The prognostic value of 18F-FDG PET-CT in the management of Hodgkin’s lymphoma: preliminary results of a prospective study

BACKGROUND: To date, Hodgkin’s lymphoma (HL) patients have achieved long-term survival of more than 80%. Unfortunately, longer follow-up has shown serious adverse effects of the treatments used. For this reason, therapeutic strategies are becoming more tailored to the individual patient´s prognosis. Pre-treatment risk factors for early-stage and advanced-stage HL are well known indicators of prognosis. Recently, early interim 18F-FDG PET has been shown as a strong and independent predictor of progression-free survival in HL. Our aim was to assess response to therapy by repeating 18F-FDG-PET/CT after four and six chemotherapy cycles. MATERIAL AND METHODS: We evaluated 21 consecutive patients affected by (HL) and presenting for assessment over a period of three years. All patients underwent initial staging with 18F-FDG-PET/CT along with standard staging procedures. We tailored an individual treatment plan dependent on pre-treatment risk factors and initial 18F-FDG-PET/CT. With the aim of the best definition of response to treatment, we repeated 18F-FDG-PET/CT after two (FDG-PET 2), four (FDG-PET 4) and six (FDG-PET 6) chemotherapy cycles. Chemotherapy was typically given for four cycles in early disease stages and was prolonged to six to eight cycles in advanced disease stages, depending on PET findings. RESULTS: Our results showed a strong negative predictive value in detecting responders in early stage HL and a positive predictive value in advanced-stage patients. Clinical stage, extra-nodal sites and the positivity of the 18F-FDG-PET/CT performed during chemotherapy were also noted as strong determinants of response to treatment. Moreover, in our series the 18F-FDG-PET/CT data obtained after only two chemotherapy cycles (FDG-PET 2) were the same of those obtained after FDGPET 4 and FDG-PET 6 controls. CONCLUSION: The preliminary data of the present study confirm those of previous published studies about the negative predictive value of 18F-FDG-PET/CT performed after four and six chemotherapy cycles, which contributed to the decision to stop treatment and to avoid radiotherapy in HL patients. Nonetheless, our preliminary data seems to suggest that only the 18F-FDG-PET/CT performed after two cycles of chemotherapy (FDG-PET 2) is able to provide the same prognostic information of the FDG-PET 4 and FDG-PET 6 earlier

plasma matrix metalloprotease 9 correlates with blood lymphocytosis leukemic cell invasiveness and prognosis in b cell chronic lymphocytic leukemia

The complex biology underlying chronic lymphocytic leukemia cell migration and tissue invasiveness is not yet completely understood and might provide novel predictive markers and therapeutic targets. A total of 36 patients out of treatment from at least 3 months were enrolled and followed up for a median period of 44.2 months (range: 4.4-99.2). Matrix metalloprotease 9 and tissue inhibitor of metalloproteases 1 plasma levels and production/release from lymphoid cells were measured by zymography and enzyme-linked immunosorbent assay (ELISA) analysis. Malignant and normal lymphocyte mobility and matrix-degradation capability were studied using a Boyden chamber system, with and without autologous plasma. Free matrix metalloprotease 9 plasma levels were related with blood lymphocytosis, especially in more advanced stages (p = 0.003), and higher concentrations were associated with an increased disease progression risk (hazard ratio = 9.0, 95% confidence interval = 1.5-13.8). Leukemic cells expressed and secreted very little matrix metalloprotease 9. On the contrary, normal lymphocytes derived from the same leukemic patients showed matrix metalloprotease 9 intracellular levels that were lower in subjects with higher blood lymphocytosis (p = 0.024) and more advanced stages (p = 0.03); the released quantities were inversely associated with matrix metalloprotease 9 plasma concentrations (p = 0.035). Leukemic cells had a reduced spontaneous mobility and matrix-degradation capability that were stimulated by autologous plasma (p = 0.001) and normal lymphocytes (p = 0.005), respectively. Matrix metalloprotease 9 affected cell invasiveness depending on concentration and disease stage. In conclusion, chronic lymphocytic leukemia cells have a reduced mobility, matrix-degradation capability, and matrix metalloprotease 9 production compared to their own autologous normal lymphocytes. They are exposed to matrix metalloprotease 9 of prevalently systemic origin whose higher levels are associated with both leukemic and normal lymphocyte accumulation in the peripheral blood and have a negative prognostic value

Antihypertensive Treatment in the Elderly and Very Elderly: Always “the Lower, the Better?”

