Recognizing ASIA secondary to surgical mesh complications may hold the key to predicting high risk patients for implant procedures: Supporting arguments for research grants to investigate links between secondary to mesh autoimmune disease exacerbation and or initiation
Back Ground :
A significant subset of patients experiencing surgical mesh implant complications after mesh augmented repairs for prolapse (POP) stress urinary incontinence(SUI) repair and hernia repair, are reporting to their doctors and social media support forums that the complications they are experiencing after being implanted with surgical mesh products are not as rare as they were lead to believe, that the seriousness of the possible complications were minimalized and that a significant secondary to mesh complication is being completely overlooked.
Patients notice symptoms of autoimmune disorders:
Many patients noticed pre-existing autoimmune problems were exacerbated post mesh implantation while others reported new diagnoses of autoimmune diseases post mesh implantation. This is a cohort of mesh implanted patients that have all experienced varying degrees of mesh complications. I believe that the patients' criticisms that autoimmune responses to surgical mesh implantation not being noticed are very valid, that the symptoms when reported to physicians are minimalized, not investigated and referrals to autoimmune specialists are delayed, or denied.
Doctors not looking for symptoms of autoimmune problems:
These observations that autoimmune symptoms are missed, dismissed, not even looked for, are valid and should be of great concern to surgeons, researchers and health authorities. The cascade of health problems patients experience after complications caused by implant materials and devices need to be addressed by teams of doctors with specialities in more than one discipline. It is my experience as a patient, not enough attention is paid to the secondary to mesh complication of autoimmune dis-regulation and immune system fatigue. This opinion has been conveyed to me by hundreds of patients with diagnosed surgical mesh complications. It is interesting that a group of 10,000 younger women have the same complaint regarding autoimmune dis-regulation after complications with their implanted Essure contraceptive devices. (7 )
The Problems:
My position as a mesh complication survivor support group administrator gives me access to volumes of observations of reported symptoms and to witness the daily struggles of women and men struggling to regain quality of life after difficult and multiple mesh removal procedures, to witness the fear and confusion of those patients just in the process of self diagnosing their mesh related complications when doctors have failed to listen to them and investigate their suspicions with open minds. Many doctors do not offer a partnering relationship to their patients to safe guard the health of their patient. It appears we have been historically conditioned by a paternal once male dominated society to blindly trust the medical profession. Many doctors are annoyed or offended when patients question or put forth opinions as to why they are in need of medical intervention or dare to disagree with their doctors. Doctors seem to forget that many patients do research valid sources of information and do possess critical thinking skills and can often accurately diagnose their malaise. Communication between patients and doctors is key to make accurate diagnosis. More respectful dialogue needs to happen.
1St & 2nd & 3rd Common denominators:
The 1st common denominator with this group of patients I interact with is surgical mesh. The 2nd common denominator is that construction of most of the mesh types is polymeric, with most of them being made of polypropylene (PP). The 3rd commonality patients report is a reluctance by the medical community to accept that even the learned medical profession have been mislead by incomplete information, false assumptions of long term studies and clinical trials proving benefit over risk, and that the medical profession was influenced by a very well funded effort by mesh manufacturers to promote their products as safer than they actually were in a race to gain a much of the mesh sales market as possible as fast as possible.
Too many doctors promoting products in medical societies receive grants and benefits from manufacturers. It appears by the reluctance of the AUGS, to reclassify mesh to class three, invested doctors try to influence the FDA when it seems a lucrative part of their practice comes under scrutiny. It is easy to ignore the subset of patients who do not do well with mesh, when many appear to do very well. Sadly mesh using surgeons profit surgeons profit from inserting mesh into people and then profit from the many surgeries required to remove degraded mesh. Sadly, it is a win-win situation for surgeons with financial gain objectives over ruling ethical practices. The cost for publicly funded health insurance is enormous when women undergo up to 18 to 20 mesh removal attempts. The cost to these patients quality of life is unmeasurable. No amount of compensation can turn back the hands of time to when their bodies were mesh free. To go back in time to say the benefit does not outweigh the risk would be the greatest wish of hundreds of thousands of women with POP and SUI mesh repairs and the greatest wish of millions of patients living in chronic pain caused by mesh repaired hernias.
What we know about polypropylene:
What we know about PP is that contrary to popular belief PP does not remain inert in the human body when subjected to a chronic oxidation process in foreign body reaction (FBR) ( 6 ). We know that FBR in the cohort of patients with mesh complications has not been transitory as surgeons and manufacturers had claimed it would be ( 8 ).We know that during the degradation process of PP in the human body the leachates of the degradation of PP are free radicals, and depending on the residues of the manufacturing and sterilization processes adsorption of toxic residues into the human body can occur (9). We also know biofilms can form on mesh implants and harbour bacteria that becomes a source of chronic infection. Bacteria are implicated in the hastening of polypropylene degradation ( 10 ). We know that polypropylene can have an adjuvant effect in the human body (11). It has long been understood that adjuvants help elict strong immune responses.
Surgical polypropylene (PP) mesh is not inert according to peer reviewed published research ( 2 ). The foreign body response uses an oxidation process to degrade the mesh filaments, so phagocytes can attempt to dispose of the foreign body which in this case is mesh (3). The oxidation process makes surgical mesh stiff and brittle in a flexible weight bearing part of the body. The painful mechanical and chemical irritation of degrading mesh is well documented with over 60 thousand lawsuits against mesh manufacturers(12).
Mesh fragmentation, migration, leachates and the peroxide secretions meant to destroy the mesh, do collateral damage. Peroxide irritates and damage surrounding tissues invoking a stronger foreign body response as free radicals leach into surrounding tissues ( 4 ). However disturbing the failure of PP mesh to remain inert when it is permanency planned, the most troublesome property of polypropylene mesh may be the adjuvant effect it has in the human body. According to researchers(Bennewitz, Biomaterials, 2005) This results in a “detrimental humoral or cytotoxic response” around the implant causing an “inflammatory tissue reaction.” What do we know about adjuvants? The purpose of adjuvants in vaccines is to trigger a strong immune response. It is well documented that adjuvants in vaccines have caused autoimmune diseases in a subset of patients over exposed or hypersensitive to adjuvants (5). Can it be argued that permanently implanted devices or materials that have an adjuvant effect, over expose patients to the damaging effects of constant immune system stimulation? Can this chronic stimulation of the immune system by a surgical mesh agent that elicits an adjuvant effect, be a cause of ASIA? Can this this be identified as pathogenisis to autoimmne exacerbation and or initiation? I believe so. I believe this deserves to be researched in depth, arms length from invested parties such as manufacturers and researchers benefiting from manufacturer grants and sponsorships.
The connection of adjuvant activity to autoimmune:
Many patients reported symptoms that are best described by Autoimmune/inflammatory Syndrome Induced by Adjuvants, (ASIA) (13). Their complaints also fit into the description of HAD (14), Implant Syndrome (15) and SIN (16). The definition, or explanation of ASIA, is found in publications of Yehuda Shoenfeld and Nancy Agmon-Levina at the Zabludowicz Center for Autoimmune Diseases, ( 1 ) According to these leading researchers in the newly burgeoning field of autoimmunity this syndrome appears following chronic stimulation of the immune system by agents which have adjuvant characteristics.
Does it matter the adjuvant?
The definition of an adjuvant: an adjuvant is a substance that enhances the antigen-specific immune response, induces the release of inflammatory cytokines, and interacts with Toll-like receptors and the NALP3 inflammasome.
According to Bennawitz, Biomaterials,2005 and Matzelle , Biomaterials, 2004 tissue engineered constructs act as adjuvants as do polymeric scaffolds .
