Background and Aims
Hepatitis C virus (HCV)‐viremic organs are underutilized, and there is limited real‐world experience on the transplantation of HCV‐viremic solid organs into recipients who are HCV ...negative.
Approach and Results
Patients listed or being evaluated for solid organ transplant after January 26, 2018, were educated and consented by protocol on the transplantation of HCV‐viremic organs. All recipients were HCV nucleic acid test and anti‐HCV antibody negative at the time of transplant and received an HCV‐viremic organ. The primary outcome was sustained virological response (SVR) at 12 weeks after completion of direct‐acting antiviral (DAA) therapy (SVR12). Seventy‐seven patients who were HCV negative underwent solid organ transplantation from a donor who was HCV viremic. No patients had evidence of advanced hepatic fibrosis. Treatment regimen and duration were at the discretion of the hepatologist. Sixty‐four patients underwent kidney transplant (KT), and 58 KT recipients had either started or completed DAA therapy. Forty‐one achieved SVR12, 10 had undetectable viral loads but are not eligible for SVR12, and 7 remain on treatment. One KT recipient was a nonresponder because of nonstructural protein 5A resistance. Four patients underwent liver transplant and 2 underwent liver‐kidney transplant. Three patients achieved SVR12, 1 has completed DAA therapy, and 2 remain on treatment. Six patients underwent heart transplant and 1 underwent heart‐kidney transplant. Six patients achieved SVR12 and 1 patient remains on treatment.
Conclusions
Limited data exist on the transplantation of HCV‐viremic organs into recipients who are HCV negative. Our study is the largest to describe a real‐world experience of the transplantation of HCV‐viremic organs into recipients who are aviremic. In carefully selected patients, the use of HCV‐viremic grafts in the DAA era appears to be efficacious and well tolerated.
Coherently moving flocks of birds, beasts, or bacteria are examples of living matter with spontaneous orientational order. How do these systems differ from thermal equilibrium systems with such ...liquid crystalline order? Working with a fluidized monolayer of macroscopic rods in the nematic liquid crystalline phase, we find giant number fluctuations consistent with a standard deviation growing linearly with the mean, in contrast to any situation where the central limit theorem applies. These fluctuations are long-lived, decaying only as a logarithmic function of time. This shows that flocking, coherent motion, and large-scale inhomogeneity can appear in a system in which particles do not communicate except by contact.
SARS‐CoV2, first described in December 2019, was declared a pandemic by the World Health Organization in March 2020. Various surgical and medical societies promptly published guidelines, based on ...expert opinion, on managing patients with COVID‐19, with a consensus to postpone elective surgeries and procedures. We describe the case of an orthotopic liver transplantation (OLT) in a young female who presented with acute liver failure secondary to acetaminophen toxicity to manage abdominal pain and in the setting of a positive SARS‐CoV2 test. Despite a positive test, she had no respiratory symptoms at time of presentation. The positive test was thought to be residual viral load. The patient had a very favorable outcome, likely related to multiple factors including her young age, lack of respiratory COVID‐19 manifestations and plasma exchange peri‐operatively. We recommend a full work‐up for OLT in COVID‐19 patients with uncomplicated disease according to standard of care, with careful interpretation of COVID‐19 testing in patients presenting with conditions requiring urgent or emergent surgery as well as repeat testing even a few days after initial testing, as this could alter management.
A young patient with a positive SARS‐CoV‐2 test and recent COVID‐19 undergoes successful liver transplantation for acute liver failure secondary to acetaminophen overdose.
