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1.
PLoS One ; 18(9): e0285230, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37682920

RESUMO

BACKGROUND: Burn injuries are the fourth most common type of trauma and are associated with substantial morbidity and mortality. The impact of burn injury is clinically significant as burn injuries often give rise to exuberant scarring. Hypertrophic scarring (HTS) is a particular concern as up to 70% of burns patients develop HTS. Laser therapy is used for treating HTS and has shown positive clinical outcomes, although the mechanisms remain unclear limiting approaches to improve its effectiveness. Emerging evidence has shown that fibroblasts and senescent cells are important modifiers of scarring. This study aims to investigate the cellular kinetics in HTS after laser therapy, with a focus on the association of scar reduction with the presence of senescent cells. METHODS: We will conduct a multicentre, intra-patient, single-blinded, randomised controlled longitudinal pilot study with parallel assignments to achieve this objective. 60 participants will be recruited to receive 3 interventional ablative fractional CO2 laser treatments over a 12-month period. Each participant will have two scars randomly allocated to receive either laser treatment or standard care. Biopsies will be obtained from laser-treated, scarred-no treatment and non-scarred tissues for immune-histological staining to investigate the longitudinal kinetics of p16INK4A+-senescent cells and fibroblast subpopulations (CD90+/Thy1+ and αSMA+). Combined subjective scar assessments including Modified Vancouver Scar Scale, Patient and Observer Scar Assessment Scale and Brisbane Burn Scar Impact Profile; and objective assessment tools including 3D-Vectra-H1 photography, DermaScan® Cortex, Cutometer® and ColoriMeter®DSMIII will be used to evaluate clinical outcomes. These will then be used to investigate the association between senescent cells and scar reduction after laser therapy. This study will also collect blood samples to explore the systemic biomarkers associated with the response to laser therapy. DISCUSSION: This study will provide an improved understanding of mechanisms potentially mediating scar reduction with laser treatment, which will enable better designs of laser treatment regimens for those living with HTS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04736251.


Assuntos
Cicatriz Hipertrófica , Lasers de Gás , Terapia com Luz de Baixa Intensidade , Humanos , Projetos Piloto , Lasers de Gás/uso terapêutico , Estudos Prospectivos , Cicatriz Hipertrófica/radioterapia , Dióxido de Carbono , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto
2.
Pediatr Transplant ; 27(3): e14473, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36694298

RESUMO

BACKGROUND: Late airway complications, as consequence of immunosuppression following pediatric liver transplantation are uncommonly reported. METHODS: In this retrospective case series, we describe two young children presenting with symptoms of airway obstruction, secondary to differing pathologies in the supraglottic airway, as a result of immunosuppression following liver transplantation. RESULTS: Case 1, a 2-year-old girl who presented with stridor 12-months following liver transplantation, was found to have a proliferative soft tissue mass involving the supraglottic larynx. Biopsies were consistent with infiltrative eosinophilic laryngitis and associated eosinophilic esophagitis. Case 2, a 12-month-old female who presented with stridor 5-months following liver transplantation, was found to have an exophytic soft tissue mass involving the supraglottis and hypopharynx. Biopsies revealed polymorphic Epstein-Barr virus (EBV) driven post-transplant lymphoproliferative disease (PTLD). Case 1 was managed with local resection and high dose oral corticosteroids. Case 2 responded to debulking of the necrotic supraglottic mass, reduction of immunosuppression and rituximab. CONCLUSION: A high index of suspicion needs to be maintained for complications of immunosuppression for appropriate diagnosis of airway presentations following pediatric liver transplantation. Further research is necessary to improve early detection and consolidate management strategies for these airway lesions.


