F-18 FDG PET/CT and F-18 FLT PET/CT as predictors of outcome in patients with multiple myeloma. A pilot study.

OBJECTIVES: We evaluated the prognostic significance of the combined use of F-18 FDG (FDG) and F-18 FLT (FLT) PET/CT (PET/CT) in patients (pts) with multiple myeloma (MM) suspected relapse after a first line chemotherapy. METHODS: twenty-eight patients (57 ± 12 years) underwent both PET/CT scans over 2-4 weeks. Patients were grouped according to imaging results (FDG+/-; FLT+/-) and the findings compared to the event free survival (EFS). RESULTS: five pts had FDG+; FLT+, 8 showed FDG+;FLT-, two had FDG-;FLT + and 13 presented FDG-;FLT-, mostly (87 %) of FDG+;FLT- pts had destructive lytic bone lesions. At Cox regression analysis the FDG PET/CT (HR 4.4, 95 % CI 1.3-15.4, p < 0.05) and FLT PET/CT (HR 5.8, 95 % CI 1.7-19.3, p < 0.01) were predictive of worst prognosis. The Kaplan-Meier analysis showed that FDG and FLT PET/CT independently influenced the survival. FDG-;FLT-patients had better EFS as compared to FDG+; FLT + pts and FDG-;FLT + pts, those of FDG+;FLT- group also had worsened EFS. CONCLUSIONS: results from the aggregate use of PET/CT FDG and FLT in MM represent a valuable prognostic indicator for identifying patients at higher risk of undue events and may help to correctly stratify the patients with suspected relapse.

Assessment of Residual Radioactivity by a Comprehensive Wireless, Wearable Device in Thyroid Cancer Patients Undergoing Radionuclide Therapy and Comparison With the Results of a Home Device: A Feasibility Study.

Objective: To investigate the feasibility of using a wireless wearable device (WD) in differentiated thyroid cancer (DTC) patients undergoing radionuclide therapy with I-131 (RAI) and protected hospitalization, this study compared the measurements of residual radioactivity obtained with those registered by a permanent environmental home device (HD). Methods: Twenty consecutive patients undergoing RAI hospitalized in restricted, controlled areas were enrolled. The patients underwent comprehensive monitoring of vital/nonvital parameters. We obtained 45580± 13 measurements from the WD, detecting the residual radioactivity for each patient during approximately 56 hours of hospitalization, collecting data 53 times per hour. The samples, collected during daily activities, were averaged every two hours, and the results correlated with those from the HD. Bland-Altman analysis was also used to evaluate the agreement between the two techniques. Results: A significant relationship between the WD and HD was observed (r = 0.96, p < 0.0001). Bland-Altman analysis recognized the agreement between measurements by the WD and HD. The mean value at the end of the first day of hospitalization was 80.81 microSv/h and 60.77 microSv/h (p = ns for WD and HD), whereas those at the end of the second day were 47.08 and 24.96 (p = ns). In the generalized linear model (GLM), a similar trend in performance across time was found with the two techniques. Conclusion: This study demonstrates good agreement between the residual radioactivity measures estimated by the WD and HD modalities, rendering them interchangeable. This approach will allow both the optimization of medical staff exposure and safer patient discharge. Abbreviations: wireless device (WD); differentiated thyroid cancer (DTC); radionuclide therapy with I-131 (RAI); home device (HD); generalized linear model (GLM).

Potential role of the heat shock protein 90 (hsp90) in buffering mutations to favour cyclical parthenogenesis in the peach potato aphid Myzus persicae (Aphididae, Hemiptera).

Heat-shock proteins 90 (hsp90s) are a class of molecules able to stabilize a network of 'client' proteins that are involved in several processes. Furthermore, recent studies indicated that mutations in the hsp90-encoding gene induce a wide range of phenotypic abnormalities, which have been interpreted as an increased sensitivity of different developmental pathways to hidden/cryptic mutations. In order to verify the role of hsp90 in aphids, we amplified and sequenced the hsp90 gene in 17 lineages of the peach potato aphid Myzus persicae (Sulzer, 1776) looking for the presence of mutations. In particular, we compared lineages with different reproductive modes (obligate vs. cyclical parthenogenesis), propensity to develop winged females and karyotype stability. Differently from the cyclical parthenogenetic lineages that possessed functional hsp90 genes, the seven analysed asexual lineages showed severe mutations (including frameshift and non-sense mutations). In vivo functional assays with the hsp90-inhibitor geldanamycin showed that some lineages with cyclical parthenogenesis may lose their ability to induce sexuales in the absence of active hsp90 revealing the presence of cryptic mutations in their genomes. As a whole, our data suggest that hsp90 could play in aphids a role in buffering hidden/cryptic mutations that disrupt cyclical parthenogenesis.

