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• We externally validated the Gastric Cancer Collaborative Group nomograms to assess prognosis following curative surgery for gastric cancer. • The nomograms include age, sex, tumor site, depth of invasion and LNR as factors that influence survival. • The nomograms demonstrated good performance in terms of prediction of both OS (C-index 0.75) and DFS (C-index 0.72) on external validation. • The nomograms are easy to apply, and variables included are widely available to most facilities, making them a useful tool for clinicians and patients. Nomograms have been proposed to assess prognosis following curative surgery for gastric cancer. The objective of the current study was to evaluate the performance of the Gastric Cancer Collaborative Group nomograms developed in 2014 by Kim et al. , using a cohort of patients from a 10-year single institution experience in gastric cancer management. We retrospectively reviewed patients who underwent curative-intent surgery for histologically confirmed gastric cancer at First Surgical Clinic of Padua University Hospital (Italy) from January 2010 to May 2020. Univariable and multivariable Cox proportional hazard models were employed to assess the effect of the variables of interest on mortality and recurrence. Multivariable analysis was performed by considering the variables included in the Gastric Cancer Collaborative Group nomograms in order to validate them. The performance of the nomograms was evaluated using Harrell's C-index and calibration plots. Overall, 168 patients were included, with a median follow-up of 20.1 months. On multivariable analysis, tumor location, lymph node ratio, and pathological T stage were associated with recurrence; age, tumor location, lymph node ratio, and pT stage were associated with OS (overall survival). The nomograms had good discriminatory capability to classify both OS (C-index: 0.75) and DFS (disease-free survival) (C-index 0.72). The corrected C-Index for DFS based on the AJCC staging system revealed better prediction (C-Index 0.75), while the corrected C-Index for OS had worse discrimination ability compared with the current nomogram (C-Index 0.72). The Gastric Cancer Collaborative Group nomograms demonstrated good performances in terms of prediction of both OS and DFS on external validation. The two nomograms are easy to apply, and variables included are widely available to most facilities. [ABSTRACT FROM AUTHOR]

This article investigates the densification of AlN ceramics through both Gas Pressure Sintering (GPS) and Spark Plasma Sintering (SPS) methods, employing cerium aluminates (CeAlO 3) as sintering aids and comparing their influence to that of the usual cerium oxide (CeO 2). While sintering aids like CeO 2 promote densification, CeAlO 3 exhibited lower reactivity during both SPS and GPS sintering. Chemical reactions between cerium oxide and aluminium oxide primarily involved the reduced phase as cerium sesquioxide (Ce 2 O 3). On the basis on the Ce 2 O 3 –Al 2 O 3 pseudo-binary system, the formation of secondary phases, such as CeAlO 3 and CeAl 11 O 18 , during sintering was explained and confirmed by XRD. From complementary characterizations, it has been shown that sintering significantly impacted secondary phase composition and distribution. By employing specific densification cycles, SPS yielded smaller grains and thicker secondary phase cordons which led to enhanced electrical conductivity. Conversely, GPS produced coarser microstructures including larger grains and a network of secondary phases and some agglomerations at the triple points. These modifications influenced the overall conductivity. SPSed samples with 3 wt.% CeO 2 and short dwelling times demonstrated higher electrical conductivity, exceeding by about 6 orders of magnitude the electrical conductivity of those obtained by GPS. [ABSTRACT FROM AUTHOR]

Summary The transcription factor EB (TFEB) is an essential component of lysosomal biogenesis and autophagy for the adaptive response to food deprivation. To address the physiological function of TFEB in skeletal muscle, we have used muscle-specific gain- and loss-of-function approaches. Here, we show that TFEB controls metabolic flexibility in muscle during exercise and that this action is independent of peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α). Indeed, TFEB translocates into the myonuclei during physical activity and regulates glucose uptake and glycogen content by controlling expression of glucose transporters, glycolytic enzymes, and pathways related to glucose homeostasis. In addition, TFEB induces the expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, and oxidative phosphorylation. This coordinated action optimizes mitochondrial substrate utilization, thus enhancing ATP production and exercise capacity. These findings identify TFEB as a critical mediator of the beneficial effects of exercise on metabolism. [ABSTRACT FROM AUTHOR]

