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There is an established correlation between the PNPLA3 rs738409 C > G single nucleotide polymorphism (SNP) and hepatic steatosis and fibrosis in hepatitis C virus (HCV) infected patients. However not all data is convergent regarding the exact impact of this SNP on the pattern of disease progression in different clinical settings. In this study, we aimed to further bridge the knowledge gap on this topic by investigating the role of the G allele in promoting steatosis, fibrosis and disease progression in relation to other metabolic and anthropometric host factors. Two hundred and fifty consecutive patients, previously diagnosed with chronic hepatitis C (CHC) underwent liver biopsy. Histology was assessed using the Metavir scoring system. Transient elastography was used for follow-up. Ninety-eight patients were genotyped for PNPLA3 rs738409 and followed up for fibrosis progression. PNPLA3 rs738409[G] allele was significantly correlated with severe steatosis (P = 0.04), severe fibrosis at the time of enrollment (P = 0.0005) and fibrosis progression with an OR of 10.31 (95% CI 1.06 - 99.59, P = 0.04), after a mean follow-up time of 62.85 (95%CI: 52.21 - 76.15) months. Severe steatosis at the time of enrollment had an OR of 11.02 (95% CI 1.48 - 82.09, P = 0.01) for the association with fibrosis progression. The HOMA-IR index was also positively correlated with severe fibrosis (P = 0.03) and fibrosis progression on univariate analysis (P = 0.02). PNPLA3 rs738409[G] allele is a reliable predictor for steatosis and fibrosis in CHC. The presence of G allele, along with severe steatosis and insulin resistance are significant predictors for fibrosis progression. [ABSTRACT FROM AUTHOR]

Introduction: Liver represents the main place of drug metabolisation. Drugs and toxic substances reach the level of liver after absorption at gastro-intestinal level. Drug hepatotoxicity represents an important chapter of iatrogenic pathology, because the hepatic lesions induced by drugs include extremely diverse clinical, biological and histological expressions that can take the aspect of any form of acute or chronic hepatobiliary disease. Hepatic lesions induced by drugs (LHIM) represent a histological and/or biochemical alteration caused and attributed to the consumption of a drug. Hepatic elastography (Fibroscan) represents a noninvasive method of quantification of hepatic fibrosis. Material and method: We carried out a retrospective study and longitudinally prospective study that included a set of patients under treatment with Methotrexate, amounting to 76, divided into 2 subsets: a subset consisting of patients with hepatitis to Methotrexate, subset 1, of 23 patients, a subset of patients under treatment with Methotrexate but with normal hepatic samples, subset b, of 53 patients. Results: We carried out fibroscan at all the patients treated with Methotrexate, obtaining a medium score of fibrosis of 6.23 for the subset a with hepatitis at Methotrexate and of 5.33 for the subset b with normal hepatic samples. We made a correlation between the cumulated dose of Methotrexate and the change of hepatic samples. Conclusions: There is a significant correlation between hepatic fibrosis induced by Methotrexate and the cumulated dose of Methotrexate. The possibility of utilization of fibroscan which is a completely painless method, reproducible, for the monitoring of the treatment with Methotrexate both at patients with changed values of the hepatic tests as weir as those with normal values must be considered. [ABSTRACT FROM AUTHOR]

X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analyses have been used to characterize the structure of a La2O3-promoted MnOx/SiO2 catalyst, before and after its utilization in the oxidative dehydrogenation of ethylbenzene (EB). MnOx/SiO2 and MnOx/La2O3/SiO2 catalysts were prepared by pore volume impregnation, using aqueous solutions of (i) La3+-nitrate at an atomic ratio of La/Si = 0.08, and (ii) Mn2+-nitrate at an atomic ratio of Mn/Si = 0.10, followed by drying and calcination at 500°C in air. XRD data show no diffraction patterns specific to MnOx on the La2O3-promoted MnOx/SiO2 catalyst, after calcination. Thus, the presence of La2O3 apparently favors the dispersion of manganese oxides during calcination, presumably by forming mixed Mn-La oxides. On the fresh promoted and unpromoted catalysts, after calcination, XRD and XPS analyses indicated that Mn was present mostly as MnO2 and Mn2O3. In the used catalyst, Mn from the unpromoted catalyst degenerated from Mn4+ to Mn2+, resulting in formation of Mn3O4 species, whereas in the case of La2O3-promoted catalyst Mn remained well dispersed as MnO2 and Mn2O3. It appears that La2O3 precludes the formation of Mn3O4 during the EB dehydrogenation, conserving Mn structure and oxidation state. [ABSTRACT FROM AUTHOR]

