Abstract Autologous cell therapies including platelet-rich plasma (PRP) and bone marrow concentrate (BMC) are increasingly popular options for soft tissue and joint-related diseases. Despite ...increased clinical application, conflicting research has been published regarding the efficacy of PRP, and few clinical publications pertaining to BMC are available. Preparations of PRP (and BMC) can vary in many areas, including platelet concentration, number of white blood cells, presence or absence of red blood cells, and activation status of the preparation. The potential effect of PRP characteristics on PRP efficacy is often not well understood by the treating clinician, and PRP characteristics, as well as the volume of PRP delivered, are unfortunately not included in the methods of many published research articles. It is essential to establish a standard reporting system for PRP that facilitates communication and the interpretation and synthesis of scientific investigations. Herein, the authors propose a new PRP classification system reflecting important PRP characteristics based on contemporary literature and recommend adoption of minimal standards for PRP reporting in scientific investigations. Widespread adoption of these recommendations will facilitate interpretation and comparison of clinical studies and promote scientifically based progress in the field of regenerative medicine.
The 1986 Chernobyl nuclear power plant accident increased papillary thyroid carcinoma (PTC) incidence in surrounding regions, particularly for radioactive iodine (
I)-exposed children. We analyzed ...genomic, transcriptomic, and epigenomic characteristics of 440 PTCs from Ukraine (from 359 individuals with estimated childhood
I exposure and 81 unexposed children born after 1986). PTCs displayed radiation dose-dependent enrichment of fusion drivers, nearly all in the mitogen-activated protein kinase pathway, and increases in small deletions and simple/balanced structural variants that were clonal and bore hallmarks of nonhomologous end-joining repair. Radiation-related genomic alterations were more pronounced for individuals who were younger at exposure. Transcriptomic and epigenomic features were strongly associated with driver events but not radiation dose. Our results point to DNA double-strand breaks as early carcinogenic events that subsequently enable PTC growth after environmental radiation exposure.
Although generally curable with intensive chemotherapy in resource-rich settings, Burkitt lymphoma (BL) remains a deadly disease in older patients and in sub-Saharan Africa. Epstein-Barr virus (EBV) ...positivity is a feature in more than 90% of cases in malaria-endemic regions, and up to 30% elsewhere. However, the molecular features of BL have not been comprehensively evaluated when taking into account tumor EBV status or geographic origin. Through an integrative analysis of whole-genome and transcriptome data, we show a striking genome-wide increase in aberrant somatic hypermutation in EBV-positive tumors, supporting a link between EBV and activation-induced cytidine deaminase (AICDA) activity. In addition to identifying novel candidate BL genes such as SIN3A, USP7, and CHD8, we demonstrate that EBV-positive tumors had significantly fewer driver mutations, especially among genes with roles in apoptosis. We also found immunoglobulin variable region genes that were disproportionally used to encode clonal B-cell receptors (BCRs) in the tumors. These include IGHV4-34, known to produce autoreactive antibodies, and IGKV3-20, a feature described in other B-cell malignancies but not yet in BL. Our results suggest that tumor EBV status defines a specific BL phenotype irrespective of geographic origin, with particular molecular properties and distinct pathogenic mechanisms. The novel mutation patterns identified here imply rational use of DNA-damaging chemotherapy in some patients with BL and targeted agents such as the CDK4/6 inhibitor palbociclib in others, whereas the importance of BCR signaling in BL strengthens the potential benefit of inhibitors for PI3K, Syk, and Src family kinases among these patients.
•Tumor EBV status is more strongly associated with distinct genetic and etiological mechanisms than geographic origin.•EBV-positive BL genomes feature fewer driver mutations despite their greater mutational load that is partly a result of increased AICDA activity.
