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1.
Ann R Coll Surg Engl ; 106(3): 213-218, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37218655

RESUMO

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


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Estudos Transversais , Estudos Prospectivos , Hepatectomia , Neoplasias Hepáticas/cirurgia , Neoplasias Colorretais/cirurgia
2.
BMC Surg ; 22(1): 201, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35598012

RESUMO

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


Assuntos
Cirurgia Colorretal , Veteranos , Feminino , Hospitais , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Hernia ; 26(3): 751-759, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34718903

RESUMO

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


Assuntos
Pesquisa Biomédica , Procedimentos Cirúrgicos do Sistema Digestório , Hérnia Abdominal , Técnica Delphi , Herniorrafia , Humanos
6.
J Plast Reconstr Aesthet Surg ; 74(2): 401-406, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33097434

RESUMO

At the time of writing, coronavirus disease-2019 (COVID-19) has affected 6.42 million people globally and over 380,000 deaths, with the United Kingdom now having the highest death rate in Europe. The plastic surgery department at Leeds Teaching Hospitals put necessary steps in place to maintain an excellent urgent elective and acute service whilst also managing COVID-positive medical patients in the ward. We describe the structures and pathways implemented together with complex decision-making, which has allowed us to respond early and effectively. We hope these lessons will prove a useful tool as we look to open conversations around the recovery of normal activity.


Assuntos
COVID-19 , Departamentos Hospitalares , Controle de Infecções , Neoplasias/cirurgia , Cirurgia Plástica , Ferimentos e Lesões/cirurgia , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/terapia , Gestão de Mudança , Criança , Transmissão de Doença Infecciosa/prevenção & controle , Procedimentos Cirúrgicos Eletivos , Departamentos Hospitalares/métodos , Departamentos Hospitalares/organização & administração , Departamentos Hospitalares/estatística & dados numéricos , Humanos , Controle de Infecções/métodos , Controle de Infecções/normas , Neoplasias/epidemiologia , Procedimentos de Cirurgia Plástica , SARS-CoV-2 , Cirurgia Plástica/educação , Cirurgia Plástica/organização & administração , Cirurgia Plástica/tendências , Ensino/organização & administração , Ensino/tendências , Reino Unido/epidemiologia , Ferimentos e Lesões/epidemiologia
7.
Ann Med Surg (Lond) ; 57: 228-235, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32802324

RESUMO

BACKGROUND: Closure of the appendiceal stump is a key step performed during laparoscopic appendicectomy. Inadequate management of the appendiceal stump has the potential to cause significant morbidity. Several methods of stump closure have been described, however high-level evidence is limited. We performed a systematic review evaluating clinical outcomes and quality of the evidence for the methods of appendiceal stump closure. METHODS: A systematic literature search was performed using Medline, Embase, Cochrane Database and Google Scholar to identify studies comparing appendiceal stump closure methods in laparoscopic appendectomy for acute appendicitis from inception to October 2019. Data regarding operative duration, peri-operative complications, length of stay and costs were collated from all included studies. RESULTS: From 160 identified studies, 19 met the inclusion criteria. Endoloops and endoclips provide equivalent clinical outcomes at lower cost, while operative duration was shortest with endoclip closure. Endostapler devices have the lowest rate of peri-operative complications (3.56%), however their cost limits their regular use in many healthcare environments. Post-operative complication rate and length of stay were similar for all stump closure methods. Conclusion: Although there are no significant differences in method of stump closure in laparoscopic appendectomy, closure with endoclips provides the shortest operative duration. There is a need for robust and standardized reporting of cost data when comparing stump closure methods, together with higher level evidence in the form of multi-centre randomized controlled trials before firm conclusions can be drawn regarding the optimal method of stump closure.

