Pre-existing invasive fungal infection is not a contraindication for allogeneic HSCT for patients with hematologic malignancies: a CIBMTR study.

Patients with prior invasive fungal infection (IFI) increasingly proceed to allogeneic hematopoietic cell transplantation (HSCT). However, little is known about the impact of prior IFI on survival. Patients with pre-transplant IFI (cases; n=825) were compared with controls (n=10247). A subset analysis assessed outcomes in leukemia patients pre- and post 2001. Cases were older with lower performance status (KPS), more advanced disease, higher likelihood of AML and having received cord blood, reduced intensity conditioning, mold-active fungal prophylaxis and more recently transplanted. Aspergillus spp. and Candida spp. were the most commonly identified pathogens. 68% of patients had primarily pulmonary involvement. Univariate and multivariable analysis demonstrated inferior PFS and overall survival (OS) for cases. At 2 years, cases had higher mortality and shorter PFS with significant increases in non-relapse mortality (NRM) but no difference in relapse. One year probability of post-HSCT IFI was 24% (cases) and 17% (control, P<0.001). The predominant cause of death was underlying malignancy; infectious death was higher in cases (13% vs 9%). In the subset analysis, patients transplanted before 2001 had increased NRM with inferior OS and PFS compared with later cases. Pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT but significant survivorship was observed. Consequently, pre-transplant IFI should not be a contraindication to allogeneic HSCT in otherwise suitable candidates. Documented pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT. However, mortality post transplant is more influenced by advanced disease status than previous IFI. Pre-transplant IFI does not appear to be a contraindication to allogeneic HSCT

Bone pain and extremely low bone mineral density due to severe vitamin D deficiency in celiac disease

Case report A 29-year-old wheelchair-bound woman was presented to us by the gastroenterologist with suspected osteomalacia. She had lived in the Netherlands all her life and was born of Moroccan parents. Her medical history revealed iron deficiency, growth retardation, and celiac disease, for which she was put on a gluten-free diet. She had progressive bone pain since 2 years, difficulty with walking, and about 15 kg weight loss. She had a short stature, scoliosis, and pronounced kyphosis of the spine and poor condition of her teeth. Laboratory results showed hypocalcemia, an immeasurable serum25-hydroxyvitamin D level, and elevated parathyroid hormone and alkaline phosphatase levels. Spinal radiographs showed unsharp, low contrast vertebrae. Bone mineral density measurement at the lumbar spine and hip showed a T-score of -6.0 and -6.5, respectively. A bone scintigraphy showed multiple hotspots in ribs, sternum, mandible, and long bones. A duodenal biopsy revealed villous atrophy (Marsh 3C) and positive antibodies against endomysium, transglutaminase, and gliadin, compatible with active celiac disease. A bone biopsy showed severe osteomalacia but normal bone volume. She was treated with calcium intravenously and later orally. Furthermore, she was treated with high oral doses of vitamin D and a gluten-free diet. After a few weeks of treatment, her bone pain decreased, and her muscle strength improved. Discussion In this article, the pathophysiology and occurrence of osteomalacia as a complication of celiac disease are discussed. Low bone mineral density can point to osteomalacia as well as osteoporosis. © International Osteoporosis Foundation and National Osteoporosis Foundation 2011

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

Underrepresented drivers of and variability in volatile organic compound emissions from plants

2022 Summer.Includes bibliographical references.Volatile organic compounds released from plants interact with the atmosphere in complex ways, e.g., by contributing to the formation and removal of atmospheric oxidants and the production of secondary organic aerosol. These organic compounds include terpenes (polymers of C5H8), organic acids (e.g., formic and acetic), aldehydes (e.g., glycoaldehyde and 2-hexenal), and many other classes of compounds. These compounds are diverse in structure, preventing many assumptions as the physiochemical properties of each species is diverse. Even among the same class of compounds (e.g., C10H16 monoterpene isomers), the atmospheric implications of their emission and reactivity potential can range greatly, as some species contribute more towards the removal of ozone while others are more relevant to secondary organic aerosol formation. Given the diversity of these effects, the quantification and identification of these plant-emitted compounds is a key step to improve predictive models of their emissions and subsequent atmospheric impacts. Measuring the emission of these volatile organic compounds is compounded by their low concentrations, high reactivity, and chemical diversity, and, as of today, there is no single instrument capable of fully investigating the suite of plant-derived emissions. To address this knowledge gap, we used a commercial portable photosynthesis system in combination with numerous analytical instruments, namely chemical ionization mass spectrometry, proton transfer reaction mass spectrometry, and thermal desorption gas chromatography mass spectrometry. We present the modularity of this coupled technique and identify its limitations and the considerations which must be made when performing measurements in the field. We can investigate a greater suite of compounds by coupling the portable photosynthesis system with multiple trace gas instruments simultaneously. The system controls environmental conditions over a broad range applicable to plant physiology and we highlight how background interferences can be mitigated with pre- and post-leaf characterization. This technique provides photosynthetic parameters and direct measurements of leaf-level emissions to improve our understanding of the forces driving these emissions. In addition to developing new analytical techniques, this dissertation identifies numerous environmental factors impacting volatile organic compound emissions that have been so far overlooked or incorrectly represented and expands upon their atmospheric implications. Specifically, we find that the first seasonal snow events cause an initial burst of emissions from a deciduous tree and further changes the identity of speciated compounds compared pre-snow conditions. In this case, excluding speciation of these compounds leads to an underestimation of the atmospheric burden on reactivity and secondary organic aerosol formation. We further identify humidity, which does not exist as a direct emission forcer in most models, as a necessary consideration. Humidity can either have a discrete or synergistic effect with temperature, again complicating integration into models, but inclusion is necessary to address changes in absolute emission rates and the temperature dependence of these emissions. As an overarching theme, this dissertation further presents compelling evidence for considering multiple scales of variability in leaf-level measurements; these measurements are often time consuming, but failure to account for such variability can grossly bias results