Oligometastatic sarcoma treated with Curative intent Ablative Radiotherapy (OSCAR): A multicenter study on behalf of AIRO (Italian association of Radiotherapy and clinical Oncology).

BACKGROUND AND PURPOSE: Stereotactic Ablative Radiotherapy (SABR) is emerging as a valid alternative to surgery in the oligometastatic setting in soft tissue sarcomas (STS), although robust data are lacking. The aim of this study is to evaluate toxicity and efficacy of SABR in oligometastatic STS. MATERIALS AND METHODS: This is a retrospective multicenter study including adult patients affected by stage IV STS, treated with SABR for a maximum of 5 cranial or extracranial metastases in up to 3 different organs. SABR was delivered with ablative purposes. Study endpoints were overall survival (OS), local control (LC), distant progression free survival (DPFS), time to polymetastatic progression (TTPP), time to new systemic therapy (TTNS) and toxicity. RESULTS: From 10 Italian RT centers, 138 patients (202 metastases) treated between 2010 and 2022 were enrolled in the study. Treatment was generally well tolerated, no acute or late toxicity ≥ G3 was recorded. Median follow up was 42.5 months. Median OS was 39.7 months. Actuarial OS at 1 and 2 years was 91.5 % and 72.7 %. Actuarial LC at 1 and 2 years was 94.8 % and 88.0 %. Median DPFS was 9.7 months. Actuarial DPFS at 1 and 2 years was 40.8 % and 19.4 %. CONCLUSION: SABR is a safe and effective approach for the treatment of oligometastatic sarcoma. One out of 5 patients is free of progression at 2-years.

Stereotactic Body Radiotherapy for Spine Oligometastases: A Multicentre Retrospective Study From the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

AIM: To evaluate the efficacy of stereotactic body radiotherapy (SBRT) for spine oligometastases. MATERIALS AND METHODS: This was a multicentre retrospective study of a series of patients who received SBRT for spine oligometastases. The efficacy of SBRT was evaluated in terms of local control as the primary endpoint. Survival outcomes were also analysed to identify predictive factors for clinical outcomes. Toxicity was assessed according to CTCAE v4.0. RESULTS: Between March 2018 and July 2022, 183 lesions in 177 patients were analysed. In most patients, SBRT was delivered to a single spine metastasis (82%) for a median total dose of 21 Gy (14-35 Gy) in three fractions (one to five fractions) and a median BED10 = 119 Gy (57.7-152 Gy). Local control rates were 90.3% at 1 year, 84.3% at 2 years and 84.3% at 3 years. Distant progression-free survival rates were 33.1%, 18.5% and 12.4% at 1, 2 and 3 years, with prostate histology (P = 0.023), oligorecurrent disease (P = 0.04) and BED10 > 100 Gy (P = 0.04) found to be predictive on univariate analysis. A further oligometastatic progression was observed in 33 patients (18.6%) treated with a second course of SBRT, reporting at univariate analysis improved overall survival rates (P = 0.01). Polymetastases-free survival rates were 57.8%, 43.4% and 32.4%; concurrent therapy was related to improved outcomes at multivariate analysis (P = 0.009). Overall survival rates were 91.8%, 79.6% and 65.9%, with prostate histology and non-cervical metastases related to better overall survival at multivariate analysis. Pain-flare after SBRT was recorded in 3.3%; five patients underwent surgical decompression after SBRT; there were no grade ≥3 adverse events. CONCLUSIONS: In our experience of only oligometastatic patients, spine SBRT gave excellent results in terms of safety and efficacy. Prostate histology and oligorecurrent disease were predictive factors for improved clinical outcomes; also, patients who experienced a further oligoprogression after SBRT maintained a survival advantage compared with polymetastatic progression. No severe adverse events were reported.

Management of Patients with Gastric or Gastroesophageal Junction Cancer: From Theory to Integrated Clinical Path- ways Implementation in the Real World.