Abstract: We report a new synthesis and characterization of Ir(C2H4)2(C5H7O2) [(acetylacetonato)-bis(η2-ethene)iridium(I)], prepared from (NH4)3IrCl6 ·H2O in a yield of about 45%. The compound has been characterized by X-ray diffraction crystallography, infrared, Raman, and NMR spectroscopies and calculations at the level of density functional theory. Ir(C2H4)2(C5H7O2) is isostructural with Rh(C2H4)2(C5H7O2), but there is a substantial difference in the ethylene binding energies, with Ir–ethylene having a stronger interaction than Rh–ethylene; two ethylenes are bound to Ir with a binding energy of 94kcal/mol and to Rh with a binding energy of 70kcal/mol. [Copyright &y& Elsevier]

The ligand binding energies (LBEs) of N -heterocyclic carbenes (NHCs) and CH 2 and CF 2 adducts with group 1, 2, 10, and 11 metals and complexes with metals from these groups are predicted at the coupled cluster CCSD(T) level of theory by using density functional theory optimized geometries. The differences in LBEs as a function of the metal and the types of bonding interactions as well as the type of carbene are described. The bonding between the alkali cations and alkaline earth dications is predominantly ionic with a linear correlation between the LBEs and the cation hardness. In contrast, the bonding behaviors of the group 10 and 11 metals and metal complexes have only a weak, indirect correlation between the LBEs and the metal hardness. The difference in bonding behavior between the groups of metals arises due to the accessibility of electron donation between the ligand and the metal in the transition metal complexes, which results in more covalent-like bonding behavior. The presence of the methyl groups on the NHC nitrogen results in only slightly more delocalized charge from the metal onto the ring, but there is significant redistribution of the charge on the ring. Saturation of the NHC ring had a much smaller effect on how the charge was distributed on the ring. The analysis of the bonding behavior of NHCs with various metal groups enables improved understanding of carbene-metal interactions to inform rational design of NHC-based systems.

