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1.
Tech Coloproctol ; 28(1): 15, 2023 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-38095756

RESUMEN

BACKGROUND: Postoperative ileus (POI) remains a common phenomenon following loop ileostomy closure. Our aim was to determine whether preoperative physiological stimulation (PPS) of the efferent limb reduced POI incidence. METHODS: A PRISMA-compliant meta-analysis searching PubMed, EMBASE and CENTRAL databases was performed. The last search was carried out on 30 January 2023. All randomized studies comparing PPS versus no stimulation were included. The primary endpoint was POI incidence. Secondary endpoints included the time to first passage of flatus/stool, time to resume oral diet, need for nasogastric tube (NGT) placement postoperatively, length of stay (LOS) and other complications. Random effects models were used to calculate pooled effect size estimates. Trial sequential analyses (TSA) were also performed. RESULTS: Three randomized studies capturing 235 patients (116 PPS, 119 no stimulation) were included. On random effects analysis, PPS was associated with a quicker time to resume oral diet (MD - 1.47 days, 95% CI - 2.75 to - 0.19, p = 0.02), shorter LOS (MD - 1.47 days, 95% CI - 2.47 to - 0.46, p = 0.004) (MD - 1.41 days, 95% CI - 2.32 to - 0.50, p = 0.002, I2 = 56%) and fewer other complications (OR 0.42, 95% CI 0.18 to 1.01, p = 0.05). However, there was no difference in POI incidence (OR 0.35, 95% CI 0.10 to 1.21, p = 0.10), the requirement for NGT placement (OR 0.50, 95% CI 0.21 to 1.20, p = 0.12) or time to first passage of flatus/stool (MD - 0.60 days, 95% CI - 1.95 to 0.76, p = 0.39). TSA revealed imprecise estimates for all outcomes (except LOS) and further studies are warranted to meet the required information threshold. CONCLUSIONS: PPS prior to stoma closure may reduce LOS and postoperative complications albeit without a demonstrable beneficial effect on POI. Further high-powered studies are required to confirm or refute these findings.


Asunto(s)
Ileostomía , Ileus , Humanos , Ileostomía/efectos adversos , Flatulencia/complicaciones , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Ileus/etiología
2.
Immunobiology ; 228(5): 152410, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37478687

RESUMEN

Complement factor I (FI) is the nexus for classical, lectin and alternative pathway complement regulation. FI is an 88 kDa plasma protein that circulates in an inactive configuration until it forms a trimolecular complex with its cofactor and substrate whereupon a structural reorganization allows the catalytic triad to cleave its substrates, C3b and C4b. In keeping with its role as the master complement regulatory enzyme, deficiency has been linked to immunopathology. In the setting of complete FI deficiency, a consumptive C3 deficiency results in recurrent infections with encapsulated microorganisms. Aseptic cerebral inflammation and vasculitic presentations are also less commonly observed. Heterozygous mutations in the factor I gene (CFI) have been demonstrated to be enriched in atypical haemolytic uraemic syndrome, albeit with a very low penetrance. Haploinsufficiency of CFI has also been associated with decreased retinal thickness and is a strong risk factor for the development of age-related macular degeneration. Supplementation of FI using plasma purified or recombinant protein has long been postulated, however, technical difficulties prevented progression into clinical trials. It is only using gene therapy that CFI supplementation has reached the clinic with GT005 in phase I/II clinical trials for geographic atrophy.


Asunto(s)
Síndrome Hemolítico Urémico Atípico , Factor I de Complemento , Humanos , Factor I de Complemento/química , Complemento C3/genética , Mutación , Inflamación , Complemento C3b
3.
Surgeon ; 21(5): 285-288, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36446700

RESUMEN

The surgical learning curve is an observable and measurable phenomenon. In the era of competency-based approaches to surgical training, monitoring the trajectory of individual trainee competence attainment could represent a meaningful method of formative and summative assessment. While technology can assist this approach, a number of significant barriers to the implementation of such assessment methods remain, including: accurate data collection, standard setting, and reliable assessment. Translating individual learning curve data into quantifiable case minimum targets in training poses further difficulties, and may not be possible for all procedures, particularly those that are less frequently performed and assessed. In spite of these challenges, significant benefits could be realized through an individualized approach to competency assessment using trainee learning curve data. Tracking competence acquisition against criterion-referenced standards could allow for targeted training and remediation, conforming with modern theories of adult education and empowering trainees to take control of their own learning. Learning curve data could also be used to assess the effects of educational interventions such as simulation-based training on subsequent competence acquisition rates. Ultimately, the individual learning curves of trainees could be used to inform personalised decisions regarding entrustment, credentialing, and certification, allowing training programmes to move beyond minimum operative experience targets as a crude proxy measure of competence.


