loss. Here, we investigate the current-induced nucleation and motion of skyrmions in ferrimagnetic Pt/CoGd/(W or Ta) thin films. We first reveal field-free skyrmion nucleation mediated by Joule heating. We then achieve fast skyrmion motion driven by SOTs with velocities as high as 610 m s-1 and a small skyrmion Hall angle |θSkHE| ≲ 3°. Our results show that ferrimagnets are better candidates for fast skyrmion-based memory devices with low risk of information loss.

6.
Phys Rev Lett ; 128(24): 247204, 2022 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-35776458

RESUMEN

The effect of spin currents on the magnetic order of insulating antiferromagnets (AFMs) is of fundamental interest and can enable new applications. Toward this goal, characterizing the spin-orbit torques (SOTs) associated with AFM-heavy-metal (HM) interfaces is important. Here we report the full angular dependence of the harmonic Hall voltages in a predominantly easy-plane AFM, epitaxial c-axis oriented α-Fe_{2}O_{3} films, with an interface to Pt. By modeling the harmonic Hall signals together with the α-Fe_{2}O_{3} magnetic parameters, we determine the amplitudes of fieldlike and dampinglike SOTs. Out-of-plane field scans are shown to be essential to determining the dampinglike component of the torques. In contrast to ferromagnetic-heavy-metal heterostructures, our results demonstrate that the fieldlike torques are significantly larger than the dampinglike torques, which we correlate with the presence of a large imaginary component of the interface spin-mixing conductance. Our work demonstrates a direct way of characterizing SOTs in AFM-HM heterostructures.

7.
BMC Vet Res ; 17(1): 299, 2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34488771

RESUMEN

BACKGROUND: Avoidance of unnecessary antimicrobial administration is a key tenet of antimicrobial stewardship; knowing the optimal duration of therapy obviates over-treatment. However, little research has been performed to establish course lengths for common canine infections. In clinical practice, antimicrobial therapy is frequently prescribed in dogs presenting lower urinary tract signs (haematuria, pollakiuria and dysuria/stranguria). The proposed length of treatment in International Consensus guidelines has decreased with each iteration, but these recommendations remain arbitrary and largely extrapolated from experience in people. METHODS: The objective of this prospective, multi-centre study is to find the shortest course duration that is non-inferior to the standard duration of 7 days of amoxicillin/clavulanate in terms of clinical outcomes for female dogs with lower urinary tract signs consistent with a urinary tract infection. An electronic data capture platform will be used by participating veterinarians working in clinical practice in the United Kingdom. Eligible dogs must be female, aged between 6 months and 10 years and have lower urinary tract signs of up to seven days' duration. Enrolment will be offered in cases where the case clinician intends to prescribe antimicrobial therapy. Automatic pseudo-randomisation to treatment group will be based on the day of presentation (Monday-Friday); all antimicrobial courses will be completed on the Sunday after presentation generating different treatment durations. Follow-up data will be collected 1, 8 and 22-26 days after completion of the antimicrobial course to ensure effective safety netting, and to monitor short-term outcome and recurrence rates. Informed owner consent will be obtained in all cases. The study is approved by the Ethical Review Board of the University of Nottingham and has an Animal Test Certificate from the Veterinary Medicine's Directorate. DISCUSSION: This study has been designed to mirror current standards of clinical management; conclusions should therefore, be widely applicable and guide practising veterinarians in their antimicrobial decision-making process. A duration-response curve will be created allowing determination of the optimal treatment duration for the management of female dogs with lower urinary tract signs. It is hoped that these results will contribute valuable information to improve future antimicrobial stewardship as part of a wider one-health perspective.


Asunto(s)
Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Antibacterianos/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Infecciones Urinarias/veterinaria , Animales , Perros , Duración de la Terapia , Femenino , Estudios Prospectivos , Reino Unido , Infecciones Urinarias/tratamiento farmacológico
8.
Phys Rev Lett ; 124(19): 197204, 2020 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-32469573

RESUMEN

An important goal of spintronics is to covert a charge current into a spin current with a controlled spin polarization that can exert torques on an adjacent magnetic layer. Here we demonstrate such torques in a two ferromagnet system. A CoNi multilayer is used as a spin current source in a sample with structure CoNi/Au/CoFeB. Spin torque ferromagnetic resonance is used to measure the torque on the CoFeB layer. The response as a function of the applied field angle and current is consistent with the symmetry expected for a torque produced by the planar Hall effect originating in CoNi. We find the strength of this effect to be comparable to that of the spin Hall effect in platinum, indicating that the planar Hall effect holds potential as a spin current source with a controllable polarization direction.