“Biomaterial adjuvant effect
We have demonstrated that the biomaterial component of a tissue-engineered contruct acts as an adjuvant in the enhancement of the adaptive immune response to associated shed cellular antigens (Matzelle, Biomaterials 2004). This would result in detrimental humoral or cytotoxic response around the implant to enhance an inflammatory tissue reaction. Furthermore, the biomaterial adjuvant effect depends on the form of the biomaterial carrier vehicle (implanted polymer scaffolds vs. minimally invasive injected polymer microparticles) (Bennewitz, Biomaterials, 2005).”
We can safely say PP mesh has an adjuvant effect. Because the adjuvant effect from adjuvants used in vaccinations that induce ASIA can develop into irreversible autoimmune diseases, such as Lupus, this patient researcher turned her research direction into markers of auotimmune disease predisposition, suspecting it matters not what adjuvant that triggers an autoimmune reaction, but what matters most that as humans our bodies react in a predictable manner, but that owing to genetic difference and differences in environmental exposures, we see different manifestations of autoimmune disregulation that explain the differences in types of autoimmune disorders being recognized. The suspicion it matters not the type of adjuvant, but the effect of adjuvant activity that leads to autoimmune pathogenesis has already been considered by researchers already. For example ,Expert Rev Clin Immunol. 2013 Apr;9(4):361-73. doi: 10.1586/eci.13.2.(21)
“Forty-one patients were injected with mineral oil, nine patients received other substances: three iodine gadital, one guayacol, one guayacol plus silicone fluid, two collagen, two silicone fluid. The sites of application were: buttocks (36), legs and/or thighs (11), breasts (eight) hands and face (one), face (two) (seven patients received an injection to more than one site). Thirty patients presented with non-specific autoimmune manifestations, whereas 20 patients fulfilled the criteria for a defined autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, overlap syndrome,autoimmune hemolytic anemia, autoimmune thyroiditis, autoimmune hepatitis, and ulcerative colitis.
Thus came my hope that because there has been more research into triggers of autoimmune diseases there would be more identified markers that could be the same predictors for adjuvant initiated autoimmune diseases and therefore be possible markers for polypropylene mesh adjuvant effect initiated autoimmune pathogenesis. Notably there is an abundance of research into adjuvants, as adjuvants are a key part of vaccine development. It seems there may be some research to draw from to predict the at risk population for foreign body implant complications associated with polypropylene mesh. We need more research.
Millions of people have polymeric implants. Investigations should be ongoing, considering there is a noticable increase of autoimmune disorders in the general population. Millions of people with autoimmune dis-regulating surgical mesh implants might be one reason.
Remember, research into mesh implant complications reveals that FBR is not a transitory reaction in the subset of patients with mesh degradation and the cascading complications of implant failure. FBR appears to continue in the hypersensitive subset of patients for as long as the inflammation producing implants remain inside the bodies of patients. The inflammation is not transitory. Foreign body giant cells are found on explanted meshes that have been inside women for years, not months. As stated previously the foreign body response is not transitory, and affects a significant subset of patients. Complications arise years away from the date the mesh materials and devices are implanted into the host body. This is common knowledge among patients with mesh complications. FBR, caused by polypropylene, stimulates the immune system. This is an adjuvant effect.
Because the common denominator in mesh complication support groups is surgical mesh, this should make it easy for researchers to “mine” a wealth of observations from patients that share their experiences and observations without the censorship of guided biased research to shed light on the most positive attributes of a lucrative medical procedure using lucrative products cleared for sale, not approved for sale by the FDA. Note the distinction. Cleared for sale means class 2 products that could be fast tracked via the 510k did not have to be tested on their own merits but gained, as in this example of surgical medical mesh products, clearance for sale because they were substantially equivalent to a predicate device that was approved for sale; a predicate device that was recalled.
A reminder that research is lacking brings me to point out Protogen mesh was the first and only transvaginal mesh approved for sale and then it was recalled(17). All the subsequent products that gained clearance without testing by being substantially the same as Protogen have never been recalled. J&J removed 4 mesh products off the market in 2012 when post market studies were demanded by the FDA. Removing products was a market strategy according to J&J and not an admission of a defective product to be considered a recall. Over 100,000 lawsuits brought against mesh manufacturers suggests that perhaps recalls were in order. Mesh products have been judged defective, poorly designed, and mesh manufacturers have been collectively penalized to the tune of over 100 million dollars to date for failure to warn of all the risks associated with their products. Mesh manufacturers are putting billions of dollars aside to settle mesh injury lawsuits. (18) The old saying where there is smoke there is fire, comes to mind.
Why look at ASIA?
However it is time to draw your attention to the theme of this article that recognizing ASIA may hold the key to predicting the subset of patients that it would be risky to implant synthetic surgical mesh products into. When looking into the causes of autoimmune diseases, we should be heeding the words of a leading autoimmunity expert, Noel Rose, M.D., Ph. D., described by colleagues as one of the founding fathers of immunology and autoimmunity research. Rose said when talking about traits of autoimmune diseases and their traits “If we are ever going to find a way of actually curing an autoimmune disease I believe it is going to come from our understanding of what those common traits are.” In a presentation he emphasized seemingly diverse autoimmune diseases belong to the same family and have many common genetic traits and environmental triggers. He explained that these common traits determine whether an organism will be susceptible or resistant to developing autoimmune disorders.” Furthermore he stated, “The most efficient way of preventing autoimmune diseases would be by identifying and separating the susceptible human from the responsible environmental factor,” (19).
Elaborating on that concept “separating the susceptible human from the responsible environmental factors” it would seem plausible, conceivable, prudent to reason that the most efficient way of protecting patients from surgical mesh complications would be to separate the susceptible patient from the responsible environmental factor which is surgical mesh implantation. It would seem beneficial to know what common traits patients share that have the same responsible environmental triggers, which in the case of mesh complication cohorts the obvious trigger is the first common denominator. It is the implantation of a polymeric foreign body implant that is known to produce a chronic adjuvant effect. This fact needs the attention it deserves, that patients with chronic FBR need recognized.
My hypothesis is that those patient identified as high responders to FBR that develop mesh complications, displaying ASIA, may also have the same traits and markers as the same four groups of individuals being identified by researchers as being susceptible to develop vaccination -induced ASIA . What would make me believe this ? The many key words and phrases in researching the cause of foreign body reaction, and the key words and clues in research related to autoimmune diseases, that were in common between the two searches made me question if there were commonalities in markers for both ASIA and mesh complication susceptibility. It would be advantageous to investigate this correlation to be able to predict with a reasonable degree of certainty who would be at a higher risk for complications caused by implant devices and material augmentation.
Going back to the fact that a large cohort of the mesh implant complication patients notice signs of autoimmune exacerbation and are being diagnosed with autoimmune diseases post mesh implantation , it would be easy to conclude that autoimmune susceptible people, or those with underlying autoimmune conditions would be the population to separate from surgical mesh implantation. However revealing the research is, that is available already, I believe I have a strong argument for funding research. Millions of patients each year are implanted with polymeric meshes. To reduce the risk of complications it is imperative to identifying those at risk thereby allowing surgeons to look for alternatives to synthetic mesh and justify the extra surgery time of non mesh repairs of POP, SUI and hernias . Would it be far better to repair a non mesh repaired re-occurrence of a hernia than to remove a degraded folded deformed mesh after it has damaged nerves and caused chronic pain and caused a cascade of systemic responses ? Would it be far better to spend extra time doing the old fashioned suture methods and use a patients own fascia than risk multiple surgeries to remove defective mesh, and then do surgeries to repair mesh erosion, fistula, adhesions as well as the reason for using mesh in the first place, the prolapses and stress urinary incontinence problems ? For patients at a higher risk it is well worth not using the quick fixes of mesh materials. Reserve the use of mesh for those at low risk,who are willing to consent when fully informed.