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Abstract The area of regenerative medicine, through the use of cell-based or biologic therapies, affords various options even with the choice of autologous stem cells and requires the clinician to ...use the currently evolving science along with the art of medicine. Potential sources for stem cells are embryos, fetuses, and adults (adipose tissue or adult cells, usually from skin induced pluripotent, amniotic fluid, cartilage, bone marrow, menstrual blood, peripheral blood, placenta, skin, teeth, synovium, or umbilical cord blood). Issues regarding the source of stem cells include ethical and political/regulatory concerns, cell frequency, ease/difficulty of extraction, ease/difficulty of graft preparation, and host reaction to the implant. The most common sources of stem cells for orthopedic conditions are adipose tissue and bone marrow. Various opinions are expressed within the medical literature for and against both of these stem cell sources. This article will review patient concerns and preparation for obtaining cells; equipment, supplies, and staffing for the procedures; techniques, pearls, pitfalls, and risks of the procedures; and the manner of/options for processing the cells.
Purpose Nerve repair after a segmental defect injury remains a challenge for surgeons. Fibrin glue can be used to expedite surgical procedures and maintain proper nerve spatial orientation to ...potentially optimize recovery, yet surgeons hesitate to use it owing to concerns about fibrin's inhibiting regeneration and increasing scar formation. The purpose of these experiments was to evaluate whether fibrin glue impedes nerve regeneration. Methods A critical-size defect of 10 mm was created in 32 Sprague-Dawley rats with 4 different forms of repair: a collagen type-I conduit (n = 8), a collagen type-I conduit filled with fibrin glue (n = 8), an autologous nerve graft (n=8), and an autologous nerve graft with fibrin glue (n = 8). Behavioral tests, including sciatic functional indices, were used to evaluate functional recovery. Neurophysiology, immunohistochemistry, and nerve morphometry were used to critically analyze nerve regeneration. Results Multiple outcome parameters for nerve regeneration, remyelination, behavior, and electrophysiology were used to determine that the addition of fibrin did not influence recovery for the autograft groups. Similarly, within the conduit group, behavioral tests showed comparable functional recovery and indistinguishable results in compound motor action potential and nerve morphometry. Immunohistochemistry revealed identical degrees of Wallerian degeneration and scarring between conduit groups. Conclusions The addition of fibrin to either the conduit or the autograft group did not result in any meaningful differences in recovery. Our data demonstrate that fibrin glue does not impede nerve regeneration or functional recovery after surgical repair of a segmental nerve defect in a rat model. Clinical relevance The clinical use of fibrin glue as an adjunct with peripheral nerve repair may be considered safe because it does not impair nerve regeneration with critical size defects in an animal model.
Objectives
Single‐use rhinolaryngoscopes were brought to market in 2019 as an alternative to traditional reusable scopes and have garnered interest across settings given portability and potential ...cost advantages. While single‐use was previously evaluated compared to traditional devices, the overall impact to the consult experience for both users and patients has not been captured.
Methods
Eighteen residents performed consults with both single‐use and reusable rhinolaryngoscope systems on alternating weeks. A five‐question cumulative survey administered across three assessment points over a 12‐week period using a five‐point rating system to rate favorability. Residents and patients also completed four‐point scale surveys following procedure(s) to capture the consult experience. Statistical analyses were performed to measure significance differences between survey responses between the two systems.
Results
Single‐use rhinolaryngoscopes received higher overall ratings compared with reusables across each metric captured including overall consult time (4.3 vs. 2.2, p < .001), multiscope consults (4.4 vs. 3.1, p < .001), patient communication (4.6 vs. 2.1, p < .001), teaching opportunities (4.6 vs. 2.1, p < .001), and overall ease of use (4.7 vs. 2.6, p < .001). Residents rated single‐use higher than reusable after each procedure in terms of ease of use (1.07 vs. 2.68, p < .001) and visual clarity (1.27 vs. 1.89, p = .003), while patients rated single‐use higher for understanding of illness (3.9 vs. 3.1, p < .001) and understanding of treatment rationale (3.9 vs. 3.1, p < .001).
Conclusion
Resident and patient experience feedback favored single‐use rhinolaryngoscopes compared to reusable scope technology across multiple surveyed measurables. Single‐use rhinolaryngoscopes provide a viable tool for otorhinolaryngologist and other clinicians to perform rhinolaryngoscopy consults.