9.
J Minim Invasive Gynecol ; 27(1): 141-147, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-30885782

RESUMEN

STUDY OBJECTIVE: To examine whether existing quality of health outcome measures can be used to predict or have an association with nonresponse surgery for endometriosis. DESIGN: Retrospective cohort study. SETTINGS: Single endometriosis referral center. PATIENTS: Women (n = 198) undergoing surgery for endometriosis. INTERVENTIONS: Validated health questionnaires and visual analogue scales. MEASUREMENTS AND MAIN RESULTS: Patients were given validated health questionnaires, including Endometriosis Health Profile 30, Gastrointestinal Quality of Life Index, EuroQol-5, Hospital Anxiety and Depression Scale, preoperatively and at 12 months after full surgical excision of endometriosis. Visual analogue scales were also used that measured dyschezia, dysmenorrhea, dyspareunia, and chronic pelvic pain. Surgical management was dependent on severity of disease. Superficial disease was treated by laparoscopic peritoneal excision or laser ablation. Deep infiltrating disease involving the bowel was excised completely together with laparoscopic bowel surgery (shave, disc, or segmental resection) with/without concomitant total hysterectomy and bilateral salpingo-oophorectomy. Nonresponders were defined as women who failed to demonstrate an improvement in pain scores 12 months postoperatively. We examined preoperative and postoperative questionnaires, visual analogue scores, and other variables such as age at onset of symptoms, type of surgery, and the presence of postoperative complications comparing responder and nonresponder women to identify the factors associated with nonresponse. Of 102 women treated for superficial endometriosis, 25 (24.51%) were nonresponders. No factors were associated with nonresponse at 12 months. Of 96 women treated for severe endometriosis involving the bowel, 10 (10.41%) were nonresponders. Nonresponders had significantly less preoperative pain (p = .031) and feeling of control (p = .015) than responders. There was no association between nonresponders and women who underwent a hysterectomy with bilateral salpingo-oophorectomy or those with complications. Radical bowel surgery (resection) was associated with nonresponders. CONCLUSION: Minimal preoperative factors are associated with nonresponse for women having surgery for endometriosis. The severity of pain experienced by women with endometriosis may be used to predict their response to surgery.


Asunto(s)
Endometriosis/cirugía , Enfermedades Intestinales/cirugía , Enfermedades Peritoneales/cirugía , Complicaciones Posoperatorias/diagnóstico , Adulto , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Procedimientos Quirúrgicos del Sistema Digestivo/estadística & datos numéricos , Endometriosis/epidemiología , Femenino , Humanos , Enfermedades Intestinales/epidemiología , Laparoscopía/efectos adversos , Laparoscopía/estadística & datos numéricos , Persona de Mediana Edad , Enfermedades Peritoneales/epidemiología , Complicaciones Posoperatorias/epidemiología , Periodo Preoperatorio , Pronóstico , Calidad de Vida , Estudios Retrospectivos , Factores de Riesgo , Encuestas y Cuestionarios/estadística & datos numéricos , Insuficiencia del Tratamiento
10.
BMC Med Ethics ; 21(1): 98, 2020 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-33059675