10.
Colorectal Dis ; 21(7): 775-781, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30848537

RESUMO

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


Assuntos
Fatores Etários , Neoplasias Colorretais/mortalidade , Procedimentos Cirúrgicos Eletivos/mortalidade , Tratamento de Emergência/mortalidade , Fatores de Tempo , Idoso , Viés , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Prospectivos
11.
Lung Cancer ; 129: 22-27, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30797487

RESUMO

OBJECTIVES: There has been evidence of an association between patient outcomes and the number of surgeries performed at a hospital. To our knowledge, there are no Australian data on hospital cancer surgery volumes and patient outcomes. We evaluated the relationship between hospital non-small cell lung cancer (NSCLC) surgery volume and patient outcomes in Victoria. MATERIALS AND METHODS: Patients with a primary diagnosis of NSCLC between 2008 and 2014 were identified in the Victorian Cancer Registry (n = 15,369), 3,420 (22%) of whom had lung cancer surgery. Primary outcome was death within 90 days of surgery and secondary outcomes included overall survival, use of postoperative ventilation and ≥24hours spent in ICU. Hospital volume was measured as the average number of lung surgeries performed per year, with quartiles Q1: 1-17, Q2: 18-34, Q3: 35-58 and Q4: 59 + . RESULTS: 57% (1,941/3,420) lung cancer patients underwent lobectomy, 38% (1,299/3,420) sub-lobar resection and 5% (180/3,420) pneumonectomy. The overall 90-day mortality after lung surgery was 3.5%, and was 2.6% and 4.5% for patients undergoing lobectomy and sub-lobar resection respectively. There was no difference in 90-day mortality and overall survival between low- and high-volume centres regardless of procedure. Patients operated on in lower volume centres had more admissions to ICU ≥24hours (Q1. 55% vs. Q4. 11%, p-trend <0.001). A higher proportion of patients attending private hospitals (19%) had an ASA score of 4 compared with patients attending a public hospital (9%). CONCLUSION: We observed no evidence of survival differences between lung cancer patients attending low- and high-volume hospitals for cancer surgery. A higher proportion of patients had an ICU admission ≥24hours in lower volume centres and there are a higher proportion of patients with an ASA score of 4 in private hospitals compared to public hospitals.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Hospitais com Alto Volume de Atendimentos , Neoplasias Pulmonares/epidemiologia , Pneumonectomia/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Hospitalização , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento
12.
Br J Surg ; 106(2): e62-e72, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30620075

RESUMO

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


Assuntos
Big Data , Cirurgia Geral/normas , Melhoria de Qualidade/estatística & dados numéricos , Países em Desenvolvimento , Cirurgia Geral/estatística & dados numéricos , Humanos , Avaliação de Resultados em Cuidados de Saúde
13.
Lung Cancer ; 124: 148-153, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30268454

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in populations eligible for lung cancer screening. The aim of this study was to determine whether a brief CV risk assessment, delivered as part of a targeted community-based lung cancer screening programme, was effective in identifying individuals at high risk who might benefit from primary prevention. METHODS: The Manchester Lung Screening Pilot consisted of annual low dose CT (LDCT) over 2 screening rounds, targeted at individuals in deprived areas at high risk of lung cancer (age 55-74 and 6-year risk ≥1.51%, using PLCOM2012 risk model). All participants of the second screening round were eligible to take part in the study. Ten-year CV risk was estimated using QRISK2 in participants without CVD and compared to age (±5 years) and sex matched Health Survey for England (HSE) controls; high risk was defined as QRISK2 score ≥10%. Coronary artery calcification (CAC) was assessed on LDCT scans and compared to QRISK2 score. RESULTS: Seventy-seven percent (n=920/1,194) of screening attendees were included in the analysis; mean age 65.6 ± 5.4 and 50.4% female. QRISK2 and lung cancer risk (PLCOM2012) scores were correlated (r = 0.26, p < 0.001). Median QRISK2 score was 21.1% (IQR 14.9-29.6) in those without established CVD (77.6%, n = 714/920), double that of HSE controls (10.3%, IQR 6.6-16.2; n = 714) (p < 0.001). QRISK2 score was significantly higher in those with CAC (p < 0.001). Screening attendees were 10-fold more likely to be classified high risk (OR 10.2 [95% CI 7.3-14.0]). One third (33.7%, n = 310/920) of all study participants were high risk but not receiving statin therapy for primary CVD prevention. DISCUSSION: Opportunistic CVD risk assessment within a targeted lung cancer screening programme is feasible and is likely to identify a very large number of individuals suitable for primary prevention.