Asunto(s)
Competencia Clínica , Curva de Aprendizaje , Adulto , Humanos
4.
Tech Coloproctol ; 26(11): 851-862, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35596904

RESUMEN

BACKGROUND: Formation of a defunctioning loop ileostomy is common after mid and low rectal resection. Historically, they were reversed between 3 and 6 months after initial resection. Recently, earlier closure (< 14 days) has been suggested by some current randomised controlled trials. The aim of this study was to investigate the effect of early stoma closure on surgical and patient outcomes. METHODS: A systematic review of the current randomised controlled trial literature comparing early and standard ileostomy closure after rectal surgery was performed. Specifically, we examined surgical outcomes including; morbidity, mortality and quality of life. RESULTS: Six studies met the predefined criteria and were included in our analysis. 275 patients underwent early stoma closure compared with 259 patients having standard closure. Overall morbidity was similar between both groups (25.5% vs. 21.6%) (OR, 1.47; 95% CI 0.75-2.87). However, there tended to be more reoperations (8.4 vs. 4.2%) (OR, 2.02, 95% CI 0.99-4.14) and small bowel obstructions/postoperative ileus (9.3% vs. 4.4%) (OR 0.44, 95% CI 0.22-0.90) in the early closure group, but no difference across the other domains. CONCLUSIONS: Early closure appears to be a feasible in highly selective cases after good perioperative counselling and shared decision-making. Further research on quality of life outcomes and long term benefits is necessary to help define which patients are suitable candidates for early closure.


Asunto(s)
Ileostomía , Neoplasias del Recto , Humanos , Ileostomía/efectos adversos , Ileostomía/métodos , Ileus , Complicaciones Posoperatorias/epidemiología , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias del Recto/cirugía
5.
Hum Mol Genet ; 30(13): 1188-1199, 2021 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-33783477

RESUMEN

Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease with behavioral and genetic etiology and is the leading cause of irreversible vision loss among elderly Caucasians. Functionally significant genetic variants in the alternative pathway of complement have been strongly linked to disease. More recently, a rare variant in the terminal pathway of complement has been associated with increased risk, Complement component 9 (C9) P167S. To assess the functional consequence of this variant, C9 levels were measured in two independent cohorts of AMD patients. In both cohorts, it was demonstrated that the P167S variant was associated with low C9 plasma levels. Further analysis showed that patients with advanced AMD had elevated sC5b-9 compared to those with non-advanced AMD, although this was not associated with the P167S polymorphism. Electron microscopy of membrane attack complexes (MACs) generated using recombinantly produced wild type or P167S C9 demonstrated identical MAC ring structures. In functional assays, the P167S variant displayed a higher propensity to polymerize and a small increase in its ability to induce hemolysis of sheep erythrocytes when added to C9-depleted serum. The demonstration that this C9 P167S AMD risk polymorphism displays increased polymerization and functional activity provides a rationale for the gene therapy trials of sCD59 to inhibit the terminal pathway of complement in AMD that are underway.


Asunto(s)
Complemento C9/genética , Predisposición Genética a la Enfermedad/genética , Degeneración Macular/genética , Mutación , Anciano , Animales , Células CHO , Estudios de Casos y Controles , Estudios de Cohortes , Complemento C9/metabolismo , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Proteínas del Sistema Complemento/genética , Proteínas del Sistema Complemento/metabolismo , Cricetinae , Cricetulus , Femenino , Cobayas , Hemólisis , Humanos , Degeneración Macular/sangre , Degeneración Macular/metabolismo , Masculino , Polimerizacion , Factores de Riesgo , Ovinos
7.
Clin Exp Immunol ; 202(3): 379-383, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32640035

RESUMEN

Primary pneumococcal peritonitis is a rare infection that has been described in women but has not been previously linked with immunodeficiency. The complement system plays a central role in immune defence against Streptococcus pneumoniae and, in order to evade complement attack, pneumococci have evolved a large number of mechanisms that limit complement-mediated opsonization and subsequent phagocytosis. We investigated an apparently immunocompetent woman with primary pneumococcal peritonitis and identified a family with deficiency for complement factor I. Primary pneumococcal peritonitis should be considered a possible primary immunodeficiency presentation.