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Fígado , Transtornos Linfoproliferativos , Criança , Humanos , Feminino , Pré-Escolar , Lactente , Infecções por Vírus Epstein-Barr/etiologia , Herpesvirus Humano 4 , Estudos Retrospectivos , Transplante de Fígado/efeitos adversos , Sons Respiratórios/etiologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/terapia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia
3.
J Pain Symptom Manage ; 63(6): e601-e610, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35595373

RESUMO

BACKGROUND: Each year, approximately one million older adults die in American intensive care units (ICUs) or survive with significant functional impairment. Inadequate symptom management, surrogates' psychological distress and inappropriate healthcare use are major concerns. Pioneering work by Dr. J. Randall Curtis paved the way for integrating palliative care (PC) specialists to address these needs, but convincing proof of efficacy has not yet been demonstrated. DESIGN: We will conduct a multicenter patient-randomized efficacy trial of integrated specialty PC (SPC) vs. usual care for 500 high-risk ICU patients over age 60 and their surrogate decision-makers from five hospitals in Pennsylvania. INTERVENTION: The intervention will follow recommended best practices for inpatient PC consultation. Patients will receive care from a multidisciplinary SPC team within 24 hours of enrollment that continues until hospital discharge or death. SPC clinicians will meet with patients, families, and the ICU team every weekday. SPC and ICU clinicians will jointly participate in proactive family meetings according to a predefined schedule. Patients in the control arm will receive routine ICU care. OUTCOMES: Our primary outcome is patient-centeredness of care, measured using the modified Patient Perceived Patient-Centeredness of Care scale. Secondary outcomes include surrogates' psychological symptom burden and health resource utilization. Other outcomes include patient survival, as well as interprofessional collaboration. We will also conduct prespecified subgroup analyses using variables such as PC needs, measured by the Needs of Social Nature, Existential Concerns, Symptoms, and Therapeutic Interaction scale. CONCLUSIONS: This trial will provide robust evidence about the impact of integrating SPC with critical care on patient, family, and health system outcomes.


Assuntos
Estado Terminal , Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Idoso , Cuidados Críticos , Estado Terminal/terapia , Humanos , Unidades de Terapia Intensiva , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Cuidados Paliativos/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Cureus ; 13(4): e14649, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-34055509

RESUMO

Eosinophilic granulomatosis with polyangiitis (EGPA) is an exceptionally rare systemic necrotizing vasculitis. The disease is clinically characterized by asthma with concomitant blood and tissue eosinophilia, often progressing to eosinophilic vasculitis. From the onset of asthma, there is usually a three to nine year delay of EGPA diagnosis. We report a case of this highly uncommon disease identified in an early stage.

6.
Am J Med Genet A ; 185(7): 2168-2174, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33960657

RESUMO

Ring-finger protein 213 (RNF213) encodes a protein of unknown function believed to play a role in cellular metabolism and angiogenesis. Gene variants are associated with susceptibility to moyamoya disease. Here, we describe two children with moyamoya disease who also demonstrated kidney disease, elevated aminotransferases, and recurrent skin lesions found by exome sequencing to have de novo missense variants in RNF213. These cases highlight the ability of RNF213 to cause Mendelian moyamoya disease in addition to acting as a genetic susceptibility locus. The cases also suggest a new, multi-organ RNF213-spectrum disease characterized by liver, skin, and kidney pathology in addition to severe moyamoya disease caused by heterozygous, de novo C-terminal RNF213 missense variants.


Assuntos
Adenosina Trifosfatases/genética , Nefropatias/genética , Doença de Moyamoya/genética , Dermatopatias/genética , Ubiquitina-Proteína Ligases/genética , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Nefropatias/complicações , Nefropatias/patologia , Masculino , Doença de Moyamoya/complicações , Doença de Moyamoya/patologia , Neovascularização Fisiológica/genética , Dermatopatias/complicações , Dermatopatias/patologia , Transaminases/genética , Sequenciamento do Exoma
7.
J Paediatr Child Health ; 56(11): 1685-1693, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33197972

