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Invasive mold infections are a major cause of mortality in immunosuppressed and cancer patients. Diagnosis is challenging, requiring invasive procedures or reliance on fungal biomarkers with limited sensitivity and an inability to detect non-Aspergillus molds. Here, we perform whole-body 18 F-fluorodeoxysorbitol ( 18 F-FDS) positron emission tomography (PET) in nine prospectively enrolled patients with high-suspicion of invasive mold infections (eventually confirmed using culture or molecular assays, n = 4) or other pathologies (n = 5) with localization of 18 F-FDS PET signal to infection sites as the primary outcome (NCT05611892). 18 F-FDS PET (120 or 180 min after injection), rapidly detects and localizes invasive pulmonary and cerebral infections due to Aspergillus , non- Aspergillus (galactomannan-negative), or azole-resistant molds, and differentiates them from sterile inflammation or cancer. Moreover, 18 F-FDS selectively and rapidly accumulates intracellularly in a range of clinically relevant molds, including azole-resistant molds, via a saturable process. In animals, 18 F-FDS PET is able to detect and localize pulmonary and cerebral aspergillosis, as well as rhinosinusal infections due to Aspergillus , Rhizopus , and Mucor , confirming the clinical data. 18 F-FDS can be easily synthesized from 18 F-fluorodeoxyglucose ( 18 F-FDG), which is widely available, and represents a promising, noninvasive diagnostic tool for detecting, localizing and monitoring of invasive mold infections throughout the body. In this study, the authors describe an imaging technology, 18 F-FDS PET, for noninvasive detection, localization and monitoring of invasive mold infections, including Aspergillus , non- Aspergillus and azole-resistant molds, throughout the body.

Recipients of solid organ transplant (SOT) experience decreased immunogenicity after COVID-19 vaccination. To summarize current evidence on vaccine responses and identify risk factors for diminished humoral immune response in recipients of SOT. A literature search was conducted from existence of database through December 15, 2021, using MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov. Studies reporting humoral immune response of the COVID-19 vaccines in recipients of SOT were reviewed. Two reviewers independently extracted data from each eligible study. Descriptive statistics and a random-effects model were used. This report was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were analyzed from December 2021 to February 2022. The total numbers of positive immune responses and percentage across each vaccine platform were recorded. Pooled odds ratios (pORs) with 95% CIs were used to calculate the pooled effect estimates of risk factors for poor antibody response. A total of 83 studies were included for the systematic review, and 29 studies were included in the meta-analysis, representing 11 713 recipients of SOT. The weighted mean (range) of total positive humoral response for antispike antibodies after receipt of mRNA COVID-19 vaccine was 10.4% (0%-37.9%) for 1 dose, 44.9% (0%-79.1%) for 2 doses, and 63.1% (49.1%-69.1%) for 3 doses. In 2 studies, 50% of recipients of SOT with no or minimal antibody response after 3 doses of mRNA COVID-19 vaccine mounted an antibody response after a fourth dose. Among the factors associated with poor antibody response were older age (mean [SE] age difference between responders and nonresponders, 3.94 [1.1] years), deceased donor status (pOR, 0.66 [95% CI, 0.53-0.83]; I2 = 0%), antimetabolite use (pOR, 0.21 [95% CI, 0.14-0.29]; I2 = 70%), recent rituximab exposure (pOR, 0.21 [95% CI, 0.07-0.61]; I2 = 0%), and recent antithymocyte globulin exposure (pOR, 0.32 [95% CI, 0.15-0.71]; I2 = 0%). In this systematic review and meta-analysis, the rates of positive antibody response in solid organ transplant recipients remained low despite multiple doses of mRNA vaccines. These findings suggest that more efforts are needed to modulate the risk factors associated with reduced humoral responses and to study monoclonal antibody prophylaxis among recipients of SOT who are at high risk of diminished humoral response.

Research involving recently deceased humans that are physiologically maintained following declaration of death by neurologic criteria—or ‘research involving the recently deceased’—can fill a translational research gap while reducing harm to animals and living human subjects. It also creates new challenges for honouring the donor’s legacy, respecting the rights of donor loved ones, resource allocation and public health. As this research model gains traction, new empirical ethics questions must be answered to preserve public trust in all forms of tissue donation and in the practice of medicine while respecting the legacy of the deceased and the rights of donor loved ones. This article suggests several topics for immediate investigation to understand the attitudes and experiences of researchers, clinical collaborators, donor loved ones and the public to ensure research involving the recently deceased advances ethically.

