On-Line Evaluation and Monitoring of Security Features of an RO-Based PUF/TRNG for IoT Devices.

The proliferation of devices for the Internet of Things (IoT) and their implication in many activities of our lives have led to a considerable increase in concern about the security of these devices, posing a double challenge for designers and developers of products. On the one hand, the design of new security primitives, suitable for resource-limited devices, can facilitate the inclusion of mechanisms and protocols to ensure the integrity and privacy of the data exchanged over the Internet. On the other hand, the development of techniques and tools to evaluate the quality of the proposed solutions as a step prior to their deployment, as well as to monitor their behavior once in operation against possible changes in operating conditions arising naturally or as a consequence of a stress situation forced by an attacker. To address these challenges, this paper first describes the design of a security primitive that plays an important role as a component of a hardware-based root of trust, as it can act as a source of entropy for True Random Number Generation (TRNG) or as a Physical Unclonable Function (PUF) to facilitate the generation of identifiers linked to the device on which it is implemented. The work also illustrates different software components that allow carrying out a self-assessment strategy to characterize and validate the performance of this primitive in its dual functionality, as well as to monitor possible changes in security levels that may occur during operation as a result of device aging and variations in power supply or operating temperature. The designed PUF/TRNG is provided as a configurable IP module, which takes advantage of the internal architecture of the Xilinx Series-7 and Zynq-7000 programmable devices and incorporates an AXI4-based standard interface to facilitate its interaction with soft- and hard-core processing systems. Several test systems that contain different instances of the IP have been implemented and subjected to an exhaustive set of on-line tests to obtain the metrics that determine its quality in terms of uniqueness, reliability, and entropy characteristics. The results obtained prove that the proposed module is a suitable candidate for various security applications. As an example, an implementation that uses less than 5% of the resources of a low-cost programmable device is capable of obfuscating and recovering 512-bit cryptographic keys with virtually zero error rate.

Multi-Unit Serial Polynomial Multiplier to Accelerate NTRU-Based Cryptographic Schemes in IoT Embedded Systems.

Concern for the security of embedded systems that implement IoT devices has become a crucial issue, as these devices today support an increasing number of applications and services that store and exchange information whose integrity, privacy, and authenticity must be adequately guaranteed. Modern lattice-based cryptographic schemes have proven to be a good alternative, both to face the security threats that arise as a consequence of the development of quantum computing and to allow efficient implementations of cryptographic primitives in resource-limited embedded systems, such as those used in consumer and industrial applications of the IoT. This article describes the hardware implementation of parameterized multi-unit serial polynomial multipliers to speed up time-consuming operations in NTRU-based cryptographic schemes. The flexibility in selecting the design parameters and the interconnection protocol with a general-purpose processor allow them to be applied both to the standardized variants of NTRU and to the new proposals that are being considered in the post-quantum contest currently held by the National Institute of Standards and Technology, as well as to obtain an adequate cost/performance/security-level trade-off for a target application. The designs are provided as AXI4 bus-compliant intellectual property modules that can be easily incorporated into embedded systems developed with the Vivado design tools. The work provides an extensive set of implementation and characterization results in devices of the Xilinx Zynq-7000 and Zynq UltraScale+ families for the different sets of parameters defined in the NTRUEncrypt standard. It also includes details of their plug and play inclusion as hardware accelerators in the C implementation of this public-key encryption scheme codified in the LibNTRU library, showing that acceleration factors of up to 3.1 are achieved when compared to pure software implementations running on the processing systems included in the programmable devices.

Risk factors for pleural effusion recurrence in patients with malignancy.