RESUMEN

BACKGROUND: The Arab population in Israel is a minority ethnic group with its own distinct cultural subgroups. Minority populations are known to underutilize genetic tests and counseling services, thereby undermining the effectiveness of these services among such populations. However, the general and culture-specific reasons for this underutilization are not well defined. Moreover, Arab populations and their key cultural-religious subsets (Muslims, Christians, and Druze) do not reside exclusively in Israel, but are rather found as a minority group in many European and North American countries. Therefore, focusing on the Arab population in Israel allows for the examination of attitudes regarding genetic testing and counseling among this globally important ethnic minority population. METHODS: We used a qualitative research method, employing individual interviews with 18 women of childbearing age from three religious subgroups (i.e., Druze, Muslim, and Christian) who reside in the Acre district, along with focus group discussions with healthcare providers (HCPs; 9 nurses and 7 genetic counselors) working in the same geographical district. RESULTS: A general lack of knowledge regarding the goals and practice of genetic counseling resulting in negative preconceptions of genetic testing was identified amongst all counselees. Counselors' objective of respecting patient autonomy in decision-making, together with counselees' misunderstanding of genetic risk data, caused uncertainty, frustration, and distrust. In addition, certain interesting variations were found between the different religious subgroups regarding their attitudes to genetic counseling. CONCLUSIONS: The study highlights the miscommunications between HCPs, particularly counselors from the majority ethno-cultural group, and counselees from a minority ethno-cultural group. The need for nuanced understanding of the complex perspectives of minority ethno-cultural groups is also emphasized. Such an understanding may enhance the effectiveness of genetic testing and counseling among the Arab minority group while also genuinely empowering the personal autonomy of counselees from this minority group in Israel and other countries.


Asunto(s)
Asesoramiento Genético , Grupos Minoritarios , Árabes/genética , Consejo , Femenino , Pruebas Genéticas , Humanos , Israel , América del Norte , Investigación Cualitativa
11.
J Obstet Gynaecol ; 40(1): 83-89, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31328629

RESUMEN

A Cross-sectional study was undertaken at a specialist centre in the United Kingdom investigating duration and causes of delay in the diagnosis of endometriosis. One hundred and one women completed a self-reported questionnaire containing 20 items about their psychosocial, symptoms and experiences. The statistical analysis included a Mann-Whitney U test. A p value of .05 was considered statistically significant. The Spearman's rank correlation was also calculated. Overall, there was a median delay of 8 years (Q1-Q3: 3-14) from the onset of symptoms to a diagnosis of endometriosis. Factors such as menstrual cramps in adolescence, presence of rectovaginal endometriosis, normalisation of pain and the attitudes of health professionals contributed to a delayed diagnosis (p values<.05). There was a negative correlation indicating the earlier the onset of symptoms, the greater the delay to diagnosis (Spearman's Rank Correlation Coefficient -0.63, p<.01). The results of this study highlight a considerable diagnostic delay associated with endometriosis and the need for clinician education and public awareness.Impact statementWhat is already known on this subject? The diagnostic delay of 7-9 years with endometriosis has been reported globally. In an effort to standardise surgical treatment, improve outcomes, and shorten delays specialist endometriosis centres were introduced in 2011. There has been no recent quality improvement assessment since the establishment of such centres.What do the results of this study add? This is the most recent evaluation in the United Kingdom since the introduction of specialist endometriosis centres. There is a considerable diagnostic delay associated endometriosis in the United Kingdom with a median of 8 years. The delays seem not to have improved over the last two decades. We have identified medical and psychosocial factors that may contribute to such delays. These include factors such as menstrual cramps in adolescence, presence of rectovaginal endometriosis, normalisation of pain and attitudes of health professionals contribute to a delayed diagnosis.What are the implications of these findings for clinical practice and/or further research? The results of this study, highlight the need for clinician education and public awareness to decrease the long term-morbidity and complications that result from untreated endometriosis.


Asunto(s)
Diagnóstico Tardío , Endometriosis/diagnóstico , Adolescente , Adulto , Actitud Frente a la Salud , Estudios Transversales , Femenino , Humanos , Umbral del Dolor , Encuestas y Cuestionarios , Factores de Tiempo , Reino Unido , Adulto Joven
12.
Nat Mater ; 22(9): 1051-1052, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37644226
13.
J Obstet Gynaecol ; 39(3): 345-348, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30422734