Level of Evidence
4.
Single‐use rhinolaryngoscopes came to market in 2019 as an alternative to reusable rhinolaryngoscopes. This study aimed to compile resident and patient feedback of a new single‐use rhinolaryngoscope system compared to a reusable scope platform during use for inpatient bedside ENT consults.
Modeling of genomic profiles from the Cancer Genome Atlas (TCGA) by using recently developed mathematical frameworks has associated a genome-wide pattern of DNA copy-number alterations with a ...shorter, roughly one-year, median survival time in glioblastoma (GBM) patients. Here, to experimentally test this relationship, we whole-genome sequenced DNA from tumor samples of patients. We show that the patients represent the U.S. adult GBM population in terms of most normal and disease phenotypes. Intratumor heterogeneity affects
≈
11
% and profiling technology and reference human genome specifics affect <1% of the classifications of the tumors by the pattern, where experimental batch effects normally reduce the reproducibility, i.e., precision, of classifications based upon between one to a few hundred genomic loci by >30%. With a 2.25-year Kaplan–Meier median survival difference, a 3.5 univariate Cox hazard ratio, and a 0.78 concordance index, i.e., accuracy, the pattern predicts survival better than and independent of age at diagnosis, which has been the best indicator since 1950. The prognostic classification by the pattern may, therefore, help to manage GBM pseudoprogression. The diagnostic classification may help drugs progress to regulatory approval. The therapeutic predictions, of previously unrecognized targets that are correlated with survival, may lead to new drugs. Other methods missed this relationship in the roughly 3B-nucleotide genomes of the small, order of magnitude of 100, patient cohorts, e.g., from TCGA. Previous attempts to associate GBM genotypes with patient phenotypes were unsuccessful. This is a proof of principle that the frameworks are uniquely suitable for discovering clinically actionable genotype–phenotype relationships.
Objectives
To examine the degree of agreement between MRI and histologically generated volumetric measurements of residual injection laryngoplasty material.
Methods
Following left recurrent laryngeal ...nerve transection, rabbit vocal cords were injected with jellyfish collagen, Cymetra®, or Restylane®. Laryngeal tissue was harvested 4 or 12 weeks post injection followed by MRI imaging and histologic cross‐sectioning. Two raters estimated the volume of remaining injection material in specimens within MRI and histologic axial cross sections. Wilcoxon signed rank tests were employed to detect gross differences between inter‐rater measurements and between imaging modalities across time. Agreement between rater measurements and imaging (histology and MRI) was assessed using intra‐class correlation coefficients.
Results
Data was available from 16 rabbits sacrificed at 4 weeks (n = 8) and 12 weeks (n = 8). Inter‐rater testing of MRI imaging revealed no significant differences (p > .05) between rater measurements across time points, and excellent agreement (0.93; 95% confidence interval 0.80–0.98) while histologically estimated volumes demonstrated a significant difference at 4 weeks (p < .05) and overall good agreement (0.89; 95% confidence interval 0.59–0.97). Comparison of MRI and histologically estimated volume measurements revealed significant differences at the 4‐week time point (p < .05) but not at 12 weeks (p > .05). Overall, there is only moderate agreement between MRI and histology estimates (0.72; 95% confidence interval 0.22–0.90).
Conclusions
MRI imaging demonstrates good reliability and similar estimates of volume to histologically estimated measurements of residual injection laryngoplasty material at time points clinically relevant for future injection laryngoplasty experiments.
Level of Evidence
NA.
MRI and histologically generated volumetric measurements of residual injection laryngoplasty material were compared over several time points in a rabbit model of injection laryngoplasty using an assortment of injection laryngoplasty materials including jellyfish collagen, Cymetra®, or Restylane®. MRI demonstrated good reliability and similar estimates of volume to histologically estimated measurements of residual injection laryngoplasty material at time points clinically relevant for future injection laryngoplasty experiments.
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