Screening for nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus using transient elastography - a prospective, cross sectional study.

AIM: To investigate the prevalence and severity of nonalcoholic fatty liver disease (NAFLD) in patients with diabetes mellitus type 2 (T2DM), based on increased controlled attenuation parameter (CAP) and liver stiffness measurements obtained by transient elastography. In addition, we aimed to identify parameters that correlate with increased elastographic parameters of steatosis and fibrosis to provide a better indication when a patient with T2DM should be screened for NAFLD. METHODS: We conducted prospective, cross-sectional study of 679 consecutive adult patients with diagnosed T2DM mean age 65.2±11.6. NAFLD was defined by transient elastography. In 105 patients a percutaneous liver biopsy (LB) was done. RESULTS: The prevalence of NAFLD based on transient elastography was 83.6%. Independent factors associated with increased CAP were higher body mass index, longer T2DM duration, higher serum triglyceride, lower levels of vitamin D, higher C-reactive protein, and higher HOMA-IR. The prevalence of moderate liver fibrosis was 26.9% and advanced liver fibrosis 12.6%. Independent factors associated with moderated fibrosis based on elastography were higher body mass index and higher levels of alanine aminotransferase (ALT), while independent factors associated with advanced fibrosis were female gender, higher body mass index, higher levels of ALT, gama-glutamil transferase and C-reactive protein. Sixty-four (60.9%) of 105 patients with LB had NAFLD activity score ≥5. Regarding the presence and stages of fibrosis based on LB, moderate fibrosis was found in 29.5% of patients, while 29.5% had advanced fibrosis and 6.7% cirrhosis. CONCLUSION: This study supports more aggressive screening for NAFLD and fibrosis in patients with T2DM.

Prospective evaluation of non-alcoholic fatty liver disease by elastographic methods of liver steatosis and fibrosis; controlled attenuation parameter and liver stiffness measurements.

AIMS: To examine the temporal changes of both controlled attenuation parameter (CAP) and liver stiffness measurements (LSM), assessed by Fibroscan, in a large sample of patients with non-alcoholic fatty liver disease (NAFLD). METHODS: In this prospective, observational study, we consecutively enrolled 507 adult individuals with Fibroscan-defined NAFLD who were followed for a mean period of 21.2 ±â€¯11.7 months. RESULTS: During the follow-up period, 84 patients (16.5%) had a progression of CAP of at least 20% with a median time of 39.93 months, while 201 (39.6%) patients had a progression of LSM of at least 20% with median time of 30.46 months. There were significant differences in the proportion of LSM progression across body mass index (BMI) categories, with obese patients having the highest risk of progression over the follow-up (hazard ratio 1.66; 95%CI 1.23-2.25). Multivariable regression analysis showed that BMI and serum creatinine levels were the strongest predictors for CAP progression in the whole population, while HOMA-estimated insulin resistance was an independent predictor of LSM progression over time in the subgroup of obese patients. CONCLUSION: This prospective study shows for the first time that the progression risk of both liver steatosis and fibrosis, detected non-invasively by Fibroscan, is relevant and shares essentially the same metabolic risk factors that are associated with NAFLD progression detected by other invasive methods.

Nonalcoholic fatty liver and the severity of acute pancreatitis.

