A Case Report: Idiopathic or Drug-Induced Autoimmune Hepatitis-Can We Draw a Line?

Idiosyncratic drug-induced liver injury (DILI) is an unpredictable reaction of individuals exposed to a certain drug, and drug-induced autoimmune hepatitis (DIAIH) presents a DILI phenotype that mimics idiopathic autoimmune hepatitis (AIH) when considering the clinical, biochemical, serological and histological parameters. We present a case report of a 48-year-old male who was hospitalized due to severe hepatocellular liver injury two months after self-treatment with a muscle-building dietary supplement based on arginine-alpha-ketoglutarate, L-citrulline, L tyrosine, creatine malate and beet extract. His immunology panel was positive with increased IgG levels, and radiologic methods showed no signs of chronic liver disease. He underwent corticosteroid treatment with adequate response. After therapy withdrawal, a clinical relapse occurred. Seven months after the initial presentation, liver MR suggested initial cirrhotic changes in the right liver lobe. A liver biopsy revealed abundant lymphoplasmacytic infiltrate with piecemeal necrosis and grade 2 fibrosis. He responded well to the corticosteroid treatment again, and was further treated with low-dose prednisone without additional relapses. Several years later, further management confirmed the presence of liver cirrhosis with no histological or biochemical signs of disease activity. DIAIH is a DILI phenotype that is difficult to distinguish from idiopathic AIH despite a wide armamentarium of diagnostic methods. It should always be considered among the differential diagnoses in patients presenting with hepatocellular liver injury.

CDC25c expression in patients with myelofibrosis is associated with stronger myeloproliferation and shorter overall survival.

BACKGROUND: Cell division cycle 25c (CDC25c) is a gene coding a phosphatase controlling entry into mitosis upon activation through Polo-like kinase 1 (PLK1) and serves as a key regulator of cell division. The CDC25c was reported to be dysregulated in some malignant diseases, but its role in myelofibrosis has not yet been elucidated. METHODS: We have retrospectively investigated CDC25c mRNA expression in bone marrow aspirates of 43 patients with myelofibrosis (28 primary [PMF] and 15 secondary myelofibrosis [SMF]) and 12 controls. RESULTS: CDC25c mRNA expression did not significantly differ between PMF, SMF and controls (median ∆CT 3.08 vs 2.86 vs 2.29 for PMF, SMF and controls, respectively; P = 0.162). Patients presenting with higher CDC25c mRNA expression were of older age (P = 0.037), had statistically significantly higher white-blood-cells (P = 0.017), larger liver size (P = 0.022), higher absolute neutrophil (P = 0.010), monocyte (P = 0.050), basophil (P = 0.012), and eosinophil counts (P = 0.013). Patients presenting with high CDC25c mRNA expression had statistically significantly inferior overall survival compared to low CDC25c expression group (HR = 2.99; P = 0.049). Median overall survival was not reached in patients with low and was 44 months in patients with high CDC25c expression. CONCLUSION: Our data suggest that higher CDC25c expression is associated with more proliferative phenotype of myelofibrosis and is prognostic of worse survival. Future studies investigating these interesting associations are warranted.

Assessment of FreeStyle Libre Flash Glucose Monitoring System Implementation in Real Life Clinical Setting: A Prospective Observational Study.

BACKGROUND: In this study, we investigated the effectiveness of FreeStyle Libre Flash Glucose Monitoring (FGM) implementation in a real life clinical setting with the emphasis on the effect of initial education on the use of the FGM system. METHODS: This prospective observational study included 425 diabetes type 1 subjects followed up for 3 to 12 months (320 were followed up to 3 months, 267 up to 6 months and 147 up to period of one year). An FGM sensor was placed at study entry and all participants were educated through a period of 5 days on sensor usage and self-management of glycemia with follow up visits every 3 months. RESULTS: HbA1c values significantly decreased from baseline (T0) to 3 months (T3) (p < 0.001), with a drop from 7.48% ± 0.1% to 7.30 ± 0.1%. There was no change in time spent in hypoglycemia from T3 to T12, although there was a decreasing trend present. The change in HbA1c values in the entire cohort was driven by change in the subgroup of patients with HbA1c ≥7% with a drop from 8.22% ± 1.14% to 7.68% ± 1.26% (p < 0.0001) in the first 3 months. Also, in individuals performing SMBG less than 5 times per day, there was a steady decrease in HbA1c levels up to 6 months (p < 0.05 and p < 0.001, respectively) as opposed to those who performed SMBG ≥5 times per day. CONCLUSIONS: The improvement in HbA1c was mainly driven by the increase in the number of scans per day. The subjects with poorer glycemic control and those who seldom performed SMBG benefited the most.

