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1.
BMC Surg ; 22(1): 201, 2022 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-35598012

RESUMEN

BACKGROUND: Enhanced Recovery Pathways (ERP) have been shown to reduce racial disparities following surgery. The objective of this study is to determine whether ERP implementation mitigates racial disparities at a Veterans Affairs Hospital. METHODS: A retrospective cohort study was conducted using data obtained from the Veterans Affairs Surgical Quality Improvement Program. All patients undergoing elective colorectal surgery following ERP implementation were included. Current procedural terminology (CPT) codes were used to identify patients who underwent similar procedures prior to ERP implementation. RESULTS: Our study included 417 patients (314 pre-ERP vs. 103 ERP), 97.1% of which were male, with an average age of 62.32 (interquartile range (IQR): 25-90). ERP patients overall had a significantly shorter post-operative length of stay (pLOS) vs. pre-ERP patients (median 4 days (IQR: 3-6.5) vs. 6 days (IQR: 4-9) days (p < 0.001)). Within the pre-ERP group, median pLOS for both races was 6 days (IQR: 4-6; p < 0.976) and both groups experienced a decrease in median pLOS (4 vs. 6 days; p < 0.009 and p < 0.001) following ERP implementation. CONCLUSIONS: Racial disparities did not exist in patients undergoing elective surgery at a single VA Medical Center. Implementation of an ERP significantly reduced pLOS for black and white patients.


Asunto(s)
Cirugía Colorrectal , Veteranos , Femenino , Hospitales , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
2.
Br J Dermatol ; 183(4): 702-709, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-31970750

RESUMEN

BACKGROUND: Content-valid and clinically meaningful instruments are required to evaluate outcomes of therapeutic interventions in alopecia areata (AA). OBJECTIVES: To develop an Investigator's Global Assessment (IGA) to interpret treatment response in AA treatment studies. METHODS: Qualitative interviews were conducted in the USA with expert dermatologists and with patients with AA who had experienced ≥ 50% scalp-hair loss. Thematic data analysis identified critical outcomes and evaluated the content validity of the new IGA. RESULTS: Expert clinicians (n = 10) judged AA treatment success by the amount of scalp-hair growth (median 80% scalp hair). Adult (n = 25) and adolescent (n = 5) patients participated. Scalp-hair loss was the most bothersome AA sign/symptom for most patients. Perceived treatment success - short of 100% scalp hair - was the presence of ~ 70-90% scalp hair (median 80%). Using additional clinician and patient insights, the Alopecia Areata Investigator Global Assessment (AA-IGA™) was developed. This clinician-reported outcome assessment is an ordinal, static measure comprising five severity categories of scalp-hair loss. Nearly all clinicians and patients in this study agreed that, for patients with ≥ 50% scalp-hair loss, successful treatment would be hair regrowth resulting in ≤ 20% scalp-hair loss. CONCLUSIONS: We recommend using the Severity of Alopecia Tool to assess the extent (0-100%) of scalp-hair loss. The AA-IGA is a robust ordinal measure providing distinct and clinically meaningful gradations of scalp-hair loss that reflects patients' and expert clinicians' perspectives and treatment expectations. What is already known about this topic? The Severity of Alopecia Tool is widely used to assess the extent of scalp-hair loss in patients with alopecia areata. Guidelines define treatment success as a 50% improvement in scalp hair, and clinical trials have used dynamic thresholds of 50% and 90%. However, there is no clinical consensus on these endpoints, and patient perspectives on treatment success are unknown. What does this study add? Through qualitative interviews with 10 expert dermatologists and 30 patients with alopecia areata who had experienced ≥ 50% scalp-hair loss, we developed the Alopecia Areata Investigator Global Assessment (AA-IGA™) to measure five clinically meaningful gradations of alopecia areata scalp-hair loss that reflects patients' and clinicians' perspectives and expectations of treatment success in alopecia areata treatment studies. What are the clinical implications of this work? The AA-IGA is a robust ordinal measure that can inform clinical evaluation of alopecia areata treatment outcomes. The AA-IGA can be used to determine clinically meaningful treatment success for alopecia areata, with success defined by patients and clinicians as reaching ≤ 20% scalp-hair loss. Linked Comment: Blome. Br J Dermatol 2020; 183:609.


