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Objective Stentless bioprosthetic valves such as the Freestyle conduit have been widely used as an option for aortic root replacement in the setting of aortic root aneurysms with acceptable long-term outcomes. However, there is a paucity of data regarding the use of the Freestyle prosthesis in patients with aortic stenosis. Methods All patients with a primary diagnosis of severe aortic stenosis who underwent complete aortic root replacement with Freestyle conduits were included. Primary outcomes included survival and readmissions for heart failure. Secondary outcomes included immediate postoperative complications. Results In total, 2529 patients with severe aortic stenosis who needed an open aortic valve replacement with a biological prosthesis were operated on between 2011 and 2017. Of these, 294 patients underwent aortic root replacements using the Freestyle conduit with a primary diagnosis of native or prosthetic aortic stenosis. Eighty-four (28.6%) of the patients underwent reoperative sternotomy. The majority (53.7%) of the cohort were men. The mean age was 67.5 ± 13.0 years. Mean Society of Thoracic Surgeons Predicted Risk of Mortality when calculated with the assumption of aortic valve replacement ± coronary artery bypass grafting was 8.10% ± 10.8. The median follow-up time for the entire group was 2.7 years (interquartile range 0.9-4.5 years). Operative (30-day) mortality was 7.1% (n = 21). Kaplan–Meier mortality estimates at 1 and 5 years are 16.6% and 27.6%, respectively. Mean gradients were 7.15 ± 4.47 mm Hg at 1 month and 6.32 ± 4.76 mm Hg at 1 year. Readmissions for heart failure at 30 days, 1 year, and 5 years were 5.6%, 11.8%, and 17.4%, respectively. Conclusions Aortic root replacement using Freestyle bioprostheses is a viable option for patients with severe aortic stenosis with low risk of hospital readmission for heart failure.

Surgical implantation of a prosthetic aortic valve is typically done with multiple interrupted sutures. We adapted a running suture line technique for prostheses implantation to decrease the rate of complete heart block necessitating permanent pacemaker. 374 patients undergoing isolated aortic valve replacements were identified between 2015 and 2017. Patients with preoperative heart block, patients undergoing concomitant MAZE procedure and those undergoing multivalve procedures were excluded. Interrupted technique was performed with multiple non-pledgeted sutures. Running technique was performed with three 2–0 polypropylene sutures. Propensity-score matching (caliper distance = 0.10) was used to match based on patient age, gender, BMI, diabetes mellitus, renal failure, heart failure, arrythmias, use of anti-arrhythmics, and STS PROM. Propensity score matching yielded 103 pairs of running technique and interrupted technique patients for analysis. Within the propensity score-matched cohort, there were no differences in sustained complete heart block and need for pacemaker, 4 (3.8%) for running technique vs 3 (2.9%) for interrupted technique (p = 0.307). At 4 weeks, there was no difference in mean prosthetic aortic valve gradients calculated on transthoracic echocardiogram (6.39 ± 2.47 mmHg vs 6.46 ± 2.86, p = 0.850). There was no difference in paravalvular leak (0 (0%) vs 2 (1.9%), p = 0.070). Surgical implantation of a prosthetic aortic valve may be performed with a running suture technique without any significant increase in risk of heart block, need for permanent pacemaker or paravalvular leak. Long-term data will be critical to evaluate any development of paravalvular leaks in the future.

Heteropolymers are important examples of self-assembling systems. However, in the design of artificial heteropolymers the control over the single chain self-assembling properties does not reach that of the natural bio-polymers, and in particular proteins. Here, we introduce a sufficiency criterion to identify polymers that can be designed to adopt a predetermined structure and show that it is fulfilled by polymers made of monomers interacting through directional (anisotropic) interactions. The criterion is based on the appearance of a particular peak in the radial distribution function, that we show being a universal feature of all designable heteropolymers, as it is present also in natural proteins. Our criterion can be used to engineer new self-assembling modular polymers that will open new avenues for applications in materials science.

