Elastographic parameters of liver steatosis and fibrosis predict independently the risk of incident chronic kidney disease and acute myocardial infarction in patients with type 2 diabetes mellitus.

AIMS: The aim of this prospective study was to examine the relationship between controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) with the risk of developing a composite endpoint inclusive of incident acute myocardial infarction (AMI), cerebrovascular insult (CVI) or chronic kidney disease (CKD) in people with type 2 diabetes mellitus (T2DM). METHODS: This study included 238 T2DM outpatients without chronic liver diseases. RESULTS: The patient population was followed for a median period of 7.6 years. Kaplan-Meier survival analyses showed that there was a higher proportion of patients who developed the aforementioned composite outcome (P < 0.001 by the log-rank test), as well as CKD (P < 0.001) or AMI alone (P = 0.014) among those with elevated CAP values (≥238 dB/m) at baseline. Similarly, Kaplan-Meier survival analyses showed that there was a higher proportion of patients who developed the composite outcome (P < 0.001), as well as CKD (P < 0.001), or AMI alone (P < 0.001) among those with elevated LSM values (≥7.0/6.2 kPa). In multivariable regression analyses, the presence of elevated CAP (adjusted-hazard ratio 2.34, 95% CI 1.32-4.15) and elevated LSM (adjusted-hazard ratio 2.84, 95% CI 1.92-4.21), independently of each other, were associated with a higher risk of developing the composite outcome, as well as incident AMI or CKD alone after adjusting for traditional cardiovascular risk factors and diabetes-related variables. CONCLUSIONS: Our study shows that the elastographic parameters of liver steatosis and fibrosis independently predict the long-term risk of developing chronic vascular complications in T2DM patients.

Significant liver fibrosis, as assessed by fibroscan, is independently associated with chronic vascular complications of type 2 diabetes: A multicenter study.

AIMS: The aim of this study was to investigate whether controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), as assessed by vibration-controlled transient elastography (VCTE), are associated with chronic vascular complications of diabetes mellitus type 2 (T2DM). METHODS: We studied 442 outpatients with established T2DM, and who underwent VCTE and extensive assessment of chronic vascular complications of diabetes. RESULTS: A quarter of analyzed patients had a previous history of myocardial infarction and/or ischemic stroke, and about half of them had at least one microvascular complication (chronic kidney disease (CKD), retinopathy or polyneuropathy). The prevalence of liver steatosis (i.e., CAP ≥ 238 dB/m) and significant liver fibrosis (i.e., LSM ≥ 7.0/6.2 kPa) was 84.2% and 46.6%, respectively. Significant liver fibrosis was associated with an increased likelihood of having myocardial infarction (adjusted-odds ratio 6.61, 95%CI 1.66-37.4), peripheral polyneuropathy (adjusted-OR 4.55, 95%CI 1.25-16.6), CKD (adjusted-OR 4.54, 95%CI 1.24-16.6) or retinopathy (adjusted-OR 1.81, 95%CI 1.62-1.97), independently of cardiometabolic risk factors, diabetes-related variables, and other potential confounders. Liver steatosis was not independently associated with any macro-/microvascular diabetic complications. CONCLUSIONS: Significant liver fibrosis is strongly associated with the presence of macro-/microvascular complications in patients with T2DM. These results offer a new perspective on the follow-up of people with T2DM.

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.

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.

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.

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.

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.

Renin-angiotensin-aldosterone system inhibitors lower hemoglobin and hematocrit only in renal transplant recipients with initially higher levels.

