Utility of the Khorana and the new-Vienna CATS prediction scores in cancer patients of the HYPERCAN cohort.

BACKGROUND: Risk assessment models (RAMs) are relevant approaches to identify cancer outpatients at high risk of venous thromboembolism (VTE). Among the proposed RAMs, the Khorana (KRS) and the new-Vienna CATS risk scores have been externally validated in ambulatory patients with cancer. OBJECTIVES: To test KRS and new-Vienna CATS scores in 6-month VTE prediction and mortality in a large prospective cohort of metastatic cancer outpatients during chemotherapy. PATIENTS/METHODS: Newly diagnosed patients with metastatic non-small cell lung, colorectal, gastric, or breast cancers were analyzed (n = 1286). The cumulative incidence of objectively confirmed VTE was estimated with death as a competing risk and multivariate Fine and Gray regression. RESULTS: Within 6 months, 120 VTE events (9.7%) occurred. The KRS and the new-Vienna CATS scores showed comparable c-stat. Stratification by KRS provided VTE cumulative incidences of 6.2%, 11.4%, and 11.5% in the low-, intermediate-, and high-risk categories, respectively (p = ns), and of 8.5% vs. 11.8% (p = ns) in the low- vs. high-risk group by the single 2-point cut-off value stratification. Using a pre-defined 60-point cut-off by the new-Vienna CATS score, 6.6% and 12.2% cumulative incidences were obtained in the low- and high-risk groups, respectively (p < 0.001). Furthermore, having a KRS ≥2 = or a new-Vienna CATS score >60 points was also an independent risk factor for mortality. CONCLUSION: In our cohort, the 2 RAMs showed a comparable discriminating potential; however, after the application of cut-off values, the new-Vienna CATS score provided statistically significant stratification for VTE. Both RAMs proved to be effective in identifying patients at increased risk of mortality.

Approaches in Sustainable, Biobased Multilayer Packaging Solutions.

The depletion of fossil resources and the growing demand for plastic waste reduction has put industries and academic researchers under pressure to develop increasingly sustainable packaging solutions that are both functional and circularly designed. In this review, we provide an overview of the fundamentals and recent advances in biobased packaging materials, including new materials and techniques for their modification as well as their end-of-life scenarios. We also discuss the composition and modification of biobased films and multilayer structures, with particular attention to readily available drop-in solutions, as well as coating techniques. Moreover, we discuss end-of-life factors, including sorting systems, detection methods, composting options, and recycling and upcycling possibilities. Finally, regulatory aspects are pointed out for each application scenario and end-of-life option. Moreover, we discuss the human factor in terms of consumer perception and acceptance of upcycling.

COVID-19: Has the Liver Been Spared?

The liver is a secondary and often collateral target of COVID-19 disease but can lead to important consequences. COVID-19 might directly cause a high number of complications in patients with pre-existing chronic liver disease, increasing their risk of hepatic decompensation. Moreover, it also determines indirect consequences in the management of patients with liver disease, especially in those suffering from decompensated cirrhosis and HCC, as well as in the execution of their follow-up and the availability of all therapeutic possibilities. Liver imaging in COVID-19 patients proved to be highly nonspecific, but it can still be useful for identifying the complications that derive from the infection. Moreover, the recent implementation of telemedicine constitutes a possible solution to both the physical distancing and the re-organizational difficulties arising from the pandemic. The present review aims to encompass the currently hypothesized pathophysiological mechanisms of liver injury in patients with COVID-19 mediated by both the direct invasion of the virus and its indirect effects and analyze the consequence of the pandemic in patients with chronic liver disease and liver tumors, with particular regard to the management strategies that have been implemented to face this worldwide emergency and that can be further improved.

Nanoparticles of Lignins and Saccharides from Fishery Wastes as Sustainable UV-Shielding, Antioxidant, and Antimicrobial Biofillers.

Lignin nanoparticles containing saccharides from fishery wastes were prepared as sustainable biofillers for advanced materials. Organosolv lignin and Kraft lignin were used as polyphenol components in association with chitosan and chitooligosaccharides. The chemophysical and biological activities of lignin/saccharide nanoparticles, such as UV-shielding, antioxidant, and antimicrobial activities, were found to be dependent on both molecular weight and deacetylation degree of saccharides, with the best performance being obtained in the presence of low-molecular-weight and highly deacetylated chitooligosaccharides. In addition, chitooligosaccharides showed a synergistic antioxidant effect with lignins, associated with antimicrobial activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive).

