Background Prompt identification of patients suspected to have COVID-19 is crucial for disease control. We aimed to develop a deep learning algorithm on the basis of chest CT for rapid triaging in fever clinics. Methods We trained a U-Net-based model on unenhanced chest CT scans obtained from 2447 patients admitted to Tongji Hospital (Wuhan, China) between Feb 1, 2020, and March 3, 2020 (1647 patients with RT-PCR-confirmed COVID-19 and 800 patients without COVID-19) to segment lung opacities and alert cases with COVID-19 imaging manifestations. The ability of artificial intelligence (AI) to triage patients suspected to have COVID-19 was assessed in a large external validation set, which included 2120 retrospectively collected consecutive cases from three fever clinics inside and outside the epidemic centre of Wuhan (Tianyou Hospital [Wuhan, China; area of high COVID-19 prevalence], Xianning Central Hospital [Xianning, China; area of medium COVID-19 prevalence], and The Second Xiangya Hospital [Changsha, China; area of low COVID-19 prevalence]) between Jan 22, 2020, and Feb 14, 2020. To validate the sensitivity of the algorithm in a larger sample of patients with COVID-19, we also included 761 chest CT scans from 722 patients with RT-PCR-confirmed COVID-19 treated in a makeshift hospital (Guanggu Fangcang Hospital, Wuhan, China) between Feb 21, 2020, and March 6, 2020. Additionally, the accuracy of AI was compared with a radiologist panel for the identification of lesion burden increase on pairs of CT scans obtained from 100 patients with COVID-19. Findings In the external validation set, using radiological reports as the reference standard, AI-aided triage achieved an area under the curve of 0·953 (95% CI 0·949–0·959), with a sensitivity of 0·923 (95% CI 0·914–0·932), specificity of 0·851 (0·842–0·860), a positive predictive value of 0·790 (0·777–0·803), and a negative predictive value of 0·948 (0·941–0·954). AI took a median of 0·55 min (IQR: 0·43–0·63) to flag a positive case, whereas radiologists took a median of 16·21 min (11·67–25·71) to draft a report and 23·06 min (15·67–39·20) to release a report. With regard to the identification of increases in lesion burden, AI achieved a sensitivity of 0·962 (95% CI 0·947–1·000) and a specificity of 0·875 (95 %CI 0·833–0·923). The agreement between AI and the radiologist panel was high (Cohen's kappa coefficient 0·839, 95% CI 0·718–0·940). Interpretation A deep learning algorithm for triaging patients with suspected COVID-19 at fever clinics was developed and externally validated. Given its high accuracy across populations with varied COVID-19 prevalence, integration of this system into the standard clinical workflow could expedite identification of chest CT scans with imaging indications of COVID-19. Funding Special Project for Emergency of the Science and Technology Department of Hubei Province, China.
The enormous research progress in autoimmune disorders makes the establishment of long-term clinical tolerance to autoantigens an accessible goal. This strategy endows lymphoid tissues with the tolerogenic ability to induce an unresponsive state toward autoantigens. Lymphoid tissues, as the crossroads, play integral roles in initiating immune activation and immunoregulation. Enormous efforts have driven the exploration of targeting delivery of tolerogenic agents to lymphoid tissues to reverse autoimmune disorders. Herein, the development of various tolerogenic therapies for autoimmune diseases are reviewed, the mechanisms of action from various lymphoid tissues to appropriate cell types by different administration routes are highlighted, and examples of lymphoid tissue-targeting strategies to improve tolerogenic therapy potency are discussed. First lymph nodes-targeting strategies for tolerance induction after interstitial or intra-lymph node (i.LN) injection are summarized, then liver and spleen-mediated tolerance after intravenous administration are described, and finally oral tolerance-based therapies are discussed. It is envisioned that tolerogenic therapy will emerge as a novel treatment for autoimmune diseases.
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