Many studies on the benefits of risk over safety state use of polymeric scaffolding mesh materials conclude mesh for the treatment of POP and SUI should be considered novel. In other words experimental, as in needing more studies before concluding that synthetic mesh use is deserving of the gold standard acceptance status. Long term research is almost non-existent because the subsequent mesh products cleared by the recalled Protogen mesh were never studied in depth or made to face the standards of class three products which would have forced toxicity, leachabilty, degradation, immune stimulation, etc., testing that patients and doctors alike would have expected were done on products designed to come into permanent contact with blood, bone, and tissue. Even with class 3 approval, products like Essure implants can be identified as causing more harm than giving benefit, failing to prevent pregnancy and causing symptoms of ASIA. 10,000 in one support group alone women claim Essure is not safe or effective. We need arms length research from mesh manufacturers that looks at the autoimmune reactions of mesh implanted patients, and perhaps all implant receiving patients, and does not exclude the cohort of susceptible to autoimmune disease patient groups. The vulnerable patients need to be included in research as they are represented in the numbers of patients suffering from autoimmune symptoms starting after or being exacerbated after receiving a foreign body implant.
Why is this vital ?
Researching the autoimmune symptoms being reported by mesh complication patients would validate that this cohort of patients may have common genetic traits that predisposes them to be hypersensitive to adjuvant activity which can lead to developing autoimmune diseases when exposed to a common adjuvant. Professor Shoenfeld Yehuda , Nancy Agmon-Levina 2010 (20) claim” Environmental factors that comprise an immune adjuvant effect have been recognized for several decades. These adjuvants (i.e. silicone, alum, pristane, infectious components) were found to induce autoimmunity by themselves in different animal models and may possibly provoke AI/AIFD in humans.[9e13]. Exposure to these substances were documented in the four medical conditions conversed herein, suggesting that the common denominator to these syndromes is a trigger entailing adjuvant activity. Therefore, in this review we suggest to include these conditions under a common syndrome entitled ASIA, “Autoimmune (Auto-inflammatory) Syndrome Induced by Adjuvants”. In another discussion by Dr. Sheonfeld Yehuda is a simple description of ASIA. “It is a new syndrome., which refers to autoimmune syndrome induced by adjuvants. It includes several conditions that are not fully characterized as autoimmune diseases like systemic lupus,rheumatoid arthritis or scleroderma, but that are induced by chronic stimulation of the immune system by substances which may react as adjuvants . This chronic stimulation leads to the emergence of these new signs and symptoms , which include fatigue, arthritis, myalgia and neurological manifestations.” (http://www.biomedcentral.com/1741-7015/11/118)
Just as researchers (Alessandra Sorianoa, Gideon Nesherb, and Yehuda Shoenfeld 2014) note that “the relationship between vaccines and autoimmunity is bi-directional”, so would I hazard to state that the relationship between autoimmune disease pathogenesis and surgical mesh implant complications may also be considered bi- directional.
Diagnostic measurements of cytokines, genotypes, ANA, inflammation markers, glutathione measurements, etc. become important to note and correlate. Patients with mesh have developed Lupus post mesh implantation. Patients with synthetic mesh implants complain of exacerbated autoimmune symptoms. Clearly formal research is needed.
For example (http://link.springer.com/article/10.1007/BF02231697) consider the article Dermatomyositis exacerbated by abdominal Marlex® mesh implantation: Adjuvant effect? This article by G. Bernard-Medina, M.D., S. Gutierrez-Urena M.D., J.Orozco-AlcalaM.D., 1996 describes a woman that had her dermatomyositis severely exacerbated post mesh implantation. They summarize the mesh implant may have triggered the flare up of her underlying autoimmune disorder.
Many mesh patients on support forums report flare ups of their underlying underlying autoimmune disorders. Mesh complication patients report symptoms of autoimmune diseases that started post mesh implantation. There is enough evidence to investigate. There are patients willing to be part of research initiatives. It would be a disservice to all to ignore the opportunity to study the relationship of adjuvant effects of implant materials and the links to autoimmune pathogenesis in patients with foreign body implant materias and devices, especially if the subset of patients with complications have similar body and genetic makeup that could identify those at risk of hypersensitive reactions to foreign body implants.
We already know those with underlying autoimmune disorders, (eg. Asthmatics, smokers, diabetics,) are not good candidates for mesh. We should be suspecting that those with chemical sensitivities and food sensitivities may not be good candidates for foreign body implants. We should be very suspicious when patients have a family history of being sensitive to vaccine adjuvants. One patient known to me who has autoimmune disease post mesh, lost a baby son to a vaccination reaction, and two of her other children had bad reactions to vaccinations. Is it coincidence that she reacted badly to mesh? What is it about her genetics that should have warned doctors an adjuvant effect from an implant material could harm her? Are her remaining children vulnerable to any adjuvant triggers? This is vital information for consideration when choosing patients to exclude for mesh augmentation in any form, POP, SUI or hernia procedures. This would help with informed consent.
Prevention is always preferable to finding the cure for the cure. It makes common sense to spend money in prevention of mismatching patients with biologics. The savings in quality of life should be of the most important consideration, but the biggest factor will probably be the savings in health care costs for medical insurance providers and tax payers; two very good reasons to demand research grants to identify at risk patients for foreign body implants. Autoimmune diseases are on the rise, and the adjuvant effect of synthetic mesh in the human body may be a significant preventable trigger. Millions of people have been implanted with synthetic mesh. Perhaps plastic body parts were not such a good invention. We deserve the truth, the facts, the hope for validation that the adjuvant effect of polypropylene can cause autoimmune disease. Hundreds of women with mesh complications have conveyed the same message to me. They want their suffering, their pain, to count towards the limiting of synthetic mesh usage to those who have no alternatives, and have doctors prepared to manage their transvaginal mesh complications skillfully, being ready for the secondary problems such as autoimmune exacerbation, or initiation. Bring ready for the autoimmune symptoms means not dismissing symptoms that do not fit the the already recognized symptoms. Closed minds leave no room for learning and discoveries. Closed minds allow symptoms that could have signalled early and swift interventions to be missed . It is no wonder that the complications of surgical mesh compound and cascade into life threatening and life altering expereineces. Investigative open minds invite hope and discovery. I hope I have provided hope and a reason to demand research into the adjuvant effect of polymeric surgical mesh exacerbating and initiating autoimmune diseases. I hope and pray I have excited the readers to investigate and use use the research already being done into the populations of people defined by genetic markers as being high risk for adjuvant effect initiated autoimmune diseases.
1)http://www.the-rheumatologist.org/details/article/1081203/ASIA_A_New_Way_to_Put_the_Puzzle_Together.html
http://www.biomedcentral.com/1741-7015/11/118
2)http://www.ncbi.nlm.nih.gov/pubmed/20052576
http://www.ncbi.nlm.nih.gov/pubmed/22578730
http://books.google.ca/books?id=9TA_AAAAQBAJ&pg=PA155&lpg=PA155&dq=Surgical++polypropylene+(PP)+mesh+is+not+inert.&source=bl&ots=d6Wv1ogc_l&sig=vTpY7798UoNM_0x9n_E9I87w0TI&hl=en&sa=X&ei=chs0VMLrE43WigKniYFo&ved=0CCwQ6AEwADgK#v=onepage&q=Surgical%20%20polypropylene%20(PP)%20mesh%20is%20not%20inert.&f=false
page 155, Andrew Kingsnorth, Karl A LeBlanc 2013
3) http://www.uweb.engr.washington.edu/research/tutorials/woundhealing.html
http://link.springer.com/chapter/10.1007/978-0-387-37880-0_10
6) http://waset.org/publications/9999333/pathology-of-explanted-transvaginal-meshes
Abstract—The use of polypropylene mesh devices for Pelvic Organ Prolapse (POP) spread rapidly during the last decade, yet our knowledge of the mesh-tissue interaction is far from complete. We aimed to perform a thorough pathological examination of explanted POP meshes and describe findings that may explain mechanisms of complications resulting in product excision. We report a spectrum of important findings, including nerve ingrowth, mesh deformation, involvement of detrusor muscle with neural ganglia, and polypropylene degradation. Analysis of these findings may improve and guide future treatment strategies. .......One specimen was received as one intact excision, while the remaining 23 were received in fragments with fragment size ranging from 0.4 to 12.0cm. For 21(87%) patients the samples were available in formalin for gross comparative assessment. Grossly the explanted meshes were described as firm. Subjectively, by palpation, the explanted lightweight meshes felt softer than the heavyweight designs, while both were firmer than either a new mesh or vaginal tissue excised during non-mesh surgeries. Of all specimens, 14 (58%) were received in fragments large enough to assess for gross deformations, which ranged from mild banding to more complex folding and edge curling.
