Background Procalcitonin testing has been adopted by antimicrobial stewardship programs as a means of reducing inappropriate antibiotic use, including within intensive care units (ICUs). However, concerns regarding procalcitonin’s sensitivity exist. The purpose of this study is to calculate the sensitivity of procalcitonin for bacteremia among hospitalized patients. Methods This was a retrospective cohort study of adult patients admitted to an academic medical center between July 1, 2018, and June 30, 2019, with ≥1 positive blood culture within 24 hours of admission and procalcitonin testing within 48 hours. Low procalcitonin was defined as 24-hour delayed receipt of antibiotic therapy (3% vs 8%; P = .04), including among patients admitted to the ICU (1% vs 18%; P = .02). Conclusions The sensitivity of procalcitonin for bacteremia is unacceptably low for a rule-out test. Antimicrobial stewardship programs should use caution before promoting the withholding of antibiotic therapy for patients with low initial procalcitonin values. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Background Sharing needles and ancillary injecting equipment is a primary risk exposure for hepatitis C virus (HCV) infection among people who inject drugs (PWID); however, infectivity of these exposures is not well quantified. We aimed to estimate per-event HCV infectivity associated with receptive needle sharing (RNS) among susceptible PWID. Methods Participants in a prospective cohort study of young adult PWID who were anti-HCV and HCV RNA negative at baseline and attended at least 2 follow-up study visits between 2003 and 2014 were eligible. Data were selected from the first HCV-negative through the first HCV-positive visit (or last HCV-negative among those uninfected). Anti-HCV and HCV-RNA tests were used to determine infection status. A probabilistic exposure model linking observed HCV infection outcomes to self-reported exposure events was applied to estimate infectivity. Results Among 344 participants, a maximum likelihood estimate considering RNS yielded a pooled population per RNS event HCV probability of 0.25% (95% confidence interval [CI], 0.10%-0.43%), and 1.12% (95% CI, 0.48%-2.35%) among those who acquired any HCV infection (primary or reinfection). Conclusions HCV is highly infectious in association with RNS, a primary injection-related risk exposure. Our infectivity estimate among participants who acquired any HCV infection is 1.7 times higher than that estimated for HIV infection in PWID and 2.24 times higher than that estimated among health care workers exposed through needle sticks. The strengths of this study include the assessment of receptive needle sharing events, the prospective design, and relatively short recall and testing periods. These results can inform transmission models and research to prevent HCV infection. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Patients with Mycobacterium avium complex lung disease treated with amikacin liposome inhalation suspension (ALIS) at 2 clinics in the United States were surveyed to assess the frequency and management of ALIS-associated respiratory adverse events. Most respondents experienced these events, but management through physician-guided measures (eg, bronchodilator use, oral rinses, and/or temporary dosing adjustments) resulted in symptomatic improvement. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.In clinical ophthalmology, a variety of image-related diagnostic techniques have begun to offer unprecedented insights into eye diseases based on morphological datasets with millions of data points. Artificial intelligence (AI), inspired by the human multilayered neuronal system, has shown astonishing success within some visual and auditory recognition tasks. In these tasks, AI can analyze digital data in a comprehensive, rapid and non-invasive manner. Bioinformatics has become a focus particularly in the field of medical imaging, where it is driven by enhanced computing power and cloud storage, as well as utilization of novel algorithms and generation of data in massive quantities. Machine learning (ML) is an important branch in the field of AI. The overall potential of ML to automatically pinpoint, identify and grade pathological features in ocular diseases will empower ophthalmologists to provide high-quality diagnosis and facilitate personalized health care in the near future. This review offers perspectives on the origin, development, and applications of ML technology, particularly regarding its applications in ophthalmic imaging modalities. © The Author(s) 2020.The immune response elicited by the protective whole-cell pertussis (wP) versus the less-protective acellular pertussis (aP) vaccine has been well characterized; however, important clinical problems remain unsolved, as the inability of the currently administered aP vaccine is resulting in the reemergence of clinical disease (i.e., whooping cough). Strong evidence has shown that original, childhood aP and wP priming vaccines provide a long-lasting imprint on the CD4+ T cells that impacts protective immunity. However, aP vaccination might prevent disease but not infection, which might also affect the breadth of responses to Bordetella pertussis (BP) antigens. Thus, characterizing and defining novel targets associated with T cell reactivity are of considerable interest. Here, we compare the T cell reactivity of original aP and wP priming for different antigens contained or not contained in the aP vaccine and define the basis of a full-scale genomic map of memory T cell reactivity to BP antigens in humans. Our data show that the original priming after