Objective To study mid-term survival in patients with infective endocarditis as a result of IV drug use undergoing aortic root replacement with cryopreserved aortic homograft. Methods Patients undergoing aortic root homograft replacement from 2011-2017 were studied retrospectively. Aortic root replacement was performed using a modified Bentall technique. Primary outcomes included both short-term and mid-term survival. Secondary outcomes included immediate postoperative complications. Results A total of 138 patients underwent cryopreserved homograft replacement of the aortic root for aortic root abscesses. Eighty-five patients (61.6%) underwent reoperative sternotomy, and 12 patients (8.7%) underwent second or third reoperative sternotomy. Sixty-seven (48.5%) patients had severe aortic insufficiency preoperatively. Operative mortality was 12.3% (17 patients). Five patients (3.6%) sustained a permanent stroke. Twenty-one patients (15.2%) required dialysis for renal failure, and 21 patients (15.2%) had complete heart block necessitating a permanent pacemaker. Estimated 5-year mortality for the cohort was 43%. Conclusions Cryopreserved homograft replacement is a safe and desirable option for high-risk patients with infective endocarditis and aortic root abscess. Homograft accommodation for a widely debrided aortic annular bed provides a reasonable surgical strategy for patients needing aortic root replacement with annular abscess.

Background Thoracic esophageal diverticula are uncommon, and controversies exist regarding their management. The objective of this study was to evaluate the outcomes of a relatively large cohort of patients with thoracic esophageal diverticula treated with minimally invasive surgical techniques. Methods We conducted a retrospective review of patients who underwent minimally invasive surgical treatment for symptomatic esophageal diverticula during a 15-year period. The primary end point was 30-day mortality. In addition, we evaluated the morbidity, improvement in dysphagia (score: 1, best to 5, worst), and quality of life (Gastroesophageal Reflux Disease–Health-Related Quality of Life score: 0, best to 50, most symptoms). Results Fifty-seven patients underwent minimally invasive surgical treatment of symptomatic thoracic esophageal diverticula. The most common symptom was dysphagia (45 of 57; 79%). A motility disorder or distal mechanical obstruction was identified in 49 patients (86%). Approaches used included video-assisted thoracoscopic surgery (n = 33), laparoscopy (n = 18), and combined video-assisted thoracoscopic surgery and laparoscopy (n = 6). The most common procedure performed was diverticulectomy and myotomy (47 of 57 patients; 82.5%). The 30-day mortality was 0%. There were 4 patients (7%) with postoperative leaks requiring reoperation. During follow-up, the median dysphagia score improved from 3 to 1 ( p Conclusions A minimally invasive surgical approach for the management of thoracic esophageal diverticula is safe and effective during intermediate-term follow-up when performed by surgeons experienced in esophageal surgery and minimally invasive techniques. Further follow-up is required to assess the durability of these results. The optimal approach and procedures performed should be determined on an individualized basis after a thorough investigation.

Proteins work only if folded in their native state, but changes in temperature T and pressure P induce their unfolding. Therefore for each protein there is a stability region (SR) in the T-P thermodynamic plane outside which the biomolecule is denaturated. It is known that the extension and shape of the SR depend on i) the specific protein residue-residue interactions in the native state of the amino acids sequence and ii) the water properties at the hydration interface. Here we analyze by Monte Carlo simulations of different coarse-grained protein models in explicit water how changes in i) and ii) affect the SR. We show that the solvent properties ii) are essential to rationalize the SR shape at low T and high P and that our finding are robust with respect to parameter changes and with respect to different protein models. These results can help in developing new strategies for the design of novel synthetic biopolymers., 15 pages, 10 figures

A re-entrant gas-liquid spinodal was proposed as a possible explanation of the apparent divergence of the compressibility and specific heat off supercooling water. Such a counter-intuitive possibility, e.g., a liquid that becomes unstable to gas-like fluctuations on cooling at positive pressure, has never been observed, neither in real substances nor in off-lattice simulations. More recently, such a re-entrant scenario has been dismissed on the premise that the re-entrant spinodal would collide with the gas-liquid coexisting curve (binodal) in the pressure-temperature plane. Here we study, numerically and analytically, two previously introduced one-component patchy particle models that both show (i) a re-entrant limit of stability of the liquid phase and (ii) a re-entrant binodal, providing a neat in silico (and in charta) realization of such unconventional thermodynamic scenario. info:eu-repo/semantics/publishedVersion

We analyze the role of water at biological and inorganic interfaces. In fields like food processing, food preservation or bionanotechnology the fluctuations in density and entropy due to hydration water have consequences that go from damaging the tissues to reducing the cell death for dehydration to regulating the food stability to controlling the heat-exchange at the nanoscale. We focus on the thermodynamics of hydration water at cryopreservation temperatures and its effects on the dynamics of nano-confined and protein-hydration water. We consider the relevance of confining heterogeneities for controlling the physical properties of hydration water and the effects of interfacial water on protein stability. To this aim, we describe a coarse-grained model of water that allows us to perform theoretical calculations and numerical simulations, presenting our latest results and the work in progress. Our investigation is at the frontier of knowledge in Physics, Chemistry and Biology, with a potential impact on fields such as Nanoscience, Nanotechnology and Food Science.

