The Musculoskeletal Tumor Society Scoring system is a valid subjective and objective tool to evaluate outcomes of surgical treatment of patients affected by upper and lower extremity tumors.

PURPOSE: The main purpose of the present study was to evaluate if there is a difference between objective or subjective administration of the MSTS score in a cohort of patients affected by musculoskeletal oncological diseases. MATERIALS AND METHODS: All patients who underwent surgery for bone or soft tissue localization of neoplastic disease in lower or upper limb from June 2015 to June 2020 were considered eligible. In order to administer the score as a PROM, the MSTS was first translated and cross-culturally adapted in Italian. During follow up visits, all patients filled out Italian versions of SF36, TESS and MSTS. Psychometric properties of the Italian version of MSTS were analyzed. Correlation between objective and self-administered MSTS score was assessed through Pearson's coefficient. RESULTS: A finale sample of 110 patients were included: 59 affected by lower extremity involvement and 51 affected by upper extremity involvement. The Italian version of the MSTS score showed good psychometric properties for both lower and upper extremity. The correlation between self-administered and hetero-administered version of the questionnaire was as high as r = 0.97 for lower extremities and r = 0.96 for upper extremities. CONCLUSIONS: The Italian version of the MSTS is a valid tool to evaluate outcomes of surgical treatment of patients affected by extremities tumors and it can be used as a subjective tool for both lower and upper extremity.

Morphological and molecular characterization of Trichuris muris (Nematoda: Trichuridae): studies from two commensal rodent species.

In this paper we re-describe Trichuris muris based on morphological data following isolation from two commensal rodent species, Mus musculus from Mexico and Rattus rattus from Argentina. Furthermore, we provide a molecular characterization based on mitochondrial (cytochrome c oxidase subunit 1 mitochondrial gene) and nuclear (internal transcribed spacer 2 region) markers in order to support the taxonomic identification of the studied specimens of T. muris from M. musculus. We distinguished T. muris from 29 species of Trichuris found in American rodents based on morphological and biometrical features, such as the presence of a spicular tube, length of spicule, size of proximal and distal cloacal tube and non-protrusive vulva. We suggest that spicular tube patterns can be used to classify Trichuris species in three groups. Considering that the diagnosis among the species of this genus is mainly based on morphometry, this proposal represents a relevant contribution. We provide molecular studies on two markers, making this the first contribution for T. muris in the Americas. This study makes an important contribution to the integrative taxonomy of cosmopolitan nematode species, and its correct determination from the parasitological study of commensal rodents.

Open-source navigation system for tracking dissociated parts with multi-registration.

PURPOSE: During reconstructive surgery, knee and hip replacements, and orthognathic surgery, small misalignments in the pose of prosthesis and bones can lead to severe complications. Hence, the translational and angular accuracies are critical. However, traditional image-based surgical navigation lacks orientation data between structures, and imageless systems are unsuitable for cases of deformed anatomy. We introduce an open-source navigation system using a multiple registration approach that can track instruments, implants, and bones to precisely guide the surgeon in emulating a preoperative plan. METHODS: We derived the analytical error of our method and designed a set of phantom experiments to measure its precision and accuracy. Additionally, we trained two classification models to predict the system reliability from fiducial points and surface matching registration data. Finally, to demonstrate the procedure feasibility, we conducted a complete workflow for a real clinical case of a patient with fibrous dysplasia and anatomical misalignment of the right femur using plastic bones. RESULTS: The system is able to track the dissociated fragments of the clinical case and average alignment errors in the anatomical phantoms of [Formula: see text]  mm and [Formula: see text]. While the fiducial-points registration showed satisfactory results given enough points and covered volume, we acknowledge that the surface refinement step is mandatory when attempting surface matching registrations. CONCLUSION: We believe that our device could bring significant advantages for the personalized treatment of complex surgical cases and that its multi-registration attribute is convenient for intraoperative registration loosening cases.