RESUMO

Coeliac disease (CD) is an autoimmune condition, characterised by an immunological response to ingestion of gluten in genetically susceptible individuals, affecting about 1% of the population in many regions of the world. Increased knowledge regarding the pathogenesis, improved diagnostic techniques and increased awareness over the years have transformed our understanding of CD such that it is no longer a rare enteropathy, but rather a common multisystem disorder which affects individuals of all ages and results in wide-ranging clinical manifestations. Only a minority of children now present with the classical clinical picture of profound diarrhoea and malnutrition. An increasing number of children with CD present with either mild, non-specific gastrointestinal symptoms or extra-intestinal manifestations or even be asymptomatic, as in many screening-detected children. Knowledge about these diverse manifestations and a high index of suspicion is essential so that appropriate investigations can be undertaken, diagnosis established and treatment initiated. Although traditionally small bowel biopsy is considered essential for the diagnosis, recent guidelines from various professional bodies have paved the way to a biopsy-free diagnosis in a subset of symptomatic children. Life long, strict gluten-free diet still remains the only effective treatment at present, although several novel therapeutic agents are in various phases of clinical trials.


Assuntos
Doença Celíaca , Biópsia , Causalidade , Doença Celíaca/diagnóstico , Doença Celíaca/terapia , Criança , Dieta Livre de Glúten , Glutens , Humanos
8.
JGH Open ; 4(4): 642-648, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32782951

RESUMO

BACKGROUND AND AIM: High rates of inflammatory bowel disease (IBD) have been documented in New Zealand (NZ) children. The objectives of this study were to describe the outcomes and disease course of childhood IBD in the first 3 years following diagnosis. METHODS: All children diagnosed with IBD in 2015 in NZ were included. Clinical data obtained during routine care for 3 years following diagnosis were analyzed. Growth parameters, disease activity scores, and blood parameters were compared at diagnosis and follow up. RESULTS: Three-year outcome data were available for 48 of 51 children. At follow up, median age was 15.1 years, and 34 had Crohn's disease (CD), 11 had ulcerative colitis (UC), and three had IBD-unclassified (IBDU). Although disease progression including development of perianal disease occurred in 13 (38%) of 34 children with CD, the majority (n = 30) had inflammatory disease at follow up. Disease extension occurred in 25% (2/8) of children initially diagnosed with UC. Of all IBD patients, the mean body mass index z-score increased from -0.40 to +0.10 (P = 0.01). Disease activity scores reduced from diagnosis to follow up in both CD (mean pediatric Crohn's disease activity index 35-6, P < 0.001) and UC (mean pediatric ulcerative colitis activity index 44-6, P < 0.001). Overall, 56% of children received steroids, 44% of children with CD received biologic therapy, and four children with CD or UC had intestinal surgery. CONCLUSIONS: Most children with IBD were in remission with improved growth 3 years after diagnosis. Biologic therapies were commonly prescribed. This is the first NZ study assessing disease course in pediatric IBD. Ongoing follow up will continue to inform outcomes.

9.
EClinicalMedicine ; 20: 100296, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32300742

RESUMO

BACKGROUND: The incidence of knife-related injuries is rising across the UK. This study aimed to determine the spectrum of knife-related injuries in a major UK city, with regards to patient and injury characteristics. A secondary aim was to quantify their impact on secondary care resources. METHODS: Observational study of patients aged 16+ years admitted to a major trauma centre following knife-related injuries resulting from interpersonal violence (May 2015 to April 2018). Patients were identified using Emergency Department and discharge coding, blood bank and UK national Trauma Audit and Research prospective registries. Patient and injury characteristics, outcome and resource utilisation were collected from ambulance and hospital records. FINDINGS: 532 patients were identified; 93% male, median age 26 years (IQR 20-35). Median injury severity score was 9 (IQR 3-13). 346 (65%) underwent surgery; 133 (25%) required intensive care; 95 (17·9%) received blood transfusion. Median length of stay was 3·3 days (IQR 1·7-6·0). In-hospital mortality was 10/532 (1·9%). 98 patients (18·5%) had previous attendance with violence-related injuries. 24/37 females (64·9%) were injured in a domestic setting. Intoxication with alcohol (19·2%) and illicit drugs (17·6%) was common. Causative weapon was household knife in 9%, knife (other/unspecified) in 38·0%, machete in 13·9%, small folding blade (2·8%) and, unrecorded in 36·3%. INTERPRETATION: Knife injuries constitute 12·9% of trauma team workload. Violence recidivism and intoxication are common, and females are predominantly injured in a domestic setting, presenting opportunities for targeted violence reduction interventions. 13·9% of injuries involved machetes, with implications for law enforcement strategies.

