Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Adipokine serum levels are related to liver histology in severely obese patients undergoing bariatric surgery

Background: Leptin, adiponectin, and resistin are adipokines linked to the development of insulin resistance, which plays a central role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We aimed to define adipokine serum levels in severely obese patients undergoing bariatric surgery and to correlate these with anthropometric and metabolic variables, liver function tests, and histopathological parameters of NAFLD and nonalcoholic steatohepatitis (NASH). Methods: Surgical liver biopsies were obtained from 50 bariatric patients with no history of liver disease or significant alcohol consumption. Serum leptin, adiponectin, and resistin levels were measured, and histology was assessed using Brunt's and Kleiner's scoring systems. Results: Waist/hip ratio was significantly higher in men (p=0.0001), and leptin (p=0.036) and adiponectin (p=0.0001) serum levels were higher in women. Forty-one of 50 patients (82%) had histological NAFLD, including 10 (20%) with NASH. Nine patients (18%) had normal liver histology (obese control subgroup). In NAFLD patients, serum adiponectin was negatively correlated with activity grade and fibrosis stage, resistin was negatively correlated with steatosis grade (p=0.033), while leptin was not related to histology. Leptin/adiponectin ratio showed positive association with stage (p=0.044). In the subgroup of NASH patients, adiponectin was negatively correlated only with stage (p=0.01), while there was no correlation between leptin, resistin, or leptin/adiponectin and histology. Conclusions: Serum adiponectin and resistin levels are related to liver histology in bariatric patients and may be indicative of the histological severity of NAFLD and the extent of hepatic steatosis, respectively. Serum leptin levels are not informative of underlying liver histology in severely obese patients. © 2009 Springer Science + Business Media, LLC

Modulating the surface and mechanical properties of textile by oil-in-water emulsion design

The synergistic effect of oil viscosity and oil droplet size on the deposition profile of oil on cotton fabric was studied using polydimethylsiloxane (PDMS) as a model oil-in-water emulsion system. Under the same preparation conditions, low viscosity PDMS produced emulsions containing small droplets, which resulted in a uniform surface deposition profile, whilst high viscosity PDMS resulted in a localised deposition profile. Interfacial phenomena such as wicking and penetration of PDMS into cotton fabrics were found to be viscosity-dependent, which agrees with the surface deposition data. Both mechanical characterisation (friction, compression, stiffness) and consumer evaluation confirm that the fabrics treated by the emulsion containing low viscosity PDMS were preferred, suggesting that a homogeneous surface deposition and an excellent penetration profile of PDMS are critical for maximising tactile sensorial benefits, which could be accomplished by optimising the emulsion formulation to contain oil of low viscosity and small PDMS droplets

Liver FOXP3 and PD1/PDL1 expression is down-regulated in chronic HBV hepatitis on maintained remission related to the degree of inflammation

Background and Aim: T cell expression of PD1 and inhibition of T effector cells by Foxp3(+)-T regulatory cells are among the most powerful mechanisms for achieving a balanced immune response. Our aim was to investigate, how liver FOXP3 and PD1/PDL1 expression is regulated in chronic HBV hepatitis (CHB) on maintained long-term remission in comparison with active disease, and whether they are correlated to the expression of pro- and anti-inflammatory cytokines and apoptosis mediators, along with the degree of histological inflammation and markers of T cell effector restoration. Methods: Fifty-three HBeAg-negative CHB patients with both active (30) and completely remitted disease on long-term antiviral treatment (23) and four controls (submitted to liver biopsy due to a mild increase of aminotransferases but without liver necroinflammatory and architecture changes) were enrolled in the study. Liver mRNA levels of immunoregulatory genes (FOXP3, IL 10, TGFB1, and those of PD1/PDL1/PDL2 pathway), major apoptosis mediators (FAS, FASL, TNFA, TRAIL), cytokines of effector T cell restoration (IL2, IFNG), and those of IL 18, CD4, and CDS, were evaluated by quantitative real-time reverse-transcriptase PCR and were correlated with each other, along with the intensity of liver inflammation and fibrosis staging. The expression and localization of FOXP3, PD1, PDL1, CD4, and CD8 were also assessed by immunohistochemistry. Results: The expression of FOXP3, IL10, TGFB1, PD1, PDL1, FASL, and CDS was significantly down-regulated in the remission state. In contrast, liver expression of IL2 and IFNG, along with CD4, IL1B,TNFA, and FAS did not change significantly. Moreover, FOXP3, PD1, PDL1, and CDS transcripts were positively correlated to the intensity of liver inflammation. Conclusion: Our data indicate that in the CHB disease model, the immunosuppressive liver environment is down-regulated in the maintained on-treatment long-term remission state and correlates with the intensity of liver inflammation, but not liver T cell restoration

Survivin isoform expression patterns in CML patients correlate with resistance to imatinib and progression, but do not trigger cytolytic responses

Tyrosine-kinase inhibitors are very effective in patients with CML, but in most cases the disease relapses after their discontinuation. As a result, novel approaches should be considered, such as anti-survivin treatment or anti-survivin-based immunotherapy. To gain insight into the roles of survivin isoform expression and specific CD8(+) T cells in CML, we investigated 51 patients at different stages, both at diagnosis and during treatment. We demonstrated that (i) patients at advanced-stage displayed an increased expression of the standard-survivin form along with a significant decrease of survivin-2B and -Delta Ex3 levels, (ii) patients in chronic phase with higher expression of the standard-survivin exhibited a 3.5-fold increased probability not to achieve an optimal response to imatinib (p=0.048), (iii) responders displayed a significant up-regulation of all survivin isoforms in bone marrow, and (iv) anti-survivin CD8(+) T cells were undetectable both at diagnosis and during treatment. Accordingly, our results question the validity of innmunotherapeutic approaches targeting survivin in CML. (C) 2011 Elsevier Inc. All rights reserved

TGF-β signaling is activated in patients with chronic HBV infection and repressed by SMAD7 overexpression after successful antiviral treatment

Objectives: Although animal studies demonstrated that Smad7 induction ameliorates TGF-β/SMAD-mediated fibrogenesis, its role in human hepatic diseases is rather obscure. Our study explored the activation status of TGF-β/activin pathway in patients with chronic liver diseases, and how it is affected by successful antiviral treatment in chronic HBV hepatitis (CHB). Methods: Thirty-seven CHB patients (19 with active disease, 14 completely remitted on long-term antiviral treatment and 4 with relapse after treatment withdrawal), 18 patients with chronic HCV hepatitis, 12 with non-alcoholic fatty liver disease (NAFLD), and 3 controls were enrolled in the study. Liver mRNA levels of CTGF, all TGF-β/activin isoforms, their receptors and intracellular mediators (SMADs) were evaluated using qRT-PCR and were correlated with the grade of liver inflammation and fibrosis staging. The expression and localization of pSMAD2 and pSMAD3 were assessed by immunohistochemistry. Results: TGF-β signalling is activated in CHB patients with active disease, while SMAD7 is up-regulated during the resolution of inflammation after successful treatment. SMAD7 overexpression was also observed in NAFLD patients exhibiting no or minimal fibrosis, despite the activation of TGF-β/activin signaling. Conclusions: SMAD7 overexpression might represent a mechanism limiting TGF-β-mediated fibrogenesis in human hepatic diseases; therefore, SMAD7 induction likely represents a candidate for novel therapeutic approaches. © 2016, Springer International Publishing