Afit: a bioinformatic tool for measuring aphid fitness and invasiveness.

A careful measure of fitness represents a crucial target in crop pest management and becomes fundamental considering extremely prolific insects. In the present paper, we describe a standardized rearing protocol and a bioinformatics tool to calculate aphid fitness indices and invasiveness starting from life table data. We tested the protocol and the bioinformatic tool using six Myzus persicae (Sulzer) asexual lineages in order to investigate if karyotype rearrangements and ecotype could influence their reproductive performances. The tool showed that different karyotypes do not influence adaptive success and put in evidence a marked invasive potential of the M. persicae lineage 64. The presence of a similar fitness rate of 33H and 7GK asexual lineages (both possessing intra-individual karyotype variations) in respect to the asexual lineage 1 (with a standard karyotype) represents an important demonstration of the potentiality of holocentric chromosomes to reduce the effects of chromosome rearrangements.

Therapeutic Strategies in HCC: Radiation Modalities.

Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with (131)I Lipiodol or (90)Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment.

Modifiable and non-modifiable risk factors affecting walking recovery after hip fracture.

UNLABELLED: Modifiable and non-modifiable predictors of mobility recovery were analyzed on a sample of 774 hip fracture patients according to pre-fracture abilities. Overall predictors were mostly non-modifiable factors related to frailty of patients with the exception of 25-hydroxyvitamin D concentration which significantly affected walking recovery, especially in patients with higher pre-fracture performance. INTRODUCTION: This study aims to investigate mobility changes after hip fracture with the aim of identifying modifiable and non-modifiable predictors of mobility recovery according to different pre-fracture abilities. METHODS: This is a prospective inception cohort study of consecutive older patients, admitted with a fragility hip fracture in three Hospitals of Emilia Romagna (Italy). A sample of 774 patients alive at the sixth month was divided into three groups according to pre-fracture ambulation ability (group 1: mobile outdoors; group 2: mobile indoors; and group 3: mobile with help). The relationship between baseline characteristics of patients and the odds of walking recovery was analyzed using multivariate regression analysis. RESULTS: Mortality differed significantly among the three groups and was the highest in patients needing help to walk. Among the survivors, only 50.3 % of patients recovered walking ability. In a multivariate analysis, independent risk factors were different among the three groups. In group 1, older age, comorbidities, the use of walking devices before fracture, and low albumin level acted as negative factors while male gender, a pre-fracture high functional status, and higher 25-hydroxyvitamin D levels increased the probability of full recovery. In group 2, only pre-fracture functional status and 25-hydroxyvitamin D concentration were related to the recovery of walking ability. Pre-fracture functional status was also the only significant predictor for patients in group 3. CONCLUSIONS: Several baseline characteristics of patients are related to the likelihood of recovering walking ability after hip fracture. The 25-hydroxyvitamin D level seems to be the only relevant modifiable factor even if the effectiveness of its supplementation has yet to be demonstrated.

Should post-mortem brain dissection be performed in Parkinson's disease with atypical dementia?

We describe a patient affected by PD with a rapid progression of cognitive decline. This case could suggest the coexistence of many neurodegenerative diseases, which is a common condition in older patients. We propose an hypothetical trajectory of the cognitive impairment usually associated with motor symptoms in the later phase of Parkinsonian patients. The trajectory is almost linear in classical Parkinson's disease dementia (PDD), while a constant acceleration of the cognitive decline with a subsequent change of the slope of the direction could suggest the coexistence of PD with other neurodegenerative disease. Finally, if the cognitive decline in PD is comparable to a "stepped" decline, vascular lesions could be the cause of the change of the slope. This case could suggest to request an autopsy in all cases of unexplained PDD, for better understanding the mixture of non-motor symptoms in PD.