Nutritional Status and Indicators of 2-Year Mortality and Re-Hospitalizations: Experience from the Internal Clinic Departments in Tertiary Hospital in Croatia.

We aimed to provide insight into nutritional and clinical indicators of malnutrition risk and their influence on two-year mortality and re-hospitalization rate among patients hospitalized in internal clinic departments in the tertiary hospital in Croatia. Initially, data on 346 participants were obtained, while 218 of them where followed-up two years later. At baseline, the majority of participants were old and polymorbid (62.1% suffered from arterial hypertension, 29.5% from cancer, and 29.2% from diabetes). Even apparently presenting with satisfying anthropometric indices, 38.4% of them were at-risk for malnutrition when screened with the Nutritional Risk Screening-2002 (NRS-2002) questionnaire (NRS-2002 ≥ 3). More importantly, only 15.3% of all participants were prescribed an oral nutritional supplement during hospitalization. Those that were at-risk for malnutrition suffered significantly more often from cancer (54.9% vs. 20.6%; p < 0.001) and died more often in the follow-up period (42.7% vs. 23.5%; p < 0.003). Their anthropometric indices were generally normal and contradictory 46.3% were overweight and obese (body mass index (BMI) > 25 kg/m2). Only 36.6% of nutritionally endangered participants used an oral supplement in the follow-up period. NRS-2002 ≥ 3 correlated with anthropometric indices, glomerular filtration rate, age, and length of the initial hospital stay. Unlike other studies, NRS-2002 ≥ 3 was not an independent predictor of mortality and re-hospitalizations; other clinical, rather than nutritional parameters proved to be better predictors. Patients in our hospital are neither adequately nutritionally assessed nor managed. There is an urgent need to develop strategies to prevent, identify, and treat malnutrition in our hospital and post-discharge.

A novel mutation of the MEN1 gene in a patient with multiple endocrine neoplasia type 1 and recurrent fibromyxoid sarcoma - a case report.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) syndrome is usually accompanied by endocrine tumors, but non-endocrine tumors can occur as well. However, the coexistence of MEN1 syndrome and malignant tumor such as low-grade fibromyxoid sarcoma has not been described in the literature. Moreover, the MEN1 gene mutations have not been identified in patients with fibromyxoid sarcoma, so far. CASE PRESENTATION: We present a patient with a long-year endocrine follow-up due to multiple endocrine tumors. During his lifespan, he has been surgically treated for pancreatic gastrinoma, parathyroid hyperplasia, atypical pulmonary carcinoid, various benign mesenchymal, and several skin tumors (basocellular tumor, lipomas, and fibromas) which raised a high clinical suspicion of MEN1 syndrome but the patient refused genetic testing. Recently, he developed a novel malignant tumor - recurrent low-grade fibromyxoid sarcoma of the trunk and extremities with multiple subsequent operations. The patient eventually accepted the genetic testing which proved him to be a carrier of a novel mutation in the MEN1 gene. CONCLUSIONS: Unlike some other syndromes where a genetic mutation can predict clinical course, there is no genotype-phenotype correlation in MEN1 syndrome. Therefore, these patients require lifelong and multidisciplinary surveillance, not only for typical endocrine and benign non-endocrine tumors but also for diverse and even more malignant forms. The atypical clinical presentation should pose suspicion about new gene mutation and serve as a warning in the further follow-up.

Patterns of Glucose Fluctuation are Challenging in Patients Treated for Non-Hodgkin's Lymphoma.

