RESUMO
BACKGROUND: Chimeric antigen receptor (CAR) T cells targeted to the CD19 B-cell antigen form an approved treatment for patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). However, since this therapy is administered after multiple lines of treatment and exposure to lymphotoxic agents, there is an urgent need to optimize this modality of treatment. METHODS: To circumvent the difficulties of harvesting adequate and optimal T cells from DLBCL patients and improve CART therapy, we suggest an earlier lymphopheresis (i.e. at first relapse, before salvage treatment). We conducted a prospective study and evaluated the potential benefit of an earlier lymphopheresis (early group, n = 22) on the clinical outcome of CD19-CART infused DLBCL patients, in comparison with standard lymphopheresis (i.e. at second relapse and beyond; standard group, n = 23). RESULTS: An increased percentage of naïve T cells and increased in vitro T-cell functionality were observed in the early group. Additionally, these cells exhibit a lower exhaustion profile than T cells collected in the standard group. CONCLUSION: While improved T-cell phenotype and function in the lymphopheresis product did not translate into significantly improved clinical outcomes, a trend towards better overall survival (OS) and progression-free survival (PFS) was observed. Early lymphopheresis maximizes the potential of salvage therapies, without compromising CAR T-cell quality.
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Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Antígenos CD19 , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Prospectivos , Receptores de Antígenos de Linfócitos T , Linfócitos TRESUMO
In recent years, anti-CD20 antibodies have been increasingly used to treat lymphoproliferative and immune disorders. Chronic viral infections are infrequently reported in patients receiving these therapies. Enteroviral infection can cause life-threatening meningoencephalitis and other systemic chronic syndromes in immune deficient patients. We describe the clinical courses and outcomes of 6 patients from 2 tertiary care institutions who developed chronic enteroviral infection with neurological manifestations, after combined chemoimmunotherapy with rituximab for B-cell lymphoma. We review the literature that includes 10 sporadic reported cases of chronic enteroviral meningoencephalitis attributed to rituximab therapy. It is a rare disease, and its diagnosis is often elusive. We propose that low immunoglobulin G levels are the main risk factor for developing chronic enteroviral infection and emphasize the need for a high index of suspicion, early diagnosis, and intervention in this iatrogenic and potentially fatal complication.
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Antineoplásicos Imunológicos/efeitos adversos , Infecções por Enterovirus/etiologia , Linfoma não Hodgkin/complicações , Rituximab/efeitos adversos , Adulto , Idoso , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Biópsia , Medula Óssea/patologia , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/tratamento farmacológico , Evolução Fatal , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêuticoRESUMO
Patients with cancer-related lymphoedema (CRL) commonly refuse treatment with bandaging or hosiery because of hot and humid weather conditions. This review aims to determine the effectiveness and safety of kinesiotaping (KT) in the management of CRL compared to compression bandaging or hosiery. A systematic search of the literature was conducted until July 2015. The primary outcomes were reduction in body part volume or circumference and adverse effects of the interventions. The secondary outcomes were subjective experience of the treatment, severity of lymphoedema-related symptoms and patients' quality of life (QoL). Six randomised controlled trials (RCTs) were included in this review. Five were included in the meta-analysis of the primary outcome limb volume (n = 203, KTn = 91, compression n = 112). It revealed no significant difference between the interventions [WMD -205.33 mL CI (-454.69 to 44.04) P = 0.11]. An increased risk of skin complications with KT was reported in five studies affecting between 10% and 21% of patients. Where lymphoedema-related symptoms were reported KT was found to be superior to compression. Paradoxically, patients receiving bandaging reported a higher QoL. KT was not found to be more comfortable than bandaging. KT should only be used with great caution where bandaging cannot be used.
