Beneficial hemodynamic effects of inhibiting ANP catabolism in congestive heart failure

Pepper, Beverly (escultora)Primer pla de l'obra. També conegut com a "Cel caigut, Espiral arbrada", realitzat amb ceràmica

The complex TIE between macrophages and angiogenesis

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway

Hepatitis C of genotype 2: the role of medical invasive exams.

BACKGROUND AND AIM: Hepatitis C virus genotype 2 is the third in order of frequency in Belgium. The aim of this study was to better define the genotype 2 carriers' epidemiology characteristics. METHODS: In a database comprising 1726 viremic hepatitis C virus patient from the south part of Belgium, the files of 98 genotype 2 carriers were reviewed. RESULTS: There was a strong association between genotype 2 and the mode of transmission. The rate of contamination by invasive medical exams was very high (23%), and statistically different from the one of the others genotypes. Eligibility for antiviral therapies and the rate of sustained viral response were high. CONCLUSION: HCV genotype 2 was highly associated with transmission by invasive medical exams.Peer reviewe

Bioreactor technologies to support liver function in vitro

Liver is a central nexus integrating metabolic and immunologic homeostasis in the human body, and the direct or indirect target of most molecular therapeutics. A wide spectrum of therapeutic and technological needs drives efforts to capture liver physiology and pathophysiology in vitro, ranging from prediction of metabolism and toxicity of small molecule drugs, to understanding off-target effects of proteins, nucleic acid therapies, and targeted therapeutics, to serving as disease models for drug development. Here we provide perspective on the evolving landscape of bioreactor-based models to meet old and new challenges in drug discovery and development, emphasizing design challenges in maintaining long-term liver-specific function and how emerging technologies in biomaterials and microdevices are providing new experimental models.National Institutes of Health (U.S.) (R01 EB010246)National Institutes of Health (U.S.) (P50-GM068762-08)National Institutes of Health (U.S.) (R01-ES015241)National Institutes of Health (U.S.) (P30-ES002109)5UH2TR000496-02National Science Foundation (U.S.). Emergent Behaviors of Integrated Cellular Systems (CBET-0939511)United States. Defense Advanced Research Projects Agency. Microphysiological Systems Program (W911NF-12-2-0039

The Use of a Compression Device as an Alternative to Hand-Sewn and Stapled Colorectal Anastomoses: Is Three a Crowd?

BackgroundThe NiTi CAR™ 27 is a newer device that uses compression to create an anastomosis. An analysis of this device in the creation of colorectal anastomoses in humans has yet to be reported in the USA.MethodsA non-randomized, prospective pilot study of the NiTi CAR™ 27 device in patients undergoing a left-sided colectomy between March 2008 and August 2009 was performed.ResultsTwenty-three patients (9 men and 14 women) underwent a left-sided colectomy and compression anastomosis with the CAR™ 27 device. Minor morbidities, 3 of 23 (13%) patients, included one small postoperative abscess requiring antibiotics alone and two postoperative anastomotic strictures requiring balloon dilation. Major morbidities, 1 of 23 (4%) patients, included a partial anastomotic dehiscence/leak requiring surgical dismantling of the anastomosis and diversion.ConclusionThe CAR™ 27 device shows promise as a safe and effective alternative for the creation of colorectal anastomoses. However, studies in a larger patient population are warranted to demonstrate equivalence of this device

Liver Resection and Ablation for Squamous Cell Carcinoma Liver Metastases

Background Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS). Method Members of the European–African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS. Results Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30). Conclusion Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome

Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial

Importance: The etiology of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is unknown. However, neuroinflammation and complement activation may play a role in disease progression. Objective: To determine the effects of zilucoplan, an inhibitor of complement C5, in individuals with ALS. Design, Setting, and Participants: Zilucoplan was tested as regimen A of the HEALEY ALS Platform Trial, a phase 2 to 3 multicenter, randomized, double-blind, placebo-controlled perpetual platform clinical trial with sharing of trial infrastructure and placebo data across multiple regimens. Regimen A was conducted from August 17, 2020, to May 4, 2022. A total of 162 participants were randomized to receive zilucoplan (122 [75.3%]) or regimen-specific placebo (40 [24.7%]). An additional 124 concurrently randomized participants were randomized to receive placebo in other regimens. Interventions: Eligible participants were randomized in a 3:1 ratio to receive zilucoplan or matching placebo within strata of edaravone and/or riluzole use for a planned duration of 24 weeks. Active drug (zilucoplan, 0.3 mg/kg) and placebo were provided for daily subcutaneous dosing. Main Outcomes and Measures: The primary end point was change in disease severity from baseline through 24 weeks as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) total score and survival, analyzed using a bayesian shared-parameter model and reported as disease rate ratio (DRR; Results: Among the 162 participants who were randomized (mean [SD] age, 59.6 [11.3]; 99 [61.1%] male), 115 (71.0%) completed the trial. The estimated DRR common to ALSFRS-R and survival was 1.08 (95% credible interval, 0.87-1.31; posterior probability of superiority, 0.24). The trial was stopped early for futility. No unexpected treatment-related risks were identified. Conclusions and Relevance: In this randomized clinical trial of zilucoplan in ALS, treatment did not alter disease progression. The adaptive platform design of the HEALEY ALS Platform Trial made it possible to test a new investigational product with efficient use of time and resources. Trial Registration: ClinicalTrials.gov Identifier: NCT04297683</p

Primary percutaneous metal stenting above the ampulla in resectable perihilar cholangiocarcinoma.

peer reviewed[en] INTRODUCTION: We present a case of a patient with resectable perihilar cholangiocarcinoma (pCCA) who underwent primary metal stenting above the ampulla, followed by a successful surgical resection. Biliary drainage is a crucial step in the preoperative management of pCCA, yet there is no consensus on the optimal approach. Traditional drainage methods involve passing through the ampulla and/or the skin barrier, thereby increasing the risk of bacterial contamination of the biliary tree and secondary cholangitis. METHOD: A novel drainage technique was utilised in this case. A metal stent was percutaneously placed across the malignant hilar stenosis without external biliary drainage. During the procedure, both guidewires and stents were meticulously prevented from passing through the ampulla. Additionally, percutaneous access to the biliary tree was removed during the index procedure to minimise the risk of biliary colonisation and cholangitis. RESULTS: Following the drainage, bilirubin levels rapidly normalised, and no clinical or biochemical signs of cholangitis were observed. This allowed for rapid and uncomplicated surgical resection. CONCLUSION: This case illustrates the potential of a novel biliary drainage technique in patients with pCCA. By minimising the risk of biliary colonisation and cholangitis, this approach could potentially improve surgical outcomes

Liver resection and ablation for squamous cell carcinoma liver metastases.

Funder: Region StockholmFunder: Region Stockholm (clinical postdoctoral appointment)BACKGROUND: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS). METHOD: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS. RESULTS: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30). CONCLUSION: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome

Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease

Background: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy. Methods: Patients with a diagnosis of pCCA between 1997–2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS. Results: Overall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p &lt; 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently &gt;200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55–1.07). Conclusions: Palliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality.</p