BACKGROUND AND OBJECTIVE: The main purpose of treatment in patients with malignant pleural effusion (MPE) is symptom palliation. Currently, patients undergo repeat thoracenteses prior to receiving a definitive procedure as clinicians are not aware of the risk factors associated with fluid recurrence. The primary objective of this study was to identify risk factors associated with recurrent symptomatic MPE. METHODS: Retrospective multicentre cohort study of patients who underwent first thoracentesis was performed. The primary outcome was time to fluid recurrence requiring intervention in patients with evidence of metastatic disease. We used a cause-specific hazard model to identify risk factors associated with fluid recurrence. We also developed a predictive model, utilizing Fine-Gray subdistribution hazard model, and externally validated the model. RESULTS: A total of 988 patients with diagnosed metastatic disease were included. Cumulative incidence of recurrence was high with 30% of patients recurring by day 15. On multivariate analysis, size of the effusion on chest X-ray (up to the top of the cardiac silhouette (hazard ratio (HR): 1.84, 95% CI: 1.21-2.80, P = 0.004) and above the cardiac silhouette (HR: 2.22, 95% CI: 1.43-3.46, P = 0.0004)), larger amount of pleural fluid drained (HR: 1.06, 95% CI: 1.04-1.07, P < 0.0001) and higher pleural fluid LDH (HR: 1.008, 95% CI: 1.004-1.011, P < 0.0001) were associated with increased hazard of recurrence. Negative cytology (HR: 0.52, 95% CI: 0.43-0.64, P < 0.0001) was associated with decreased hazard of recurrence. The model had low prediction accuracy. CONCLUSION: Pleural effusion size, amount of pleural fluid drained, LDH and pleural fluid cytology were found to be risk factors for recurrence.

VLSI Design of Trusted Virtual Sensors.

This work presents a Very Large Scale Integration (VLSI) design of trusted virtual sensors providing a minimum unitary cost and very good figures of size, speed and power consumption. The sensed variable is estimated by a virtual sensor based on a configurable and programmable PieceWise-Affine hyper-Rectangular (PWAR) model. An algorithm is presented to find the best values of the programmable parameters given a set of (empirical or simulated) input-output data. The VLSI design of the trusted virtual sensor uses the fast authenticated encryption algorithm, AEGIS, to ensure the integrity of the provided virtual measurement and to encrypt it, and a Physical Unclonable Function (PUF) based on a Static Random Access Memory (SRAM) to ensure the integrity of the sensor itself. Implementation results of a prototype designed in a 90-nm Complementary Metal Oxide Semiconductor (CMOS) technology show that the active silicon area of the trusted virtual sensor is 0.86 mm 2 and its power consumption when trusted sensing at 50 MHz is 7.12 mW. The maximum operation frequency is 85 MHz, which allows response times lower than 0.25 µ s. As application example, the designed prototype was programmed to estimate the yaw rate in a vehicle, obtaining root mean square errors lower than 1.1%. Experimental results of the employed PUF show the robustness of the trusted sensing against aging and variations of the operation conditions, namely, temperature and power supply voltage (final value as well as ramp-up time).

miR-9-5p suppresses pro-fibrogenic transformation of fibroblasts and prevents organ fibrosis by targeting NOX4 and TGFBR2.

Uncontrolled extracellular matrix (ECM) production by fibroblasts in response to injury contributes to fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Reactive oxygen species (ROS) generation is involved in the pathogenesis of IPF. Transforming growth factor-ß1 (TGF-ß1) stimulates the production of NADPH oxidase 4 (NOX4)-dependent ROS, promoting lung fibrosis (LF). Dysregulation of microRNAs (miRNAs) has been shown to contribute to LF. To identify miRNAs involved in redox regulation relevant for IPF, we performed arrays in human lung fibroblasts exposed to ROS. miR-9-5p was selected as the best candidate and we demonstrate its inhibitory effect on TGF-ß receptor type II (TGFBR2) and NOX4 expression. Increased expression of miR-9-5p abrogates TGF-ß1-dependent myofibroblast phenotypic transformation. In the mouse model of bleomycin-induced LF, miR-9-5p dramatically reduces fibrogenesis and inhibition of miR-9-5p and prevents its anti-fibrotic effect both in vitro and in vivo. In lung specimens from patients with IPF, high levels of miR-9-5p are found. In omentum-derived mesothelial cells (MCs) from patients subjected to peritoneal dialysis (PD), miR-9-5p also inhibits mesothelial to myofibroblast transformation. We propose that TGF-ß1 induces miR-9-5p expression as a self-limiting homeostatic response.

MRI fused with prone FDG PET/CT improves the primary tumour staging of patients with breast cancer.