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Fita Atlética , Linfedema/terapia , Neoplasias/complicações , Linfedema Relacionado a Câncer de Mama/terapia , Bandagens Compressivas , Humanos , Linfedema/etiologia , Qualidade de Vida , Resultado do TratamentoRESUMO
OBJECTIVE: To determine risk of Down syndrome (DS) in multiple relative to singleton pregnancies, and compare prenatal diagnosis rates and pregnancy outcome. DESIGN: Population-based prevalence study based on EUROCAT congenital anomaly registries. SETTING: Eight European countries. POPULATION: 14.8 million births 1990-2009; 2.89% multiple births. METHODS: DS cases included livebirths, fetal deaths from 20 weeks, and terminations of pregnancy for fetal anomaly (TOPFA). Zygosity is inferred from like/unlike sex for birth denominators, and from concordance for DS cases. MAIN OUTCOME MEASURES: Relative risk (RR) of DS per fetus/baby from multiple versus singleton pregnancies and per pregnancy in monozygotic/dizygotic versus singleton pregnancies. Proportion of prenatally diagnosed and pregnancy outcome. STATISTICAL ANALYSIS: Poisson and logistic regression stratified for maternal age, country and time. RESULTS: Overall, the adjusted (adj) RR of DS for fetus/babies from multiple versus singleton pregnancies was 0.58 (95% CI 0.53-0.62), similar for all maternal ages except for mothers over 44, for whom it was considerably lower. In 8.7% of twin pairs affected by DS, both co-twins were diagnosed with the condition. The adjRR of DS for monozygotic versus singleton pregnancies was 0.34 (95% CI 0.25-0.44) and for dizygotic versus singleton pregnancies 1.34 (95% CI 1.23-1.46). DS fetuses from multiple births were less likely to be prenatally diagnosed than singletons (adjOR 0.62 [95% CI 0.50-0.78]) and following diagnosis less likely to be TOPFA (adjOR 0.40 [95% CI 0.27-0.59]). CONCLUSIONS: The risk of DS per fetus/baby is lower in multiple than singleton pregnancies. These estimates can be used for genetic counselling and prenatal screening.
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Síndrome de Down/diagnóstico , Síndrome de Down/epidemiologia , Gravidez Múltipla , Diagnóstico Pré-Natal , Adulto , Europa (Continente)/epidemiologia , Feminino , Humanos , Idade Materna , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez , Prevalência , Risco , Medição de Risco , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Adulto JovemRESUMO
PURPOSE: Colistin is increasingly used as the last-resort treatment option against infections caused by multidrug-resistant (MDR) Gram-negative pathogens, but its nephrotoxicity is of concern, especially in severely ill patients. The aim of this study was to analyze the toxicity of colistin therapy in adults and children with hematological malignancies (HM) and hematopoietic stem cell transplantation (HSCT) recipients. METHODS: Data on HSCT recipients and HM patients, treated with intravenous colistin (2.5-5 mg/kg/day in children and 3-6 million international units (IU) in adults, adjusted to renal function) during the period 2008-2011 in our center, were retrospectively collected and analyzed. Nephrotoxicity was defined according to the RIFLE criteria (Risk, Injury, Failure, Loss, and End-stage kidney disease). RESULTS: Twenty-nine children and adults received 38 courses of intravenous colistin (2.5-5 mg/kg/day in children and 3-6 × 10(6) IU in adults, adjusted to renal function) [allogeneic HSCT (22 courses) and HM (16 courses)] for 3-28 days (median 10 days) for empirical therapy for nosocomial clinical sepsis (28) or local infection (6), and bacteremia with MDR Gram-negative rods (4). Nephrotoxicity was observed at the end of 4 (10.5%) courses. In 32 (84%) courses, nephrotoxic medications were concomitantly administered. Two patients had convulsions, probably unrelated to colistin. Seven patients (18%) died while on colistin therapy. No death was attributed to an adverse effect of colistin. CONCLUSIONS: Treatment with intravenous colistin, with dosage adjusted to renal function, was relatively safe for HM/HSCT patients, even with concomitantly administered nephrotoxic medications. Concern about nephrotoxicity should not justify a delay in initiating empirical colistin treatment in situations where infection with MDR Gram-negative rods is likely.