PURPOSE: This cohort study aimed to determine patterns of glycemic fluctuation and changes in metabolic parameters during and after corticosteroid administration in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP chemotherapy. PATIENTS AND METHODS: The study was performed in 20 patients of whom 11 had diabetes and 9 were nondiabetics. Anthropometric parameters were collected, and blood samples were taken four times during the study to analyze metabolic parameters. Capillary glucose was measured seven times a day (fasting, before mean meals, postprandial, and before bedtime) to evaluate the glycemic profile. RESULTS: In all 20 patients, acute glucocorticoid administration resulted in the elevation of average glucose levels, dominantly postprandial in the afternoon which correlates with corticosteroid peak action. In 7 out of 11 diabetics, prandial insulin was started during corticosteroid administration and discontinued afterward. Although none of our nondiabetic patients met diabetes criteria, evident is the elevation in average glycemia levels six weeks after corticosteroid administration. Potentially, even transient corticosteroid administration reduces insulin sensitivity and contributes to later glycemic disturbances. HbA1c levels were higher at the end of the study while fructosamine levels were higher during the study. CONCLUSION: Patients and health-care professionals need to be aware of corticosteroid-induced hyperglycemia. We recommend identifying risk factors, measuring glycemia before, during, and after corticosteroid administration, and starting the adequate therapy as soon as possible.

Higher AURKA and PLK1 expression are associated with inferior overall survival in patients with myelofibrosis.

Aurora-kinase-A (AURKA), BORA and Polo-like-kinase-1 (PLK1) are regulating cell-cycle control and promotion of mitosis entry. AURKA contributes to Janus-kinase-2 (JAK2) activation and increased AURKA protein levels were reported in CD34+ and CD41+ cells of myeloproliferative neoplasm patients, leading to aneuploidy and aberrant megakaryopoiesis. We aimed to investigate AURKA, BORA and PLK1 mRNA expression in unfractionated bone-marrow aspirates of 43 patients with myelofibrosis (28 primary-/PMF, 15 secondary-myelofibrosis/SMF) and 12 controls and to assess their clinical correlations. AURKA expression did not significantly differ between myelofibrosis and controls (P = 0.466). Higher AURKA expression was significantly associated with higher absolute monocyte-count (P = 0.024) and shorter overall survival (HR = 3.77; P = 0.012). Patients with both PMF and SMF had lower BORA expression than controls (P = 0.009). Higher BORA expression was significantly associated with absence of constitutional symptoms (P = 0.049), absence of circulatory blasts (P = 0.047), higher monocyte- (P = 0.040) and higher eosinophil-counts (P = 0.016) and had neutral effect on survival (P > 0.05). PLK1 expression did not significantly differ between myelofibrosis and controls (P = 0.103). Higher PLK1 expression was significantly associated with higher white-blood-cell-count (P = 0.042) and inferior overall survival (HR = 5.87; P = 0.003). In conclusion, AURKA, BORA and PLK1 are involved in pathogenesis of myelofibrosis and may affect survival. Future studies investigating these interesting associations are warranted.

Laugier-Hunziker syndrome in endocrine clinical practice.

Laugier-Hunziker syndrome (LHS) is a rare, benign and acquired disorder characterized by hyperpigmentation of the oral cavity and lips along with longitudinal melanonychia. No underlying systemic abnormalities or malignant predisposition is associated with it. In everyday clinical practice, an endocrinologist encounters certain endocrine conditions (e.g. Addison's disease, McCune-Albright syndrome) that present with, inter alia, mucocutaneous hyperpigmentation. Even though LHS is easily distinguished from endocrine entities mentioned earlier, diagnostic evaluation usually requires skilled and thorough practitioner. Since it is the diagnosis of exclusion, a number of systemic conditions must be ruled out prior to making the final diagnosis. However, its major differential diagnosis is primarily Peutz-Jeghers syndrome, which carries an increased risk of cancer. Here, we report a case of a young woman who was referred to the endocrinologist for diagnostic evaluation of dark-colored lesions of the oral cavity and nails. All performed laboratory tests were within reference range. Endoscopic gastrointestinal evaluation did not reveal neoplastic formations. Owing to an adult-onset, asymptomatic clinical course and negative diagnostic findings, we made a final diagnosis. In this case, target diagnostic evaluation notably reduced the need for additional expensive and invasive procedures and treatments. LEARNING POINTS: Laugier-Hunziker syndrome is a rare, acquired cause of asymptomatic, benign mucocutaneous hyperpigmentation.Prior to making a final diagnosis, certain medical entities with overlapping clinical features must be excluded.Endocrine conditions that usually present with the hyperpigmentation of the skin and mucous membranes (e.g. Addison's disease, McCune-Albright syndrome) can be easily ruled out based on clinical and laboratory findings.Its major differential diagnosis, Peutz-Jeghers syndrome is characterized by melanotic macules of the face and mouth, intestinal polyposis and significantly increased risk of different types of cancer, especially gastrointestinal.Anamnesis, physical examination and target diagnostic evaluation reduce the need for additional invasive and expensive procedures and treatment.

