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1.
Aliment Pharmacol Ther ; 57(5): 454-463, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36691947

RESUMO

BACKGROUND: Advanced chronic liver disease is an increasing cause of premature morbidity and mortality in the UK. Portal hypertension is the primary driver of decompensation, including the development of ascites, hepatic encephalopathy and variceal haemorrhage. Non-selective beta blockers (NSBB) reduce portal pressure and are well established in the prevention of variceal haemorrhage. Carvedilol, a newer NSBB, is more effective at reducing portal pressure due to additional α-adrenergic blockade and has additional anti-oxidant, anti-inflammatory and anti-fibrotic effects. AIM: To summarise the available evidence on the use of beta blockers, specifically carvedilol, in cirrhosis, focussing on when and why to start METHODS: We performed a comprehensive literature search of PubMed for relevant publications. RESULTS: International guidelines advise the use of NSBB in primary prophylaxis against variceal haemorrhage in those with high-risk varices, with substantial evidence of efficacy comparable with endoscopic band ligation (EBL). NSBB are also well established in secondary prophylaxis, in combination with EBL. More controversial is their use in patients without large varices, but with clinically significant portal hypertension. However, there is gathering evidence that NSBB, particularly carvedilol, reduce the risk of decompensation and improve survival. While caution is advised in patients with advanced cirrhosis and refractory ascites, recent evidence suggests that NSBB can continue to be used safely, and that premature discontinuation may be detrimental. CONCLUSIONS: With increasing evidence of benefit independent of variceal bleeding, namely retardation of decompensation and improvement in survival, it is time to consider whether carvedilol should be offered to all patients with advanced chronic liver disease.


Assuntos
Varizes Esofágicas e Gástricas , Hipertensão Portal , Varizes , Humanos , Carvedilol/uso terapêutico , Varizes Esofágicas e Gástricas/tratamento farmacológico , Varizes Esofágicas e Gástricas/prevenção & controle , Varizes Esofágicas e Gástricas/complicações , Ascite/etiologia , Ascite/complicações , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/prevenção & controle , Antagonistas Adrenérgicos beta/uso terapêutico , Hipertensão Portal/complicações , Hipertensão Portal/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Varizes/complicações
2.
World J Transplant ; 12(6): 120-130, 2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35979539

RESUMO

BACKGROUND: Pre-transplant muscle wasting measured by computed tomography has been associated with adverse clinical outcomes after liver transplantation including increased rates of sepsis and hospitalisation days. Upper limb lean mass (LM) measured by dual-energy X-ray absorptiometry (DEXA) was recently identified as a novel predictor of sarcopenia-associated mortality in men waitlisted for transplantation. AIM: To investigate the use of DEXA LM in predicting gender-stratified early post-transplant outcomes. METHODS: Liver transplant recipients who underwent pre-transplant DEXA body composition imaging between 2002 and 2017 were included. Endpoints included post-transplant mortality and graft failure, bacterial infections, acute cellular rejection (ACR) and intensive care and total hospital length of stay. RESULTS: Four hundred and sixty-nine patients met inclusion criteria of which 338 were male (72%). Median age was 55.0 years (interquartile range 47.4, 59.7) and model for end-stage liver disease (MELD) score 16. Median time from assessment to transplantation was 7 mo (3.5, 12). Upper limb LM was inversely associated with bacterial infections at 180 d post-transplant (hazard ratio = 0.42; 95% confidence interval: 0.20-0.89; P = 0.024) in males only. There was a negative correlation between upper limb LM and intensive care (τb = -0.090, P = 0.015) and total hospital length of stay (τb = -0.10, P = 0.0078) in men. In women, neither MELD nor body composition parameters were associated with post-transplant adverse outcomes or increased length of stay. Body composition parameters, MELD and age were not associated with 90-d mortality or graft failure in either gender. There were no significant predictors of early ACR. CONCLUSION: Sarcopenia is an independent and potentially modifiable predictor of increased post-transplant bacterial infections and hospital length of stay in men with cirrhosis. DEXA upper limb LM provides a novel measure of muscle wasting that has prognostic value in this cohort. The lack of association in women requires further investigation.