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Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Colistina/administração & dosagem , Colistina/efeitos adversos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Neoplasias Hematológicas/microbiologia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Idoso , Bacteriemia/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate time trends in preterm birth in Europe by multiplicity, gestational age, and onset of delivery. DESIGN: Analysis of aggregate data from routine sources. SETTING: Nineteen European countries. POPULATION: Live births in 1996, 2000, 2004, and 2008. METHODS: Annual risk ratios of preterm birth in each country were estimated with year as a continuous variable for all births and by subgroup using log-binomial regression models. MAIN OUTCOME MEASURES: Overall preterm birth rate and rate by multiplicity, gestational age group, and spontaneous versus non-spontaneous (induced or prelabour caesarean section) onset of labour. RESULTS: Preterm birth rates rose in most countries, but the magnitude of these increases varied. Rises in the multiple birth rate as well as in the preterm birth rate for multiple births contributed to increases in the overall preterm birth rate. About half of countries experienced no change or decreases in the rates of singleton preterm birth. Where preterm birth rates rose, increases were no more prominent at 35-36 weeks of gestation than at 32-34 weeks of gestation. Variable trends were observed for spontaneous and non-spontaneous preterm births in the 13 countries with mode of onset data; increases were not solely attributed to non-spontaneous preterm births. CONCLUSIONS: There was a wide variation in preterm birth trends in European countries. Many countries maintained or reduced rates of singleton preterm birth over the past 15 years, challenging a widespread belief that rising rates are the norm. Understanding these cross-country differences could inform strategies for the prevention of preterm birth.
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Nascimento Prematuro/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Nascido Vivo/epidemiologia , Prole de Múltiplos Nascimentos/estatística & dados numéricos , GravidezRESUMO
OBJECTIVE: To assess the public health consequences of the rise in multiple births with respect to congenital anomalies. DESIGN: Descriptive epidemiological analysis of data from population-based congenital anomaly registries. SETTING: Fourteen European countries. POPULATION: A total of 5.4 million births 1984-2007, of which 3% were multiple births. METHODS: Cases of congenital anomaly included live births, fetal deaths from 20 weeks of gestation and terminations of pregnancy for fetal anomaly. MAIN OUTCOME MEASURES: Prevalence rates per 10,000 births and relative risk of congenital anomaly in multiple versus singleton births (1984-2007); proportion prenatally diagnosed, proportion by pregnancy outcome (2000-07). Proportion of pairs where both co-twins were cases. RESULTS: Prevalence of congenital anomalies from multiple births increased from 5.9 (1984-87) to 10.7 per 10,000 births (2004-07). Relative risk of nonchromosomal anomaly in multiple births was 1.35 (95% CI 1.31-1.39), increasing over time, and of chromosomal anomalies was 0.72 (95% CI 0.65-0.80), decreasing over time. In 11.4% of affected twin pairs both babies had congenital anomalies (2000-07). The prenatal diagnosis rate was similar for multiple and singleton pregnancies. Cases from multiple pregnancies were less likely to be terminations of pregnancy for fetal anomaly, odds ratio 0.41 (95% CI 0.35-0.48) and more likely to be stillbirths and neonatal deaths. CONCLUSIONS: The increase in babies who are both from a multiple pregnancy and affected by a congenital anomaly has implications for prenatal and postnatal service provision. The contribution of assisted reproductive technologies to the increase in risk needs further research. The deficit of chromosomal anomalies among multiple births has relevance for prenatal risk counselling.
Assuntos
Anormalidades Congênitas/epidemiologia , Morte Fetal/epidemiologia , Prole de Múltiplos Nascimentos , Complicações na Gravidez/epidemiologia , Natimorto/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Gravidez , Resultado da Gravidez , Diagnóstico Pré-Natal , Prevalência , Sistema de Registros , RiscoRESUMO
The consensus panel 2 (CP2) of the 11th International Workshop on Waldenström's macroglobulinemia (IWWM-11) has reviewed and incorporated current data to update the recommendations for treatment approaches in patients with relapsed or refractory WM (RRWM). The key recommendations from IWWM-11 CP2 include: (1) Chemoimmunotherapy (CIT) and/or a covalent Bruton tyrosine kinase (cBTKi) strategies are important options; their use should reflect the prior upfront strategy and are subject to their availability. (2) In selecting treatment, biological age, co-morbidities and fitness are important; nature of relapse, disease phenotype and WM-related complications, patient preferences and hematopoietic reserve are also critical factors while the composition of the BM disease and mutational status (MYD88, CXCR4, TP53) should also be noted. (3) The trigger for initiating treatment in RRWM should utilize knowledge of patients' prior disease characteristics to avoid unnecessary delays. (4) Risk factors for cBTKi related toxicities (cardiovascular dysfunction, bleeding risk and concurrent medication) should be addressed when choosing cBTKi. Mutational status (MYD88, CXCR4) may influence the cBTKi efficacy, and the role of TP53 disruptions requires further study) in the event of cBTKi failure dose intensity could be up titrated subject to toxicities. Options after BTKi failure include CIT with a non-cross-reactive regimen to one previously used CIT, addition of anti-CD20 antibody to BTKi, switching to a newer cBTKi or non-covalent BTKi, proteasome inhibitors, BCL-2 inhibitors, and new anti-CD20 combinations are additional options. Clinical trial participation should be encouraged for all patients with RRWM.
