Stability of Oscillating Gaseous Masses in Massive Brans-Dicke Gravity

This paper explores the instability of gaseous masses for the radial oscillations in post-Newtonian correction of massive Brans-Dicke gravity. For this purpose, we derive linearized perturbed equation of motion through Lagrangian radial perturbation which leads to the condition of marginal stability. We discuss radius of instability of different polytropic structures in terms of the Schwarzschild radius. It is concluded that our results provide a wide range of difference with those in general relativity and Brans-Dicke gravity.Comment: 31 pages, 11 figures, to appear in IJMP

Implementation of a patient blood management in an Italian City Hospital: is it effective in reducing the use of red blood cells?

To evaluate the effect of patient blood management (PBM) since its introduction, we analyzed the need for transfusion and the outcomes in patients undergoing abdominal surgery for different types of tumor pre- and post-PBM. Patients undergoing elective gastric, liver, pancreatic, and colorectal surgery between 2017 and 2020 were included. The implementation of the PBM program was completed on May 1, 2018. The patients were grouped as follows: those who underwent surgery before the implementation of the program (pre-PBM) versus after the implementation (post-PBM). A total of 1302 patients were included in the analysis (445 pre-PBM vs. 857 post-PBM). The number of transfused patients per year decreased significantly after the introduction of PBM. A strong tendency for a decreased incidence of transfusion was evident in gastric and pancreatic surgery and a similar decrease was statistically significant in liver surgery. With regard to gastric surgery, a single-unit transfusion scheme was used more frequently in the post-PBM group (7.7% vs. 55% after PBM; p = 0.049); this was similar in liver surgery (17.6% vs. 58.3% after PBM; p = 0.04). Within the subgroup of patients undergoing liver surgery, a significant reduction in the use of blood transfusion (20.5% vs. 6.7%; p = 0.002) and a decrease in the Hb trigger for transfusion (8.5, 8.2-9.5 vs. 8.2, 7.7-8.4 g/dl; p = 0.039) was reported after the PBM introduction. After the implementation of a PBM protocol, a significant reduction in the number of patients receiving blood transfusion was demonstrated, with a strong tendency to minimize the use of blood products for most types of oncologic surgery

Surgical treatment of hepatic metastases from gastric cancer

The purpose of the study was to investigate the clinical factors influencing the prognosis of patients submitted to hepatectomy for metastases from gastric cancer and their clinical role. We conducted a retrospective multicentre review. We evaluated how survival from surgery was influenced by patient-related, tumour-related and treatment-related prognostic factors. We analysed data on 144 patients submitted to hepatectomy for metastases from gastric cancer, in the synchronous and metachronous setting. In 117 cases, an R0 resection was achieved, while in 27 an R\u2009+\u2009hepatic resection was performed. Chemotherapy was administered to 55 patients. Surgical mortality was 2.1% and morbidity 21.5%. One-, 3-, and 5-year OS rates after surgery were 49.9, 19.4 and 11.6%, respectively, with a median OS of 12.0 months. T4 gastric cancer, H3 hepatic involvement, non-curative resection, recurrence after surgery, and abstention from chemotherapy were associated with a worse prognosis. Factor T and H displayed a clear (p\u2009<\u20090.001) cumulative effect. Our data show that R0 resection must be pursued whenever possible. The treatment of T4 gastric cancer with hepatic bilateral and diffuse metastasis (H3) should be considered carefully or it should be probably avoided. Finally, a multimodal treatment associating surgery and chemotherapy offers the best survival results

Current status of the self-expandable metal stent as a bridge to surgery versus emergency surgery in colorectal cancer. Results from an updated systematic review and meta-analysis of the literature