birth with aP vaccines has higher T cell reactivity than originally expected against a variety of BP antigens and that the genome-wide mapping of BP using an ex vivo screening methodology is feasible, unbiased, and reproducible. This could provide invaluable knowledge towards the direction of a new and improved pertussis vaccine design. Copyright © 2020 Ricardo da Silva Antunes et al.The function of natural killer (NK) cells, defending against virus infection and tumour progression, is regulated by multiple activating and inhibiting receptors expressed on NK cells, among which sialic acid-bind immunoglobulin-like lectins (Siglecs) act as a vital inhibitory group. Previous studies have shown that Siglec7 and Siglec9 are expressed on NK cells, which negatively regulate the function of NK cells and modulate the immune response through the interaction of sialic acid-containing ligands. Siglec7 and Siglec9 are very similar in distribution, gene encoding, protein sequences, ligand affinity, and functions in regulating the immune system against virus and cancers, but differences still exist between them. In this review, we aim to discuss the similarities and differences between Siglec7 and Siglec9 and analyze their functions in virus infection and tumour progression in order to develop better anti-viral and anti-tumor immunotherapy in the future. Copyright © 2020 Yayun Zheng et al.Cutaneous squamous cell carcinoma (cSCC) is a common form of skin cancer with a complex but not fully understood pathogenesis. Recent research suggests the role of beta human papillomavirus (HPV) types and HPV-associated inflammatory processes in cSCC development. Beta HPV types are components of the normal flora; however, under the influence of certain cofactors, the virus may trigger a malignant process. Dysregulation of the immune system (chronic inflammation and immunosuppression), environmental factors (ultraviolet radiation), and genetic factors are the most important cofactors involved in beta HPV-related carcinogenesis. In addition, the oncoproteins E6 and E7 of beta HPV types differ biochemically from their counterparts in the structure of alpha HPV types, resulting in different mechanisms of action in carcinogenesis. The aim of our manuscript is to present an updated point of view on the involvement of beta HPV types in cSCC pathogenesis. Copyright © 2020 Mircea Tampa et al.The success of peptide-based dendritic cell (DC) cancer vaccines mainly depends on the utilized peptides and selection of an appropriate adjuvant. Herein, we aimed to evoke a broad immune response against multiple epitopes concurrently in the presence of immunoadjuvant. Three synthetic HLA-A∗0201-restricted peptides were separately linked with HMGB1-derived peptide (SAFFLFCSE, denoted as HB100-108) as immunoadjuvant via double arginine (RR) linker and loaded onto human monocyte-derived DCs. Peptide uptake was detected by immunofluorescence microscopy and flow cytometry. The maturation and activation status of pulsed DCs were monitored by detection of the expression of specific markers and released cytokines. The ability of peptide-pulsed DCs to activate allogeneic T cells has been assessed by a degranulation assay and detection of secreted cytokines. The lytic activity of effector T cells against cancer cells in vitro was analyzed by a lactate dehydrogenase (LDH) assay. Results revealed that DCs efficiently take up peptides+HB100-108 and expressed higher levels of surface markers (HLA-ABC, HLA-DR, CD80, CD86, CD83, CD40, and CCR7) and proinflammatory cytokines (IL-6, IFN-γ, TNF-α, and IL-12) than control DCs, free peptide-pulsed DCs, and free HB100-108-pulsed DC groups. Moreover, peptides+HB100-108/pulsed DCs were capable of activating allogeneic T cells and enhance their lytic activity against a pancreatic cancer cell line (PANC-1) in vitro. These findings suggest that antigenic peptides covalently linked with HB100-108/pulsed DCs could be a promising strategy to improve the current DC-based cancer vaccines. Copyright © 2020 Chumeng Chen et al.A complex mixture of peptides plays a key role in the regulation of the immune system; different sources as raw materials mainly from animals and vegetables have been reported to provide these extracts. The batch-to-batch product consistency depends on in-process controls established. However, when an immunomodulator is a customized product obtained from the same volunteer who will receive the product to personalize the treatment, the criteria to establish the consistency between volunteers are different. In this sense, it is expected to have the same molecular weight range although the profile of peptide abundance is different. Here, we characterized the peptide profile of three extracts of an immunomodulator obtained from the urine of different volunteers suffering from three different diseases (i.e., allergic rhinitis, rheumatoid arthritis, and chronic rhinopharyngitis), using size exclusion chromatography (SEC) and mass spectrometry (MS). The peptides contained in the immunomodulators were stable after six months, stored in a refrigerator. Our results showed a chromatographic profile with the same range of low molecular weight (less than 17 kDa) in all analyzed samples by SEC; these results were also confirmed by MS showing an exact mass spectrum from 3 to 13 kDa. The fact that the peptide profiles were conserved during a six-month period at refrigeration conditions (2 to 8°C) maintaining the quality and stability of the immunomodulator supports the notion that it might be an alternative in the treatment of chronic hypersensibility disorders. Copyright © 2020 Alberto Fragoso et al.