We study the translocation of polymers across varying-section channels. Using systematic approximations, we derive a simplified model that reduces the problem of polymer translocation through varying-section channels to that of a point-like particle under the action of an effective potential. Such a model allows us to identify the relevant parameters controlling the polymer dynamics and, in particular, their translocation time. By comparing our analytical results with numerical simulations we show that, under suitable conditions, our model provides reliable predictions of the dynamics of both Gaussian and self-avoiding polymers, in two- and three-dimensional confinements. Moreover, both theoretical predictions, as well as Brownian dynamic results, show a non-monotonous dependence of polymer translocation velocity as a function of polymer size, a feature that can be exploited for polymer separation.

The mechanisms of cold and pressure denaturation of proteins are a matter of debate, but it is commonly accepted that water plays a fundamental role in the process. It has been proposed that the denaturation process is related to an increase of hydrogen bonds among hydration water molecules. Other theories suggest that the causes of denaturation are the density fluctuations of surface water, or the destabilization of hydrophobic contacts as a consequence of water molecule inclusions inside the protein, especially at high pressures. We review some theories that have been proposed to give insight into this problem, and we describe a coarse-grained model of water that compares well with experiments for proteins’ hydration water. We introduce its extension for a homopolymer in contact with the water monolayer and study it by Monte Carlo simulations in an attempt to understand how the interplay of water cooperativity and interfacial hydrogen bonds affects protein stability.

Water is essential for the activity of proteins. However, the effect of the properties of water on the behavior of proteins is only partially understood. Recently, several experiments have investigated the relation between the dynamics of the hydration water and the dynamics of protein. These works have generated a large amount of data whose interpretation is debated. New experiments measure the dynamics of water at low temperature on the surface of proteins, finding a qualitative change (crossover) that might be related to the slowing down and stop of the protein’s activity (protein glass transition), possibly relevant for the safe preservation of organic material at low temperature. To better understand the experimental data several scenarios have been discussed. Here, we review these experiments and discuss their interpretations in relation with the anomalous properties of water. We summarize the results for the thermodynamics and dynamics of supercooled water at an interface. We consider also the effect of water on protein stability, making a step in the direction of understanding, by means of Monte Carlo simulations and theoretical calculations, how the interplay of water cooperativity and hydrogen bonds interfacial strengthening affects the protein cold denaturation.

Objective Lung transplantation is a life-saving procedure for patients who have end-stage lung disease. The frequency and severity of complications have not been fully characterized. We hypothesized that early in-hospital, postoperative complications decrease long-term survival. Methods We retrospectively identified in-hospital complications in lung transplant recipients, from the period January 2007 to October 2013. Complications were graded using the extended Accordion Severity Grading System (ASGS). Complications were categorized by event and organ system. Survival analysis was performed ( P Results Among 748 eligible patients, 3381 independent in-hospital, postoperative complications occurred in 92.78% of patients. Median follow-up was 5.4 years. Complications associated with significant decrease in 5-year survival were: renal (hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.40-4.48); hepatic (HR 4.08, 95% CI 2.86-5.82); cardiac (HR 1.95, 95% CI 1.56-2.45). The maximum ASGS of ≥5 (18.5% vs 73.8%), and the weighted ASGS sum >10 (2.5% vs 73.8%), were found to be significant predictors of long-term survival. Multivariate analysis identified a weighted ASGS sum of >10, and renal, cardiac, and vascular complications as predictors of decreased long-term survival. Conclusions Rigorous delineation of complications after lung transplantation showed that grade 5 ASGS in-hospital postoperative complications, and a weighted ASGS sum >10, were independent predictors of decreased long-term survival well beyond the initial perioperative period. These results may identify important targets for best practice guidelines and quality-of-care measures after lung transplantation.