Age-dependent systemic DNA damage in early Type 2 Diabetes mellitus.

Oxidative stress, capable of eliciting damage to various biomolecules including DNA, is a recognized component of diabetes mellitus and its complications. Metabolic syndrome (MetS) is associated with the development of type 2 diabetes mellitus (T2DM), as well as other unfavorable outcomes. The aim of this study was to elucidate the role of oxidative stress in the development of T2DM, by investigating association of oxidative DNA damage with metabolic parameters in subjects with MetS and early T2DM. Selected anthropometric and biochemical parameters of MetS, inflammation and oxidative DNA damage: body mass index (BMI), fatty liver index (FLI), waist circumference (WC), total cholesterol, HDL and LDL-cholesterol, gamma-glutamyl transpeptidase (GGT), uric acid, C-reactive protein (CRP), total leukocyte/neutrophil count, and urinary 8-hidroxy-deoxyguanosine (u-8-OHdG) were assessed in male subjects with MetS and both younger (≤55 years) and older (>55 years) subjects with T2DM of short duration without complications. BMI, FLI, WC, total and LDL-cholesterol and uric acid were higher, while the u-8-OHdG was lower in MetS group, when compared to older T2DM subjects. None of these parameters were different neither between MetS and younger T2DM, nor between two sub-groups of subjects with T2DM. Values of CRP, HDL-cholesterol, triglycerides, GGT, leukocytes and neutrophils were not different between all examined groups of subjects. Higher 8-OHdG in older subjects with T2DM suggests that both aging process and diabetes could contribute to the development of DNA damage. Oxidative DNA damage cannot serve as an universal early marker of T2DM.

Severe war-related trauma and personality pathology: a case-control study.

BACKGROUND: Exposure to war-related trauma has long been recognised to have an adverse effect on mental health. We attempted to investigate whether people who have clinically significant personality-related problems 15 years after a war are more likely to have been exposed to severe war-related trauma than those who do not have significant personality difficulties. METHODS: A case -control study was conducted in southern Croatia, fifteen years after the 1991-1995 war. We recruited 268 participants: 182 cases who scored positively on the International Personality Disorder Examination scale (IPDE), and 86 controls who were IPDE negative. Severity of war-related trauma was assessed according to the 17 items on the Harvard Trauma Questionnaire (HTQ) trauma event scale, which were considered to be of severe (catastrophic) nature based on the ICD-10 description of catastrophic trauma and the opinion of trauma experts. All participants also completed measures of mental health (depression, anxiety and PTSD), social functioning and current substance misuse. RESULTS: Cases (IPDE positive) were eight times more likely to report exposure to severe war-related trauma than controls. This association increased after adjustments for demographic factors (OR = 10.1, 95% CI 5.0 to 20.4). The types of severe trauma most frequently reported were either the participants'own life being in direct danger or witnessing extreme violence inflicted on others or the result of violence towards others (murder, torture, seeing burned or disfigured bodies). Prevalences of depression, anxiety and PTSD were high among IPDE positive participants 15 years after exposure to war trauma. Their level of interpersonal dysfunction was considerably higher than that in controls (OR = 10.39, 95% CI 3.51 to 30.75). Alcohol consumption in cases was significantly higher with a mean of 14.24 units per week (sd = 11.03) when compared to controls whose mean number of alcohol units was 9.24 (sd = 7.25), t (73) = 2.16, p < 0.05, mean difference 4.99 (95% CI = 0.39 to 9.60). Similarly, a significantly higher number of cases reported current substance misuse (8.2% vs. 0.0%) X2 (1, n = 268) = 7.51, p < 0.05). CONCLUSION: Exposure to severe war-related trauma is a risk factor for interpersonal dysfunction15 years after people were exposed to an armed conflict. These findings have implications for assessing and meeting the long-term mental health needs of people in war-affected regions. Further research needs to be done to increase our understanding about the relationship between severe war trauma and personality related problems.

[CROATIAN GUIDELINES FOR THE PHARMACOTHERAPY OF TYPE 2 DIABETES]. / HRVATSKE SMJERNICE ZA FARMAKOLOSKO LIJECENJE SECERNE BOLESTI TIPA 2.

INTRODUCTION: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the pharmacotherapy of type 2 diabetes in the Republic of Croatia. PARTICIPANTS: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. EVIDENCE: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. CONCLUSIONS: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes' patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglyce- mia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes.

