A premature infant with skin injury successfully treated with bilayered cellular matrix

The immature skin of premature infants is functionally less effective than the skin of full-term infants and therefore more vulnerable to injury. This article discusses the use of a biologic wound healing agent--bilayered cellular matrix--to heal a denuded hip wound in a premature infant. The treatment involved a compassionate use, single application of an investigational biologic wound healing agent to a 2.0-cm x 1.5-cm hip wound in a 23-week gestational age premature infant. A sterile, nonadherent dressing containing 3% bismuth tribromophenate in a special petrolatum blend on a fine mesh gauze also was applied over the biologic dressing and changed as needed. Wound closure was evaluated by photographs taken before and after the application of the bilayered cellular matrix. Wound measurements were reduced to 1.0 cm x 0.5 cm by day 4 post application of the bilayered cellular matrix, and clean granulation tissue was present. The wound was healed 10 days later. No signs or symptoms of infection were evident during the follow-up period and no adverse events were recorded. Comparative studies are warranted to fully evaluate the utility of bilayered cellular matrix in this clinical setting.     

Identification of substance use disorders in burn patients using simple diagnostic screening tools (AUDIT/DAST-10)

Introduction and objectivesSubstance use is disproportionately high in burn patients and associated with adverse outcomes. Screening methods for substance use disorders may help predict or avoid adverse outcomes.The University of Utah Burn Center records self-reported Alcohol Use Disorders Identification Tests (AUDIT) and Drug Abuse Screening Tests (DAST-10) for all adult burn admissions. This study assessed for association between AUDIT/DAST-10 scores and burn patient outcomes.MethodsA retrospective chart review of adult burn patients admitted to the University of Utah from 05/01/2014–06/30/2017. Patient demographics, injury data, and substance use data were collected and analyzed.Results322 patients underwent AUDIT/DAST-10 screening (n = 322). 56 (17.4%) had positive AUDIT screens (score ≥ 8). 15/50 with alcohol use at time of injury (TOI) had negative AUDIT screens. Median AUDIT score with TOI alcohol use was 12, without TOI alcohol use was 1. 30/55 patients offered alcohol counseling accepted.14 patients (4.3%) had positive DAST-10 screens (score ≥3). 9/25 with drug use at TOI had negative DAST-10 screens. No patients without TOI drug use had DAST-10 scores >2. 9/11 patients offered drug counseling accepted.Mean standardized length of stay (LOS) per TBSA burn injury was 1.7 days for positive AUDIT, 1.6 days for negative AUDIT. Median standardized LOS was 1.4 days for positive DAST-10, 1.7 days for negative DAST-10.ConclusionsAUDIT and DAST-10 screens can identify burn patients with problematic substance use, allowing early intervention. Positive screening scores do not independently predict longer hospital stays, increased wound severity, or treatment noncompliance.     

Effect of chemotherapy on default mode network connectivity in older women with breast cancer

Brain Imaging and Behavior - Chemotherapy may impair cognition and contribute to accelerated aging. The purpose of this study was to assess the effects of chemotherapy on the connectivity of the...     

HIV legal precedent useful for microbial forensics

The field of microbial forensics was formalized because of the need for attribution in events where a bioweapon has been used. Microbial forensics has its origins in traditional forensics, microbiology, and epidemiology. Microbial forensics can be defined as a scientific discipline dedicated to analyzing evidence for attribution purposes from a bioterrorism act, biocrime, hoax, or inadvertent microorganism/toxin release. This is a very challenging task, since there are myriad microorganisms that can pose a threat, and analytical methods need to be used reliably. The Scientific Working Group on Microbial Genetics and Forensics (SWGMGF) has addressed some quality assurance and control issues, and particularly validation criteria (focusing on preliminary validation) due to the dynamic nature of evolving investigations. Unique identification of a microorganism may never be possible. Yet, qualitative and/or quantitative assessments of the evidence can be made. One approach to provide direction on gaps in the microbial forensics effort is to perform an end-to-end retrospective analysis of past cases. As an example, the case of a gastroenterologist who was accused of second degree attempted murder of his paramour using HIV as the weapon was reviewed. The scientific evaluation involves epidemiology, molecular biology, phylogenetics, and legal deliberations.     

Comparison of synthetic surfactants and biosurfactants in enhancing biodegradation of polycyclic aromatic hydrocarbons

Polycyclic aromatic hydrocarbon (PAH) contamination of the environment represents a serious threat to the health of humans and ecosystems. Given the human health effects of PAHs, effective and cost-competitive remediation technologies are required. Bioremediation has shown promise as a potentially effective and low-cost treatment option, but concerns about the slow process rate and bioavailability limitations have hampered more widespread use of this technology. An option to enhance the bioavailability of PAHs is to add surfactants directly to soil in situ or ex situ in bioreactors. Surfactants increase the apparent solubility and desorption rate of the PAH to the aqueous phase. However, the results with some synthetic surfactants have shown that surfactant addition can actually inhibit PAH biodegradation via toxic interactions, stimulation of surfactant degraders, or sequestration of PAHs into surfactant micelles. Biosurfactants have been shown to have many of the positive effects of synthetic surfactants but without the drawbacks. They are biodegradable and nontoxic, and many biosurfactants do not produce true micelles, thus facilitating direct transfer of the surfactant-associated PAH to bacteria. The results with biosurfactants to date are promising, but further research to elucidate surfactant-PAH interactions in aqueous environments is needed to lead to predictive, mechanistic models of biosurfactant-enhanced PAH bioavailability and thus better bioremediation design.     