10.
Lancet Glob Health ; 7(9): e1280-e1286, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31402008

RESUMO

BACKGROUND: There is ongoing debate on the clinical benefits of antibiotic prophylaxis for reducing pelvic infection after miscarriage surgery. We aimed to study the cost-effectiveness of antibiotic prophylaxis in the surgical management of miscarriage in low-income countries. METHODS: We did an incremental cost-effectiveness analysis using data from 3412 women recruited to the AIMS trial, a randomised, double-blind, placebo-controlled trial designed to evaluate the effectiveness of antibiotic prophylaxis in the surgical management of miscarriage in Malawi, Pakistan, Tanzania, and Uganda. Economic evaluation was done from a health-care-provider perspective on the basis of the outcome of cost per pelvic infection avoided within 2 weeks of surgery. Pelvic infection was broadly defined by the presence of clinical features or the clinically identified need to administer antibiotics. We used non-parametric bootstrapping and multilevel random effects models to estimate incremental mean costs and outcomes. Decision uncertainty was shown via cost-effectiveness acceptability frontiers. The AIMS trial is registered with the ISRCTN registry, number ISRCTN97143849. FINDINGS: Between June 2, 2014, and April 26, 2017, 3412 women were assigned to receive either antibiotic prophylaxis (1705 [50%] of 3412) or placebo (1707 [50%] of 3412) in the AIMS trial. 158 (5%) of 3412 women developed pelvic infection within 2 weeks of surgery, of whom 68 (43%) were in the antibiotic prophylaxis group and 90 (57%) in the placebo group. There is 97-98% probability that antibiotic prophylaxis is a cost-effective intervention at expected thresholds of willingness-to-pay per additional pelvic infection avoided. In terms of post-surgery antibiotics, the antibiotic prophylaxis group was US$0·27 (95% CI -0·49 to -0·05) less expensive per woman than the placebo group. A secondary analysis, a sensitivity analysis, and all subgroup analyses supported these findings. Antibiotic prophylaxis, if implemented routinely before miscarriage surgery, could translate to an annual total cost saving of up to $1·4 million across the four participating countries and up to $8·5 million across the two regions of sub-Saharan Africa and south Asia. INTERPRETATION: Antibiotic prophylaxis is more effective and less expensive than no antibiotic prophylaxis. Policy makers in various settings should be confident that antibiotic prophylaxis in miscarriage surgery is cost-effective. FUNDING: UK Medical Research Council, Wellcome Trust, and the UK Department for International Development.


Assuntos
Aborto Espontâneo/cirurgia , Antibioticoprofilaxia/economia , Adolescente , Adulto , Análise Custo-Benefício , Países em Desenvolvimento , Método Duplo-Cego , Feminino , Humanos , Malaui , Paquistão , Gravidez , Tanzânia , Resultado do Tratamento , Uganda , Adulto Jovem
11.
N Engl J Med ; 380(11): 1012-1021, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30865795