Asunto(s)
Complemento C3/deficiencia , Enfermedades por Deficiencia de Complemento Hereditario/inmunología , Peritonitis/inmunología , Infecciones Neumocócicas/inmunología , Streptococcus pneumoniae/inmunología , Adolescente , Complemento C3/inmunología , Femenino , Enfermedades por Deficiencia de Complemento Hereditario/patología , Humanos , Peritonitis/patología , Infecciones Neumocócicas/patología
8.
J R Soc Interface ; 17(166): 20200066, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32453981

RESUMEN

Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare disorder with devastating sequelae resulting in early death, presently thought to stem primarily from cardiovascular events. We analyse novel longitudinal cardiovascular data from a mouse model of HGPS (LmnaG609G/G609G) using allometric scaling, biomechanical phenotyping, and advanced computational modelling and show that late-stage diastolic dysfunction, with preserved systolic function, emerges with an increase in the pulse wave velocity and an associated loss of aortic function, independent of sex. Specifically, there is a dramatic late-stage loss of smooth muscle function and cells and an excessive accumulation of proteoglycans along the aorta, which result in a loss of biomechanical function (contractility and elastic energy storage) and a marked structural stiffening despite a distinctly low intrinsic material stiffness that is consistent with the lack of functional lamin A. Importantly, the vascular function appears to arise normally from the low-stress environment of development, only to succumb progressively to pressure-related effects of the lamin A mutation and become extreme in the peri-morbid period. Because the dramatic life-threatening aortic phenotype manifests during the last third of life there may be a therapeutic window in maturity that could alleviate concerns with therapies administered during early periods of arterial development.


Asunto(s)
Cardiopatías , Progeria , Animales , Aorta , Ratones , Músculo Liso Vascular , Mutación , Progeria/genética , Análisis de la Onda del Pulso
9.
Bone ; 136: 115329, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32224162

RESUMEN

Pyrophosphate (PPi) serves as a potent and physiologically important regulator of mineralization, with systemic and local concentrations determined by several key regulators, including: tissue-nonspecific alkaline phosphatase (ALPL gene; TNAP protein), the progressive ankylosis protein (ANKH; ANK), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1; ENPP1). Results to date have indicated important roles for PPi in cementum formation, and we addressed several gaps in knowledge by employing genetically edited mouse models where PPi metabolism was disrupted and pharmacologically modulating PPi in a PPi-deficient mouse model. We demonstrate that acellular cementum growth is inversely proportional to PPi levels, with reduced cementum in Alpl KO (increased PPi levels) mice and excess cementum in Ank KO mice (decreased PPi levels). Moreover, simultaneous ablation of Alpl and Ank results in reestablishment of functional cementum in dKO mice. Additional reduction of PPi by dual deletion of Ank and Enpp1 does not further increase cementogenesis, and PDL space is maintained in part through bone modeling/remodeling by osteoclasts. Our results provide insights into cementum formation and expand our knowledge of how PPi regulates cementum. We also demonstrate for the first time that pharmacologic manipulation of PPi through an ENPP1-Fc fusion protein can regulate cementum growth, supporting therapeutic interventions targeting PPi metabolism.


Asunto(s)
Cementogénesis , Difosfatos , Animales , Cemento Dental , Ratones , Osteoclastos
10.
Surgeon ; 18(2): 80-90, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31345681

RESUMEN

BACKGROUND: Emergency abdominal surgery is associated with poorer clinical outcomes than similar procedures in the elective setting. Research into emergency laparotomy (EL) care is moving from observational studies which simply measure EL outcomes to interventional research evaluating the implementation of care strategies designed to improve the quality and outcomes from EL care. There is no consensus as to the optimal approach to conducting research in this sphere. The primary objective of this review was to examine how mortality and other outcome measures were reported in previous EL research and to identify what might be the most appropriate methods in future outcome research. METHODS: A systematic review was performed in accordance with the PRISMA principles. Electronic databases were interrogated with a pre-specified search strategy to identify English language studies addressing outcomes from EL care. Retrieved papers were screened and assessed according to pre-defined eligibility criteria. The mortality and other outcomes reported in each paper were extracted and examined. RESULTS: 16 studies were included. They demonstrated significant heterogeneity in case definition, outcome reporting and data processing. A wide range of mortality and other outcome measures were applied and reported. Only few studies included on patient-reported outcomes measures. CONCLUSION: The heterogeneity in EL research, demonstrated by this review must be considered when EL outcomes are compared. A standardized approach with respect to case definition, outcome measurement, and data analysis would provide for more valid and comparable evaluation of EL outcomes. Future EL research should include more patient centred outcomes.