Arterial hypertension (HT) is age dependent and, with the prolongation of life expectancy, affects more and more elderly people. In the elderly, HT is a risk factor for organ damage and cardiovascular (CV) events. Both pharmacologic and nonpharmacologic reduction of blood pressure (BP) is associated with a corresponding decrease in systolic-diastolic or isolated systolic HT. Clinical trials have shown that BP lowering is associated with a decrease in stroke and other CV events. Therefore, BP reduction per se appears more important than a particular class of antihypertensive drugs. The benefit of antihypertensive treatment has been confirmed up to the age of 80 years, remaining unclear in the octogenarians. The benefit in lowering diastolic BP between 80 and 90 mmHg is well established, while that of lowering systolic BP below 140 mmHg requires further confirmations

The importance of mechanics in the pathogenesis of fragility fractures of the femur and vertebrae

This review highlights the role played by mechanical imbalances in the pathogenesis of fragility fractures of the femur and vertebrae. Particular attention is paid to vertebral fractures, and the consequences arising from mechanical imbalances are analyzed and evaluated to determine how much they contribute to worsening vertebral deformity and creating a domino effect

Nutraceuticals for Serum Lipid and Blood Pressure Control in Hypertensive and Hypercholesterolemic Subjects at Low Cardiovascular Risk

INTRODUCTION: Primary cardiovascular (CV) prevention may be achieved by lifestyle/nutrition changes, although a relevant role is now emerging for specific, functional foods and nutraceutical compounds (NCs). The aim of this study was to investigate the efficacy and safety of NCs in lowering blood pressure (BP) and improving lipid profile, when added to diet and lifestyle management versus diet alone in a group of patients with hypertension (HT) and hypercholesterolemia (HCh) with low CV risk. METHODS: Sixty-six patients with HT and HCh with grade 1 essential HT (mean age 56.0 \ub1 4.6 years) without history of CV diseases or organ damage were analyzed. These subjects were started on one tablet of an NC-containing red yeast rice, policosanol, berberine, folic acid and coenzyme Q10 once daily for 6 months and were age and gender matched with subjects following a diet program. Differences in clinic BP, 24-h ambulatory BP (24 h-ABPM), serum total cholesterol, low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C) and triglyceride values were compared by analysis of variance. RESULTS: In the treatment group, a significant reduction of systolic 24 h-ABPM (141.6 \ub1 6.4 vs. 136.2 \ub1 4.8 mmHg; p < 0.05) and pulse pressure 24 h-ABPM (52.6 \ub1 7.2 vs. 47.3 \ub1 5.4 mmHg; p < 0.05) was found at the end of follow-up. A reduction of total cholesterol (-19.2%), LDL-C (-17.4%) and triglycerides (-16.3%) was observed (p < 0.001 for all); HDL-C remained unchanged. No difference was found in the control group. CONCLUSIONS: The tested NCs was found to be safe, well tolerated and effective in reducing mean 24-h systolic and 24-h pulse pressure and in improving lipid pattern

Asymptomatic hyperuricemia is a strong risk factor for resistant hypertension in elderly subjects from general population