RESUMO

BACKGROUND: Surgical intervention is needed in some cases of spontaneous abortion to remove retained products of conception. Antibiotic prophylaxis may reduce the risk of pelvic infection, which is an important complication of this surgery, particularly in low-resource countries. METHODS: We conducted a double-blind, placebo-controlled, randomized trial investigating whether antibiotic prophylaxis before surgery to complete a spontaneous abortion would reduce pelvic infection among women and adolescents in low-resource countries. We randomly assigned patients to a single preoperative dose of 400 mg of oral doxycycline and 400 mg of oral metronidazole or identical placebos. The primary outcome was pelvic infection within 14 days after surgery. Pelvic infection was defined by the presence of two or more of four clinical features (purulent vaginal discharge, pyrexia, uterine tenderness, and leukocytosis) or by the presence of one of these features and the clinically identified need to administer antibiotics. The definition of pelvic infection was changed before the unblinding of the data; the original strict definition was two or more of the clinical features, without reference to the administration of antibiotics. RESULTS: We enrolled 3412 patients in Malawi, Pakistan, Tanzania, and Uganda. A total of 1705 patients were assigned to receive antibiotics and 1707 to receive placebo. The risk of pelvic infection was 4.1% (68 of 1676 pregnancies) in the antibiotics group and 5.3% (90 of 1684 pregnancies) in the placebo group (risk ratio, 0.77; 95% confidence interval [CI], 0.56 to 1.04; P = 0.09). Pelvic infection according to original strict criteria was diagnosed in 1.5% (26 of 1700 pregnancies) and 2.6% (44 of 1704 pregnancies), respectively (risk ratio, 0.60; 95% CI, 0.37 to 0.96). There were no significant between-group differences in adverse events. CONCLUSIONS: Antibiotic prophylaxis before miscarriage surgery did not result in a significantly lower risk of pelvic infection, as defined by pragmatic broad criteria, than placebo. (Funded by the Medical Research Council and others; AIMS Current Controlled Trials number, ISRCTN97143849.).


Assuntos
Aborto Espontâneo/cirurgia , Antibioticoprofilaxia , Doxiciclina/uso terapêutico , Metronidazol/uso terapêutico , Infecção Pélvica/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios , Administração Oral , Adolescente , Adulto , África Subsaariana , Países em Desenvolvimento , Método Duplo-Cego , Doxiciclina/efeitos adversos , Feminino , Humanos , Metronidazol/efeitos adversos , Paquistão , Infecção Pélvica/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Gravidez , Resultado do Tratamento
12.
Br J Ophthalmol ; 103(10): 1491-1494, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30636208

RESUMO

BACKGROUND/AIM: Historic data suggest that open globe injuries should be repaired within 12-24 hours to reduce the risk of endophthalmitis. However, endophthalmitis is uncommon when systemic antibiotic prophylaxis is given. It is not clear whether delayed primary repair impacts visual outcomes in other ways or what is the optimum time to repair. We aimed to examine the effect of time to primary repair on visual outcomes. METHODS: This is a retrospective comparative case series including all open globe injuries presenting to the Birmingham Midland Eye Centre between 1 January 2014 and 15 March 2016. Presenting features, mechanism of injury, visual acuity at 6-12 months and demographic data were examined. RESULTS: 56 open globe injuries were repaired, of which sufficient data for analysis were available on 52 cases. The mean time to primary repair was 1 day after injury (range 5 hours to 7 days). Final visual acuity at 6-12 months was related to the presenting visual acuity and the Ocular Trauma Score and to the time between injury and primary repair, with a reduction in predicted visual acuity of logarithm of the minimum angle of resolution of 0.37 for every 24 hours of delay (95% CI 0.14 to 0.6). DISCUSSION: Open globe injuries should be repaired promptly. Presenting visual acuity remains the strongest predictor of outcome; however, delay to primary repair also reduced final visual acuity, and any significant delay from injury to repair is likely to negatively impact final visual outcome.


Assuntos
Corpos Estranhos no Olho/cirurgia , Ferimentos Oculares Penetrantes/cirurgia , Tempo para o Tratamento , Acuidade Visual/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoftalmite/fisiopatologia , Corpos Estranhos no Olho/fisiopatologia , Ferimentos Oculares Penetrantes/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Oftalmológicos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
13.
Pediatr Transplant ; : e13234, 2018 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-29877025

RESUMO

We report the first two pediatric patients with CF who underwent successful combined liver-pancreas transplantation in Australia and New Zealand for CF liver disease and CF-related diabetes mellitus.

