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Bothin vivodata in preclinical cancer models andin vitrodata with T cells from patients with advanced cancer support a role for Tim-3 blockade in promoting effective anti-tumor immunity. Consequently, there is considerable interest in the clinical development of antibody-based therapeutics that target Tim-3 for cancer immunotherapy. A challenge to this clinical development is the fact that several ligands for Tim-3 have been identified: galectin-9, phosphatidylserine, HMGB1, and most recently, CEACAM1. These observations raise the important question of which of these multiple receptor:ligand relationships must be blocked by an anti-Tim-3 antibody in order to achieve therapeutic efficacy. Here, we have examined the properties of anti-murine and anti-human Tim-3 antibodies that have shown functional efficacy and find that all antibodies bind to Tim-3 in a manner that interferes with Tim-3 binding to both phosphatidylserine and CEACAM1. Our data have implications for the understanding of Tim-3 biology and for the screening of anti-Tim-3 antibody candidates that will have functional propertiesin vivo. [ABSTRACT FROM AUTHOR]

Robotic-assisted devices help provide precise component positioning in conversion of unicompartmental knee arthroplasty (UKA) to total knee arthroplasty (TKA). A few studies offer surgical techniques for computed tomography (CT) based robotic-assisted conversion of UKA to TKA; however, no studies to date detail this procedure utilizing a non-CT-based robotic-assisted device. This article introduces a novel technique employing a non-CT-based robotic-assisted device (ROSA Knee System, Zimmer Biomet, Warsaw, IN) for converting UKA to TKA with a focus on its efficacy in gap balancing. We present three patients (ages 46-66 years) who were evaluated for conversion of UKA to TKA for aseptic loosening, stress fracture, and progressive osteoarthritis. Each patient underwent robotic-assisted conversion to TKA. Postoperative assessments at 6 months revealed improved pain, function, and radiographic stability. Preoperative planning included biplanar long leg radiographs to determine the anatomic and mechanical axis of the leg. After arthrotomy with a standard medial parapatellar approach, infrared reflectors were pinned into the femur and tibia, followed by topographical mapping of the knee with the UKA in situ. The intraoperative software was utilized to evaluate flexion and extension balancing and plan bony resections. Then, the robotic arm guided placement of the femoral and tibial guide pins and the UKA components were removed. After bony resection of the distal femur and proximal tibia, the intraoperative software was used to reassess the extension gap, and plan posterior condylar resection to have the flexion gap match the extension gap. The use of a non-CT-based robotic-assisted device in conversion of UKA to TKA is a novel technique and a good option for surgeons familiar with robotic-assisted arthroplasty, resulting in excellent outcomes at 6 months., Competing Interests: M.A.C. and W.T.N. receive compensation for consulting and research support from Zimmer-Biomet. All other authors do not have any disclosures at this time., (Thieme. All rights reserved.)

Aims: In order to determine acute cardiac involvement in patients with COVID-19, we quantitatively evaluated tissue characteristics and mechanics by non-invasive cardiac magnetic resonance (CMR) in a cohort of patients within the first 10 days of the onset of COVID symptoms., Methods and Results: Twenty-five patients with reverse transcription polymerase chain reaction confirmed COVID-19 and at least one marker of cardiac involvement [cardiac symptoms, abnormal electrocardiograph (ECG), or abnormal cardiac biomarkers] and 25 healthy age- and gender-matched control subjects were recruited to the study. Patients were divided into those with elevated (n = 8) or normal TnI (n = 17). There were significant differences in global longitudinal strain among patients who were positive and negative for hs-TnI, and controls [-12.3 (-13.3, -11.5)%, -13.1 (-14.2, -9.8)%, and -15.7 (-18.3, -12.7)%, P = 0.004]. Native myocardial T1 relaxation times in patients with positive and negative hs-TnI manifestation (1169.8 ± 12.9 and 1113.2 ± 31.2 ms) were significantly higher than the normal (1065 ± 57 ms) subjects, respectively (P < 0.001). The extracellular volume (ECV) of patients who were positive and negative for hs-TnI was higher than that of the normal controls [32 (31, 33)%, 29 (27, 30)%, and 26 (24, 27.5)%, P < 0.001]. In our study, quantitative T2 mapping in patients who were positive and negative for hs-TnI [51 (47.9, 52.8) and 48 (47, 49.4) ms] was significantly higher than the normal [42 (41, 45.2) ms] subjects (P < 0.001)., Conclusion: In patients with early-stage COVID-19, myocardial oedema, and functional abnormalities are a frequent finding, while irreversible regional injury such as necrosis may be infrequent., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)