Cholangiocarcinoma, the second most common liver malignancy, after hepatocarcinoma is highly aggressive and usually diagnosed in advanced cases. In the era of personalized medicine, targeted therapy protocols are limited for cholangiocarcinoma and the only potential curative treatment, surgical resection, is seldom applicable.This retrospective study included all cases with pathology-confirmed intrahepatic cholangiocarcinoma admitted in a tertiary healthcare facility during a 10-year timeframe. Clinical information, laboratory values, imaging studies, and survival data were retrieved, and PD-L1 immunostaining was performed on representative pathology slides, for each case. From the total of 136 included cases (49 surgical resections and 87 liver biopsies), 38.97% showed PD-L1 positivity on tumoral cells, 34.8% on tumor infiltrating immune cells, 10.11% on epithelial cells within the peritumoral area and 15.95% on immune cells from the peritumoral area. Overall survival was significantly higher in the first two scenarios. However, after adjusting for age, tumor number, tumor size, and tumor differentiation in a multivariate analysis, only PD-L1 positivity on tumor infiltrating immune cells remained a favorable prognostic for survival. High immune cell counts also correlated with increased overall survival.Our study demonstrated that PD-1/PD-L1 checkpoint pathway in the microenvironment of intrahepatic cholangiocarcinoma bears prognostic significance. PD-L1 expression on immune cells, in both resection and biopsy specimens, might be a strong independent predictor for a favorable outcome., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The systemic nature of cirrhosis and portal hypertension has long been recognized, and the amount of data characterizing the interplay between each system is becoming ever so complex. Lung involvement was among the first described associated entities in cirrhosis, with reports dating back to the late nineteenth century. However, it appears that throughout the years, interest in the pulmonary complications of portal hypertension has generally faded, especially in contrast to other decompensating events, as expertise in this field has primarily been concentrated in highly experienced tertiary care facilities and liver transplantation centers. Despite affecting up to 10%-15% of patients with advanced liver disease and having a proven prognostic impact, hepato-pulmonary syndrome, porto-pulmonary hypertension, and hepatic hydrothorax are frequently misdiagnosed, mistreated, or misinterpreted. This lack of precision might adversely impact patient care, referral to expert centers, and, ultimately, liver disease-related mortality and successful transplantation odds. The present minireview aims to increase awareness of the pulmonary complications of chronic liver disease by providing a brief overview of each of the three entities. The paper focuses on the essential theoretical aspects, addressing the most critical knowledge gaps on the one hand and, on the other hand, critically discussing one key issue for each complication., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest regarding the contents of the current manuscript., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Malnutrition predicts a worse outcome for critically ill patients. However, quick, easy-to-use nutritional risk assessment tools have not been adequately validated., Aims and Methods: The study aimed to evaluate the role of four biological nutritional risk assessment instruments (the Prognostic Nutritional Index-PNI, the Controlling Nutritional Status Score-CONUT, the Nutrition Risk in Critically Ill-NUTRIC, and the modified NUTRIC-mNUTRIC), along with CT-derived fat tissue and muscle mass measurements in predicting in-hospital mortality in a consecutive series of 90 patients hospitalized in the intensive care unit for COVID-19-associated ARDS., Results: In-hospital mortality was 46.7% ( n = 42/90). Non-survivors had a significantly higher nutritional risk, as expressed by all four scores. All scores were independent predictors of mortality on the multivariate regression models. PNI had the best discriminative capabilities for mortality, with an area under the curve (AUC) of 0.77 for a cut-off value of 28.05. All scores had an AUC above 0.72. The volume of fat tissue and muscle mass were not associated with increased mortality risk., Conclusions: PNI, CONUT, NUTRIC, and mNUTRIC are valuable nutritional risk assessment tools that can accurately predict mortality in critically ill patients with COVID-19-associated ARDS.

A range of carbene structures and their adducts with one another and with a selection of small-molecule electrophiles and nucleophiles were examined at the composite correlated molecular orbital theory G3MP2 level to explore ground-state "carbenic" structures, their stabilities, and reactivities. Differences between carbene general classification as a singlet electrophilic carbene or singlet nucleophilic carbene and their given reactivity are discussed. A key quantity is the carbon-carbon bond dissociation energy for carbene dimers or the carbene-adduct dissociation energy for other species. The carbene dimer bond dissociation energies span a wide range from 10 to 170 kcal/mol. The hydrogenation energies and singlet-triplet splitting were found to correlate best with the carbene's self-dimerization energy, whereas other descriptors do not. The proton and fluoride affinities of the carbenes alone prove inadequate for classifying reactivity among classes of carbenes. The self-dimerization bond dissociation energy, hydrogenation energy, and singlet-triplet splitting of various carbenes, despite sometimes large differences in proton affinity and other indicators of reactivity, provide usable metrics to correlate substantial amounts of thermodynamic and kinetic (reactivity) information regarding these structures.

The use of contrast-enhanced ultrasonography (CEUS) has recently become synonymous with high-standard ultrasonography (US). From expanding the reach of US diagnostics to improving the precision of various invasive procedures, CEUS is rapidly becoming a standard in numerous niches. However, proficiency in CEUS comes with a cost, both from a learning curve and material standpoint, and as every growing field, lacks firm evidence and standardization. Therefore, in the current paper, we aim to provide an evidence-based review of available methods and to discuss the advantages and pitfalls of CEUS in interventional procedures, trying to provide strong evidence whenever available, or at least an educated expert opinion if data are lacking.