Assuntos
Doenças Cardiovasculares/diagnóstico , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Idoso , Calcinose , Doenças Cardiovasculares/epidemiologia , Inglaterra/epidemiologia , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Risco , Medição de Risco
14.
Eur J Surg Oncol ; 44(12): 1929-1934, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30262326

RESUMO

INTRODUCTION: The objective of this study was to report a 30-year experience of PE for gynecologic malignancies in a cancer center. MATERIALS AND METHODS: A retrospective study was conducted at Institut Paoli-Calmette including patients who underwent PE for gynecologic malignancies. Four periods were evaluated: P1 before 1992, P2 between 1993 and 1999, P3 between 2000 and 2006 and P4 after 2006. The study evaluated the number of PE performed during each period, the type of PE, its level, indication, location of the primary tumor, patient age, previous radiotherapy ≥45 Gy, the rate of "curative" PE and exenteration-related reconstructive techniques. 90-day post-operative mortality and morbidity using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 4.03 were reported. RESULTS: 277 PE were performed. The number of PE performed for recurrences rose during the study period (p = 0.042), PE performed for central tumors increased during P3 (64.4%) and P4 (67.4%) (p < 0.0001) and administration of radiotherapy ≥45 Gy was more frequent (p < 0.0001). The rate of "curative" PE increased (p < 0.0001). In multivariate analysis, "curative" PE were correlated with PE type, central locations and study period. Pelvic filling was progressively more frequently performed (p = 0.002). 90-day complication rate was 56.3%. In multivariate analysis there was a significant difference in distribution of CTCAE grade 3-4-5 morbidity depending on the period. Overall survival (OS) improved during the 2 last periods (p = 0.008). CONCLUSION: A better selection of eligible patients for PE, namely through improvement in imaging techniques, has enabled to raise the rate of curative PE.


Assuntos
Neoplasias dos Genitais Femininos/cirurgia , Exenteração Pélvica/métodos , Adulto , Idoso , Feminino , Neoplasias dos Genitais Femininos/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Seleção de Pacientes , Complicações Pós-Operatórias/epidemiologia , Procedimentos de Cirurgia Plástica , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
15.
J Gynecol Obstet Hum Reprod ; 47(9): 431-435, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30149209

RESUMO

Over the past 20 years, feasibility of laparoscopic approaches has been validated in gynecologic surgery. This procedure has specific challenges due its longer learning curve and the limits imposed by the technique. For the surgical treatment of recurrent pelvic cancers or locally advanced tumors, open surgery remains the gold standard for most surgical teams. Robotic assistance could be an interesting alternative. The aim of this study is to present our department's robotic surgical procedures in this specific field and show its feasibility and reproducibility on several patients.


Assuntos
Neoplasias dos Genitais Femininos/cirurgia , Procedimentos Cirúrgicos em Ginecologia/métodos , Laparoscopia/métodos , Recidiva Local de Neoplasia/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Feminino , Humanos
16.
Ann R Coll Surg Engl ; 100(6): 454-458, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29543058

RESUMO

Introduction The use of polymeric clips in securing the appendiceal stump has been increasingly reported as a viable alternative to current methods in emergency laparoscopic appendicectomy. We evaluated the operative outcomes following the use of polymeric clips versus endoscopic ligatures. The primary endpoint was operative time, with secondary outcomes including complications, inpatient stay, and cost analysis. Materials and methods Operative records were retrospectively analysed to identify patients undergoing laparoscopic appendicectomy between January 2014 and June 2015. Data collected included age, gender, body mass index, duration of surgery, length of hospital stay, antibiotic use, preoperative haematological and biochemical parameters, 30-day readmission rate and complications. Results A total of 125 patients were included within the study, with 78 within the endoloop group and 47 in the polymeric clip group. There were no differences in age, gender, body mass index, hospital stay, antibiotic use, 30-day readmission rates or postoperative complications. Operative time was significantly reduced in the polymeric clip group (59 vs. 68 minutes, P = 0.00751). The use of polymeric clips cost £21 compared with £49 for endoloops per operation, which rose to £70 if both clips and endoloops were used during the procedure. Discussion Polymeric clips are a safe, viable and economical method for securing the appendiceal stump during laparoscopic appendicectomy. The clinical significance of nine minutes of reduced operating time in the polymeric clip cohort warrants further study with an adequately powered randomised controlled trial.


