Prognostic impact of pretreatment cell-free DNA concentration in newly diagnosed peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) have a poor prognosis and, to date, there are no reliable predictive biomarkers of response. In this work we explored the prognostic impact of cell-free DNA (cfDNA) concentration in 75 newly diagnosed patients enrolled in a prospective multicenter study. Pre-treatment cfDNA was strongly associated with clinical risk factors and was identified as a superior predictor for shorter progression-free survival in multivariable analysis, outweighing canonical risk parameters. Furthermore, we identified a cfDNA value above which survival worsens. In conclusion, pre-treatment cfDNA concentration represents an easily usable predictive biomarker that is highly associated with survival of PTCL patients.

Two different pathogenetic mechanisms may play a role in acne and in hirsutism.

OBJECTIVE: Acne is one of the most common skin disorders. Androgens are known to play an important and possibly central role. Androgens secreted from ovaries and adrenal glands (androstenedione, dehydroepiandrosterone and its sulphate, testosterone) and target tissue-produced androgens (testosterone and its 5 alpha-reduced metabolite, dihydrotestosterone) have been implicated. Although the sebaceous gland and the hair follicle form a single morphological entity, the pilosebaceous unit, acne and hirsutism do not always appear concomitantly, thus leading to the supposition that these two structures may have different degrees of sensitivity to similar androgenic stimulation. DESIGN AND PATIENTS: To determine whether acne and hirsutism are the clinical expression of a different androgen metabolism at target tissue levels we studied 90 randomly selected patients who came to our Out-patient Department for diagnosis and treatment during the last 2 years with isolated acne of mild to severe degree and 52 patients with idiopathic hirsutism without acne or history of acne. Twenty-four women without acne or hirsutism and without a history of endocrine disease were studied as controls. MEASUREMENTS: In both groups of patients, plasma levels of sex hormone binding globulin, of dihydrotestosterone, and of 3 alpha-androstanediol and of its glucuronide were evaluated. In all patients the percentage of free testosterone and the testosterone/sex hormone binding globulin ratio were also calculated. RESULTS: Patients with acne and those with isolated hirsutism showed significantly decreased sex hormone binding globulin plasma levels. The values of the percentage free testosterone and those of the testosterone/sex hormone binding globulin ratio were, on the contrary, higher with respect to the controls, although there were no statistically significant differences between the two groups. Significantly increased plasma levels of dihydrotestosterone with respect to the controls were observed in patients with acne or in those with hirsutism. However, while all patients with hirsutism showed increased plasma values of 3 alpha-androstanediol and its glucuronide, all patients with acne showed plasma levels within the normal range, independently of the precursor plasma levels. CONCLUSIONS: Our results demonstrate that dihydrotestosterone is further reduced to 3 alpha-androstanediol and its glucuronide only in hirsute patients but not in acne patients. These results suggest that dihydrotestosterone may undergo different metabolic pathways at skin levels and support the hypothesis that the two clinical manifestations may be the expression of the different metabolic fate of dihydrotestosterone itself. Moreover, our results demonstrate that 3 alpha-androstanediol and its glucuronide cannot be used as plasma markers of target-tissue produced androgens in all hyperandrogenic conditions.

[Therapy of hypercholesterolemia and hypertriglyceridemia. Comparison of hypolipemic effects of lovastatin and gemfibrozil]. / Sulla terapia dell'ipercolesterolemia e dell'ipertigliceridemia. Confronto sull'effetto ipolipemizzante fra lovastatina e gemfibrozil.

The authors report the results of a comparative study of the effects of lovastatin and gemfibrozil on plasma cholesterol. Both drugs inhibit the enzyme systems responsible for cholesterol synthesis at the initial stages. The trial was conducted in 40 patients with nonfamilial hypercholesterolemia of whom 20 were treated with lovastatin and 20 with gemfibrozil. Throughout the trial, subjects took a dietary regime of about 1500 cal. Thirty days' before the start of the trial, patients received a placebo daily. Before and after the placebo period and at the end of 30 days treatment with either drug, cholesterol, esterified cholesterol, VLDL, LDL, and HDL cholesterol, apolipoprotein B, phospholipid, triglyceride and free fatty acid blood levels were tested, as well as the level of fatty acid saturation (iodine number), and the activities of lipase and plasma heparin. The results obtained showed both drugs to induce significant reductions of total, VLDL- and LDL-cholesterol and apolipoprotein B, and a relative increase in HDL-cholesterol. Triglyceride blood level was more markedly reduced in patients treated with gemfibrozil compared to those treated with lovastatin, a difference accounted for by the different levels at which the two drugs interfere with the enzymes of the initial stages of cholesterol synthesis. Plasma free fatty acids rose more markedly under gemfibrozil while plasma lipase and heparin activity did not show any appreciable changes under either drugs. The authors conclude by pointing out that the use of these drugs should be decided according to the type of metabolic disorder to be corrected.

[Comparison of the lowering effect on blood cholesterol of clofibrate and simvastatin]. / Confronto sull'effetto ipocolesterolemizzante fra clofibrato e simvastatina.

The authors report the results obtained in a comparative study of effects of clofibrate and simvastatin. The investigation was carried out on 44 patients with type IIB hypercholesterolemia subdivided into two groups. Throughout the study, patients observed a diet of about 1500 Kcal daily. Thirty days before starting drug treatment, all patients were given a placebo daily, either of the two drugs being administered during the subsequent 30 days. Plasma cholesterol level was examined before starting placebo and before drug treatment and every five days throughout drug treatment. The results obtained showed that both drugs reduced cholesterol plasma level significantly but the reduction obtained with simvastatin was greater than that obtained with clofibrate. The specificity of the use of these drugs in the management of hypercholesterolemia is stressed.

[Therapy of hypercholesterolemia and hypertriglyceridemia. Comparison of the lipid-lowering effect of simvastatin and tiadenol]. / Sulla terapia dell'ipercolesterolemia e dell'ipertrigliceridemia. Confronto sull'effetto ipolipemizzante fra simvastatina e tiadenolo.

A comparative trial was carried out on the effect on lipid metabolism of two drugs which inhibit the enzyme systems involved in cholesterol synthesis: tiadenol and simvastatin. The trial was performed in 40 patients with non familial and non secondary hypercholesterolemia. Subjects were divided into two groups of 20 patients each, one to be treated with tiadenol, the other with simvastatin. During the study period all patients followed a dietary regime of about 1500 cal daily. Thirty days before the trial, patients were given a placebo daily, and this was followed by thirty days with the drugs studied. Prior to the placebo period and at the end of the experimental period, blood was drawn for the assessment of total cholesterol, esterified cholesterol, VLDL-, LDL- and HDL-cholesterol, apolipoprotein B, phospholipids, and triglycerides. Both drugs were found to induce significant reductions of total cholesterol, VLDL, and LDL, a relative increase of HDL, and reduction of apolipoprotein B. Triglyceride blood level was markedly reduced in tiadenol-treated subjects, and to a lesser extent also in simvastatin-treated ones. This difference is attributed to the different levels at which the drugs interfere with the early steps of cholesterol synthesis. The authors conclude by pointing out that the two drugs should be used selectively according to the type of metabolic disorder prevalent in the individual patient.