Liver involvement in Coronavirus Disease 2019 (COVID-19) has been widely documented. However, data regarding liver-related prognosis are scarce and heterogeneous. The current study aims to evaluate the role of abnormal liver tests and incidental elevations of non-invasive fibrosis estimators on the prognosis of hospitalized COVID-19 patients. We conducted a retrospective cohort study to investigate the impact of elevated liver tests, non-invasive fibrosis estimators (the Fibrosis-4 (FIB-4), Forns, APRI scores, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio), and the presence of computed tomography (CT)-documented liver steatosis on mortality in patients with moderate and severe COVID-19, with no prior liver disease history. A total of 370 consecutive patients were included, of which 289 patients (72.9%) had abnormal liver biochemistry on admission. Non-survivors had significantly higher FIB-4, Forns, APRI scores, and a higher AST/ALT ratio. On multivariate analysis, severe FIB-4 (exceeding 3.25) and elevated AST were independently associated with mortality. Severe FIB-4 had an area under the receiver operating characteristic (AUROC) of 0.73 for predicting survival. The presence of steatosis was not associated with a worse outcome. Patients with abnormal liver biochemistry on arrival might be susceptible to a worse disease outcome. An FIB-4 score above the threshold of 3.25, suggestive of the presence of fibrosis, is associated with higher mortality in hospitalized COVID-19 patients.

Hilar cholangiocarcinoma (hCCA) is a primary liver tumor associated with a dim prognosis. The role of preoperative and palliative biliary drainage has long been debated. The most common techniques are endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD); however, recently developed endoscopic ultrasound-assisted methods are gaining more atention. Selecting the best available method in any specific scenario is crucial, yet sometimes challenging. Thus, this review aimed to discuss the available techniques, indications, perks, pitfalls, and timing-related issues in the management of hCCA. In a preoperative setting, PTBD appears to have some advantages: low risk of postprocedural complications (namely cholangitis) and better priming for surgery. For palliative purposes, we propose ERCP/PTBD depending on the experience of the operators, but also on other factors: the level of bilirubin (if very high, rather PTBD), length of the stenosis and the presence of cholangitis (PTBD), ERCP failure, or altered biliary anatomy., Competing Interests: Conflict-of-interest statement: The authors have nothing to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The time for battling cancer has never been more suitable than nowadays and fortunately against hepatocellular carcinoma (HCC) we do have a far-reaching arsenal. Moreover, because liver cancer comprises a plethora of stages-from very early to advanced disease and with many treatment options-from surgery to immunotherapy trials-it leaves the clinician a wide range of options. The scope of our review is to throw light on combination treatments that seem to be beyond guidelines and to highlight these using evidence-based analysis of the most frequently used combination therapies, discussing their advantages and flaws in comparison to the current standard of care. One particular combination therapy seems to be in the forefront: Transarterial chemoembolization plus ablation for medium-size non-resectable HCC (3-5 cm), which is currently at the frontier between Barcelona Clinic Liver Cancer classification A and B. Not only does it improve the outcome in contrast to each individual therapy, but it also seems to have similar results to surgery. Also, the abundance of immune checkpoint inhibitors that have appeared lately in clinical trials are bringing promising results against HCC. Although the path of combination therapies in HCC is still filled with uncertainty and caveats, in the following years the hepatology and oncology fields could witness an HCC guideline revolution., Competing Interests: Conflict-of-interest statement: Jean-François Dufour: Advisory committees: Abbvie, Bayer, BMS, Falk, Genfit, Genkyotex, Gilead Science, HepaRegenix, Intercept, Lilly, Merck, Novartis. Speaking and teaching: Abbvie, Bayer, BMS, Genfit, Gilead Science, Novartis., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Hepatic hydrothorax (HH) is an understudied complication of decompensated cirrhosis. We aimed to evaluate the long-term prognosis of patients with HH by comparing them with a matched non-HH group. Methods: This retrospective study included 763 consecutive patients hospitalized for decompensated cirrhosis and ascites. Ninety-seven patients with HH were matched for survival analysis with non-HH patients based on liver disease severity. Results: The prevalence of HH was 13.1%. Patients with HH had significantly worse overall liver function. Upon matching, patients with HH had a lower long-term survival (15.4% vs. 30.9% at 5 years) with a mean overall survival of 22.2 ± 2.2 months for the HH group vs. 27.1 ± 2.6 months for the non-HH group (Log Rank-0.05). On multivariate survival analysis using Cox regression, the MELD-Na score, ALBI grade, hepato-renal syndrome, and grade III ascites had a significant impact on mortality in patients with HH. In patients with HH, a MELD-Na score ≥ 16, ALBI grade III, hepato-renal syndrome, or severe ascites delineated high-mortality risk groups. Conclusions: HH is consistently associated with more advanced liver disease. Patients with HH have worse long-term survival, their prognosis being closely intertwined with overlapping decompensating events.