4.
Clin Endocrinol (Oxf) ; 96(4): 549-557, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34697809

RESUMO

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been associated with diabetic ketoacidosis at the time of colonoscopy. This study aimed to identify factors associated with ketone concentrations in SGLT2i-treated type 2 diabetes compared with non-SGLT2i-treated diabetes, and those with impaired fasting glycaemia (IFG) and normoglycaemia. DESIGN: Cross-sectional, multicentre, observational study June-December 2020 in four Australian tertiary hospitals. PARTICIPANTS: Capillary glucose and ketones were measured in people undergoing colonoscopy: 37 SGLT2i-treated and 105 non-SGLT2i-treated type 2 diabetes, 65 IFG and 151 normoglycaemia. MEASUREMENTS: Body mass index (BMI), age, glucose, fasting duration and where relevant, HbA1c and time since last SGLT2i dose. RESULTS: In SGLT2i-treated diabetes, BMI (ρ = -0.43 [95% confidence interval: -0.67, -0.11]) and duration since last SGLT2i dose (ρ = -0.33 [-0.60, 0.00]) correlated negatively with increasing ketones, but there was no correlation with fasting duration. In non-SGLT2i-treated diabetes, BMI correlated negatively (ρ = -0.24 [-0.42, -0.05]) and fasting duration positively (ρ = 0.26 [0.07, 0.43]) with ketones. In IFG participants, only fasting duration correlated with ketones (ρ = 0.28 [0.03, 0.49]). In normoglycaemic participants, there were negative correlations with BMI (ρ = -0.20 [-0.35, -0.04]) and fasting glucose (ρ = -0.31 [-0.45, -0.15]) and positive correlations with fasting duration (ρ = 0.20 [0.04, 0.35]) and age (ρ = 0.19 [0.03, 0.34]). Multiple regression analysis of the entire cohort showed BMI, age and fasting glucose remained independently associated with ketones, but in SGLT2i-treated participants only BMI remained independently associated. CONCLUSIONS: In SGLT2i-treated diabetes, lower BMI was a novel risk factor for higher ketones precolonoscopy. Pending larger confirmatory studies, extra vigilance for ketoacidosis is warranted in these people.


Assuntos
Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Inibidores do Transportador 2 de Sódio-Glicose , Austrália , Índice de Massa Corporal , Colonoscopia , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose , Humanos , Cetonas/uso terapêutico , Estado Pré-Diabético/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
8.
World J Hepatol ; 11(7): 586-595, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31388400

RESUMO

BACKGROUND: Acute liver failure (ALF) is a life-threatening syndrome with varying aetiologies requiring complex care and multidisciplinary management. Its changing incidence, aetiology and outcomes over the last 16 years in the Australian context remain uncertain. AIM: To describe the changing incidence, aetiology and outcomes of ALF in South Eastern Australia. METHODS: The database of the Victorian Liver Transplant Unit was interrogated to identify all cases of ALF in adults (> 16 years) in adults hospitalised between January 2002 and December 2017. Overall, 169 patients meeting criteria for ALF were identified. Demographics, aetiology of ALF, rates of transplantation and outcomes were collected for all patients. Transplant free survival and overall survival (OS) were assessed based on survival to discharge from hospital. Results were compared to data from a historical cohort from the same unit from 1988-2001. RESULTS: Paracetamol was the most common aetiology of acute liver failure, accounting for 50% of cases, with an increased incidence compared with the historical cohort (P = 0.046). Viral hepatitis and non-paracetamol drug or toxin induced liver injury accounted for 15% and 10% of cases respectively. Transplant free survival (TFS) improved significantly compared to the historical cohort (52% vs 38%, P = 0.032). TFS was highest in paracetamol toxicity with spontaneous recovery in 72% of cases compared to 31% of non-paracetamol ALF (P < 0.001). Fifty-nine patients were waitlisted for emergency liver transplantation. Nine of these died while waiting for an organ to become available. Forty-two patients (25%) underwent emergency liver transplantation with a 1, 3 and 5 year survival of 81%, 78% and 72% respectively. CONCLUSION: Paracetamol toxicity is the most common aetiology of ALF in South-Eastern Australia with a rising incidence over 30 years. TFS has improved, however it remains low in non-paracetamol ALF.