Asunto(s)
Investigación Biomédica , Urgencias Médicas , Laparotomía/métodos , Humanos , Laparotomía/mortalidad , Evaluación de Resultado en la Atención de Salud
11.
Front Surg ; 6: 25, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31157232

RESUMEN

Background: Small bowel bleeding accounts for 5-10% of all gastrointestinal bleeding. Despite advances in imaging, endoscopy and minimally invasive therapeutic techniques, its diagnosis and treatment remains a challenge and a standardized algorithm for approaching suspected small bowel bleeding remains elusive. Furthermore, the choice of investigation is subject to timing of presentation and accessibility to investigations. The aim of this study was to construct a narrative review of recent literature surrounding the diagnosis and management of small bowel bleeding. Methods: A literature review was conducted examining the database pubmed with the following key words and Boolean operators: occult GI bleed OR mesenteric bleed OR gastrointestinal hemorrhage OR GI hemorrhage AND management. Articles were selected and reviewed based on relevance to the research topic. Where necessary, the full text was sought to further assess relevance. Results: In overt GI bleeding, CT angiography and red cell scintigraphy are both feasible and reliable diagnostic imaging modalities if standard endoscopy is negative. Red cell scintigraphy may be advantageous through detection of lower bleeding rates but it is subject to availability. Overt bleeding and a positive CT angiogram or red cell scan improves the diagnostic yield of formal angiography ± embolization. Video capsule endoscopy or double balloon endoscopy can be considered in occult GI bleeding following normal upper and lower endoscopy. Conclusions: Small bowel bleeding remains a rare but significant diagnostic and therapeutic challenge. Technological advances in diagnostics have aided evaluation but have not broadened the range of therapeutic interventions.

12.
Br J Surg ; 106(10): 1298-1310, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31216064

RESUMEN

BACKGROUND: The current standard of care in locally advanced rectal cancer (LARC) is neoadjuvant long-course chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). Surgery is conventionally performed approximately 6-8 weeks after nCRT. This study aimed to determine the effect on outcomes of extending this interval. METHODS: A systematic search was performed for studies reporting oncological results that compared the classical interval (less than 8 weeks) from the end of nCRT to TME with a minimum 8-week interval in patients with LARC. The primary endpoint was the rate of pathological complete response (pCR). Secondary endpoints were recurrence-free survival, local recurrence and distant metastasis rates, R0 resection rates, completeness of TME, margin positivity, sphincter preservation, stoma formation, anastomotic leak and other complications. A meta-analysis was performed using the Mantel-Haenszel method. RESULTS: Twenty-six publications, including four RCTs, with 25 445 patients were identified. A minimum 8-week interval was associated with increased odds of pCR (odds ratio (OR) 1·41, 95 per cent c.i. 1·30 to 1·52; P < 0·001) and tumour downstaging (OR 1·18, 1·05 to 1·32; P = 0·004). R0 resection rates, TME completeness, lymph node yield, sphincter preservation, stoma formation and complication rates were similar between the two groups. The increased rate of pCR translated to reduced distant metastasis (OR 0·71, 0·54 to 0·93; P = 0·01) and overall recurrence (OR 0·76, 0·58 to 0·98; P = 0·04), but not local recurrence (OR 0·83, 0·49 to 1·42; P = 0·50). CONCLUSION: A minimum 8-week interval from the end of nCRT to TME increases pCR and downstaging rates, and improves recurrence-free survival without compromising surgical morbidity.


