RESUMO
BACKGROUND: This study describes the epidemiology and clinical features of hepatocellular carcinoma (HCC), and it investigates any association between Child-Pugh's classification and HCC. MATERIALS AND METHODS: A retrospective chart review was performed for HCC cases diagnosed between 2008 and 2014 at King Abdulaziz University Hospital. We documented the age at cancer diagnosis, gender, occupation, ethnic origin, HCC etiology, Child-Pugh scores, tumor characteristics, alpha-fetoprotein (AFP), and alkaline phosphatase (ALP) levels at diagnosis, and treatment administered. The Chi-square test was used to determine differences between categorical variables. RESULTS: We included 128 patients. Hepatitis B and C viral infections were documented in 24.2% and 33.6% of the patients, respectively. Patients with tumors >5 cm were more likely to have Child's Class C disease, whereas those with tumors ≤2 cm were more likely to have Child's Class A (P < 0.001). Similarly, patients with bilobular or metastatic tumors were more likely to have Child's Class C disease (P = 0.001 and 0.002, respectively). No difference in Child-Pugh score was found between patients with single or multiple tumors (P = 0.480). Furthermore, patients who were both hepatitis B and C positive were more likely to have Child's Class C disease (P = 0.018). Likewise, those who had abnormal AFP and ALP levels ≥1000 ng/mL were more likely to have Child-Pugh's Class C liver disease (P = 0.021 in both cases). CONCLUSION: Hepatitis C and B infections were the main risk factors associated with HCC.
Assuntos
Carcinoma Hepatocelular/epidemiologia , Neoplasias Hepáticas/epidemiologia , alfa-Fetoproteínas/análise , Adulto , Idoso , Fosfatase Alcalina/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Feminino , Hepatite B/complicações , Hepatite B/epidemiologia , Hepatite C/complicações , Hepatite C/epidemiologia , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Arábia Saudita/epidemiologia , Centros de Atenção TerciáriaRESUMO
Biomechanical investigations are increasingly using commercially available synthetic femurs as surrogates for human cadaveric femurs. However, the rate of force application in testing these artificial femurs appears to be chosen arbitrarily without much consideration to their visco-elastic time-dependent nature. The aim of this study, therefore, was to examine the effect of loading rate on the mechanical behaviour of synthetic femurs. Ten left, medium, fourth-generation composite femurs (Model 3403, Pacific Research Laboratories, Vashon, WA, USA) were fixed distally into cement-filled steel cubic chambers for mounting into a mechanical tester. In randomized order, each of the ten femurs was loaded at rates of 1, 2.5, 5, 7.5, 10, 20, 30, 40, 50, and 60 mm/min to obtain axial, lateral, and torsional stiffness. Axial stiffness showed an aggregate average value of 1742.7 +/- 174.7 N/mm with a high linear correlation with loading rate (R2 = 0.80). Lateral stiffness yielded an aggregate average value of 56.9 +/- 10.2 N/mm and was linearly correlated with loading rate (R2 = 0.85). Torsional stiffness demonstrated an aggregate average value of 176.9 +/- 14.5 N/mm with a strong linear correlation with loading rate (R2 = 0.59). Despite the high correlations between stiffness and speed, practically this resulted in an overall average difference between the lowest and highest stiffness of only 4 per cent. Moreover, no statistical comparisons between loading rates for axial, lateral, or torsional test modes showed differences (p > or = 0.843). Future biomechanical investigators utilizing these synthetic femurs need not be concerned with loading rate effects over the range tested presently. This is the first study in the literature to perform such an assessment.
