Relative Adrenal Insufficiency is Associated with the Clinical Outcome in Patients with Stable Decompensated Cirrhosis.

BACKGROUND: The clinical impact of relative adrenal insufficiency (AI) on patients with stable decompensated cirrhosis (DeCi) has not been yet elucidated. AIM: Explore the association between AI and outcome [death or liver transplantation (LT)] in patients with DeCi. MATERIAL AND METHODS: Patients with DeCi presenting no active complication have been included. Clinical and laboratory data, including serum levels of corticosteroid-binding globulin (CBG), interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNFα) were recorded in each participant. Salivary cortisol (SC) and serum total cortisol (STC) were assessed at (T0) and 1 h (T60) after intravenous injection of 250 µg corticotropin. RESULTS: 113 consecutive patients were totally tested. Median SC was 3.9 ng/mL and 15.5 ng/mL and median STC was 10.7 µg/dL and 22.7 µg/dL at T0 and T60 respectively. The patients with AI [group 1, n = 34 (30%)] had significantly lower systolic blood pressure (106 ± 12 vs. 113 ± 13 mmHg, p = 0.05), serum sodium (133 ± 7 vs. 137 ± 12 mEq/ L, p = 0.04), HDL (29.9 ± 14 vs. 38.6 ± 18 mg/dL, p = 0.034) and albumin (2.7 ± 0.5 vs. 3.1 ± 0.5 g/dL, p = 0.002), but higher direct bilirubin (median: 1.6 vs. 0.8 mg/dL, p = 0.029) compared to those without AI [group 2, n = 79 (70%)]. Moreover, group 1 patients presented more frequently past history of spontaneous bacterial peritonitis (SBP) [10/34 (29.4%) vs. 6/79 (7.5%), p = 0.002]. AI was significantly associated with death [HR = 2.65, 95% C.I.: 1.55 - 4.52, p = 0.003 over a follow up period of 12 (6-48) months.] Conclusions. The presence of AI in patients with stable DeCi predispose to obvious clinical implications since it is associated with circulatory dysfunction, previous history of SBP and worse survival.

Glomerular filtration rate is an independent factor of mortality in patients with decompensated cirrhosis.

AIM: Although serum creatinine is included in the Model for End-Stage Liver Disease (MELD) score, it is an inaccurate marker of renal function, namely, of glomerular filtration rate ("true" GFR) in patients with decompensated cirrhosis. Our aim was to investigate the impact of MELD score and "true" GFR as determinants of survival in patients with decompensated cirrhosis. METHODS: We included all consecutive patients with decompensated cirrhosis who were admitted to our department. Renal function was assessed by creatinine- and cystatin-based estimated GFR and "true" GFR using (51) Cr-ethylenediaminetetraacetic acid. The independent factors associated with survival were evaluated. The discriminative ability of the prognostic scores (MELD and modifications of MELD score) were evaluated by using the area under the receiver-operator curve (AUC). RESULTS: One hundred and ten consecutive patients (77 men, aged 56 ± 12 years); at the end of follow up (8 months; range, 6-18), 92 patients (84%) were alive and 18 (16%) had died. In multivariate analysis, serum bilirubin (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.05-1.26; P = 0.020) and "true" GFR (HR, 0.96; 95% CI, 0.93-0.98; P = 0.003) were the only independent factors significantly associated with the outcome. The derived new prognostic model had high discriminative ability (AUC, 0.90), which was confirmed in the validation sample of 77 patients. CONCLUSION: In our cohort of patients with decompensated cirrhosis, "true" GFR and bilirubin were the independent factors of the outcome.

Association between ratio of sodium to potassium in random urine samples and renal dysfunction and mortality in patients with decompensated cirrhosis.