Microscopically, all (100%) meshes were invested with collagenous scar, with chronic and foreign body inflammatory reaction.
18) http://rxinjurylaw.com/830m-vaginal-mesh-settlement-will-be-paid-by-endo-to-settle-20000- mesh-injury-lawsuits/
clinical manifestations [7,8]. Environmental factors that comprise an immune adjuvant effect have been recognized for several decades. These adjuvants (i.e. silicone, alum, pristane, infectious components) were found to induce autoimmunity by themselves in different animal models and may possibly provoke AI/AIFD in....
21) 21) Expert Rev Clin Immunol. 2013 Apr;9(4):361-73. doi: 10.1586/eci.13.2.
Matters not the trigger supporting evidence ....Forty-one patients were injected with mineral oil, nine patients received other substances: three iodine gadital, one guayacol, one guayacol plus silicone fluid, two collagen, two silicone fluid. The sites of application were: buttocks (36), legs and/or thighs (11), breasts (eight) hands and face (one), face (two) (seven patients received an injection to more than one site). Thirty patients presented with non-specific autoimmune manifestations, whereas 20 patients fulfilled the criteria for a defined autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, overlap syndrome, autoimmune hemolytic anemia, autoimmune thyroiditis, autoimmune hepatitis, and ulcerative colitis.
http://freepdfhosting.com/962132b4b7.pdf Review‘ASIA’ e Autoimmune/inflammatory syndrome induced by adjuvantsYehuda Shoenfeld a,b,*, Nancy Agmon-Levin a
a The Zabludowicz Center for Autoimmune Diseases, Department of Medicine B’ Sheba Medical Center, Tel-Hashomer, Israel b Incumbent of the Laura Schwarz-kipp Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Israel article info Article history: Received 16 June 2010 Received in revised form 15 July 2010 ,Accepted 20 July 2010)
.......................more info to incorporate ...........................................................................
adjuvant information
An adjuvant is a substance that enhances the antigen-specific immune response, induces the release of inflammatory cytokines, and interacts with Toll-like receptors and the NALP3 inflammasome
Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld's syndrome): clinical and immunological spectrum. Vera-Lastra O, Medina G, Cruz-Dominguez Mdel P, Jara LJ, Shoenfeld Y.
http://www.ncbi.nlm.nih.gov/pubmed/23557271
Human adjuvant disease induced by foreign substances: a new model of ASIA (Shoenfeld's syndrome). Vera-Lastra O, Medina G, Cruz-Dominguez Mdel P, Ramirez P, Gayosso-Rivera JA, Anduaga-Dominguez H, Lievana-Torres C, Jara LJ.
http://www.ncbi.nlm.nih.gov/pubmed/22235042
21) Expert Rev Clin Immunol. 2013 Apr;9(4):361-73. doi: 10.1586/eci.13.2.
Matters not the trigger supporting evidence ....Forty-one patients were injected with mineral oil, nine patients received other substances: three iodine gadital, one guayacol, one guayacol plus silicone fluid, two collagen, two silicone fluid. The sites of application were: buttocks (36), legs and/or thighs (11), breasts (eight) hands and face (one), face (two) (seven patients received an injection to more than one site). Thirty patients presented with non-specific autoimmune manifestations, whereas 20 patients fulfilled the criteria for a defined autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, overlap syndrome, autoimmune hemolytic anemia, autoimmune thyroiditis, autoimmune hepatitis, and ulcerative colitis.
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http://www.termedia.pl/Czasopismo/Reumatologia-18/Streszczenie-21947
Artykuł przeglądowy
Autoimmunologiczny/autozapalny zespół indukowany przez adiuwanty – nowy problem diagnostyczny czy rozwiązanie zagadki diagnostycznej Maria Maślińska, Carlo Perricone, Yehuda Shoenfeld Reumatologia 2013; 51, 6: 437–444
DOI (digital object identifier): 10.5114/reum.2013.39662
Chronic stimulation of the immune system by substances used as adjuvants may lead to the occurrence of numerous symptoms such as chronic fatigue, arthritis, myalgia, cognitive impairment and neurological disorders. The aim of this article is to present how and why adjuvants – while allegedly causing no specific immune response – may become a cause of development of autoimmune diseases.
słowa kluczowe:
adiuwanty, odpowiedź immunologiczna, choroby autoimmunologiczne .....................................................................................................................................................................................................
Abdominal Wall Hernias: Principles and Management books.google.ca/books?isbn=0387950044
Robert Bendavid - 2001 - Medical
Prosthetic mesh material is presumed to have a foreign body adjuvant effect in the wound. The coarse weave of polypropylene mesh with interdigitated .
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Biomaterial adjuvant effect
We have demonstrated that the biomaterial component of a tissue-engineered contruct acts as an adjuvant in the enhancement of the adaptive immune response to associated shed cellular antigens (Matzelle, Biomaterials 2004). This would result in detrimental humoral or cytotoxic response around the implant to enhance an inflammatory tissue reaction. Furthermore, the biomaterial adjuvant effect depends on the form of the biomaterial carrier vehicle (implanted polymer scaffolds vs. minimally invasive injected polymer microparticles) (Bennewitz, Biomaterials, 2005).
..................................................................................................................................................................................................Tt
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988402/
Published online Jun 2,Biomaterial adjuvant effect is attenuated by anti-inflammatory drug delivery or material selection
Lori W. Norton, Jaehyung Park, and Julia E. Babensee
2010. doi: 10.1016/j.jconrel.2010.05.032PMCID: PMC298840NIHMSID: NIHMS237733
Lori W. Norton, Jaehyung Park, and Julia E. Babensee*
these studies have demonstrated the potential for biomaterial scaffolds to act as adjuvants in enhancing the adaptive immune response to co-delivered antigen, presumably due to a material effect on DC maturation. Furthermore, tissue damage associated with the implantation of a construct may prime the site for the biomaterial adjuvant effect due to the generation of endogenous ‘danger signals’.
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Back Ground :
A significant subset of patients experiencing surgical mesh implant complications after mesh augmented repairs for prolapse (POP) stress urinary incontinence(SUI) repair and hernia repair, are reporting to their doctors and social media support forums that the complications they are experiencing after being implanted with surgical mesh products are not as rare as they were lead to believe, that the seriousness of the possible complications were minimalized and that a significant secondary to mesh complication is being completely overlooked.
Patients notice symptoms of autoimmune disorders:
Many patients noticed pre-existing autoimmune problems were exacerbated post mesh implantation while others reported new diagnoses of autoimmune diseases post mesh implantation. This is a cohort of mesh implanted patients that have all experienced varying degrees of mesh complications. I believe that the patients' criticisms that autoimmune responses to surgical mesh implantation not being noticed are very valid, that the symptoms when reported to physicians are minimalized, not investigated and referrals to autoimmune specialists are delayed, or denied.
