The Association of Cardiovascular and Neurological Comorbidities in Geriatric Patients Sustaining Ocular Trauma.

Purpose: Falls are associated with ocular trauma in the elderly. However, it is unlikely for a fall to cause ocular injury unless there is a disruption in the protective maneuvers that shield the face. We suspect ocular injury may be an early indicator of systemic or neurologic degeneration. This study investigates the 5-year incidence of cardiovascular and neurodegenerative diseases in older patients who sustained ocular or periorbital injuries. Patients and Methods: This was a retrospective cohort study. The study population included 141 patients over the age of 65 who sustained trauma to the eye, orbit, or eyelid between April 2011 and June 2016. The control population included 141 patients with a similar range of comorbidities who received cataract surgery during the same period. The study measured new diagnoses of various disorders during the 5-year period following presentation. Results: There were a total of 180 females and 102 males in the study. The mean ages of the control and subject group were 76 and 81.8, respectively. Of our twelve tested comorbidity types, patients that suffered a periocular trauma were more likely to develop heart failure (p=0.00244), dementia (p=0.00002), Alzheimer's disease (p=0.00087), and vascular disease (p=0.00037). Conclusion: Geriatric patients who sustained ocular and periocular injuries had a greater incidence of heart failure, dementia, Alzheimer's disease, and atherosclerosis diagnoses in the 5-year period following injury. The findings of this study suggest that periocular trauma may be an early indicator of underlying degenerative or systemic disease. Ophthalmologists should ensure proper primary care follow-up in conjunction with recovery from injury.

Characterization and Function of Cryopreserved Bone Marrow from Deceased Organ Donors: A Potential Viable Alternative Graft Source.

Despite the readily available graft sources for allogeneic hematopoietic cell transplantation (alloHCT), a significant unmet need remains in the timely provision of suitable unrelated donor grafts. This shortage is related to the rarity of certain HLA alleles in the donor pool, nonclearance of donors owing to infectious disease or general health status, and prolonged graft procurement and processing times. An alternative hematopoietic progenitor cell (HPC) graft source obtained from the vertebral bodies (VBs) of deceased organ donors could alleviate many of the obstacles associated with using grafts from healthy living donors or umbilical cord blood (UCB). Deceased organ donor-derived bone marrow (BM) can be preemptively screened, cryogenically banked for on-demand use, and made available in adequate cell doses for HCT. We have developed a good manufacturing practice (GMP)-compliant process to recover and cryogenically bank VB-derived HPCs from deceased organ donor (OD) BM. Here we present results from an analysis of HPCs from BM obtained from 250 deceased donors to identify any substantial difference in composition or quality compared with HPCs from BM aspirated from the iliac crests of healthy living donors. BM from deceased donor VBs was processed in a central GMP facility and packaged for cryopreservation in 5% DMSO/2.5% human serum albumin. BM aspirated from living donor iliac crests was obtained and used for comparison. A portion of each specimen was analyzed before and after cryopreservation by flow cytometry and colony-forming unit potential. Bone marrow chimerism potential was assessed in irradiated immunocompromised NSG mice. Analysis of variance with Bonferroni correction for multiple comparisons was used to determine how cryopreservation affects BM cells and to evaluate indicators of successful engraftment of BM cells into irradiated murine models. The t test (with 95% confidence intervals [CIs]) was used to compare cells from deceased donors and living donors. A final dataset of complete clinical and matched laboratory data from 226 cryopreserved samples was used in linear regressions to predict outcomes of BM HPC processing. When compared before and after cryopreservation, OD-derived BM HPCs were found to be stable, with CD34+ cells maintaining high viability and function after thawing. The yield from a single donor is sufficient for transplantation of an average of 1.6 patients (range, 1.2 to 7.5). CD34+ cells from OD-derived HPCs from BM productively engrafted sublethally irradiated immunocompromised mouse BM (>44% and >67% chimerism at 8 and 16 weeks, respectively). Flow cytometry and secondary transplantation confirmed that OD HPCs from BM is composed of long-term engrafting CD34+CD38-CD45RA-CD90+CD49f+ HSCs. Linear regression identified no meaningful predictive associations between selected donor-related characteristics and OD BM HPC quality or yield. Collectively, these data demonstrate that cryopreserved BM HPCs from deceased organ donors is potent and functionally equivalent to living donor BM HPCs and is a viable on-demand graft source for clinical HCT. Prospective clinical trials will soon commence in collaboration with the Center for International Blood and Marrow Research to assess the feasibility, safety, and efficacy of Ossium HPCs from BM (ClinicalTrials.gov identifier NCT05068401).

Comparison of Time-to-Surgery and Outcomes in Transferred Vs Non-Transferred Open Globe Injuries.