Introduction: Best care of esophagogastric junction and gastric cancer (EGC) requires a complex, timely interaction between members of a multi-disciplinary team (MDT). An integrated clinical pathway (ICP) is necessary to achieve this goal as well as the implementation of its use in daily practice. The objective of this study was to elaborate on an integrated clinical pathway for the multi-disciplinary management of ECG. Authors also put in act an implementation program to improve adherence to guidelines thought an ICP. Method: This prospective work carried out by a multi-institutional MDT in Italy identified expert panel extracted relevant recommendations and/or statements from published papers and guidelines obtaining a set of crucial interventions employed the Estimate-Talk-Estimate method. A flow-chart diagram was elaborated to elicit the process at a glance. The primary outcome measure was the elaboration of an ICP with a high consensus rate also reported as a snapshot diagram and its implementation in daily clinical practice. An accredited certification body agency validated results, and an implementation process was started in several hospitals known to treat ECG. Results: A methodologist aggregated a multi-disciplinary panel of experts from different institutions. The panel elaborated a flow-chart diagram with crucial intervention highlight and connecting lines, as well as outcome measures. An accredited certification body agency validated the entire process, representing the basis for empowerment and implementation among patients and oncological professionals in various hospitals. Conclusion: The multi-disciplinary and multi-institutional expert panel successfully elaborated on a validated ICP for all stages ECG. An in-hospital implementation program has been programmed.

A multicenter LArge retrospectIve daTabase on the personalization of stereotactic ABlative radiotherapy use in lung metastases from colon-rectal cancer: The LaIT-SABR study.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic disease, but local control of colorectal metastases remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate the progression to the polymetastatic disease (PMD). MATERIAL AND METHODS: The study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1033 lung metastases were reported. Clinical and biological parameters were evaluated as predictive for freedom from local progression-free survival (FLP). Secondary end-point was the time to the polymetastatic conversion (tPMC). RESULTS: Two-year FLP was 75.4%. Two-year FLP for lesions treated with a BED < 00 Gy, 100-124 Gy, and ≥125 Gy was 76.1%, 70.6%, and 94% (p = 0.000). Two-year FLP for lesion measuring ≤10 mm, 10-20 mm, and >20 mm was 79.7%, 77.1%, and 66.6% (p = 0.027). At the multivariate analysis a BED ≥125 Gy significantly reduced the risk of local progression (HR 0.24, 95%CI 0.11-0.51; p = 0.000). Median tPMC was 26.8 months. Lesions treated with BED ≥125 Gy reported a significantly longer tPMC as compared to lower BED. The median tPMC for patients treated to 1, 2-3 or 4-5 simultaneous oligometastases was 28.5, 25.4, and 9.8 months (p = 0.035). CONCLUSION: The present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Predictive factors were identified for treatment personalization.

Cognitive function modulation during aging: a focus on L-alpha-GPE.

OBJECTIVE: The objectives of this review are to explore the neuronal pathways and cellular and molecular mechanisms involved in both healthy and impaired cognitive function and to discuss the role of nootropics, in particular, those with cholinergic activity, as promising interventions to preserve and/or improve cognitive performance in patients in the symptomatic pre-dementia stage, known as mild cognitive impairment (MCI). MATERIALS AND METHODS: Papers were retrieved by a PubMed search, using different combinations of keywords (e.g., cognitive function AND aging AND nootropics), without limitations in terms of publication date or language. RESULTS: Nootropics modulate the activities of specific brain pathways involving neurotransmitters and neuromodulators that have distinct roles in the cognitive processes. The nootropic L-a-glyceryl-phosphoryl-ethanolamine (L-a GPE), by virtue of its action as a phospholipid (PL) precursor and acetylcholine (Ach) donor, targets neural stem cell aging, cholinergic depletion, oxidative stress and microglia activation, loss of entorhinal cortex neurons, and reduced hippocampal volume. Cognitive reserve levels may be linked to the resilience and adaptability of the brain to cope with age-related cognitive decline. L-a GPE may contribute to cognitive reserve preservation via its neuronal well-being promoting action. CONCLUSIONS: The substantial burden of age-related cognitive decline demands effective long-term and well-tolerated interventions aimed at maximizing the span of effective functioning. The use of inappropriate medication may lower cognitive reserve, thus hastening the onset of symptomatic AD, while the use of nootropics, such as L-a GPE may contribute to cognitive reserve preservation via its neuronal well-being promoting action.

