Bone substitutes are being increasingly used in surgery as over two millions bone grafting procedures are performed worldwide per year. Autografts still represent the gold standard for bone substitution, though the morbidity and the inherent limited availability are the main limitations. Allografts, i.e. banked bone, are osteoconductive and weakly osteoinductive, though there are still concerns about the residual infective risks, costs and donor availability issues. As an alternative, xenograft substitutes are cheap, but their use provided contrasting results, so far. Ceramic-based synthetic bone substitutes are alternatively based on hydroxyapatite (HA) and tricalcium phosphates, and are widely used in the clinical practice. Indeed, despite being completely resorbable and weaker than cortical bone, they have exhaustively proved to be effective. Biomimetic HAs are the evolution of traditional HA and contains ions (carbonates, Si, Sr, Fl, Mg) that mimic natural HA (biomimetic HA). Injectable cements represent another evolution, enabling mininvasive techniques. Bone morphogenetic proteins (namely BMP2 and 7) are the only bone inducing growth factors approved for human use in spine surgery and for the treatment of tibial nonunion. Demineralized bone matrix and platelet rich plasma did not prove to be effective and their use as bone substitutes remains controversial. Experimental cell-based approaches are considered the best suitable emerging strategies in several regenerative medicine application, including bone regeneration. In some cases, cells have been used as bioactive vehicles delivering osteoinductive genes locally to achieve bone regeneration. In particular, mesenchymal stem cells have been widely exploited for this purpose, being multipotent cells capable of efficient osteogenic potential. Here we intend to review and update the alternative available techniques used for bone fusion, along with some hints on the advancements achieved through the experimental research in this field.

IMPORTANCE There are limited data on mortality and complications rates in patients with coronavirus disease 2019 (COVID-19) who undergo surgery. OBJECTIVE To evaluate early surgical outcomes of patients with COVID-19 in different subspecialties. DESIGN, SETTING, AND PARTICIPANTS This matched cohort study conducted in the general, vascular and thoracic surgery, orthopedic, and neurosurgery units of Spedali Civili Hospital (Brescia, Italy) included patients who underwent surgical treatment from February 23 to April 1, 2020, and had positive test results for COVID-19 either before or within 1 week after surgery. Gynecological and minor surgical procedures were excluded. Patients with COVID-19 were matched with patients without COVID-19 with a 1:2 ratio for sex, age group, American Society of Anesthesiologists score, and comorbidities recorded in the surgical risk calculator of the American College of Surgeons National Surgical Quality Improvement Program. Patients older than 65 years were also matched for the Clinical Frailty Scale score. EXPOSURES Patients with positive results for COVID-19 and undergoing surgery vs matched surgical patients without infection. Screening for COVID-19 was performed with reverse transcriptase-polymerase chain reaction assay in nasopharyngeal swabs, chest radiography, and/or computed tomography. Diagnosis of COVID-19 was based on positivity of at least 1 of these investigations. MAIN OUTCOMES AND MEASURES The primary end point was early surgical mortality and complications in patients with COVID-19; secondary end points were the modeling of complications to determine the importance of COVID-19 compared with other surgical risk factors. RESULTS Of 41 patients (of 333 who underwent operation during the same period) who underwent mainly urgent surgery, 33 (80.5%) had positive results for COVID-19 preoperatively and 8 (19.5%) had positive results within 5 days from surgery. Of the 123 patients of the combined cohorts (78 women [63.4%]; mean [SD] age, 76.6 [14.4] years), 30-day mortality was significantly higher for those with COVID-19 compared with control patients without COVID-19 (odds ratio [OR], 9.5; 95% CI, 1.77-96.53). Complications were also significantly higher (OR, 4.98; 95% CI, 1.81-16.07); pulmonary complications were the most common (OR, 35.62; 95% CI, 9.34-205.55), but thrombotic complications were also significantly associated with COVID-19 (OR, 13.2; 95% CI, 1.48-ϱ). Different models (cumulative link model and classification tree) identified COVID-19 as the main variable associated with complications. CONCLUSIONS AND RELEVANCE In this matched cohort study, surgical mortality and complications were higher in patients with COVID-19 compared with patients without COVID-19. These data suggest that, whenever possible, surgery should be postponed in patients with COVID-19.

The paper introduces a systematic procedure to coarse-grain atomistic models of the largest family of synthetic polymers into a mesoscopic model that is able to keep detailed information about chain stereosequences. The mesoscopic model consists of sequences of superatoms centered on methylene carbons of two different types according to the kind of diad (m or r) they belong to. The corresponding force-field contains three different bonds, six angle and three nonbonded terms. Recently developed analytical potentials, based on sums of Gaussians for bond and angle terms of the mesoscale force field have been used. For the nonbonded part, numerical potentials optimized by pressure-corrected iterative Boltzmann inversion have been used. As test case we coarse-grained an atomistic all-atom model of atactic polystyrene. The proposed mesoscale model has been successfully tested against structural and dynamical properties for different chain lengths and opens the possibility of relaxing melts of high molecular weight vinyl polymers.

As in ref 6, each coarse-grained distribution of an internal bonded co-ordinate θ is expressed in terms of a sum of n Gaussian functions g i (θ ), each characterized by its center (θ ci ), integral area (A i ) and width (w i ):