AIM: To explore the effect of nonalcoholic fatty liver as a hepatic manifestation of metabolic syndrome on the severity of acute pancreatitis. We hypothesized that patients with nonalcoholic fatty liver would have a more severe form of acute pancreatitis. PATIENTS AND METHODS: We retrospectively analyzed 822 patients hospitalized with acute pancreatitis. We diagnosed acute pancreatitis and determined its severity according the revised Atlanta classification criteria from 2012. We assessed nonalcoholic fatty liver with computed tomography. RESULTS: There were 198 (24.1%) patients out of 822 analyzed who had nonalcoholic fatty liver. Patients with nonalcoholic fatty liver had statistically higher incidence of moderately severe (35.4% vs. 14.6%; p=0.02) and severe acute pancreatitis (20.7% vs. 9.6%; p<0.001) compared to patients without nonalcoholic fatty liver. At the admission patients with nonalcoholic fatty liver had higher values of C-reactive protein as well as at day three, higher APACHE II score at admission and significantly higher incidence of organ failure and local complications as well as higher values of computed tomography severity index compared to patients without nonalcoholic fatty liver. We found independent association between the occurrence of moderately severe and severe acute pancreatitis and nonalcoholic fatty liver (OR 2.13, 95%CI 1.236-3.689). Compared to patients without nonalcoholic fatty liver, patients with nonalcoholic fatty liver had a higher death rate, however not statistically significant (5.6% vs. 4.3%; p=NS). CONCLUSION: Presence of nonalcoholic fatty liver at admission can indicate a higher risk for developing more severe forms of acute pancreatitis and could be used as an additional prognostic tool.

Non-alcoholic fatty liver disease and colorectal cancer.

As a significant cause of cancer death worldwide, colorectal cancer (CRC) is still one of the most common cancers in the world. The most efficient strategies to reduce CRC incidence include identifying risk factors for CRC and performing a preventive colonoscopy in high-risk populations. Some well-established risk factors for CRC development include hereditary syndromes and inflammatory bowel disease. Of note, in recent years, attention has been given to new evidence indicating that more than 75%-95% of CRC occurs in individuals with little or no genetic risk. For these individuals, the risk for CRC is associated with their lifestyle and dietary factors, including central obesity, overweight and physical inactivity. Recently, evidence demonstrated a connection between non-alcoholic fatty liver disease (NAFLD) and CRC. Insulin resistance and metabolic syndrome (MetS) are common risks that NAFLD and colorectal neoplasms share. The incidence of NAFLD is increasing in parallel with an increasing prevalence of MetS and obesity. Consequently, the question arises: will the incidence of CRC increase together with this dramatic increase in obesity, MetS and ultimately NAFLD prevalence? Recent studies of adenomatous polyps, CRC and NAFLD are discussed in this manuscript.

Metabolic syndrome and acute pancreatitis.

AIM: The aim of our study was to investigate the influence of metabolic syndrome on the course of acute pancreatitis determined by disease severity, the presence of local and systemic complications and survival rate. PATIENTS AND METHODS: 609 patients admitted to our hospital in the period from January 1, 2008 up to June 31, 2015 with the diagnosis of acute pancreatitis were analyzed. The diagnosis and the severity of acute pancreatitis were made according to the revised Atlanta classification criteria from 2012. RESULTS: Of 609 patients with acute pancreatitis, 110 fulfilled the criteria for metabolic syndrome. Patients with metabolic syndrome had statistically significantly higher incidence of moderately severe (38.2% vs. 28.5%; p=0.05) and severe (22.7% vs. 12.8%; p=0.01) acute pancreatitis in comparison to those without metabolic syndrome, while patients without metabolic syndrome had higher incidence of mild acute pancreatitis in comparison to those patients with metabolic syndrome (58.7% vs. 39.1%; p<0.001). Patients with metabolic syndrome had a higher number of local and systemic complications, and higher APACHE II score in comparison to patients without metabolic syndrome. In multivariable logistic regression analysis, the presence of metabolic syndrome was independently associated with moderately severe and severe acute pancreatitis. Comparing survival rates, patients suffering from metabolic syndrome had a higher death rate compared to patients without metabolic syndrome (16% vs. 4.5%; p<0.001). CONCLUSION: The presence of metabolic syndrome at admission portends a higher risk of moderately severe and severe acute pancreatitis, as well as higher mortality rate.

Early nasojejunal tube feeding versus nil-by-mouth in acute pancreatitis: A randomized clinical trial.