RESUMEN

The aim of this study was to evaluate the practices of laparoscopic specimen retrieval among Gynaecologists in the United Kingdom and to determine any variation in practice. A survey of Consultant Gynaecologist members of the British Society of Gynaecological Endoscopy (BSGE) was conducted using Survey Monkey™. Of the 460 registered consultants, 187 (40%) responded to the questionnaire. Sixty-two percent (62%) of the respondents considered themselves to be advanced laparoscopic surgeons whilst 34% considered themselves to be intermediate laparoscopic surgeons. The umbilical port was the most commonly used port for specimen retrieval and it was used to remove 49% of ectopic pregnancies, 43% of ovarian cysts and 43% of endometrioma. Most respondents would not insert an extra port or extend the existing port just for the retrieval of a specimen. The level of laparoscopic experience and the gender did not affect the method of specimen retrieval in cases of ectopic pregnancies, endometrioma and ovarian cysts (p value >.05, not significant). The majority of respondents used power morcellation for a laparoscopic myomectomy (85% of respondents) and laparoscopic subtotal hysterectomy (93% of respondents), despite the recent concerns surrounding power morcellation. Impact statement What is already known on this subject? There is a paucity of literature regarding laparoscopic specimen retrieval in gynaecology. In view of recent controversy pertaining to the potential upstaging of leiomyosarcoma with morcellation, other methods of specimen retrieval are gaining an importance. What do the results of this study add? This study shows that the umbilical port is the most commonly used port for specimen retrieval among UK gynaecologists and that most gynaecologists would not insert an additional port purely for specimen retrieval. Most respondents would still use power morcellation for a laparoscopic myomectomy and subtotal hysterectomy, despite the recent concerns over morcellation and its safety. What are the implications of these findings for clinical practice and/or further research? This paper demonstrates the need for development of a database of morcellation practices to enable analysis of both benefits and potential adverse outcomes. This paper will also encourage future research and the audit of specimen retrieval.


Asunto(s)
Ginecología/métodos , Laparoscopía/métodos , Morcelación/psicología , Manejo de Especímenes/métodos , Análisis de Varianza , Actitud del Personal de Salud , Femenino , Humanos , Laparoscopía/estadística & datos numéricos , Morcelación/educación , Pautas de la Práctica en Medicina , Encuestas y Cuestionarios , Reino Unido
14.
Nanotechnology ; 29(32): 325302, 2018 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-29749959

RESUMEN

A spin-polarized current in a nanocontact to a magnetic film can create collective magnetic oscillations by compensating the magnetic damping. In particular, in materials with uniaxial magnetic anisotropy, droplet solitons have been observed-a self-localized excitation consisting of partially reversed magnetization that precesses coherently in the nanocontact region. It is also possible to generate topological droplet solitons, known as dynamical skyrmions (DSs). Here, we show that spin-polarized current thresholds for DS creation depend not only on the material's parameters but also on the initial magnetization state and the rise time of the spin-polarized current. We study the conditions that promote either droplet or DS formation and describe their stability in magnetic films without Dzyaloshinskii-Moriya interactions. The Oersted fields from the applied current, the initial magnetization state, and the rise time of the injected current can determine whether a droplet or a DS forms. DSs are found to be more stable than droplets. We also discuss electrical characteristics that can be used to distinguish these magnetic objects.

15.
BMC Pregnancy Childbirth ; 18(1): 156, 2018 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-29747597

RESUMEN

BACKGROUND: Antenatal depression is associated with harmful consequences for both the mother and child. One intervention that might be effective is participation in regular physical activity although data on this question in pregnant smokers is currently lacking. METHODS: Women were randomised to six-weekly sessions of smoking cessation behavioural-support, or to the same support plus 14 sessions combining treadmill exercise and physical activity consultations. RESULTS: Among 784 participants (mean gestation 16-weeks), EPDS was significantly higher in the physical activity group versus usual care at end-of-pregnancy (mean group difference (95% confidence intervals (CIs)): 0.95 (0.08 to 1.83). There was no significant difference at six-months postpartum. CONCLUSION: A pragmatic intervention to increase physical activity in pregnant smokers did not prevent depression at end-of-pregnancy or at six-months postpartum. More effective physical activity interventions are needed in this population. TRIAL REGISTRATION: Current Controlled Trials ISRCTN48600346 . The trial was prospectively registered on 21/07/2008.