Association of Asymmetric Dimethylarginine With Acute Pancreatitis-Induced Hyperglycemia.

OBJECTIVE: The objective of this study was to investigate the relationship between asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, oxidative-nitrosative damage, and glucoregulation in acute pancreatitis (AP). METHODS: The study evaluated serum levels of ADMA, nitrotyrosine, and urinary 8-hydroxydeoxyguanosine in 40 male patients hospitalized for AP at baseline and at 2 and 10 days of treatment, respectively. The patients were classified into a mild and a moderately severe AP group (MAP and MSAP, respectively) according to Atlanta classification criteria. Glycemic status was evaluated by a 75-g oral glucose tolerance test 1 month after AP onset. Forty age-matched healthy subjects served as control subjects. RESULTS: Significant decrease of ADMA and increased levels of nitrotyrosine and urinary 8-hydroxydeoxyguanosine were found in MSAP, but not in MAP at baseline, with ADMA correction toward control levels at the 10th day of treatment. Fructosamine was found to significantly influence ADMA levels (r = -0.362, P = 0.002). After AP recovery, either impaired glucose tolerance or diabetes was identified with the oral glucose tolerance test in 10.5% and 92.8% of patients with MAP and MSAP, respectively. CONCLUSIONS: Insufficient inhibition of nitric oxide synthesis, through reduced bioavailability of ADMA, might be a novel significant contributory factor to the severity of AP and subsequent development of hyperglycemia.

Acute application of antioxidants protects against hyperoxia-induced reduction of plasma nitrite concentration.

We investigated the effects of acute intake of antioxidants on hyperoxia-induced oxidative stress, reduction of plasma nitrite and change in arterial stiffness. Twelve healthy males randomly consumed either placebo or an oral antioxidant cocktail (vitamin C, 1000 mg; vitamin E, 600 IU; alpha-lipoic acid, 600 mg). Every therapy was consumed once, a week apart, in a cross-over design, 30 min before the experiment. The volunteers breathed 100% normobaric oxygen between 30th and 60th min of 1-h study protocol. Plasma levels of nitrite, lipid peroxides (LOOH) and vitamin C, arterial stiffness (indicated by augmentation index, AIx) and arterial oxygen (Ptc O2 ) pressure were measured before and after hyperoxia. Exposure to oxygen caused a similar increase of Ptc O2 in both placebo and antioxidants groups, confirming comparable exposure to hyperoxia (438 ± 100 versus 455 ± 83 mm Hg). Vitamin C was increased in the antioxidants group confirming successful application of antioxidants (69 ± 14 versus 57 ± 15 µm). Hyperoxia resulted in increased AIx and LOOH and decreased nitrite in placebo (-32 ± 11 versus -47 ± 13%, 72 ± 7 versus 62 ± 6 µm H2 O2 and 758 ± 184 versus 920 ± 191 nm, respectively), but not in the antioxidants group (-42 ± 13 versus -50 ± 13%, 64 ± 9 versus 61 ± 8 µm H2 O2 and 847 ± 156 versus 936 ± 201 nm, respectively). The acute intake of selected antioxidants was effective in preserving bioavailabity of ˙NO and vascular function, against hyperoxia-induced oxidative stress.

LC-MS/MS and GC-MS/MS measurement of plasma and urine di-paracetamol and 3-nitro-paracetamol: proof-of-concept studies on a novel human model of oxidative stress based on oral paracetamol administration.