Assuntos
Apendicectomia/instrumentação , Apendicite/cirurgia , Laparoscopia/instrumentação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Apendicectomia/economia , Apendicectomia/métodos , Apendicite/economia , Criança , Feminino , Custos Hospitalares/estatística & dados numéricos , Humanos , Laparoscopia/economia , Laparoscopia/métodos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Ligadura , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
Int J Surg ; 51: 199-204, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29407251

RESUMO

AIMS: Intravenous (IV) fluid administration continues to be a mainstay of care in General Surgery. Yet if they are prescribed incorrectly significant morbidity including electrolyte abnormalities, renal impairment and cardiac failure can develop. Despite this, it is frequently the responsibility of the most junior staff to prescribe IV fluids. We aim to analyse the understanding of IV fluid prescribing amongst junior doctors and to describe variability in clinical practice. METHODS: We undertook a multicentre questionnaire study. Foundation doctors and specialty trainees were invited to undertake a two part paper-based questionnaire. Part one analysed baseline knowledge of the concentration of commonly prescribed fluids. Part two consisted of four clinical vignettes requiring a IV fluid prescribing decision by the surveyed doctor. RESULTS: A total of 143 Doctors working in 8 hospitals were recruited. 65 (45.5%) doctors correctly stated the daily maintenance fluid requirements of water for an adult (25-30 mls/kg/day), while only 54 (37.8%) knew the sodium concentration of 0.9% NaCl. Lack of postgraduate experience (p = 0.011), qualifying from a medical school outside the United Kingdom (p < 0.0001) and working in one of the eight hospitals in this study (p < 0.0001) were associated with a lower knowledge level. There was limited consensus in prescribing in the responses to the 4 clinical scenarios, with 69 unique combinations of fluid choice, rate and volume prescribed. CONCLUSIONS: Knowledge of the constituents of common IV fluids and routine requirement for fluid and common electrolytes is poor across junior doctors of all grades, driving large variation in clinical practice.


Assuntos
Hidratação/métodos , Adulto , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Infusões Intravenosas , Médicos , Prescrições , Inquéritos e Questionários
18.
Leukemia ; 32(2): 332-342, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28584254

RESUMO

Chronic lymphocytic leukaemia (CLL) consists of two biologically and clinically distinct subtypes defined by the abundance of somatic hypermutation (SHM) affecting the Ig variable heavy-chain locus (IgHV). The molecular mechanisms underlying these subtypes are incompletely understood. Here, we present a comprehensive whole-genome sequencing analysis of somatically acquired genetic events from 46 CLL patients, including a systematic comparison of coding and non-coding single-nucleotide variants, copy number variants and structural variants, regions of kataegis and mutation signatures between IgHVmut and IgHVunmut subtypes. We demonstrate that one-quarter of non-coding mutations in regions of kataegis outside the Ig loci are located in genes relevant to CLL. We show that non-coding mutations in ATM may negatively impact on ATM expression and find non-coding and regulatory region mutations in TCL1A, and in IgHVunmut CLL in IKZF3, SAMHD1,PAX5 and BIRC3. Finally, we show that IgHVunmut CLL is dominated by coding mutations in driver genes and an aging signature, whereas IgHVmut CLL has a high incidence of promoter and enhancer mutations caused by aberrant activation-induced cytidine deaminase activity. Taken together, our data support the hypothesis that differences in clinical outcome and biological characteristics between the two subgroups might reflect differences in mutation distribution, incidence and distinct underlying mutagenic mechanisms.


Assuntos
Genes de Cadeia Pesada de Imunoglobulina/genética , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Leucemia Linfocítica Crônica de Células B/genética , Mutação/genética , Idoso , Idoso de 80 Anos ou mais , Citidina Desaminase/genética , Elementos Facilitadores Genéticos/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas/genética , Proteína 1 com Domínio SAM e Domínio HD/genética , Sequenciamento Completo do Genoma/métodos
20.
Osteoarthritis Cartilage ; 25(5): 676-684, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27923602

RESUMO

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


Assuntos
Cartilagem Articular/parasitologia , Luxação do Quadril/diagnóstico por imagem , Luxação do Quadril/cirurgia , Imageamento Tridimensional , Osteotomia/métodos , Estresse Mecânico , Acetábulo/diagnóstico por imagem , Acetábulo/fisiopatologia , Adulto , Fenômenos Biomecânicos , Estudos de Casos e Controles , Feminino , Análise de Elementos Finitos , Humanos , Masculino , Estudos Prospectivos , Valores de Referência , Medição de Risco , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Adulto Jovem
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