Lipoprotein (a) behaviour in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignancy representing in Europe the 3-5% of all malignant tumors. Metabolic pathway of Lipoprotein(a) [Lp(a)] is influenced by various cytokines delivered during inflammatory and neoplastic diseases. Liver seems to be the main site of Lp(a) synthesis. METHODS: A group of patients affected by HCC was studied in order to evaluate the changes in serum Lp(a) levels and their significance. PARTICIPANTS: 40 patients (25 males and 15 females) affected by primary HCC and 25 control healthy subjects (12 males and 13 females). In HCC patients we evaluated the following serological parameters: Lp(a), total cholesterol (TC), LDL-Cholesterol (LDL-C), HDL-Cholesterol (HDL-C), triglycerides (TG), albumin, (pseudo)cholinesterase (CHE), aspartate amino-transpeptidase (AST), alanine amino-transpeptidase (ALT), gamma-glutamyl transpeptidase (g-GT), alkaline phosphatase (ALP), ferritin, alpha fetoprotein, partial thromboplastin time (PTT), Quick time, prothrombinic activity (PA) and fibrinogen. Statistical analysis of the data obtained was performed using the variance analysis (ANOVA method) and Student's OtO for non-paired data test. For Lp(a), Wilcoxon's non parametric test was used. The correlations between examined parameters were performed by Pearson's correlation test. RESULTS: In patients with HCC, mean serum TC, LDL-C TG and Lp(a) levels were significantly lower than in controls. HDL-C did not show a statistically significant difference between the two groups studied. Furthermore, we found a positive correlation between: Lp(a) and CHE, Lp(a) and albumin, CHE and LDL-C; while a negative correlation has been found between: Lp(a) and alpha-fetoprotein, Lp(a) and ferritin, CHE and alpha-fetoprotein. CONCLUSIONS: On the basis of the relationship with alfa fetoprotein and ferritin serum levels, Lp(a) seems to represent an indirect index of liver damage. Lp(a) is a risk factor for vascular diseases and seems to have an interesting role in the liver functions. We conclude that the evaluation of Lp(a) serum levels may contribute, among other markers, to a more complete evaluation of the liver function in patients with HCC suggesting a predictive role for this lipoprotein.

Use of interleukin-2 in advanced renal carcinoma: meta-analysis and review of the literature.

OBJECTIVE: Interleukin-2 (IL-2) is a glycoprotein that influences the immunoendocrine network by several actions. This cytokine is commonly used in the patients with renal carcinoma, both as neo-adjuvant treatment prior to surgery and as adjuvant therapy. The aims of our study were to evaluate the IL-2 efficacy on postoperative survival rate in patients with metastatic renal carcinoma, to compare the efficacy of treatment with IL-2 alone with the results achieved by conventional systemic chemotherapy or association protocols IL-2-based and to examine the toxic effects of the IL-2-based therapeutic regimens in renal cell carcinoma (RCC). DESIGN: We enrolled 7 randomised trials concerning the IL-2-based treatments of RCC and performed meta-analytic processing by the Mantel-Haenszel-Peto method in order to achieve odds ratios and 95% confidence intervals of the examined treatments. We also considered 11 non-randomised trials, evaluating them in terms of survival rate through the endpoints available. In all trials taken into account, we finally examined the toxic effects as WHO grade, specifying study by study the main site involved. RESULTS AND CONCLUSIONS: Complete or partial response rates have been obtained in 6% to 30% of treated patients in all the trials considered. Our study revealed the need for careful screening as well as a continuous adjustment of doses when an immunotherapeutic protocol is employed in order to treat a metastatic renal carcinoma. Treatment with IL-2 alone achieves better results than systemic chemotherapy, even if the two types of treatment showed an almost overlapping medium- to long-term mortality rate. IL-2 plus lymphokine-activated killer cells accomplish only a partial response. The protocol with IL-2 plus IFN alpha displayed an interesting efficacy associated with a low toxicity even if the cumulative toxic effect of the two drugs should be carefully monitored. To date, the association of tumour-infiltrating lymphocytes, IL-2 and IFN alpha provided the best results in terms of survival and toxicity.