Hemostasis is a complex physiological process based on the balance between pro-coagulant and anticoagulant systems to avoid pathological bleeding or thrombosis. The changes in standard coagulation tests in liver disease were assumed to reflect an acquired bleeding disorder, and cirrhotic patients were considered naturally anticoagulated. In the light of the new evidence, the theory of rebalanced hemostasis replaced the old concept. According to this model, the hemostatic alteration leads to a unique balance between pro-coagulant, anticoagulant, and fibrinolytic systems. But the balance is fragile and may prone to bleeding or thrombosis depending on various risk factors. The standard coagulation tests [INR (international normalized ratio), platelet count and fibrinogen] only explore parts of the hemostasis, not offering an entire image of the process. Rotational thromboelastometry (ROTEM) and thromboelastography (TEG) are both point of care viscoelastic tests (VET) that provide real-time and dynamic information about the entire hemostasis process, including clot initiation (thrombin generation), clot kinetics, clot strength, and clot stability (lysis). Despite prolonged PT/INR (international normalized ratio of prothrombin time) and low platelet counts, VET is within the normal range in many patients with both acute and chronic liver disease. However, bleeding remains the dominant clinical issue in patients with liver diseases, especially when invasive interventions are required. VET has been shown to asses more appropriately the risk of bleeding than conventional laboratory tests, leading to decrial use of blood products transfusion. Inappropriate clotting is common but often subtle and may be challenging to predict even with the help of VET. Although VET has shown its benefit, more studies are needed to establish cut-off values for TEG and ROTEM in these populations and standardization of transfusion guidelines before invasive interventions in cirrhotic patients/orthotopic liver transplantation., Competing Interests: Conflict-of-interest statement: The authors have no other disclosures., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: There have been great advances in hepatocellular carcinoma management over the last years. However, there are still no prognostic biomarkers that can identify patients who will benefit the most from curative treatments. We aimed to investigate whether sPD-L1 levels measured before curative treatment is a prognostic biomarker of survival in patients with HCC., Methods: HCC patients from a prospectively collected database were selected and soluble programmed death-ligand1(sPD-L1) levels were determined. The association of sPD-L1 levels and overall survival (OS) and disease-free survival (DFS) was assessed., Results: One hundred twenty-one patients with HCC were included. The best cut-off value of sPD-L1 for both DFS and OS was 96 pg/mL. Patients with a high sPD-L1 value (>96 pg/mL) had a shorter disease free survival and OS (hazard ratio 5.42, 95% confidence interval 2.28-12.91, p < 0.001, and hazard ratio 9.67, 95% confidence interval 4.33-21.59, p < 0.001). High sPD-L1 levels were associated with mortality independently from other known survival predictors. We found a positive correlation between sPD-L1 and PD-L1 expression in cancer cells (p = 0.01). In 16 out of 38 patients, sPD-L1 levels decreased from baseline value on week 6 after treatment and in 22 out of 38 patients, sPD-L1 levels increased from the baseline value. However, fluctuations of sPD-L1 in time had no influence on survival (p = 0.148)., Conclusion: We conclude that a high sPD-L1 level is a biomarkerfor a poor outcome in HCC. The predictive value of sPD-L1 levels for a successful anti-PD1/PD-L1 therapy should be investigated in the future., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) is probably the epitome of a screening target, with a well-defined high-risk population, accessible screening methods, and multiple curative-intent treatments available for early disease. Per major societies guideline consensus, biannual ultrasound (US) surveillance of the at-risk patients is the current standard of care worldwide. Yet, despite its documented success in the past decades, this standard is far from perfect. While the whole community is working to further tighten the knots, a worrying number of cases still slip through this safety net. Consequently, these patients lose their chance to a curative solution which leads to a high disease burden with disproportionate mortality. While US will probably remain the fundamental staple in the screening strategy, key questions are seeking better answers. How can its caveats be addressed, and the technique be improved? When are further steps needed? How to increase accuracy without giving up on accessibility? This narrative review discusses the place of US surveillance in the bigger HCC picture, trying to navigate through its strengths and limits based on the most recent available evidence., Competing Interests: The authors declare no conflict of interest.