ANTECEDENTES: El tratamiento estándar actual del cáncer de recto localmente avanzado (locally advanced rectal cancer, LARC) consiste en quimiorradioterapia neoadyuvante de ciclo largo (neoadjuvant, long-course chemoradiation, nCRT) seguida de exéresis total del mesorrecto (total mesorectal excision, TME). De forma convencional, la cirugía se realiza a las 6-8 semanas después de la nCRT. Este estudio tuvo como objetivo determinar el efecto sobre los resultados de ampliar este intervalo. MÉTODOS: Se realizó una búsqueda sistemática de los estudios que analizaban los resultados oncológicos, comparando el intervalo clásico (< 8 semanas) desde el final de la nCRT hasta la TME con un intervalo mínimo de 8 semanas, en pacientes con LARC. El criterio de valoración principal fue la tasa de respuesta patológica completa (pathologic complete response, pCR). Los criterios de valoración secundarios fueron las tasas de supervivencia sin recidiva (recurrence-free survival, RFS), recidiva local (local recurrence, LR) y metástasis a distancia (distant metastasis, DM), tasas de resección R0, integridad (completeness) del mesorrecto, afectación del margen de resección, preservación esfinteriana, formación de estoma, fuga anastomótica y otras complicaciones. Se realizó un metaanálisis utilizando el método de Mantel-Haenszel. RESULTADOS: Se identificaron 26 publicaciones, incluidos cuatro ensayos clínicos aleatorizados, con 17.220 pacientes. Un intervalo mínimo de 8 semanas se asoció con un aumento de la razón de oportunidades (odds ratio, OR) de pCR (OR, 1,68, i.c. del 95% 1,37-2,06, P < 0,001) y de disminución del estadio tumoral (OR 1,18, i.c. del 95% 1,05-1,32, P = 0,004). Los porcentajes de resección R0, integridad del mesorrecto, ganglios linfáticos identificados, preservación esfinteriana, formación de estoma y complicaciones fueron similares entre los dos grupos. El aumento del porcentaje de pCR se tradujo en una disminución de las DM (OR 0,71, i.c. del 95% 0,54-0,93, P = 0,01) y de la recidiva global (OR 0,76, i.c. del 95% 0,58-0,98, P = 0,04), pero no de la LR (OR 0,83, i.c. del 95% 0,49-1,42, P = 0,50). CONCLUSIÓN: Un intervalo mínimo de 8 semanas entre el final de la nCRT y la TME aumenta las tasas de pCR y la reducción del estadio tumoral, así como mejora la RFS sin comprometer la morbilidad quirúrgica.


Asunto(s)
Quimioradioterapia Adyuvante/métodos , Neoplasias del Recto/terapia , Recto/cirugía , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Ensayos Clínicos como Asunto , Supervivencia sin Enfermedad , Humanos , Estudios Observacionales como Asunto , Tempo Operativo , Tratamientos Conservadores del Órgano/métodos , Complicaciones Posoperatorias/etiología , Neoplasias del Recto/mortalidad , Neoplasias del Recto/cirugía , Reoperación/estadística & datos numéricos , Factores de Tiempo , Resultado del Tratamiento
13.
Surgeon ; 17(2): 119-126, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30031668

RESUMEN

PURPOSE: Total mesorectal excision (TME) is the gold standard resectional strategy for rectal cancer to minimize loco-regional recurrence and optimize oncological outcomes. This plane is described by many as 'bloodless' but it does contain important pelvic neural plexuses and dissection may be close to the ureters and major vascular structures, particularly in inflammatory conditions of the distal colon and rectum. In such benign diseases a more conservative excision, so-called close rectal dissection, has been advocated to minimize damage to these structures. METHODS: A review of the literature was conducted to document the evolution of this procedure. Contemporary literature was interrogated to ascertain how this approach is adopted in minimally invasive surgery. Post-operative outcomes are compared to those from TME surgery. RESULTS: From early descriptions in 1956, this procedure has been adapted for use in laparoscopic surgery. It may be particularly useful in trans-anal mesorectal surgery. Reported benefits include reduced nerve injury and pelvic sepsis. However, this must be balanced against risks of mesorectal bleeding, rectal injury, and ongoing inflammation from the retained mesorectum. CONCLUSION: Rectal surgery in inflammatory conditions is technically challenging. Close rectal dissection is an alternate approach available to colorectal surgeons in these cases to minimize pelvic morbidity and optimize postoperative outcomes.