The mechanisms of cold and pressure denaturation of proteins are matter of debate and are commonly understood as due to water-mediated interactions. Here, we study several cases of proteins, with or without a unique native state, with or without hydrophilic residues, by means of a coarse-grain protein model in explicit solvent. We show, using Monte Carlo simulations, that taking into account how water at the protein interface changes its hydrogen bond properties and its density fluctuations is enough to predict protein stability regions with elliptic shapes in the temperature-pressure plane, consistent with previous theories. Our results clearly identify the different mechanisms with which water participates to denaturation and open the perspective to develop advanced computational design tools for protein engineering.

A variety of important cellular processes require, for functional purposes, the colocalization of multiple DNA loci at specific time points. In most cases, the physical mechanisms responsible for bringing them in close proximity are still elusive. Here we show that the interaction of DNA loci with a concentration of diffusing molecular factors can induce spontaneously their colocalization, through a mechanism based on a thermodynamic phase transition. We consider up to four DNA loci and different valencies for diffusing molecular factors. In particular, our analysis illustrates that a variety of nontrivial stable spatial configurations is allowed in the system, depending on the details of the molecular factor/DNA binding-sites interaction. Finally, we discuss as a case study an application of our model to the pairing of X chromosome at X inactivation, one of the best-known examples of DNA colocalization. We also speculate on the possible links between X colocalization and inactivation.

Esophageal cancer is one of the most common malignancies in the world today and the sixth-leading cause of cancer-related mortality. Accurate preoperative staging of esophageal cancer is imperative to the selection of appropriate treatments. Patients with esophageal carcinomas typically undergo a multimodality staging process including noninvasive imaging techniques, such as computed tomography (CT) and positron emission tomography (PET), as well as endoscopic ultrasound (EUS), which is slightly more invasive. Minimally invasive surgical staging, with laparoscopy, occasionally in combination with video-assisted thoracoscopy, is used in the staging process at select institutions and has been shown to be more accurate than noninvasive staging modalities. Two major advantages of minimally invasive surgical staging over conventional techniques are the improved assessment of locoregional disease and enhanced identification of distant metastases. These advantages decrease the likelihood that the patient will undergo a nontherapeutic laparotomy. Currently, no clear consensus exists regarding which patients with esophageal cancer would benefit most from the addition of minimally invasive surgical staging. We have, however, found that minimally invasive surgical staging with laparoscopy is particularly valuable in detection of occult distant metastases. In this article, we summarize the staging modalities for esophageal cancer including minimally invasive surgical staging.

The properties of water can have a strong dependence on the confinement. Here, we consider a water monolayer nanoconfined between hydrophobic parallel walls under conditions that prevent its crystallization. We investigate, by simulations of a many-body coarse-grained water model, how the properties of the liquid are affected by the confinement. We show, by studying the response functions and the correlation length and by performing finite-size scaling of the appropriate order parameter, that at low temperature the monolayer undergoes a liquid-liquid phase transition ending in a critical point in the universality class of the two-dimensional (2D) Ising model. Surprisingly, by reducing the linear size L of the walls, keeping the walls separation h constant, we find a 2D-3D crossover for the universality class of the liquid-liquid critical point for L=h ≃ 50, i.e. for a monolayer thickness that is small compared to its extension. This result is drastically different from what is reported for simple liquids, where the crossover occurs for L=h ≃ 5, and is consistent with experimental results and atomistic simulations. We shed light on these findings showing that they are a consequence of the strong cooperativity and the low coordination number of the hydrogen bond network that characterizes water.

Background A significant number of patients have recurrent or persistent lung cancer despite complete resection or treatment with definitive chemoradiation. Stereotactic radiosurgery (SRS)/stereotactic body radiation therapy is emerging as an important modality for the treatment of early-stage lung neoplasm; SRS may also offer an alternative treatment option for patients with recurrent lung disease. We evaluated outcomes after treatment with SRS for recurrent lung neoplasm in a large series of patients. Methods Selected patients with limited recurrent, persistent, or progressive disease after one or more prior treatments for lung cancer were offered SRS. Thoracic surgeons evaluated all patients, placed fiducials when needed, and planned treatment in close collaboration with radiation oncologists and medical physicists. In our early experience, a single fraction of 20 Gy radiation was prescribed and was subsequently increased to 45 to 60 Gy in three to five fractions. The primary endpoint evaluated was overall survival. Results We treated 100 patients with recurrent lung cancer (median age 72 years) with SRS. The postprocedure 30-day mortality rate was 0%; median follow-up was 51 months (range, 5 to 123). The median overall survival for the entire group was 23 months (95% confidence interval: 19 to 41). The probability of 2-year and 5-year overall survival was 49% (95% confidence interval: 40% to 60%) and 31% (95% confidence interval: 23% to 43%), respectively. Conclusions Our experience indicates that SRS is safe, and offers an alternative modality for selected patients with recurrent oligometastatic or persistent lung cancer. Thoracic surgeons should actively participate in SRS and continue to evaluate the efficacy of this treatment strategy.