BACKGROUND/OBJECTIVES: There is substantial evidence of superiority of enteral nutrition (EN) to parenteral nutrition in acute pancreatitis (AP) treatment, but few studies evaluated its effectiveness compared to no intervention. The objective of our trial was to compare the effects of EN to a nil-by-mouth (NBM) regimen in patients with AP. METHODS: Patients with AP were randomized to receive either EN via a nasojejunal tube initiated within 24 h of admission or no nutritional support. Systemic inflammatory response syndrome (SIRS) was assessed as the primary outcome. Secondary outcomes included mortality, organ failure, local complications, infected pancreatic necrosis, surgical interventions, length of hospital stay, adverse events and inflammatory response intensity. Outcomes were compared using Student's t-test and Mann-Whitney U test as appropriate. RESULTS: 214 patients were randomized in total, 107 to each group. SIRS occurrence was similar between groups, with 48 (45%) versus 51 (48%), respectively (RR 0.94; 95% CI 0.71-1.26). No significant reduction of persistent organ failure (RR 0.81; 95% CI 0.52-1.27) and mortality (RR 0.59; 95% CI 0.28-1.23) was present in the EN group. There were no significant differences in other outcomes between the groups. When analyzing the occurrence of SIRS and mortality in subgroup of patients with severe disease no significant differences were noted. CONCLUSION: Our results showed no significant reduction of persistent organ failure and mortality in patients with AP receiving early EN compared to patients treated with no nutritional support (NCT01965873).

Is there a relationship between hypomagnesemia and proton-pump inhibitors in patients on chronic hemodialysis?

AIM: We investigated the association among long-term proton-pump inhibitors (PPIs) use with serum magnesium (Mg) levels in chronic hemodialysis (HD) patients, as well as possible association among PPI use and increased risk of cardiovascular (CVD) morbidity in HD patients. METHODS: Of 418 HD patients that were screened for inclusion, 136 were excluded due to incomplete medical data, duration of renal replacement therapy (RRT) for less than 12months, use of Mg-based-phosphate binders or other Mg-based medications or either to presence of chronic increased GI losses. Among 282 patients included in the study, 170 patients were on PPIs. RESULTS: Serum Mg levels were significantly lower among PPI users vs. non-users (0.94±0.2 vs. 1.03±0.2mmol/L; p<0.0001). The median duration of PPI use was 27±9.6months (range from 12 to 108) and it was not significantly associated with Mg levels (r=0.116; p=0.167). Additionally, residual renal function didn't show a significant correlation with Mg concentration (r=-0.102; p=NS) in both groups of patients. The use of PPIs was an independent and strong predictor of low Mg concentrations even in multivariate analysis (OR 3.05; 95% CI 1.2498-7.4594, p=0.01). On the other hand, the daily dose of PPIs was not associated with low Mg levels. PPI users had a higher rate of adverse CVD events during the 1 year of follow-up in comparison to non-PPI users but that difference wasn't statistically significant (17.6% vs. 10.7%; p=0.110). CONCLUSION: We have found a significant association between PPI use and lower serum Mg levels in chronic HD patients.

Body mass index: short- and long-term impact on kidney transplantation.

AIM: The topic of pretransplantation body mass index (BMI) is still a matter of controversy. The aim of this study was to investigate the influence of pretransplant BMI on short- and long-term outcomes in patients receiving kidney transplant. METHODS: We have analysed 521 renal transplant recipients (RTRs). BMI was categorised as follows: less than or equal to 20, more than 20 to less than or equal to 25, more than 25 to less than or equal to 30 and more than 30 RESULTS: The distribution of the RTRs per category of BMI at baseline was: ≤ 20 (14.4%), > 20 to ≤ 25 (50.9%), > 25 ≤ 30 (26.9%) and > 30 (7.9%). In further analysis, the patients were stratified into four groups according to their pretransplant BMI values. There was no difference in the rates of delayed graft function between the four analysed groups of patients. Recipients with normal pre-transplant BMI were less likely to develop wound complications in comparison to the recipients with high BMI (p = 0.04) and obese recipients (p = 0.0001). RTRs with normal BMI were less likely to develop lymphoceles in comparison to the recipients with high BMI (p = 0.0003). Obese patients were more likely to develop lymphocele in comparison to the recipients with high BMI (p = 0.01). Obese recipients had a longer mean length of hospital stay in comparison to the recipients with normal BMI (p = 0.04). There was no significant difference regarding 1-year graft and patient survival, as well as because of acute rejection crisis between the investigated groups of recipients. We did not find any significant difference in 5-year patients and graft survival between those RTRs with BMI > 20 to ≤ 25 and to those recipients with BMI > 25. CONCLUSION: Overweight and obese transplant candidates should not be excluded from kidney transplantation.