Assuntos
Materiais Biomiméticos , Fêmur/fisiologia , Suporte de Carga/fisiologia , Força Compressiva/fisiologia , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Estresse MecânicoRESUMO
Orthopaedic fracture fixation constructs are typically mounted on to human long bones using cortical screws. Biomechanical studies are increasingly employing commercially available synthetic bones. The aim of this investigation was to examine the effect of the screw pull-out rate and canal reaming on the cortical bone screw purchase strength in synthetic bone. Cylinders made of synthetic material were used to simulate unreamed (foam-filled) and reamed (hollow) human long bone with an outer diameter of 35 mm and a cortex wall thickness of 4 mm. The unreamed and reamed cylinders each had 56 sites along their lengths into which orthopaedic cortical bone screws (major diameter, 3.5 mm) were inserted to engage both cortices. The 16 test groups (n = 7 screw sites per group) had screws extracted at rates of 1 mm/ min, 5 mm/min, 10 mm/min, 20 mm/min, 30 mm/min, 40 mm/min, 50 mm/min, and 60 mm/ min. The failure force and failure stress increased and were highly linearly correlated with pull-out rate for reamed (R2 = 0.60 and 0.60), but not for unreamed (R2 = 0.00 and 0.00) specimens. The failure displacement and failure energy were relatively unchanged with pull-out rate, yielding low coefficients for unreamed (R2 = 0.25 and 0.00) and reamed (R2 = 0.27 and 0.00) groups. Unreamed versus reamed specimens were statistically different for failure force (p = 0.000) and stress (p = 0.000), but not for failure displacement (p = 0.297) and energy (0.054 < p < 1.000). This is the first study to perform an extensive investigation of the screw pull-out rate in unreamed and reamed synthetic long bone.
Assuntos
Parafusos Ósseos , Osso e Ossos/fisiologia , Osso e Ossos/cirurgia , Implantação de Prótese/métodos , Análise de Falha de Equipamento , Fricção , Humanos , Desenho de PróteseRESUMO
BACKGROUND AND AIMS: Lower Gastrointestinal Bleeding (LGIB) is one of the leading causes of ER visits. Colonoscopy is indicated in all patients with LGIB, yet the time frame for performing colonoscopy remains unclear. Whether or not urgent endoscopic evaluation improves outcomes of LGIB has been questioned. We therefore aimed to examine the success of urgent colonoscopy in identifying the source of LGIB. PATIENTS AND METHODS: A retrospective study was conducted in which timing of colonoscopy was divided into urgent (performed within the first 24 hours of presentation) and delayed (performed following 24 hours of hospitalization). Data on clinical presentation, investigations and endoscopic findings was collected. Risk ratios were calculated and regression analysis was used to examine associations and identify predictors of endoscopic success. RESULT: A total of 183 patients underwent colonoscopies. 55.4% of colonoscopies were performed within 24 hours of presentation. A source of LGIB was identified in 55.7% of first attempt colonoscopies. Endoscopic intervention was required in 10.9% of cases and rebleeding occurred in 24.6%, of which 6.5% required hospital re-admission. 2.7% required emergency colectomy and the calculated mortality rate was 1%. Risk ratios comparing urgent to delayed colonoscopy for source of LGIB identification, colectomy and mortality were 1.01, 4.8 and 1.2, respectively. Age and timing of colonoscopy appeared to be predictive of colectomy on regression analysis. CONCLUSIONS: Urgent colonoscopy for LGIB did not improve the rate of identification of the source of bleeding, colectomy rate or mortality rate and was predictive of the need for emergency colectomy.