There are emerging data depicting the clinical presentation of coronavirus disease 19 (COVID‐19) in solid organ transplant recipients but negligible data‐driven guidance on clinical management. A ...biphasic course has been described in some infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), beginning with a flu‐like illness followed by an intense inflammatory response characterized by elevated c‐reactive protein (CRP), interleukin 6 (IL‐6), and acute respiratory distress syndrome (ARDS) associated with high mortality. The exuberant and possibly dysregulated immune response has prompted interest in therapeutic agents that target the cytokines involved, particularly IL‐6. Tocilizumab is an IL‐6 receptor antagonist with a record of use for a variety of rheumatologic conditions and cytokine release syndrome due to chimeric antigen receptor T‐cell therapy but experience in solid organ and composite tissue transplant recipients (SOT/CTTRs) with SARS‐CoV‐2‐related ARDS has not been previously reported in detail. We present the clinical course of 5 SOT/CTTRs with SARS‐CoV‐2‐related ARDS that received tocilizumab with favorable short‐term outcomes in 4. Responses were characterized by reductions in CRP, discontinuation of vasopressors, improved oxygenation and respiratory mechanics, and variable duration of ventilator support. Four bacterial infections occurred within 2 weeks of tocilizumab administration. We discuss safety concerns and the need for randomized comparative trials to delineate tocilizumab's clinical utility in this population.
The authors describe the clinical course of solid organ and vascularized composite allograft recipients with COVID‐19–related ARDS treated with tocilizumab.
Smooth wrinkles and sharply crumpled regions are familiar motifs in biological or synthetic sheets, such as rapidly growing plant leaves and crushed foils. Previous studies have addressed both ...morphological types, but the generic route whereby a featureless sheet develops a complex shape remains elusive. Here we show that this route proceeds through an unusual sequence of distinct symmetry-breaking instabilities. The object of our study is an ultrathin circular sheet stretched over a liquid drop. As the curvature is gradually increased, the surface tension stretching the sheet over the drop causes compression along circles of latitude. The compression is relieved first by a transition into a wrinkle pattern, and then into a crumpled state via a continuous transition. Our data provide conclusive evidence that wrinkle patterns in highly bendable sheets are not described by classical buckling methods, but rather by a theory which assumes that wrinkles completely relax the compressive stress. With this understanding we recognize the observed sequence of transitions as distinct symmetry breakings of the shape and the stress field. The axial symmetry of the shape is broken upon wrinkling but the underlying stress field preserves this symmetry. Thus, the wrinkle-to-crumple transition marks symmetry-breaking of the stress in highly bendable sheets. By contrast, other instabilities of sheets, such as blistering and cracking, break the homogeneity of shape and stress simultaneously. The onset of crumpling occurs when the wrinkle pattern grows to half the sheet’s radius, suggesting a geometric, material-independent origin for this transition.
When a thin sheet is crushed into a small three-dimensional volume, it invariably forms a structure with a low volume fraction but high resistance to further compression. Being a far-from-equilibrium ...process, forced crumpling is not necessarily amenable to a statistical description in which the parameters of the initially flat sheet and the final confinement fully specify the resulting crumpled state. Instead, the internal geometry and mechanical properties of the crumpled ball may reflect the history of its preparation. Our X-ray microtomography experiments reveal that the internal three-dimensional geometry of a crumpled ball is in many respects isotropic and homogeneous. In these respects, crumpling recapitulates other classic nonequilibrium problems such as turbulence, where a system driven by long-wavelength, low-symmetry, forcing shows only rather subtle fingerprints of the forcing mechanism. However, we find local nematic ordering of the sheet into parallel stacks. The layering proceeds radially inward from the outer surface. The extent of this layering increases with the volume fraction, or degree of compression.
Many complex fluids rely on surfactants to contain, protect, or isolate liquid drops in an immiscible continuous phase. Thin elastic sheets can wrap liquid drops in a spontaneous process driven by ...capillary forces. For encapsulation by sheets to be practically viable, a rapid, continuous, and scalable process is essential. We exploit the fast dynamics of droplet impact to achieve wrapping of oil droplets by ultrathin polymer films in a water phase. Despite the violence of splashing events, the process robustly yields wrappings that are optimally shaped to maximize the enclosed fluid volume and have near-perfect seams. We achieve wrappings of targeted three-dimensional (3D) shapes by tailoring the 2D boundary of the films and show the generality of the technique by producing both oil-in-water and water-in-oil wrappings.
Patients with hepatocellular carcinoma (HCC) outside Milan criteria (MC) may be candidates for liver transplantation (LT) after successful downstaging. Factors that predict successful downstaging are ...unclear. We aimed to identify the predictors of successful downstaging of HCC in patients outside MC.
