For your delectation and delight, desultory dicta on the law of delicts.

More Case Report Mischief in the Gadolinium Litigation

November 28th, 2014

The Decker case is one curious decision, by the MDL trial court, and the Sixth Circuit. Decker v. GE Healthcare Inc., ___ F.3d ___, 2014 FED App. 0258P, 2014 U.S. App. LEXIS 20049 (6th Cir. Oct. 20, 2014). First, the Circuit went out of its way to emphasize that the trial court had discretion, not only in evaluating the evidence on a Rule 702 challenge, but also in devising the criteria of validity[1]. Second, the courts ignored the role and the weight being assigned to Federal Rule of Evidence 703, in winnowing the materials upon which the defense expert witnesses could rely. Third, the Circuit approved what appeared to be extremely asymmetric gatekeeping of plaintiffs’ and defendant’s expert witnesses. The asymmetrical standards probably were the basis for emphasizing the breadth of the trial court’s discretion to devise the criteria for assessing scientific validity[2].

In barring GEHC’s expert witnesses from testifying about gadolinium-naive nephrogenic systemic fibrosis (NSF) cases, Judge Dan Polster, the MDL judge, appeared to invoke a double standard. Plaintiffs could adduce any case report or adverse event report (AER) on the theory that the reports were relevant to “notice” of a “safety signal” between gadolinium-based contrast agents in MRI and NSF. Defendants’ expert witnesses, however, were held to the most exacting standards of clinical identity with the plaintiff’s particular presentation of NSP, biopsy-proven presence of Gd in affected tissue, and documentation of lack of GBCA-exposure, before case reports would be permitted as reliance materials to support the existence of gadolinium-naïve NSF.

A fourth issue with the Decker opinion is the latitude it permitted the district court to allow testimony from plaintiffs’ pharmacovigilance expert witness, Cheryl Blume, Ph.D., over objections, to testify about the “signal” created by the NSF AERs available to GEHC. Decker at *11. At the same trial, the MDL judge prohibited GEHC’s expert witness, Dr. Anthony Gaspari, to testify that the AERs described by Blume did not support a clinical diagnosis of NSF.

On a motion for reconsideration, Judge Polster reaffirmed his ruling on grounds that

(1) the AERs were too incomplete to rule in or rule out a diagnosis of NSF, although they were sufficient to create a “signal”;

(2) whether the AERs were actual cases of NSF was not relevant to their being safety signals;

(3) Dr. Gaspari was not an expert in pharmacovigilance, which studied “signals” as opposed to causation; and

(4) Dr. Gaspari’s conclusion that the AERs were not NSF was made without reviewing all the information available to GEHC at the time of the AERs.

Decker at *12.

The fallacy of this stingy approach to Dr. Gaspari’s testimony lies in the courts’ stubborn refusal to recognize that if an AER was not, as a matter of medical science, a case of NSF, then it could not be a “signal” of a possible causal relationship between GBCA and NSF. Pharmacovigilance does not end with ascertaining signals; yet the courts privileged Blume’s opinions on signals even though she could not proceed to the next step and evaluate diagnostic accuracy and causality. This twisted logic makes a mockery of pharmacovigilance. It also led to the exclusion of Dr. Gaspari’s testimony on a key aspect of plaintiffs’ liability evidence.

The erroneous approach pioneered by Judge Polster was compounded by the district court’s refusal to give a jury instruction that AERs were only relevant to notice, and not to causation. Judge Polster offered his reasoning that “the instruction singles out one type of evidence, and adds, rather than minimizes, confusion.” Judge Polster cited the lack of any expert witness testimony that suggested that AERs showed causation and “besides, it doesn’t matter because those patients are not, are not the plaintiffs.” Decker at *17.

The lack of dispute about the meaning of AERs would have seemed all the more reason to control jury speculation about their import, and to give a binding instruction on AERs and their limited significance. As for the AER patients’ not being the plaintiffs, well, the case report patients were not the plaintiffs, either. This last reason is not even wrong[3]. The Circuit, in affirming, turned a blind eye to the district court’s exercise of discretion in a way that systematically increased the importance of Blume’s testimony on signals, while systematically hobbling the defendant’s expert witnesses.