Electronic nose and isotope ratio mass spectrometry in combination with chemometrics for the characterization of the geographical origin of Italian sweet cherries.

Sweet cherries from two Italian regions, Apulia and Emilia Romagna, were analysed using electronic nose (EN) and isotope ratio mass spectrometry (IRMS), with the aim of distinguishing them according to their geographic origin. The data were elaborated by statistical techniques, examining the EN and IRMS datasets both separately and in combination. Preliminary exploratory overviews were performed and then linear discriminant analyses (LDA) were used for classification. Regarding EN, different approaches for variable selection were tested, and the most suitable strategies were highlighted. The LDA classification results were expressed in terms of recognition and prediction abilities and it was found that both EN and IRMS performed well, with IRMS showing better cross-validated prediction ability (91.0%); the EN-IRMS combination gave slightly better results (92.3%). In order to validate the final results, the models were tested using an external set of samples with excellent results.

F-18 FDG PET/CT in the assessment of patients with unexplained CEA rise after surgical curative resection for colorectal cancer.

PURPOSE: We evaluated the role of quantitative assessment by maximum standardized uptake value (SUVmax) on F-18 fluorodeoxyglucose [F-18]FDG positron emission tomography/computed tomography (PET/CT) in stratifying colorectal cancer (CRC) patients with unexplained carcinoembryonic antigen (CEA) rise after surgical curative resection. MATERIAL AND METHODS: Forty asymptomatic patients (mean age, 64 ± 12 years) with previous CRC and current serum CEA levels >5 ng/ml underwent [F-18] FDG PET/CT 13 ± 3 months after complete surgical resection. The SUVmax was registered on anastomosis and peri-anastomotic tissue lesions, if present. The patients were followed for 24 ± 9 months thereafter. Re-intervention, evidence of newly discovered distant metastases, and death were recognized as main events and constituted surrogate end points. The receiver-operator-curve (ROC) analysis was performed to estimate the optimal SUVmax cut-off to predict patients at high risk of main events. PET/CT results were then related to disease outcome (overall survival; OS). RESULTS: The mean SUVmax at the anastomotic site was 6.2 ± 3 (range 2.6-15). At multivariate logistic regression analysis, the anastomotic SUVmax remained as the only significant contributor to the prediction of the events (p = 0.004; OR 1.97). The ROC analysis recognized that the optimal threshold of SUVmax to differentiate patients was 5.7. A worse OS was observed in patients presenting with a SUVmax greater than 5.7 as compared to those having lesser (median survival: 16 vs. 31 months; p = 0.002). CONCLUSIONS: The quantitative assessment by SUVmax on [F-18]FDG PET/CT may be helpful in patients presenting with unexplained CEA rise after curative resection of CRC, by identifying those at risk of main events.

Theoretical study of sulfur L-edge XANES of thiol protected gold nanoparticles.

The Scalar Relativistic-Zero Order Regular Approximation-Time Dependent Density Functional Theory has been employed to study the sulfur L-edge XANES spectrum of the [Au(25)(SCH(3))(18)](+) model cluster, with the aim to reproduce and rationalize previous experimental data. The salient experimental features are properly described by the present calculation. The model cluster contains two different types of bidentate "staple" ligand thiol fragments, and it has been possible to assign the spectral features according to the different location of the initial core orbital on one of the two different fragments. This finding suggests that in the real nanoparticle two different non-equivalent type of sulfur bidentate ligands are present, arranged with the typical staple geometry.

Spin-orbit effects in the photoabsorption of WAu12 and MoAu12: a relativistic time dependent density functional study.

The electronic structure of both WAu12 and MoAu12 has been calculated at the density functional theory (DFT) level, employing the zero order regular approximation at the scalar relativistic level and including a spin-orbit coupling. The effect of the inclusion of the spin-orbit coupling is discussed, and the differences assigned to the nature of the encaged atom (W or Mo) are identified. Then, the excitation spectra of both clusters are calculated at the time-dependent DFT level, also in this case at both scalar relativistic and spin-orbit levels. The inclusion of spin-orbit coupling is mandatory for an accurate description in the low energy region. At higher energy, where the density of states is higher, the convoluted intensity can be properly described already at the scalar relativistic level. The consequences of the spin-orbit coupling on the excitation spectrum of the clusters indicate that while in WAu12 the lowest excitations are essentially shifted in energy with respect to the scalar relativistic results, in MoAu12, a dramatic splitting in many lines is actually predicted, revealing a quite different behavior of the two clusters.