Alpha-interferon (IFN-alpha) treatment of chronic hepatitis C: analysis of some predictive factors for the response.

Interferon (IFN)-alpha is recognized today as the treatment of choice for chronic hepatitis virus C-related disease. Several factors are able to influence the response to the therapy. In the last few years, several types of IFN-alpha have been used with varying therapeutic results. In order to define the role played by the type of IFN-alpha, as a predictive factor of response to therapy, we studied clinical and biological features of 128 patients (80 males and 48 females, mean age 58.5+/-9.7 years) divided into four homogeneous groups. Four types of IFN-alpha were administered at the same dose and for an identical period. Lymphoblastoid was administered to Group A; recombinant 2a to Group B; recombinant 2b to Group C and leukocyte to Group D. The results showed that the best response was achieved using natural IFN. Statistical evaluation of the predictive factors was carried out using bivariate and multivariate analysis. IFN-alpha was associated with different response rates for viral and biochemical remission at the end of the treatment and at the end of 12 months' follow-up period. Therefore, the type of IFN administered may influence the response to therapy and important independent single predictive factors of response should be taken into account. The type of IFN used may determine how well the disease is controlled.

Neuropsychiatric effects and type of IFN-alpha in chronic hepatitis C.

Chronic hepatitis is often associated with neuropsychiatric disorders. Interferon (IFN) is the drug most widely used to treat this disease, and its side effects, such as depression, often involve the central nervous system (CNS). Symptoms include a slowing down of psychomotor functions, loss of interest, frontal lobe dysfunction, parkinsonism, and delirium. The occurrence of these complications calls for dropping out of IFN treatment or for a significant dose reduction and administration of antidepressants. Efficacy and side effects vary on the basis of the IFN type employed. The aim of our study was to evaluate if the frequency, form, and degree of depression induced are related to the type of IFN employed. We studied 96 patients with chronic hepatitis C. Our study series was divided into four groups according to the type of IFN-alpha administered. Depression degree was clinically evaluated using the Hamilton Depression Rating Scale (HAM-D). All patients were tested before treatment and 1, 3, and 6 months (15 days after the end of treatment) later. Our results showed that the type of IFN used seemed to influence the depression onset rate, with the leukocyte type inducing the lowest level of depression. However, when a number of symptoms associated with the depression were considered, the results of other types of IFN-alpha were found to be better. Use of the most suitable type of IFN-alpha could thus lead to more personalized treatment, with fewer side effects. The type of IFN used seems to influence the psychological side effects and the adaptation rate to therapy. It would be appropriate to choose the type of IFN on the basis of a neuropsychiatric assessment carried out before treatment.

Conserved regions of the Drosophila erect wing protein contribute both positively and negatively to transcriptional activity.

Genetic studies of the Drosophila erect wing (ewg) gene have revealed that ewg has an essential function in the embryonic nervous system and is required for the specification of certain muscle cells. We have found that EWG is a site-specific transcriptional activator, and we report here that evolutionarily conserved regions of EWG contribute both positively and negatively to transcriptional activity. Using gel mobility shift assays, we have shown that an EWG dimer binds specifically to DNA. In transfection assays, EWG activated expression of a reporter gene bearing specific binding sites. Analysis of deletion mutants and fusions of EWG to the Gal4 DNA binding domain has identified a transcriptional activation domain in the C terminus of EWG. Deletion analysis also revealed a novel inhibitory region in the N terminus of EWG. Strikingly, both the activation domain and the inhibitory region are conserved in EWG homologs including human nuclear respiratory factor 1 (NRF-1) and the sea urchin P3A2 protein. The strong conservation of elements that determine transcriptional activity suggests that the EWG, NRF-1, and P3A2 family of proteins shares common mechanisms of action and has maintained common functions across evolution.

