Safety of Lumason® (SonoVue®) in special populations and critically ill patients.

Evidence for the safe use of Lumason® (SonoVue®), an ultrasound enhancing agent (UEA), in special patient populations is critical to enable healthcare professionals to make informed decisions concerning its use in such patients. Herein, we provide insight on the safety and tolerability of Lumason® in special patient populations. Findings are presented from clinical pharmacology studies conducted in patients with compromised cardiopulmonary conditions, from a retrospective study performed in critically ill patients, and from post-marketing surveillance data from over 20 years of market use of Lumason® (SonoVue®). No detrimental effects of Lumason® on cardiac electrophysiology were observed in patients with coronary artery disease (CAD), and no significant effects on pulmonary hemodynamics were noted in patients with pulmonary hypertension or congestive heart failure. Similarly, no effects on several assessments of pulmonary function (e.g., FVC) were observed in patients with chronic obstructive pulmonary disease (COPD), and no clinically meaningful changes in O2 saturation or other safety parameters were observed after administration of Lumason® to patients with diffuse interstitial pulmonary fibrosis (DIPF). The retrospective study of critically ill patients revealed no significant difference for in-hospital mortality between patients administered Lumason® for echocardiography versus those who had undergone echocardiography without contrast agent. Post-marketing surveillance revealed very low reporting rates (RR) for non-serious and serious adverse events and that serious hypersensitivity reactions were rare. These findings confirm that Lumason® is a safe and well tolerated UEA for use in special populations and critically ill patients.

PD1/PD-L1 immune checkpoint as a potential target for preventing brain tumor progression.

Programmed death-1 (PD-1) is a cell surface receptor that functions as a T cell checkpoint and plays a central role in regulating T cell collapse. The binding of PD-1 to its ligand programmed death-ligand 1 (PD-L1) activates downstream signaling pathways and inhibits T cell activation in the perspective of immune system mechanism and regulation in tumor progression. It is well reported that tumors adopt certain immune-checkpoint pathways as a mechanism of resistance against immune cells such as T cells that are specific for tumor antigens. Indeed, the PD-1/PD-L1 pathway controls the induction and maintenance of immune tolerance within the tumor microenvironment. Thus, the PD-1/PD-L1 checkpoint regulation appears to be of extreme importance as well as the immunotherapy targeting that via and the using of PD-1/PD-L1 inhibitors that have changed the scenario of brain cancer treatment and survival. Here, we review the mechanism of action of PD-1 and PD-L1, the PD/PDL-1 signaling pathway involved in the progression of brain tumors, and its application as cancer immunotherapy counteracting tumor escape in central nervous system.

Protective effect of sodium propionate in Aß1-42 -induced neurotoxicity and spinal cord trauma.

Sodium propionate (SP) is one of the main short chain fatty acids (SCFA) that can be produced naturally through host metabolic pathways. SP have been documented and include the reduction of pro-inflammatory mediators in an in vivo model of colitis. The aim of this study is to evaluate the neuroprotective effects of SP in reducing inflammatory process associated to neurological disorders. We performed both in vitro model of Alzheimer's disease, induced by oligomeric Aß1-42 stimulation, and in in vivo model of spinal cord injury (SCI) in which neuroinflammation plays a crucial role. For in vitro model, the human neuroblastoma SH-SY5Y cell line was first differentiated with retinoic acid (100 µM) for 24 h and then stimulated by oligomeric Aß1-42 (1 µg/ml) and treated with SP at 0.1- 1-10 µM concentrations for another 24 h. Instead, the in vivo model of SCI was induced by extradural compression of the spinal cord at T6-T8 levels, and animals were treated with SP (10-30-100 mg/kg o.s) 1 and 6 h after SCI. Our results demonstrated that both in in vitro neuroinflammatory model and in vivo model of SCI the treatment with SP significantly reduced NF-κB nuclear translocation and IκBα degradation, as well as decreases COX-2 and iNOS expressions evaluated by Western blot analysis. Moreover, we showed that SP treatment significantly ameliorated histopathology changes and improved motor recovery in a dose-dependent manner. In conclusion, our results demonstrated that SP possesses neuroprotective effects, suggesting it could represent a target for therapeutic intervention in neuroinflammatory disorders.