Doctors not looking for symptoms of autoimmune problems:
These observations that autoimmune symptoms are missed, dismissed, not even looked for, are valid and should be of great concern to surgeons, researchers and health authorities. The cascade of health problems patients experience after complications caused by implant materials and devices need to be addressed by teams of doctors with specialities in more than one discipline. It is my experience as a patient, not enough attention is paid to the secondary to mesh complication of autoimmune dis-regulation and immune system fatigue. This opinion has been conveyed to me by hundreds of patients with diagnosed surgical mesh complications. It is interesting that a group of 10,000 younger women have the same complaint regarding autoimmune dis-regulation after complications with their implanted Essure contraceptive devices. (7 )
The Problems:
My position as a mesh complication survivor support group administrator gives me access to volumes of observations of reported symptoms and to witness the daily struggles of women and men struggling to regain quality of life after difficult and multiple mesh removal procedures, to witness the fear and confusion of those patients just in the process of self diagnosing their mesh related complications when doctors have failed to listen to them and investigate their suspicions with open minds. Many doctors do not offer a partnering relationship to their patients to safe guard the health of their patient. It appears we have been historically conditioned by a paternal once male dominated society to blindly trust the medical profession. Many doctors are annoyed or offended when patients question or put forth opinions as to why they are in need of medical intervention or dare to disagree with their doctors. Doctors seem to forget that many patients do research valid sources of information and do possess critical thinking skills and can often accurately diagnose their malaise. Communication between patients and doctors is key to make accurate diagnosis. More respectful dialogue needs to happen.
1St & 2nd & 3rd Common denominators:
The 1st common denominator with this group of patients I interact with is surgical mesh. The 2nd common denominator is that construction of most of the mesh types is polymeric, with most of them being made of polypropylene (PP). The 3rd commonality patients report is a reluctance by the medical community to accept that even the learned medical profession have been mislead by incomplete information, false assumptions of long term studies and clinical trials proving benefit over risk, and that the medical profession was influenced by a very well funded effort by mesh manufacturers to promote their products as safer than they actually were in a race to gain a much of the mesh sales market as possible as fast as possible.
Too many doctors promoting products in medical societies receive grants and benefits from manufacturers. It appears by the reluctance of the AUGS, to reclassify mesh to class three, invested doctors try to influence the FDA when it seems a lucrative part of their practice comes under scrutiny. It is easy to ignore the subset of patients who do not do well with mesh, when many appear to do very well. Sadly mesh using surgeons profit surgeons profit from inserting mesh into people and then profit from the many surgeries required to remove degraded mesh. Sadly, it is a win-win situation for surgeons with financial gain objectives over ruling ethical practices. The cost for publicly funded health insurance is enormous when women undergo up to 18 to 20 mesh removal attempts. The cost to these patients quality of life is unmeasurable. No amount of compensation can turn back the hands of time to when their bodies were mesh free. To go back in time to say the benefit does not outweigh the risk would be the greatest wish of hundreds of thousands of women with POP and SUI mesh repairs and the greatest wish of millions of patients living in chronic pain caused by mesh repaired hernias.
What we know about polypropylene:
What we know about PP is that contrary to popular belief PP does not remain inert in the human body when subjected to a chronic oxidation process in foreign body reaction (FBR) ( 6 ). We know that FBR in the cohort of patients with mesh complications has not been transitory as surgeons and manufacturers had claimed it would be ( 8 ).We know that during the degradation process of PP in the human body the leachates of the degradation of PP are free radicals, and depending on the residues of the manufacturing and sterilization processes adsorption of toxic residues into the human body can occur (9). We also know biofilms can form on mesh implants and harbour bacteria that becomes a source of chronic infection. Bacteria are implicated in the hastening of polypropylene degradation ( 10 ). We know that polypropylene can have an adjuvant effect in the human body (11). It has long been understood that adjuvants help elict strong immune responses.
Surgical polypropylene (PP) mesh is not inert according to peer reviewed published research ( 2 ). The foreign body response uses an oxidation process to degrade the mesh filaments, so phagocytes can attempt to dispose of the foreign body which in this case is mesh (3). The oxidation process makes surgical mesh stiff and brittle in a flexible weight bearing part of the body. The painful mechanical and chemical irritation of degrading mesh is well documented with over 60 thousand lawsuits against mesh manufacturers(12).
Mesh fragmentation, migration, leachates and the peroxide secretions meant to destroy the mesh, do collateral damage. Peroxide irritates and damage surrounding tissues invoking a stronger foreign body response as free radicals leach into surrounding tissues ( 4 ). However disturbing the failure of PP mesh to remain inert when it is permanency planned, the most troublesome property of polypropylene mesh may be the adjuvant effect it has in the human body. According to researchers(Bennewitz, Biomaterials, 2005) This results in a “detrimental humoral or cytotoxic response” around the implant causing an “inflammatory tissue reaction.” What do we know about adjuvants? The purpose of adjuvants in vaccines is to trigger a strong immune response. It is well documented that adjuvants in vaccines have caused autoimmune diseases in a subset of patients over exposed or hypersensitive to adjuvants (5). Can it be argued that permanently implanted devices or materials that have an adjuvant effect, over expose patients to the damaging effects of constant immune system stimulation? Can this chronic stimulation of the immune system by a surgical mesh agent that elicits an adjuvant effect, be a cause of ASIA? Can this this be identified as pathogenisis to autoimmne exacerbation and or initiation? I believe so. I believe this deserves to be researched in depth, arms length from invested parties such as manufacturers and researchers benefiting from manufacturer grants and sponsorships.
The connection of adjuvant activity to autoimmune:
Many patients reported symptoms that are best described by Autoimmune/inflammatory Syndrome Induced by Adjuvants, (ASIA) (13). Their complaints also fit into the description of HAD (14), Implant Syndrome (15) and SIN (16). The definition, or explanation of ASIA, is found in publications of Yehuda Shoenfeld and Nancy Agmon-Levina at the Zabludowicz Center for Autoimmune Diseases, ( 1 ) According to these leading researchers in the newly burgeoning field of autoimmunity this syndrome appears following chronic stimulation of the immune system by agents which have adjuvant characteristics.
Does it matter the adjuvant?
The definition of an adjuvant: an adjuvant is a substance that enhances the antigen-specific immune response, induces the release of inflammatory cytokines, and interacts with Toll-like receptors and the NALP3 inflammasome.
According to Bennawitz, Biomaterials,2005 and Matzelle , Biomaterials, 2004 tissue engineered constructs act as adjuvants as do polymeric scaffolds .
“Biomaterial adjuvant effect
We have demonstrated that the biomaterial component of a tissue-engineered contruct acts as an adjuvant in the enhancement of the adaptive immune response to associated shed cellular antigens (Matzelle, Biomaterials 2004). This would result in detrimental humoral or cytotoxic response around the implant to enhance an inflammatory tissue reaction. Furthermore, the biomaterial adjuvant effect depends on the form of the biomaterial carrier vehicle (implanted polymer scaffolds vs. minimally invasive injected polymer microparticles) (Bennewitz, Biomaterials, 2005).”
We can safely say PP mesh has an adjuvant effect. Because the adjuvant effect from adjuvants used in vaccinations that induce ASIA can develop into irreversible autoimmune diseases, such as Lupus, this patient researcher turned her research direction into markers of auotimmune disease predisposition, suspecting it matters not what adjuvant that triggers an autoimmune reaction, but what matters most that as humans our bodies react in a predictable manner, but that owing to genetic difference and differences in environmental exposures, we see different manifestations of autoimmune disregulation that explain the differences in types of autoimmune disorders being recognized. The suspicion it matters not the type of adjuvant, but the effect of adjuvant activity that leads to autoimmune pathogenesis has already been considered by researchers already. For example ,Expert Rev Clin Immunol. 2013 Apr;9(4):361-73. doi: 10.1586/eci.13.2.(21)
“Forty-one patients were injected with mineral oil, nine patients received other substances: three iodine gadital, one guayacol, one guayacol plus silicone fluid, two collagen, two silicone fluid. The sites of application were: buttocks (36), legs and/or thighs (11), breasts (eight) hands and face (one), face (two) (seven patients received an injection to more than one site). Thirty patients presented with non-specific autoimmune manifestations, whereas 20 patients fulfilled the criteria for a defined autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, overlap syndrome,autoimmune hemolytic anemia, autoimmune thyroiditis, autoimmune hepatitis, and ulcerative colitis.