Purpose To investigate clinical factors influencing the prognosis of patients submitted to hepatectomy for metastases from gastric cancer and their clinical role. Methods Retrospective multi-center chart review. We evaluated how survival from surgery was influenced by patient-related, gastric cancer-related, metastasis-related and treatment-related candidate prognostic factors. Results One hundred and five patients submitted to hepatectomy for metastases from gastric cancer, in the synchronous and metachronous setting of the disease. In 89 cases a R0 resection was achieved, while in 16 a R+ hepatic resection was performed. Adjuvant chemotherapy was administered to 29 patients. Surgical mortality was 1% and morbidity 13.3%. Median disease-free survival was 10 months, median overall survival was 14.6 months. Overall 1, 3, and 5-year survival rates were 58.2%, 20.3%, and 13.1%, respectively. Survival was influenced independently by the factor T of the gastric primary (p < 0.001), by the curativity of surgical procedure (p = 0.001), by the timing of hepatic involvement (p < 0.001) and by adjuvant chemotherapy (p < 0.001). T4 gastric cancer, R+ resection, synchronous metastases, and abstention from adjuvant chemotherapy were associated with a worse prognosis; T4 gastric cancer and R+ resections displayed a cumulative effect (p < 0.001). Conclusions Our data show that R0 resection must be pursued whenever possible. Furthermore, in the synchronous setting, the coexistence of T4 gastric primaries and R+ resections suggests prudence and probably abstention from hepatectomy. Finally, a multimodal treatment associating surgery and chemotherapy offers the best survival results. [ABSTRACT FROM AUTHOR]

Summary Increased levels of the mitochondria-shaping protein Opa1 improve respiratory chain efficiency and protect from tissue damage, suggesting that it could be an attractive target to counteract mitochondrial dysfunction. Here we show that Opa1 overexpression ameliorates two mouse models of defective mitochondrial bioenergetics. The offspring from crosses of a constitutive knockout for the structural complex I component Ndufs4 ( Ndufs4 −/− ), and of a muscle-specific conditional knockout for the complex IV assembly factor Cox15 ( Cox15 sm/sm ), with Opa1 transgenic ( Opa1 tg ) mice showed improved motor skills and respiratory chain activities compared to the naive, non- Opa1- overexpressing, models. While the amelioration was modest in Ndufs4 −/− ::Opa1 tg mice, correction of cristae ultrastructure and mitochondrial respiration, improvement of motor performance and prolongation of lifespan were remarkable in Cox15 sm/sm ::Opa1 tg mice. Mechanistically, respiratory chain supercomplexes were increased in Cox15 sm/sm ::Opa1 tg mice, and residual monomeric complex IV was stabilized. In conclusion, cristae shape amelioration by controlled Opa1 overexpression improves two mouse models of mitochondrial disease. [ABSTRACT FROM AUTHOR]

Summary: Mitochondrial disorders are highly heterogeneous conditions characterized by defects of the mitochondrial respiratory chain. Pharmacological activation of mitochondrial biogenesis has been proposed as an effective means to correct the biochemical defects and ameliorate the clinical phenotype in these severely disabling, often fatal, disorders. Pathways related to mitochondrial biogenesis are targets of Sirtuin1, a NAD+-dependent protein deacetylase. As NAD+ boosts the activity of Sirtuin1 and other sirtuins, intracellular levels of NAD+ play a key role in the homeostatic control of mitochondrial function by the metabolic status of the cell. We show here that supplementation with nicotinamide riboside, a natural NAD+ precursor, or reduction of NAD+ consumption by inhibiting the poly(ADP-ribose) polymerases, leads to marked improvement of the respiratory chain defect and exercise intolerance of the Sco2 knockout/knockin mouse, a mitochondrial disease model characterized by impaired cytochrome c oxidase biogenesis. This strategy is potentially translatable into therapy of mitochondrial disorders in humans. [Copyright &y& Elsevier]