Infusion of Non-HLA-Matched Off-the-Shelf Ex Vivo Expanded Cord Blood Progenitors in Patients Undergoing Cord Blood Transplantation: Result of a Phase II Clinical Trial.

Recipients of myeloablative cord blood transplants (CBT) are known to experience delayed hematopoietic recovery and an increased risk of transplant related mortality (TRM). We developed methods for ex vivo expansion and cryopreservation of CB stem and progenitor cells. 15 patients with hematologic malignancies were enrolled in this single center phase II trial between September 2010 and August 2012 to assess the safety of infusing a non-HLA-matched expanded CB product to bolster a conventional CBT. On the day of transplant, an infusion of the expanded CB product followed the primary graft (1 or 2 unmanipulated CB units). All patients engrafted. Median time to neutrophil and platelet recovery was 19 and 35 days, respectively. Early myelomonocytic recovery was almost entirely due to cells arising from the non-HLA-matched expansion product and were no longer detected at day 14 in all but 2 patients. The probability of 3-years disease free survival was 86%. No TRM was observed throughout the study period, and only 2 patients relapsed. All patients presented with grade II acute graft-versus-host disease (aGVHD) at a median time of 32 days, with no grade III-IV aGVHD observed. At 2 years only 2 patients remain on immunosuppressive therapy for mild chronic GVHD. This phase II safety study demonstrate that infusion of an off-the-shelf non-HLA-matched expanded CB product in addition to a conventional CB graft was safe and led to sustained myeloid recovery. Based on these encouraging results, a prospective multicenter randomized trial utilizing this product has been conducted and results will be soon released. ClinicalTrials.gov Identifier: NCT01175785.

An unusual case of death using a compacting machine.

ABSTRACT: In the large series of forensic injury, death from accidental me-chanical asphyxiation in adults is rare and is usually secondary to suffocation, aspiration, strangulation caused by entrapment of clothing in machinery (deaths at work) or asphyxiation in the course of erotic maneuvers. Compression asphyxia is a form of violent mechanical asphyxia in which the asphyxiated insult is produced by means of a compression and constriction mechanism of the thoracic cage. The authors report an unusual case of asphyxiated death from chest com-pression resulting from the action of a compacting machine, which occurred in a person who had fallen asleep in a waste bin.

Impact of T Cell Repertoire Diversity on Mortality Following Cord Blood Transplantation.

INTRODUCTION: Cord blood transplantation (CBT) recipients are at increased risk of mortality due to delayed immune recovery (IR). Prior studies in CBT patients have shown that recovery of absolute lymphocyte count is predictive of survival after transplant. However, there are no data on the association of T-cell receptor (TCR) and clinical outcomes after CBT. Here we retrospectively performed TCR beta chain sequencing on peripheral blood (PB) samples of 34 CBT patients. METHODS: All patients received a total body irradiation based conditioning regimen and cyclosporine and MMF were used for graft versus host disease (GvHD) prophylaxis. PB was collected pretransplant on days 28, 56, 80, 180, and 1-year posttransplant for retrospective analysis of IR utilizing high-throughput sequencing of TCRß rearrangements from genomic DNA extracted from PB mononuclear cells. To test the association between TCR repertoire diversity and patient outcomes, we conducted a permutation test on median TCR repertoire diversity for patients who died within the first year posttransplant versus those who survived. RESULTS: Median age was 27 (range 1-58 years) and most of the patients (n = 27) had acute leukemias. There were 15 deaths occurring between 34 to 335 days after transplant. Seven deaths were due to relapse. Rapid turnover of T cell clones was observed at each time point, with TCR repertoires stabilizing by 1-year posttransplant. TCR diversity values at day 100 for patients who died between 100 and 365 days posttransplant were significantly lower than those of the surviving patients (p = 0.01). CONCLUSIONS: Using a fast high-throughput TCR sequencing assay we have demonstrated that high TCR diversity is associated with better patient outcomes following CBT. Importantly, this assay is easily performed on posttransplant PB samples, even as early as day 28 posttransplant, making it an excellent candidate for early identification of patients at high risk of death.