Asunto(s)
Alopecia Areata , Adolescente , Adulto , Alopecia , Alopecia Areata/tratamiento farmacológico , Cabello , Humanos , Cuero Cabelludo
3.
Br J Dermatol ; 183(6): 1065-1072, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32163589

RESUMEN

BACKGROUND: Valid patient-reported outcome (PRO) measures are required to evaluate alopecia areata (AA) treatments. OBJECTIVES: To develop a content-valid and clinically meaningful PRO measure to assess AA scalp hair loss with scores comparable with the five-response-level Alopecia Areata Investigator Global Assessment (AA-IGA™). METHODS: A draft PRO measure was developed based on input from 10 clinical experts in AA. The PRO measure was cognitively debriefed, modified and finalized through two rounds of qualitative semistructured interviews with patients with AA who had experienced ≥ 50% scalp hair loss. Data were thematically analysed. RESULTS: Adults (round 1: n = 25; round 2: n = 15) and adolescents aged 15-17 years (round 1: n = 5) in North America participated. All patients named scalp hair loss as a key AA sign or symptom. Patients demonstrated the ability to self-report their current amount of scalp hair using percentages. In round 1 not all patients interpreted the measurement concept consistently; therefore, the PRO was modified to clarify the measurement concept to improve usability. Following modifications, patients in round 2 responded without difficulty to the PRO measure. Patients confirmed that they could use the five-level response scale to rate their scalp hair loss: no missing hair, 0%; limited, 1-20%; moderate, 21-49%; large, 50-94%; nearly all or all, 95-100%. Almost all patients deemed hair regrowth resulting in ≤ 20% scalp hair loss a treatment success. CONCLUSIONS: The Scalp Hair Assessment PRO™ is a content-valid, clinically meaningful assessment of distinct gradations of scalp hair loss for evaluating AA treatment for patients with ≥ 50% hair loss at baseline.


Asunto(s)
Alopecia Areata , Adolescente , Adulto , Alopecia , Alopecia Areata/diagnóstico , Cabello , Humanos , América del Norte , Medición de Resultados Informados por el Paciente , Cuero Cabelludo
4.
Br J Surg ; 106(2): e62-e72, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30620075

RESUMEN

BACKGROUND: Technological advances have led to the generation of large amounts of data, both in surgical research and practice. Despite this, it is unclear how much originates in low- and middle-income countries (LMICs) and what barriers exist to the use of such data in improving surgical care. The aim of this review was to capture the extent and impact of programmes that use large volumes of patient data on surgical care in LMICs. METHODS: A PRISMA-compliant systematic literature review of PubMed, Embase and Google Scholar was performed in August 2018. Prospective studies collecting large volumes of patient-level data within LMIC settings were included and evaluated qualitatively. RESULTS: A total of 68 studies were included from 71 LMICs, involving 708 032 patients. The number of patients in included studies varied widely (from 335 to 428 346), with 25 reporting data on 3000 or more LMIC patients. Patient inclusion in large-data studies in LMICs has increased dramatically since 2015. Studies predominantly involved Brazil, China, India and Thailand, with low patient numbers from Africa and Latin America. Outcomes after surgery were commonly the focus (33 studies); very few large studies looked at access to surgical care or patient expenditure. The use of large data sets specifically to improve surgical outcomes in LMICs is currently limited. CONCLUSION: Large volumes of data are becoming more common and provide a strong foundation for continuing investigation. Future studies should address questions more specific to surgery.


Asunto(s)
Macrodatos , Cirugía General/normas , Mejoramiento de la Calidad/estadística & datos numéricos , Países en Desarrollo , Cirugía General/estadística & datos numéricos , Humanos , Evaluación de Resultado en la Atención de Salud
5.
Colorectal Dis ; 21(7): 775-781, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30848537

RESUMEN

AIM: Studies addressing the benefit of early intervention are prone to lead-time bias, which results in an artificial improvement in cancer-specific mortality. We have previously compared the age at death for patients with colorectal cancer presenting on an emergency or elective basis. In this study, we aimed to repeat the analysis with a minimum follow-up of 10 years. METHOD: A nonscreen-detected cohort of patients presenting with colorectal cancer to three Lanarkshire Hospitals between 2000 and 2006 were entered into a prospective database, with analysis performed on 28 November 2016. The following data were collected: age at death, presentation type (emergency/elective), operative intent (palliative/curative) and Dukes stage. Results are presented as [mean (95% confidence intervals)]. Statistical analysis was undertaken using Student's t-test and multivariate analysis performed using Cox proportional hazard models. RESULTS: One thousand six hundred and thirty-six patients were identified. Elective patients presented younger than emergency patients [67.9 (67.3-68.5) vs 70.9 (69.6-72.2) years; P < 0.0001]. Overall mortality was 71.1% at time of analysis; no difference was seen in the mean age at death between emergency and elective presentation [73.5 (72.4-74.8) vs 73.6 (72.3-74.9) years; P = 0.841]. CONCLUSION: Current early detection strategies to diagnose colorectal cancer may improve cancer-specific survival by increasing lead-time bias. However, in our cohort of symptomatic patients, treatment on an elective or emergency basis does not influence overall survival. These data suggest that in selected patients, particularly where there is comorbidity, it may be reasonable to adopt a more expectant approach to investigate and treat colorectal symptoms.