Purpose: It is widely accepted in the field of ophthalmology that closure of open globes within 24 hours of the injury results in the best visual outcomes. This study investigates the time-to-surgery and visual outcomes of open globe injury patients in North Carolina that were transferred to our institution before receiving surgical intervention as compared to those that were not transferred. Patients and methods: This is a retrospective cohort study using data from UNC Hospitals trauma registry. Demographics, time of injury, final clinical outcomes, time to surgical intervention, and transfer history were extracted and analyzed. The study population includes open globe injury patients of all ages that were seen and treated at our institution from 2005 to 2020. Patients were divided based on transfer history. The transfer group consisted of patients who were transferred from an outside hospital to our tertiary care facility for surgical treatment. The non-transfer group consisted of patients who arrived at our tertiary care facility directly after injury. Results: In total, 238 open globe injuries were evaluated. Of those, 197 were transferred and 41 were not transferred. Compared to non-transfer patients, transfer patients had longer delays between injury and surgery, between presentation at the initial ED and surgery, and between injury and arrival at the tertiary care center. On average, the delay between injury and surgical intervention was 3 hours and 51 minutes longer for transfer patients compared to non-transfer patients. Eight patients in the transfer group were delayed >24 hours due to inter-hospital transfer. Additionally, transfer patients on average suffered from poorer final visual acuities, with an average final visual acuity of 1.84 logMAR in the transfer group and 1.35 logMAR in the non-transfer group. Conclusion: Our study found that inter-hospital transfer leads to significant delays in primary closure of open globe injuries. Injuries that were transferred to a tertiary care center before receiving surgical intervention on average resulted in worse final visual acuities.

Identification and characterization of a large source of primary mesenchymal stem cells tightly adhered to bone surfaces of human vertebral body marrow cavities.

BACKGROUND: Therapeutic allogeneic mesenchymal stromal cells (MSCs) are currently in clinical trials to evaluate their effectiveness in treating many different disease indications. Eventual commercialization for broad distribution will require further improvements in manufacturing processes to economically manufacture MSCs at scales sufficient to satisfy projected demands. A key contributor to the present high cost of goods sold for MSC manufacturing is the need to create master cell banks from multiple donors, which leads to variability in large-scale manufacturing runs. Therefore, the availability of large single donor depots of primary MSCs would greatly benefit the cell therapy market by reducing costs associated with manufacturing. METHODS: We have discovered that an abundant population of cells possessing all the hallmarks of MSCs is tightly associated with the vertebral body (VB) bone matrix and only liberated by proteolytic digestion. Here we demonstrate that these vertebral bone-adherent (vBA) MSCs possess all the International Society of Cell and Gene Therapy-defined characteristics (e.g., plastic adherence, surface marker expression and trilineage differentiation) of MSCs, and we have therefore termed them vBA-MSCs to distinguish this population from loosely associated MSCs recovered through aspiration or rinsing of the bone marrow compartment. RESULTS: Pilot banking and expansion were performed with vBA-MSCs obtained from 3 deceased donors, and it was demonstrated that bank sizes averaging 2.9 × 108 ± 1.35 × 108 vBA-MSCs at passage 1 were obtainable from only 5 g of digested VB bone fragments. Each bank of cells demonstrated robust proliferation through a total of 9 passages, without significant reduction in population doubling times. The theoretical total cell yield from the entire amount of bone fragments (approximately 300 g) from each donor with limited expansion through 4 passages is 100 trillion (1 × 1014) vBA-MSCs, equating to over 105 doses at 10 × 106 cells/kg for an average 70-kg recipient. DISCUSSION: Thus, we have established a novel and plentiful source of MSCs that will benefit the cell therapy market by overcoming manufacturing and regulatory inefficiencies due to donor-to-donor variability.

Potential for Beneficial Reuse of Oil and Gas-Derived Produced Water in Agriculture: Physiological and Morphological Responses in Spring Wheat (Triticum aestivum).

Produced water (PW) from oil and gas operations is considered a potential resource for food crop irrigation because of increasing water scarcity in dryland agriculture. However, efforts to employ PW for agriculture have been met with limited success. A greenhouse study was performed to evaluate the effects of PW on physiological and morphological traits of spring wheat (Triticum aestivum). Plants were irrigated with water treatments containing 10 and 50% PW (PW10 and PW50, respectively) and compared to a matching 50% salinity (NaCl50) and 100% tap water controls. Compared to controls, plants watered with PW10 and PW50 exhibited developmental arrest and reductions in aboveground and belowground biomass, photosynthetic efficiency, and reproductive growth. Decreases in grain yield ranged from 70 to 100% in plants irrigated with PW compared to the tap water control. Importantly, the PW10 and NaCl50 treatments were comparable for morphophysiological effects, even though NaCl50 contained 5 times the total dissolved solids, suggesting that constituents other than NaCl in PW contributed to plant stress. These findings indicate that despite discharge and reuse requirements focused on total dissolved solids, salinity stress may not be the primary factor affecting crop health. The results of the present study are informative for developing guidelines for the use of PW in agriculture to ensure minimal effects on crop morphology and physiology. Environ Toxicol Chem 2019;38:1756-1769. © 2019 SETAC.