Obtaining accurate and calibrated coil models for transcranial magnetic stimulation using magnetic field measurements.

Currently, simulations of the induced currents in the brain produced by transcranial magnetic stimulation (TMS) are used to elucidate the regions reached by stimuli. However, models commonly found in the literature are too general and neglect imperfections in the windings. Aiming to predict the stimulation sites in patients requires precise modeling of the electric field (E-field), and a proper calibration to adequate to the empirical data of the particular coil employed. Furthermore, most fabricators do not provide precise information about the coil geometries, and even using X-ray images may lead to subjective interpretations. We measured the three components of the vector magnetic field induced by a TMS figure-8 coil with spatial resolutions of up to 1 mm. Starting from a computerized tomography-based coil model, we applied a multivariate optimization algorithm to automatically modify the original model and obtain one that optimally fits the measurements. Differences between models were assessed in a human brain mesh using the finite-elements method showing up to 6% variations in the E-field magnitude. Our calibrated model could increase the precision of the estimated E-field induced in the brain during TMS, enhance the accuracy of delivered stimulation during functional brain mapping, and improve dosimetry for repetitive TMS. Graphical Abstract Geometrical model of TMS coil based on TAC images is optimally deformed to match magnetic field measurements. The calibrated model's induced electric field in the brain differs from the original.

In Vitro Comparative Study Between Conventional and Computer-Assisted Surgery Methods for Planning and Resection of Bone Sarcomas.

This poster aims to achieve an "in vitro" comparative study between three methods: 2D digital images planning and execution without navigation (freehand with ruler and caliper), 3D planning and execution without navigation (freehand with ruler and caliper) and 3D planning and execution guided with navigation. 3D planning and navigated procedures potentially improve sarcoma resection.

Cord blood transplantation: rewind to fast forward.

The utilization of cord blood as a source of stem cells for transplantation has decreased in recent years. Although cord blood transplantation (CBT) is an established practice for the treatment of adult and pediatric patients with hematological malignancies, the high acquisition cost of CB units along with high transplant-related mortality due to delayed hematopoietic recovery and immune reconstitution have contributed to the slowing in widespread adoption of CBT. Strategies aimed to enhance speed of engraftment and ongoing clinical trials are investigating ways to make CBT more widely available. Meanwhile, the recent clinical data suggest that the choice of CBT might be preferable for patients with pre-transplant minimal residual disease. We review here the background data on the utilization of CB for the treatment of hematological malignancies, and discuss the current challenges and future directions in the field of CBT.

Chronic graft versus host disease burden and late transplant complications are lower following adult double cord blood versus matched unrelated donor peripheral blood transplantation.

Adult umbilical cord blood transplantation (CBT) has emerged as an important option for patients lacking matched related (MRD) and matched unrelated donors (MUD). We compared chronic GVHD (cGVHD) incidence, immunosuppression burden and late infections and hospitalizations in consecutive patients undergoing CBT (n=51) versus peripheral blood MUD transplant (n=57) at our center between June 2009 and April 2014. At 3 years post transplantation, the cumulative incidence (CI) of moderate to severe cGVHD was 44% following MUD versus 8% following CBT (P=0.0006) and CI of any cGVHD was 68% following MUD versus 32% following CBT (P=0.0017). Median time to being off immunosuppression among CB patients was 268 days versus not reached among MUD patients (P<0.0001). Late infections and late hospitalized days were reduced in CB patients (P=0.1 and <0.001, respectively). Three-year CI of transplant-related mortality (TRM) and relapse as well as 3-year overall survival (OS) were similar following CB and MUD transplantation. We demonstrate a significantly lower incidence of cGVHD, immunosuppression burden and late complication rate following UCB versus peripheral blood MUD transplant without decreased OS, increased relapse or early TRM. Combined with the rapid availability of UCB, these findings have led our center to move primarily to UCB over peripheral blood MUD when a MRD is not available.