Nonalcoholic fatty liver disease (NAFLD)--is it a new marker of hyporesponsiveness to recombinant human erythropoietin in patients that are on chronic hemodialysis?

Anemia is a major consequence of chronic kidney disease (CKD) that develops early in the course of illness and affects most patients who exhibit some degree of reduced renal function. Erythropoietin (EPO) deficiency is considered the most important cause of anemia in CKD. Renal anemia has serious clinical consequence. In addition to reducing patient physical capacity and quality of life, anemia induces adaptive cardiovascular mechanisms that increase the risk of cardiovascular disease and death. Thus, treatment of anemia in CKD is very important. While EPO is effective in correcting anemia in most cases, up to 10% of patients however, have an inadequate response to therapy. The two most common and important reasons why patients become relatively unresponsive to EPO therapy are the development of true iron deficiency and the onset of an inflammatory state that impairs the response to EPO. Indeed, the role of inflammation and pro-inflammatory cytokines in resistance to EPO therapy is gaining increasing recognition. On the other hand, the main organ for C-reactive protein (CRP) synthesis is the liver and it is well known that the synthesis of an acute-phase proteins by the liver is up regulated by inflammation. The main consequence of nonalcoholic fatty liver disease (NAFLD) is sub-chronic liver inflammation that leads and contributes to dyslipidemia, inflammation, enhanced oxidative stress and endothelial dysfunction. Considering the recent data about high prevalence of NAFLD in CKD patients, probably due to shared metabolic risk factors, we hypothesized that end-stage renal disease (ESRD) patients with NAFLD will need a much higher dose of EPO to achieve the target hemoglobin levels in comparison with ESRD patients without NAFLD. The possible underlying mechanism is sub-chronic liver inflammation in NAFLD patients that leads and contributes to poor response to EPO. Therefore, we believe that NAFLD could be a new clinical marker of poor response to EPO therapy in ESRD patients. Optimizing response to EPO therapy is important for both patient outcomes and the cost of treatment, and require consideration of a growing number of factors. Detection of NAFLD by some of non-invasive methods in ESRD patients could identify responsiveness and resistance to EPO therapy. Furthermore, we propose that all the patients who undergo dialysis treatment should be screened for NAFLD in order to identify the patients that will have a poor response to EPO therapy. The work could help to determine whether we have a new marker of poor EPO response in ESRD patients.

Transient elastography: a new noninvasive diagnostic tool for assessment of chronic allograft nephropathy.

PURPOSE: Chronic allograft nephropathy (CAN) is the most common cause of kidney allograft failure. Protocol biopsies remain the "gold standard" in CAN recognition. However, renal allograft biopsies have numerous limitations. It is an invasive procedure connected with risk of complications, patient discomfort, and sampling errors. The aim of our study was to investigate the usefulness of transient elastography (TE) for the assessment of kidney allograft fibrosis in renal transplant recipients (RTRs). METHODS: In this cross-sectional study, we involved 52 RTRs. Renal allograft stiffness was used to assess its fibrosis by using transient elastography (Fibroscan, Echosense, Paris, France). In 23 patients with a deterioration of graft function, percutaneous renal allograft biopsy was performed closely around the time of TE. RESULTS: We have found that the renal allograft stiffness was highly negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.640; p < 0.0001). However, renal allograft stiffness showed a statistically significant difference between patients who had an eGFR > 50 ml/min per 1.73 m(2) and patients with eGFR < 50 ml/min per 1.73 m(2) (28 ± 2.7 vs. 33.9 ± 5.5 kPa; p = 0.0003). Also, there was a highly positive correlation between renal allograft stiffness and extent of interstitial fibrosis on renal biopsy (r = 0.727; p = 0.0001). CONCLUSION: According to our results, parenchymal stiffness obtained by TE reflects interstitial fibrosis. Therefore, TE provides the opportunity for noninvasive screening of CAN.