Asunto(s)
Depresión/terapia , Ejercicio Físico/psicología , Complicaciones del Embarazo/terapia , Atención Prenatal/métodos , Cese del Hábito de Fumar/psicología , Adulto , Depresión/psicología , Femenino , Humanos , Embarazo , Complicaciones del Embarazo/psicología , Resultado del Tratamiento
16.
Gastroenterology ; 149(3): 681-91.e10, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26001928

RESUMEN

BACKGROUND & AIMS: The mechanisms of tissue destruction during progression of celiac disease are poorly defined. It is not clear how tissue stress and adaptive immunity contribute to the activation of intraepithelial cytotoxic T cells and the development of villous atrophy. We analyzed epithelial cells and intraepithelial cytotoxic T cells in family members of patients with celiac disease, who were without any signs of adaptive antigluten immunity, and in potential celiac disease patients, who have antibodies against tissue transglutaminase 2 in the absence of villous atrophy. METHODS: We collected blood and intestinal biopsy specimens from 268 patients at tertiary medical centers in the United States and Italy from 2004 to 2012. All subjects had normal small intestinal histology. Study groups included healthy individuals with no family history of celiac disease or antibodies against tissue transglutaminase 2 (controls), healthy family members of patients with celiac disease, and potential celiac disease patients. Intraepithelial cytotoxic T cells were isolated and levels of inhibitory and activating natural killer (NK) cells were measured by flow cytometry. Levels of heat shock protein (HSP) and interleukin 15 were measured by immunohistochemistry, and ultrastructural alterations in intestinal epithelial cells (IECs) were assessed by electron microscopy. RESULTS: IECs from subjects with a family history of celiac disease, but not from subjects who already had immunity to gluten, expressed higher levels of HS27, HSP70, and interleukin-15 than controls; their IECs also had ultrastructural alterations. Intraepithelial cytotoxic T cells from relatives of patients with celiac disease expressed higher levels of activating NK receptors than cells from controls, although at lower levels than patients with active celiac disease, and without loss of inhibitory receptors for NK cells. Intraepithelial cytotoxic T cells from potential celiac disease patients failed to up-regulate activating NK receptors. CONCLUSIONS: A significant subset of healthy family members of patients with celiac disease with normal intestinal architecture had epithelial alterations, detectable by immunohistochemistry and electron microscopy. The adaptive immune response to gluten appears to act in synergy with epithelial stress to allow intraepithelial cytotoxic T cells to kill epithelial cells and induce villous atrophy in patients with active celiac disease.


Asunto(s)
Inmunidad Adaptativa , Enfermedad Celíaca/inmunología , Comunicación Celular , Células Epiteliales/inmunología , Mucosa Intestinal/inmunología , Intestino Delgado/inmunología , Estrés Fisiológico , Linfocitos T Citotóxicos/inmunología , Autoanticuerpos/sangre , Estudios de Casos y Controles , Enfermedad Celíaca/sangre , Enfermedad Celíaca/patología , Células Epiteliales/metabolismo , Células Epiteliales/ultraestructura , Proteínas de Unión al GTP/inmunología , Proteínas de Choque Térmico HSP27/inmunología , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas HSP70 de Choque Térmico/inmunología , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas de Choque Térmico , Humanos , Interleucina-15/inmunología , Interleucina-15/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/ultraestructura , Intestino Delgado/metabolismo , Intestino Delgado/ultraestructura , Italia , Chaperonas Moleculares , Fenotipo , Proteína Glutamina Gamma Glutamiltransferasa 2 , Factores de Riesgo , Transducción de Señal , Linfocitos T Citotóxicos/metabolismo , Linfocitos T Citotóxicos/ultraestructura , Transglutaminasas/inmunología , Estados Unidos
17.
Surg Endosc ; 30(12): 5380-5387, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27059971