[2]Gadolinium, Nephrogenic Systemic Fibrosis, and Case Reports” (Nov. 24, 2014).

[3] “Das ist nicht nur nicht richtig, es ist nicht einmal falsch!” The quote is attributed to Wolfgang Pauli in R. E. Peierls, “Wolfgang Ernst Pauli, 1900-1958,” 5 Biographical Memoirs Fellows Royal Soc’y 175, 186 (1960).


The Shyster Files – Racketeering in Silicosis Litigation

November 26th, 2014

David Rosner and Gerald Markowitz trace the silicosis compensation issues back to debates at the 1935 National Silicosis Conference, where representatives of labor and management squared off on the appropriate criteria for compensation.

David Rosner & Gerald Markowitz, Deadly Dust: Silicosis and the On-Going Struggle to Protect Workers’ Health at 110-15 (Ann Arbor 2006). Labor’s representative argued that silicosis should be defined by inhaling silica dust, which would have made every case of respiratory disease compensable. A lawyer who represented industry, Alfred C. Hirth, argued that compensation should be tied to disability.

Although Hirth acknowledged that silicosis was an employer problem[1], Rosner and Markowitz give a typically uncharitable assessment of Hirth’s ideas, even though the labor view that any silica inhalation constituted silicosis was demonstrably wrong at the time, and more so today. The authors quote Hirth as decrying the “[i]gnorance and sensational journalism” that has given rise to the then “the popular belief … that to inhale silica is to have silicosis.” Plus ça change, plus c’est la même chose!

Rosner and Markowitz then hone in on one sentence in Hirth’s presentation, where he criticizes the:

“shyster lawyer and quack doctor, who have been with the United States always, but whom we hope we may someday exterminate.”

Deadly Dust at 113. Here they launch the charge that Hirth was an anti-semite because he was against shysters and quacks, and even hoped, not unreasonably, that someday we might be rid of them.  The historians urge that we:

“Note the anti-Semitism implied by the use of shyster and the call for extermination, which echoed the views of the Nazi and the anti-Semites during the 1930s.”

Id. at 113n.19. Really?

Now when I first read this passage in Deadly Dust, I was puzzled. My grandmother, a sweet, charming Jewish lady, who could curse in several languages, including Yiddish, would regularly rant about the shysters about in the world. As far as I can recall, her usage was non-denominational, non-racial, non-ethnic. It was an equal opportunity epithet. So I decided to dig a little deeper into the alleged “implication” seen by Markowitz and Rosner. Everything I could find pointed to both Jewish hypersensitivity and linguistic ignorance in the authors of the Deadly Dust.

Fanciful Etymology

Here is what the venerable Oxford English Dictionary has to say about shyster:

shyster slang. [Of obscure origin. It might be f. shy a. (sense 7, disreputable) + -ster; but this sense of the adj. is app. not current in the U.S.]

1. A lawyer who practises in an unprofessional or tricky manner; especially, one who haunts the prisons and lower courts to prey on petty criminals; hence, any one who conducts his business in a tricky manner.”

Nothing there to support the authors’ character assassination, but perhaps the English are just too polite? Here is the earthier, more down-to-Earth, American Heritage Dictionary (4th ed. 2000):

“shyster.  NOUN: Slang An unethical, unscrupulous practitioner, especially of law.

ETYMOLOGY: Probably alteration of German Scheisser, son of a bitch, bastard, from scheissen, to defecate … .”

Now we are getting to fundamentals. The Merriam Webster dictionary is in line with the defecator, which accords with my sense of lawyers who file fraudulent lawsuits:

a person who is professionally unscrupulous especially in the practice of law or politics :  pettifogger.  Origin of SHYSTER: probably from German Scheisser, literally, defecator.  First Known Use: 1844”

The less venerable, crowd-sourced Wikipedia notes that

“Various false etymologies have suggested an anti-Semitic origin, but there is no proof for that.[3]

Wikipedia entry for “shyster” (citing Michael Quinion “Shyster” World Wide Words (19 May 2007).