OBJECTIVE: Our aim was to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) fused with prone 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in primary tumour staging of patients with breast cancer. METHODS: This retrospective study evaluated 45 women with 49 pathologically proven breast carcinomas. MRI and prone PET-CT scans with time-of-flight and point-spread-function reconstruction were performed with the same dedicated breast coil. The studies were assessed by a radiologist and a nuclear medicine physician, and evaluation of fused images was made by consensus. The final diagnosis was based on pathology (90 lesions) or follow-up ≥ 24 months (17 lesions). RESULTS: The study assessed 72 malignant and 35 benign lesions with a median size of 1.8 cm (range 0.3-8.4 cm): 31 focal, nine multifocal and nine multicentric cases. In lesion-by-lesion analysis, sensitivity, specificity, positive and negative predictive values were 97%, 80%, 91% and 93% for MRI, 96%, 71%, 87%, and 89% for prone PET, and 97%. 94%, 97% and 94% for MRI fused with PET. Areas under the curve (AUC) were 0.953, 0.850, and 0.983, respectively (p < 0.01). CONCLUSIONS: MRI fused with FDG-PET is more accurate than FDG-PET in primary tumour staging of breast cancer patients and increases the specificity of MRI. KEY POINTS: • FDG PET-CT may improve the specificity of MRI in breast cancer staging. • MRI fused with prone 2-[fluorine-18]-fluoro-2-deoxy-D-glucose PET-CT has better overall diagnostic performance than MRI. • The clinical role of fused PET-MRI has not yet been established.

Pilot randomized trial of selective internal radiation therapy vs. chemoembolization in unresectable hepatocellular carcinoma.

BACKGROUND & AIMS: To compare selective internal radiation therapy (SIRT) with transarterial chemoembolization (TACE), the standard-of-care for intermediate-stage unresectable, hepatocellular carcinoma (HCC), as first-line treatment. METHODS: SIRTACE was an open-label multicenter randomized-controlled pilot study, which prospectively compared primarily safety and health-related quality of life (HRQoL) changes following TACE and SIRT. Patients with unresectable HCC, Child-Pugh ≤B7, ECOG performance status ≤2 and ≤5 liver lesions (≤20 cm total maximum diameter) without extrahepatic spread were randomized to receive either TACE (at 6-weekly intervals until tumour enhancement was not observed on MRI or disease progression) or single-session SIRT (yttrium-90 resin microspheres). RESULTS: Twenty-eight patients with BCLC stage A (32.1%), B (46.4%) or C (21.4%) received either a mean of 3.4 (median 2) TACE interventions (N = 15) or single SIRT (N = 13). Both treatments were well tolerated. Despite SIRT patients having significantly worse physical functioning at baseline, at week-12, neither treatment had a significantly different impact on HRQoL as measured by Functional Assessment of Cancer Therapy-Hepatobiliary total or its subscales. Both TACE and SIRT were effective for the local control of liver tumours. Best overall response-rate (RECIST 1.0) of target lesions were 13.3% and 30.8%, disease control rates were 73.3% and 76.9% for TACE and SIRT, respectively. Two patients in each group were down-staged for liver transplantation (N = 3) or radiofrequency ablation (N = 1). CONCLUSIONS: Single-session SIRT appeared to be as safe and had a similar impact on HRQoL as multiple sessions of TACE, suggesting that SIRT might be an alternative option for patients eligible for TACE.

Partial liver volume radioembolization induces hypertrophy in the spared hemiliver and no major signs of portal hypertension.

BACKGROUND: Post-treatment contralateral hemiliver hypertrophy has created an interest in lobar liver radioembolization (RE) as a pre-surgery tool. METHODS: Liver and spleen volumes and function were studied in 83 patients submitted to partial liver volume RE at 4-8 weeks (T1), 10-26 weeks (T2), and >26 weeks (T3) after RE. RESULTS: More than half of the patients had cirrhosis with hepatocellular carcinoma. The main finding was a progressive increase in the volume of the spared hemiliver (mean absolute increase at T3: 230 ml). The percentage of patients in whom the baseline ratio of spared volume to total liver volume was <40% dropped from 56.6% at baseline to 29.4% at T2 (P < 0.001). A significant and progressive increase in spleen volume but not in portal vein diameter was also observed. A small percentage of patients developed hypersplenism, mostly those without cirrhosis (16.0% at T2). Six patients (five with portal vein thrombosis, cirrhosis or both) developed signs of portal hypertension by T2. CONCLUSIONS: The present results warrant further studies to better elucidate the mechanism underlying this phenomenon of spared hemiliver hypertrophy and to investigate its role as an alternative to portal vein embolization in the management of patients with potentially resectable liver tumours.

