Red Cell Depletion of Major ABO Incompatible Bone Marrow Hematopoietic Progenitor Cells HPC(M) with the Spectra Optia®.

OBJECTIVE: Major ABO incompatible hematopoietic progenitors from bone marrow (HPC(M)) donor collections that are destined for clinical transplantation are typically processed to deplete products of red blood cells (RBCs). The purpose of this study was to compare RBC depletion when using the Spectra Optia® relative to a 2-step method involving a COBE2991 instrument to obtain a buffy coat followed by a hydroxyethyl starch (HES) density gradient (COBE+HES) of the buffy coat. METHODS: Post-processing recoveries of products undergoing 4, 8, and 10 bone marrow processing (BMP) cycles (i.e. 1 cycle=1 volume of HPC(M)) with the Spectra Optia® were determined for volume, RBC content, viable total nucleated cells (vTNC), viable CD34+ cells (vCD34), viable CD3+ cells (vCD3) and colony-forming-cells (CFC). Subsequent RBC depletions with Spectra Optia® were then performed with 10 BMP cycles on additional HPC(M) collections and were compared against a retrospective analysis of historical COBE+HES post-processing data. RESULTS: Ten BMP cycles of HPC(M) (n=6) products were identified as optimal with volume reductions of 81.3±1.6 % and RBC reductions of 97.0±0.6 % with the Spectra Optia®. This also resulted in an average of 0.28 ±0.14 mL of RBC/kg (mean±SD; n=6) with vTNC yields of 65.0±10.9%, vCD34+ yields of 98.5±12.7%, and vCD3+ yields of 90.6±10.0%. Recoveries with the COBE+HES methodology resulted in vTNC recoveries of 62.9±20.5% (mean±SD; n=30) and 0.63±0.71 mL of RBC/kg (mean±SD; n=30). CONCLUSIONS: The Spectra Optia® is a viable option for depleting HPC(M) harvests of contaminating RBC in situations of ABO incompatibility. Target cells from a MNC rich fractionation were preserved through processing while eliminating RBC contaminants.

Screening for Periprosthetic Joint Infections With ESR and CRP: The Ideal Cutoffs.

BACKGROUND: The purpose of this study was to (1) determine the sensitivity and specificity of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) when screening for a periprosthetic joint infection (PJI) using the standard MSIS cutoff of 30 mm/h and 10 mg/L, respectively, and (2) determine the optimal ESR and CRP cutoff to achieve a sensitivity ≥95%. METHODS: We retrospectively analyzed 81 PJI patients and 83 noninfected arthroplasty patients. We calculated the sensitivity and specificity (and 95% confidence intervals) for ESR and CRP at thresholds of 30 mm/h and 10 mg/L, respectively. We determined the optimal cutoff for both ESR and CRP to yield a sensitivity greater than or equal to 95%. RESULTS: The ESR cutoff that resulted in a sensitivity ≥ to 95% (95% CI: 85.2-97.6%) was 10 mm/h, and the CRP cutoff that resulted in a sensitivity ≥ to 95% (95% CI: 87.1-98.4%) was 5 mg/L. The sensitivity and specificity with a combined ESR and CRP of 10 mm/h and 5 mg/L was 100% (95% CI: 94.1-100%) and 54.7% (95% CI: 46.4-62.3%). CONCLUSION: When using ESR and CRP as a screening tool with the accepted cutoffs of 30 mm/h and 10 mg/L, there is an unacceptably low sensitivity and a high number of false negatives. Therefore, further recommendation must be given to lowering these thresholds to avoid the devastating morbidity of a missed PJI. LEVEL OF EVIDENCE: III.

Costs of open, arthroscopic and combined surgery for developmental dysplasia of the hip.