9.
JHEP Rep ; 1(2): 107-113, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32039358

RESUMO

BACKGROUND & AIMS: Portal hypertension contributes to the pathogenesis of malnutrition and sarcopenia in cirrhosis via multiple mechanisms. Terlipressin is a vasopressin analogue that we administer via continuous outpatient infusion, as a bridge to transplantation in patients with hepatorenal syndrome or refractory ascites. We describe, for the first time, the impact of outpatient terlipressin on nutritional and muscle parameters. METHODS: Nutrition (subjective global assessment), handgrip strength, dietary intake (energy, protein), frequency of paracentesis and severity of liver disease (model for end-stage liver disease score) were prospectively recorded at terlipressin commencement and follow-up (transplantation, cessation or census date). RESULTS: Nineteen patients were included (89% male, median age 59.6 years, median model for end-stage liver disease score 24), of whom 12 had hepatorenal syndrome and 7 had refractory ascites. All patients were malnourished at baseline, 63% (n = 12) had sarcopenic-range grip strength, and mean paracentesis frequency was 2.86 ± 1.62/month. Median duration of terlipressin was 51 days (interquartile range 29-222). Fourteen patients (74%) were transplanted, 2 delisted (10%) and 3 (16%) continued terlipressin. Energy and protein intake improved significantly following terlipressin, from 17.94 ± 5.43 kcal/kg to 27.70 ± 7.48 kcal/kg, and 0.74 ± 0.28 g/kg to 1.16 ± 0.31 g/kg, respectively (both p < 0.001). Handgrip strength increased from 25.36 ± 8.13 kg to 28.49 ± 7.63 kg (p = 0.001). Linear regression analysis demonstrated hand grip strength increased 0.075% for every 1-day of terlipressin (p = 0.005). The frequency of large-volume paracentesis reduced by 46%, to 1.57 ± 1.51/month (p = 0.001). CONCLUSION: Continuous terlipressin infusion reduces the complications of portal hypertension and is associated with an improvement in nutritional and muscle parameters in patients on the liver transplant waiting list, in whom such characteristics usually demonstrate progressive decline. This validates both the aetiological role of portal hypertension in malnutrition and represents a promising new anabolic therapy. LAY SUMMARY: Malnutrition and poor muscle strength are common in liver disease and often get worse while patients await liver transplant. Terlipressin is a medication used to treat portal hypertension in patients with hepatorenal syndrome. It is usually given for a few days or weeks in patients confined to hospital. Our centre provides outpatient terlipressin for weeks to months as a bridge to liver transplant. In patients treated with terlipressin at our hospital, we observed a substantial increase in their dietary intake and muscle strength, which may improve their quality of life and outcomes after liver transplant.

11.
Int J Antimicrob Agents ; 46(3): 249-53, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26141230

RESUMO

Vancomycin is a glycopeptide antibiotic widely used in the management of meticillin-resistant Staphylococcus aureus (MRSA). Guidelines currently recommend vancomycin be administered by intermittent infusion, despite recent research suggesting that continuous infusion (CI) may be associated with lower rates of vancomycin-associated nephrotoxicity. In 2012, Cataldo et al. presented a meta-analysis supporting the use of CI. Here we present an updated meta-analysis, inclusive of a recently published large-scale retrospective study. PubMed, EMBASE and Cochrane Reviews databases were searched using the keywords 'vancomycin' and 'continuous' or 'intermittent' or 'infusion' or 'discontinuous' or 'administration'. Seven studies were included in the final analysis. Using a random-effects model, a non-significant trend of reduced nephrotoxicity in those who received vancomycin by CI (risk ratio=0.799, 95% confidence interval 0.523-1.220; P=0.299) was identified. A large, randomised controlled trial is necessary to confirm these results.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/administração & dosagem , Vancomicina/efeitos adversos , Humanos , Infusões Intravenosas/métodos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Estudos Retrospectivos , Infecções Estafilocócicas/microbiologia
13.
Crit Care Med ; 42(12): 2527-36, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25083977