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Antineoplásicos , Macroglobulinemia de Waldenstrom , Humanos , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética , Fator 88 de Diferenciação Mieloide/genética , Consenso , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico , Antineoplásicos/uso terapêuticoRESUMO
AIM: The safety, feasibility and short-term outcomes of laparoscopic resection were assessed in patients with recurrent ileocolic Crohn's disease. METHOD: A consecutive series of patients was identified from a prospectively collated database. Data included patient demographics, previous medical and surgical treatment, operative details and postoperative course. Data from the original index open operation were collected retrospectively by review of the case notes. RESULTS: Between 2005 and 2009, 27 patients [21 women, mean (range) age 31 years (16-51 years)] underwent laparoscopic resection for recurrent ileocolic Crohn's disease. All had histologically confirmed recurrent disease at the ileocolic anastomosis. Five (18.5%) patients required extended resection for Crohn's colitis, three (11.1%) had fistulating disease and one (3.4%) patient had a psoas abscess. The median (range) operative time was 110 min (70-170 min) with a conversion rate of two (7.4%) of 27 patients. The length of stay was 4 days (2-7 days) with time to return to work or full activity of 3.5 weeks (2-7 weeks). CONCLUSION: Laparoscopic resection of recurrent ileocolic Crohn's disease is safe, feasible and associated with short-term benefits.
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Doença de Crohn/cirurgia , Laparoscopia , Adolescente , Adulto , Doença de Crohn/complicações , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
EUROCAT is a European network of population-based congenital anomaly (CA) registries. Twenty-one registries agreed to participate in the EUROlinkCAT study to determine if reliable information on the survival of children born with a major CA between 1995 and 2014 can be obtained through linkage to national vital statistics or mortality records. Live birth children with a CA could be linked using personal identifiers to either their national vital statistics (including birth records, death records, hospital records) or to mortality records only, depending on the data available within each region. In total, 18 of 21 registries with data on 192,862 children born with congenital anomalies participated in the study. One registry was unable to get ethical approval to participate and linkage was not possible for two registries due to local reasons. Eleven registries linked to vital statistics and seven registries linked to mortality records only; one of the latter only had identification numbers for 78% of cases, hence it was excluded from further analysis. For registries linking to vital statistics: six linked over 95% of their cases for all years and five were unable to link at least 85% of all live born CA children in the earlier years of the study. No estimate of linkage success could be calculated for registries linking to mortality records. Irrespective of linkage method, deaths that occurred during the first week of life were over three times less likely to be linked compared to deaths occurring after the first week of life. Linkage to vital statistics can provide accurate estimates of survival of children with CAs in some European countries. Bias arises when linkage is not successful, as early neonatal deaths were less likely to be linked. Linkage to mortality records only cannot be recommended, as linkage quality, and hence bias, cannot be assessed.
Assuntos
Declaração de Nascimento , Anormalidades Congênitas/epidemiologia , Estatísticas Vitais , Anormalidades Congênitas/patologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Sistema de RegistrosRESUMO
BACKGROUND: Inadequate gut function is common and may adversely affect prognosis. However, it is difficult to measure and treatment options are limited. This study evaluated whether gut-specific nutrients (GSNs) could stimulate the return of gut function in critically ill patients, and assessed what effect, if any, this would have on patient outcomes. METHODS: Consecutive critically ill patients intolerant to enteral feeding were randomized to receive a cocktail of GSNs or placebo. Administration was for 1 month and patients were followed for 3 months. The primary endpoint was the time to return of normal gut function. RESULTS: Twenty-five patients were randomized to each group. GSN administration was associated with a quicker return of normal gut function (median 164 versus 214 h; P = 0.016), attenuation of the acute-phase response and a lower incidence of sepsis (4 versus 13 patients, P = 0.015) compared with placebo. There were fewer deaths by 3 months in the GSN group but this did not achieve significance (2 versus 7 deaths; P = 0.138). CONCLUSION: GSNs expedite the return of gut function in the critically ill and improve outcomes. Inadequate gut function may be associated with poor prognosis similar to that of other single organ failures. REGISTRATION NUMBER: ISRCTN61157513 (http://www.controlled-trials.com).