Chronic kidney disease and nonalcoholic Fatty liver disease-is there a link?

Research in recent years has led to the recognition of the importance of nonalcoholic fatty liver disease (NAFLD) and its relationship to the metabolic syndrome (MS). This has led to a growing interest in the potential prognostic value of NAFLD for adverse cardiovascular disease (CVD) outcome. On the other hand, searching for new risk factors for chronic kidney disease (CKD) development and progression is very important. Growing evidence suggests that the MS is an important factor in the pathogenesis of CKD. The best confirmation of this pathogenic link is hypertensive and diabetic nephropathy as the main causes of CKD. Furthermore, the possible link between NAFLD and CKD has also attracted research interest and recent data suggest an association between these two conditions. These findings have fuelled concerns that NAFLD may be a new and added risk factor for the development and progression of CKD. NAFLD and CKD share some important cardiometabolic risk factors and possible common pathophysiological mechanisms, and both are linked to an increased risk of incident CVD events. Therefore, common factors underlying the pathogenesis of NAFLD and CKD may be insulin resistance, oxidative stress, activation of rennin-angiotensin system, and inappropriate secretion of inflammatory cytokines by steatotic and inflamed liver.

The Role of IL-6, 8, and 10, sTNFr, CRP, and Pancreatic Elastase in the Prediction of Systemic Complications in Patients with Acute Pancreatitis.

Background and Aim. Early assessment of severity in acute pancreatitis (AP) is a key measure to provide rational and effective management. The aim of our study is to determine the prognostic value of interleukins (IL) 6, 8, and 10, soluble receptor for tumor necrosis factor (sTNFr), pancreatic elastase (E1), and C-reactive protein (CRP) as predictors of systemic complications in AP. Patients and Methods. A hundred and fifty patients with confirmed AP were enrolled in the study. The severity of AP was defined according to Atlanta criteria. Measurements of interleukins and sTNFr were performed on the first day of admission. CRP and E1 levels were assessed on admission and after 48 hours. ROC analysis was performed for all parameters. Results. Interleukins and sTNFr significantly differentiated patients with systemic complications from those without. Elevation of IL-6 showed the highest significance as a predictor (P = 0.001). CRP and elastase levels did not differ between mild and severe cases on admission, but reached statistical significance when measured on the third day (P = 0.002 and P = 0.001, resp.). Conclusion. Our study confirmed that IL-6, IL-8, IL-10, and sTNFr measured on admission, and CRP and pancreatic elastase measured on third day of admission represent valuable prognostic factors of severity and systemic complications of AP.

Acid inhibition and peptic ulcer bleeding.

Peptic ulcer bleeding is one of the most common emergency situations in medicine. Combined pharmacological and endoscopic therapy together with emerging interventional radiological procedures are successfully treating peptic ulcer disease, reserving surgical procedures for only a small portion of patients unresponsive to 'conventional' therapy. Technological advancement has seen a great improvement in the field of endoscopic treatment in the form of various methods of hemostasis. However, pharmacological therapy with proton pump inhibitors still plays the central role in the peptic ulcer bleeding treatment algorithm.

Rational therapy of acute pancreatitis.

Management of acute pancreatitis represents a challenging aspect of everyday clinical practice that requires a multimodal and interdisciplinary approach. Mild cases of acute pancreatitis are usually self-limiting and treated with fluid resuscitation, analgesics, oxygen administration, and antiemetics. In addition to this, the role of nutritional support has been established for patients with severe acute pancreatitis with more evidence demonstrating its beneficial effects. Antibiotic prophylaxis, even though widely studied and often administrated, does not seem to have an effect on the development of complications and mortality. Patients who develop infected necrosis of the pancreatic tissue require surgical assistance. Various techniques of necrosectomy and drainage are accepted as promising methods in the management of severe acute pancreatitis.