14.
J Pediatr Gastroenterol Nutr ; 67(6): 749-754, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29916948

RESUMO

OBJECTIVE: The 2012 European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guideline for diagnosis of celiac disease (CD) questioned the requirement for intestinal biopsy to confirm the diagnosis. The guideline recommends that in symptomatic patients with consistent human leukocyte antigen (HLA) subtypes, the diagnostic accuracy of strongly positive serology is sufficient to confirm the diagnosis. We prospectively assessed these guidelines in a "real-life" clinical setting. METHODS: One hundred and four children referred for evaluation of possible CD were prospectively recruited. Following informed consent, blood was drawn for serological testing and HLA analysis at upper gastrointestinal endoscopy. Histological findings according to Marsh criteria were correlated with blood results and the accuracy of the guideline analyzed.The study also examined the role of deamidated gliadin peptide (DGP) in the diagnosis of CD. RESULTS: For symptomatic patients with consistent HLA subtypes, strongly positive serology (as described in the ESPGHAN guidelines) accurately predicted biopsy-proven CD in >95% of cases. DGP was positive in fewer patients than anti-TG2 or EMA. Incorporation of DGP as a second confirmatory serological test in place of EMA was associated with maintained predictive value of guideline, but fewer patients fulfilling criteria for biopsy-free diagnosis. CONCLUSIONS: The ESPGHAN guideline performs well in our population. Adoption of the guideline would reduce the number of patients requiring endoscopy without compromise in diagnostic accuracy. The involvement of pediatric gastroenterological expertise, however, remains key to diagnosis of CD.


Assuntos
Doença Celíaca/diagnóstico , Gastroenterologia/normas , Ciências da Nutrição/normas , Pediatria/normas , Testes Sorológicos/estatística & dados numéricos , Adolescente , Autoanticorpos/sangue , Autoanticorpos/imunologia , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Proteínas de Ligação ao GTP/imunologia , Gliadina/sangue , Antígenos HLA/sangue , Humanos , Masculino , Nova Zelândia , Peptídeos/sangue , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Estudos Prospectivos , Proteína 2 Glutamina gama-Glutamiltransferase , Testes Sorológicos/normas , Transglutaminases/imunologia
15.
J Paediatr Child Health ; 54(6): 609-619, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29768684

RESUMO

Cystic fibrosis (CF) is the most common, life-shortening, genetic illness affecting children in Australia and New Zealand. The genetic abnormality results in abnormal anion transport across the apical membrane of epithelial cells in a number of organs, including the lungs, gastrointestinal tract, liver and genito-urinary tract. Thus, CF is a multi-system disorder that requires a multi-disciplinary approach. Respiratory disease is the predominant cause of both morbidity and mortality in patients with CF. However, there are significant and clinically relevant gastrointestinal, liver, pancreatic and nutritional manifestations that must be detected and managed in a timely and structured manner. The aim of this review is to provide evidence-based information and clinical algorithms to guide the nutritional and gastrointestinal management of patients with CF.


Assuntos
Fibrose Cística/complicações , Gastroenteropatias/etiologia , Gastroenteropatias/fisiopatologia , Dor Abdominal/tratamento farmacológico , Austrália , Criança , Transtornos da Nutrição Infantil , Refluxo Gastroesofágico/etiologia , Humanos , Hepatopatias/etiologia , Nova Zelândia
16.
Blood Adv ; 2(3): 240-251, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29437639

RESUMO

Soluble glycoprotein VI (sGPVI) is shed from the platelet surface and is a marker of platelet activation in thrombotic conditions. We assessed sGPVI levels together with patient and clinical parameters in acute and chronic inflammatory conditions, including patients with thermal injury and inflammatory bowel disease and patients admitted to the intensive care unit (ICU) for elective cardiac surgery, trauma, acute brain injury, or prolonged ventilation. Plasma sGPVI was measured by enzyme-linked immunosorbent assay and was elevated on day 14 after thermal injury, and was higher in patients who developed sepsis. sGPVI levels were associated with sepsis, and the value for predicting sepsis was increased in combination with platelet count and Abbreviated Burn Severity Index. sGPVI levels positively correlated with levels of D-dimer (a fibrin degradation product) in ICU patients and patients with thermal injury. sGPVI levels in ICU patients at admission were significantly associated with 28- and 90-day mortality independent of platelet count. sGPVI levels in patients with thermal injury were associated with 28-day mortality at days 1, 14, and 21 when adjusting for platelet count. In both cohorts, sGPVI associations with mortality were stronger than D-dimer levels. Mechanistically, release of GPVI was triggered by exposure of platelets to polymerized fibrin, but not by engagement of G protein-coupled receptors by thrombin, adenosine 5'-diphosphate, or thromboxane mimetics. Enhanced fibrin production in these patients may therefore contribute to the observed elevated sGPVI levels. sGPVI is an important platelet-specific marker for platelet activation that predicts sepsis progression and mortality in injured patients.