BACKGROUND & AIMS: Estimates of glomerular filtration rate (GFR) are used to assess renal function and are an independent prognostic factor for patients with decompensated cirrhosis, but are impractical for routine use. We investigated whether the ratio of sodium to potassium in randomly collected urine samples (UNa/K) is associated with mortality and renal dysfunction in patients with decompensated cirrhosis and ascites. METHODS: We assessed data from 126 consecutive patients with decompensated cirrhosis and ascites (93 men; age, 56 ± 12 y; 55% with viral-related disease) admitted to the Hippokration General Hospital of Thessaloniki, Greece, from September 2010 through January 2012. At admission, clinical and laboratory variables were recorded, including GFR, measured with (51)Cr-EDTA. Urine samples were collected, and UNa/K was determined. We evaluated the association between UNa/K and patient mortality using the area under the receiver operating characteristic curve analysis. RESULTS: Forty-one patients (32%; group 1) had a GFR less than 60 mL/min, and 85 patients (68%; group 2) had a GFR of 60 mL/min or greater. In the multivariable analysis, 3 variables were associated independently with the presence of severe renal dysfunction (GFR, <60 mL/min): age (odds ratio [OR], 0.93; P = .008), systolic blood pressure (OR, 1.05; P = .022), and UNa/K (OR, 1.5; P = .025). A UNa/K less than 1.0 had high sensitivity and a negative predictive value for the presence of GFR less than 60 mL/min (79% and 87%, respectively) and mortality (68% and 91%, respectively). CONCLUSIONS: In patients with decompensated cirrhosis and ascites, a ratio of sodium to potassium of less than 1 in randomly collected urine samples was associated with renal dysfunction and short-term mortality. These findings require confirmation in additional studies.

IGF-IEc Expression Is Associated With Advanced Differentiated Thyroid Cancer.

BACKGROUND/AIM: Recent knowledge implicates a differential expression of the insulin-like growth factor-I (IGF-I) mRNA splice variants (i.e., IGF-IEa, IGF-IEb and IGF-IEc) in cancerous tissues, implying possible specific roles of the encoded IGF-I protein isoforms in cancer biology. In particular, there is growing evidence that the IGF-IEc isoform may play a distinct biological role in various types of cancers. The present study investigated whether IGF-IEc expression is associated with a particular type of thyroid cancer. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissue specimens of different types of thyroid cancers from 92 patients were assessed for IGF-IEc expression by immunohistochemistry. In addition, thyroid cancer biopsies of different TNM staging histological types were evaluated for mRNA expression of the IGF-IEc transcript by real-time polymerase chain reaction (PCR). RESULTS: From the total number of 92 samples, 2 were anaplastic, 10 medullary, 4 hyperplasias of C-cells, 11 follicular, 5 hurtle cell carcinomas, 2 poorly differentiated, 5 nodular hyperplasias, 1 lymphoma and 52 were papillary thyroid cancers. The age of cancer diagnosis or tumor size did not significantly affect the IGF-IEc expression. Among all types of cancers, IGF-IEc was expressed in papillary differentiated thyroid cancer. Its expression/localization was mainly cytoplasmic and significantly associated with TNM staging and the presence of muscular and capsule cancerous invasion (p<0.05). Similarly, a differential profile was revealed regarding the mRNA expression of the IGF-IEc transcript, that exhibited a higher expression in aggressive compared to the non-aggressive papillary cancers. CONCLUSION: IGF-IEc isoform expression in thyroid cancer is positively associated with more advanced stages of papillary thyroid cancer.

Procalcitonin: A New Biomarker for Medullary Thyroid Cancer? A Systematic Review.

Medullary thyroid cancer (MTC) is a rare but aggressive thyroid malignancy. The gold-standard biomarker for its diagnosis and follow-up is calcitonin (CT); however, it has a variable half-life dependent on its circadian variability. It has been suggested that a more stable hormone, procalcitonin (PCT), may overcome these problems and its introduction to routine practice may give more accurate results in the diagnosis and follow-up of MTC. We systematically reviewed Pubmed, Scopus, Biosis Previews and Embase databases up to March 2016. A total of 15 out of 184 articles were retrieved and analyzed. Of these 15 studies, 3 were case reports. In these 15 studies, the values of CT and PCT were assessed in both patients with MTC and patients that were either healthy volunteers or with benign/malignant thyroid nodular disease or with bacterial infection. Our search suggests that PCT seems to be a useful biomarker for the diagnosis and follow-up of MTC when used in conjunction with CT, particularly in a small proportion of tumors that are CT-negative or secrete low levels of CT. So far, there has not been enough data to suggest a specific threshold for normal PCT. However, most studies indicate a value of 0.1 ng/ml as an acceptable cut-off in everyday clinical practice. At present, CT should continue to be the primary biomarker in MTC with the addition of PCT in some patient groups. Nevertheless, larger patient series need to be conducted in order to provide safer and more accurate results.