As colorectal cancer (CRC) is one of the forms of cancer with the highest prevalence globally and with a high mortality, screening and early detection remains a major issue. Colonoscopy is still the gold standard for detecting premalignant lesions, but it is burdened by some complications. For instance, it is laborious, with some difficulties of acceptance for some patients, and is ultimately an imperfect standard, given that some premalignant lesions or incipient malignancies can be missed by colonoscopic evaluation. In this context, new non-invasive approaches such as surface-enhanced Raman spectroscopy (SERS) based liquid biopsy have gained ground in recent years, showing promising results in oncological pathology diagnosis. These new methods have enabled the detection of subtle molecular profile alterations prior to any macroscopic morphological changes, thus providing a useful tool for early CRC detection. In the present review, we provide a summary of published studies applying SERS in CRC detection, along with our personal experience in using SERS in the diagnosis of different oncological pathologies, including CRC., (Copyright © 2020, Spandidos Publications.)

Background: Malnutrition is frequently encountered in patients with cirrhosis and appears to significantly impact their prognosis. While evaluating the burden of malnutrition in cirrhosis is gathering momentum, as suggested by multiple recently published reports, there is still a persistent scarcity of solid data in the field, especially with regards to the role of nutritional interventions., Aim: To assess the prevalence of malnutrition in patients with advanced cirrhosis and to evaluate its impact on survival., Methods: One hundred and one consecutive patients with advanced cirrhosis were screened for malnutrition using the Subjective Global Assessment (SGA) criteria and the mid-arm circumference (MAC). Malnutrition was defined as SGA class B and C and MAC < 10 th percentile. All patients were interviewed regarding their food intake using an adapted questionnaire. Subsequently, total energy intake was calculated and further subdivided in main nutrients. The data were then compared to the available recommendations at the time of analysis to assess adherence., Results: 54/79 patients (68.4%) in the decompensated group had malnutrition, while only 3/22 patients (13.6%) were malnourished in the compensated group. After a median follow-up time of 27 mo (0-53), the overall mortality was 70%. Survival was significantly lower among patients with malnutrition. The mortality rates were 50% at 1 year and 63% at 2 years for the patients with malnutrition, compared to 21% at 1 year and 30% at 2 years for patients without malnutrition ( P = 0.01). On multivariate analysis, the factors independently associated with mortality were age, creatinine level and adherence to the protein intake recommendations. The mortality was lower in patients with the appropriate protein intake: 8% at 1 year and 28% at 2 years in the adherent group, compared to 47% at 1 year and 56% at 2 years in the non-adherent group., Conclusion: The prevalence of malnutrition is high among patients with advanced cirrhosis and might be related in part to a low adherence to nutritional recommendations, especially with regards to protein intake., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: The link between the pro-inflammatory status, tumor aggressiveness and treatment response has been well established in multiple cancers. Various hematologic and biochemical variables representing surrogates for inflammation have been used as predictive markers. Our primary aim was to assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in evaluating neoadjuvant treatment response in locally advanced rectal cancer (LARC)., Methods: We included 60 consecutive patients with LARC, admitted for surgery, after completing a standard full-course neoadjuvant radio-chemotherapy regimen. NLR and other hematologic parameters were collected one day prior to surgery. Treatment response was assessed on the resection specimens., Results: On univariate analysis, poor responders had a significantly higher NLR value when compared with good responders: 5.81 (5.40-7.28) vs. 3.51 (2.36-4.04), p<0.0001. NLR retained its significance on multivariate analysis, with an OR of 3.51 (1.54-6.57), p=0.001. A NLR cut-off value of 4.50 had the best predictive value for poor response, with an area under the curve (AUC) of 0.85, sensitivity of 83.3% and specificity of 83.3% (p<0.001). Other hematologic ratios, such as the derived NLR (dNLR) and platelet-to-lymphocyte ratio (PLR) were also significant predictors for poor response, although to a lesser extent when compared to NLR., Conclusion: NLR is a simple and cost-effective predictor for neoadjuvant treatment response in LARC. As more data is generated, clear cut-off values could provide valuable insight regarding the management of LARC.