Introduction: Breast cancer has shown a significant improvement in survival in recent years, so that more than 80% of affected women have a survival longer than 5 years after diagnosis and treatment; this figure is closer to the best European results (collectively, the breast cancer survival at 5 years is 87%, with values close to 89% in the Centre-North and 85% in the South of Italy). This is an indicator of good quality performances of all healthcare professionals involved and of the effective organization of services. Objective: The objective of this study is to highlight, through a review of existing literature, the treatments of proven effectiveness to be performed before and after surgery for breast cancer, with the goal of draw up appropriate procedures to be adopted uniformly throughout ASS n. 3 “Alto Friuli”. Materials and methods: In order to reach the drafting of appropriate procedures, supported by evidence of proven effectiveness, a literature review on biomedical Pubmed database was conducted, as well as were analyzed magazines such as Rivista Medica, Riabilitazione Oggi, Informandos etc, conference proceedings, business protocols and guidelines of the Region and SSN, brochures and advice for patients undergoing mastectomy in public and private institutions. Then the selected bibliography was critically analyzed and, through a process of synthesis, conclusions were drawn. The main aim was to verify the status of the scientific methods and treatments currently more widespread. Therefore the literature was analyzed in two major sections: the exercise and physiotherapy treatments more effective and most used, and the methods for the prevention of lymphedema. Results: This literature review has shown that surgery for breast cancer is fraught with many local and general complications, early and late, iatrogenic and evolutionary, which can take advantage of rehabilitation. The rehabilitation is also of particular psychological value as well as functional recovery, as it allows the woman to better deal with the trauma. It uses a pre-operative phase (through physiatric evaluation, the treatment of any joint stiffness and improvement of ventilatory capacity) and one in the immediate post-operative in order to promote the early mobilization, the prevention and treatment of the various complications and in particular of lymphedema. Conclusions: The taking into care on the part of the rehabilitation team allows you to monitor the patient over time, to set and change treatment depending on the complications that may arise related to intervention and progressive illness. [ABSTRACT FROM AUTHOR]

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Abstract: Background: The prognostic value of T subclassification in patients with gastric carcinoma has been just implemented in the new AJCC TNM staging system, which has reclassified T2a and T2b into T2 and T3 tumors, respectively. The aim of the present study was to validate the prognostic significance of the new T categorization within the frame of the latest TNM staging system. Methods: We retrospectively reviewed the records of 686 T2/T3 patients among 2155 subjects who underwent radical resection for gastric carcinoma at six Italian centers from 1988 through 2006. Results: Upon multivariate analysis, the new T categories, extent of lymph node dissection (D) and patient’s age were retained by the survival model as independent prognostic factors. In particular, the death risk for patients with T3 tumors was higher than that of patients with T2 tumors (HR: 1.42, P = 0.005). Among the 686 patients previously classified as having T2 tumors, patients with T2 and T3 disease were 270 (39.4%) and 416 (60.6%), respectively. After a median follow-up of 55 months, the 5-year overall survival rates were 67.3% and 52.3% for patients with T2 and T3 tumors, respectively (P < 0.001). The survival advantage for the T2 as compared to T3 category was maintained even when N0 and N+ patients were separately considered (P = 0.0154 and P < 0.001, respectively). Conclusions: Our data confirm the prognostic difference between the newly proposed T2 and T3 categories, which should be implemented in the routine clinical practice to improve risk stratification of patients with gastric cancer. [Copyright &y& Elsevier]

Background: The role of EUS in the locoregional staging of gastric carcinoma is undefined. Objective: We aimed to comprehensively review and quantitatively summarize the available evidence on the staging performance of EUS. Design: We systematically searched the MEDLINE, Cochrane, CANCERLIT, and EMBASE databases for relevant studies published until July 2010. Setting: Formal meta-analysis of diagnostic accuracy parameters was performed by using a bivariate random-effects model. Patients: Fifty-four studies enrolling 5601 patients with gastric cancer undergoing disease staging with EUS were eligible for the meta-analysis. Main Outcome Measurements: EUS staging accuracy across eligible studies was measured by computing overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Results: EUS can differentiate T1-2 from T3-4 gastric cancer with high accuracy, with overall sensitivity, specificity, PLR, NLR, and DOR of 0.86 (95% CI, 0.81-0.90), 0.91 (95% CI, 0.89-0.93), 9.8 (95% CI, 7.5-12.8), 0.15 (95% CI, 0.11-0.21), and 65 (95% CI, 41-105), respectively. In contrast, the diagnostic performance of EUS for lymph node status is less reliable, with overall sensitivity, specificity, PLR, NLR, and DOR of 0.69 (95% CI, 0.63-0.74), 0.84 (95% CI, 0.81-0.88), 4.4 (95% CI, 3.6-5.4), 0.37 (95% CI, 0.32-0.44), and 12 (95% CI, 9-16), respectively. Results regarding single T categories (including T1 substages) and Bayesian nomograms to calculate posttest probabilities for any target condition prevalence are also provided. Limitations: Statistical heterogeneity was generally high; unfortunately, subgroup analysis did not identify a consistent source of the heterogeneity. Conclusions: Our results support the use of EUS for the locoregional staging of gastric cancer, which can affect the therapeutic management of these patients. However, clinicians must be aware of the performance limits of this staging tool. [Copyright &y& Elsevier]

