Role of perfusion machines in the setting of clinical liver transplantation. A qualitative systematic review

Growing enthusiasm around machine perfusion (MP) in clinical liver transplantation (LT) may be the preamble for standardized practice to expand the donors' pool. The present systematic review investigated all the liver transplantations performed using grafts treated with MP. A systematic review of 309 papers was performed. Eventually, 27 articles were enrolled for the study. A total number of 173 cases was reported. Only 12 cohort studies were identified: the remaining ones were case reports or case series. Hypothermic machine perfusion was performed in 102 (59.0%), normothermic machine perfusion in 65 (37.6%), and controlled oxygenated rewarming in the remaining 6 (3.4%) cases. Donor characteristics, evaluation of graft quality and end-points were not homogeneous among the studies. Overall, post-LT results were excellent, with 1.2 and 4.0% of patients experienced primary non-function and ischemic-type biliary lesions, respectively

Predictive and Protective Factors for Partial Necrosis in DIEP Flap Breast Reconstruction. Does Nulliparity Bias Flap Viability?

Although success rate of deep inferior epigastric perforator (DIEP) flap breast reconstruction has greatly improved, complications still occasionally occur. Perfusion-related complications (PRCs) (ie, fat necrosis and partial flap necrosis) are the most frequent concern, affecting aesthetic final result of the reconstructed breast.The aim of our study was to retrospectively investigate 287 consecutive DIEP flap breast reconstructions to investigate predictive and protective factors for PRCs.From May 2004 to February 2012, 287 DIEP flap breast reconstructions were performed on 270 patients; 247 unilateral flaps, including Holm vascular zones I to III, were retrospectively selected and analyzed. Tobacco use, mean blood pressure over the first postoperative 48 hours, superficial epigastric vein drainage, medial/lateral row perforator, nulliparity, crystalloid versus combined crystalloid/colloid intravenous fluid infusion therapy, and learning curve were evaluated by univariate and multivariate logistic regression analyses.Perfusion-related complications occurred 32 (12.9%) times, 79 (31.9%) patients were smokers, 48 (19.4%) showed postoperative mean blood pressure less than 75 mm Hg, 29 (11.7%) were nulliparous, and 173 (70%) had superficial epigastric vein drainage. Selected perforators were 110 (44.5%) from lateral row, 137 (55.5%) from medial row; 91 (36.8%) received crystalloid fluid infusion, whereas 156 (63.2%) combined crystalloid/colloid fluid infusion. From univariate analysis emerged significance of nulliparity, perforator row and intravenous fluid infusion for PRC. Nevertheless, multivariate model confirmed only nulliparity as a significant risk factor (P = 0.029), although variable correlations to other predictors were found: both medial row perforator and combined crystalloid/colloid fluid infusion potentially decrease the PRC risk of 11.6% and 27.6%, respectively. Learning curve did not show significant decrease of PRC risk over time.Our study first proved nulliparity as a statistically significant predictor for PRCs in DIEP flap breast reconstruction, possibly due to different superficial abdominal perfusion between pluriparous and nulliparous women, with potential weaker pattern of perforators and smaller angiosomes in the latter. The choice of medial row perforators and combined crystalloid/colloid fluid infusion might reduce PRC risk

Numerical wave interaction with tetrapods breakwater

ABSTRACT: The paper provides some results of a new procedure to analyze the hydrodynamic aspects of the interactions between maritime emerged breakwaters and waves by integrating CAD and CFD. The structure is modeled in the numerical domain by overlapping individual three-dimensional elements (Tetrapods), very much like the real world or physical laboratory testing. Flow of the fluid within the interstices among concrete blocks is evaluated by integrating the RANS equations. The aim is to investigate the reliability of this approach as a design tool. Therefore, for the results' validation, the numerical run-up and reflection effects on virtual breakwater were compared with some empirical formulae and some similar laboratory tests. Here are presented the results of a first simple validation procedure. The validation shows that, at present, this innovative approach can be used in the breakwater design phase for comparison between several design solutions with a significant minor cost. KEY WORDS: Volume of Fluid (VOF), Wave, Run up, Reflection, Rubble mound, Numerical simulations, Tetrapod Flow 3D®, RANS equation

Simple and complex images: Operationalization and first calibration

The aim of this study is to operationalize the construction of the complexity related to images. In particular, we want to calibrate the judgments of complexity related to colourful images and black and white images who belong to different categories (animals, fruit, transports, technological tools and faces) and examine the parameters related to the different levels of their categorical complexity.The first part of this composition put forward a definition of the construction, a comparison between the various theories of the complexity of the images and an analysis of the various fields of application.In the second part, the purpose is to operationalize the construction, together with the method, the procedures used, and the sample that are described in detail.The article ends with a debate about the results and some thoughts about the importance to operationalize the construct of the complexity.The added value of this study is to provide, for the first time, a contribution to the operationalization of the construct of complexity. The complex and simple images can be used by the scientific community as a catalog that could be used in different fields of application (for example clinical/experimental, marketing/advertising, etc.)