Sodium Butyrate Exerts Neuroprotective Effects in Spinal Cord Injury.

Sodium butyrate (SB) is a dietary microbial fermentation product and serves as an important neuromodulator in the central nervous system. Recent experimental evidence has suggested potential therapeutic applications for butyrate, including its utility in treating metabolic and inflammatory diseases. The aim of the present study was to evaluate the potential beneficial effects of SB in a mouse model of spinal cord injury (SCI) and its possible mechanism of action. SCI was induced by extradural compression for 1 min of the spinal cord at the T6-7 level using an aneurysm clip, and SB (10-30-100 mg/kg) was administered by oral gavage 1 and 6 h after SCI. For locomotor activity, study mice were treated with SB once daily for 10 days. Morphological examination was performed by light microscopy through hematoxylin-eosin (H&E) staining. In addition, NF-κB, IκB-α, COX-2, and iNOS expressions were assayed by western blot analysis and IL-1ß and TNF-α levels by immunohistochemistry analysis. The results showed that SB treatment significantly ameliorated histopathology changes and improved recovery of motor function changes in spinal cord injury in a dose-dependent manner. Moreover, we demonstrated that SB modulated the NF-κB pathway showing a significant reduction in cytokine expression. Thus, this study showed that SB exerts neuroprotective effects anti-inflammatory properties following spinal cord injury suggesting that SB may serve as a potential candidate for future treatment of spinal cord injury.

Peritonectomy and hyperthermic chemotherapy in patients with advanced or recurrent ephitelial ovarian cancer: a single center cohort study.

AIM: The present study reports our experience concerning with the advanced cancer treatment (cytoreductive surgery and hyperthermic intraperitoneal chemotherapy) in patients with advanced ovarian cancer ephitelial (AEOS) or recurrent ovarian cancer ephitelial (REOC). METHODS: In a period from October 2006 to December 2009, we observed 25 patients affected by advanced ephitelial ovarian cancer or recurrent ephitelial ovarian cancer. All patients underwent CRS + HIPEC procedures. Peritoneal involvement was valued according to the Peritoneal Cancer Index (PCI) and the remaining postoperative disease according to the Completeness of Cytoreduction score (CC). HIPEC was always performed with closed technique for 60 min, with an average inflow temperature of 42.5 °C. The drugs were administered in combination according two schemes: 1) cisplatin 60 mg/m2/L and caelyx 20 mg/m2/L; 2) 60 mg/m2/L taxotere and caelyx 20 mg/m2/L. Morbidity and mortality were evaluated in accordance with the NCI CTCAE v. 3.0 (USA). Finally, the Disease Free Survival and Overall Survival by the Kaplan-Meier method was rated. RESULTS: The average age observed was 64 years (range 46-76). Fourteen patients (56%) were affected by AEOC. From this group, 12 (48%) were subjected to neoadjuvant therapy and 2 (8%) to surgery as a first; 11 (44%) patients had REOC and all of them had previously undergone to surgery and adjuvant CHT. The average PCI was 12.63 (range 2-27). In 22 patients (88%), cytoreduction was considered total or almost total (CC-0 in 14 patients, CC-1 in 8); in 3 patients (12%), it had not been optimal (CC-2 or CC-3). In all 18 patients with PCI less than 15, it was possible to achieve an optimal cytoreduction, and this was possible only in 3 of the 7 patients who had a PCI greater than 15. The average operative time, including HIPEC, was of 612 min (range 425 min-840 min). In 9 patients (36%), the postoperative course was uncomplicated, in 10 patients (40%) complications were minor (G1-G2) and in 4 patients (16%) morbidity was important (G4). Mortality rate was 8%. The average OS was 30.8 months and the median OS was 30.8 months (respectively 36.5 months for AEOC and 27 months for REOC). The median DFS total (calculated from the day of surgery or from the day of the beginning of the CHT) was 12months (respectively 12.9 months for AEOC, 11.9 months for REOC). CONCLUSION: Although the CRS and HIPEC procedure in the treatment of advanced or recurrent ovarian cancer represents now a reliable method with good results both in terms of morbidity and of distance results, there are still many controversial aspects that may in the future be better clarified only with a randomized phase III study, which is in progress, involving international working groups and experts on the procedure.