Early diagnosis based on screening is recognized as one of the most efficient ways of mitigating cancer-associated morbidity and mortality. Therefore, reliable but cost-effective methodologies are needed. By using a portable Raman spectrometer, a small and easily transportable instrument, the needs of modern diagnosis in terms of rapidity, ease of use and flexibility are met. In this study, we analyzed the diagnostic accuracy yielded by the surface-enhanced Raman scattering (SERS)-based profiling of serum, performed with a portable Raman device operating in a real-life hospital environment, in the case of 53 patients with gastrointestinal tumors and 25 control subjects. The SERS spectra of serum displayed intense bands attributed to carotenoids and purine metabolites such as uric acid, xanthine and hypoxanthine, with different intensities between the cancer and control groups. Based on principal component analysis-quadratic discriminant analysis (PCA-QDA), the cancer and control groups were classified with an accuracy of 76.92%. By combining SERS spectra with general inflammatory markers such as C-reactive protein levels, neutrophil counts, platelet counts and hemoglobin levels, the discrimination accuracy was increased to 83.33%. This study highlights the potential of SERS-based liquid biopsy for the point-of-care diagnosis of gastrointestinal tumors using a portable Raman device operating in a clinical setting.

Aim: Percutaneous radiofrequency (RFA) and microwave ablation (MWA) are currently the best treatment options forpatients with liver metastases (LM) who cannot undergo a liver resection procedure. Presently, few studies have evaluated theefficacy of tumor ablation in beginner's hands but none at all in hepatic metastasis. Our aim was to report the initial experiencewith ultrasound as a tool to guide tumor ablation in a low volume center with no experience in tumor ablation., Material and Methods: We conducted a retrospective cohort study, on a series of 61 patients who had undergone percutaneous US-guided ablations for 82 LM between 2010 and 2015. Long term outcome predictors were assessed using univariate and multivariate analysis., Results: Complete ablation was achieved in 86.9% of cases (53/61). All MWA sessions (20/20) attained ablation margins >5mm, compared to 79% (49/62) for RFA sessions (p=0.031). Ablation time was significantly shorter for MWA, with a median duration of 10 minutes (range: 6-12) vs. 14 minutes (range: 10-19.5, p=0.003). There was no statistically significant difference in local tumor progression (LTP)-free survival rates between MWA and RFA (p=0.154). On univariate analysis, significant predictors for local recurrence were multiple metastases (p=0.013) and ablation margins <5 mm (p<.001), both retaining significance on multivariate analysis. Significant predictors for distant recurrence on both univariate and multivariate analysis were multiple metastases (p<0.001) and non-colorectal cancer metastases (p<0.05)., Conclusion: A larger than 5 mm ablation size is critical for local tumor control. We favor the use of MWA due to its ability to achieve ablation in significantlyshorter times with less incomplete ablations.