Orthopantomography Versus Cone Beam Computed Tomography for the Assessment of the Proximity of Posterior Maxillary Apexes with the Maxillary Sinus: A Cross-sectional Study.

BACKGROUND: The lack of knowledge of the relation of the maxillary sinus with the apexes of maxillary posterior teeth can lead to important complications during common dental procedures. This can be avoided using different imaging techniques, such as orthopantomography (OPG) and cone beam computed tomography (CBCT). The present study aims to compare the performance of OPG with CBCT in measuring the vertical distance of the apexes of posterior-superior teeth to the maxillary sinus. METHODS: This study corresponded to a cross-sectional study. OPGs and CBCT scans were obtained from the same individuals, and the qualitative and quantitative vertical distance of the apexes in relation to the maxillary sinus was categorized and measured in mm. RESULTS: A total of 28 pairs of OPGs and CBCT scans from the same patients were obtained. About 381 roots were analysed, which included 89 upper first premolars, 51 upper second premolars, 115 upper first molars, and 126 upper second molars. Projection/protrusion was observed with more frequency in molars, specially 1º molars in both OPG (n= 75, 65.2%) and CBCT (n= 31, 27%); however, 106 more cases (27.9%) were classified as projected in the OPG compared to CBCT (p < 0.05). When comparing the performance of the OPG and CBTC for analysing all roots qualitatively, there was a 57.8% agreement between both techniques. This difference was statistically significant (p <0.0001). Statistically significant differences were also observed when comparing the millimetric differences. CONCLUSION: This study showed that OPG is not an accurate technique to observe the relationship between the maxillary sinus and the apexes of the upper posterior teeth. In those cases where precision is required when performing dental procedures in this area, CBCT should be used. When not available, the clinicians should be aware of the limitations of the OPG and add other complementary techniques.

Comparison of the survival and tolerability of radioembolization in elderly vs. younger patients with unresectable hepatocellular carcinoma.

BACKGROUND & AIMS: The European Network on Radioembolization with Yttrium-90 resin microspheres study group (ENRY) conducted a retrospective study to evaluate the outcomes among elderly (≥ 70 years) and younger patients (<70 years) with unresectable hepatocellular carcinoma (HCC) who received radioembolization at 8 European centers. METHODS: Patients with confirmed diagnosis of unresectable HCC who either progressed following resection or locoregional treatment and/or who were considered poor candidates for chemoembolization were evaluated by a multidisciplinary team for radioembolization with (90)Y-resin microspheres (SIR-Spheres; Sirtex Medical). The survival outcome and all adverse events were compared between the two age groups. RESULTS: Between 2003 and 2009, 128 elderly and 197 younger patients received radioembolization. Patients in both groups had similar demographic characteristics. Many elderly and younger patients alike had multinodular, BCLC stage C disease, invading both lobes (p = 0.648). Elderly patients had a lower tumor burden, a smaller median target liver volume (p = 0.016) and appeared more likely to receive segmental treatment (p = 0.054). Radioembolization was equally well tolerated in both cohorts and common procedure-related adverse events were predominantly grade 1-2 and of short duration. No significant differences in survival between the groups were found (p = 0.942) with similar median survival in patients with early, intermediate or advanced BCLC stage disease. CONCLUSIONS: Radioembolization appears to be as well-tolerated and effective for the elderly as it is for younger patients with unresectable HCC. Age alone should not be a discriminating factor for the management of HCC patients.

Anatomical variations and abnormalities of the maxillary region and clinical implications: A systematic review and metaanalysis.