The leisure time and the third age: the experience of a geriatric day hospital.

Leisure time represents an important part of the so-called 'successful aging' and contributes to overcome the problems related to the reduction of the social roles, favoring a better subjective adaptation to old age. In this work we observed the elderly population frequenting our Day Hospital, by estimating the affective sphere (geriatric depression scale, GDS), the autosufficiency (activity of daily living, ADL; and instrumental activity of daily living, IADL) and the schooling years in correlation with the type and length of leisure time activities during the day. These data have been compared with those of the national statistics (ISTAT). The analyses revealed a very wide diffusion of the utilization of mass media and a large interindividual differentiation of the modes of using leisure time. The correlations between the indices of affectivity and autosufficiency show an effect on the types of leisure time activities, while the scholarity of the subjects has no influence on it. These results suggest considering leisure time as an indispensable part of the relational life of elderly subjects, having an important 'valency' for the affective sphere and the individual expectations and needs.

Increase of serum beta2-microglobulin in patients affected by HCV correlated hepatocellular carcinoma.

OBJECTIVE: HLA antigens influence tumour growth and spreading, but the mechanism is still unclear. Increased serum levels of beta2-microglobulin (beta2MG) have been found in several chronic inflammatory and tumour diseases. The aim of the present study was to analyse the relationship between serum beta2MG levels and some markers of tumour progression, to verify the reliability of this parameter as a marker of hepatocellular carcinoma (HCC) progression. DESIGN: We studied 50 patients with hepatitis C virus (HCV) correlated HCC, 50 patients affected by chronic hepatitis C and 20 healthy controls. We performed a statistical analysis on the data obtained from haematological withdrawals in patients and healthy subjects. METHODS: Serum beta2MG levels were determined by an immunoturbidimetric method (normal values range from 0.8 to 27 microg/ml). Diagnosis of HCC was performed on the basis of haematochemical parameters (alpha-fetoprotein) and instrumental examinations (ultrasonography and computed tomography). In order to perform the statistical analysis we used the Wilcoxon non-parametric rank test and the Spearman log-rank correlation test RESULTS: Patients with HCC showed higher serum beta2MG levels than did chronic hepatitis C patients (36+/-16.5 microg/ ml versus 2.3+/-0.8 microg/ml; P<0.0001) or healthy subjects (36+/-16.5 microg/ml versus 1.6+/-0.4 microg/ml; P<0.0001). We found a positive correlation between beta2MG and interleukin-6 (IL-6) (r = +0.3; P = 0.05), beta2MG and alpha-fetoprotein (r = +0.4; P = 0.005), beta2MG and tumour size (r = +0.3; P = 0.02). CONCLUSIONS: An increase in the beta2MG serum level reflects the tumour size and seems to be a consequence of the stimulation on hepatocytes by humoral components of immunological response, such as IL-6. Weakening of the immune system, due to IL-6, may be responsible for a more severe progression of HCC and the hyperexpression of beta2MG.

The comorbidities of elderly oncologic patients.

The scope of this study was to evaluate the prevalence of comorbidity in elderly subjects with neoplastic diseases, and to compare it to those without tumor pathologies. Three groups of patients have been considered: (A)35 elderly oncological patients; (B)38 young/adult oncological patients; (C)25 elderly patients without oncological pathology. After clinical evaluation and pathohistological diagnostic analysis, the concomitant pathologies have been estimated by means of two methods: (i)the Satariano's score; and (ii)the Charlson Comorbidity Index (CCI). Statistical analyses performed by using the Chi-square and the Student's t-test gave coherent results, and revealed that the prevalence of comorbidities was the highest in Group C, and displayed significantly reduced prevalences in the sequence Group B, Group A.