RESUMEN

BACKGROUND: The advent of three-dimensional passive stereoscopic imaging has led to the development of 3D laparoscopy. In simulation tasks, a reduction in error rate and performance time is seen with 3D compared to two-dimensional (2D) laparoscopy with both novice and expert surgeons. Robotics utilises 3D and instrument articulation through a console interface. Robotic trials have demonstrated that tasks performed in 3D produced fewer errors and quicker performance times compared with those in 2D. It was therefore perceived that the main advantage of robotic surgery was in fact 3D. Our aim was to compare 3D straight-stick laparoscopic task performance (3D) with robotic 3D (Robot), to determine whether robotic surgery confers additional benefit over and above 3D visualisation. METHODS: We randomised 20 novice surgeons to perform four validated surgical tasks, either with straight-stick 3D laparoscopy followed by 3D robotic surgery or in the reverse order. The trial was conducted in two fully functional operating theatres. The primary outcome of the study was the error rate as defined for each task, and the secondary outcome was the time taken to complete each task. The participants were asked to perform the tasks as quickly and as accurately as possible. Data were analysed using SPSS version 21. RESULTS: The median error rate for completion of all four tasks with the robot was 2.75 and 5.25 for 3D with a P value <0.001. The median performance time for completion of all four tasks with the robot was 157.1 and 342.5 s for 3D with a P value <0.001. CONCLUSIONS: Our study has shown that for novice surgeons, there is a significant benefit in a simulated setting of 3D robotic systems over 3D straight-stick laparoscopy, in terms of reduced error rate and quicker task performance time.


Asunto(s)
Competencia Clínica/estadística & datos numéricos , Imagenología Tridimensional/métodos , Laparoscopía/métodos , Errores Médicos/estadística & datos numéricos , Procedimientos Quirúrgicos Robotizados/métodos , Adulto , Estudios Cruzados , Femenino , Humanos , Laparoscopía/instrumentación , Masculino , Cirujanos , Análisis y Desempeño de Tareas
18.
Acta Obstet Gynecol Scand ; 95(9): 984-90, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27223683

RESUMEN

INTRODUCTION: The risk of morcellation of occult uterine leiomyosarcomas (LMS) during laparoscopic procedures has been under scrutiny over recent years. The objective of this study was to assess the operative treatment performed in women with uterine LMS in Norway in 2000-2012, including the number of morcellated LMS. MATERIAL AND METHODS: Retrospective nationwide cohort study. The study participants were all women with histopathologically verified uterine LMS in Norway during 2000-2012. The data were collected from the Cancer Registry of Norway, National Patient Registry and medical records. RESULTS: There were 212 women diagnosed with uterine LMS in Norway in 2000-2012. Mean age at time of diagnosis was 58.1 years (SD ± 12.5). The most frequent symptom in women suffering from LMS was abnormal uterine bleeding [110/212 (51.9%)]. LMS was histopathologically verified in 49/212 (23.1%) preoperatively. In 48/212 (22.6%), a malignant condition was suspected and they were treated accordingly. In 115/212 (54.2%), malignancy was not suspected at time of surgery and the women were treated according to the treatment protocol for fibroids. In only four patients was tissue retrieval by power morcellation conducted, accounting for 1.9% of all LMS cases. CONCLUSIONS: In more than 50% of women suffering from LMS, a malignant diagnosis was not confirmed or suspected prior to surgery. In our material, power morcellation of LMS has not lead to reduced survival. We suggest that power morcellators may be used in surgical treatment of selected cases of premenopausal women with symptomatic, presumed benign uterine leiomyomas.


Asunto(s)
Leiomiosarcoma/epidemiología , Leiomiosarcoma/cirugía , Morcelación , Neoplasias Uterinas/epidemiología , Neoplasias Uterinas/cirugía , Estudios de Cohortes , Femenino , Humanos , Histerectomía/estadística & datos numéricos , Incidencia , Leiomioma/diagnóstico , Leiomioma/epidemiología , Leiomioma/cirugía , Leiomiosarcoma/diagnóstico , Escisión del Ganglio Linfático/estadística & datos numéricos , Menorragia/epidemiología , Menorragia/etiología , Persona de Mediana Edad , Noruega/epidemiología , Epiplón/cirugía , Dolor Pélvico/epidemiología , Dolor Pélvico/etiología , Posmenopausia , Estudios Retrospectivos , Hemorragia Uterina/epidemiología , Hemorragia Uterina/etiología , Neoplasias Uterinas/diagnóstico
19.
Acta Obstet Gynecol Scand ; 95(11): 1228-1234, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27564388