Background: The current use of endoscopic stenting as a bridge to surgery is not always accepted in standard clinical practice to treat neoplastic colonic obstructions. Objectives: The role of colonic self-expandable metal stent (SEMS) positioning as a bridge to resective surgery versus emergency surgery (ES) for malignant obstruction, using all new data and available variables, was studied and we focused on short- and long-term results. Materials and Methods: A systematic review with meta-analysis was performed. PubMed, SCOPUS and Web of Science databases were included. The search comprised only randomized controlled trials (RCTs) investigating the interventions that included SEMS positioning versus ES. The primary outcomes were the rates of overall postoperative mortality, clinical and technical success. The secondary outcomes were the short- and long-term results. Results: A total of 12 studies were eligible for further analyses. A laparoscopic colectomy was the most common operation performed in the SEMS group, whereas the traditional open approach was commonly used in the ES group. Intraoperative colonic lavage was seldomly performed during ES. There were no differences in mortality rates between the two groups (RR 1.06, 95% CI 0.55 to 2.04; I2 = 0%). In the SEMS group, the rate of successful primary anastomosis was significantly higher in of SEMS (69.75%) than in the ES (55.07%) (RR 1.26, 95% 245 CI 1.01 to 1.57; I2 = 86%). Conversely, the upfront Hartmann procedure was performed more frequently in the ES (39.1%) as compared to the SEMS group (23.4%) (RR 0.61, 95% CI 0.45 to 0.85; I2 = 23%). The overall postoperative complications rate was significantly lower in the SEMS group (32.74%) than in the ES group (48.25%) (RR 0.61, 95% CI 0.41 to 0.91; I2 = 65%). Conclusions: In the presence of malignant colorectal obstruction, SEMS is safe and associated with the same mortality and significantly lower morbidity than the ES group. The rate of successful primary anastomosis was significantly higher than the ES group. Nevertheless, recurrence and survival outcomes are not significantly different between the two groups. The analysis of short- and long-term results can suggest the use of SEMS as a bridge to resective surgery when it is performed by an endoscopist with adequate expertise in both colonoscopy and fluoroscopic techniques and who performed commonly colonic stenting

Long-Term Oral Administration of Theaphenon-E Improves Cardiomyocyte Mechanics and Calcium Dynamics by Affecting Phospholamban Phosphorylation and ATP Production

Background/Aims: Dietary polyphenols from green tea have been shown to possess cardioprotective activities in different experimental models of heart diseases and age-related ventricular dysfunction. The present study was aimed at evaluating whether long term in vivo administration of green tea extracts (GTE), can exert positive effects on the normal heart, with focus on the underlying mechanisms. Methods: The study population consisted of 20 male adult Wistar rats. Ten animals were given 40 mL/day tap water solution of GTE (concentration 0.3%) for 4 weeks (GTE group). The same volume of water was administered to the 10 remaining control rats (CTRL). Then, in vivo and ex vivo measurements of cardiac function were performed in the same animal, at the organ (hemodynamics) and cellular (cardiomyocyte mechanical properties and intracellular calcium dynamics) levels. On cardiomyocytes and myocardial tissue samples collected from the same in vivo studied animals, we evaluated: (1) the intracellular content of ATP, (2) the endogenous mitochondrial respiration, (3) the expression levels of the Sarcoplasmic Reticulum Ca2+-dependent ATPase 2a (SERCA2), the Phospholamban (PLB) and the phosphorylated form of PLB, the L-type Ca2+ channel, the Na+-Ca2+ exchanger, and the ryanodine receptor 2. Results: GTE cardiomyocytes exhibited a hyperdynamic contractility compared with CTRL (the rate of shortening and re-lengthening, the fraction of shortening, the amplitude of calcium transient, and the rate of cytosolic calcium removal were significantly increased). A faster isovolumic relaxation was also observed at the organ level. Consistent with functional data, we measured a significant increase in the intracellular ATP content supported by enhanced endogenous mitochondrial respiration in GTE cardiomyocytes, as well as higher values of the ratios phosphorylated-PLB/PLB and SERCA2/PLB. Conclusions: Long-term in vivo administration of GTE improves cell mechanical properties and intracellular calcium dynamics in normal cardiomyocytes, by increasing energy availability and removing the inhibitory effect of PLB on SERCA2

Preoperative Chemotherapy and Resection Margin Status in Colorectal Liver Metastasis Patients: A Propensity Score-Matched Analysis