Assuntos
Fibrina/fisiologia , Inflamação/sangue , Ativação Plaquetária , Glicoproteínas da Membrana de Plaquetas/análise , Valor Preditivo dos Testes , Biomarcadores/sangue , Queimaduras/sangue , Queimaduras/mortalidade , Queimaduras/patologia , Progressão da Doença , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Inflamação/mortalidade , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/mortalidade , Doenças Inflamatórias Intestinais/patologia , Mortalidade , Contagem de Plaquetas , Glicoproteínas da Membrana de Plaquetas/metabolismo , Sepse/sangue , Sepse/mortalidade , Sepse/patologia , Solubilidade
17.
Leuk Res ; 62: 51-55, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28985622

RESUMO

Patients with Acute Myeloid Leukemia (AML) have compromised marrow function and chemotherapy causes further suppression. As a result complications are frequent, and patients may require admission to the intensive care unit (ICU). How codes status changes when these events occur and how those changes influence outcome are largely unknown. Outcomes for adult patients with AML, undergoing induction chemotherapy, and transferred to the ICU between January 2000 and December 2013 were analyzed. 94 patients were included. Median survival was 1.3 months. At 3 and 6 months overall survival (OS) was 27% and 18% respectively. Respiratory failure was the most common reason for transfer to ICU (88%), with 63% requiring mechanical ventilation at transfer. Other reasons included: cardiac arrest (18%), septic shock (17%), hypotension (9%), and acute renal failure (9%). The most frequent interventions were mechanical ventilation in 85%, vasopressors in 62%, and hemodialysis in 30%. Following transfer 55 patients (58%) had a change in code status. Overall, 46 patients (49%) changed from Full Code (FC) to Comfort Care (CC), 7 (7%) from FC to Do Not Resuscitate (DNR), and 2 (2%) from DNR to CC. For the entire cohort, ICU mortality (IM) was 61% and hospital mortality (HM) was 71%. For FC or DNR patients, IM was 30% and HM was 41%. For CC patients, IM was 90% and HM was 100%. Overall, 27 patients (29%) survived to discharge. Of those discharged, 22 (81%) were alive at 3 months and 17 (63%) were alive at 6 months. In conclusion, patients that required ICU admission during induction chemotherapy have a poor prognosis. Code status changed during the ICU stay for the majority of patients and always to a less aggressive status.


Assuntos
Unidades de Terapia Intensiva/estatística & dados numéricos , Leucemia Mieloide Aguda/mortalidade , Ordens quanto à Conduta (Ética Médica) , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Quimioterapia de Indução/métodos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Transferência de Pacientes/estatística & dados numéricos , Estudos Retrospectivos
18.
Sci Rep ; 7(1): 1233, 2017 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-28450739

RESUMO

Proximal femoral fractures are a major public health concern with estimated annual direct and social costs amounting to £2 billion and average 30-day mortality risk of 7.5%. In response to the recent debate over out-of-hours hospital provision we investigated the 'weekend effect' at a major trauma centre, caring for acute injuries. A single centre, multi-surgeon review of 2060 patients performed. The distribution of patient and treatment variables compared in patients admitted on a weekday or the weekend. Fewer patients met performance indicators during weekend admission, time to surgery (63 vs. 71%) and time to geriatric review (86 vs. 91%). Weekend admission 30-day mortality was marginally lower than weekday (9.7% vs. 10.2%, OR 0.94, 95% CI 0.67 to 1.32, p = 0.7383). Increasing age, female gender, co-morbidities and confusion increased mortality risk. Binary regression analysis including these variables found no significant 'weekend effect'. Despite the unit observing an increasing workload in the last five years, with meticulous workforce planning, senior doctor provisions and careful use of resources, it is possible to provide a seven-day fracture neck of femur service with no variation in thirty-day mortality by the day of admission.