RESUMEN

INTRODUCTION: The goal of this study was to assess the sensitivity of different preoperative diagnostic tools used in women with uterine leiomyosarcomas. MATERIAL AND METHODS: Retrospective cohort study of all women with verified uterine leiomyosarcoma in Norway in the period 2000 to 2012. Data were collected from the Cancer Registry of Norway and medical records. RESULTS: There were 212 women diagnosed with uterine leiomyosarcoma in the 13-year period. Histopathological examinations by fractional curettage or endometrial biopsies verified malignancy in 55/142 (38.7%). MRI suggested malignancy in 45/55 (81%) of the examinations. CT evaluations indicated suspected malignancy in 64/107 women (59.8%). Biomarkers had low sensitivity for leiomyosarcoma, but suggested more advanced stage disease when high values were detected. Stage IV disease was present in 53.1% versus 25.5% (p = 0.01) of women with CA 125 values above 35 kU/L, compared with women with normal CA 125 values. In 115/212 (54.2%), leiomyosarcoma was only diagnosed postoperatively by histopathological examination of the removed specimen. CONCLUSIONS: Preoperative diagnostic modalities appear to have low sensitivity for differentiating leiomyosarcoma from fibroids. In Norway, approximately 54% of uterine leiomyosarcoma are unidentified before surgery. MRI evaluation was the imaging modality with the greatest sensitivity in identifying leiomyosarcoma preoperatively.


Asunto(s)
Endometrio/patología , Leiomiosarcoma/diagnóstico por imagen , Leiomiosarcoma/patología , Cuidados Preoperatorios/métodos , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/patología , Biomarcadores de Tumor/metabolismo , Biopsia , Diagnóstico Diferencial , Femenino , Humanos , Histerectomía , Leiomioma/diagnóstico por imagen , Leiomioma/metabolismo , Leiomioma/patología , Leiomioma/cirugía , Leiomiosarcoma/metabolismo , Leiomiosarcoma/cirugía , Imagen por Resonancia Magnética , Estadificación de Neoplasias , Noruega , Sistema de Registros , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/cirugía
20.
J Minim Invasive Gynecol ; 23(2): 163, 2016 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-26454193

RESUMEN

STUDY OBJECTIVE: To show the steps involved in a bilateral tubal adhesiolysis and cuff salpingostomy. DESIGN: Technical video showing tubal adhesiolysis and cuff salpingostomy in a step-by-step approach. SETTING: Minimal Access Therapy Training Unit, Royal Surrey County Hospital, Guildford, UK, a tertiary referral unit for complex gynecologic endoscopic surgery. INTERVENTIONS: A 38-year-old woman presented with left-sided pelvic pain and primary infertility for 13 years. An ultrasound scan showed bilateral hydrosalpinges with suspected adnexal adhesions. Hysterosalpingography did not show spill of dye. After counseling, she opted to have tubal adhesiolysis and bilateral cuff salpingostomy. CONCLUSION: Tubal surgery for occlusion has become less popular because of the superior success rates of assisted reproductive techniques. As a result, tubal surgery may eventually become a historic operation. However, in cases of distal tubal blockage after adhesionlysis and cuff salpingostomy or neosalpingostomy, pregnancy rates up to 35% have been reported in the literature. Furthermore, performing a bilateral salpingectomy instead in these cases renders a patient entirely dependent on assisted reproductive techniques for tubal factor infertility. Therefore, a bilateral cuff salpingostomy should be considered in a select group of patients.


Asunto(s)
Enfermedades de las Trompas Uterinas/complicaciones , Enfermedades de las Trompas Uterinas/cirugía , Infertilidad Femenina/cirugía , Salpingostomía , Adherencias Tisulares/complicaciones , Adherencias Tisulares/cirugía , Adulto , Consejo Dirigido , Disección/efectos adversos , Enfermedades de las Trompas Uterinas/patología , Femenino , Humanos , Infertilidad Femenina/etiología , Infertilidad Femenina/patología , Dolor Pélvico/etiología , Embarazo , Salpingostomía/métodos , Adherencias Tisulares/patología , Resultado del Tratamiento
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