Is there a bias in patient choices for hospital care? Evidence from three Italian regional health systems.

Patients choice is at the core of competition in hospital care. In spite of a flourishing literature, little is known about the true process leading patients to choose a specific provider. Most models in this literature assume - without testing - that hospitals are perceived to be homogeneous providers. In this article we take a different direction. We assume that patients have a bias towards some types of hospitals, we test this hypothesis and show which attributes determine this bias. We exploit the characteristic of Italian health care organization, where devolution has allowed regional systems to choose the level of competition and the private-public hospitals mix. We estimate conditional logit models for hip replacement admissions in three regions (Lombardy, Veneto, and Emilia-Romagna) over the period 2014- 2016. We show that, depending on the competition framework (peculiar to each region) patients are aware that some hospitals are best performers in their area and are willing to travel more to be admitted there. This is particularly true for regional health care systems where competition between public and private providers is well developed. Our model provides interesting policy implications: a) the idea that hospitals are different in patients perception should be kept in mind in the architecture of the market for hospital care; b) clinical quality as a driver to patients choice seems to work better in a less regulated competition settings.

MRI Features and Clinical Significance of Spinal Epidural Lipomatosis: All You Should Know.

Spinal epidural lipomatosis (SEL) is defined as the abnormal accumulation of unencapsulated adipose tissue in the spinal epidural space. SEL can be asymptomatic or can cause a wide range of symptoms, the most common of which is neurogenic claudication. Several other neurological manifestations may also occur, above all myelopathy and radicular symptoms. The spinal level most frequently involved in patients with SEL is the lumbar one, followed by the thoracic one. Imaging plays a key role in the disease assessment. MRI is considered the most effective and sensitive modality for diagnosing and staging SEL. Anyway, also CT scan can diagnose SEL. The diagnosis may be incidental (in mild-moderate disease) or may be taken into account in cases with neurological symptoms (in moderate-severe disease). There are some recognized risk factors for SEL, the most common of which are exogenous steroid use and obesity. Recent studies have found an association between SEL and obesity, hyperlipidemia and liver fat deposition. As a matter of fact, SEL can be considered the spinal hallmark of metabolic syndrome. Risk factors control represents the initial treatment strategy in patients with SEL (e.g. weight loss, steroid therapy suspension). Surgical decompression may be required when conservative treatment fails or when the patient develops acute/severe neurological symptoms.

Proposal of standardization of every step of angiographic procedure in bleeding patients from pelvic trauma.

Trauma accounts for a third of the deaths in Western countries, exceeded only by cardiovascular disease and cancer. The high risk of massive bleeding, which depends not only on the type of fractures, but also on the severity of any associated parenchymal injuries, makes pelvic fractures one of the most life-threatening skeletal injuries, with a high mortality rate. Therefore, pelvic trauma represents an important condition to correctly and early recognize, manage, and treat. For this reason, a multidisciplinary approach involving trauma surgeons, orthopedic surgeons, emergency room physicians and interventional radiologists is needed to promptly manage the resuscitation of pelvic trauma patients and ensure the best outcomes, both in terms of time and costs. Over the years, the role of interventional radiology in the management of patient bleeding due to pelvic trauma has been increasing. However, the current guidelines on the management of these patients do not adequately reflect or address the varied nature of injuries faced by the interventional radiologist. In fact, in the therapeutic algorithm of these patients, after the word "ANGIO", there are no reports on the different possibilities that an interventional radiologist has to face during the procedure. Furthermore, variations exist in the techniques and materials for performing angioembolization in bleeding patients with pelvic trauma. Due to these differences, the outcomes differ among different published series. This article has the aim to review the recent literature on optimal imaging assessment and management of pelvic trauma, defining the role of the interventional radiologist within the multidisciplinary team, suggesting the introduction of common and unequivocal terminology in every step of the angiographic procedure. Moreover, according to these suggestions, the present paper tries to expand the previously drafted algorithm exploring the role of the interventional radiologist in pelvic trauma, especially given the multidisciplinary setting.

Homogentisic Acid and Gentisic Acid Biosynthesized Pyomelanin Mimics: Structural Characterization and Antioxidant Activity.