Thus came my hope that because there has been more research into triggers of autoimmune diseases there would be more identified markers that could be the same predictors for adjuvant initiated autoimmune diseases and therefore be possible markers for polypropylene mesh adjuvant effect initiated autoimmune pathogenesis. Notably there is an abundance of research into adjuvants, as adjuvants are a key part of vaccine development. It seems there may be some research to draw from to predict the at risk population for foreign body implant complications associated with polypropylene mesh. We need more research.
Millions of people have polymeric implants. Investigations should be ongoing, considering there is a noticable increase of autoimmune disorders in the general population. Millions of people with autoimmune dis-regulating surgical mesh implants might be one reason.
Remember, research into mesh implant complications reveals that FBR is not a transitory reaction in the subset of patients with mesh degradation and the cascading complications of implant failure. FBR appears to continue in the hypersensitive subset of patients for as long as the inflammation producing implants remain inside the bodies of patients. The inflammation is not transitory. Foreign body giant cells are found on explanted meshes that have been inside women for years, not months. As stated previously the foreign body response is not transitory, and affects a significant subset of patients. Complications arise years away from the date the mesh materials and devices are implanted into the host body. This is common knowledge among patients with mesh complications. FBR, caused by polypropylene, stimulates the immune system. This is an adjuvant effect.
Because the common denominator in mesh complication support groups is surgical mesh, this should make it easy for researchers to “mine” a wealth of observations from patients that share their experiences and observations without the censorship of guided biased research to shed light on the most positive attributes of a lucrative medical procedure using lucrative products cleared for sale, not approved for sale by the FDA. Note the distinction. Cleared for sale means class 2 products that could be fast tracked via the 510k did not have to be tested on their own merits but gained, as in this example of surgical medical mesh products, clearance for sale because they were substantially equivalent to a predicate device that was approved for sale; a predicate device that was recalled.
A reminder that research is lacking brings me to point out Protogen mesh was the first and only transvaginal mesh approved for sale and then it was recalled(17). All the subsequent products that gained clearance without testing by being substantially the same as Protogen have never been recalled. J&J removed 4 mesh products off the market in 2012 when post market studies were demanded by the FDA. Removing products was a market strategy according to J&J and not an admission of a defective product to be considered a recall. Over 100,000 lawsuits brought against mesh manufacturers suggests that perhaps recalls were in order. Mesh products have been judged defective, poorly designed, and mesh manufacturers have been collectively penalized to the tune of over 100 million dollars to date for failure to warn of all the risks associated with their products. Mesh manufacturers are putting billions of dollars aside to settle mesh injury lawsuits. (18) The old saying where there is smoke there is fire, comes to mind.
Why look at ASIA?
However it is time to draw your attention to the theme of this article that recognizing ASIA may hold the key to predicting the subset of patients that it would be risky to implant synthetic surgical mesh products into. When looking into the causes of autoimmune diseases, we should be heeding the words of a leading autoimmunity expert, Noel Rose, M.D., Ph. D., described by colleagues as one of the founding fathers of immunology and autoimmunity research. Rose said when talking about traits of autoimmune diseases and their traits “If we are ever going to find a way of actually curing an autoimmune disease I believe it is going to come from our understanding of what those common traits are.” In a presentation he emphasized seemingly diverse autoimmune diseases belong to the same family and have many common genetic traits and environmental triggers. He explained that these common traits determine whether an organism will be susceptible or resistant to developing autoimmune disorders.” Furthermore he stated, “The most efficient way of preventing autoimmune diseases would be by identifying and separating the susceptible human from the responsible environmental factor,” (19).
Elaborating on that concept “separating the susceptible human from the responsible environmental factors” it would seem plausible, conceivable, prudent to reason that the most efficient way of protecting patients from surgical mesh complications would be to separate the susceptible patient from the responsible environmental factor which is surgical mesh implantation. It would seem beneficial to know what common traits patients share that have the same responsible environmental triggers, which in the case of mesh complication cohorts the obvious trigger is the first common denominator. It is the implantation of a polymeric foreign body implant that is known to produce a chronic adjuvant effect. This fact needs the attention it deserves, that patients with chronic FBR need recognized.
My hypothesis is that those patient identified as high responders to FBR that develop mesh complications, displaying ASIA, may also have the same traits and markers as the same four groups of individuals being identified by researchers as being susceptible to develop vaccination -induced ASIA . What would make me believe this ? The many key words and phrases in researching the cause of foreign body reaction, and the key words and clues in research related to autoimmune diseases, that were in common between the two searches made me question if there were commonalities in markers for both ASIA and mesh complication susceptibility. It would be advantageous to investigate this correlation to be able to predict with a reasonable degree of certainty who would be at a higher risk for complications caused by implant devices and material augmentation.
Going back to the fact that a large cohort of the mesh implant complication patients notice signs of autoimmune exacerbation and are being diagnosed with autoimmune diseases post mesh implantation , it would be easy to conclude that autoimmune susceptible people, or those with underlying autoimmune conditions would be the population to separate from surgical mesh implantation. However revealing the research is, that is available already, I believe I have a strong argument for funding research. Millions of patients each year are implanted with polymeric meshes. To reduce the risk of complications it is imperative to identifying those at risk thereby allowing surgeons to look for alternatives to synthetic mesh and justify the extra surgery time of non mesh repairs of POP, SUI and hernias . Would it be far better to repair a non mesh repaired re-occurrence of a hernia than to remove a degraded folded deformed mesh after it has damaged nerves and caused chronic pain and caused a cascade of systemic responses ? Would it be far better to spend extra time doing the old fashioned suture methods and use a patients own fascia than risk multiple surgeries to remove defective mesh, and then do surgeries to repair mesh erosion, fistula, adhesions as well as the reason for using mesh in the first place, the prolapses and stress urinary incontinence problems ? For patients at a higher risk it is well worth not using the quick fixes of mesh materials. Reserve the use of mesh for those at low risk,who are willing to consent when fully informed.
Many studies on the benefits of risk over safety state use of polymeric scaffolding mesh materials conclude mesh for the treatment of POP and SUI should be considered novel. In other words experimental, as in needing more studies before concluding that synthetic mesh use is deserving of the gold standard acceptance status. Long term research is almost non-existent because the subsequent mesh products cleared by the recalled Protogen mesh were never studied in depth or made to face the standards of class three products which would have forced toxicity, leachabilty, degradation, immune stimulation, etc., testing that patients and doctors alike would have expected were done on products designed to come into permanent contact with blood, bone, and tissue. Even with class 3 approval, products like Essure implants can be identified as causing more harm than giving benefit, failing to prevent pregnancy and causing symptoms of ASIA. 10,000 in one support group alone women claim Essure is not safe or effective. We need arms length research from mesh manufacturers that looks at the autoimmune reactions of mesh implanted patients, and perhaps all implant receiving patients, and does not exclude the cohort of susceptible to autoimmune disease patient groups. The vulnerable patients need to be included in research as they are represented in the numbers of patients suffering from autoimmune symptoms starting after or being exacerbated after receiving a foreign body implant.
Why is this vital ?