OBJECTIVE: The objective of this review is to investigate and analyze the anatomical variations present in the maxillary sinus (MS), through the examination of the prevalence of these variations, as well as the corresponding prevalence of clinically significant pathologies and complications associated with them. METHODS: The search process was carried out in the following databases; MEDLINE, SCIELO, WOS, CINHAL, SCOPUS, and GOOGLE SCHOLAR, using as search terms; "Maxillary bone," "Maxillary sinus," "Paranasal sinus," "Anatomical variations," "Sinusitis" and "Clinical anatomy." RESULTS: A total of 26 articles and 12969 samples were included, from which 12,594 subjects had their sex recorded giving a total of 5802 males and 6792 females. The variants reported by the included were Haller cells, Concha Bullosa, Number of septa, Hypoplastic sinus, Agger Nasi, Thickening of the MS mucosa, Deviation of the nasal septum, Accessory ostium, and Onodi cells. Among the mentioned, the ones that presented the greatest number of studies (between 8 and 10 studies included) were: the Haller Cells, the Concha Bullosa, and the Number of septa, where prevalence was 0.30, 0.36, 0.39 respectively. These variations can lead to sinusitis, cause some types of tumors, or affect neighboring structures that could be compromised by this variation. CONCLUSION: As a result, it is certainly complex to distinguish the presence of anatomical variations from pathological abnormalities. Therefore, knowledge of the different variations and their clinical relationships could be a useful asset for clinicians dedicated to this region.

Treatment With Adalimumab 80 mg Every Other Week in Inflammatory Bowel Disease: Results of Treatment Intensification in Clinical Practice.

Background: Loss of response to anti-tumor necrosis factor drugs in patients with inflammatory bowel disease (IBD) is frequent and, in case of low drug levels, treatment intensification is recommended. In addition, in cases in which clinical response without attainment of remission (clinical, endoscopic, or radiological), intensification could be justified since higher drug levels are associated with better outcomes. For adalimumab (ADA), the standard intensification regimen is 40 mg every week (ew). Availability of ADA 80 mg prefilled pens has enabled every other week (eow) intensification. We assessed the clinical efficacy of intensification with ADA 80 mg eow. Methods: This retrospective study was conducted at a tertiary hospital in Spain. Patients with IBD receiving maintenance ADA 80 mg eow with clinical, biomarker, and drug-level assessments were included. Demographics and clinical, biological, and endoscopic evaluation of the disease before and after ADA intensification, and pharmacokinetic assessments, were collected. Results: Eighty-seven patients (72 Crohn's disease, 15 ulcerative colitis; average age 50 years) were included. Reasons for ADA intensification were: low ADA levels-<5 µg mL-1-(17%), low ADA levels-<5 µg mL-1-without clinical response (63%), clinical response without clinical remission (15%) and active disease on objective evaluation (including colonoscopy, magnetic resonance imaging, capsule endoscopy, and/or intestinal ultrasound; 5%). Following treatment intensification to ADA 80 mg eow, 75 patients (86%) were in clinical remission and 69 (79.3%) were in biologic remission (clinical remission and normalization of biomarkers). After a median follow-up of 19 months (interquartile range 13-25), 63 patients (72%) remained on treatment and in clinical remission. There were no serious infections, hospitalizations, or deaths. Drug costs did not increase with the 80 mg eow regimen versus a standard intensification regimen. Conclusions: ADA intensification to 80 mg eow was safe, effective, and did not increase drug costs versus standard intensification to 40 mg ew in our experience.

Treatment alternatives for dry mouth: A scoping review.

Background: Saliva is a biological fluid essential for the maintenance of a proper oral health. Its absence predisposes to differences pathologies, including dental caries, fungal infections among many others, significantly affecting the oral health related quality of life (OHRQoL). There is a large variety of treatment alternatives available for dry mouth, which increases constantly. Objective: To identify new treatment alternatives for dry mouth. Material and Methods: We conducted a systematic search in PubMed/MEDLINE, Web of Science, Scopus and Ebsco. Articles published between January 2015 and January 2020 were retrieved and reviewed by two independent evaluators. Results: Nineteen studies met the inclusion criteria and were included for analysis. Local therapies were the most evaluated agents, followed by systemic and non-conventional treatments. Most local therapies showed certain utility for the management of dry mouth and the improvement of OHRQoL. These formulations were mainly based on natural agents, including malic acid, thyme honey, ginger, among others. Conclusions: Local agents are first line treatment alternatives for dry mouth sensation, with a reported efficiency that varies between studies, and with a low number of reported adverse side-effects. Nevertheless, care must be taken when interpreting these results, as is difficult to compare studies within each other due large heterogeneity in study design and outcomes being measured. Key words:Xerostomia, dry mouth, hyposalivation, saliva, mouth dryness.