“Shysters” in Court

My view of the usage and etymology of shyster would appear to have the highest judicial authority. When some puglistic contracts turned puglistic, Lennox Lewis sued Don King in cases that spanned the Atlantic Ocean. At some point, King, with his gloves off and his mouth open, called Judd Berstein, Lewis’s attorney, a “shyster lawyer.” Berstein claimed that these were fighting words, or at least suing words, but the House of Lords disagreed. Lennox Lewis v Don King, [2004] EWCA Civ1329 (House of Lords, Supreme Court of Judicature).

Burstein’s claim, in his action for libel, turned on the assertion that calling a Jewish lawyer a “shyster lawyer” was anti-semitic (and defamatory). The appellate court (Lord Chief Justice Mummery and the eponymously named Lord Justice Laws) noted, with apparent approval, that the court below had diligently searched but failed to find any support for Burstein’s claim:

“It seems clear from a web search of 900 dictionaries (including specifically American ones) that there is no support for the word ‘shyster’ having any anti-semitic connotations.”

Id. at para. 18.

Shysters to the Right of Me; Shysters to the Left

In playing the “shyster” card, Rosner and Markowitz protest too much. They are so intent upon painting industry as unreasonable, that they overlook that the litigious behavior of the shyster lawyers in the 1930s embarrassed labor. There were, to be sure, real cases of silicosis, with real impairment, and real disability, even if the diagnostic criteria and classification of silicosis were in flux. Liability was contested in many of the “real cases,” which made administrative compensation boards such as workman’s compensation courts more attractive to many in labor unions than were litigation solutions. Here is what one labor union publication of the time had to say about the explosion of silicosis litigation in the 1930s:

“It is estimated that today in the United States there are approximately $500,000,000 in damage suits pending against employers. Many of these are legitimate, many admittedly racketeering. But just as medical research has demonstrated that one disease can be cured by the injection of another into the system, so in the end this regretable [sic] racketeering in damage suits — this ambulance chasing and canvassing of hospital beds by shyster lawyers and quack doctors — may prove to be the beneficent agent that shall cure big business of the greed and insensitiveness that places profits above human lives.”

“Silicosis Prevention” 72 Internat’l Molders’ J. 1 (July 1936) (emphasis added) (republished from the American Federationist (June 1936)).

So everyone agreed that there were shysters out in the land, and in court. The difference between labor and management is that labor wanted to use the shysters and fraudulent lawsuits in the hope that they would pressure industry into providing safer workplaces. And industry somehow objected to being besmirched by the shysters.


[1] See Alfred C. Hirth, Silicosis as an Employer Problem (1935).


History – Lies My Teacher Told Me

November 26th, 2014

James W. Loewen, a professor of history, has been one of the most untiring critics of how history is taught and practiced in the United States. A large part of his criticism derives from the overt politicization of the teaching of history, especially the heavy hand of school boards and textbook committees in their selection of “appropriate textbooks” for high school students. See James W. Loewen, Lies My Teacher Told Me: Everything Your American History Textbook Got Wrong (2007). The disgraceful “conservative” sanitizing of United States highschoolers’ history textbooks is almost equal to the heavy-handed Marxist bent of some University professors. The politicization of history may be unavoidable, but we should be alert to the intellectual depredations from the right and the left.

*     *     *     *     *     *

I recently saw the self-styled social history of silicosis, Deadly Dust, by David Rosner and Gerald Markowitz, cited in a trial court brief. The cite was to the original edition, but it led me to read the “new and expanded” edition[1], published in 2006. Expanded, but not exactly super-sized, and with the same empty calories as before. The authors’ Preface to the second edition relays an air of excitement about recent (at the time of publication) media suggestions that silicosis may be the “new asbestosis.[2]” Of course, the authors were excited because the uptick in silicosis litigation around 2003, based almost exclusively upon fraudulent filings, brought them engagements as compensated expert witnesses for plaintiffs’ counsel.