We performed a retrospective cohort study on consecutive patients with HCC outside MC who received downstaging with locoregional therapy. Clinical and laboratory variables, tumor characteristics including total tumor volume (TTV) and up-to-7 criteria were recorded. We performed univariate and multivariate logistic regression analyses to identify variables associated with successful downstaging.
Of 675 patients with HCC, 90 patients outside MC received downstaging. Fifty-three (59%) patients were successfully downstaged, 37 (41%) failed downstaging. University of California at San Francisco criteria, α-fetoprotein, up-to-7 criteria, TTV, and platelet count were predictors of successful downstaging on univariate analysis. Total tumor volume was an independent predictor of successful downstaging on multivariate logistic regression (P = 0.04, area under receiver operating characteristic curve 0.89 (95% confidence interval, 0.82-0.96). Fifty-two (76%) of 68 patients with TTV less than 200 cm were successfully downstaged, whereas only 1 (4.5%) of 22 patients with TTV greater than 200 cm were successfully downstaged. Forty-five (50%) patients underwent LT. Kaplan-Meier survival rates at 1 and 5 years post-LT were 95.3% and 79.4%, respectively. Patients who were successfully downstaged had better survival than patients who failed downstaging (P < 0.01).
Total tumor volume is a good predictor of successful downstaging of HCC. Patients with TTV less than 200 cm may be considered good candidates for downstaging. Further studies with larger cohort of patients are needed to validate this approach in patients with HCC outside Milan.
An array of spheres descending slowly through a viscous fluid always clumps J. M. Crowley, J. Fluid Mech. 45, 151 (1971). We show that anisotropic particle shape qualitatively transforms this iconic ...instability of collective sedimentation. In experiment and theory on disks, aligned facing their neighbors in a horizontal one-dimensional lattice and settling at Reynolds number∼10−4in a quasi-two-dimensional slab geometry, we find that for large enough lattice spacing the coupling of disk orientation and translation rescues the array from the clumping instability. Despite the absence of inertia, the resulting dynamics displays the wavelike excitations of a mass-and-spring array, with a conserved “momentum” in the form of the collective tilt of the disks and an effective spring stiffness emerging from the viscous hydrodynamic interaction. However, the non-normal character of the dynamical matrix leads to algebraic growth of perturbations even in the linearly stable regime. Stability analysis demarcates a phase boundary in the plane of wave number and lattice spacing, separating the regimes of algebraically growing waves and clumping, in quantitative agreement with our experiments. Through the use of particle shape to suppress a classic sedimentation instability, our work uncovers an unexpected conservation law and hidden Hamiltonian dynamics which in turn open a window to the physics of transient growth of linearly stable modes.
Little is known about the utility of transcatheter aortic valve implantation (TAVI) in patients with cirrhosis of the liver, and their outcomes have not been studied extensively in literature. We ...performed a retrospective analysis of patients with severe symptomatic aortic stenosis (AS) who underwent transfemoral TAVI with a SAPIEN 3 valve at our institution between April 2015 and December 2018. We identified 32 consecutive patients with evidence of cirrhosis of the liver on imaging (including ultrasound and/or computed tomography) and patients with severe symptomatic AS who underwent transfemoral TAVI with a SAPIEN 3 valve. Among 1,028 patients, 32 had cirrhosis of the liver and 996 constituted the control group without cirrhosis. Mean age in the cirrhosis group was 74.5 years compared with 81.2 years in the control group. Baseline variables were comparable between the groups. Compared with the noncirrhotic group, patients with cirrhosis had a similar 1-year mortality (12% vs 12%, p = 1), a lower 30-day new pacemaker after TAVI rate (6% vs 9%, p = 0.85), a higher 30-day and 1-year readmission rate for heart failure (11% vs 1% and 12% vs 5%, p = 0.12, respectively), and a similar 1-year major adverse cardiac and cerebrovascular event rate (15% vs 14%, p = 0.98). In conclusion, patients with severe AS with concomitant liver cirrhosis who underwent TAVI demonstrated comparable outcomes to their noncirrhotic counterparts.
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