In this article, we compared the early and long-term outcomes of patients with metastatic colorectal cancer treated with chemotherapy followed by resection with those of patients undergoing surgery first, focusing our analysis on resection margin status. Patients who underwent liver resection with curative intent for colorectal liver metastases from July 2001 to January 2018 were included in the analysis. Propensity score matching was used to reduce treatment allocation bias. The cohort comprised 164 patients; 117 (71.3%) underwent liver resection first, whereas the remaining 47 (28.7%) had preoperative chemotherapy. After a 1:1 ratio of propensity score matching, 47 patients per group were evaluated. A positive resection margin was found in 13 patients in the surgery-first group (25.5%) versus 4 (8.5%) in the preoperative chemotherapy group (P = 0.029). Postmatched logistic regression analysis showed that only preoperative chemotherapy was significantly associated with the rate of positive resection margin (odds ratio 0.24, 95% confidence interval 0.07-0.81; P = 0.022). Median follow-up was 41 months (interquartile range 8-69). Cox proportional hazard regression analysis revealed that only positive resection margin was a significant negative prognostic factor (hazard ratio 2.2, 95% CI 1.18-4.11; P = 0.014). Within the preoperative chemotherapy group, median overall survival was 40 months in R0 patients and 10 months in R1 patients (P = 0.016). Although preoperative chemotherapy in colorectal liver metastasis patients may affect the rate of positive resection margin, its impact on survival seems to be limited. In the present study, the most important prognostic factor was the resection margin status

Profile of lenvatinib in the treatment of hepatocellular carcinoma: design, development, potential place in therapy and network meta-analysis of hepatitis B and hepatitis C in all Phase III trials

Purpose: Sorafenib is the only approved drug in first-line treatment for hepatocellular carcinoma. Recently, the Phase III REFLECT trial proved lenvatinib not inferior to sorafenib, potentially establishing a new standard of care in this setting. The study showed that both have similar overall survivals, yet with longer time to progression for lenvatinib. Currently, the selection of one or other is not based on clinical or biological parameters for this reason we performed a network meta-analysis and we also analyzed the REFLECT trial and its implications in the current and future clinical practice. Materials and methods: We performed the meta-analysis according to the Prisma statement recommendations. HR was the measure of association for time to progression and overall survival. The pooled analysis of HR was performed using a random effect model, fixing a 5% error as index of statistical significance. Results: For HBV-positive patients, there was a clear trend in favor of lenvatinib over sorafenib (HR 0.82 95% credible interval [CrI] 0.60\u20131.15). For HCV-positive no differences between lenvatinib and sorafenib were observed (HR 0.91 95% CrI 0.41\u20132.01). The data showed that lenvatinib could be the best drug for HBV-positive patients in 59% of cases compared to only 1% of patients treated with sorafenib. Conclusion: The identification of clinical or biological markers that could predict response or resistance to treatments is needed to guide treatment decision. This network meta-analysis demonstrates that the etiology is a good candidate and this result should be validated in a specific trial.Purpose: Sorafenib is the only approved drug in first-line treatment for hepatocellular carcinoma. Recently, the Phase III REFLECT trial proved lenvatinib not inferior to sorafenib, potentially establishing a new standard of care in this setting. The study showed that both have similar overall survivals, yet with longer time to progression for lenvatinib. Currently, the selection of one or other is not based on clinical or biological parameters for this reason we performed a network meta-analysis and we also analyzed the REFLECT trial and its implications in the current and future clinical practice.Materials and methods: We performed the meta-analysis according to the Prisma statement recommendations. HR was the measure of association for time to progression and overall survival. The pooled analysis of HR was performed using a random effect model, fixing a 5% error as index of statistical significance.Results: For HBV-positive patients, there was a clear trend in favor of lenvatinib over sorafenib (HR 0.82 95% credible interval [CrI] 0.60-1.15). For HCV-positive no differences between lenvatinib and sorafenib were observed (HR 0.91 95% CrI 0.41-2.01). The data showed that lenvatinib could be the best drug for HBV-positive patients in 59% of cases compared to only 1% of patients treated with sorafenib.Conclusion: The identification of clinical or biological markers that could predict response or resistance to treatments is needed to guide treatment decision. This network meta-analysis demonstrates that the etiology is a good candidate and this result should be validated in a specific trial