Asunto(s)
Factores de Edad , Neoplasias Colorrectales/mortalidad , Procedimientos Quirúrgicos Electivos/mortalidad , Tratamiento de Urgencia/mortalidad , Factores de Tiempo , Anciano , Sesgo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Prospectivos
6.
Tech Coloproctol ; 23(11): 1065-1072, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31720908

RESUMEN

BACKGROUND: Rectal prolapse is a disease presentation with a prevalence of about 1%, mainly affecting older women. It usually presents with symptoms of rectal mass, rectal bleeding, fecal incontinence or constipation, with patients frequently feeling socially isolated as a result. Perineal rectosigmoidectomy is associated with lesser morbidity and mortality than the abdominal procedure, but with a much higher recurrence rate. Therefore, this technique is mainly suitable for the frail elderly patient. Specific outcomes in an elderly population have been described in only a few studies. We evaluated the morbidity, mortality, recurrence rate and functional results after this procedure related to age. METHODS: All patients who underwent a perineal rectosigmoidectomy over a 10-year period in two tertiary referral centers were included in the study. American Society of Anesthesiology (ASA) grade, pre- and postoperative symptoms, pathology-reported post-fixation specimen length, length of in-patient stay, 30-day morbidity/mortality, and recurrence were measured. RESULTS: A total of 45 patients underwent a perineal rectosigmoidectomy. Forty-three (95%) were female, with a median age of 82.0 years (IQR 70.5-86.5), ASA grade III and median follow-up of 20 months (range 8.5-45.5 months). Half of the cohort was over 80 years old. Significant symptomatic relief was achieved, predominantly the resolution of rectal mass (8.9% vs. 60.0% preoperatively), fecal incontinence (15.6% vs. 46.7%) and constipation (4.4% vs. 26.7%). The median length of stay was 6 days, while morbidity occurred in 14 patients (31.1%) and recurrence occurred in 6 patients (13%). There were no deaths within 30 days of the procedure and outcomes were comparable in the < 80 and ≥ 80 age group. CONCLUSIONS: Perineal rectosigmoidectomy is safe for older patients with greater comorbidities resulting in good functional results and is associated with low morbidity and mortality.


Asunto(s)
Colon Sigmoide/cirugía , Proctectomía/efectos adversos , Proctectomía/métodos , Prolapso Rectal/cirugía , Anciano , Anciano de 80 o más Años , Estreñimiento/etiología , Incontinencia Fecal/etiología , Femenino , Anciano Frágil , Estado de Salud , Humanos , Tiempo de Internación , Masculino , Perineo , Prolapso Rectal/complicaciones , Recurrencia , Evaluación de Síntomas , Centros de Atención Terciaria , Resultado del Tratamiento , Reino Unido
7.
Osteoarthritis Cartilage ; 25(5): 676-684, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-27923602

RESUMEN

OBJECTIVE: Using a validated, patient-specific finite element (FE) modeling protocol, we evaluated cartilage and labrum (i.e., chondrolabral) mechanics before and after peri-acetabular osteotomy (PAO) to provide insight into the ability of this procedure to improve mechanics in dysplastic hips. DESIGN: Five patients with acetabular dysplasia were recruited in this case-controlled, prospective study. Models, which included anatomy for bone, cartilage, and labrum, were generated from computed tomography (CT) arthrography scans acquired before and after PAO. Cartilage and labrum contact stress and contact area were quantified overall and regionally. Load supported by the labrum, expressed as a percentage of the total hip force, was analyzed. RESULTS: Percent cartilage contact area increased post-operatively overall, medially, and superiorly. Peak acetabular contact stress decreased overall, laterally, anteriorly, and superiorly. Average contact stress decreased overall, laterally, anteriorly, and posteriorly. Only average contact stress on the superior labrum and peak labrum stress overall decreased. Load supported by the labrum did not change significantly. CONCLUSIONS: PAO was efficacious at medializing cartilage contact and reducing cartilage contact stresses, and therefore may minimize deleterious loading to focal cartilage lesions, subchondral cysts, and cartilage delaminations often observed in the lateral acetabulum of dysplastic hips. However, the excessively prominent, hypertrophied labrum of dysplastic hips remains in contact with the femoral head, which continues to load the labrum following PAO. The clinical ramifications of continued labral loading following PAO are not known. However, it is plausible that failure to reduce the load experienced by the labrum could result in end-stage hip OA following PAO.


