NCT00455793.

Cells of the osteoblast lineage play an important role in regulating the hematopoietic stem cell (HSC) niche and early B cell development in animal models, perhaps via parathyroid hormone (PTH) dependent mechanisms. There are few human clinical studies investigating this phenomenon. We studied the impact of long-term daily teriparatide (PTH 1-34) treatment on cells of the hematopoietic lineage in postmenopausal women. Twenty-three postmenopausal women at high risk of fracture received teriparatide 20 mcg SC daily for 24 months as part of a prospective longitudinal trial. Whole blood measurements were obtained at baseline, 3, 6, 12, and 18 months. Flow cytometry was performed to identify hematopoietic subpopulations, including HSCs (CD34+/CD45(moderate); ISHAGE protocol) and early transitional B cells (CD19+, CD27−, IgD+, CD24[hi], CD38[hi]). Serial measurements of spine and hip bone mineral density as well as serum P1NP, osteocalcin, and CTX were also performed. The average age of study subjects was 64 ± 5. We found that teriparatide treatment led to an early increase in circulating HSC number of 40% ± 14% (p=0.004) by month 3, which persisted to month 18 before returning to near baseline by 24 months. There were no significant changes in transitional B cells or total B cells over the course of the study period. In addition, there were no differences in complete blood count profiles as quantified by standard automated flow cytometry. Interestingly, the peak increase in HSC number was inversely associated with increases in bone markers and spine BMD. Daily teriparatide treatment for osteoporosis increases circulating HSCs by 3 to 6 months in postmenopausal women. This may represent a proliferation of marrow HSCs or increased peripheral HSC mobilization. This clinical study establishes the importance of PTH in the regulation of the HSC niche within humans.

Background Despite widespread clinical use, lymph node fine‐needle aspiration cytology (LN‐FNAC) lacks universal acceptance for definitively diagnosing lymphomas. This is likely due to reports of lower diagnostic performance, inconsistent terminology use in cytopathology diagnostic reports, and only limited data on the clinical implications of LN‐FNAC diagnoses. Recently, a uniform LN‐FNAC cytopathological diagnostic reporting system was proposed (the Sydney System). This study evaluated LN‐FNAC diagnostic performance and risks of malignancy associated with the proposed diagnostic categories. Methods LN‐FNAC specimens obtained in 2018‐2019, with and without concurrent core biopsy, to evaluate for suspected lymphoma were analyzed (n = 349). LN‐FNAC diagnoses were compared with final diagnoses obtained via subsequent tissue biopsy and/or clinical assessment. Results The mean patient age was 57.6 years, and 41% were female. LN‐FNAC was the initial diagnostic test in 223 (63.9%), and it was used to evaluate for recurrence in 126 (36.1%). LN‐FNAC diagnosed 202 hematological malignancies (57.9%), 23 nonhematological malignancies (6.6%), and 124 reactive processes (35.5%). Subsequent tissue biopsy was performed in 42 (12%). The risks of malignancy per diagnostic category were as follows: inadequate, 58.3%; benign, 6.4%; atypical, 69.2%; suspicious, 96.7%; and malignant, 99.3%. LN‐FNAC demonstrated up to 96.3% sensitivity, 91.91% specificity, and 87.35% accuracy. Optimal specimen quality and the use of intradepartmental consultation reduced diagnostic error rates in FNA cases without concurrent core biopsy (P = .029 and P = .0002 respectively). Conclusions LN‐FNAC is accurate and reliable for the diagnosis of lymphoma. Inadequate LN‐FNAC samples should be resampled due to a significant associated risk of lymphoma. The diagnostic performance of LN‐FNAC may be improved with good specimen quality and reviews by multiple pathologists. Understanding the risks of malignancy associated with LN‐FNAC diagnostic categories will help to guide optimal patient management.

Background: Flow cytometric measurement of monocyte surface CD36 is relevant to several conditions including diabetes, cardiovascular disease, lipid disorders, platelet isoimmunization, and susceptibility to P falciparum malaria. CD36 is also strongly expressed on platelets where it is also known as platelet glycoprotein IV.Methods: Whole blood samples, containing identical monocyte concentrations, were adjusted to contain platelets ranging from 20,000/uL to 600,000/uL, were stained with fluorescent-labeled anti-CD36, and analyzed by flow cytometry.Results: CD36 median fluorescent intensity (MFI) observed on monocytes decreased as the platelet concentration in the sample increased with more than a 50% decline in monocyte MFI over the normal range of platelet values. The effect was not abolished by using larger volumes of monoclonal antibody and was observed with different clones of reagent anti-CD36. The findings were most consistent with competition by platelets for the CD36 reagent. Similar findings were observed with antibody to class I HLA. Under defined assay conditions, monocyte CD36 MFI declined with rising platelet concentration in a predictable fashion following an inverse linear relationship.Conclusions: Measurement of CD36 expression on monocytes by flow cytometry in whole blood samples is affected by the sample platelet count. When comparing the monocyte CD36 expression among different individuals, our approach can be used to adjust measured monocyte CD36 expression for the effect of the platelet concentration in the sample. Competition by platelets for monoclonal reagents may occur in other settings when whole blood assays are used and when the target antigen is strongly expressed on both platelets and leukocytes.