Paracetamol (acetaminophen) is a widely used safe analgesic drug when administered at therapeutic doses. Given the chemical reactivity of its phenolic group towards electrophilic species, we assumed that detection of paracetamol metabolites distinctly different from its known phase I metabolite N-acetyl-p-benzoquinone imine (NAPQI) and the phase II glucuronic, sulfuric and mercapturic acids in biological samples upon oral administration of paracetamol (e.g., a 500-mg tablet) may represent a novel model of oxidative stress in humans. Such potential paracetamol metabolites are di-paracetamol and 3-nitro-paracetamol, in analogy to the well-investigated endogenous biomarkers di-tyrosine and 3-nitro-tyrosine. Di-paracetamol and 3-nitro-paracetamol are known to be formed both by enzymatic and non-enzymatic routes. In the present work we report on mouse and human pilot studies on the formation and appearance of di-paracetamol and 3-nitro-paracetamol in blood of mice intraperitoneally administered paracetamol, as well as in plasma and urine samples of healthy subjects who received a 500-mg paracetamol tablet or placebo. For the analysis of di-paracetamol and 3-nitro-paracetamol in plasma and urine samples, analytes were extracted by solvent extraction with ethyl acetate and subsequently analyzed by LC-MS/MS without and with derivatization with pentafluorobenzyl bromide. GC-MS/MS was used to detect 3-nitro-paracetamol and quantify paracetamol as pentafluorobenzyl derivatives. Our studies indicate that di-paracetamol and 3-nitro-paracetamol appear in plasma and urine when paracetamol is given orally to healthy humans at the therapeutic dosage of 5-7 mg/kg. The molar ratio of di-paracetamol to paracetamol in urine was determined to be 1:535 in the paracetamol group and 1:6844 in the placebo group; the molar ratio of 3-nitro-paracetamol to paracetamol in urine was determined to be 1:199 in the paracetamol group and 1:8657 in the placebo group. Our studies suggest that a fraction of circulating and excretory di-paracetamol and 3-nitro-paracetamol may be formed artefactually during sample workup including derivatization. Further studies based on the quantitative determination of di-paracetamol and 3-nitro-paracetamol in biological samples by LC-MS/MS and/or GC-MS/MS using stable-isotope labeled analogues as internal standards are warranted to test the utility of paracetamol as a probe of oxidative stress in animals and in humans in health and disease.

[METHODS FOR DETECTION OF ANTIBODIES TO HLA ANTIGENS IN PATIENTS AWAITING KIDNEY TRANSPLANTATION AND COMBINED PANCREAS-KIDNEY TRANSPLANTATION]. / METODE OTKRIVANJA ANTITIJELA NA HLA ANTIGENE KOD BOLESNIKA KOJI CEKAJU BUBREZNU TRANSPLANTACIJU TE KOMBINIRANU TRANSPLANTACIJU GUSTERACA-BUBREG.

The best possibility to treat chronic renal disease is renal transplantation. Especially important fact in transplantation is the percentage of so-called panel reactive antibody (PRA) that is focused on the human leukocyte antigen. There are several methods to determine the percentage of PRA in sensitized patients awaiting kidney transplants. The most important is the complement-dependent cytotoxicity. A higher value of PRA implies greater likelihood of positive cross-match with random donor and lower probability of receiving a transplant. Comparing the sensitivity of laboratory tests for determination of PRA percentage in patient serum, it is concluded that ELISA and flow cytometry proved to be more sensitive and specific.

Early initiation of enteral nutrition improves outcomes in burn disease.

BACKGROUND: Burned patients have increased level of mortality, possibly due to late introduction of enteral feeding. The aim of this study was to compare the benefits and safety of very early enteral nutrition introduction compared to the normal diet among burns patients in an intensive care unit. PARTICIPANTS AND METHODS: Participants consisted of 101 patients, aged 20-76 years (mean age 48 years), 49 men and 52 women, with burns that covered more than 20% of the body. The intervention group consisted of 52 subjects fed via introduced nasojejunal probe that started within four hours after admission to the hospital. The control group consisted of fifty patients fed in standard manner per os (three standard hospital meals) immediately after the first wound dressing. RESULTS: The average decline BMI in control group was 2.27±0.56 kg/m2, while the average reduction in BMI in the intervention group was 1.77±0.38 kg/m2 (p<0.001). The largest drop of albumin concentration in the control group was 28.5%, whereas in the intervention group was 23.8%. (p<0.001). The greatest decrease of transferrin concentration in the control group was 31.1%, while the average reduction in the intervention group was 18.3%. (p<0.001). C-reactive protein values were statistically higher in control group (p<0.001). Intervention group had lower rate of complications and infection rates. CONCLUSION: Enteral nutrition in burned patients should begin within few hours of burn onset. Such approach leads to better outcomes, reduces complications, and improves nutritional profile.

Level of primary DNA damage in the early stage of metabolic syndrome.