AIM: We have analyzed the effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on evolution of hemoglobin (Hb) and hematocrit (Htc) levels as well as on the evaluation of kidney graft function in stable renal transplant recipients (RTRs) in respect with initially higher or lower Hb and Htc values. METHODS: The study group comprised of 270 RTRs with stable graft function. Besides other prescribed antihypertensive therapy, 169 of them have been taking RAAS inhibitors. RESULTS: We wanted to analyze the effect of the use of RAAS inhibitors on Hb and Htc in patients with initially higher or lower Hb/Htc values. For this analysis, only RTRs that were taking RAAS inhibitors were stratified into two groups: one with higher Hb and Htc (initial Hb≥150g/L and Htc≥45%) and another one with lower Hb and Htc (initial Hb<150g/L and Htc<45%) values. Thirty-four RTRs with initially higher Hb and 41 RTRs with initially higher Htc had a statistically significant decrease in Hb (p=0.006) and Htc (p<0.0001) levels after 12-months of follow-up. In the group of patients with initially lower Hb (135 RTRs) and Htc (128 RTRs) there was a significant increase in Hb (p=0.0001) and Htc (p=0.004) levels through the observed period. The use of RAAS inhibitors has been associated with a trend of slowing renal insufficiency in RTRs (p=0.03). CONCLUSION: RAAS inhibitors lower Hb and Htc only in RTRs with initially higher levels. In patients with initially lower Hb and Htc levels, the use of these drugs is followed by beneficial impact on erythropoiesis and kidney graft function.

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.

Outcomes following renal transplantation in older renal transplant recipients: a single-center experience and "Croatian senior program".

BACKGROUND/OBJECTIVE: Outcomes of kidney transplantation in older patients have not, however, been fully defined. The aims of this study were to analyze the number of new end-stage renal disease (ESRD) patients ≥65 years of age who were managed with kidney transplantation and their survival through the study period. In addition, we have analyzed post-transplantation outcomes in younger and older renal transplant recipients (RTRs). METHODS: We have analyzed the mean age of 505 RTRs transplanted between January 1990 and December 2013. Older people were defined as aging 65 years or older. Of 505 RTRs, there were 73 (14.5 %) patients who were ≥65 years of age. Therefore, in further analysis, patients were divided into two subgroups: younger recipients (younger than 65 years) and older recipients (aging 65 years or older). RESULTS: In the period from 1990 to 2001, patients who were 65 years of age and older were only sporadically treated with kidney transplantation in Croatia. Since 2002, the number of patients older than 65 years undergoing renal transplantation has been increasing. The older recipients were more likely to receive organs from older donors (52.6 ± 16.8 vs. 45.8 ± 13.2; p = 0.0001). There were no significant differences due to HLA mismatch between the two groups of analyzed patients. There was no difference in the rates of DGF between the older and younger recipients. Older recipients were less likely than younger recipients to have acute rejection crisis during the first-ear after transplantation (16.4 vs. 34.7 %; p = 0.03). There were no significant differences due to readmission rates in the first-year post-transplantation between the two groups. There was no significant difference due to graft function and 1-year graft and patient's survival between young and older recipients. Serum creatinine values at 1 year were higher in older recipients who received kidneys from elderly donor. CONCLUSION: Our experience supports the use of kidney transplantation in the population of older ESRD patients. We can increase patients and graft survivals in elderly individuals with careful pre-transplant evaluation and HLA matching. "Croatian senior program" that includes HLA matching represents a good approach for kidney transplantation in older ESRD patients.

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.

Nonalcoholic Fatty liver disease in renal transplant recipients proven by transient elastography.

BACKGROUND: The increasing recognition of the importance of nonalcoholic fatty liver disease (NAFLD) and its strong association with the metabolic syndrome has stimulated interest in the putative role of NAFLD in the development and progression of cardiovascular disease. Furthermore, recent studies investigated the association of NAFLD and chronic kidney disease. We analyzed the incidence of NAFLD diagnosed by transient elastography (TE) in renal transplant recipients (RTRs). We also assessed whether TE-defined NAFLD is associated with decreased graft function in RTRs. METHODS: Our study included 73 RTRs with a functioning graft for more than 1 year. Liver stiffness was used to assess liver fibrosis and the controlled attenuation parameter (CAP) was used to detect and quantify liver steatosis by using TE (Fibroscan, Echosense, Paris, France). Therefore, with CAP being implemented on TE, both steatosis and fibrosis could be evaluated simultaneously. According to this evaluation, NAFLD was defined by the presence of steatosis with CAP values ≥ 238 dB.m(-1) regardless of presence or absence of any stage of fibrosis. RESULTS: According to the TE findings, NAFLD was present in 57.5% of RTRs. We have found that the severity of liver steatosis was positively correlated with serum creatinine levels (r = 0.664; P < .0001) and negatively correlated with estimated glomerular filtration rate (eGFR; r = -0.692; P < .0001) levels. The severity of liver fibrosis was positively correlated with the serum creatinine, serum iron, and C-reactive protein levels indicating a more severe form of NAFLD in those patients. None of the investigated liver tests showed any differences between those RTR patients who had NAFLD compared to those without NAFLD. CONCLUSION: Our results showed that RTRs have high prevalence of TE-defined NAFLD which possibly contributes to graft dysfunction. Measuring aminotransferase levels would not be a useful tool for NAFLD detection in RTRs. Our study showed the value of TE as an effective, noninvasive screening method for the diagnosis of NAFLD in RTRs.