Abstract Health care workers have been prioritized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, but vaccine hesitancy among workers may limit uptake. Institutions may wish to consider SARS-CoV-2 vaccine mandates for health care workers, but such proposals raise important ethical questions. Arguments supporting mandates emphasize the proposed favorable balance of harms and benefits for both individuals and communities, as well as moral duties of health care workers and organizations. Arguments in opposition seek to challenge some claims about utility and raise additional concerns about infringement on autonomy, damage to organizational relationships, and injustice. While available SARS-CoV-2 vaccines remain under an experimental designation, mandates may be excessively problematic, but following approval by the Food and Drug Administration mandates may be reconsidered. The authors summarize ethical arguments and practical considerations, concluding that mandates may be ethically permissible in select circumstances. The authors critically evaluate ethical arguments for and against mandatory SARS-CoV-2 vaccination for the healthcare workforce, addressing utility, social and organizational obligations, bodily autonomy, justice and equity. The authors go on to offer recommendations for healthcare institutions considering such mandates.

Abstract We describe an unusual case of posttransplant tuberculosis reactivation in a man who underwent allogeneic hematopoietic cell transplant. Concomitant with disseminated adenovirus infection, reactivation of tuberculosis manifested as disseminated, nonfollicular pustules on day +49. Skin biopsy was obtained on day +50. Initial histopathologic evaluation did not suggest mycobacterial infection, but tissue stain showed acid-fast organisms, which were subsequently identified as Mycobacterium tuberculosis. Shortly after the cutaneous presentation of tuberculosis, the patient died on day +52. Our case is among a paucity of reports describing tuberculosis reactivation in hematopoietic cell transplant patients in the early posttransplant period. It highlights the difficulty of diagnosing contemporaneous systemic infections, and it presents a rare and atypical cutaneous manifestation of tuberculosis in a hematopoietic cell transplant patient. Our case and review of the literature emphasize the need for further research to elucidate risk factors associated with early posttransplant reactivation of tuberculosis, and the importance of remaining vigilant for active tuberculosis in hematopoietic cell transplant patients with epidemiologic risk factors.

Abstract Background Antimicrobial utilization at end of life is common, but whether advance directives correlate with usage is unknown. We sought to determine whether Washington State Physician Orders for Life Sustaining Treatment (POLST) form completion or antimicrobial preferences documented therein correlate with subsequent inpatient antimicrobial prescribing at end of life. Methods This was a single-center, retrospective cohort study of adult patients at a cancer center who died between January 1, 2016, and June 30, 2019. We used negative binomial models adjusted for age, sex, and malignancy type to test the relationship between POLST form completion ≥30 days before death, antimicrobial preferences, and antimicrobial days of therapy (DOT) per 1000 inpatient-days in the last 30 days of life. Results Among 1295 eligible decedents with ≥1 inpatient-day during the last 30 days of life, 318 (24.6%) completed a POLST form. Of 318, 120 (37.7%) were completed ≥30 days before death, 35/120 (29.2%) specified limited antimicrobials, 55/120 (45.8%) specified full antimicrobial use, and 30/120 (25%) omitted antimicrobial preference. Eighty-three percent (1070/1295) received ≥1 inpatient antimicrobial. The median total and intravenous (IV) antimicrobial DOT/1000 inpatient-days were 1077 and 667. Patients specifying limited antimicrobials had significantly lower total antimicrobial DOT (adjusted incidence rate ratio [IRR], 0.68; 95% CI, 0.49–0.95; P = .02) and IV antimicrobial DOT (IRR, 0.57; 95% CI, 0.38–0.86; P = .008) compared with those without a POLST. Conclusions Indicating a preference for limited antimicrobials on a POLST form ≥30 days before death may lead to less inpatient antimicrobial use in the last 30 days of life. In a retrospective cohort, patients who indicated a preference for limited antimicrobials on a common order form for end-of-life treatments received fewer antimicrobial days of therapy in the 30 before death compared to patients who never completed the form.

Invasive mold infections are a major cause of mortality in immunosuppressed and cancer patients. Diagnosis is challenging, requiring invasive procedures or reliance on fungal biomarkers with limited sensitivity and an inability to detect non-Aspergillus molds. Here, we perform whole-body F-fluorodeoxysorbitol ( F-FDS) positron emission tomography (PET) in nine prospectively enrolled patients with high-suspicion of invasive mold infections (eventually confirmed using culture or molecular assays, n = 4) or other pathologies (n = 5) with localization of F-FDS PET signal to infection sites as the primary outcome (NCT05611892). F-FDS PET (120 or 180 min after injection), rapidly detects and localizes invasive pulmonary and cerebral infections due to Aspergillus, non-Aspergillus (galactomannan-negative), or azole-resistant molds, and differentiates them from sterile inflammation or cancer. Moreover, F-FDS selectively and rapidly accumulates intracellularly in a range of clinically relevant molds, including azole-resistant molds, via a saturable process. In animals, F-FDS PET is able to detect and localize pulmonary and cerebral aspergillosis, as well as rhinosinusal infections due to Aspergillus, Rhizopus, and Mucor, confirming the clinical data. F-FDS can be easily synthesized from F-fluorodeoxyglucose ( F-FDG), which is widely available, and represents a promising, noninvasive diagnostic tool for detecting, localizing and monitoring of invasive mold infections throughout the body.