Assuntos
Colonoscopia , Hemorragia Gastrointestinal , Doença Aguda , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hospitalização , Humanos , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the prevalence of fat-soluble vitamin (A, D, and E) and zinc deficiency in patients with cirrhosis being assessed for liver transplantation and the correlations between vitamin deficiencies, nutritional markers, and severity of liver disease. METHODS: This is a single centre retrospective study. Serum vitamin A, D, E, and zinc levels were collected in adult patients being assessed for liver transplantation between January and July 2012. Patient and liver disease demographics, nutritional markers, Child-Pugh score, and MELD-Na score were collected. Fisher's exact test and multiple variable logistic regression was used for statistical analysis. RESULTS: A total of 109 adult patients were assessed for liver transplantation during the 6-month period. The mean patient age was 54 ± 10 years and 66% were males. Mean BMI was 27 ± 6 kg/m2, pre-albumin was 0.10 ± 0.07 g/L, albumin was 33 ± 6 g/L, total bilirubin was 48 ± 61 mmol/L, MELD-Na score was 16 ± 5 (range 6-33), and 15% had hepatocellular carcinoma. The Child-Pugh score was A in 29%, B in 54%, and C in 17%. The causes of liver disease were hepatitis C in 36%, alcohol in 20%, non-alcoholic fatty liver disease in 17%, and other in 27%. The mean vitamin A level was 0.88 ± 0.86 umol/L, D was 69 ± 52 nmol/L, E was 24 ± 17 umol/L, and zinc was 477 ± 145 ug/L. Vitamin A deficiency was prevalent in 77%, D in 63%, E in 37%, and zinc in 84%. On multiple variable analysis, low albumin (OR = 0.78, 95% CI = 0.65-0.94, p = 0.0069) was a predictor of vitamin A deficiencyâ¯; cholestatic liver enzyme elevation (OR = 3.53, 95%CI = 1.40-8.89, p = 0.0073) and low albumin (OR = 0.83, 95%CI = 0.73-0.94, p = 0.0032) were predictors of vitamin D deficiencyâ¯; low albumin (OR = 0.85, 95% CI = 0.74-0.97, p = 0.015) was a predictor of vitamin E deficiencyâ¯; and age (OR = 0.83, 95% CI = 0.72-0.96, p = 0.012), low albumin (OR = 0.59, 95% CI = 0.42-0.84, p = 0.0036), and high MELD-Na (1.43, 95% CI = 1.05-1.94, p = 0.021) were predictors of zinc deficiency. Vitamin A (p = 0.0034), D (p = 0.020), E (p = 0.012), and zinc (p<0.001) deficiency correlated with a higher Child-Pugh. CONCLUSION: Low albumin was a recurrent predictor of fat-soluble vitamin (A, D, and E) and zinc deficiency while other predictors varied depending on the vitamin or mineral. Further studies need to be conducted on fat-soluble vitamin and zinc supplementation in deficient patients with cirrhosis to assess clinical outcomes.
Assuntos
Deficiências Nutricionais , Cirrose Hepática , Vitamina A/sangue , Vitamina D/sangue , Vitamina E/sangue , Zinco/sangue , Adulto , Deficiências Nutricionais/sangue , Deficiências Nutricionais/epidemiologia , Deficiências Nutricionais/etiologia , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/cirurgia , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Albumina Sérica Humana/análise , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Minimising placebo response is essential for drug development. AIM: To conduct a meta-analysis to determine placebo response and remission rates in trials and identify the factors affecting these rates. METHODS: MEDLINE, EMBASE and CENTRAL were searched from inception to April 2014 for placebo-controlled trials of pharmacological interventions for Crohn's disease. Placebo response and remission rates for induction and maintenance trials were pooled by random-effects and mixed-effects meta-regression models to evaluate effects of study-level characteristics on these rates. RESULTS: In 100 studies containing 67 induction and 40 maintenance phases and 7638 participants, pooled placebo remission and response rates for induction trials were 18% [95% confidence interval (CI) 16-21%] and 28% (95% CI 24-32%), respectively. Corresponding values for maintenance trials were 32% (95% CI 25-39%) and 26% (95% CI 19-35%), respectively. For remission, trials enrolling patients with more severe disease activity, longer disease duration and more study centres were associated with lower placebo rates, whereas more study visits and longer study duration was associated with higher placebo rates. For response, findings were opposite such that trials enrolling patients with less severe disease activity and longer study duration were associated with lower placebo rates. Placebo rates varied by drug class and route of administration, with the highest placebo response rates observed for biologics. CONCLUSIONS: Placebo rates vary according to whether trials are designed for induction or maintenance and the factors influencing them differ for the endpoints of remission and response. These findings have important implications for clinical trial design in Crohn's disease.