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.

Non-alcoholic fatty liver disease; a part of the metabolic syndrome in the renal transplant recipient and possible cause of an allograft dysfunction.

Despite all improvements in transplant medicine, renal transplant recipients have a high risk for cardiovascular mortality. A high prevalence of cardiovascular complications in renal transplant recipients (RTR) is explained by cardiovascular risk factors present before transplantation, in addition to the development of new risk factors as well as worsening of preexisting risk factors after transplantation. A majority ot these patients develop metabolic syndrome within a year after the transplantation. The metabolic syndrome (MS) is associated with impaired renal allograft function and increased insulin resistance. Non alcoholic fatty liver disease (NAFLD) represents a liver manifestation of metabolic syndrome and it development is strongly associated with all components of MS in general population. The current importance of NAFLD and its link to the MS has encouraged an interest in its possible role in the development of atherosclerosis in recent years. Considering the fact that all components of MS are more common among renal transplant recipients compared to general population, it would be expected that RTR may have a much higher incidence of NAFLD compared to general population. We propose that the presence of NAFLD in RTR could be a strong predictor in cardiovascular morbidity and mortality. Also, according to the recent investigations about the possible link between NAFLD and chronic kidney disease, we hypothesis that NAFLD may be associated with deteriorating graft function, causing a chronic allograft nephropathy and graft loss. Common factors underlying the pathogenesis of NAFLD and chronic allograft dysfunction may be insulin resistance, oxidative stress, activation of rennin-angiotensin system, and inappropriate secretion of inflammatory cytokines by steatotic and inflamed liver.

Nonalcoholic fatty liver disease (NAFLD): a new risk factor for adverse cardiovascular events in dialysis patients.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. Today it is believed that NAFLD is a hepatic manifestation of metabolic syndrome, and thus it is closely related to the cardiovascular morbidity and mortality. Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in patients with end-stage-renal disease (ESRD). NAFLD and ESRD share some important cardiometabolic risk factors and possible common pathophyisiological mechanisms, and are linked to an increased risk of incident CVD events. We hypothesize that the coexistence of these two conditions could lead to much faster progress of the aterogenic process. Furthermore, patients with ESRD who suffer from NAFLD have a much higher risk for the development of adverse CVD events. Given the high prevalence of NAFLD, and its tight association with other manifestations of the metabolic syndrome and thus cardiovascular complications, it is important to recognize and aggressively treat this condition in ESRD patients. To evaluate this hypothesis, we propose the use of non-invasive methods such as transient elastography (TE) (Fibroscan-CAP) for the detection and quantification of liver steatosis and fibrosis, as well as an abdominal ultrasound for detecting liver steatosis. We focus on their correlation with carotid intima-media thickness (IMT) and plaque as surrogate measures of increased cardiovascular risk in HD patients in order to investigate the association of NAFLD and increase risk of adverse CVD events. This evaluation will prove useful in assessing the risk in HD patients with NAFLD for increase CVD mortality.

Infection with Helicobacter pylori and long-term use of non-steroidal antiinflammatory drugs.