Metabolic syndrome (MetS) is a multi-component disease, characterised by abdominal obesity, hypertension, hyperglycaemia and dyslipidaemia. Since the number of MetS patients has significantly increased over the past two decades and because MetS may lead to development of cardiovascular diseases, diabetes type-2, and cancer, it has become important to extend the knowledge on the pathogenesis of MetS and to establish its possible early biomarkers. Studies on MetS and DNA damage are few and are inconclusive. The aim of this study was to elucidate the involvement of DNA damage in the development of MetS and to establish if DNA damage can serve as early biomarker of MetS. A total of 121 subjects participated in the study: 56 healthy controls and 65 MetS patients who were diagnosed with MetS for the first time. The amount of primary DNA damage in peripheral leukocytes of the subjects was assessed with three types of comet assay: the alkaline, the hOGG1-modified, and the neutral comet assay. In addition, the extent of oxidative DNA damage was monitored in urine by assessing 8-oxo-dG. The parameters of the three types of comet assay did not differ between the control and the MetS group. Interestingly, urinary 8-oxo-dG level in the control group was higher than in the MetS group. Our results imply that DNA damage is not involved in the early stage of MetS and, therefore, DNA damage cannot serve as an early marker of MetS.

Preliminary report of hypoglycemic response in obese metabolic syndrome males treated with metformin after weight loss intervention.

We conducted this study to determine the degree of obesity influence on the hypoglycemic response of growth hormone and cortisol after weight loss of 5%. A total of 45 non-diabetic, male subjects followed in the outpatient endocrinological departments were divided into three groups comprising 15 subjects in each group, based upon body mass index (BMI) to healthy, overweight and obese group. Metformin was administered in the dose of 50 mg daily to the overweight and obese participants. Cortisol was measured at 0, 60 and 120 minutes. Growth hormone (GH) was measured at -15, 0, 30, 60, 90 and 120 minutes. Values of cortisol and GH were compared upon changes in hypothalamo-pituitary-adrenal (HPA) response to insulin induced hypoglycemia initially and after weight loss of 5% for overweight and obese participants. The BMI of the healthy group ranged 20.0-24.5 kg/m2 (median: 22.8); overweight group ranged 25.9-29.7 kg/m2 (median: 28.3); and obese group ranged 30.9-34.6 kg/m2 (median: 32.6). There were no significant differences of cortisol values among groups at 0 (chi2 = 2.0; p = 0.365); 60 (chi2 = 0.754; P = 0.686) and at 120 minutes (chi2 = 0.466; p = 0.792). The comparisons among groups were significant for differences of GH values at -15 (chi2 = 25.0; p < 0.01); 0 (chi2 = 16.2; p < 0.01); 30 (chi2 = 16.2; p < 0.01); 60 (chi2 = 32.8; p < 0.01); 90 (chi2 = 30.2; p < 0.01) and at 120 minutes (chi2 = 27.3; p < 0.01). Healthy and obese subjects significantly differed in growth hormone response at -15 (Z = 4.67; p < 0.01); 0 (Z = 3.83; p < 0.01); 60 (Z = 2.78; p = 0.05); 90 (Z = 4.67; p < 0.01) and at 120 minutes (Z = 4.23; p < 0.01). Changes on the various levels of HPA axis, when it is activated by a stress as it is the case in insulin-induced hypoglycemia correspond to the degree of obesity. Weight loss of 5% was not enough for restoration of a normal stimulated growth hormone release and did not influence on the level of cortisol.

Influence of hypertension and type 2 diabetes mellitus on cerebrovascular reactivity in diabetics with retinopathy.

BACKGROUND AND OBJECTIVES: Cerebrovascular reactivity (CVR) provides information on the intracerebral arterioles capacity to react to vasodilatory stimuli. The current study aimed to investigate the influence of hypertension and type 2 diabetes mellitus on CVR in diabetics with retinopathy. DESIGN AND SETTING: Retrospective analysis of data prospectively collected over a 1-year period. SUBJECT AND METHODS: Subjects were classified into four groups each comprised of 30 participants: diabetic retinopathy with hypertension (DRH), diabetic retinopathy without hypertension (DR), hypertension without diabetes mellitus (H), and healthy controls without diabetes and hypertension (C). CVR was estimated in relation to the increase in the mean flow velocity compared with the basal velocity in both middle cerebral arteries during hypercapnia. RESULTS: In the DRH group, the mean (SD) increase in CVR was 8.8 (2.49) cm/s, in the H group 14.4 (2.59) cm/s and in the DR group 9.7 (2.97) cm/s. The analysis of variance showed significant differences among the groups in blood flow velocity after a breath-holding test (F=89.83; df=3.116; P < .001). CONCLUSIONS: Diabetes mellitus influences CVR more than hypertension.