Repeated Pulses of Methyl-Prednisolone in Adults Hospitalized With COVID-19 Pneumonia and Acute Respiratory Distress Syndrome: A Preliminary Before-After Study (CortiCOVID Study).

Introduction: The use of systemic corticosteroids in severely ill patients with coronavirus disease 2019 (COVID-19) is controversial. We aimed to evaluate the efficacy and safety of corticosteroid pulses in patients with COVID-19 pneumonia. Methods: A quasi-experimental study, before and after, was performed in a tertiary referral hospital, including admitted patients showing COVID-19-associated pneumonia. The standard treatment protocol included targeted COVID-19 antiviral therapy from 23rd March 2020, and additionally pulses of methylprednisolone from 30th March 2020. The primary outcome was a composite endpoint combining oro-tracheal intubation (OTI) and death within 7 days. Results: A total of 24 patients were included. Standard of care (SOC) (before intervention) was prescribed in 14 patients, while 10 received SOC plus pulses of methylprednisolone (after intervention). The median age of patients was 64.5 years and 83.3% of the patients were men. The primary composite endpoint occurred in 13 patients (92.9%) who received SOC vs. 2 patients (20%) that received pulses of methylprednisolone (odds ratio, 0.02; 95% confidence interval, 0.001 to 0.25; p = 0.019). Length of hospitalization in survivors was shorter in the corticosteroids group (median, 14.5 [8.5-21.8] days vs. 29 [23-31] days, p = 0.003). There were no differences in the development of infections between both groups. There were 3 deaths, none of them in the corticosteroids group. Conclusions: In patients with severe pneumonia due to COVID-19, the administration of methylprednisolone pulses was associated with a lower rate of OTI and/or death and a shorter hospitalization episode.

Introducción: El uso de corticosteroides sistémicos en pacientes gravemente enfermos por enfermedad coronavírica de 2019 (covid-19) es controvertido. Nuestro objetivo fue evaluar la eficacia y la seguridad de los pulsos de corticoesteroides en los pacientes con neumonía por covid-19. Métodos: Se realizó un ensayo cuasiexperimental, tipo antes y después, en un hospital terciario de referencia que incluyó a pacientes ingresados por neumonía asociada a covid-19. El protocolo de tratamiento estándar incluía un tratamiento antiviral dirigido contra el virus de la covid-19 desde el 23 de marzo de 2020 y añadió pulsos de metilprednisolona desde el 30 de marzo de 2020. El resultado primario fue un criterio combinado compuesto por la intubación orotraqueal y el fallecimiento durante los siguientes siete días. Resultados: Se incluyó un total de 24 pacientes. El protocolo de tratamiento (antes de la intervención) se prescribió en 14 pacientes, mientras que 10 recibieron el protocolo de tratamiento además de los pulsos de metilprednisolona (después de la intervención). La edad media de los pacientes fue de 64,5 años y el 83,3% de los pacientes eran hombres. El resultado combinado primario tuvo lugar en 13 pacientes (92,9%) que recibieron el protocolo de tratamiento frente a 2 pacientes (20%) que recibieron los pulsos de metilprednisolona (odds ratio = 0,02; intervalo de confianza del 95% = 0,001-0,25; p = 0,019). La duración de la hospitalización en los supervivientes fue más corta en el grupo que recibió corticoesteroides (media = 14,5 [8,5-21,8] días frente a 29 [23-31] días, p = 0,003). No hubo diferencias en el desarrollo de infecciones entre ambos grupos. Hubo tres fallecimientos, ninguno de ellos en el grupo que recibió corticoesteroides. Conclusiones: En los pacientes con neumonía grave por covid-19, la administración de pulsos de metilprednisolona se asoció a unas tasas menores de intubación orotraqueal y/o muerte y a episodios de hospitalización más cortos.