Pyomelanin mimics from homogentisic acid (HGA) and gentisic acid (GA) were biosynthesized by the oxidative enzyme T. versicolor laccase at physiological pH to obtain water soluble melanins. The pigments show brown-black color, broad band visible light absorption, a persistent paramagnetism and high antioxidant activity. The EPR approach shows that at least two different radical species are present in both cases, contributing to the paramagnetism of the samples. This achievement can also shed light on the composition of the ochronotic pigment in the Alkaptonuria disease. On the other hand, these soluble pyomelanin mimics, sharing physico-chemical properties with eumelanin, can represent a suitable alternative to replace the insoluble melanin pigment in biotechnological applications.

Standardization of conventional chemoembolization for hepatocellular carcinoma.

INTRODUCTION AND OBJECTIVES: Conventional transarterial chemoembolization (cTACE) has several limitations due to the lack of standardization. The aim of this study was to evaluate the chemical and physical characteristics and behaviors over time of emulsions for cTACE and to assess intra- and inter-operator variabilities in the preparation processes. MATERIALS AND METHODS: This in vitro study involved evaluation of emulsions for cTACE prepared using two methods: water-in-oil (WiO) and chemotherapeutic-in-oil (CiO). Three emulsions were prepared with each method and obtained after 20, 50, and 100 pumping exchanges. A drop from each final mixture was analyzed via light microscopy (time 1) and after 5, 10, 15, and 20min since the end of preparation. After 20min, all preparations were re-mixed and new drops were re-evaluated. The intra- and inter-operator variabilities were analyzed. RESULTS: The mean droplet diameter decreased non-significantly when the number of pumping exchanges increased and increased significantly over time for both WiO and CiO. The droplets returned to their initial diameters after re-mixing. There were no significant differences in the intra- and inter-operator variabilities (P>0.01). CONCLUSIONS: Any interventional radiologist, regardless of their experience, may prepare these emulsions. These data may represent a set of instructions to standardize cTACE.

A New Quantitative Classification of the Extrahepatic Biliary Tract Related to Cystic Duct Implantation.

BACKGROUND: Knowledge regarding biliary anatomy and its variations, including the cystic duct (CD), is important in the pre-surgical setting and for predicting biliary diseases. However, no large series has focused on CD evaluation using a quantitative analysis. The primary aim of this prospective study was to create a 'taxonomic' classification of CD anatomy in a large cohort of subjects who underwent magnetic resonance cholangiopancreatography (MRCP). The secondary aim was to evaluate the correlations between extrahepatic bile duct (EHBD) variants and biliary diseases. METHODS: We enrolled patients who underwent MRCP for different clinical indications from January 2017 to May 2019. Demographical, anatomical and clinical data were evaluated using statistical analyses, as appropriate. The anatomical assessment of EHBD was performed using the standard classification for CD in low, medium, and high insertions, and the lengths of CD to the duodenal papilla (DP), and EHBD was determined to conduct a new quantitative analysis. RESULTS: The final study population comprised 1004 subjects. A new classification for EHBD as per the percentile distribution of the ratio CDDP/EHBD was designed, and the following categories were obtained: type 1 (below the 25th percentile) for CDDP/EHBD ratio ≤ 50%; type 2 (25th to 75th percentile) for CDDP/EHBD ratio 51-75% and type 3 (above the 75th percentiles) for CDDP/EHBD ratio > 75%. Type 1 of the new classification of CD implantation was significantly superior in terms of the detection of low, medial and intra-pancreatic CD that was significantly correlated with a high risk of choledochal lithiasis in comparison with the standard classification (P < 0.001). CONCLUSIONS: The new classification of CD implantation enables identification of the vast majority of intra-pancreatic CDs that are correlated with a high risk of choledochal lithiasis in a single category (type 1) that is easy to identify using imaging.

Gastric Cancer Staging: Is It Time for Magnetic Resonance Imaging?