Intractable gastroesophageal reflux disease (GERD) after antireflux operations presents a challenge-particularly in obese patients and patients with esophageal dysmotility-and increases the complexity of the redo operation. This study evaluated the results of Roux-en-Y near esophagojejunostomy (RNYNEJ) in the management of recurrent GERD after antireflux operations.We conducted a retrospective review of overweight patients with intractable GERD who underwent RNYNEJ for failed antireflux operations. We evaluated perioperative outcomes, dysphagia (ranging from 1 = no dysphagia to 5 = unable to swallow saliva), and quality of life (QOL) (assessed using the GERD health-related quality-of-life instrument (HRQOL).Over a 12-year period, 105 patients with body mass index (BMI) greater than 25 underwent RNYNEJ for failed antireflux operations. Most were obese (BMI30; 82 patients [78%]); esophageal dysmotility was demonstrated in more than one-third of patients. Forty-eight (46%) patients had multiple antireflux operations before RNYNEJ, and 27 patients had undergone a previous Collis gastroplasty. There was no perioperative mortality. Major complications, including anastomotic leak requiring surgical intervention (n = 3 [2.9%]), were noted in 25 patients (24%).The median length of stay was 6 days. During follow-up (mean, 23.39 months), median BMI decreased from 35 to 27.6 (p0.0001), and the mean dysphagia score decreased from 2.9 to 1.5 (p0.0001). The median GERD HRQOL score, assessed in a subset of patients, was 9 (classified as excellent).RNYNEJ for persistent GERD after antireflux operations in appropriately selected patients can be performed safely with good results in experienced centers. RNYNEJ should be considered an important option for the treatment of intractable recurrent symptoms after antireflux operations, particularly in obese patients.

Background We have previously described our technique of robotic-assisted giant paraesophageal hernia repair (RA-GPEHR). The purpose of this study was to report our initial experience, early outcomes and learning curve with RA-GPEHR using a four-arm robotic platform. Methods 24 consecutive patients presenting with symptomatic giant paraesophageal hernias (GPEH) underwent RA-GPEHR from April 2011 to February 2014. Peri-operative data and short-term patient outcomes were assessed by retrospective review of a prospectively maintained database. Results Median age was 62 years (range 44–84). 15 (63%) patients underwent fundoplication and 9 (37%) gastropexy. Median procedure time was 277 min (range: 185–485) and decreased steadily over the experience. There were no intra-operative complications or surgical mortality. No patients experienced dysphagia in the early post-operative period. Conclusions RA-GPEHR is safe, with reported short-term operative and functional outcomes similar to conventional laparoscopic approaches. The initial learning curve appears relatively short for experienced minimally invasive esophageal surgeons. Copyright © 2016 John Wiley & Sons, Ltd.

In this work, we study by means of simulations of hard spheres the equilibrium between a spherical solid cluster and the fluid. In the NVT ensemble we observe stable/metastable clusters of the solid phase in equilibrium with the fluid, representing configurations that are global/local minima of the Helmholtz free energy. Then, we run NpT simulations of the equilibrated system at the average pressure of the NVT run and observe that the clusters are critical because they grow/shrink with a probability of 1/2. Therefore, a crystal cluster equilibrated in the NVT ensemble corresponds to a Gibbs free energy máximum where the nucleus is in unstable equilibrium with the surrounding fluid, in accordance with what has been recently shown for vapor bubbles in equilibrium with the liquid. Then, within the Seeding framework, we use Classical Nucleation Theory to obtain both the interfacial free energy γ and the nucleation rate. The latter is in very good agreement with independent estimates using techniques that do not rely on Classical Nucleation Theory when the mislabeling criterion is used to identify the molecules of the solid cluster. We therefore argue that the radius obtained from the mislabeling criterion provides a good approximation for the radius of tension, R_s . We obtain an estimate of the Tolman length by extrapolating the difference between R e (the Gibbs dividing surface) and R s to infinite radius. We show that such definition of the Tolman length coincides with that obtained by fitting γ versus 1/R_s to a straight line as recently applied to hard spheres.