Giampaolo Bianchi

Health-related quality of life in patients with thyroid disorders.

Limited reports are available on quality of life (HRQL) in thyroid diseases, and no data are available in euthyroid disorders, such as goiter and Hashimoto thyroiditis. Also, asymptomatic patients may suffer a reduction in perceived health status due to distress related to physical appearance and awareness of disease. We measured HRQL by means of Medical Outcome Study Short Form-36 (SF-36) and Nottingham Health Profile (NHP) questionnaires in 368 patients (hypothyroid, 81; hyperthyroid, 45 (for both states including overt and subclinical states); Hashimoto thyroiditis, 51; euthyroid goiter, 191). The final scores of the domains were compared with age- and sex-adjusted Italian normative values, by computing the effect size. All domains of SF-36, except bodily pain, were reduced in thyroid disease; this was mainly the case of role limitation (both physical and emotional), general health and social functioning. The domains of NHP were less severely affected. HRQL was impaired also in the absence of altered hormone levels. Mood/behavior disturbances were present in a large proportion of patients and were significantly associated with poor HRQL. HRQL was significantly reduced in patients with thyroid diseases referred to a secondary level endocrinology unit. Perceived health status may be considered as an additional outcome of management and therapy of thyroid disorders.

Serum C3 is a stronger inflammatory marker of insulin resistance than C-reactive protein, leukocyte count, and erythrocyte sedimentation rate: comparison study in an elderly population.

OBJECTIVE—This study was performed to ascertain the relative relevance of some inflammatory markers in insulin resistance. RESEARCH DESIGN AND METHODS—Four inflammatory markers (leukocyte count, erythrocyte sedimentation rate [ESR], high-sensitivity C-reactive protein [CRP], and C3 complement) were assessed as possible determinants of the homeostasis model assessment (HOMA) index, together with the five elements of the metabolic syndrome (National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel III] definition), total cholesterol, physical activity, and four indicators of adiposity (BMI, waist circumference, percent body fat, and hepatic steatosis) in an unselected population of 990 subjects aged 65–91 years (the Pianoro Study). RESULTS—In univariable analysis, C3, CRP, and leukocyte count, but not ESR, were significantly correlated with HOMA index. In multivariable analysis, C3 remained associated with insulin resistance with the highest partial R2 value (0.049), independently of all other covariates. The other most significant (P < 0.0001) determinants of HOMA index were total cholesterol (inverse association, R2 = 0.026), waist circumference (R2 = 0.023), triglycerides (R2 = 0.022), and hepatic steatosis (R2 = 0.021) (R2 = 0.450 for the whole model). The adjusted relative risks of having the metabolic syndrome for the subjects with inflammatory markers in the high tertile, with respect to those with lower values, were (prevalence ratio [95% CI]): 1.77 (1.41–2.22) for C3, 1.38 (1.12–1.70) for leukocyte count, 1.17 (0.94–1.46) for CRP, and 1.13 (0.91–1.40) for ESR. CONCLUSIONS—Of the four inflammatory markers simultaneously assessed in our elderly population, only C3 was strongly associated with insulin resistance, independently of the components of the metabolic syndrome and the main indexes of abdominal and general obesity.

Chronic endurance exercise training prevents aging-related cognitive decline in healthy older adults: a randomized controlled trial

To evaluate the effects of endurance exercise training (EET) on the cognitive status of healthy community‐dwelling older adults.

Branched-Chain Amino Acid Supplementation in Patients with Liver Diseases

Because of their peculiar role in whole-body nitrogen metabolism and the competitive action on amino acid transport across the blood-brain barrier, branched-chain amino acids (BCAAs) have been extensively used in subjects with liver disease to preserve or to restore muscle mass and to improve hepatic encephalopathy. There are no data regarding safe limits of BCAA administration; the results appear to be better when BCAA-enriched formulas or BCAA-supplemented diets are preferred to pure BCAA formulas. Improved nitrogen retention might ameliorate the nutritional status, a prognostic index of long-term survival in cirrhosis and of short-term survival in patients undergoing surgical procedures. The effects on nutrition and ultimately on prognosis of patients with advanced cirrhosis were confirmed in a large multicenter, long-term trial where oral BCAA supplements were compared with equicaloric or equinitrogenous-equicaloric supplements (maltodextrin or lactoalbumin). Similarly, BCAA treatment improved the prognosis of patients with hepatocellular carcinoma, treated by surgical resection or chemoembolization, and of liver transplant patients. The mechanism(s) for the beneficial effects of BCAAs might be mediated by their stimulating activity on hepatocyte growth factor, favoring liver regeneration. The debate regarding the potential effectiveness of BCAAs dates back to the early 1980s. The number of patients who cannot tolerate dietary proteins in amounts sufficient to meet the higher catabolism of advanced liver disease is probably low, but BCAAs remain the sole treatment of proved efficacy in this specific setting.

Reduced prevalence of ischemic events and abnormal supraortic flow patterns in patients with liver cirrhosis

Background: A reduced prevalence of cardiovascular diseases has been reported in liver cirrhosis. However, studies focusing on supraortic district of cirrhotic patients are lacking.

