Utility of Serial Microbial Cell-free DNA Sequencing for Inpatient and Outpatient Pathogen Surveillance Among Allogeneic Hematopoietic Stem Cell Transplant Recipients.

BACKGROUND: This study characterizes the clinical utility and validity of the Karius test (KT), a plasma microbial cell-free DNA sequencing platform, as an infection surveillance tool among hematopoietic stem cell transplant (HCT) recipients, including monitoring for cytomegalovirus (CMV) and detecting infections relative to standard microbiologic testing (SMT). METHODS: A prospective, observational cohort study was performed among adult HCT recipients as inpatients and outpatients. Serial KTs were performed starting with 1 sample within 14 days before HCT, then weekly from 7-63 days posttransplant then monthly from 3-12 months post-HCT. Diagnostic performance of KT versus CMV polymerase chain reaction was evaluated with positive percent agreement and negative percent agreement. Infectious events (<12 months post-HCT) were extracted from medical records. For infectious events without positive SMT, 2 clinicians adjudicated KT results to determine if any detections were a probable cause. Difference in time from KT pathogen detection and infection onset was calculated. RESULTS: Of the 70 participants, mean age was 49.9 years. For CMV surveillance, positive percent agreement was 100% and negative percent agreement was 90%. There was strong correlation between CMV DNA and KT molecules per microliter (r 2: 0.84, P < .001). Of the 32 SMT+/KT+ infectious events, KT identified 26 earlier than SMT (median: -12 days) and an additional 5 diagnostically difficult pathogens identified by KT but not SMT. CONCLUSIONS: KT detected CMV with high accuracy and correlation with quantitative polymerase chain reaction. Among infectious events, KT demonstrated additive clinical utility by detecting pathogens earlier than SMT and those not detected by SMT

Update of the tolerable upper intake level for vitamin D for infants

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to revise the tolerable upper intake level (UL) for vitamin D for infants ( 64 1 year) set in 2012. From its literature review, the Panel concluded that the available evidence on daily vitamin D intake and the risk of adverse health outcomes (hypercalciuria, hypercalcaemia, nephrocalcinosis and abnormal growth patterns) cannot be used alone for deriving the UL for infants. The Panel conducted a meta-regression analysis of collected data, to derive a dose\u2013response relationship between daily supplemental intake of vitamin D and mean achieved serum 25(OH)D concentrations. Considering that a serum 25(OH)D concentration of 200 nmol/L or below is unlikely to pose a risk of adverse health outcomes in infants, the Panel estimated the percentage of infants reaching a concentration above this value at different intakes of vitamin D. Based on the overall evidence, the Panel kept the UL of 25 \u3bcg/day for infants aged up to 6 months and set a UL of 35 \u3bcg/day for infants 6\u201312 months. The Panel was also asked to advise on the safety of the consumption of infant formulae with an increased maximum vitamin D content of 3 \u3bcg/100 kcal (Commission Delegated Regulation (EU) 2016/127 repealing Directive 2006/141/EC in 2020). For infants aged up to 4 months, the intake assessment showed that the use of infant formulae containing vitamin D at 3 \u3bcg/100 kcal may lead some infants to receive an intake above the UL of 25 \u3bcg/day from formulae alone without considering vitamin D supplemental intake. For infants aged 4\u201312 months, the 95th percentile of vitamin D intake (high consumers) estimated from formulae and foods fortified or not with vitamin D does not exceed the ULs, without considering vitamin D supplemental intake

A review of the growing risk of vitamin D toxicity from inappropriate practice

Vitamin D is a particularly important sterol hormone, with evidence emerging of its beneficial effects well beyond bone. In consequence of this and increased global recognition of vitamin D deficiency in the general population, there has been a resurgence in treatment with vitamin D preparations. However, the increasing use of vitamin D treatments has also seen a substantial increase in the number of reports of vitamin D intoxication, with the majority (75%) of reports published since 2010. Many of these cases are a consequence of inappropriate prescribing, and the use of high‐dose over‐the‐counter preparations or unlicensed preparations. This review highlights that the majority of cases were preventable and discusses the inappropriate use of poorly formulated, and unlicensed vitamin D preparations

National Poison Data System (NPDS) review of intentional sodium nitrite ingestions 2009–2019

AbstractIngesting sodium nitrite as a suicide method appears to be gaining popularity, spurred by online suicide blogs and an easily obtainable product. However, the exact nature of this trend has not been studied. We conducted an 11-year retrospective review of intentional sodium nitrite ingestions reported to the National Poison Data System from January 1, 2009-December 31, 2019. We included all cases coded as “nitrite or nitrate” in the initial request. We requested full case records for the initial cohort to confirm details. NPDS recorded 390 individual “nitrite or nitrate” exposures during the study period, and 42 met inclusion criteria. We received full case records for 35/42 patients, and 17 were included in the final cohort (N = 17). The mean age was 23.2 years old. Visible cyanosis was present in 13/17 patients with a mean oxygen saturation of 85%. Methylene blue was administered in 14/17 cases with 8/17 requiring advanced cardiac life support. The overall mortality rate was 41% (7/17). All patients presented in the final two years of the study period. Intentionally ingesting sodium nitrite represents a novel, growing trend and carries a high mortality rate among young adults.Abbreviations: AAPCC, American Association of Poison Control Center; ACLS, Advanced Cardiac Life Support; CPCS, California Poison Control System; NPDS, National Poison Data System; PCC, Poison Control Center; SPI, Specialist in Poison Information