The use of nonsteroidal anti inflammatory drugs (NSAID) is associated with an increased risk of peptic ulcer and of ulcer complications. However, the relation between Helicobacter pylori infection and gastroduodenal damage associated with NSAID use is unclear. This study investigated the prevalence of Helicobacter pylori infection in patients with arthritis (n = 85) taking NSAID, trying to find out whether the patients taking NSAID and infected with H. pylori were more likely to have dyspepsia, mucosal damage or chronic active gastritis than those without H. pylori infection. H. pylori was identified by biopsy, rapid urease test and histologic test. Dispeptic symptoms were assessed according to a standardized questionnaire. Gastroduodenal mucosal damage was graded endoscopically (using a modified Lanza scale) and the diagnosis of chronic gastritis was based on the histologic criteria of the Sydney system. The frequency of H. pylori infection was found to increase with age. No statistically significant difference was observed in the presence of damage to gastroduodenal mucosa between the patients with and without H. pylori infection. H. pylori infection was found to be associated with an increased frequency and severity of dyspeptic symptoms in patients with arthritis taking long-term NSAID. Chronic active gastritis was only present in patients with H. pylori infection. H. pylori infection was shown to be associated with an increased frequency and severity of dyspeptic symptoms in patients with arthritis on long-term NSAID therapy, without causing an increased damage to gastroduodenal mucosa.

External fixation as a primary and definitive treatment of open limb fractures.

This paper analyses the medical records of 5024 injured persons treated and operated on at the Surgical Clinic of the Clinical Hospital in Osijek, during the war against Croatia (1991 and 1992). There were 1653 (33.0 per cent) admitted, while the rest were treated as out-patients. Of the admitted patients 82.7 per cent (1372) had limb injuries. In 760 (15.0 per cent) of the wounded, 1320 limb fractures caused by explosives were diagnosed, out of which 856 were of the lower and 464 of the upper limbs. One hundred and ninety-two (3.9 per cent) were treated by external fixation. External fixators were applied to 147 lower and 68 upper open long bones, respectively. Adequate reconstructive operations were performed on 106 (2.1 per cent) patients with associated injuries to important blood vessels. The stabilization of the open and unstable external fractures was achieved by external fixation, mostly at one level, regardless of the wound size. The importance of good wound cleaning has been particularly stressed as well as bone fragment reposition. Special attention has been given to the preoperative and intra-operative assessment of the limbs. In 20 patients (9.3 per cent) treated with external fixation, osteitis occurred. Twenty-one more patients (9.7 per cent), because of bad fracture healing after external fixation, were submitted to secondary internal bone fixation combined with bone grafts. Out of these, nine (42.8 per cent) developed osteitis as a consequence of the additional treatment.

[Personal experience in the care of open fractures using external fixation during the hostilities in Osijek and surrounding region]. / Nase iskustvo u zbrinjavanju otvorenih prijeloma metodom vanjske fiksacije u periodu agresije na Osijek i okolinu.

In the period of aggression of the Federal Army and Serbian paramilitary forces on the City of Osijek and its surrounding, beginning in the summer of 1991, 4036 wounded were treated at the Department of Surgery, Osijek General Hospital. Extremity injuries were documented in 3889 patients, including 959 bone fractures. The majority of patients had wounds caused by highly destructive explosives filled with metal fragments of different shapes and dimensions, and having sharp and uneven edges. One hundred and forty wounded were treated by external fixators. In 102 patients this mode of fixation was applied for gun- and explosive-related long bone fractures of the lower extremities. External fixator for the upper and forearm fractures was used in 38 cases. During this period, different types of external fixators were used and experience in this work has been gained. Stability of both open and unstable bone fractures of the extremities, caused by explosive devices, has been obtained by the external fixation mostly in one plane, regardless of the type of external fixator used. The advantages of use of external fixators of the types Instrumentarija Zagreb 1 and 2 for the treatment of long bone fractures has been emphasized as well as the possibility of the subsequent corrections owing to the technical construction of the bone spike. The usefulness of the longitudinal bar of the AO/ASIF fixator for the healing of fractures of the upper leg with subsequent callus formation is also stressed. The same stability has been achieved by the CMC fixator. The external fixators of a type Zagreb 2 have been a satisfactory treatment for forearm fractures as well.(ABSTRACT TRUNCATED AT 250 WORDS)