Gastric cancer (GC) is a common cancer worldwide. Its incidence and mortality vary depending on geographic area, with the highest rates in Asian countries, particularly in China, Japan, and South Korea. Accurate imaging staging has become crucial for the application of various treatment strategies, especially for curative treatments in early stages. Unfortunately, most GCs are still diagnosed at an advanced stage, with the peritoneum (61-80%), distant lymph nodes (44-50%), and liver (26-38%) as the most common metastatic locations. Metastatic disease is limited to the peritoneum in 58% of cases; in nonperitoneal distant metastases, the most involved GC metastasization site is the liver (82%). The eighth edition of the tumor-node-metastasis staging system is the most commonly used system for determining GC prognosis. Endoscopic ultrasonography, computed tomography, and 18-fluorideoxyglucose positron emission tomography are historically the most accurate imaging techniques for GC staging. However, studies have recently shown renewed interest in magnetic resonance imaging (MRI) as a useful tool in GC staging, especially for distant metastasis assessment. The technical improvement of diffusion-weighted imaging and the increasing use of hepatobiliary contrast agents have been shown to increase the diagnostic performance of MRI, particularly for detecting peritoneal and liver metastasis. However, no principal oncological guidelines have included the use of MRI as a first-line technique for distant metastasis evaluation during the GC staging process, such as the National Comprehensive Cancer Network Guidelines. This review analyzed the role of the principal imaging techniques in GC diagnosis and staging, focusing on the potential role of MRI, especially for assessing peritoneal and liver metastases.

Thrombin generation predicts early recurrence in breast cancer patients.

BACKGROUND: Cancer patients present with a hypercoagulable state often associated with poor disease prognosis. OBJECTIVES: This study aims to evaluate whether thrombin generation (TG), a global coagulation test, may be a useful tool to improve the identification of patients at high risk of early disease recurrence (ie, E-DR within 2 years) after breast cancer surgery. PATIENTS/METHODS: A cohort of 522 newly diagnosed patients with surgically resected high-risk breast cancer were enrolled in the ongoing prospective HYPERCAN study. TG potential was measured in plasma samples collected before starting systemic chemotherapy. Significant predictive hemostatic and clinic-pathological parameters were identified in the derivation cohort by Cox regression analysis. A risk prognostic score for E-DR was generated in the derivation and tested in the validation cohort. RESULTS: After a median observation period of 3.4 years, DR occurred in 51 patients, 28 of whom were E-DR. E-DR subjects presented with the highest TG values as compared to both late-DR (from 2 to 5 years) and no relapse subjects (P < .01). Multivariate analysis in the derivation cohort identified TG, mastectomy, triple negative and Luminal B HER2-neg molecular subtypes as significant independent predictors for E-DR, which were utilized to generate a risk assessment score. In the derivation and validation cohorts, E-DR rates were 2.3% and 0% in the low-risk, 10.1% and 6.3% in the intermediate-risk, and 18.2% and 16.7%, in the high-risk categories, respectively. CONCLUSIONS: Inclusion of TG in a risk-assessment model for E-DR significantly helps the identification of operated breast cancer patients at high risk of very early relapse.

Treatment of Combined Hepatocellular and Cholangiocarcinoma.

Combined hepatocellular and cholangiocarcinoma (HCC-CC) is a rare primary liver cancer. It is constituted by neoplastic cells of both hepatocellular and cholangiocellular derivation. Different histology types of HCC-CC have been reported, hinting at heterogeneous carcinogenic pathways leading to the development of this cancer. Due to its rarity and complexity, mixed HCC-CC is a scantly investigated condition with unmet needs and unsatisfactory outcomes. Surgery remains the preferred treatment in resectable patients. The risk of recurrence, however, is high, especially in comparison with other primary liver cancers such as hepatocellular carcinoma. In unresectable or recurring patients, the therapeutic options are challenging due to the dual nature of the neoplastic cells. Consequently, the odds of survival of patients with HCC-CC remains poor. We analysed the literature systematically about the treatment of mixed HCC-CC, reviewing the main therapeutic options and their outcomes and analysing the most interesting developments in this topic with a focus on new potential therapeutic avenues.

Diagnostic Accuracy of North America Expert Consensus Statement on Reporting CT Findings in Patients Suspected of Having COVID-19 Infection: An Italian Single-Center Experience.