Asunto(s)
Disección/métodos , Proctectomía/efectos adversos , Proctectomía/métodos , Enfermedades del Recto/cirugía , Humanos , Mesocolon/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control
14.
Ir J Med Sci ; 187(2): 297-300, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-28866790

RESUMEN

INTRODUCTION: Recent implementation of the European Working Time Directive in Ireland has resulted in a change from thetraditional model of patient care to a system characterised by shift work among clinicians. Effective handover ofpatient information is essential for transfer of responsibility between clinicians and maintaining continuity of care. The weekend has been identified as a particularly vulnerable transition of patient care. AIMS AND METHODS: Our study aims to determine if implementing a formal face-to-face handover accompanied by an electronictemplate in our surgical department can improve the number of adverse events reported back to the primary teamafter a weekend on call. Data was collected over 12 weekends between February and May 2016. A list of adverseevents was established, and during an initial observation period of 6 weeks, we documented the number of adverseevents that were informally handed over. A 6-week intervention was then performed, involving a formal face-to-facehandover on Monday morning supported by an electronic patient census using a red-flag system to highlightpatients who experienced an adverse event over the weekend. RESULTS: Our results showed the mean number of adverse events recorded pre-intervention was 3.17 ± 0.6 over the 6-week period. Following the introduction of weekend face-to-face handover, there was 147% increase in the number of adverse events recorded with a mean of 7.83 ± 1.2. CONCLUSION: The introduction of a formal face-to-face weekend handover with a red-flag system resulted in increased reporting of patient adverse events, allowing earlier recognition and management.


Asunto(s)
Continuidad de la Atención al Paciente/organización & administración , Pase de Guardia/normas , Evaluación del Resultado de la Atención al Paciente , Humanos , Irlanda
15.
Surgeon ; 14(5): 287-93, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26805472

RESUMEN

The benefits of laparoscopic versus open surgery for patients with both benign and malignant colorectal disease have been well established. Re-laparoscopy in patients who develop complications following laparoscopic colorectal surgery has recently been reported by some groups and the aim of this systematic review was to summarise this literature. A literature search of PubMed, Medline and EMBASE identified a total of 11 studies that reported laparoscopic re-intervention for complications in 187 patients following laparoscopic colorectal surgery. The majority of these patients required re-intervention in the immediate postoperative period (i.e. less than seven days). Anastomotic leakage was the commonest complication requiring re-laparoscopy reported (n = 139). Other complications included postoperative hernia (n = 12), bleeding (n = 9), adhesions (n = 7), small bowel obstruction (n = 4), colonic ischaemia (n = 4), bowel and ureteric injury (n = 3 respectively) and colocutaneous fistula (n = 1). Ninety-seven percent of patients (n = 182) who underwent re-laparoscopy had their complications successfully managed by re-laparoscopy, maintaining the benefits of the laparoscopic approach and avoiding a laparotomy. We conclude that re-laparoscopy for managing complications following laparoscopic colorectal surgery appears to be safe and effective in highly selected patients.


Asunto(s)
Cirugía Colorrectal/efectos adversos , Laparoscopía/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Enfermedades del Colon/cirugía , Medicina Basada en la Evidencia , Humanos , Periodo Posoperatorio , Enfermedades del Recto/cirugía , Reoperación , Factores de Riesgo , Resultado del Tratamiento
16.
Hum Mol Genet ; 25(5): 1001-7, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-26740555

RESUMEN

Schizophrenia is a highly heritable disorder. Genome-wide association studies based largely on common alleles have identified over 100 schizophrenia risk loci, but it is also evident from studies of copy number variants (CNVs) and from exome-sequencing studies that rare alleles are also involved. Full characterization of the contribution of rare alleles to the disorder awaits the deployment of sequencing technology in very large sample sizes, meanwhile, as an interim measure, exome arrays allow rare non-synonymous variants to be sampled at a fraction of the cost. In an analysis of exome array data from 13 688 individuals (5585 cases and 8103 controls) from the UK, we found that rare (minor allele frequency < 0.1%) variant association signal was enriched among genes that map to autosomal loci that are genome-wide significant (GWS) in common variant studies of schizophrenia genome-wide association study (PGWAS = 0.01) as well as gene sets known to be enriched for rare variants in sequencing studies (PRARE = 0.026). We also identified the gene-wise equivalent of GWS support for WDR88 (WD repeat-containing protein 88), a gene of unknown function (P = 6.5 × 10(-7)). Rare alleles represented on exome chip arrays contribute to the genetic architecture of schizophrenia, but as is the case for GWAS, very large studies are required to reveal additional susceptibility alleles for the disorder.