Abstract: Background: The treatment of hepatic metastases from gastric cancer is controversial, due to biologic aggressiveness of the disease. Objective: To survey the clinical approach to the subset of patients presenting with metachronous hepatic metastases as sole site of recurrence after curative resection of gastric cancer, focusing on the results achieved by different therapies and to investigate the prognostic factors of major clinical relevance. Methods: Retrospective multi-center chart review evaluating 73 patients, previously submitted to D ≥2 gastrectomy for gastric cancer, who developed exclusive hepatic recurrence. Prognostic factors related to the patient, to the gastric malignancy and its treatment, and to the metastatic disease and its therapy were evaluated. Results: Forty-five patients received supportive care, 17 were submitted to chemotherapy, and 11 to hepatic resection. Survival was independently influenced by the variables T (p =0.019), N (p =0.05) and G (p =0.018) of the gastric primary and by the therapeutic approach to the metastases (p <0.005). In particular, T4 gastric cancer, presence of lymph-node metastases and G3 tumor displayed a negative prognostic value. Therapeutic approach to the metastases was the principal prognostic variable: 1, 2, and 3 years survival rates were 22.2%, 4.4% and 2.2%, respectively, for patients without specific treatment; 44.9%, 12.8% and 6.4% after chemotherapy (p =0.08) and 80.8%, 30.3% and 20.2% after surgical resection (p <0.001). Conclusions: Our data suggest some clinical criteria that may facilitate selection of therapy for patients with hepatic recurrence after primary gastric cancer resection. The best survival rates are associated with surgical treatment, which should be chosen whenever possible. [Copyright &y& Elsevier]

• We evaluate the effectiveness of a Digital Social Market tool to promote active travel in an empirical context. • Exploratory factor analysis and negative binomial regression are used for the investigation. • Results show a positive correlation between DSM app engagement (posts, "claps", non-monetary rewards) and the level of active travel. • Lifestyles, attitudes, and social influence also explain the variability in cycling and walking. Information and communication technologies (ICTs), such as mobile communication networks, and behaviour-based approaches for citizen engagement play a key role in making future cities sustainable and tackling persistent problems in high-density urban areas. In the context of Sharing Cities, an EU-funded programme aiming to deliver smart city solutions in areas such as citizen participation and infrastructure improvements of buildings and mobility, a prominent intervention has been the deployment and monitoring of a Digital Social Market (DSM) tool in Milan (Italy). The DSM allows cities to engage with residents and encourage sustainable behaviours by offering non-monetary rewards. This paper aims to evaluate the effectiveness of the DSM approach to promote active travel (cycling and walking) by analysing the data collected through the app as well as through participant surveys. Our model results show that a broader engagement with the DSM app (number of claps to posts, number of posts made, non-monetary rewards earned by participating in non-travel events) is positively correlated with the monitored level of active travel. Lifestyles, attitudes, and social influence also explain the variability in cycling and walking. This highlights the importance of investigating these factors when replicating such initiatives on a large scale. [ABSTRACT FROM AUTHOR]

Background & Aims: The Helicobacter pylori gene cagA and s1 or m1 forms of vacA are more common in disease-associated strains. Recently, forms of cagA encoding multiple type C EPIYA segments (which increase phosphorylation-dependent CagA activity) and a new type i1 “intermediate region” polymorphism in vacA (which confers toxicity) have been described. We assessed the association of new and established cagA and vacA polymorphisms with disease. Methods: We studied 203 H pylori–infected subjects (53 gastric cancer [GC], 52 peptic ulcer [PU], and 98 gastritis). vacA signal, mid and intermediate region polymorphisms, cagA presence, and EPIYA-C segment number were analyzed by polymerase chain reaction. Results: cagA-positive strains were significantly associated with GC and PU (P < .001 and P < .05). GC risk was further associated with the number of cagA EPIYA-C segments (odds ratio [OR] = 7.37, 95% confidence interval [CI] = 1.98–27.48 for 1 EPIYA-C segment; OR = 32.5, 95% CI = 8.41–125.58 for 2 or more EPIYA-C segments). Increasing number of EPIYA-C segments also increased the risk of intestinal metaplasia. Type s1 and i1 vacA alleles were also associated with GC and type i1 vacA with PU (OR = 2.58, 95% CI = 1.19–5.61), including a significant association with duodenal ulcer. In multivariate analysis, the associations of cagA EPIYA-C segment number with GC and intestinal metaplasia as well as vacA i1 type association with PU remained. Conclusions: We confirmed the associations of cagA and vacA polymorphisms with disease but now define their most important features. For cancer risk, among Western strains, the most important factor is the number of cagA EPIYA-C segment. For PU risk, it is the intermediate region type of vacA. [Copyright &y& Elsevier]