A variety of options exist for management of patients with developmental dysplasia of the hip (DDH). Most studies to date have focused on clinical outcomes; however, there are currently no data on comparative cost of these techniques. The purpose of this study was to evaluate in-hospital costs between patients managed with periacetabular osteotomy, hip arthroscopy or a combination for DDH. One hundred and nine patients were included: 35 PAO + HA, 32 PAO and 42 HA. There were no significant differences in the demographic parameters. Operative times were significantly different between groups with a mean of 52 min for PAO, 100 min for HA and 155 min for PAO + HA, (P < 0.001). Total direct medical costs were calculated and adjusted to nationally representative unit costs in 2017 inflation-adjusted dollars. Total in-hospital costs were significantly different between each of the three treatment groups. PAO + HA was the most expensive with a median of $21 852, followed by PAO with a median of $15 124, followed by HA with a median of $11 582 (P < 0.001). There was a significant difference between outpatient median costs of $11 385 compared with $24 320 for inpatients (P < 0.001). Procedures with greater complexity were more expensive. However, a change from outpatient to inpatient status with HA moved that group from the least expensive to similar to PAO and PAO + HA. These data provide an important complement to clinical outcomes reports as surgeons and policymakers aim to provide optimal value.

Expression of schizophrenia biomarkers in extraocular muscles from patients with strabismus: an explanation for the link between exotropia and schizophrenia?

Recent studies have implicated exotropia as a risk factor for schizophrenia. We determined whether schizophrenia biomarkers have abnormal levels of expression in extraocular muscles from patients with strabismus and explored whether differences in gene expression between medial and lateral rectus muscles may explain the specific association of schizophrenia with exotropia but not esotropia. Samples from horizontal extraocular muscles were obtained during strabismus surgery and compared with age- and muscle type-matched normal muscles from organ donors. We used PCR arrays to identify differences in gene expression among 417 signaling molecules. We then focused on established schizophrenia-related growth factors, cytokines, and regulators of the extracellular matrix. Among 36 genes with significantly altered gene expression in dysfunctional horizontal rectus muscles, over one third were schizophrenia-related: CTGF, CXCR4, IL1B, IL10RA, MIF, MMP2, NPY1R, NRG1, NTRK2, SERPINA3, TIMP1, TIMP2, and TNF (adjusted p value ≤ 0.016667). By PCR array, expression of three of these genes was significantly different in medial rectus muscles, while eleven were significantly altered in lateral rectus muscles. Comparing baseline levels between muscle types, three schizophrenia-related genes (NPY1R, NTRK2, TIMP2) had lower levels of expression in medial rectus muscles. Despite the surprisingly large number of schizophrenia-related genes with altered gene expression levels in dysfunctional muscles, the lack of specificity for medial rectus muscles undermines a model of shared, region-specific gene expression abnormalities between exotropia and schizophrenia, but rather suggests consideration of the alternative model: that exotropia-induced aberrant early visual experiences may enable and/or contribute as a causative factor to the development of schizophrenia.

Long-term effects of cryopreservation on clinically prepared hematopoietic progenitor cell products.

BACKGROUND AIMS: The question of how long hematopoietic progenitor cells (HPCs) destined for clinical applications withstand long-term cryopreservation remains unanswered. To increase our basic understanding about the stability of HPC products over time, this study focused on characterizing long-term effects of cryopreservation on clinically prepared HPC products. METHODS: Cryovials (n = 233) frozen for an average of 6.3 ± 14.2 years (range, 0.003-14.6 years) from HPC products (n = 170) representing 75 individual patients were thawed and evaluated for total nucleated cells (TNCs), cell viability, viable CD34+ (vCD34+) cells and colony-forming cells (CFCs). TNCs were determined by use of an automated cell counter, and cell viability was measured with the use of trypan blue exclusion. Viable CD34 analysis was performed by means of flow cytometry and function by a CFC assay. RESULTS: Significant losses in TNCs, cell viability, vCD34+ cells and CFC occurred on cryopreservation. However, once frozen, viable TNCs, vCD34+ cells and CFC recoveries did not significantly change over time. The only parameter demonstrating a change over time was cell viability, which decreased as the length of time that an HPC product was stored frozen increased. A significant negative correlation (correlation coefficient = -0.165) was determined between pre-freeze percent granulocyte content and post-thaw percent viability (n = 170; P = 0.032). However, a significant positive correlation was observed between percent viability at thaw and pre-freeze lymphocyte concentration. CONCLUSIONS: Once frozen, HPC products were stable for up to 14.6 years at <-150°C. Post-thaw viability was found to correlate negatively with pre-freeze granulocyte content and positively with pre-freeze lymphocyte content.