Asunto(s)
Cartílago Articular/parasitología , Luxación de la Cadera/diagnóstico por imagen , Luxación de la Cadera/cirugía , Imagenología Tridimensional , Osteotomía/métodos , Estrés Mecánico , Acetábulo/diagnóstico por imagen , Acetábulo/fisiopatología , Adulto , Fenómenos Biomecánicos , Estudios de Casos y Controles , Femenino , Análisis de Elementos Finitos , Humanos , Masculino , Estudios Prospectivos , Valores de Referencia , Medición de Riesgo , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Adulto Joven
8.
Am J Transplant ; 16(9): 2545-55, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-26946212

RESUMEN

The increased demand for organs has led to the increased usage of "higher risk" kidney and liver grafts. These grafts from donation after circulatory death or expanded criteria donors are more susceptible to preservation injury and have a higher risk of unfavorable outcomes. Dynamic, instead of static, preservation could allow for organ optimization, offering a platform for viability assessment, active organ repair and resuscitation. Ex situ machine perfusion and in situ regional perfusion in the donor are emerging as potential tools to preserve and resuscitate vulnerable grafts. Preclinical findings have ignited clinical organ preservation research that investigates dynamic preservation, its various modes (continuous, preimplantation) and temperatures (hypo-, sub, or normothermic). This review outlines the current status of dynamic preservation of kidney and liver grafts and describes ongoing research and emerging clinical trials.


Asunto(s)
Supervivencia de Injerto , Trasplante de Riñón/tendencias , Trasplante de Hígado/tendencias , Preservación de Órganos/métodos , Resucitación , Donantes de Tejidos/provisión & distribución , Animales , Humanos , Soluciones Preservantes de Órganos
9.
Clin Genet ; 90(3): 258-62, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-26954065

RESUMEN

Kabuki syndrome is a heterogeneous condition characterized by distinctive facial features, intellectual disability, growth retardation, skeletal abnormalities and a range of organ malformations. Although at least two major causative genes have been identified, these do not explain all cases. Here we describe a patient with a complex Kabuki-like syndrome that included nodular heterotopia, in whom testing for several single-gene disorders had proved negative. Exome sequencing uncovered a de novo c.931_932insTT variant in HNRNPK (heterogeneous nuclear ribonucleoprotein K). Although this variant was identified in March 2012, its clinical relevance could only be confirmed following the August 2015 publication of two cases with HNRNPK mutations and an overlapping phenotype that included intellectual disability, distinctive facial dysmorphism and skeletal/connective tissue abnormalities. Whilst we had attempted (unsuccessfully) to identify additional cases through existing collaborators, the two published cases were 'matched' using GeneMatcher, a web-based tool for connecting researchers and clinicians working on identical genes. Our report therefore exemplifies the importance of such online tools in clinical genetics research and the benefits of periodically reviewing cases with variants of unproven significance. Our study also suggests that loss of function variants in HNRNPK should be considered as a molecular basis for patients with Kabuki-like syndrome.


Asunto(s)
Anomalías Múltiples/genética , Discapacidades del Desarrollo/genética , Cara/anomalías , Enfermedades Hematológicas/genética , Discapacidad Intelectual/genética , Ribonucleoproteínas/genética , Enfermedades Vestibulares/genética , Anomalías Múltiples/fisiopatología , Secuencia de Bases , Discapacidades del Desarrollo/fisiopatología , Exoma , Cara/fisiopatología , Femenino , Mutación del Sistema de Lectura , Enfermedades Hematológicas/fisiopatología , Ribonucleoproteína Heterogénea-Nuclear Grupo K , Humanos , Discapacidad Intelectual/fisiopatología , Masculino , Malformaciones del Sistema Nervioso/genética , Malformaciones del Sistema Nervioso/fisiopatología , Enfermedades Vestibulares/fisiopatología
11.
Opt Lett ; 40(12): 2688-91, 2015 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-26076237