Quantifying the role of angiogenesis in malignant progression of gliomas: in silico modeling integrates imaging and histology

Gliomas are uniformly fatal forms of primary brain neoplasms that vary from low- to high-grade (glioblastoma). Whereas low-grade gliomas are weakly angiogenic, glioblastomas are among the most angiogenic tumors. Thus, interactions between glioma cells and their tissue microenvironment may play an important role in aggressive tumor formation and progression. To quantitatively explore how tumor cells interact with their tissue microenvironment, we incorporated the interactions of normoxic glioma cells, hypoxic glioma cells, vascular endothelial cells, diffusible angiogenic factors, and necrosis formation into a first-generation, biologically based mathematical model for glioma growth and invasion. Model simulations quantitatively described the spectrum of in vivo dynamics of gliomas visualized with medical imaging. Furthermore, we investigated how proliferation and dispersal of glioma cells combine to induce increasing degrees of cellularity, mitoses, hypoxia-induced neoangiogenesis and necrosis, features that characterize increasing degrees of "malignancy," and we found that changes in the net rates of proliferation (ρ) and invasion (D) are not always necessary for malignant progression. Thus, although other factors, including the accumulation of genetic mutations, can change cellular phenotype (e.g., proliferation and invasion rates), this study suggests that these are not required for malignant progression. Simulated results are placed in the context of the current clinical World Health Organization grading scheme for studying specific patient examples. This study suggests that through the application of the proposed model for tumor-microenvironment interactions, predictable patterns of dynamic changes in glioma histology distinct from changes in cellular phenotype (e.g., proliferation and invasion rates) may be identified, thus providing a powerful clinical tool.     

Gene therapy enhances chemotherapy tolerance and efficacy in glioblastoma patients

BACKGROUND. Temozolomide (TMZ) is one of the most potent chemotherapy agents for the treatment of glioblastoma. Unfortunately, almost half of glioblastoma tumors are TMZ resistant due to overexpression of methylguanine methyltransferase (MGMT^hi). Coadministration of O⁶-benzylguanine (O⁶BG) can restore TMZ sensitivity, but causes off-target myelosuppression. Here, we conducted a prospective clinical trial to test whether gene therapy to confer O⁶BG resistance in hematopoietic stem cells (HSCs) improves chemotherapy tolerance and outcome.METHODS. We enrolled 7 newly diagnosed glioblastoma patients with MGMT^hi tumors. Patients received autologous gene-modified HSCs following single-agent carmustine administration. After hematopoietic recovery, patients underwent O⁶BG/TMZ chemotherapy in 28-day cycles. Serial blood samples and tumor images were collected throughout the study. Chemotherapy tolerance was determined by the observed myelosuppression and recovery following each cycle. Patient-specific biomathematical modeling of tumor growth was performed. Progression-free survival (PFS) and overall survival (OS) were also evaluated.RESULTS. Gene therapy permitted a significant increase in the mean number of tolerated O⁶BG/TMZ cycles (4.4 cycles per patient, P < 0.05) compared with historical controls without gene therapy (n = 7 patients, 1.7 cycles per patient). One patient tolerated an unprecedented 9 cycles and demonstrated long-term PFS without additional therapy. Overall, we observed a median PFS of 9 (range 3.5–57⁺) months and OS of 20 (range 13–57⁺) months. Furthermore, biomathematical modeling revealed markedly delayed tumor growth at lower cumulative TMZ doses in study patients compared with patients that received standard TMZ regimens without O⁶BG.CONCLUSION. These data support further development of chemoprotective gene therapy in combination with O⁶BG and TMZ for the treatment of glioblastoma and potentially other tumors with overexpression of MGMT.TRIAL REGISTRATION. Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00669669","term_id":"NCT00669669"}}NCT00669669.FUNDING. R01CA114218, R01AI080326, R01HL098489, P30DK056465, K01DK076973, R01HL074162, R01CA164371, R01NS060752, U54CA143970.     

Invasion and proliferation kinetics in enhancing gliomas predict IDH1 mutation status

Background

Glioblastomas with a specific mutation in the isocitrate dehydrogenase 1 (IDH1) gene have a better prognosis than gliomas with wild-type IDH1.

Methods

Here we compare the IDH1 mutational status in 172 contrast-enhancing glioma patients with the invasion profile generated by a patient-specific mathematical model we developed based on MR imaging.

Results

We show that IDH1-mutated contrast-enhancing gliomas were relatively more invasive than wild-type IDH1 for all 172 contrast-enhancing gliomas as well as the subset of 158 histologically confirmed glioblastomas. The appearance of this relatively increased, model-predicted invasive profile appears to be determined more by a lower model-predicted net proliferation rate rather than an increased model-predicted dispersal rate of the glioma cells. Receiver operator curve analysis of the model-predicted MRI-based invasion profile revealed an area under the curve of 0.91, indicative of a predictive relationship. The robustness of this relationship was tested by cross-validation analysis of the invasion profile as a predictive metric for IDH1 status.

Conclusions

The strong correlation between IDH1 mutation status and the MRI-based invasion profile suggests that use of our tumor growth model may lead to noninvasive clinical detection of IDH1 mutation status and thus lead to better treatment planning, particularly prior to surgical resection, for contrast-enhancing gliomas.