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Malaria Sporozoite Vaccine Each year, hundreds of millions of people are infected with Plasmodium falciparum, the mosquito-borne parasite that causes malaria. A preventative vaccine is greatly needed. Seder et al. (p. 1359, published online 8 August; see the Perspective by Good) now report the results from a phase I clinical trial where subjects were immunized intravenously with a whole, attenuated sporozoite vaccine. Three of 9 subjects who received four doses and zero of 6 subjects who received five doses of the vaccine went on to develop malaria after controlled malaria infection. Both antibody titers and cellular immune responses correlated positively with the dose of vaccine received, suggesting that both arms of the adaptive immune response may have participated in the observed protection. Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine—composed of attenuated, aseptic, purified, cryopreserved PfSPZ—was safe and wel-tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 × 105 PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards. Intravenous immunization with an attenuated whole malaria sporozoite vaccine protected volunteers in a phase I clinical trial. [Also see Perspective by Good] Intravenous immunization with an attenuated whole malaria sporozoite vaccine protected volunteers in a phase I clinical trial. [Also see Perspective by Good]

Musculoskeletal Aspects Increased urinary calcium, with the occasional formation of urinary calculi, and muscular atrophy are not uncommon clinical occurrences among long-term bedridden patients.28...

Background: The evidence supporting best practice guidelines in the field of cartilage repair of the ankle is based on both low quality and low levels of evidence. Therefore, an international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to report the consensus statements on “terminology for osteochondral lesions of the ankle” developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Methods: Forty-three international experts in cartilage repair of the ankle representing 20 countries were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within four working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed, and the available evidence for each statement was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held, and the strength of consensus was characterised as follows: consensus, 51%–74%; strong consensus, 75%–99%; unanimous, 100%. Results: A total of 11 statements on terminology and classification reached consensus during the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Definitions are provided for osseous, chondral and osteochondral lesions, as well as bone marrow stimulation and injury chronicity, among others. An osteochondral lesion of the talus can be abbreviated as OLT. Conclusions: This international consensus derived from leaders in the field will assist clinicians with the appropriate terminology for osteochondral lesions of the ankle.

Background: The evidence supporting best practice guidelines in the field of cartilage repair of the ankle are based on both low quality and low levels of evidence. Therefore, an international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to report the consensus statements on “Pediatric Ankle Cartilage Lesions” developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Methods: Forty-three international experts in cartilage repair of the ankle representing 20 countries convened to participate in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within four working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed and the available evidence for each statement was graded. Discussion and debate occurred in cases where statements were not agreed upon in unanimous fashion within the working groups. A final vote was then held, and the strength of consensus was characterised as follows: consensus: 51–74%; strong consensus: 75–99%; unanimous: 100%. Results: A total of 12 statements on paediatric ankle cartilage lesions reached consensus during the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Five achieved unanimous support, and seven reached strong consensus (>75% agreement). All statements reached at least 84% agreement. Conclusions: This international consensus derived from leaders in the field will assist clinicians with the management of paediatric ankle cartilage lesions.

Background: An international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to present the consensus statements on osteochondral lesions of the tibial plafond (OLTP) and on ankle instability with ankle cartilage lesions developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Methods: Forty-three experts in cartilage repair of the ankle were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within 4 working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed and the available evidence for each statement was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held. Results: A total of 11 statements on OLTP reached consensus. Four achieved unanimous support and 7 reached strong consensus (greater than 75% agreement). A total of 8 statements on ankle instability with ankle cartilage lesions reached consensus during the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. One achieved unanimous support, and seven reached strong consensus (greater than 75% agreement). Conclusion: These consensus statements may assist clinicians in the management of these difficult clinical pathologies. Level of Evidence: Level V, mechanism-based reasoning.

Category: Ankle; Trauma Introduction/Purpose: Weightbearing CT (WBCT) scan provides an ability to compare the ankle joints bilaterally in a 3D manner under physiologic load. According to our recent investigations, 3D volume measurement of the syndesmosis, if measured up to 5cm proximal to the tibial plafond, can detect the instability with an accuracy of 90%, sensitivity of 95.8%, and specificity of 83.3%. However, these values can differ based on the knowledge and experience of the human interpreter. Deep learning, as a subset of machine learning, has shown promising potentials in processing and analyzing images and detecting abnormalities within the images using deep convolutional neural networks (DCNN). Herein, we aimed to assess the accuracy, sensitivity, and specificity of 3D volume WBCT evaluation using DCNN algorithms in patients with subtle syndesmotic instability. Methods: In this study 140 bilateral ankle WBCT scans of patients with subtle syndesmotic instability who were diagnosed intraoperatively were allocated to the patient group. The control group comprised 140 bilateral ankle WBCT images of healthy individuals. We utilized inception V3 model for our DCNN. Data augmentation and transfer learning were used; however, the images were not preprocessed in terms of change in size and resolution. The data were divided as 80:10:10 for training, validation, and test subsets, respectively. The outcome of the study was expressed as sensitivity, specificity, F-score, and the area under the curve (AUC). Results: The performance of our DCNN algorithm showed a sensitivity of 99.41%, specificity of 99.34%, F-score of 99.37%, and 99.99% AUC ( Figure 1 ). The change in loss value of the train data was plateaued after 40 iterations. Axial images were the most appropriate images that were used by the algorithm to detect the instability. Conclusion: In this study we observed that using DCNN in the process of WBCT image interpretation for diagnosis of syndesmotic instability, particularly in subtle cases, makes this modality almost perfect with a very small chance of missing a case. Training a DCNN using a greater number of inputs is still recommended to improve the validity and reliability of this method. Providing a heat map will also help clinicians discover the process of decision-making by these algorithms as DCNNs are sometimes called 'black box'.

VASOMOTOR SYMPTOMS AFTER RISK REDUCING BILATERAL SALPINGO-OOPHORECTOMY (RRSO) IN BRCA MUTATION CARRIERS: IMPACT OF OBESITY, HORMONE REPLACEMENT THERAPY (HRT), AND DEPRESSED MOOD. L. Johnson, S. Butts, L. DiGiovanni, C. Voong, J. Chan, S. Senapati, S. Domchek. Reproductive Endocrinology and Infertility, University of Pennsylvania, Philadelphia, PA; Basser Research Center for BRCA, University of Pennsylvania, Philadelphia, PA.