A CFD approach to rubble mound breakwater design

The paper provides some developments of a numerical approach ("Numerical Calculation of Flow Within Armour Units", FWAU) to the design of rubble mound breakwaters. The hydrodynamics of wave induced flow within the interstices of concrete blocks is simulated by making use of advanced, but well tested, CFD techniques to integrate RANS equations.While computationally very heavy, FWAU is gaining ground, due to its obvious advantages over the "porous media", i.e. the possibility of accounting for the highly non stationary effects, the reduced need of ad hoc calibration of filtration parameters and also – in perspective – the evaluation of hydrodynamic forces on single blocks. FWAU however is a complex technique, and in order to turn it into a practical design tool, a number of difficulties have to be overcome.The paper presents recent results about this validation, as well as insight into fluid dynamical aspects. Keywords: Numerical simulation, Breakwaters, Run up, Reflection, Rubble moun

The evolving role of microsatellite instability in colorectal cancer: A review

Microsatellite instability (MSI) is a molecular marker of a deficient mismatch repair (MMR) system and occurs in approximately 15% of colorectal cancers (CRCs), more frequently in early than late-stage of disease. While in sporadic cases (about two-thirds of MSI-H CRCs) MMR deficiency is caused by an epigenetic inactivation of MLH1 gene, the remainder are associated with Lynch syndrome, that is linked to a germ-line mutation of one of the MMR genes (MLH1, MSH2, MSH6, PMS2). MSI-H colorectal cancers have distinct clinical and pathological features such as proximal location, early-stage (predominantly stage II), poor differentiation, mucinous histology and association with BRAF mutations. In early-stage CRC, MSI can select a group of tumors with a better prognosis, while in metastatic disease it seems to confer a negative prognosis. Although with conflicting results, a large amount of preclinical and clinical evidence suggests a possible resistance to 5-FU in these tumors. The higher mutational load in MSI-H CRC can elicit an endogenous immune anti-tumor response, counterbalanced by the expression of immune inhibitory signals, such as PD-1 or PD-L1, that resist tumor elimination. Based on these considerations, MSI-H CRCs seem to be particularly responsive to immunotherapy, such as anti-PD-1, opening a new era in the treatment landscape for patients with metastatic CRC

Clinical Management of Critical COVID-19 Patients: Insights from the Literature and "On the Field" Experience

AbstractThe recent outbreak of the coronavirus disease (COVID-19) is a health emergency all over the world. Several health care professionals are currently putting their best efforts to deal with this situation. The aim of this review is to report insights from the literature and "on the field" experience in clinical management of critical COVID-19 patients. Respiratory support varies from high flow nasal cannula (HFNC) to noninvasive and invasive mechanical ventilation, often associated with nitric oxide, prone position, and extracorporeal membrane oxygenation (ECMO). Experienced specialists have to manage the airways minimizing any contamination and virus spread. The hemodynamic management of critical COVID-19 patients requires not only an accurate fluid strategy, but also an appropriate use of vasopressors and inotropes. Various adjuvant treatments have been proposed: antiviral drugs, immunomodulators, anticoagulants, antibiotics, and nutrition

Fluorescence Lifetime Nanoscopy of Liposomal Irinotecan Onivyde: From Manufacturing to Intracellular Processing

: Onivyde was approved by the Food and Drug Administration (FDA) in 2015 for the treatment of solid tumors, including metastatic pancreatic cancer. It is designed to encapsulate irinotecan at high concentration, increase its blood-circulation lifetime, and deliver it to cells where it is enzymatically converted into SN-38, a metabolite with 100- to 1000-fold higher anticancer activity. Despite a rewarding clinical path, little is known about the physical state of encapsulated irinotecan within Onivyde and how this synthetic identity changes throughout the process from manufacturing to intracellular processing. Herein, we exploit irinotecan intrinsic fluorescence and fluorescence lifetime imaging microscopy (FLIM) to selectively probe the supramolecular organization of the drug. FLIM analysis on the manufacturer's formulation reveals the presence of two coexisting physical states within Onivyde liposomes: (i) gelated/precipitated irinotecan and (ii) liposome-membrane-associated irinotecan, the presence of which is not inferable from the manufacturer's indications. FLIM in combination with high-performance liquid chromatography (HPLC) and a membrane-impermeable dynamic quencher of irinotecan reveals rapid (within minutes) and complete chemical dissolution of the gelated/precipitated phase upon Onivyde dilution in standard cell-culturing medium with extensive leakage of the prodrug from liposomes. Indeed, confocal imaging and cell-proliferation assays show that encapsulated and nonencapsulated irinotecan formulations are similar in terms of cell-uptake mechanism and cell-division inhibition. Finally, 2-channel FLIM analysis discriminates the signature of irinotecan from that of its red-shifted SN-38 metabolite, demonstrating the appearance of the latter as a result of Onivyde intracellular processing. The findings presented in this study offer fresh insights into the synthetic identity of Onivyde and its transformation from production to in vitro administration. Moreover, these results serve as another validation of the effectiveness of FLIM analysis in elucidating the supramolecular organization of encapsulated fluorescent drugs. This research underscores the importance of leveraging advanced imaging techniques to deepen our understanding of drug formulations and optimize their performance in delivery applications

Retrograde Positive Contrast Urethrocystography of the Fish Urogenital System

The radiological differences between the urinary tract of  Dicentrarchus labrax, Sparus aurata, Tinca tinca, and Cyprinus carpio are shown. In fresh water teleosts the urinary bladder is sigmoid and a short urethra leads to the urinary pore. Genital and anal pores are present. In Sparus aurata the urinary bladder has a globoid shape. In Dicentrarchus labrax the urinary bladder is smaller and elongate. In both marine teleosts a single urogenital pore is visible. Positive contrast was used to survey the urogenital system and evaluate shape and size of the bladder, urethra, ureter, and gonadal ducts. Results demonstrate the morphological variability of the urinary bladder and the craniodorsal entry of the ureters into the bladder. It is envisaged that this work will provide baseline information for further imaging studies for investigating the urogenital morphology and can be applied to identify disorders in fishes. Furthermore, the main interest of this study is that it demonstrates the morphological variability of the lower urinary system that exists between different species of fishes