The relation between the localization of foot dermatitis and the causative allergens in shoes: a 13-year retrospective study.

The purpose of this retrospective study was to test whether the initial pattern of clinical presentation of shoe dermatitis could indicate the causative allergen(s) and to estimate the odds on foot dermatitis in patients with a positive patch test versus those with a negative patch-test result. Between 1990 and 2002, 8543 patients were patch tested with the standard series (and additional allergens, if appropriate). Of them, 1168 (14%) had been referred because of foot dermatitis and 474 of these patients (5.5% of the total group) presented a positive reaction to one or more substances related to shoes. We found that 6 standard allergens in the male group and 8 standard allergens in the female group were statistically significant for the shoe dermatitis group. The data showed a relationship between the distribution pattern of the foot lesions and most of the allergens. These results have clinical applications since the gender of the patients and the localization of the foot eruptions can, indeed, indicate what allergen is involved.

Chemical and toxic evaluation of a biological treatment for olive-oil mill wastewater using commercial microbial formulations.

Olive-oil-mill wastewater (OMW) has significant polluting properties due to its high levels of chemical oxygen demand (COD), biochemical oxygen demand (BOD), and phenols. In the present study, different commercial bacterial formulations were used in the biological treatment of OMW. COD and toxicity testing using primary consumers of the aquatic food chain (the rotifer Brachionus calyciflorus and the crustacean Daphnia magna) were employed to evaluate abatement of the organic load and reduction of the toxic potential. In addition, the four most active formulations were tested mixed pair-wise on the basis of their unique characteristics in order to evaluate the improvement of treatment. The effect of treatment was assessed by measuring COD removal, reduction of total phenols, and decreased toxicity. The results obtained with the mixed formulations showed that the maximum removal of the organic load was about 85%, whereas phenols were reduced by about 67%. The toxicity for rotifers decreased by 43% and for crustaceans by about 83%.

New drugs, new techniques, new indications in pediatric regional anesthesia.

The use of regional anesthesia in children represents one of the most effective methods for perioperative analgesia and postoperative pain control. Things have been dramatically changed in the last two decades due to the appearance of new safer drugs and new tools; moreover new techniques were introduced showing their efficacy. In this paper we briefly describe the efficacy of new local anesthetics and adjuvants; we review the use of continuous peripheral blocks and other not very diffused techniques of regional anesthesia.

[Phono-mechano-cardiographic assessment in hypertensive heart disease: value of the apex cardiographic parameters (author's transl)]. / L'esame fono-meccano-cardiografico nella cardiopatia ipertensiva: utilità dei parametri diastolici apicografici.

In 15 normal subjects and in 19 patients with essential hypertension (NYHA I-II) systolic time intervals (STI) and diastolic more expressive parameters of the left ventricular performance were studied by phono-meccano-cardiography. ICT, LVET, ICT/LVET, iso-volumic relaxation period (A2-0) and rapid filling time (O-F) were measured. On the apexcardiogram relative height of rapid filling (RF) and atrial (A) waves measured too. "Diastolic index", a ratio between this two phenomena (hRFw/hAw) was calculated. Results were evaluated in relation with ECG, arterial pressure and subjective sympthoms. There were no statistically significant differences in mean values of the STI among normotensive and hypertensive subjects. On the contrary the parameters which explore into diastolic period result in disagreement and significantly influenced by diastolic arterial pressure. Comparison showed that patients in the hypertensive group had longer mean isovolumic relaxation period (P < 0.01), longer mean O-F time (P:ns), lower mean RF wave (P < 0,01) and higher mean atrial wave (P < 0,01). Consequently hRFw/hAw mean ratio was lower (P < 0,01) and frequently reversed. The lengthening of iso-volumic relaxation period and reduction of diastolic index were more consistent in the symtomatic patients (P:ns). It is concluded that poligraphic research, in patient with hypertensive heart disease, must not be restricted to the STI but it has to include a poliparametric evaluation of all phases of cardiac circle. The diastolic index may prove a simple, readily available and noninvasive guide in the assessment of left ventricular function.