Asunto(s)
Alelos , Predisposición Genética a la Enfermedad , Proteínas del Tejido Nervioso/genética , Proteínas/genética , Sitios de Carácter Cuantitativo , Carácter Cuantitativo Heredable , Esquizofrenia/genética , Estudios de Casos y Controles , Variaciones en el Número de Copia de ADN , Exoma , Femenino , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo de Nucleótido Simple , Tamaño de la Muestra , Esquizofrenia/patología
17.
J Thromb Haemost ; 14(1): 175-85, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26559391

RESUMEN

UNLABELLED: ESSENTIALS: Molecular diagnostics has improved the differentiation of acute thrombotic microangiopathys (TMAs). Atypical hemolytic uremic syndrome may have features mimicking thrombotic thrombocytopenic purpura. We identified novel complement mutations and a high incidence of CD46, with favorable long term outcomes. Complement mutation analysis in TMA where the diagnosis is unclear and ADAMTS-13 activity is >10%. BACKGROUND: Differentiation of acute thrombotic microangiopathy (TMA) at presentation has historically been dependent on clinical parameters. Confirmation of thrombotic thrombocytopenic purpura (TTP) is increasingly reliant on demonstrating deficient ADAMTS-13 activity. The identification of alternative complement pathway abnormalities in atypical hemolytic uremic syndrome (aHUS), along with the proven efficacy of terminal complement inhibitors in treatment, has increased the need for rapid differentiation of TTP from aHUS. OBJECTIVES: We describe the clinical phenotype and nature of complement mutations in a cohort of aHUS patients referred as acute TMAs. PATIENTS/METHODS: Fourteen consecutive aHUS patients were screened for mutations in C3, CD46, CFH, CFI, and CFB, as well as factor H (FH) antibodies. All aHUS patients had ADAMTS-13 activity > 10%. RESULTS: Of 14 aHUS patients, 11 (79%) had platelet counts < 30 × 10(9) /L during the acute phase. Median presenting creatinine level was 295 µmol L(-1) , while five (36%) of 14 presented with a serum creatinine level < 200 µmol L(-1) . Alternative complement pathway mutations were detected in 9 (64%) of 14 patients, including CD46 mutations in five (36%) of 14 patients. Patients were identified with novel mutations in CFB and C3 that have not been previously reported. CONCLUSIONS: We demonstrate that diagnostic differentiation based on platelet count and renal function is insufficient to predict an underlying complement mutation in some aHUS cases. Specifically, we demonstrate a high frequency of functionally significant CD46 mutations which may mimic TTP. ADAMTS-13 activity > 10% in a patient with a TMA should necessitate genetic screening for complement abnormalities.


Asunto(s)
Proteína ADAMTS13/genética , Proteína ADAMTS13/metabolismo , Complemento C3/genética , Factor B del Complemento/genética , Microangiopatías Trombóticas/diagnóstico , Microangiopatías Trombóticas/genética , Enfermedad Aguda , Adolescente , Adulto , Anciano , Síndrome Hemolítico Urémico Atípico/genética , Preescolar , Análisis Mutacional de ADN , Femenino , Humanos , Incidencia , Lactante , Pruebas de Función Renal , Masculino , Proteína Cofactora de Membrana/genética , Persona de Mediana Edad , Mutación , Fenotipo , Recuento de Plaquetas , Púrpura Trombocitopénica Trombótica/diagnóstico , Púrpura Trombocitopénica Trombótica/genética , Estudios Retrospectivos , Adulto Joven
18.
QJM ; 109(1): 27-33, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25899302