Diffusion-weighted magnetic resonance for prediction of response after neoadjuvant chemoradiation therapy for locally advanced rectal cancer: preliminary results of a monoinstitutional prospective study.

PURPOSE: To evaluate diffusion-weighted imaging (DWI) for assessment of treatment response in locally advanced rectal cancer (LARC) 8 weeks after neoadjuvant chemoradiotherapy (CRT). METHODS AND MATERIALS: A total of 28 patients with LARC underwent magnetic resonance imaging (MRI) prior to and 8 weeks after CRT. Tumor volume (TV) was calculated on T2-weighted MRI scans as well as the apparent diffusion coefficient (ADC) was calculated using Echo-planar DWI-sequences. All data were correlated to surgical results and histopathologic tumor regression grade (TRG), according to Mandard's classification. Post-treatment difference ADC (%ΔADC) and TV (%ΔTV) changes at 8 weeks were compared complete response (CR; TRG1) and non-complete response tumors (non-CR; TRG2-5). RESULTS: The mean % ADC increase of CR group was significantly higher compared to non-CR group (77.2 ± 54.63% vs. 36.0 ± 29.44%; p = 0.05). Conversely, the mean % TV reduction did not significantly differ in CR group from non-CR group (73.7% vs. 63.77%; p = 0.21). Accordingly, the diagnostic accuracy of the mean % ADC increase to discriminate CR from non-CR group was significantly higher than that of the mean % TV reduction (0.913 vs. 0.658; p = 0.022). No correlation was found between mean % TV reduction and TRG (rho = 0.22; p = 0.3037), whereas a negative correlation between mean % ADC increase and TRG was recorded (r = -0.69; p = 0.006). CONCLUSION: The mean % ADC increase appears to be a reliable tool to differentiate CR from non-CR after CRT in patients with LARC.

Misty mesentery: a pictorial review of multidetector-row CT findings.

The term "misty mesentery" indicates a pathological increase in mesenteric fat attenuation at computed tomography (CT). It is frequently observed on multidetector CT (MDCT) scans performed during daily clinical practice and may be caused by various pathological conditions, including oedema, inflammation, haemorrhage, neoplastic infiltration or sclerosing mesenteritis. In patients suffering from acute abdominal disease, misty mesentery may be considered a feature of the underlying disease. Otherwise, it may represent an incidental finding on MDCT performed for other reasons. This article describes the MDCT features of misty mesentery in different diseases in order to provide a rational approach to the differential diagnosis.

[The INHES cohort study on the health status of nurses in Italy: research protocol]. / Lo studio di coorte INHES sullo stato di salute negli infermieri in Italia: protocollo di ricerca.

Due to the intense emotional involvement and the often problematic working conditions characterizing their profession, Nurses appear to be especially susceptible to the negative effects of a complex set of stressors, with important repercussions to their health. Nevertheless, scientific literature assessing the health status of Nurses in Italy is still scarce. With INHES (Italian Nurses' HEalth Study), we propose to remedy this gap by implementing a cohort study which will start from the analysis of some local healthcare facilities and which may subsequently extend throughout the country. Study participants will be Nurses selected according to the following inclusion criteria: 1) age between 30 and 55 years; 2) having been employed in the current healthfacilityfor the last five years; 3) having performed care duties in wards or in day care services for the last five years. The objectives of this study, which will be carried out through the administration of a validated questionnaire, are the following: to measure the incidence and prevalence rates of a series of diseases in the nursing population, highlighting potential correlations with working activity, job-related stress or environmental and personal risk factors; to assess the quality of life and psychological health of the participants, evaluating the interference of psychophysical disorders with their work and social activities; to investigate the implementation of wellness promotion, prevention, case management and disability management policies by healthcare facilities. The evidence gathered will provide a valid scientific support for the development of more effective policies for protecting Nurses' health, with positive social and economic repercussions for the entire community.

Study on the synergic effect of natural compounds on the microbial quality decay of packed fish hamburger.

