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.

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.

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.

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.

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.

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.

Hepatoblastoma and familial adenomatous polyposis.

Eleven children have been identified as having hepatoblastoma and a family history of adenomatous polyposis, and 14 additional instances of this association have been collected from the literature. Among the 11 survivors of hepatoblastoma in the combined series, adenomatous lesions have been sought in seven and detected in six patients at ages 7 to 25 years. Five of these patients also have congenital hypertrophy of the retinal pigment epithelium, a marker for carriers of the polyposis gene. These findings strengthen the association between hepatoblastoma and familial adenomatous polyposis and have led to the establishment of the Hepatoblastoma-Adenomatous Polyposis Registry.

Gallbladder perforation: correlation of cholescintigraphic and sonographic findings with the Niemeier classification.

We retrospectively analyzed the cholescintigrams and sonograms of 36 consecutive patients with gallbladder perforation to (a) determine the sensitivity of each for the preoperative detection of gallbladder perforation and (b) correlate the findings with the modified Niemeier classification. Cholescintigraphic criteria of perforation (free spill, pericholecystic hepatic activity, and scintigraphic gallstone ileus sign) were detected in 14 of 28 (50%) cases, while sonographic criteria of perforation (pericholecystic fluid or pneumobilia with gallstones) were present in 18% (4 of 22) of patients (p less than 0.05). Cholescintigraphic patterns of perforation associated with the Niemeier classification were: Type I (acute free perforation), 3 of 7 scans demonstrated free spill; Type II (subacute pericholecystic abscess), 9 of 19 scans showed pericholecystic activity; and Type III (chronic cholecystoenteric fistula), 1 of 3 scans showed a scintigraphic gallstone ileus. Thus, although cholescintigraphy appears superior to sonography, both modalities are relatively insensitive for the detection of gallbladder perforation.

Hepatoblastoma in a patient with familial polyposis coli.

Two cases of hepatocellular carcinoma in patients with familial polyposis coli (FPC) have recently been reported in the literature. Hepatoblastoma was also reported in five children with maternal ancestors with FPC. We report a case of hepatoblastoma in a female infant whose father has FPC as further evidence of an association between hepatoblastoma and FPC.

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.

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.

[Software for record reporting and filing with the personal computer]. / Un software per refertare ed archiviare con il personal computer.

During the past four years the authors have been gaining experience in reporting radiological examinations by personal computer. Today they describe the project of a new software which allows the reporting and filing of roentgenograms. This program was realized by a radiologist, using a well known data base management system: dBASE III. The program was shaped to fit the radiologist's needs: it helps to report, and allows to file, radiological data, with the diagnostic codes used by the American College of Radiology. In this paper the authors describe the data base structure and indicate the software functions which make its use possible. Thus, this paper is not aimed at advertising a new reporting program, but at demonstrating how the radiologist can himself manage some aspects of his work with the help of a personal computer.

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.

[Congenital luxation of the hip. Clinico-echographic correlations]. / Lussazione congenita dell'anca. Correlazioni clinico-ecografiche.

The authors report their experience with US of the hip in 1000 children aged 1 day to 8 months. US study was carried out following Graf's method. All the children were previously examined by a pediatrician, who recorded all the clinical signs on a chart. After US examination, the radiologist recorded US findings on the same chart. Thus, US findings could be compared to clinical ones: there was agreement in 71% of cases, and disagreement in the extant 29%. Furthermore, clinics exhibited a high false-negative rate (64%) and a low false-positive rate (23%). This suggests US as an useful screening method able to show early morphological and functional alterations in the infant hip. The authors also examined the incidence of the single clinical signs and risk factors, and correlated them with US findings.

[Hepatic steatosis: combined echography-computerized tomography imaging]. / Steatosi epatica: imaging integrato ecografia-tomografia computerizzata.

The authors report their experience with the combined use of US and CT in the study of diffuse and subtotal fatty infiltration of the liver. An apparent disagreement was initially found between the two examinations in the study of fatty infiltration. Fifty-five patients were studied with US and CT of the upper abdomen, as suggested by clinics. US showed normal liver echogenicity in 30 patients and diffuse increased echogenicity (bright liver) in 25 cases. In 5 patients with bright liver, US demonstrated a solitary hypoechoic area, appearing as a "skip area", in the quadrate lobe. In 2 patients with bright liver, the hypoechoic area was seen in the right lobe and exhibited no typical US features of "skip area". Bright liver was quantified by measuring CT density of both liver and spleen. The relative attenuation values of spleen and liver were compared on plain and enhanced CT scans. In 5 cases with a hypoechoic area in the right lobe, CT findings were suggestive of hemangioma. A good correlation was found between bright liver and CT attenuation values, which decrease with increasing fat content of the liver. Moreover, CT attenuation values confirmed US findings in the study of typical "skip areas", by demonstrating normal density--which suggests that CT can characterize normal tissue in atypical "skip areas".