Assuntos
Fraturas do Quadril/mortalidade , Admissão do Paciente , Humanos , Medição de Risco , Fatores de Risco , Análise de Sobrevida , Centros de Traumatologia
19.
Ann Surg ; 265(6): 1241-1249, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27232244

RESUMO

OBJECTIVE: The aim of this study was to measure neutrophil function longitudinally following burn injury and to examine the relationship between neutrophil dysfunction and sepsis. BACKGROUND: Sepsis prevalence and its associated mortality is high following burn injury, and sepsis diagnosis is complicated by the ongoing inflammatory response. Previous studies have suggested that neutrophil dysfunction may underlie high infection rates and sepsis postburn; however, neutrophil dysfunction has not been thoroughly characterized over time in burns patients. METHODS: Neutrophil phagocytosis, oxidative burst capacity, and neutrophil extracellular trap (NET) generation (NETosis) were measured from 1 day to up to 1 year postburn injury in 63 patients with major burns (≥15% total body surface area). In addition, immature granulocyte (IG) count, plasma cell-free DNA (cfDNA), and plasma citrullinated histone H3 (Cit H3) levels were measured. RESULTS: Neutrophil function was reduced for 28 days postburn injury and to a greater degree in patients who developed sepsis, which was also characterized by elevated IG counts. Plasma cfDNA and Cit-H3, a specific marker of NETosis, were elevated during septic episodes. The combination of neutrophil phagocytic capacity, plasma cfDNA levels, and IG count at day 1 postinjury gave good discriminatory power for the identification of septic patients. CONCLUSION: Neutrophil function, IG count, and plasma cfDNA levels show potential as biomarkers for the prediction/early diagnosis of sepsis postburn injury and neutrophil dysfunction may actively contribute to the development of sepsis. Targeting neutrophil dysfunction and IG release may be a viable therapeutic intervention to help reduce the incidence of nosocomial infections and sepsis postburn.


Assuntos
Queimaduras/complicações , DNA/sangue , Granulócitos , Neutrófilos/fisiologia , Sepse/diagnóstico , Biomarcadores/sangue , Infecção Hospitalar/diagnóstico , Histonas/sangue , Humanos , Contagem de Leucócitos , Fagocitose , Estudos Prospectivos , Explosão Respiratória
20.
Childs Nerv Syst ; 33(2): 275-280, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27848003

RESUMO

PURPOSE: We test the hypothesis that ventriculoperitoneal (VP) shunt insertion significantly increases contralateral positional plagiocephaly. METHODS: We reviewed 339 children who had a VP shunt inserted at Birmingham Children's Hospital between 2006 and 2013, noting laterality of shunt insertion and frontal or occipital position. We ascertained the presence of post-operative positional plagiocephaly using the cranial vault asymmetry index. Multinomial logistic regression modelling was used to examine relationships between plagiocephaly, shunt position, gender and age. Adjusted odds and risk ratios for effect of variables on plagiocephaly were calculated. RESULTS: Children with occipital VP shunts are at significant risk of developing contralateral positional plagiocephaly, particularly in the first 12 months of life. CONCLUSIONS: We recommend careful follow-up and advice regarding head positioning following surgery. There should be consideration for active monitoring to avoid plagiocephaly, including physiotherapy and health visitor interventions. Endoscopic third ventriculostomy in selected cases or anterior shunt placement could be considered. A larger national study would be of interest to evaluate the extent of an otherwise correctable problem.


Assuntos
Plagiocefalia não Sinostótica/cirurgia , Derivação Ventriculoperitoneal/métodos , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Estudos Retrospectivos , Fatores Sexuais , Resultado do Tratamento , Ventriculostomia
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