The effectiveness of natural compounds in slowing down the microbial quality decay of refrigerated fish hamburger is addressed in this study. In particular, the control of the microbiological spoilage by combined use of three antimicrobials, and the determination of their optimal composition to extend the fish hamburger Microbiological Stability Limit (MAL) are the main objectives of this work. Thymol, grapefruit seed extract (GFSE) and lemon extract were tested for monitoring the cell growth of the main fish spoilage microorganisms (Pseudomonas fluorescens, Photobacterium phosphoreum and Shewanella putrefaciens), inoculated in fish hamburgers, and the growth of mesophilic and psychrotrophic bacteria. A Central Composite Design (CCD) was developed to highlight a possible synergic effect of the above natural compounds. Results showed an increase in the MAL value for hamburgers mixed with the antimicrobial compounds, compared to the control sample. The optimal antimicrobial compound composition, which corresponds to the maximal MAL value determined in this study, is: 110 mgL(-1) of thymol, 100 mgL(-1) of GFSE and 120 mgL(-1) of lemon extract. The presence of the natural compounds delay the sensorial quality decay without compromising the flavor of the fish hamburgers.

High-tech pediatric home care: a collaborative approach.

High-risk pediatric patients require specialized care. Through collaboration with medical specialty providers, home care agencies have the opportunity to go beyond providing traditional pediatric types of home care to providing successful, cutting-edge, high-tech pediatric home care.

Magnetic resonance angiography and colour-Doppler sonography in the evaluation of abdominal aortic aneurysms.

This prospective study was aimed at comparing the diagnostic accuracy of magnetic resonance angiography (MRA) with colour-Doppler ultrasonography (colour-Doppler US) in the assessment of abdominal aortic aneurysms (AAA). Twenty patients with abdominal aortic aneurysms underwent MRA, colour-Doppler US, digital subtraction angiography (DSA) and CT. The MRA technique and colour-Doppler findings were compared with DSA as well as surgical and pathological findings, which were considered as the gold standard. In 6 patients who refused surgery, CT and DSA were considered as the gold standard. The MRA technique always correctly assessed the size and site of the aneurysms, the involvement of the renal and common iliac arteries, the course of the left renal vein, the thrombotic component and the calcifications. Colour-Doppler US always correctly assessed the size and site of the aneurysms, the thrombotic component and calcifications and the involvement of the iliac arteries. Our preliminary results suggest that MRA together with colour-Doppler US represents a valid alternative to invasive imaging in the assessment of AAA.

[Assessment of the therapeutic effectiveness of alcohol administration in hepatocarcinoma: comparison of spiral computerized tomography and Doppler color ultrasonography]. / Valutazione dell' efficacia terapeutica dell' alcolizzazione nell' epatocarcinoma: confronto tra Tomografia Computerizzata spirale ed eco color Doppler.

PURPOSE: To investigate the comparative adequacy of spiral CT and color-Doppler US versus biopsy in assessing the efficacy of percutaneous ethanol injection (PEI) in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifteen patients with 30 known HCCs, 2-5 cm in diameter, underwent PEI. Arterial phase spiral CT and color-Doppler US were performed before treatment in all patients. Treatment efficacy was established on the basis of color-Doppler, spiral CT and percutaneous biopsy findings; biopsy was the gold standard. RESULTS: After PEI, 22 of 30 lesions which were negative for malignant cells at biopsy were completely necrotic at spiral CT and avascular at color-Doppler US. In the extant 8 lesions, which exhibited residual tumor tissue at biopsy, spiral CT detected early enhancement of the viable tumor portion in all cases. Color-Doppler US showed residual tumor vascularization in 4 of 8 lesions. CONCLUSIONS: Our results demonstrate that spiral CT, performed in the arterial phase, can improve the depiction of residual viable tumor tissue in HCCs treated with PEI, overcoming color-Doppler limitations.

[Aneurysm of the abdominal aorta. Angiography with magnetic resonance versus color Doppler ultrasonography]. / Aneurismi dell'aorta addominale. Angiografia con risonanza magnetica versus eco color Doppler.