Update on nutritional supplementation with branched-chain amino acids

Purpose of reviewBranched-chain amino acids (BCAAs) have a peculiar role in whole-body nitrogen metabolism. BCAAs are not only a substrate for protein synthesis, but also modulate several components of the synthetic machinery and help to conserve muscle mass; accordingly, several conditions, characterized by protein loss and catabolic status, are likely to benefit from amino acid administration. In addition, the competitive action of BCAAs on amino acid transport across the blood-brain barrier may ultimately alter the synthesis of brain neurotransmitters, involved in neurological diseases. Recent findingsBoth putative actions of BCAAs have been tested in controlled clinical studies in the last few years. The beneficial effects on nutrition were reported to improve muscle performance, reduce protein loss during bed-rest, favor weight loss in obesity, reduce catabolism in trauma patients and improve clinical outcomes in patients with advanced cirrhosis. In this last area, the effects on nutrition might be coupled with the effects on hepatic encephalopathy mediated by improved neurotransmission, successfully tested in mania, tardive dyskinesia and spinocerebellar degeneration. SummaryAfter 30 years of investigation with BCAAs, new studies each year provide further evidence supporting their beneficial effect in a variety of diseases. There is a need for long-term, randomized clinical studies, both in the prevention and in the treatment of various pathological conditions.

Update on branched-chain amino acid supplementation in liver diseases

Purpose of review Branched-chain amino acids (BCAAs) have a peculiar role in whole-body nitrogen metabolism. BCAAs are a substrate for protein synthesis, and have been used to conserve or restore muscle mass in advanced liver disease. In addition, the competitive action of BCAAs on amino acid transport across the blood-brain barrier may improve hepatic encephalopathy. Recent findings The effects of branched-chain amino acids on nutrition and ultimately on prognosis of patients with advanced cirrhosis have been confirmed in a large multicenter, long-term trial. Similarly, BCAA treatment improved the prognosis of patients with hepatocellular carcinoma, treated by chemoembolization. The mechanism for the beneficial effects of BCAA is likely to depend on the stimulating activity of BCAA on hepatocyte growth factor, favoring liver regeneration. Summary After an experience of 25 years with branched-chain amino acids, new data supports their beneficial effect in liver diseases. Although the number of patients who cannot tolerate dietary proteins in amounts sufficient to meet their increased catabolism is probably low, in this specific setting BCAAs remain the sole treatment of proved efficacy.

Hepatic Encephalopathy and Health-Related Quality of Life

The impact of overt hepatic encephalopathy on health-related quality of life is well defined, but it remains to be demonstrated how much the presence of minimal hepatic encephalopathy (MHE) might impair patients perceived health status. MHE reduces cognitive abilities, with specific impairment in manual abilities, which can lead to a depressed mood that impairs perceived health status. Therefore, all subjects with cirrhosis should be systematically screened for MHE by validated tools. Early detection and treatment is mandatory to improve the quality of life of patients with advanced cirrhosis, their social isolation, and their daily lives.

Mutations in the E2-PePHD region of hepatitis C virus type 1b in patients with hepatocellular carcinoma.

Summary.u2002 An interaction between the protein kinase (PKR)–eIF2‐alpha phosphorylation homology domain (PePHD) within the E2 protein of hepatitis C virus (HCV) and cell protein kinase (PKR) may affect the control of protein synthesis and cell growth. In an attempt to investigate the genetic variability of the E2–PePHD domain in hepatocellular carcinoma (HCC), we studied sera and liver tissues from HCC patients. The partial E2–PePHD region was analysed by direct sequencing of the sera of 47 HCCs in cirrhotic livers and 31 cases of chronic active hepatitis (CAH), and tumoral and non‐tumoral liver tissues from 13 HCC patients. A similar number of mutations was detected within the E2 domain in the HCC and CAH cases, but nine of the 47 HCCs (19%) showed an amino acid (aa) mutation at position 660, eight of which involved a change in the same aa (alanine instead of serine; A/S). No such mutation was detected in any of the PePHD sequences from the CAH patients: this difference was statistically significant (Pu2003=u20030.008). The aa change at position 660 was also found in two sequences from tumoral but not non‐tumoral tissue from the same liver. The analysis of 461 sequences obtained from GenBank supports the conclusion that the observed aa change is an infrequent event in HCV‐infected patients, thus suggesting that it could be associated with HCC.

Plasma total homocysteine and cardiovascular risk in patients submitted to liver transplantation.

Patients submitted to orthotopic liver transplantation (OLT) show an increased rate of cardiovascular events. OLT subjects have high homocysteine (Hcy) levels, but no data are available on the association of Hcy with cardiovascular events. In a cross‐sectional analysis, 230 subjects were studied at least 6 months after OLT (159 on cyclosporine, 71 on tacrolimus). Routine laboratory data and total Hcy were recorded, as well as the history of diabetes, hypertension, dyslipidemia, and overweight. Cardiovascular events occurring in a follow‐up of 2–36 months were registered. OLT subjects had higher‐than‐normal Hcy (median 16.7 μmol/L, range 6.1–171.8) without difference between the 2 immunosuppressive agents. The prevalence of Hcy >15 μmol/L was also similar, and significantly correlated with creatinine levels. A total of 28 arterial events occurred in 25 patients during follow‐up (11 in coronary arteries, 10 in peripheral arteries, and 7 in splanchnic arteries). Deep vein thromboses occurred in 2 patients, and splanchnic vein thromboses in 4 patients. Cardiovascular events were frequently associated to high Hcy and hypertension. Cox regression analysis showed that high Hcy was significantly associated with arterial events. The risk of any arterial event, coronary artery or peripheral artery event increased by nearly 10% for any increase in Hcy of 5 μmol/L. In conclusion, high Hcy may be involved in the pathogenesis of cardiovascular events in OLT patients. The usefulness of Hcy‐lowering therapy remains to be verified. Liver Transpl 12:105–111, 2006.