RESUMEN

The effect of a tunable, externally coupled Fabry-Perot cavity to resonantly enhance the optical Hall effect signatures at terahertz frequencies produced by a traditional Drude-like two-dimensional electron gas is shown and discussed in this Letter. As a result, the detection of optical Hall effect signatures at conveniently obtainable magnetic fields, for example, by neodymium permanent magnets, is demonstrated. An AlInN/GaN-based high-electron mobility transistor structure grown on a sapphire substrate is used for the experiment. The optical Hall effect signatures and their dispersions, which are governed by the frequency and the reflectance minima and maxima of the externally coupled Fabry-Perot cavity, are presented and discussed. Tuning the externally coupled Fabry-Perot cavity strongly modifies the optical Hall effect signatures, which provides a new degree of freedom for optical Hall effect experiments in addition to frequency, angle of incidence, and magnetic field direction and strength.

12.
Spinal Cord ; 53(12): 887-9, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26238317

RESUMEN

STUDY DESIGN: Two case studies. OBJECTIVES: To determine whether 6 weeks of regular pelvic floor muscle training (PFMT) can improve the strength and endurance of voluntary contractions in incomplete spinal cord injury and reduce neurogenic detrusor over-activity (NDO) and incontinence. SETTING: The London Spinal Cord Injury Centre, Stanmore, London, UK. METHODS: A 6-week programme of PFMT was conducted in two male subjects with stable supra-sacral motor incomplete (AIS C and D) spinal cord injuries. Clinical evaluations before and after training comprised measures of strength and endurance of voluntary pelvic floor contractions both objectively by anal canal-pressure measurements and subjectively using the modified Oxford grading system. NDO was determined by standard urodynamic tests of bladder function and incontinence measured by the International Consultation on Incontinence Questionnaire-Urology. RESULTS: Both subjects improved the strength and endurance of their pelvic floor muscle contractions by over 100% at the end of training. After training, Subject 1 (AIS D) was able to reduce bladder pressure during over-activity almost completely by voluntarily contracting the pelvic floor muscles. Subject 2 (AIS C) achieved a lesser reduction overall after training. Continence improved only in subject 1. CONCLUSION: These case studies provide evidence that a 6-week programme of PFMT may have a beneficial effect on promoting voluntary control of NDO and reduce incontinence in selected cases with a motor incomplete spinal cord lesion.


Asunto(s)
Terapia por Ejercicio/efectos adversos , Músculo Liso/fisiología , Diafragma Pélvico/fisiopatología , Traumatismos de la Médula Espinal/complicaciones , Vejiga Urinaria Hiperactiva/etiología , Incontinencia Urinaria/etiología , Área Bajo la Curva , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Incontinencia Urinaria/rehabilitación
13.
Am J Transplant ; 14(12): 2765-76, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25395336

RESUMEN

Invasive fungal infections (IFIs) cause significant morbidity and mortality in liver transplant recipients, but the need and best agent for prophylaxis is uncertain. A comprehensive literature search was performed to identify randomized controlled trials comparing regimens for antifungal prophylaxis in liver transplant recipients. Direct comparisons were made between treatments using random-effects meta-analysis and a Bayesian network meta-analysis was performed for the primary end point of proven IFI. Fourteen studies met inclusion criteria, reporting comparisons of fluconazole, liposomal amphotericin B (L-AmB), itraconazole, micafungin and placebo. Overall, antifungal prophylaxis reduced the rate of proven IFI (odds ratio [OR] 0.37, confidence interval [CI] 0.19-0.72, p = 0.003), suspected or proven IFI (OR 0.40, CI 0.25-0.66, p = 0.0003) and mortality due to IFI (OR 0.32, CI 0.10-0.83, p = 0.02) when compared to placebo. All-cause mortality was not significantly affected. There was no difference in risk of adverse events requiring cessation of prophylaxis (OR 1.11, 95% CI 0.48-2.55, p = 0.81). In the network meta-analysis an equivalent reduction in the rate of IFI was seen with fluconazole (OR 0.21, CI 0.06-0.57) and L-AmB (OR 0.21, CI 0.05-0.71) compared with placebo. Routine prophylaxis with fluconazole or L-AmB reduces the incidence of IFI following liver transplantation, and the available evidence suggests that the two are equivalent in efficacy.