This prospective study was aimed at comparing the diagnostic accuracy of Magnetic Resonance Angiography (MRA) with that of color-Doppler ultrasonography (color-Doppler US) in the detection and assessment of abdominal aortic aneurysms. Twenty patients with abdominal aortic aneurysms underwent MRA, color-Doppler US, digital subtraction angiography (DSA) and Computed Tomography (CT) on three consecutive days. Fourteen patients underwent surgical repair of the aneurysm. MRA and color-Doppler findings were compared with DSA, surgical and pathologic findings, which were considered as the gold standard. In the 6 patients who refused surgery, CT and DSA were considered the gold standard. MRA always correctly assessed the size and site of the aneurysm, the involvement of the renal and common iliac arteries, the retroarotic course of the left renal vein, the thrombotic component and calcifications. Color-Doppler US always correctly assessed the size and site of the aneurysm, the thrombotic component and calcifications and the involvement of the iliac arteries. In one case color-Doppler US failed to demonstrate the involvement of the renal arteries and the retroaortic course of the left renal vein. Our preliminary results suggest MRA as the best non-invasive technique to study abdominal aortic aneurysms.

[The superior and inferior venae cavae: angiography by TOF 2D magnetic resonance versus spin-echo sequences]. / Vene cave superiore e inferiore: angiografia con risonanza magnetica TOF 2D versus sequenze spin eco.

This work was aimed at assessing the usefulness of magnetic resonance angiography (MRA) in the investigation and diagnosis of vena cava conditions. Forty-five subjects that is 20 volunteers and 25 patients, were examined with MRA using a 1.5 T superconductive system (SE and angiography pulse sequences). In the 25 patients, 8 cases of thrombosis were diagnosed, together with 4 cases of suspected tumor spread into either the superior or the inferior vena cava, 2 cases of inferior vena cava agenesis, 5 cases of retroaortic left renal vein and 5 cases of abdominal aortic aneurysm. MRA was performed with the 2D time-of-flight (TOF) technique (FA 18 degrees, TR 30-40 ms, TE 10 ms); the images were acquired on the coronal, sagittal and axial planes with and without presaturation pulse and rotated in the post-processing according to the maximum intensity projection. In all volunteers MRA identified jugular veins, subclavian veins, anonymous veins, superior vena cava, inferior vena cava and common iliac veins. The main limitation of MRA was its spatial resolution. MRA proved to be less accurate than SE sequences in the assessment of tumor spread. As for thrombotic conditions, MRA provided useful additional information and is therefore considered a complementary technique to SE MRI. As for venous anomalies (double inferior vena cava, vena cava agenesis and retroaortic left renal vein) and in the study of the relationships with abdominal aortic aneurysms, MRA proved to be the more accurate of the two techniques.

Color Doppler flow imaging of renal disease. Value of a new intravenous contrast agent: SH U 508 A (Levovist).

This study was aimed at assessing the diagnostic value of a new intravenous contrast agent SH U 508 A (Levovist) in improving color Doppler detection of renal mass vascularity. The study included 30 patients with renal masses: 22 adenocarcinomas, 1 sarcoma, 1 leiomyosarcoma, 1 urothelioma, 1 hemorrhagic cyst and 4 angiomyolipomas. The vascularization of the renal masses was investigated by means of color Doppler US, before and after the intravenous injection of SH U 508 A (Levovist), on the basis of blood flow patterns within and around the lesions. At precontrast scanning, low color Doppler signal at the periphery or within the lesions was observed in 13/30 patients only. After contrast administration, the signal-to-noise ratio increased, which allowed the visualization of tumor vessels in 26/30 patients. In 4/30 patients only no major enhancement of tumor vessels was observed. Our experience suggests that SH U 508 A (Levovist) improves color Doppler sensitivity in depicting the tumor vessels which were missed at baseline exams and in evaluating renal vein and inferior vena cava involvement.

[Reproducibility of Doppler ultrasonography in the study of hepatic blood flow]. / Valutazione della ripetibilità dell'ecografia Doppler nello studio del flusso epatico.