Researching the autoimmune symptoms being reported by mesh complication patients would validate that this cohort of patients may have common genetic traits that predisposes them to be hypersensitive to adjuvant activity which can lead to developing autoimmune diseases when exposed to a common adjuvant. Professor Shoenfeld Yehuda , Nancy Agmon-Levina 2010 (20) claim” Environmental factors that comprise an immune adjuvant effect have been recognized for several decades. These adjuvants (i.e. silicone, alum, pristane, infectious components) were found to induce autoimmunity by themselves in different animal models and may possibly provoke AI/AIFD in humans.[9e13]. Exposure to these substances were documented in the four medical conditions conversed herein, suggesting that the common denominator to these syndromes is a trigger entailing adjuvant activity. Therefore, in this review we suggest to include these conditions under a common syndrome entitled ASIA, “Autoimmune (Auto-inflammatory) Syndrome Induced by Adjuvants”. In another discussion by Dr. Sheonfeld Yehuda is a simple description of ASIA. “It is a new syndrome., which refers to autoimmune syndrome induced by adjuvants. It includes several conditions that are not fully characterized as autoimmune diseases like systemic lupus,rheumatoid arthritis or scleroderma, but that are induced by chronic stimulation of the immune system by substances which may react as adjuvants . This chronic stimulation leads to the emergence of these new signs and symptoms , which include fatigue, arthritis, myalgia and neurological manifestations.” (http://www.biomedcentral.com/1741-7015/11/118)
Just as researchers (Alessandra Sorianoa, Gideon Nesherb, and Yehuda Shoenfeld 2014) note that “the relationship between vaccines and autoimmunity is bi-directional”, so would I hazard to state that the relationship between autoimmune disease pathogenesis and surgical mesh implant complications may also be considered bi- directional.
Diagnostic measurements of cytokines, genotypes, ANA, inflammation markers, glutathione measurements, etc. become important to note and correlate. Patients with mesh have developed Lupus post mesh implantation. Patients with synthetic mesh implants complain of exacerbated autoimmune symptoms. Clearly formal research is needed.
For example (http://link.springer.com/article/10.1007/BF02231697) consider the article Dermatomyositis exacerbated by abdominal Marlex® mesh implantation: Adjuvant effect? This article by G. Bernard-Medina, M.D., S. Gutierrez-Urena M.D., J.Orozco-AlcalaM.D., 1996 describes a woman that had her dermatomyositis severely exacerbated post mesh implantation. They summarize the mesh implant may have triggered the flare up of her underlying autoimmune disorder.
Many mesh patients on support forums report flare ups of their underlying underlying autoimmune disorders. Mesh complication patients report symptoms of autoimmune diseases that started post mesh implantation. There is enough evidence to investigate. There are patients willing to be part of research initiatives. It would be a disservice to all to ignore the opportunity to study the relationship of adjuvant effects of implant materials and the links to autoimmune pathogenesis in patients with foreign body implant materias and devices, especially if the subset of patients with complications have similar body and genetic makeup that could identify those at risk of hypersensitive reactions to foreign body implants.
We already know those with underlying autoimmune disorders, (eg. Asthmatics, smokers, diabetics,) are not good candidates for mesh. We should be suspecting that those with chemical sensitivities and food sensitivities may not be good candidates for foreign body implants. We should be very suspicious when patients have a family history of being sensitive to vaccine adjuvants. One patient known to me who has autoimmune disease post mesh, lost a baby son to a vaccination reaction, and two of her other children had bad reactions to vaccinations. Is it coincidence that she reacted badly to mesh? What is it about her genetics that should have warned doctors an adjuvant effect from an implant material could harm her? Are her remaining children vulnerable to any adjuvant triggers? This is vital information for consideration when choosing patients to exclude for mesh augmentation in any form, POP, SUI or hernia procedures. This would help with informed consent.
Prevention is always preferable to finding the cure for the cure. It makes common sense to spend money in prevention of mismatching patients with biologics. The savings in quality of life should be of the most important consideration, but the biggest factor will probably be the savings in health care costs for medical insurance providers and tax payers; two very good reasons to demand research grants to identify at risk patients for foreign body implants. Autoimmune diseases are on the rise, and the adjuvant effect of synthetic mesh in the human body may be a significant preventable trigger. Millions of people have been implanted with synthetic mesh. Perhaps plastic body parts were not such a good invention. We deserve the truth, the facts, the hope for validation that the adjuvant effect of polypropylene can cause autoimmune disease. Hundreds of women with mesh complications have conveyed the same message to me. They want their suffering, their pain, to count towards the limiting of synthetic mesh usage to those who have no alternatives, and have doctors prepared to manage their transvaginal mesh complications skillfully, being ready for the secondary problems such as autoimmune exacerbation, or initiation. Bring ready for the autoimmune symptoms means not dismissing symptoms that do not fit the the already recognized symptoms. Closed minds leave no room for learning and discoveries. Closed minds allow symptoms that could have signalled early and swift interventions to be missed . It is no wonder that the complications of surgical mesh compound and cascade into life threatening and life altering expereineces. Investigative open minds invite hope and discovery. I hope I have provided hope and a reason to demand research into the adjuvant effect of polymeric surgical mesh exacerbating and initiating autoimmune diseases. I hope and pray I have excited the readers to investigate and use use the research already being done into the populations of people defined by genetic markers as being high risk for adjuvant effect initiated autoimmune diseases.
1)http://www.the-rheumatologist.org/details/article/1081203/ASIA_A_New_Way_to_Put_the_Puzzle_Together.html
http://www.biomedcentral.com/1741-7015/11/118
2)http://www.ncbi.nlm.nih.gov/pubmed/20052576
http://www.ncbi.nlm.nih.gov/pubmed/22578730
http://books.google.ca/books?id=9TA_AAAAQBAJ&pg=PA155&lpg=PA155&dq=Surgical++polypropylene+(PP)+mesh+is+not+inert.&source=bl&ots=d6Wv1ogc_l&sig=vTpY7798UoNM_0x9n_E9I87w0TI&hl=en&sa=X&ei=chs0VMLrE43WigKniYFo&ved=0CCwQ6AEwADgK#v=onepage&q=Surgical%20%20polypropylene%20(PP)%20mesh%20is%20not%20inert.&f=false
page 155, Andrew Kingsnorth, Karl A LeBlanc 2013
3) http://www.uweb.engr.washington.edu/research/tutorials/woundhealing.html
http://link.springer.com/chapter/10.1007/978-0-387-37880-0_10
- http://articles.mercola.com/sites/articles/archive/2009/08/04/squalene-the-swine-flu-vaccines-dirty-little-secret-exposed.asp
6) http://waset.org/publications/9999333/pathology-of-explanted-transvaginal-meshes
Abstract—The use of polypropylene mesh devices for Pelvic Organ Prolapse (POP) spread rapidly during the last decade, yet our knowledge of the mesh-tissue interaction is far from complete. We aimed to perform a thorough pathological examination of explanted POP meshes and describe findings that may explain mechanisms of complications resulting in product excision. We report a spectrum of important findings, including nerve ingrowth, mesh deformation, involvement of detrusor muscle with neural ganglia, and polypropylene degradation. Analysis of these findings may improve and guide future treatment strategies. .......One specimen was received as one intact excision, while the remaining 23 were received in fragments with fragment size ranging from 0.4 to 12.0cm. For 21(87%) patients the samples were available in formalin for gross comparative assessment. Grossly the explanted meshes were described as firm. Subjectively, by palpation, the explanted lightweight meshes felt softer than the heavyweight designs, while both were firmer than either a new mesh or vaginal tissue excised during non-mesh surgeries. Of all specimens, 14 (58%) were received in fragments large enough to assess for gross deformations, which ranged from mild banding to more complex folding and edge curling.
Microscopically, all (100%) meshes were invested with collagenous scar, with chronic and foreign body inflammatory reaction.
- https://www.facebook.com/groups/Essureproblems/
- http://www.pelvichealthsolutions.com/risk-information
Transitory local irritation at the wound site and a transitory foreign body response may occur. This could result in extrusion, erosion, fistula formation or inflammation.
