Can intravenous antifungal therapy be safely used in the outpatient parenteral antimicrobial therapy (OPAT) setting?

Outpatient parenteral antimicrobial therapy (OPAT) is an established treatment option for patients with a variety of infections who require a period of intravenous therapy, are clinically stable, and do not require continuous monitoring. Many patients with fungal infections require prolonged therapy due to resistance or intolerance to oral antifungal agents. Despite the widespread use of OPAT by infection specialists, antifungal agents appear infrequently used in this setting. We suggest that with appropriate patient selection, patients with fungal infections could successfully be treated on OPAT.     

Utilization of conventional radiography in a regional neonatal intensive care unit in Ireland

Objective: To audit the demand and radiation exposure of conventional radiography in a regional neonatal intensive care unit (NICU) in Ireland.

Methods: A retrospective study of radiographs performed on all admissions to the NICU in University Maternity Hospital Limerick (UMHL) over 2 years.

Results: A total of 1405 radiographs were performed on 506 infants. 153.5 radiographs per 1000 live births was the observed demand and 44% of radiographs were done out of hours. 47% of all radiographs were performed on infants <1500?g. Median number of radiographs per infant was one (IQR 1–2; range 1–39). Significant negative correlation was observed between number of radiographs and gestational age. Mean lung radiation doses estimated using published values for normal weight (>2500?g), very low birth weight (VLBW), and extremely low birth weight (ELBW) infants based on the median number of chest X-rays were 31.7?µGym, 84.66 and 232.75 µGy, respectively.

Conclusions: Conventional radiography remains a key diagnostic tool in neonatology particularly in VLBW and ELBW infants and is invaluable in supporting timely clinical decision making. Clinicians should be aware of the cost and potential hazards of neonatal radiography and is recommend that the cumulative radiation exposure among the ELBW and VLBW infants is monitored. Increasing awareness and standardisation of point-of-care ultrasonography could decrease the reliance on conventional radiography in neonatal units.     

CD47 agonist peptide PKHB1 induces immunogenic cell death in T‐cell acute lymphoblastic leukemia cells

T‐cell acute lymphoblastic leukemia (T‐ALL) has a poor prognosis derived from its genetic heterogeneity, which translates to a high chemoresistance. Recently, our workgroup designed thrombospondin‐1‐derived CD47 agonist peptides and demonstrated their ability to induce cell death in chronic lymphocytic leukemia. Encouraged by these promising results, we evaluated cell death induced by PKHB1 (the first‐described serum‐stable CD47‐agonist peptide) on CEM and MOLT‐4 human cell lines (T‐ALL) and on one T‐murine tumor lymphoblast cell‐line (L5178Y‐R), also assessing caspase and calcium dependency and mitochondrial membrane potential. Additionally, we evaluated selectivity for cancer cell lines by analyzing cell death and viability of human and murine non‐tumor cells after CD47 activation. In vivo, we determined that PKHB1‐treatment in mice bearing the L5178Y‐R cell line increased leukocyte cell count in peripheral blood and lymphoid organs while recruiting leukocytes to the tumor site. To analyze whether CD47 activation induced immunogenic cell death (ICD), we evaluated damage‐associated molecular patterns (DAMP) exposure (calreticulin, CRT) and release (ATP, heat shock proteins 70 and 90, high‐mobility group box 1, CRT). Furthermore, we gave prophylactic antitumor vaccination, determining immunological memory. Our data indicate that PKHB1 induces caspase‐independent and calcium‐dependent cell death in leukemic cells while sparing non‐tumor murine and human cells. Moreover, our results show that PKHB1 can induce ICD in leukemic cells as it induces CRT exposure and DAMP release in vitro, and prophylactic vaccinations inhibit tumor establishment in vivo. Together, our results improve the knowledge of CD47 agonist peptides potential as therapeutic tools to treat leukemia.     

Exploring the half-life of glyphosate in human urine samples

Background

The International Agency for Research on Cancer (IARC) has recently classified glyphosate as a Group 2A ‘probably carcinogenic to humans’. Due to this carcinogenic classification and resulting international debate, there is an increased demand for studies evaluating human health effects from glyphosate exposures. There is currently limited information on human exposures to glyphosate and a paucity of data regarding glyphosate's biological half-life in humans.