The reproducibility of hepatic blood flow measurement with pulsed Doppler US was assessed in 6 healthy volunteers. All subjects underwent two different study sessions and were examined by three different operators after overnight fasting. Each operator was blind to his measurements. Hepatic arterial and portal venous blood flow and hepatic arterial maximum velocity were measured; resistive index (RI), pulsatility index (PI) and hepatic perfusion index (HPI) were calculated. Each measurement was repeated three times per session. The data from repeated measurements were analyzed with the analysis of variance (ANOVA) method to assess the intra- and intersubject variations for each variable. The Scheffe test was used to evaluate intra- and interobserver variations. Significant differences among the 6 examined subjects were found for all the variables measured, except for hepatic arterial maximum velocity. The same subject exhibited significant differences in mean velocity of the main portal vein trunk and of its right branch, in maximum hepatic arterial velocity, RI, portal vein section area and blood flow. No significant interobserver variation was observed in the same session and no intraobserver variation detected for all the measurements performed in different sessions. Thus, we conclude that pulsed Doppler US is a repeatable method for measuring hepatic blood flow and may therefore be useful to detect changes in hepatic perfusion.

[Color Doppler ultrasonography in the identification and characterization of secondary focal lesions of the liver]. / L'eco-color-Doppler nell'identificazione e nella caratterizzazione delle lesioni focali epatiche di natura secondaria.

This study was aimed at assessing the potentials of color Doppler US in the detection of hepatic metastases by measuring changes in hepatic perfusion. Color-Doppler US was performed on 40 patients with multiple metastatic lesions (mean theta: 3 cm). In each patient both smaller and bigger lesions were studied--80 lesions on the whole. Differences in flow distribution (peritumoral or intratumoral) and the highest systolic peak flow velocity were investigated on color Doppler US scans. Hepatic arterial and portal venous blood flow measured in 40 patients with hepatic metastases were compared with those in 40 healthy controls. The two groups were homogeneous relative to age, sex, height and weight. The ratio of hepatic arterial to total liver blood flow (Doppler perfusion index, DPI) and the ratio of hepatic arterial to portal venous blood flow (Doppler flow ratio, DFR) were calculated. Color flow US scans were obtained in 56 of 80 metastatic lesions. We observed peritumoral flow in 76% of the lesions, intratumoral flow in 6% and mixed peritumoral and intratumoral flow in 18% of cases. The DPI and DFR values were significantly higher in the patients with liver metastases than in the control group. The changes in DPI and DFR resulted from an increase in hepatic arterial flow; no changes in portal venous blood flow were observed. These results suggest that Doppler measurements of hemodynamic hepatic changes may be of great value for the earlier detection of hepatic metastases.

Credentialing of crossover privileges in fluoroscopy for nonradiologists.

PURPOSE: To comply with federal and state guidelines, a credentialing process was developed for nonradiologist medical users of fluoroscopy. MATERIALS AND METHODS: Seventy-three nonradiologist physicians participated in a program consisting of (a) an introductory 1-hour lecture; (b) a 10-page booklet providing basic information on radiation physics, radiobiology, and radiation safety; and (c) successful completion of a 15-question self-study quiz on fluoroscopy RESULTS: Mean fluoroscopy times per surgical case were compared for a 7-month period before (7.01 minutes in 201 cases) and after (4.39 minutes in 396 cases) the program and showed a 37.4% decrease (P < .05). Participating physician attitudes were surveyed at the completion of the program and showed an average physician time investment of 2 1/2 hours and a 4.1 approval rating for the credentialing program on a 5-point Likert scale. CONCLUSION: This fluoroscopic credentialing process for nonradiologist medical users (a) achieved a statistically significant reduction in fluoroscopic time per surgical case, (b) required a minimal investment of physician time, and (c) was well received by the medical staff.

Reproducibility of ultrasound measurement of pancreatic size with new advanced high-resolution dynamic image scanners.

The reproducibility of ultrasound measurements of the pancreas was investigated in 10 healthy volunteers. All subjects underwent three different evaluations, each consisting of three ultrasound examinations, at 8:00 after overnight fasting, at 12:00 after a solid, standard meal, and at 14:00. The longitudinal and anteroposterior (AP) diameters of the head, body, and tail, as well as the total areas of the gland, were measured in longitudinal and axial scans. Significant differences were observed in the head and body longitudinal diameters measured at 12:00 and in the tail AP diameter at 14:00. We conclude that ultrasonography of the pancreas should be performed in the morning with patients in the fasting state. In these conditions, the reliability of ultrasound measurements of the gland appears to be the highest.