Asunto(s)
Profilaxis Antibiótica , Antifúngicos/uso terapéutico , Rechazo de Injerto/prevención & control , Hepatopatías/cirugía , Trasplante de Hígado/efectos adversos , Micosis/prevención & control , Complicaciones Posoperatorias , Rechazo de Injerto/etiología , Humanos , Micosis/microbiología
14.
Ann R Coll Surg Engl ; 106(3): 213-218, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37218655

RESUMEN

INTRODUCTION: Colorectal liver metastases (CRLM) are associated with a high recurrence rate after surgery. There is paucity of high-quality evidence regarding the nature and overall benefit of surveillance after hepatectomy for CRLM. As part of a broader programme of research, this study aimed to assess current strategies for surveillance after liver resection for CRLM and outline surgeons' opinions regarding the benefit of postoperative surveillance. METHODS: An online survey was sent to clinicians performing surgery for CRLM at tertiary hepatobiliary centres in the UK. RESULTS: There were responses from a total of 23 centres (88% response rate); 15/23 centres used standardised surveillance protocols for all patients. Most centres followed patients up at six months, but there is variation in postoperative surveillance at 3, 9, 18 and beyond 60 months. Patient comorbidities, indeterminate findings on imaging, margin status and assessment of recurrence risk were identified as the major factors influencing personalised surveillance strategies. There was clear clinician equipoise regarding the costs and benefits of surveillance. CONCLUSION: There is heterogeneity in postoperative follow-up for CRLM in the UK. High-quality prospective studies and randomised trials are necessary to elucidate the value of postoperative surveillance and identify optimal follow-up strategies.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Estudios Transversales , Estudios Prospectivos , Hepatectomía , Neoplasias Hepáticas/cirugía , Neoplasias Colorrectales/cirugía
15.
Clin Exp Immunol ; 174(1): 109-19, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23607934

RESUMEN

Human monocyte-derived dendritic cells (DC) (MoDC) are utilized for immunotherapy. However, in-vitro immunological effects are often not mirrored in vivo. We studied the tissue-homing potential of MoDC. Circulating monocytes and DC expressed different tissue-homing markers and, during in-vitro development of MoDC, homing marker expression was lost resulting in a 'homeless' phenotype. Retinoic acid (RA) induced gut-homing markers (ß7 and CCR9) and a regulatory phenotype and function [decreased human leucocyte antigen D-related (HLA-DR) and increased ILT3 and fluorescein isothiocyanate (FITC-dextran uptake) in MoDC]. RA-MoDC were less stimulatory and primed conditioned T cells with a gut-homing profile (ß7(+)CLA(-)). Unlike the normal intestinal microenvironment, that from inflamed colon of ulcerative colitis (UC) patients did not induce regulatory properties in MoDC. However, RA-MoDC maintained their regulatory gut-specific properties even in the presence of UC microenvironment. Therefore, MoDC may be ineffectual for immunotherapy because they lack tissue-homing and tissue-imprinting specificity. However, MoDC rehabilitation with gut-homing potential by RA could be useful in promoting immunotherapy in pathologies such as UC.


Asunto(s)
Diferenciación Celular/inmunología , Movimiento Celular/inmunología , Células Dendríticas/inmunología , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/inmunología , Monocitos/inmunología , Tretinoina/farmacología , Biomarcadores/metabolismo , Diferenciación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inmunología , Colitis Ulcerosa/patología , Células Dendríticas/citología , Células Dendríticas/efectos de los fármacos , Femenino , Tracto Gastrointestinal/patología , Humanos , Masculino , Monocitos/citología , Monocitos/efectos de los fármacos , Especificidad de Órganos/efectos de los fármacos , Especificidad de Órganos/inmunología , Receptores CCR/biosíntesis , Receptores CCR7/biosíntesis , Tretinoina/uso terapéutico
16.
Br J Surg ; 100(8): 991-1001, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23754643