Incretin-Based Antidiabetic Agents for the Management of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease and is more prevalent in patients with type 2 diabetes mellitus (T2DM). Incretin-based antidiabetic agents (glucagonlike peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors) are used in the treatment of T2DM but it is unclear whether they may also play a role in the management of NAFLD. We systematically reviewed the PubMed and Scopus database up to October 2014 and also hand-searched the references of the retrieved articles for studies evaluating the effects of these agents on NAFLD. In animal studies, both GLP-1 receptor agonists and DPP-4 inhibitors reduced transaminase activity and steatosis but their effects on liver inflammation were inconsistent and fibrosis was not assessed. In clinical studies, both agents consistently reduced transaminase activity and steatosis as assessed non-invasively. There are very limited data on the effects of incretin-based treatments on liver histology. In conclusion, GLP-1 receptor agonists and DPP-4 inhibitors appear to hold promise in patients with NAFLD but larger controlled studies with histological and clinical endpoints are needed to evaluate their effects in this population.

Adrenal insufficiency in patients with decompensated cirrhosis.

Adrenal reserve depletion and overstimulation of the hypothalamus-pituitary-adrenal (HPA) axis are causes for adrenal insufficiency (AI) in critically ill individuals. Cirrhosis is a predisposing condition for AI in cirrhotics as well. Both stable cirrhotics and liver transplant patients (early and later after transplantation) have been reported to present AI. The mechanisms leading to reduced cortisol production in cirrhotics are the combination of low cholesterol levels (the primary source of cortisol), the increased cytokines production that overstimulate and exhaust HPA axis and the destruction of adrenal glands due to coagulopathy. AI has been recorded in 10%-82% cirrhotics depending on the test used to evaluate adrenal function and in 9%-83% stable cirrhotics. The similarity of those proportions support the assumption that AI is an endogenous characteristic of liver disease. However, the lack of a gold standard method for AI assessment and the limitation of precise thresholds in cirrhotics make difficult the recording of the real prevalence of AI. This review aims to summarize the present data over AI in stable, critically ill cirrhotics and liver transplant recipients. Moreover, it provides information about the current knowledge in the used diagnostic tools and the possible effectiveness of corticosteroids administration in critically ill cirrhotics with AI.

Compliance with once-daily versus twice or thrice-daily administration of antibiotic regimens: a meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate whether compliance of patients to antibiotic treatment is better when antibiotics are administered once than multiple times daily. METHODS: We performed a systematic search in PubMed and Scopus databases. Only randomized controlled trials were considered eligible for inclusion. Compliance to antibiotic treatment was the outcome of the meta-analysis. RESULTS: Twenty-six studies including 8246 patients with upper respiratory tract infections in the vast majority met the inclusion criteria. In total, higher compliance was found among patients treated with once-daily treatment than those receiving treatment twice, thrice or four times daily [5011 patients, RR=1.22 (95% CI, 1.11, 1.34]. Adults receiving an antibiotic once-daily were more compliant than those receiving the same antibiotic multiple times daily [380 patients, RR=1.09 (95% CI, 1.02, 1.16)]. Likewise, children that received an antibiotic twice-daily were more compliant than those receiving the same antibiotic thrice-daily [2118 patients, RR=1.10 (95% CI, 1.02, 1.19)]. Higher compliance was also found among patients receiving an antibiotic once compared to those receiving an antibiotic of different class thrice or four times daily [395 patients, RR=1.20 (95% CI, 1.12, 1.28)]. The finding of better compliance with lower frequency daily was consistent regardless of the study design, and treatment duration. CONCLUSION: This meta-analysis showed that compliance to antibiotic treatment might be associated with higher when an antibiotic is administered once than multiple times daily for the treatment of specific infections and for specific classes of antibiotics.