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Estado Terminal/terapia , Suplementos Nutricionais , Dipeptídeos/uso terapêutico , Trato Gastrointestinal/fisiopatologia , Recuperação de Função Fisiológica , Vitaminas/uso terapêutico , Reação de Fase Aguda/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sepse/prevenção & controle , Resultado do TratamentoRESUMO
BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are often criticized for being difficult to implement outside clinical trials. This audit evaluated compliance with an ERAS protocol and compared it with that during a trial. METHODS: Compliance was audited by case-note review of 100 consecutive patients undergoing colorectal surgery. This was compared with the compliance in a group of 95 patients who participated in a clinical trial. RESULTS: Fewer patients in the audit group than in the study group received preoperative oral carbohydrate loading (61.0 versus 96 per cent; P < 0.001), a transverse incision (25.0 versus 39 per cent; P = 0.037), early fluid and diet reintroduction (73.0 versus 99 per cent; P < 0.001), and non-opiate postoperative oral analgesia (70.0 versus 99 per cent; P < 0.001). Lower non-opiate oral analgesia use in the audit group was not associated with a commensurate increase in opiate use (P = 0.061). There was no difference between groups in length of hospital stay (median (interquartile range) 7 (5-8) versus 6 (5-7) days respectively), septic morbidity or 30-day mortality rates. CONCLUSION: Observance to some aspects of the ERAS protocol was lower outside the clinical trial. However, this made little difference to patient outcome.
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Neoplasias Colorretais/cirurgia , Cooperação do Paciente , Idoso , Neoplasias Colorretais/reabilitação , Carboidratos da Dieta/administração & dosagem , Ingestão de Líquidos , Procedimentos Cirúrgicos Eletivos/reabilitação , Feminino , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Estudos RetrospectivosRESUMO
The short-term benefits of laparoscopic resection for standard tumors of the colon and rectum are well accepted. Retrorectal tumors are relatively uncommon, and there have been few reports of laparoscopic techniques being applied to such tumors. This video article presents a laparoscopic approach to a retrorectal schwannoma, highlights the technical challenges of such a procedure, and offers some operative tips to aid management of such tumors (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A29).
Assuntos
Neurilemoma/cirurgia , Neoplasias Retais/cirurgia , Adulto , Feminino , Humanos , LaparoscopiaRESUMO
One of the rewards of having a Drosophila melanogaster whole-genome sequence will be the potential to understand the molecular bases for structural features of chromosomes that have been a long-standing puzzle. Analysis of 2.6 megabases of sequence from the tip of the X chromosome of Drosophila identifies 273 genes. Cloned DNAs from the characteristic bulbous structure at the tip of the X chromosome in the region of the broad complex display an unusual pattern of in situ hybridization. Sequence analysis revealed that this region comprises 154 kilobases of DNA flanked by 1.2-kilobases of inverted repeats, each composed of a 350-base pair satellite related element. Thus, some aspects of chromosome structure appear to be revealed directly within the DNA sequence itself.
Assuntos
Drosophila melanogaster/genética , Cromossomo X/genética , Animais , Bandeamento Cromossômico , Biologia Computacional , Cosmídeos , Elementos de DNA Transponíveis , DNA Satélite , Genes de Insetos , Hibridização In Situ , Sequências Repetitivas de Ácido Nucleico , Análise de Sequência de DNA , Cromossomo X/ultraestruturaRESUMO
BACKGROUND: Enhanced recovery after surgery (ERAS) protocols aim to reduce postoperative lengths of stay (LOS). Laparoscopic surgery shares the same objective. Whether or not laparoscopic surgery conveys additional benefits over and above those achievable with ERAS alone is unclear. METHOD: A review of the literature from January 1966 to June 2008 was performed. Randomized trial and case series investigating the role of laparoscopic surgery within ERAS protocols were included. These were assessed for LOS, readmissions, return of gut function, quality of life and cost of treatment. RESULTS: Four publications from three randomized trials and another seven case series were identified. Two randomized trials revealed no difference in the LOS and readmission rates between ERAS when used alone and ERAS with the inclusion of laparoscopic surgery. However, a third trial revealed a significantly shorter LOS and a lower readmission rate in the ERAS and laparoscopic group. CONCLUSION: The limited evidence presently available suggests that no further benefit is obtained by the inclusion of laparoscopic surgery in ERAS protocols. Further research is needed to derive more definitive conclusions.