Assuntos
Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/estatística & dados numéricos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Quimioterapia de Indução/estatística & dados numéricos , Quimioterapia de Manutenção/estatística & dados numéricos , Humanos , Placebos , Indução de Remissão , Projetos de PesquisaRESUMO
BACKGROUND: Thiopurines (Azathioprine (AZA) and 6-Mercaptopurine (6-MP) are considered a well-established therapy for patients with Inflammatory Bowel Disease (IBD) including ulcerative colitis (UC) and Crohn's Disease (CD). However, nearly 20% of patients discontinue thiopurines due to adverse events. Functional polymorphisms of several enzymes involved in the metabolism of thiopurines have been linked with toxicity. The clinical value of variant carriers such as TPMT, ITPA and GSTs in predicting toxicity and adverse events for IBD patients treated with thiopurines remains to be clarified. OBJECTIVES: To determine if variation in TPMT, ITPA and GST genotypes can predict adverse effects such as neutropenia, pancreatitis, liver enzyme elevation, as well as clinical response for patients with IBD treated with thiopurines. METHODS: Patients known to have IBD and treated with AZA or 6MP were enrolled. Adverse effects were calculated and their correlation with TPMT, ITPA and GST genotypes was evaluated. Further, the correlation between clinical response and TPMT, ITPA and GST genotypes were assessed. RESULTS: A total of 53 patients were enrolled. 16/53 patients (28.6%) responded to AZA therapy. 17 patients experienced adverse events with 10 having to discontinue treatment. Three patients (5.4%) developed severe myelosuppression (WBC< 2.0 or neutrophils <1.0). Loss of function TPMT genotype was associated with adverse events (OR 3.64, 95% CI 0.55 - 24.23, p=0.0313). ITPA and GST polymorphisms were not associated with toxicity. GSTM1 deletion was associated with poor clinical response to therapy (OR 3.75, 95% CI 0.940 - 14.97, p=0.1028), however, neither TPMT*3A nor ITPA polymorphisms were associated with clinical response. CONCLUSION: In addition to TPMT for adverse events, genotyping for GSTM1 appears to predict clinical response in IBD patients treated with thiopurines.
Assuntos
Azatioprina/efeitos adversos , Marcadores Genéticos/genética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Diarreia/induzido quimicamente , Feminino , Seguimentos , Glutationa Transferase/genética , Humanos , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/diagnóstico , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Valor Preditivo dos Testes , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Patient-reported outcomes (PROs) have an increasingly important role in the evaluation of new therapies for inflammatory bowel disease. The US Food and Drug Administration has issued formal guidance to describe the role of PRO instruments in evaluation of claims for product labelling. However, no validated PRO exists for ulcerative colitis. AIM: To investigate whether the PROs from the Mayo Clinic Score (MCS) for UC can be modified, to develop an interim PRO for use in clinical trials, alone or in combination with endoscopy. METHODS: Data from an induction trial of a mesalazine (mesalamine) formulation were used to compare effect sizes between mesalazine and placebo for PRO items (stool frequency and rectal bleeding) alone and in combination with endoscopy. The operating properties of the PRO were validated using data from a phase 2 trial of MLN02, a humanised antibody to the α4ß7 integrin in patients with UC. RESULTS: A two-item PRO (PRO2) consisting of rectal bleeding = 0 and stool frequency ≤1 or ≤2, combined with an endoscopy subscore ≤1 yielded statistically significant differences between active drug and placebo. This combination yielded the most similar effect sizes and placebo rates for remission, compared to the primary trials. Use of PRO items alone yielded high placebo remission rates in both data sets, although rates were lower when the items were combined and remission defined as PRO2 = 0. CONCLUSION: Patient-reported outcomes items derived from the Mayo Clinic Score combined with endoscopy as a co-primary endpoint may be an appropriate interim outcome measure for ulcerative colitis trials.