Elemental analysis of histological specimens: a method to unmask nano asbestos fibers.

There is recent mounting evidence that nanoparticles may have enhanced toxicological potential in comparison to the same material in the bulk form. The aim of this study was to develop a new method for unmask asbestos nanofibers from Formalin-Fixed, Paraffin-Embedded tissue. There is an increasing amount of evidence that nanoparticles may enhance toxicological potential in comparison to the same material in the bulk form. The aim of this study was to develop a new method to unmask asbestos nanofibers from Formalin-Fixed Paraffin-Embedded (FFPE) tissue. For the first time, in this study we applied Energy Dispersive X-ray (EDX) microanalysis through transmission electron microscopy to demonstrate the presence of asbestos nanofibers in histological specimens of patients with possible occupational exposure to asbestos. The diagnostic protocol was applied to 10 randomly selected lung cancer patients with no history of previous asbestos exposure. We detected asbestos nanofibers in close contact with lung cancer cells in two lung cancer patients with previous possible occupational exposure to asbestos. We were also able to identify the specific asbestos iso-type, which in one of the cases was the same rare variety used in the workplace of the affected patient. By contrast, asbestos nanofibers were not detected in lung cancer patients with no history of occupational asbestos exposure. The proposed technique can represent a potential useful tool for linking the disease to previous workplace exposure in uncertain cases. Furthermore, Formalin-Fixed Paraffin-Embedded (FFPE) tissues stored in the pathology departments might be re-evaluated for possible etiological attribution to asbestos in the case of plausible exposure. Since diseases acquired through occupational exposure to asbestos are generally covered by workers' insurance in most countries, the application of the protocol used in this study may have also relevant social and economic implications.

Assembly of a photosynthetic reaction center with ABA tri-block polymersomes: highlights on protein localization.

The reconstitution of the integral membrane protein photosynthetic reaction center (RC) in polymersomes, i.e. artificial closed vesicles, was achieved by the micelle-to-vesicle transition technique, a very mild protocol based on size exclusion chromatography often used to drive the incorporation of proteins contemporarily to liposome formation. An optimized protocol was used to successfully reconstitute the protein in a fully active state in polymersomes formed by the tri-block copolymers PMOXA22-PDMS61-PMOXA22. The RC is very sensitive to its solubilizing environment and was used to probe the positioning of the protein in the vesicles. According to charge-recombination experiments and to the enzymatic activity assay, the RC is found to accommodate in the PMOXA22 region of the polymersome, facing the water bulk solution, rather than in the PDMS61 transmembrane-like region. Furthermore, polymersomes were found to preserve protein integrity efficiently as the biomimetic lipid bilayers but show a much longer temporal stability than lipid based vesicles.

The impact of a multidisciplinary approach on response rate of mandibular advancing device therapy in patients with obstructive sleep apnoea syndrome.

The aim of the present study was to evaluate the importance of a multidisciplinary approach on increasing the response ratio expectation to mandibular advancing device (MAD) therapy in patients with obstructive sleep apnoea syndrome, especially in severe cases. Forty-two mild-to-severe OSAS patients were selected, after comprehensive evaluation by neurologists, otorhinolaryngologists and orthodontists, and treated with a Somnodent® device. Six months later, a polysomnographic exam with the MAD in situ was performed. The paired t-test evaluated the effectiveness of therapy and the results were compared with data from systematic reviews. The average treatment response was statistically significant for the apnoea/hypopnea index (AHI) and oxygen desaturation index and was higher than the outcomes presented in literature. An optimum therapy response (AHI < 5) was observed in 53% of patients (40% in severe OSAS) and a good response (AHI < 10) in 73% of patients (50% in severe OSAS). The Somnodent® device was effective and the multidisciplinary patient selection improved the response ratio compared to that reported by previous systematic reviews.

Characteristics of chronic GVHD after cord blood transplantation.