Posterior reversible encephalopathy syndrome (PRES) has been associated with many conditions - particularly inflammatory, neoplastic and following organ failure. We submit that Chronic Obstructive Pulmonary Disease (COPD) is a significant predisposing factor for a number of these cases. Increased levels of circulating TNF-alpha, IL-1 and endothelin-1 (ET-1) are herein proposed as key mediators of this association. This theory builds on the central role of endothelial dysfunction in the pathogenesis of PRES. To our knowledge, no association of PRES and COPD has been made to date. We believe that it has practical implications: it suggests a lower threshold for MRI scans in certain patients. We suggest that the diagnosis of PRES should particularly be considered in ICU patients with typical signs (seizures, blindness, encephalopathy). Prompt recognition may lead to changes in management., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The Pd-L ligand bond dissociation energies (BDEs) of cis- and trans-[L-Pd(PH(3))(2)Cl](+) were predicted using coupled cluster CCSD(T) theory and a variety of density functional theory (DFT) functionals at the B3LYP optimized geometries. trans-[L-Pd(PH(3))(2)Cl](+) is the more stable isomer when Pd forms a donor-acceptor bond with a C atom of the ligand, including the π-bond in norbornene; for the remaining complexes, the cis-[L-Pd(PH(3))(2)Cl](+) isomer is substantially lower in energy. For cis-[L-Pd (PH(3))(2)Cl](+) complexes, the Pd-L bond energies are 28 kcal/mol for CO; ∼40 kcal/mol for AH(3) (A = N, P, As, and Sb), norbornene, and CH(3)CN; and ∼53 kcal/mol for CH(3)NC, pyrazole, pyridine, and tetrahydrothiophene at the CCSD(T) level. When Pd forms a donor-acceptor bond with the C atom in the ligand (i.e., CO, CH(3)NC, and the π-bond in norbornene), the Pd-L bond energies for trans-[L-Pd(PH(3))(2)Cl](+) are generally ∼10 kcal/mol greater than those for cis-[L-Pd(PH(3))(2)Cl](+) with the same L; for the remaining ligands, the ligand bond energy increases are ∼3-5 kcal/mol from the cis-isomer to the trans-isomer. The benchmarks show that the dispersion-corrected hybrid, generalized gradient approximation, DFT functional ω-B97X-D is the best one to use for this system. Use of the ω-B97X-D/aD functional gives predicted BDEs within 1 kcal/mol of the CCSD(T)/aug-cc-pVTZ BDEs for cis-[L-Pd(PH(3))(2)Cl](+) and 1.5 kcal/mol for trans-[L-Pd(PH(3))(2)Cl](+).

High-level electronic structure calculations were used to evaluate reliable, self-consistent thermochemical data sets for the second row transition metal hexafluorides. The electron affinities, heats of formation, first (MF(6) --> MF(5) + F) and average M-F bond dissociation energies, and fluoride affinities of MF(6) (MF(6) + F(-) --> MF(7)(-)) and MF(5) (MF(5) + F(-) --> MF(6)(-)) were calculated. The electron affinities are higher than those of the corresponding third row hexafluorides, making them stronger one-electron oxidizers. The calculated electron affinities, in good agreement with the available experimental values, are 4.23 eV for MoF(6), 5.89 eV for TcF(6), 7.01 eV for RuF(6), 6.80 eV for RhF(6), 7.95 eV for PdF(6), and 8.89 eV for AgF(6). The corresponding pentafluorides are also very strong Lewis acids, although their acidities on the pF(-) scale are about one unit lower than those of the third row pentafluorides. The performance of a wide range of DFT exchange-correlation functionals was benchmarked by comparing them to our more accurate CCSD(T) results.