Toxic epidermal necrolysis associated with carvedilol treatment.

OBJECTIVE: To report a case of fatal toxic epidermal necrolysis associated with carvedilol treatment. CASE SUMMARY: Two days after the initiation of carvedilol treatment, a 70-year old woman presented with skin eruptions in the form of maculous rash with blisters that rapidly progressed to epidermal necrolysis. Although the suspected drug was withdrawn, the reaction was extremely rapid in its development with fatal outcome. DISCUSSION: Carvedilol is not a drug commonly associated with TEN. To our knowledge there are no cases of carvedilol related TEN reported in the literature. CONCLUSION: Because of the close temporal relationship between the initiation of carvedilol treatment and the appearance of skin eruptions, and because carvedilol was the only new medication the patient had taken, the etiology of TEN was most likely a reaction to this drug. Physicians should be aware of this extremely rare but serious ADR.

Haematological, biochemical and bone density parameters in vegetarians and non-vegetarians.

OBJECTIVE: The objective is to determine any possible differences between haematological, biochemical and bone mineral density in vegetarians (vegans and lacto-ovovegetarians) and non-vegeterians. METHODS: The examined group consisted of 100 individuals: 50 non-vegetarians and 50 vegetarians. The vegetarian group was further divided in 2 subgroups: 20 vegans and 30 lacto-ovovegetarians. In all participants, plasma levels of erythrocytes, haemoglobin, haematocrit, iron, low density lipoprotein, (LDL), high density lipoprotein (HDL) total cholesterol, triglycerides and glucose were measured. Quantitative ultrasound parameters of the right calcaneus were determined in all participants. RESULTS: The results showed that lacto-ovovegetarians had statistically significantly higher red blood cell counts and haematocrit values than non-vegetarians. Vegans also had higher haematocrit values than non-vegetarians. Statistically significant differences were found between iron plasma levels in the examined groups. Iron levels were lower in non-vegetarians than in vegans and lacto-ovovegetarians. Non-vegetarians had much higher levels of cholesterol, triglycerides and LDL than the other two groups, but there were no differences found between same values in vegans and lacto-ovovegetarians. CONCLUSION: A well planned and balanced vegetarian diet, with avoidance of risk factors, does not result in abnormalities in laboratory tests and bone status parameters.

New prognostic index to predict survival in patients with cancer of unknown primary site with unfavourable prognosis.

AIMS: To identify independent prognostic factors in patients with cancer of unknown primary site (CUP) who do not belong to prognostically favourable subsets, and to develop a prognostic index for predicting survival in these patients. MATERIALS AND METHODS: In this prospective study, univariate and multivariate analyses of prognostic factors were conducted in a population of 145 patients with CUP in two clinical institutions. Subsets of patients with favourable prognostic features and those requiring well-defined treatment were excluded. RESULTS: The 1-year overall survival rate for all patients was 42% and the median overall survival was 330 days. Overall survival was significantly related to the following pre-treatment prognostic factors: poor Eastern Cooperative Oncology Group performance status (ECOG PS)>or=2, presence of liver metastasis, elevated serum lactate dehydrogenase (LDH), high white blood cell count, anaemia, age>or=63 years, and prolonged QTc interval in electrocardiography (ECG). In multivariate analysis, four independent adverse prognostic parameters were retained: elevated LDH (hazard ratio 2.21; 95% confidence interval 1.41-3.47; P=0.001), prolonged QTc interval (hazard ratio 2.10; 95% confidence interval 1.28-3.44; P=0.003), liver metastasis (hazard ratio 1.77; 95% confidence interval 1.11-2.81; P=0.016) and ECOG PS>or=2 (hazard ratio 1.69; 95% confidence interval 1.05-2.73; P=0.03). We developed a prognostic index for overall survival based on the following subgroups: good prognosis (no or one adverse factor), intermediate prognosis (two adverse factors) and poor prognosis (three or four adverse factors). The median overall survival for the three subgroups was 420, 152 and 60 days, respectively, P<0.0001. CONCLUSIONS: This study validated previously identified important prognostic factors for survival in patients with CUP. Prolonged QTc was additionally identified as a strong adverse prognostic factor. We developed a simple prognostic index using performance status, LDH, presence of liver metastasis and QTc interval in ECG, which allowed assignment of patients into three subgroups with divergent outcome.