Abstract: Aims: The proportion between metastatic and examined lymph nodes (N-ratio) has been proposed as an independent prognostic factor in patients with gastric cancer. In the present work we validated the reliability of N-ratio in a large, multicenter series. Patients and methods: We retrospectively reviewed the data of 1853 patients who underwent radical resection for gastric carcinoma. Survival of patients with >15 (Group-1, n =1421) and those with ≤15 (Group-2, n =432) lymph nodes examined was separately analyzed in order to evaluate the influence of lymph node dissection on disease staging. N-ratio categories (N-ratio 0, 0%; N-ratio 1, 1–9%; N-ratio 2, 10–25%; N-ratio 3, >25%) were determined by the best cut-off approach. Results: At multivariate analysis, N-ratio (but not TNM N-category) was retained as an independent prognostic factor both in Group-1 and Group-2 (HR for N-ratio 1, N-ratio 2 and N-ratio 3=1.67, 2.96 and 6.59, and 1.56, 2.68 and 4.28, respectively). After a median follow-up of 45.5months, the 5-year overall survival rates of TNM N0, N1 and N2 patients were significantly different in Group-1 vs Group-2. This was not the case when adopting the N-ratio classification, suggesting that a low number of excised lymph nodes can lead to patients being understaged using the N-category, but not N-ratio. Moreover, N-ratio identified subsets of patients with significantly different survival rates within TNM N1 and N2 categories in both groups. Conclusions: N-ratio is a simple and reproducible prognostic tool that can stratify patients with gastric cancer, including those cases with limited lymph node dissection. These data support the rationale to propose the implementation of N-ratio into the current TNM staging system. [Copyright &y& Elsevier]

Abstract: Aims: To investigate the survival benefit of extended lymphadenectomy (D2) in EGC patients in one European Institution. Methods: A review was made of our prospective gastric database from January 1980 to December 2001. Of 527 patients with primary gastric adenocarcinoma, 119 with EGC underwent potentially curative resection (R0) with D2 lymphadenectomy. Results: There were two post-operative deaths. Of the 117 evaluable cases, 96 were classified as N0 and 21 as N+, with metastases in the perigastric lymph nodes (level 1) in 13, and beyond this site (level 2) in eight. Five-year survival was 85.9 and 83.0% in N0 and N+ patients, respectively. During a median follow-up of 90 months, five of the eight patients with level 2 metastases died of recurrent disease and three were alive. The estimated survival benefit for 119 patients with EGC was 2.5% (3/119 cases). Conclusions: In patients with EGC, metastases to level 2 are rare. Our results indicate that D2 lymphadenectomy has a limited survival benefit and that in these cases a less extensive lymphadenectomy (D1) could be performed. [Copyright &y& Elsevier]

Abstract: Aim: To report the pattern of lymphatic mapping following intrasubdermal injections of radiocolloid and of blue dye in different sites of the breast. Methods: Prior to surgery 137 breast cancer patients underwent intrasubdermal injection of 30–50MBq 99mTc-colloidal albumin over the tumour site (ISI group). Ten minutes before surgery, 2ml patent blue was injected in the subareolar area (SAI group) in 117/137 patients, while 20 patients received intrasubdermal blue-dye in the quadrant opposite the tumour site (OQI group). The different injection routes were considered concordant when the hottest sLN was also blue. Results: In 134/137 patients radiocolloid drained to one or more axillary nodes, while blue nodes were found in 98/117 SAI patients and in 17/20 OQI patients. Multiple hot nodes were found in 63/134 cases and multiple blue nodes in 35/115. In patients in whom both tracers reached the axilla, the hottest node was also blue in 108/115 cases (93/98 SAI and 15/17 OQI patients). In the seven discordant cases, the hottest node was not blue, but in two cases the blue node was also radioactive. Conclusions: Superficial lymphatic drainage from the breast most frequently merges to a single axillary lymph node, irrespective of the site of tracer injection. In a few cases different injection sites identify different, often closely interconnected sLNs. [Copyright &y& Elsevier]