Cytoreduction plus hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis in colorectal cancer patients: a single-center cohort study

BACKGROUND: In this study, we report our experience of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) in patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC), focusing on the factors affecting survival. METHODS: All patients with surgically treated PC from colorectal cancer and with no involvement of other organs referred to our institute from March 2005 to December 2017 were included in the analysis. RESULTS: Thirty-eight patients underwent CRS-HIPEC, and all had a completeness of cytoreduction score of 0 (CC0). The median operating time was 645 min (interquartile range [IQR] 565-710). Five patients (13.1%) had Clavien-Dindo grade >\u20092 postoperative complications. Median overall survival (OS) was 60 months. In the Cox regression for OS, calculated on the CRS-HIPEC group, the peritoneal cancer index (PCI) >\u20096 (hazard ratio [HR] 4.48, IQR 1.68-11.9, P = 0.003) and significant nodal involvement (N2) (HR 3.89, IQR 1.50-10.1, P = 0.005) were independent prognostic factors. Median disease-free survival (DFS) was 16 months. Only N2 (HR 2.44, IQR 1.11-5.36, P = 0.027) was a significantly negative prognostic factor for DFS in multivariate analysis. CONCLUSIONS: CRS-HIPEC can substantially improve survival. However, patients with high PCI (PCI >\u20096) and significant nodal involvement (N2) may not benefit from the procedure

Effects of standardized green tea extract and its main component, EGCG, on mitochondrial function and contractile performance of healthy rat cardiomyocytes

We recently showed that the long-term in vivo administration of green tea catechin extract (GTE) resulted in hyperdynamic cardiomyocyte contractility. The present study investigates the mechanisms underlying GTE action in comparison to its major component, epigallocatechin-3-gallate (EGCG), given at the equivalent amount that would be in the entirety of GTE. Twenty-six male Wistar rats were given 40 mL/day of a tap water solution with either standardized GTE or pure EGCG for 4 weeks. Cardiomyocytes were then isolated for the study. Cellular bioenergetics was found to be significantly improved in both GTE- and EGCG-fed rats compared to that in controls as shown by measuring the maximal mitochondrial respiration rate and the cellular ATP level. Notably, the improvement of mitochondrial function was associated with increased levels of oxidative phosphorylation complexes, whereas the cellular mitochondrial mass was unchanged. However, only the GTE supplement improved cardiomyocyte mechanics and intracellular calcium dynamics, by lowering the expression of total phospholamban (PLB), which led to an increase of both the phosphorylated-PLB/PLB and the sarco-endoplasmic reticulum calcium ATPase/PLB ratios. Our findings suggest that GTE might be a valuable adjuvant tool for counteracting the occurrence and/or the progression of cardiomyopathies in which mitochondrial dysfunction and alteration of intracellular calcium dynamics constitute early pathogenic factors

Ten years of sorafenib in hepatocellular carcinoma: Are there any predictive and/or prognostic markers?

Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma (HCC) since 2007 and numerous studies have investigated the role of markers involved in the angiogenesis process at both the expression and genetic level and clinical aspect. What results have ten years of research produced? Several clinical and biological markers are associated with prognosis. The most interesting clinical parameters are adverse events, Barcelona Clinic Liver Cancer stage, and macroscopic vascular invasion, while several single nucleotide polymorphisms and plasma angiopoietin-2 levels represent the most promising biological biomarkers. A recent pooled analysis of two phase III randomized trials showed that the neutrophil-to-lymphocyte ratio, etiology and extra-hepatic spread are predictive factors of response to sorafenib, but did not identify any predictive biological markers. After 10 years of research into sorafenib there are still no validated prognostic or predictive factors of response to the drug in HCC. The aim of the present review was to summarize 10 years of research into sorafenib, looking in particular at the potential of associated clinical and biological markers to predict its efficacy in patients with advanced HCC