RESUMEN

BACKGROUND: In 2013 NHS England commissioned the use of eculizumab for both new patients with atypical haemolytic uraemic syndrome (aHUS) and those undergoing transplantation. This national service is delivered locally but coordinated by an expert centre at the Newcastle upon Tyne Hospitals NHS Foundation Trust. RESULTS: In the first year of service, 43 aHUS patients received eculizumab, 15 children and 28 adults. Twenty-three were new patients and 20 prevalent. Fifteen of the 23 new patients required dialysis before eculizumab was started, 8 of these recovered renal function. Twelve of the 20 prevalent patients who received eculizumab were transplant patients, 8 with prophylactic use and 4 for recurrent disease; the outcome in all was good. Eculizumab was withdrawn in 14 patients, 5 were patients who had not recovered renal function. In 3 of the 14 patients, it was necessary to reintroduce eculizumab because of recurrent disease (2 extra-renal and 1 renal). There were 2 deaths in the 43 patients, and neither was associated with use of eculizumab. There were no episodes of meningococcal disease. CONCLUSIONS: The establishment of this national service has enabled aHUS patients in England to receive eculizumab when they need it for as long as they need it.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Síndrome Hemolítico Urémico Atípico/diagnóstico , Síndrome Hemolítico Urémico Atípico/tratamiento farmacológico , Riñón/fisiopatología , Adolescente , Adulto , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Niño , Preescolar , Inglaterra , Femenino , Humanos , Masculino , Infecciones Meningocócicas/prevención & control , Persona de Mediana Edad , Diálisis Renal/métodos , Adulto Joven
19.
Ir J Med Sci ; 185(1): 225-9, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25772125

RESUMEN

BACKGROUND: The implementation of the European work-time directive has created increased transitions of care during weekends as doctors adhere to a shift-work structure. This raises concerns over continuity of care and patient safety. To address this, doctors must develop a time efficient yet safe system of handover of patients to the team on-call. Intuitively weekend care provides the ideal setting to develop a handover tool. AIM: To develop and implement a process of surgical handover and to improve weekend discharge rate on a surgical service. METHODS: Data was collected at three time-points over a 6 months period (October 2013-March 2014) encompassing development, implementation, re-evaluation and modification of the handover process. The outcomes measured were: number of inpatients, number of weekend discharges, length of stay (LOS) of inpatients recorded for the four weekends within the month, and total emergency response team (ERT) calls each month. RESULTS: Mean number of included patients each month was 294 (σ = 14). Following the introduction of weekend handover there was a 40 % increase in weekend discharges which was consistent for subsequent time-points (p < 0.05). Following the second intervention there was a statistically significant reduction in mean LOS from 13 to 5.4 days (p < 0.05) and the total number of ERT calls for the month reduced from 12 to 4 (p < 0.05). CONCLUSIONS: The standardisation of weekend handover using a combination of an electronic tool supplemented with verbal handover is feasible. It resulted in a significant improvement in surrogate markers of patient care quality.


Asunto(s)
Continuidad de la Atención al Paciente/organización & administración , Cirugía General/organización & administración , Alta del Paciente/estadística & datos numéricos , Pase de Guardia/normas , Cuidados Posoperatorios/normas , Lista de Verificación , Eficiencia Organizacional , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Seguridad del Paciente , Centros de Atención Terciaria/organización & administración
20.
Aust Dent J ; 61(2): 219-26, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26086696

RESUMEN

BACKGROUND: Smoking cessation interventions delivered by dental practitioners can be as effective as those delivered by general medical practitioners. However, concern that addressing smoking may cause offence to their patients is a reason cited by dental practitioners for not regularly addressing patient smoking behaviours, despite believing they should play a role in smoking cessation. This study aimed to elicit the smoking behaviour and smoking cessation preferences of dental patients to determine if these concerns accurately reflect patient attitudes. METHODS: We surveyed 726 adult dental patients attending The University of Queensland's School of Dentistry dental clinics, Brisbane Dental Hospital and four private dental practices in South-East Queensland. RESULTS: Most (80%) current daily smokers had tried to quit smoking. Smokers and non-smokers both agreed that dentists should screen for smoking behaviour and are qualified to offer smoking cessation advice (99% and 96% respectively). Almost all participants (96%) said they would be comfortable with their dentist asking about their smoking and that if their smoking was affecting their oral health their dentist should advise them to quit. CONCLUSIONS: Patients are receptive to dental practitioners inquiring about smoking behaviour and offering advice on quitting. Smoking patients showed considerable motivation and interest in quitting smoking, particularly in the context of health problems related to smoking being identified. These results should encourage dentists to raise the issue with their patients.


Asunto(s)
Clínicas Odontológicas/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Servicios Preventivos de Salud/métodos , Cese del Hábito de Fumar , Prevención del Hábito de Fumar , Adulto , Actitud Frente a la Salud , Relaciones Dentista-Paciente , Femenino , Humanos , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto/métodos , Queensland , Cese del Hábito de Fumar/métodos , Cese del Hábito de Fumar/estadística & datos numéricos , Encuestas y Cuestionarios , Adulto Joven
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