Assuntos
Colo/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório , Laparoscopia , Tempo de Internação , Reto/cirurgia , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: SAK/PLK4 is a distinct member of the polo-like kinase family. SAK-/- mice die during embryogenesis, whereas SAK+/- mice develop liver and lung tumors and SAK+/- MEFs show mitotic abnormalities. However, the mechanism underlying these phenotypes is still not known. RESULTS: Here, we show that downregulation of SAK in Drosophila cells, by mutation or RNAi, leads to loss of centrioles, the core structures of centrosomes. Such cells are able to undergo repeated rounds of cell division, but display broad disorganized mitotic spindle poles. We also show that SAK mutants lose their centrioles during the mitotic divisions preceding male meiosis but still produce cysts of 16 primary spermatocytes as in the wild-type. Mathematical modeling of the stereotyped cell divisions of spermatogenesis can account for such loss by defective centriole duplication. The majority of spermatids in SAK mutants lack centrioles and so are unable to make sperm axonemes. Finally, we show that depletion of SAK in human cells also prevents centriole duplication and gives rise to mitotic abnormalities. CONCLUSIONS: SAK/PLK4 is necessary for centriole duplication both in Drosophila and human cells. Drosophila cells tolerate the lack of centrioles and undertake mitosis but cannot form basal bodies and hence flagella. Human cells depleted of SAK show error-prone mitosis, likely to underlie its tumor-suppressor role.
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Centríolos/fisiologia , Flagelos/fisiologia , Mitose/fisiologia , Modelos Biológicos , Proteínas Serina-Treonina Quinases/metabolismo , Fuso Acromático/fisiologia , Animais , Células Cultivadas , Centríolos/genética , Centríolos/ultraestrutura , Drosophila , Flagelos/genética , Humanos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Proteínas Serina-Treonina Quinases/genética , Interferência de RNARESUMO
Introduction One of the most feared complications of colorectal surgery is anastomotic leak. Numerous techniques have been studied in the hope of decreasing leakage. This study was designed to assess the handling characteristics of a novel adhesive tissue patch (TissuePatch™; Tissuemed, Leeds, UK) applied to colorectal anastomoses in a pilot study. This was with a view to assessing its potential role in aiding anastomotic healing in subsequent trials. Methods A patch was applied to colorectal anastomoses after the surgeon had completed the anastomosis and prior to abdominal closure. Handling characteristics and patient outcomes were recorded prospectively. Results Nine patients were recruited before the study was prematurely terminated. In one patient, the patch fell off and in another patient, the surgeon omitted to apply it. Six patients had significant postoperative problems (1 confirmed leak necessitating return to theatre and excision anastomosis, 3 suspicious of leak on computed tomography delaying discharge, 2 perianastomotic collections). One patient had an uneventful recovery. Conclusions Although the handling characteristics of this novel tissue patch were deemed satisfactory, it appears that wrapping a colorectal anastomosis with an adhesive hydrophilic patch has significant deleterious effects on anastomotic healing. This could be a consequence of the creation of a microenvironment between the patch and the anastomosis that impairs healing. Further research is required to better understand the mechanisms involved. At present, the use of such patches on colorectal anastomoses should be discouraged outside the confines of a well monitored trial.
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Fístula Anastomótica/prevenção & controle , Colo/cirurgia , Reto/cirurgia , Adesivos Teciduais/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica , Fístula Anastomótica/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Delayed sepsis, systemic inflammatory response syndrome (SIRS) and multiorgan failure remain major causes of morbidity and mortality on intensive care units. One factor thought to be important in the aetiology of SIRS is failure of the intestinal barrier resulting in bacterial translocation and subsequent sepsis. AIM: This review summarizes the current knowledge about bacterial translocation and methods to prevent it. METHODS: Relevant studies during 1966-2006 were identified from a literature search. Factors, which detrimentally affect intestinal barrier function, are discussed, as are methods that may attenuate bacterial translocation in the critically ill patient. RESULTS: Methodological problems in confirming bacterial translocation have restricted investigations to patients undergoing laparotomy. There are only limited data available relating to specific interventions that might preserve intestinal barrier function or limit bacterial translocation in the intensive care setting. These can be categorized broadly into pre-epithelial, epithelial and post-epithelial interventions. CONCLUSIONS: A better understanding of factors that influence translocation could result in the implementation of interventions which contribute to improved patient outcomes. Glutamine supplementation, targeted nutritional intervention, maintaining splanchnic flow, the judicious use of antibiotics and directed selective gut decontamination regimens hold some promise of limiting bacterial translocation. Further research is required.