- http://www.pqri.org/workshops/leach_ext/imagespdfs/posters/polymer_additives_pqri_poster.pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112322/
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988402/
Biomaterial adjuvant effect is attenuated by anti-inflammatory drug delivery or material selection
- http://meshmedicaldevicenewsdesk.com/
- http://www.the- rheumatologist.org/details/article/1081203/ASIA_A_New_Way_to_Put_the_Puzzle_Together.html
- http://www.ncbi.nlm.nih.gov/pubmed/22235042
- Human adjuvant disease induced by foreign substances: a new model of ASIA (Shoenfeld's syndrome).Vera-Lastra O1, Medina G, Cruz-Dominguez Mdel P, Ramirez P, Gayosso-Rivera JA, Anduaga- Dominguez H, Lievana-Torres C, Jara LJ.
- Implant Syndrome: http://www.ehcd.com/pdf/Implant_Syndrome_070711.pdf
- Mesh-Related SIN Syndrome. A Surreptitious Irreversible Neuralgia and Its
- Morphologic Background in the Etiology of Post-Herniorrhaphy Pain, Robert Bendavid1*#, Wendy Lou2, Andreas Koch3, Vladimir Iakovlev4*#,Shouldice Hospital, Thornhill, CanadaDepartment of Biostatistics, Dalla Lan School of Public Health, University of Toronto, Toronto, Canada 3 Day Surgery and Hernia Center, Cottbus, Germany 4Department of Laboratory Medicine and Pathobiology, Keenan Research Centre of the Li Ka Shing Knowledge Institute; Division of Pathology, St. Michael’s Hospital, University of Toronto, Toronto, CanadaEmail: *[email protected], *[email protected]Received 17 May 2014; revised 16 June 2014; accepted 15 July 201
18) http://rxinjurylaw.com/830m-vaginal-mesh-settlement-will-be-paid-by-endo-to-settle-20000- mesh-injury-lawsuits/
- 19) http://www.niehs.nih.gov/news/newsletter/2013/2/science-autoimmunity/
20) Autoimmune/inflammatory syndrome induced by adjuvants
clinical manifestations [7,8]. Environmental factors that comprise an immune adjuvant effect have been recognized for several decades. These adjuvants (i.e. silicone, alum, pristane, infectious components) were found to induce autoimmunity by themselves in different animal models and may possibly provoke AI/AIFD in....
21) 21) Expert Rev Clin Immunol. 2013 Apr;9(4):361-73. doi: 10.1586/eci.13.2.
Matters not the trigger supporting evidence ....Forty-one patients were injected with mineral oil, nine patients received other substances: three iodine gadital, one guayacol, one guayacol plus silicone fluid, two collagen, two silicone fluid. The sites of application were: buttocks (36), legs and/or thighs (11), breasts (eight) hands and face (one), face (two) (seven patients received an injection to more than one site). Thirty patients presented with non-specific autoimmune manifestations, whereas 20 patients fulfilled the criteria for a defined autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, overlap syndrome, autoimmune hemolytic anemia, autoimmune thyroiditis, autoimmune hepatitis, and ulcerative colitis.
http://freepdfhosting.com/962132b4b7.pdf Review‘ASIA’ e Autoimmune/inflammatory syndrome induced by adjuvantsYehuda Shoenfeld a,b,*, Nancy Agmon-Levin a
a The Zabludowicz Center for Autoimmune Diseases, Department of Medicine B’ Sheba Medical Center, Tel-Hashomer, Israel b Incumbent of the Laura Schwarz-kipp Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Israel article info Article history: Received 16 June 2010 Received in revised form 15 July 2010 ,Accepted 20 July 2010)
.......................more info to incorporate ...........................................................................
adjuvant information
An adjuvant is a substance that enhances the antigen-specific immune response, induces the release of inflammatory cytokines, and interacts with Toll-like receptors and the NALP3 inflammasome
Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld's syndrome): clinical and immunological spectrum. Vera-Lastra O, Medina G, Cruz-Dominguez Mdel P, Jara LJ, Shoenfeld Y.
http://www.ncbi.nlm.nih.gov/pubmed/23557271
Human adjuvant disease induced by foreign substances: a new model of ASIA (Shoenfeld's syndrome). Vera-Lastra O, Medina G, Cruz-Dominguez Mdel P, Ramirez P, Gayosso-Rivera JA, Anduaga-Dominguez H, Lievana-Torres C, Jara LJ.
http://www.ncbi.nlm.nih.gov/pubmed/22235042
21) Expert Rev Clin Immunol. 2013 Apr;9(4):361-73. doi: 10.1586/eci.13.2.
Matters not the trigger supporting evidence ....Forty-one patients were injected with mineral oil, nine patients received other substances: three iodine gadital, one guayacol, one guayacol plus silicone fluid, two collagen, two silicone fluid. The sites of application were: buttocks (36), legs and/or thighs (11), breasts (eight) hands and face (one), face (two) (seven patients received an injection to more than one site). Thirty patients presented with non-specific autoimmune manifestations, whereas 20 patients fulfilled the criteria for a defined autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, overlap syndrome, autoimmune hemolytic anemia, autoimmune thyroiditis, autoimmune hepatitis, and ulcerative colitis.
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http://www.termedia.pl/Czasopismo/Reumatologia-18/Streszczenie-21947
Artykuł przeglądowy
Autoimmunologiczny/autozapalny zespół indukowany przez adiuwanty – nowy problem diagnostyczny czy rozwiązanie zagadki diagnostycznej Maria Maślińska, Carlo Perricone, Yehuda Shoenfeld Reumatologia 2013; 51, 6: 437–444
DOI (digital object identifier): 10.5114/reum.2013.39662
Chronic stimulation of the immune system by substances used as adjuvants may lead to the occurrence of numerous symptoms such as chronic fatigue, arthritis, myalgia, cognitive impairment and neurological disorders. The aim of this article is to present how and why adjuvants – while allegedly causing no specific immune response – may become a cause of development of autoimmune diseases.
słowa kluczowe:
adiuwanty, odpowiedź immunologiczna, choroby autoimmunologiczne .....................................................................................................................................................................................................
Abdominal Wall Hernias: Principles and Management books.google.ca/books?isbn=0387950044
Robert Bendavid - 2001 - Medical
Prosthetic mesh material is presumed to have a foreign body adjuvant effect in the wound. The coarse weave of polypropylene mesh with interdigitated .
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Biomaterial adjuvant effect
We have demonstrated that the biomaterial component of a tissue-engineered contruct acts as an adjuvant in the enhancement of the adaptive immune response to associated shed cellular antigens (Matzelle, Biomaterials 2004). This would result in detrimental humoral or cytotoxic response around the implant to enhance an inflammatory tissue reaction. Furthermore, the biomaterial adjuvant effect depends on the form of the biomaterial carrier vehicle (implanted polymer scaffolds vs. minimally invasive injected polymer microparticles) (Bennewitz, Biomaterials, 2005).
..................................................................................................................................................................................................Tt
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988402/
Published online Jun 2,Biomaterial adjuvant effect is attenuated by anti-inflammatory drug delivery or material selection
Lori W. Norton, Jaehyung Park, and Julia E. Babensee
2010. doi: 10.1016/j.jconrel.2010.05.032PMCID: PMC298840NIHMSID: NIHMS237733
Lori W. Norton, Jaehyung Park, and Julia E. Babensee*
these studies have demonstrated the potential for biomaterial scaffolds to act as adjuvants in enhancing the adaptive immune response to co-delivered antigen, presumably due to a material effect on DC maturation. Furthermore, tissue damage associated with the implantation of a construct may prime the site for the biomaterial adjuvant effect due to the generation of endogenous ‘danger signals’.
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