Radioembolization with use of yttrium-90 resin microspheres in patients with hepatocellular carcinoma and portal vein thrombosis.

PURPOSE: Intraarterial delivery of yttrium-90 ((90)Y)-bound microspheres (ie, radioembolization) is a promising treatment for hepatocellular carcinoma (HCC). An early concern was the "embolic" nature of the microspheres, and their potential to reduce hepatic arterial blood flow in patients with compromised portal blood flow secondary to portal vein thrombosis/occlusion (PVT). In this situation, the risk of liver failure could be enhanced, particularly in patients with cirrhosis who have increased hepatic arterial blood flow. This retrospective analysis was undertaken to assess the safety and clinical benefits of radioembolization with (90)Y resin microspheres in HCC with branch or main PVT. MATERIALS AND METHODS: A total of 25 patients presenting with unresectable HCC and compromised portal flow received segmental, lobar, or whole-liver infusion of (90)Y resin microspheres. For the analysis of tumor response, changes in target lesions, appearance of new lesions, and changes in portal vein thrombus were studied. Controlled disease was defined by absence of progression in all these components. RESULTS: Globally, controlled disease was achieved in 66.7% of patients at 2 months and 50% of patients at 6 months. No significant changes were observed in liver-related toxicities according to Common Toxicity Criteria (version 3.0) at 1 and 2 months after treatment. Median survival time was 10 months (95% CI, 6.6-13.3 months). CONCLUSIONS: Radioembolization of unresectable HCC and branch or main PVT with (90)Y resin microspheres was associated with minimal toxicity and a favorable median survival time. Further prospective studies are warranted to validate the findings in this clinically challenging patient population.

A genetic risk score predicts recurrent events after myocardial infarction in young adults.

INTRODUCTION AND OBJECTIVES: To evaluate whether a genetic risk score (GRS) improves prediction of recurrent events in young nondiabetic patients presenting with an acute myocardial infarction (AMI) and identifies a more aggressive form of atherosclerosis. METHODS: We conducted a prospective study with consecutive nondiabetic patients aged <55 years presenting with AMI. We performed a genetic test, cardiac computed tomography, and analyzed several biomarkers. We studied the association of a GRS composed of 11 genetic variants and a primary composite endpoint (cardiovascular mortality, a recurrent event, and cardiac hospitalization). RESULTS: A total of 81 patients were studied and followed up for a median of 4.1 years. There were 24 recurrent cardiovascular events. Compared with the general population, study participants had a higher prevalence of 9 out of 11 risk alleles. The GRS was significantly associated with recurrent cardiovascular events, especially when baseline low-density lipoprotein cholesterol (LDL-C) levels were elevated. Compared with the low-risk GRS tertile, the multivariate-adjusted HR for recurrences was 10.2 (95%CI, 1.1-100.3; P=.04) for the intermediate-risk group and was 20.7 (2.4-181.0; P=.006) for the high-risk group when LDL-C was≥2.8mmol/L (≥ 110mg/dL). Inclusion of the GRS improved the C-statistic (ΔC-statistic=0.086), cNRI (continuous net reclassification improvement) (30%), and the IDI (integrated discrimination improvement) index (0.05). Cardiac computed tomography frequently detected coronary calcified atherosclerosis but had limited value for prediction of recurrences. No association was observed between metalloproteinases, GRS and recurrences. CONCLUSIONS: A multilocus GRS may identify individuals at increased risk of long-term recurrences among young nondiabetic patients with AMI and improve clinical risk stratification models, particularly among patients with high baseline LDL-C levels.

Caveolin-1-dependent and -independent membrane domains.