RESUMEN

BACKGROUND: Adequate preservation of renal allografts for transplantation is important for maintaining and improving transplant outcomes. There are two prevalent methods: hypothermic machine perfusion and static cold storage. The preferred method of storage, however, remains controversial. The objective was to review systematically the evidence comparing outcomes from these two modalities. METHODS: A literature search was performed using MEDLINE, Embase, the Cochrane Library, the Transplant Library and the International Clinical Trials Registry Platform. The final date for searches was 30 November 2012. Studies were assessed for methodological quality. Summary effects were calculated as relative risk (RR) with 95 per cent confidence interval (c.i.). Randomized clinical trials (RCTs) and non-RCTs were included, but evaluated separately. Results from RCTs alone were used for meta-analysis. RESULTS: Eighteen studies met the inclusion criteria, including seven RCTs (1475 kidneys) and 11 non-RCTs (728 kidneys). The overall risk of delayed graft function was lower with hypothermic machine perfusion than static cold storage (RR 0·81, 95 per cent c.i. 0·71 to 0·92; P = 0·002). There was no difference in the rate of primary non-function (RR 1·15, 0·46 to 2·90; P = 0·767). There was a faster initial fall in the level of serum creatinine with hypothermic machine perfusion in two RCTs, but not in another. There was no relationship between rates of acute rejection or patient survival and the method of preservation. CONCLUSION: Data from the included studies suggest that hypothermic machine perfusion reduces delayed graft function compared with static cold storage. There was no difference in primary non-function, acute rejection, long-term renal function or patient survival. A difference in renal graft survival is uncertain.


Asunto(s)
Funcionamiento Retardado del Injerto/etiología , Hipertermia Inducida/métodos , Trasplante de Riñón/métodos , Preservación de Órganos/métodos , Perfusión/métodos , Diseño de Equipo , Rechazo de Injerto/etiología , Supervivencia de Injerto/fisiología , Humanos , Hipertermia Inducida/instrumentación , Ensayos Clínicos Controlados Aleatorios como Asunto , Trasplante Homólogo , Resultado del Tratamiento
17.
Nat Genet ; 19(1): 32-8, 1998 May.
Artículo en Inglés | MEDLINE | ID: mdl-9590285

RESUMEN

X-linked recessive dyskeratosis congenita (DKC) is a rare bone-marrow failure disorder linked to Xq28. Hybridization screening with 28 candidate cDNAs resulted in the detection of a 3' deletion in one DKC patient with a cDNA probe (derived from XAP101). Five different missense mutations in five unrelated patients were subsequently identified in XAP101, indicating that it is the gene responsible for X-linked DKC (DKC1). DKC1 is highly conserved across species barriers and is the orthologue of rat NAP57 and Saccharomyces cerevisiae CBF5. The peptide dyskerin contains two TruB pseudouridine (psi) synthase motifs, multiple phosphorylation sites, and a carboxy-terminal lysine-rich repeat domain. By analogy to the function of the known dyskerin orthologues, involvement in the cell cycle and nucleolar function is predicted for the protein.


Asunto(s)
Nucléolo Celular/metabolismo , Disqueratosis Congénita/genética , Ligamiento Genético , Hidroliasas , Mutación , Ribonucleoproteínas Nucleares Pequeñas , Proteínas de Saccharomyces cerevisiae , Cromosoma X , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética , ADN Complementario , Proteínas Fúngicas/genética , Eliminación de Gen , Humanos , Proteínas Asociadas a Microtúbulos/genética , Datos de Secuencia Molecular , Proteínas Nucleares/química , Proteínas Nucleares/genética , Proteínas de Unión al ARN/genética , Ratas , Saccharomyces cerevisiae/genética , Homología de Secuencia de Aminoácido
18.
Am J Transplant ; 12(4): 896-906, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22221739

RESUMEN

Static cold storage is the most prevalent method for renal allograft preservation. Several solutions have been designed to counteract the detrimental effects of cold ischemia and reperfusion. The aim of this study was to appraise the evidence for the currently available preservation solutions. We performed a systematic literature search using MEDLINE, EMBASE, the Cochrane Library, the Transplant Library and trial registries. Inclusion criteria specified any comparative, prospective study for deceased donor renal allografts. Studies were assessed for methodological quality. The primary outcome was delayed graft function (DGF). Fifteen trials with a total of 3584 kidneys were included. Eurocollins was associated with a higher risk of DGF than University of Wisconsin solution (UW) in two randomized controlled trials (RCTs) and histidine-tryptophan-ketoglutarate (HTK) in two RCTs. UW was associated with an equal risk of DGF compared with Celsior in three RCTs and HTK in two RCTs. There was limited data regarding other comparisons and outcomes. The choice of preservation solution has an effect on the incidence of DGF, which might, in turn, affect long-term outcomes. Both UW and HTK have lower rates of DGF than Eurocollins. There is no difference in the incidence of DGF with the use of Celsior, HTK and UW. These findings are supported by registry data.