On the importance of multidimensional evaluation of elderly oncologic patients.

The role of comorbidity and the psycho-affective attitudes have been studied in 108 elderly oncological patients, in comparison with 25 elderly subjects without tumor pathologies. The results have revealed positive correlations between the activity of daily living (ADL), as well as the instrumental activity of daily living (IADL) scales and the comorbidity both in the oncological subjects and the controls. The performance status defined by the eastern cooperative oncology group (ECOG-PS) positively correlated with the parameters of ADL and IADL scales, demonstrating an increased vulnerability and fragility of the oncological patients in their everyday activities. An increased psychological fragility of the oncological patients has also been revealed by the scores of the geriatric depression scale (GDS), which might be cause and consequence at the same time of the disease itself. In addition, the polypathologies are not associated with an increased gravity of the tumor stage, although there have been 2.5 accompanying pathologies, mainly diseases of osteoarticular and cardial character. The correction of functional damages of various organs due to aging or concomitant or previous diseases is a period of fundamental importance for an adequate oncological therapy. The principal goal of any intervention in the elderly oncological patient should certainly be an improvement of the quality of life, including an alleviation of the impact of the diagnostic and therapeutic procedures on it.

Haematologic pattern in healthy elderly subjects.

BACKGROUND: A more prolonged life expectancy is associated with an increased morbidity rate with marked alterations of physiologic and metabolic functions in the body. The haematologic pattern can be modified during ageing because of reduced cellular replication and enhanced fibrosis in the bone marrow. Nevertheless it is not clear whether ageing represents the cause or the result of these phenomena. METHODS: In order to evaluate wide variation of data on the haematologic pattern in elderly subjects, we studied one hundred eight healthy subjects (27 males, 81 females; ranging from 50 to 99 years), living in their home. RESULTS: We observed a reduction in serum iron and transferrin and an increase in serum ferritin levels during ageing, with a consequential iron tissue stores increase. CONCLUSIONS: Our data suggested that senescence was associated with an increased incidence of anemia, which cannot be considered a normal feature of aging, the physicians must investigate each cause of anemia in elderly subjects. Haematological pattern is in the normal range in healthy elderly subjects, even if we found significant age-linked changes. We conclude that a progressive impairment of bone marrow functions is the most important factor in determining significant changes of hematopoiesis in healthy elderly subjects.

Rapid evolution of chronic viral hepatitis into hepatocellular carcinoma after beta-interferon treatment.

A 62-year-old man, affected by Chronic Active Hepatitis (discovered in 1993) and treated with interferon, referred to our department with increased abdominal volume, persistent abdominal pain, continuous-remittent fever and jaundice. CT scan of the liver revealed a hypodense, not capsulated, infiltrative, solid formation in the right lobe. US guided biopsy showed multinucleated giant cells, with eosinophilic cytoplasm and pleomorphism of the nuclei, arranged in several thick trabecula lined by endothelial cells or formed bile containing acini. In our case, the rapid evolution of chronic viral hepatitis towards HCC calls for a careful evaluation of the role of IFN therapy, since this drug is widely used in chronic liver diseases.

Fish oil treatment of interferon-alpha-induced dyslipidaemia: study in patients with chronic hepatitis C.

OBJECTIVE: Our study was designed to evaluate the role of omega-3 fatty acids (OFAs) in reducing serum triglyceride levels in patients with chronic hepatitis C receiving treatment with interferon-alpha (IFNalpha). DESIGN: 52 patients (23 males, 29 females) with chronic hepatitis C were randomly assigned to nonblind treatment with IFNalpha 3 million units (MU) three times weekly alone (group A) or in combination with OFAs 3 g/day for 6 months (group B). RESULTS: Hepatitis C virus (HCV) RNA serum levels decreased significantly in both groups compared with baseline, but there was no significant difference in HCV RNA levels between the 2 groups. At the end of treatment there was a statistically significant difference in ALT levels between patients in group A and in group B (72.15 vs 50.05 IU/L; p = 0.01). A statistically significant increase in triglyceride levels occurred in group A during treatment (p = 0.03 vs baseline). In contrast, a statistically significant decrease in triglyceride serum levels occurred in group B (p = 0.001 vs baseline). CONCLUSION: Concurrent administration of OFAs reversed IFNalpha-induced hypertriglyceridaemia in patients with chronic hepatitis C.