Lipid rafts defined as cholesterol- and sphingomyelin-rich domains have been isolated from different cell types that vary greatly in their lipid profiles. Here, we investigated the contribution of the structural protein caveolin-1 (Cav1) to the overall lipid composition and domain abundance in mouse embryonic fibroblasts (MEFs) from wild-type (WT) or Cav1-deficient (Cav1(-/-)) animals. Our findings show that Cav1 expression had no effect on free (membrane-associated) cholesterol levels. However, Cav1(-/-)-deficient cells did have a higher proportion of sphingomyelin, decreased abundance of unsaturated phospholipids, and a trend toward shorter fatty acid chains in phosphatidylcholine. We isolated detergent-resistant membranes (DRMs), nondetergent raft domains (NDR), and cholesterol oxidase (CO)-sensitive domains and assessed the abundance of ordered domains in intact cells using the fluorescent dye Laurdan. Despite differences in phospholipid composition, we found that cholesterol levels in DRMs, NDR, and CO-sensitive domains were similar in both cell types. The data suggest that Cav1 is not required to target cholesterol to lipid rafts and that CO does not specifically oxidize caveolar cholesterol. In contrast, the abundance of ordered domains in adherent cells is reduced in Cav1(-/-) compared with WT MEFs, suggesting that cell architecture is critical in maintaining Cav1-induced lipid rafts.

Treatment of hepatocellular carcinoma by radioembolization using 90Y microspheres.

The use of external beam radiation therapy for primary treatment of hepatocellular carcinoma (HCC) has been limited by the low radiation tolerance of the non-tumoral liver. However, technical advances allowing partial liver volume external irradiation have resulted in consistently high response rates. Internal radiation therapy, also called (90)Y radioembolization ((90)Y-RE), consists in delivering implantable microspheres labeled with (90)Y into the arteries that feed liver tumors in order to provide a high dose of radiation to tumor nodules irrespective of their number, size and location, while preserving the non-tumoral liver tissue from receiving a harmful level of radiation. Among patients with HCC, (90)Y-RE is used for those that have a preserved liver function and unresectable tumors that cannot be treated with percutaneous ablation. Although (90)Y-RE is by and large well tolerated, it may produce relevant toxic effects as a result of radiation of non-target organs including cholecystitis, gastrointestinal ulceration, pneumonitis, and most importantly, liver toxicity. A significant effect on tumor growth in the treated lesions is consistently observed with disease control rates in excess of 80%. Also, (90)Y-RE may allow downstaging large or multiple lesions to radical treatments with curative intent. When compared with the survival of HCC patients in advanced stage either not treated or treated with ineffective systemic agents, survival after (90)Y-RE is encouraging and warrants future clinical trials. Clinical research in combining the cytotoxic effect of (90)Y with the cytostatic mechanism of targeted therapies is currently in progress and will provide valuable safety and toxicity data that may translate into improved clinical outcome and overall survival.

[Usefulness of PET scans in diagnosing recurrent prostate cancer. Prostate with PSA level < 5 ng/ml]. / Valor de la PET en la recurrencia del cáncer de próstata con PSA < 5 ng/ml.

INTRODUCTION AND OBJECTIVES: We intend to evaluate the usefulness of PET scans in diagnosing recurrent prostate cancer after a curative attempt using radical treatment. MATERIAL AND METHODS: 92 consecutive prostate cancer patients in biochemical progression following radical surgery (63) or radiation treatment (29) were studied with positron emission tomography (PET). In all cases two scans were performed in the same day (11C-choline and 18F-FDG). PET efficacy was evaluated both globally (by employing the results achieved with both 11C-choline and 18F-FDG) and using both radiotracers independently to detect recurrence in patients with biochemical progression. For this purpose, we used comparison of means for k-independent samples, 2 x 2 and 2 x X contingency tables and ROC curves. RESULTS: 1. Global PET: there is evidence of PET alteration regarding the PSA level (P=.003): the clinical stage (P=.01). There are no statistically significant PET alterations regarding the affected biopsy (uni or bilateral), surgical margins, pathological stage and time to progression. ROC curve PET-PSA is statistically significant (P< .0001) permitting calculation of different cut-off points, with a specificity of 91% (highest) for a PSA of 4.3 ng/ml. 2. PET 18FDG: the area under the ROC curve is statistically significant (P< .0001) with a specificity of 91% for a PSA of 6.51 ng/ml. 3. PET 11choline: the area under the ROC curve is statistically significant (P< .0001) with a specificity of 91% for a PSA of 5.15 ng/ml. CONCLUSIONS: PET is a useful tool for diagnosing prostate cancer recurrence after a curative attempt using radical treatment.