Asunto(s)
Criopreservación/métodos , Trasplante de Riñón , Soluciones Preservantes de Órganos/uso terapéutico , Preservación de Órganos/métodos , Ensayos Clínicos como Asunto , Isquemia Fría , Funcionamiento Retardado del Injerto/fisiopatología , Supervivencia de Injerto , Humanos , Riñón/fisiopatología , Tasa de Supervivencia , Trasplante Homólogo
19.
Clin Exp Immunol ; 170(2): 122-30, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23039882

RESUMEN

Changes in phenotype and function of γδ T cells have been reported in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Dysregulation of lymphocyte migration plays a key role in IBD pathogenesis; however, data on migratory properties of γδ T cells are scarce. Human circulating γδ T cells from healthy controls (n = 27), patients with active CD (n = 15), active UC (n = 14) or cutaneous manifestations of IBD (n = 2) were characterized by flow cytometry. Circulating γδ T cells in healthy controls were CD3(hi) and expressed CD45RO. They expressed gut-homing molecule ß7 but not gut-homing molecule corresponding chemokine receptors (CCR)9, or skin-homing molecules cutaneous lymphocyte-associated antigen (CLA) and CCR4, despite conventional T cells containing populations expressing these molecules. CCR9 expression was increased on γδ T cells in CD and UC, while skin-homing CLA was expressed aberrantly on γδ T cells in patients with cutaneous manifestations of IBD. Lower levels of CD3 expression were found on γδ T cells in CD but not in UC, and a lower proportion of γδ T cells expressed CD45RO in CD and UC. Enhanced expression of gut-homing molecules on circulating γδ T cells in IBD and skin-homing molecules in cutaneous manifestations of IBD may be of clinical relevance.


Asunto(s)
Enfermedad de Crohn/metabolismo , Tracto Gastrointestinal/inmunología , Enfermedades Inflamatorias del Intestino/inmunología , Piel/inmunología , Subgrupos de Linfocitos T/inmunología , Adulto , Antígenos de Diferenciación de Linfocitos T/inmunología , Antígenos de Diferenciación de Linfocitos T/metabolismo , Complejo CD3/inmunología , Complejo CD3/metabolismo , Colitis Ulcerosa/inmunología , Colitis Ulcerosa/metabolismo , Enfermedad de Crohn/inmunología , Femenino , Tracto Gastrointestinal/metabolismo , Humanos , Enfermedades Inflamatorias del Intestino/metabolismo , Cadenas beta de Integrinas/inmunología , Cadenas beta de Integrinas/metabolismo , Antígenos Comunes de Leucocito/inmunología , Antígenos Comunes de Leucocito/metabolismo , Masculino , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/metabolismo , Receptores CCR/inmunología , Receptores CCR/metabolismo , Receptores CCR4/inmunología , Receptores CCR4/metabolismo , Piel/metabolismo , Subgrupos de Linfocitos T/metabolismo
20.
Hernia ; 26(3): 751-759, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34718903

RESUMEN

BACKGROUND: Abdominal wall hernia repair is one of the most commonly performed surgical procedures worldwide, yet despite this, there remains a lack of high-quality evidence to support best management. The aim of the study was to use a modified Delphi process to determine future research priorities in this field. METHODS: Stakeholders were invited by email, using British Hernia Society membership details or Twitter, to submit individual research questions via an online survey. In addition, questions obtained from a patient focus group (PFG) were collated to form Phase I. Two rounds of prioritization by stakeholders (phases II and III) were then completed to determine a final list of research questions. All questions were analyzed on an anonymized basis. RESULTS: A total of 266 questions, 19 from the PFG, were submitted by 113 stakeholders in Phase I. Of these, 64 questions were taken forward for prioritization in Phase II, which was completed by 107 stakeholders. Following Phase II analysis, 97 stakeholders prioritized 36 questions in Phase III. This resulted in a final list of 14 research questions, 3 of which were from the PFG. Stakeholders included patients and healthcare professionals (consultant surgeons, trainee surgeons and other multidisciplinary members) from over 27 countries during the 3 phases. CONCLUSION: The study has identified 14 key research priorities pertaining to abdominal wall hernia surgery. Uniquely, these priorities have been determined from participation by both healthcare professionals and patients. These priorities should now be addressed by well-designed, high-quality international collaborative research.


Asunto(s)
Investigación Biomédica , Procedimientos Quirúrgicos del Sistema Digestivo , Hernia Abdominal , Técnica Delphi , Herniorrafia , Humanos
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