Most reports of chronic GVHD after cord blood transplantation (CBT) have utilized traditional diagnostic criteria. We used traditional criteria and National Institutes of Health (NIH) criteria prospectively to evaluate chronic GVHD in a cohort of 87 adult and pediatric recipients of single or double unrelated CBT for treatment of hematologic malignancies. Fifty-four patients developed traditionally defined chronic GVHD, for an estimated 2-year probability of 64%. Among 54 patients, 25 (46%) met the NIH criteria for persistent, recurrent or late acute GVHD at onset. Twenty-four (44%) had overlap chronic GVHD, including one who presented initially with late acute GVHD, and only seven (13%) had classic chronic GVHD, including one who also presented initially with late acute GVHD. Among patients who successfully discontinued all systemic immunosuppression (SI), the median time to discontinuation of corticosteroid treatment was 315 days (range 28-977), and the median time to discontinuation of all SI was 353 days (range 67-977). Chronic GVHD diagnosed by traditional criteria after CBT had a predominance of acute GVHD clinical features.

Double umbilical cord blood transplantation in patients with hematologic malignancies using a reduced-intensity preparative regimen without antithymocyte globulin.

Reduced-intensity conditioning (RIC) regimens in cord blood transplant (CBT) are increasingly utilized for older patients and those with comorbidities. However, the optimal conditioning regimen has not yet been established and remains a significant challenge of this therapeutic approach. Antithymocyte globulin (ATG) has been incorporated into conditioning regimens in order to decrease the risk of graft failure; however, use of ATG is often associated with infusion reactions and risk of post-transplant complications. We report the results of a non-ATG-containing RIC regimen, where patients received 2 Gy TBI unless they were considered to be at higher risk of graft failure, in which case they received 3 Gy of TBI. Thirty patients underwent CBT using this protocol for high-risk hematological malignancies. There was only one case of secondary and no cases of primary graft failure. At 1 year, estimates of non-relapse mortality, OS and PFS were 29%, 53% and 45%, respectively. The cumulative incidences of grade III-IV acute and chronic GVHD were 14% and 18%, respectively. In summary, the results of this study demonstrate that this non-ATG-containing conditioning regimen provides a low incidence of graft failure without increasing regimen-related toxicity.

Expression pattern of immune suppressive cytokines and growth factors in oesophageal adenocarcinoma reveal a tumour immune escape-promoting microenvironment.

Immunotherapy for solid cancers, such as oesophageal adenocarcinoma (OAC), is generally hampered by an unfavourable immunological tumour microenvironment. This prompted us to investigate the nature of the OAC environment. Biopsies of tumour and normal control tissues were collected from 17 OAC patients, and investigated using fluorescent immunohistochemistry (IHC) for the expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), transforming growth factor-beta, indoleamine 2-3 dioxygenase, CXCL3 and CXCR1, and for measuring a panel of cytokines by cytometric bead array (CBA), and for Granzyme B (GrB), Perforin and PI9 detection by semi-quantitative PCR (QPCR). IHC showed that expression of all the above-mentioned factors is upregulated in 80-93% of the tumours. By QPCR, the cytokine interleukin (IL)-8 was significantly upregulated in tumour samples (P < 0.05). IL-6, IL-10, GrB and Perforin did not show any significant difference between normal and tumour samples, whereas PI9 levels were significantly higher in normal when compared with the tumour samples. CBA confirmed upregulation of IL-8 and show upregulation of IL-1beta in the tumours (P < 0.05). Regarding IL-6 and interferon (IFN)-gamma, no significant differences were observed between normal and tumour tissues. The OAC microenvironment is characterized by a lack of cytokines and factors that normally would enhance anti-cancer responses, such as IFN-gamma and GrB, and by a high expression of several immuno-suppressive factors, such as COX-2, VEGF and IL-8. For future improvement of treatment efficacy of OAC patients, it will be of importance to combine immunotherapy with immune-modulating agents.