Serum carnitine levels in chronic hepatitis C patients before and after lymphoblastoid interferon-alpha treatment.

OBJECTIVE: Chronic liver disease is often a hypocarnitinaemic condition. Since carnitine affects lipid metabolism, modifications of lipid pattern and energy metabolism can be expected in patients affected by chronic viral hepatitis. The aim of this study was to assess the relationship between serum carnitine levels and the grading of chronic hepatitis C, and to evaluate the effects of lymphoblastoid interferon (IFN)-alphan1 on carnitine levels in patients with hepatitis C. DESIGN: We evaluated carnitine serum levels in a group of 32 patients with chronic hepatitis C before and after treatment with intramuscular IFNalpha 3MU 3 times/week for 6 months, comparing them with levels in 20 healthy controls. Statistical correlations between serum carnitine, histological activity index score, duration of disease and lipid pattern were also evaluated. RESULTS: Serum carnitine levels, which were statistically lower in hepatitis C patients than in controls before therapy, increased after IFNalpha (p = 0.0003 vs pretreatment). There were no significant changes in total cholesterol in any patient after treatment, although serum triglyceride levels increased (p = 0.0003). Serum carnitine levels were correlated with age (r = 0.35; p = 0.02), type of response (r = - 03; p = 0.04), duration of disease (r = - 0.8; p = 0.0001) and high-density lipoprotein cholesterol levels (r = 0.43; p = 0.005) after completion of IFNalpha treatment. CONCLUSION: It is suggested that the post-treatment increase in serum carnitine observed in this study could be considered a new index of improved liver function. Also, exogenous administration of carnitine may be useful in patients with chronic hepatitis C who have reduced endogenous synthesis of this substance.

Tacrine treatment of Alzheimer's disease: many expectations, few certainties.

Quality of life and behavioral functions are severely reduced in patients affected by Alzheimer's disease (AD). Among the drugs employed in the treatment of this invalidating degenerative dementia, tacrine (THA) seemed to play a possible therapeutic role. Our study was aimed to evaluate the efficacy of THA in the treatment of AD, performing a comparison with lecithin and/or placebo treatment. Five randomized controlled trials on tacrine versus lecithin and/or placebo treatment were randomly selected. Mantel-Haenszel-Peto method was applied. Patients treated with tacrine achieved better results than control subjects (overall OR = 2.34; 95% CI 1.42-3.85); but long-term treatment with tacrine was not significantly more efficacious than placebo. Statistical significance in favor of THA versus other drugs employed was obtained in MMSE and ADAS-Cog tests in the studies carried out by Eagger et al. and Knapp et al. Moreover, Fitten et al. administered the highest tolerated THA dose to only a few patients enrolled in the study. The presence of broad CIs observed in the 5 meta-analytic studies infer non homogeneity of effects of treatment. Solely few patients improved, whereas the clinical conditions of the majority remained stationary. Between 5 and 10% of the outpatients in each single study presented reversible side effects calling for suspension of THA treatment. The optimal dose ranged between 80 and 160 mg THA, but often produced side effects. Comparative trials revealed the reduced efficacy and elevated toxicity of THA treatment, dampening the initial enthusiasm concerning the usefulness of this drug in AD. Furtermore, tacrine-induced side effects provoked many dropouts in all studies investigated. The effectiveness of tacrine treatment in AD disease was not fully confirmed. Other studies are required to identify doses and modalities of administration of this drug in AD.