Dataset Information

The regulatory ancestral network of surgical meshes.

ABSTRACT: BACKGROUND:All surgical meshes entering the U.S. market have been cleared for clinical use by the 510(k) process of the Food and Drug Administration (FDA), in which devices simply require proof of "substantial equivalence" to predicate devices, without the need for clinical trials. However, recalled meshes associated with adverse effects may, indirectly, continue to serve as predicates for new devices raising concerns over the safety of the 510(k) route. METHODOLOGY:Here we assess the potential magnitude of this problem by determining the ancestral network of equivalence claims linking recently cleared surgical meshes. Using the FDA website we identified all surgical meshes cleared by the 510(k) route between January 2013 and December 2015 along with all listed predicates for these devices. Using a network approach, we trace the ancestry of predicates across multiple generations of equivalence claims and identify those meshes connected to devices that have since recalled from the market along with the reason for their recall. CONCLUSIONS:We find that the 77 surgical meshes cleared between 2013 and 2015 are based on 771 interconnected predicate claims of equivalence from 400 other devices. The vast majority of these devices (97%) are descended from only six surgical meshes that were present on the market prior to 1976. One of these ancestral meshes alone, provided the basis of 183 subsequent devices. Furthermore, we show that 16% of recently cleared devices are connected through equivalence claims to the 3 predicate meshes that have been recalled for design and material related flaws causing serious adverse events. Taken together, our results show that surgical meshes are connected through a tangled web of equivalency claims and many meshes recently cleared by the FDA have connections through chains of equivalency to devices which have been recalled from the market due to concerns over clinical safety. These findings raise concerns over the efficacy of the 510(k) route in ensuring patient safety.

SUBMITTER: Zargar N

PROVIDER: S-EPMC6007828 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The regulatory ancestral network of surgical meshes.

Zargar Nasim N Carr Andrew A

PloS one 20180619 6

<h4>Background</h4>All surgical meshes entering the U.S. market have been cleared for clinical use by the 510(k) process of the Food and Drug Administration (FDA), in which devices simply require proof of "substantial equivalence" to predicate devices, without the need for clinical trials. However, recalled meshes associated with adverse effects may, indirectly, continue to serve as predicates for new devices raising concerns over the safety of the 510(k) route.<h4>Methodology</h4>Here we assess ...[more]

PMID: 29920525

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Project description:BackgroundIt is an undisputable fact that meshes have become standard for repair of abdominal wall hernias. Whereas in the late eighties there were only a couple of different devices available, today we have to choose among some hundreds, with lots of minor and major variations in polymer and structure. As most of the minor variations may not lead to significant change in clinical outcome and may be regarded as less relevant, we should focus on major differences. Eventually, this is used to structure the world of mesh by forming groups of textile devices with distinct biological response. Many experimental and some clinical studies have underlined the outstanding importance of porosity, which fortunately, in contrast to other biomechanical quanlities, is widely unaffected by the anisotropy of meshes.MethodsIn accordance with the major manufacturers of meshes, a classification of meshes was derived from a huge pool of textile data based briefly on the following: (1) large pores, (2) small pores, (3) additional features, (4) no pores, (5) 3D structure and (6) biological origin. At 1,000 explanted meshes the value of this classification was evaluated by group-specific assessment of inflammatory and connective tissue reaction.ResultsApplication of this classification to common products has proved feasable, and each of the six different classes includes devices that in clinical trials failed to show relevant differences in patients' outcome when comparing products within the same group. Furthermore, histological analysis confirmed significant differences in tissue reactions between but not within the different classes.ConclusionsClassifying implants according to a similar response enables grouping patients into comparable cohorts despite implantation of different devices. Furthermore, it enables the examination of the impact of mesh classes for the various indications even from heterogenous data of registries. Finally and not the least, any grouping supports the surgeon to select the best device to meet the individual need and to tailor patients therapy.

Project description:Echinoderms, which are phylogenetically related to vertebrates and produce large numbers of transparent embryos that can be experimentally manipulated, offer many advantages for the analysis of the gene regulatory networks (GRN) regulating germ layer formation. During development of the sea urchin embryo, the ectoderm is the source of signals that pattern all three germ layers along the dorsal-ventral axis. How this signaling center controls patterning and morphogenesis of the embryo is not understood. Here, we report a large-scale analysis of the GRN deployed in response to the activity of this signaling center in the embryos of the Mediterranean sea urchin Paracentrotus lividus, in which studies with high spatial resolution are possible. By using a combination of in situ hybridization screening, overexpression of mRNA, recombinant ligand treatments, and morpholino-based loss-of-function studies, we identified a cohort of transcription factors and signaling molecules expressed in the ventral ectoderm, dorsal ectoderm, and interposed neurogenic ("ciliary band") region in response to the known key signaling molecules Nodal and BMP2/4 and defined the epistatic relationships between the most important genes. The resultant GRN showed a number of striking features. First, Nodal was found to be essential for the expression of all ventral and dorsal marker genes, and BMP2/4 for all dorsal genes. Second, goosecoid was identified as a central player in a regulatory sub-circuit controlling mouth formation, while tbx2/3 emerged as a critical factor for differentiation of the dorsal ectoderm. Finally, and unexpectedly, a neurogenic ectoderm regulatory circuit characterized by expression of "ciliary band" genes was triggered in the absence of TGF beta signaling. We propose a novel model for ectoderm regionalization, in which neural ectoderm is the default fate in the absence of TGF beta signaling, and suggest that the stomodeal and neural subcircuits that we uncovered may represent ancient regulatory pathways controlling embryonic patterning.

Dataset Information

The regulatory ancestral network of surgical meshes.

Publications

The regulatory ancestral network of surgical meshes.

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