Search

Background: While sutureless, cryopreserved amniotic membrane (cAM) has been shown to significantly improve signs and symptoms of dry eye disease (DED), no studies have assessed the association of cAM treatment duration to the differential response in clinical outcomes.Methods: A multi-center, retrospective study was conducted on patients with moderate-to-severe DED who were treated with self-retained cAM (Prokera® Slim) for 2 to 7 days. The primary outcome measure was DEWS severity score assessed at 1 week, 1 month, and 3 months. Secondary outcome measures included ocular discomfort, visual symptoms, corneal staining, and visual acuity.Results: A total of 89 eyes (77 patients) with moderate-to-severe DED (DEWS severity 3.24 ± 0.56) received treatment with self-retained cAM for 2 days (n = 10), 3 days (n = 15), 4 days (n = 12), 5 days (n = 19), 6 days (n = 6), or 7 days (n = 27). DEWS scores significantly improved at 1 week, 1 month, and 3 months for all treatment duration groups, with no significant difference observed between groups at any timepoint. In addition to an improvement in DEWS severity scores, those receiving cAM treatment for 2 days demonstrated a significant improvement in corneal staining, visual symptoms, and ocular discomfort at 1 week, 1 month, and 3 months.Conclusion: This retrospective study suggests that a single placement of self-retained cAM for 2 days can significantly improve signs and symptoms of DED with a lasting benefit observed for up to 3 months. [ABSTRACT FROM AUTHOR]

The use of gene-editing technology has the potential to excise the CCR5 gene from haematopoietic progenitor cells, rendering their differentiated CD4-positive (CD4+) T cell descendants HIV resistant. In this manuscript, we describe the development of a mathematical model to mimic the therapeutic potential of gene editing of haematopoietic progenitor cells to produce a class of HIV-resistant CD4+ T cells. We define the requirements for the permanent suppression of viral infection using gene editing as a novel therapeutic approach. We develop non-linear ordinary differential equation models to replicate HIV production in an infected host, incorporating the most appropriate aspects found in the many existing clinical models of HIV infection, and extend this model to include compartments representing HIV-resistant immune cells. Through an analysis of model equilibria and stability and computation of |$R_0$| for both treated and untreated infections, we show that the proposed therapy has the potential to suppress HIV infection indefinitely and return CD4+ T cell counts to normal levels. A computational study for this treatment shows the potential for a successful 'functional cure' of HIV. A sensitivity analysis illustrates the consistency of numerical results with theoretical results and highlights the parameters requiring better biological justification. Simulations of varying level production of HIV-resistant CD4+ T cells and varying immune enhancements as the result of these indicate a clear threshold response of the model and a range of treatment parameters resulting in a return to normal CD4+ T cell counts. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of cryopreserved amniotic membrane (CAM) in reducing signs and symptoms of dry eye disease (DED) in a large patient population. Methods: A retrospective chart review at 10 clinical sites was done of patients with refractory DED who received CAM and completed at least 3 months of follow-up. Data collected were demographics; medical history including previous and current ocular treatment, diagnosis, clinical presentations, comorbidity, duration and frequency of treatment with CAM; and concomitant medications. The primary outcome was the change in dry eye workshop (DEWS) score after treatment. Results: A total of 97 eyes of 84 patients exhibited severe dry eye despite maximal medical treatments including topical artificial tears, cyclosporine-A, serum, antibiotics, and steroids. Patients manifested with superficial punctate keratitis (86%), filamentary keratitis (13%), exposure keratitis (19%), neurotrophic keratitis (2%), and corneal epithelial defect (7%). After CAM treatment for 5.4±2.8 days, 74 (88%) patients demonstrated an improved ocular surface along with a notable reduction of the severity as the overall DEWS score was significantly reduced from 3.25±0.5 at baseline to 1.44±0.6 at 1 week, 1.45±0.6 at 1 month, and 1.47±0.6 at 3 months (p,0.001). Ten eyes (10%) required repeated treatment to complete healing. Apart from discomfort during CAM placement, there were no adverse events. Conclusion: Placement of CAM is promising to enhance the recovery of ocular surface health and reduce signs and symptoms in patients with moderate-to-severe DED. [ABSTRACT FROM AUTHOR]

Lentivirus escape from neutralizing antibodies (NAbs) is not well understood. In this work, we quantified antibody escape of a lentivirus, using antibody escape data from horses infected with equine infectious anemia virus. We calculated antibody blocking rates of wild-type virus, fitness costs of mutant virus, and growth rates of both viruses. These quantitative kinetic estimates of antibody escape are important for understanding lentiviral control by antibody neutralization and in developing NAb-eliciting vaccine strategies. [ABSTRACT FROM AUTHOR]

B cell chronic lymphocytic leukemia (B-CLL) is known to have substantial clinical heterogeneity. There is no cure, but treatments allow for disease management. However, the wide range of clinical courses experienced by B-CLL patients makes prognosis and hence treatment a significant challenge. In an attempt to study disease progression across different patients via a unified yet exible approach, we present a mathematical model of B-CLL with immune response, that can capture both rapid and slow disease progression. This model includes four different cell populations in the peripheral blood of humans: B-CLL cells, NK cells, cytotoxic T cells and helper T cells. We analyze existing data in the medical literature, determine ranges of values for parameters of the model, and compare our model outcomes to clinical patient data. The goal of this work is to provide a tool that may shed light on factors affecting the course of disease progression in patients. This modeling tool can serve as a foundation upon which future treatments can be based. [ABSTRACT FROM AUTHOR]