RESUMO

OBJECTIVES: To evaluate the influence of vancomycin dose, serum trough concentration, and dosing strategy on the evolution of acute kidney injury in critically ill patients. DESIGN: Retrospective, single-center, observational study. SETTING: University Hospital ICU, Birmingham, UK. PATIENTS: All critically ill patients receiving vancomycin from December 1, 2004, to August 31, 2009. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The prevalence of new onset nephrotoxicity was reported using Risk, Injury, Failure, Loss, End-stage renal disease criteria, and independent factors predictive of nephrotoxicity were identified using logistic regression analysis. Complete data were available for 1,430 patients. Concomitant vasoactive therapy (odds ratio = 1.633; p < 0.001), median serum vancomycin (odds ratio = 1.112; p < 0.001), and duration of therapy (odds ratio = 1.041; p ≤ 0.001) were significant positive predictors of nephrotoxicity. Intermittent infusion was associated with a significantly greater risk of nephrotoxicity than continuous infusion (odds ratio = 8.204; p ≤ 0.001). CONCLUSIONS: In a large dataset, higher serum vancomycin concentrations and greater duration of therapy are independently associated with increased odds of nephrotoxicity. Furthermore, continuous infusion is associated with a decreased likelihood of nephrotoxicity compared with intermittent infusion. This large dataset supports the use of continuous infusion of vancomycin in critically ill patients.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Antibacterianos/efeitos adversos , Estado Terminal , Vancomicina/efeitos adversos , Injúria Renal Aguda/mortalidade , Idoso , Antibacterianos/administração & dosagem , Creatinina/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Prevalência , Análise de Regressão , Estudos Retrospectivos , Vancomicina/administração & dosagem
14.
BMJ Case Rep ; 20112011 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-22674601

RESUMO

The following case describes a 29-year-old previously well gentleman who presented with an acute onset of chest pain, dysphagia, odynophagia and vomiting without haematemesis. An oesophageal lesion was visualised on CT angiography and further investigation via oesophogastroduodenoscopy (OGD) diagnosed a spontaneous intramural oesophageal haematoma as the cause of his symptomatology. Conservative medical management in the form of triple therapy and softened diet was well tolerated and a follow-up OGD at 6 weeks after discharge from hospital showed spontaneous resolution of the haematoma.


Assuntos
Dor no Peito/etiologia , Doenças do Esôfago/complicações , Doenças do Esôfago/diagnóstico , Hematoma/complicações , Hematoma/diagnóstico , Adulto , Analgésicos/uso terapêutico , Antibacterianos/uso terapêutico , Transtornos de Deglutição/etiologia , Diagnóstico Diferencial , Dieta , Endoscopia do Sistema Digestório , Doenças do Esôfago/terapia , Hematoma/terapia , Humanos , Masculino , Inibidores da Bomba de Prótons/uso terapêutico , Descanso , Vômito/etiologia
15.
Vascular ; 15(3): 162-6, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17573023

RESUMO

Visceral artery aneurysm is a rare but clinically important form of vascular pathology, showing a high mortality rate in emergency surgery. Most often these aneurysms cause no symptoms and are therefore incidental findings. Reports on ileocolic artery aneurysms are rare and often anecdotal. Therapeutic procedures can be performed either surgically or by interventional therapeutic techniques. This article presents a case of ruptured ileocolic artery aneurysm and reviews the literature on this topic.


Assuntos
Aneurisma/diagnóstico por imagem , Artérias Mesentéricas/diagnóstico por imagem , Idoso , Aneurisma/cirurgia , Colo/irrigação sanguínea , Feminino , Humanos , Íleo/irrigação sanguínea , Imageamento Tridimensional/métodos , Artérias Mesentéricas/cirurgia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
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