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Infecções Bacterianas/imunologia , Translocação Bacteriana/fisiologia , Estado Terminal/terapia , Glutamina/administração & dosagem , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Infecções Bacterianas/dietoterapia , Humanos , Probióticos/administração & dosagem , Traumatismo por Reperfusão/imunologia , Circulação Esplâncnica/fisiologia , Síndrome de Resposta Inflamatória Sistêmica/dietoterapiaRESUMO
INTRODUCTION: A large number of femoral herniae present as emergencies accounting for significant morbidity and mortality, which have remained unchanged over the last decade. Reports of outcomes in femoral hernia surgery are scarce, even more so in district general hospitals where a significant proportion of surgeries are performed. This study compares results of emergency and elective femoral hernia surgery in four district general hospitals against published rates up to a decade ago. MATERIALS AND METHODS: A retrospective study of all patients undergoing femoral hernia surgery in four district hospitals between 2000 and 2004. RESULTS: Seventy-three patients had 75 (28 emergency, 47 elective) femoral hernia repairs. Emergency presentations were associated with increased age(P = 0.001) and right-sided hernias (P = 0.024). Emergency surgery led to increased bowel resection (10.7 vs. 0%, P < 0.001) and longer hospital stays (8 vs. 1 day, P < 0.001) compared to elective surgery. There was no difference in complication rates between emergency and elective surgery (21.4 vs. 12.8%, P = 0.322) or opposition and pectineal flap repair (12.9 vs. 36.4%, P = 0.149). Overall recurrence, morbidity, and mortality were 4.2, 16 and 1.3%, respectively. One patient (3.6%) died after emergency surgery, and no deaths occurred with elective surgery. CONCLUSION: The proportion of femoral herniae presenting as emergencies remained unchanged. This accounts for the morbidity and mortality in femoral surgery, which remains high and similar to a decade ago. Early diagnosis by clinicians and general practitioners and elective surgery are required to reduce mortality. Further investigation into the effect of the opposition technique on femoral vein compression and deep venous thrombosis is warranted.
Assuntos
Procedimentos Cirúrgicos Eletivos/métodos , Emergências , Hérnia Femoral/cirurgia , Hospitais de Distrito , Hospitais Gerais , Procedimentos de Cirurgia Plástica/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: The National Health Service (NHS) Modernisation Agency has identified ten high impact changes for health organisations to adopt in order to improve their service. Top of this list is increasing day-surgery rates. The basket of interventions offered as short-stay procedures will have to increase to achieve this target. The aim of this study was to investigate whether it is feasible to offer fashioning or reversal of loop stomas as a short-stay procedure. METHODS: Consecutive patients needing stoma fashioning or reversal were offered surgery as a day-case. All were recruited from a single colorectal consultant's caseload. Patients scheduled for stoma formation were taught how to manage the stoma by a specialist nurse prior to hospital admission. The stoma nurse then visited all patients at home one day after discharge. Laparoscopic-assisted techniques, opiate avoidance and early mobilisation were included in the management protocol. Data relating to patient demographics, length of stay and complications were collected prospectively. Results of continuous variables were presented as median and interquartile ranges (IQRs). RESULTS: All patients offered day-surgery accepted it readily. A total of twelve patients (M:F, 5:7) with a median (IQR) age of 70 (63-74) years were recruited. Seven had laparoscopically assisted loop ileostomy formation while five underwent loop stoma reversal (four loop ileostomies, one transverse colostomy). Four out of twelve patients were discharged the same day and 11/12 patients were home within 23 hours of admission. One patient needed admission for 72 hours for social reasons. None of the patients required readmission, and there were no observed complications associated with early discharge. CONCLUSIONS: With the appropriate supportive set up, 23-hour stoma surgery is indeed feasible. Day-case procedures are possible in some, however, as with all short-stay surgery, careful patient selection is required.