PURPOSE: To evaluate the diagnostic accuracy of the four standardized categories for CT reporting proposed by the Radiological Society of North America (RSNA) to support a faster triage compared with real-time reverse-transcription polymerase chain reaction (RT-PCR), which is the reference standard for suspected coronavirus disease 2019 (COVID-19), but has long reporting time (6-48 hours). MATERIALS AND METHODS: A retrospective analysis of 569 thin-section CT examinations performed for patients suspected of having COVID-19 from February 27 to March 27, 2020 (peak of infection in Italy) was conducted. The imaging pattern was classified according to the statement by the RSNA as "typical," "indeterminate," "atypical," and "negative" and compared with RT-PCR for 460 patients. Interobserver variability in reporting between a senior and a junior radiologist was evaluated. Use of the vascular enlargement sign in indeterminate cases was also assessed. RESULTS: The diagnosis of COVID-19 was made in 45.9% (211/460) of patients. The "typical" pattern (n = 172) showed a sensitivity of 71.6%, a specificity of 91.6%, and a positive predictive value of 87.8% for COVID-19. The "atypical" (n = 67) and "negative" (n = 123) pattern demonstrated a positive predictive value of 89.6% and 86.2% for non-COVID-19, respectively. The "indeterminate" (n = 98) pattern was nonspecific, but vascular enlargement was most frequently found in patients with COVID-19 (86.1%; P < .001). Interobserver agreement was good for the "typical" and "negative" pattern and fair for "indeterminate" and "atypical" (κ = 0.5; P = .002). CONCLUSION: In an epidemic setting, the application of the four categories proposed by the RSNA provides a standardized diagnostic hypothesis, strongly linked to the RT-PCR results for the "typical," "atypical," and "negative" pattern. In the "indeterminate" pattern, the analysis of the vascular enlargement sign could facilitate the interpretation of imaging features.© RSNA, 2020.

Thrombotic biomarkers for risk prediction of malignant disease recurrence in patients with early stage breast cancer.

In cancer patients, hypercoagulability is a common finding. It has been associated with an increased risk of venous thromboembolism, but also to tumor proliferation and progression. In this prospective study of a large cohort of breast cancer patients, we aimed to evaluate whether pre-chemotherapy abnormalities in hemostatic biomarkers levels: (i) are associated with breast cancer-specific clinico-pathological features; and (ii) can predict for disease recurrence. D-dimer, fibrinogen, prothrombin fragment 1+2, and FVIIa/antithrombin levels were measured in 701 early-stage resected breast cancer patients candidate to adjuvant chemotherapy and prospectively enrolled in the HYPERCAN study. Significant prognostic parameters for disease recurrence were identified by Cox regression multivariate analysis and used for generating a risk assessment model. Pre-chemotherapy D-dimer, fibrinogen, and pro-thrombin fragment 1+2 levels were significantly associated with tumor size and lymph node metastasis. After 3.4 years of follow up, 71 patients experienced a recurrence. Cox multivariate analysis identified prothrombin fragment 1+2, tumor size, and Luminal B HER2-negative or triple negative molecular subtypes as independent risk factors for disease recurrence. Based on these variables, we generated a risk assessment model that significantly differentiated patients at low- and high-risk of recurrence (cumulative incidence: 6.2 vs 20.7%; Hazard Ratio=3.5; P<0.001). Our prospective clinical and laboratory data from the HYPERCAN study were crucial for generating a scoring model for assessing risk of disease recurrence in resected breast cancer patients, candidate to systemic chemotherapy. This finding stimulates future investigations addressing the role of plasma prothrombin fragment 1+2 in the management of breast cancer patients to provide the rationale for new therapeutic strategies. (The HYPERCAN study is registered at clinicaltrials.gov identifier 02622815).

Critical Factors for the Recycling of Different End-of-Life Materials: Wood Wastes, Automotive Shredded Residues, and Dismantled Wind Turbine Blades.

Different classes of wastes, namely wooden wastes, plastic fractions from automotive shredded residues, and glass fiber reinforced composite wastes obtained from dismantled wind turbines blades were analyzed in view of their possible recycling. Wooden wastes included municipal bulky wastes, construction and demolition wastes, and furniture wastes. The applied characterization protocol, based on Fourier transform infrared (FTIR) spectroscopy in attenuated total reflection (ATR) mode, scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM/EDX), and thermogravimetric analysis (TG) coupled with FTIR spectrometry for the investigation of the evolved gases, revealed that the selected classes of wastes are very complex and heterogeneous materials, containing different impurities that can represent serious obstacles toward their reuse/recycling. Critical parameters were analyzed and discussed, and recommendations were reported for a safe and sustainable recycling of these classes of materials.