OBJECTIVE: In clinical practice, patient characteristics predicting resistant hypertension (RH) include higher blood pressure levels, left ventricular hypertrophy, older age, obesity, chronic kidney disease and diabetes. On the contrary little is known about the role of serum uric acid (SUA) as a risk factor for RH in subjects from general population. MATERIAL AND METHODS: 580 elderly subjects aged 6565 years were enrolled in the Risk Of Vascular complications Impact of Genetics in Old people (ROVIGO) study. RH was defined as the failure to maintain blood pressure values below 140mmHg (systolic) and 90mmHg (diastolic) despite therapeutic interventions that include appropriate lifestyle measures plus adherence to treatment with full doses of at least three antihypertensive drugs, including a diuretic. RH was confirmed using 24-h ambulatory blood pressure measurement. Hyperuricemic was defined as the subjects having SUA 656.8mg/dl or taking uricosuric drugs. Gender-specific odds ratio (OR) for RH was calculated by logistic regression analysis. RESULTS: The prevalence of RH was 5.7% in the cohort and was higher in women (8.3%) than in men (3.0%, p<0.05). Independent of chronic kidney disease (OR 3.89, 95% confidence interval 1.49-10.1), hyperuricemia predicted resistant hypertension in women (odds ratio 3.11, 95% confidence intervals 1.06-9.1, p=0.03) but not in men. CONCLUSIONS: In elderly women from the general population, an SUA value of 656.8mg/dl triples the risk of RH. SUA assessment should be recommended to better define the pattern of risk associated with RH

Mood Disorders in Uncontrolled Hypertension Despite Multiple Anti-Hypertensive Medications: Searching for a Link

INTRODUCTION: Resistant hypertension is a clinical condition in which blood pressure (BP) control is not achieved under a pharmacological therapy including a diuretic and at least two additional antihypertensive drug classes. AIM: To discuss an unusual presentation of uncontrolled hypertension despite multiple anti-hypertensive medications. METHODS AND RESULTS: A 46-year-old woman presented with resistant hypertension (HT) and with a long history of polydipsia, polyuria, weight loss and psychiatric symptoms (sudden onset of personality disorder with free anxiety, negativism and asthenia) unsuccessfully treated with antidepressant drugs. Tests for secondary HT showed a marked increase of serum renin and aldosterone both in clinostatic (342 pg/ml and 907 pmol/l, respectively) and orthostatic posture (351 pg/ml and 2845 pmol/l, respectively), hypokalemia (2.9 mmol/l) and macroalbuminuria (431 mg/day). Diagnostic examinations also revealed a focal stenosis of approximately 70 % of the proximal right renal artery with post-stenotic dilation. After percutaneous balloon angioplasty and stent implantation, BP was normalized with 5 mg/day amlodipine and psychiatric symptoms suddenly disappeared. CONCLUSIONS: Psychopathological symptoms are rare at the onset of hyperaldosteronism, and their aetiology is not well defined. A proper diagnostic and therapeutic process is mandatory in order to get the recommended therapeutic targets in short-midterm improving long-term prognosis. We also suggest not considering depressed or treat with antidepressant agents a young hypertensive subject with uncontrolled hypertension despite multiple anti-hypertensive medications without having ruled out a secondary form of hypertension

Domino Effect: mechanic factors role

The rapid onset of the Domino Effect following the first Vertebral Compression Fracture is a direct consequence of the mechanical variations that affect the spine when physiological curves are modified. The degree of kyphosis influences the intensity of the Flexor Moment; this is greater on vertebrae D7, D8 and on vertebrae D12, L1 when the spine flexes. Fractures of D7, D8, D12 and L1 are, by far, the most frequent and also the main cause of the mechanical alterations that can trigger the Domino Effect. For these considerations vertebrae D7, D8, D12 and L1 have to be taken in consideration as “critical". In the case of critical clinical vertebral fractures it is useful to provide an indication for minimally invasive surgical reduction or intrasomatic stabilization. When occurs a fracture of a “critical vertebra”, prompt restoration of the heights leads to a reduction in the Kyphosis Index and therefore in the Flexor Moment, not only of the fractured vertebra but also, in turn, of all the other metameres which, even if morphologically still intact, are structurally fragile; so, through the restoration of the mechanical vertebral proprieties, we can reduce the risk of the Domino Effect. At the same time the prompt implementation of osteoinductive therapy is indispensable in order to achieve rapid and intense reconstruction of the trabecular bone, the strength of which increases significantly in a short period of time. Clinical studies are necessary to confirm the reduction of the domino effect following a fragility fracture of "critical vertebrae" with the restoration of the mechanical properties together with anabolic therapy

B-lines:to count or not to count

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