A Phase II safety and effect on time to tumor progression study of intratumoral light infusion technology using talaporfin sodium in patients with metastatic colorectal cancer.

BACKGROUND AND OBJECTIVES: Twenty-seven patients with refractory liver metastases from colorectal cancer took part in a Phase II study of the light infusion technology (Litx) light-activated drug/device system to assess safety and evaluate time to tumor progression (TTP). METHODS: Litx consists of the light-activated drug, talaporfin sodium (LS11), activated intratumorally by a catheter-like array of light-emitting diodes (LEDs). After placement of the array via ultrasound or computed tomography (CT) guidance, LS11 was administered intravenously, followed 15-60 min later by light infusion for 2.8 hr. Patients were assessed for adverse events and tumor response using physical examination, laboratory values, and CT scan evaluation over a period of 60 days. RESULTS: The observed occurrence of Litx treatment-related adverse events was minimal and cumulative toxicity did not occur when combined with chemotherapy. Assessment of TTP and tumor response rate, although statistically non-robust, suggest potential improvement. CONCLUSIONS: The Litx system was shown to be safe for treating liver metastases from colorectal cancer and there was no cumulative toxicity when combined with standard systemic therapy. Preliminary assessments of TTP and tumor response rate justify further evaluation in a Phase III follow-up study.

Mediastinal necrosis in acute pancreatitis - case report.

Ascites, pseudocyst, necrosis of the retroperitoneal fat tissue and pancreatopleural fistula with left sided pleural effusion may complicate pancreatitis. However, steatonecrosis of the mediastinum and right side pleural effusion are rather rare complications of pancreatitis. We present a case of a patient with alcohol induced pancreatitis. Chest x-ray showed right sided pleural effusion. Although high levels of amylase in pleural fluid made the diagnosis of pancreatopleural fistula most likely, necrosis of the mediastinal fat tissue with right side pleural effusion was found postmortem.

Cochrane systematic review: pegylated interferon plus ribavirin vs. interferon plus ribavirin for chronic hepatitis C.

BACKGROUND: About 170 million patients worldwide have chronic hepatitis C. Pegylated interferon plus ribavirin is currently the recommended therapy. AIM: To evaluate the beneficial and harmful effects of pegylated interferon plus ribavirin vs. interferon plus ribavirin for chronic hepatitis C infection. METHODS: We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, Science Citation Index Expanded and contacted pharmaceutical companies and authors of trials (to March 2005). RESULTS: We included 18 randomized clinical trials with 4811 patients. Eleven trials (61%) had allocation bias risks and all had assessment bias risk because of lack of blinding. Compared with interferon plus ribavirin, pegylated interferon plus ribavirin had significant beneficial effects on sustained virological response [risk ratio (RR): 0.80; 95% CI: 0.74-0.88]. Data were insufficient to determine impact on long-term outcomes. Pegylated interferon plus ribavirin significantly increased dose reductions (RR: 1.44; 95% CI: 1.14-1.82) and adverse events including neutropenia (RR: 2.25; 95% CI: 1.58-3.21), thrombocytopenia (RR: 2.28; 95% CI: 1.14-4.54), arthralgia (RR: 1.19; 95% CI: 1.05-1.35), and injection-site reaction (RR: 2.56; 95% CI: 1.06-6.22). CONCLUSIONS: Pegylated interferon plus ribavirin compared with interferon plus ribavirin increased the proportion of patients with sustained virological response, but at the cost of more adverse events.