The Preface also confesses that before their initial edition, the authors were ignorant about silicosis. And because they are so well read they assumed that their not having heard of silicosis meant that silicosis must have disappeared from the literature. Id. at xiii. This fallacious confusion between absence of evidence and evidence of absence pervades the entire book. Their first edition was written with this confirmation bias dominating their narrative:

“The book we wrote tells the story of a condition that dominated public health, medical, labor, and popular discourse on disease in the 1930s but that virtually vanished from popular and professional consciousness after World War II. How, we asked, could a chronic disease that took decades to develop and that was assumed to affect hundreds of thousands of American workers disappear from the literature and public notice in less than a decade? This question is the basis for Deadly Dust, and we believe that we answered it, providing a cultural, medical, and political model of how we, as a society, decide to recognize or forget about illness.”

Deadly Dust at xiv (emphasis added). The second edition is more of the same biased narrative.

Also clear from their Preface is the authors’ messianic complex. I now know why they have repeatedly attacked me for having criticized them: It is important for them to be seen as having been resistant victims of industry, indeed, especially if they are triumphant victims:

“We are particularly proud that lawyers for various industries have sought to get judges to exclude our book from court cases.”

Id. at xvi. Of course, from the lawyers’ perspective, a book such as Deadly Dust has many layers of evidentiary problems, running from authentication of documents, to multiple layers of hearsay, legal and logical relevancy, and rampant, subjective opinion spread throughout the narrative.

The “virtually vanished” phrase caused me to revisit[3] my previous quantitative assessment of discussions of silicosis in the popular and medical literature. The National Library of Medicine PubMed database is expanding back into the past, adding old journals and their articles to the database. Here is the most recent tally, by decade of articles with keyword “silicosis”:

Date Range                    Number of Articles from Keyword Search

1940 – 1949                      119

1950 – 1959                    1,436

1960 – 1969                    1,868

1970 – 1979                    1,176

1980 – 1989                       940

1990 – 1999                       883

2000 – 2009                      860

2010 — present                  498

The Rosner/Markowitz claim about silicosis “virtually vanishing” from professional discourse after World War II, is an assertion that is completely belied by the evidence. Google’s Ngram function further confirms the incorrectness of the fundamental premise of Deadly Dust:

Silicosis Ngram 1920 - 2010

Silicosis Ngram 1920 – 2010

The Google chart shows that although there was a peak around 1940, the level of referencing silicosis remained at or above the level for the mid-1930s until 1960, and never retreated to levels as low as for 1930-32.

This false premise, that silicosis vanished, or virtually vanished, from the medical literature, is the starting point for Rosner and Markowitz’ faux conspiracy charge against industry for suppressing discussion, when the reality was exactly the opposite. What follows from the false premise is a false set of conclusions.

[1] David Rosner & Gerald Markowitz, Deadly Dust: Silicosis and the On-Going Struggle to Protect Workers’ Health (Ann Arbor 2006).

[2] citing Jonathan Glater, “Suits on Silica Being Compared to Asbestos Cases,” New York Times (Sept. 6, 2003), C-1 (quoting one defense lawyer as saying that “I actually thought that we had made the world safe for sand.”).

[3] See Schachtman, “Conspiracy Theories: Historians, In and Out of Court” (April 17, 2013).


Gadolinium, Nephrogenic Systemic Fibrosis, and Case Reports

November 24th, 2014

Gadolinium (Gd) is a rare earth element. In its ionic form (+3), gadolinium is known to be highly toxic to humans. Gadolinium is strongly paramagnetic, which makes it a valuable contrast agent in for magnetic resonance imaging (MRI). The gadolinium is administered intravenously in a chelated form before MRI. In its chelated form, the ion is escorted out of the body through the kidneys before exposure to free Gd ion occurs. Or that was the theory.

Nephrogenic systemic fibrosis (NSF) is a rare, painful, incurable progressive connective tissue disease. NSF manifests with skin thickening and fibrosis, tethering, which means it cannot be pulled away from body. Some patients may develop extracutaneous fibrosis of muscle, lymph nodes, pleura, and other internal organs. Elana J. Bernstein, Christian Schmidt-Lauber, and Jonathan Kay, “Nephrogenic systemic fibrosis: A systemic fibrosing disease resulting from gadolinium exposure,” 26 Best Practice & Research Clin. Rheum. 489, 489 (2012).

As a diagnostic entity, NSF is a relatively recent discovery. The first case was noted in 1997, in California. Within a few years, the differential diagnostic criteria to distinguish NSF from other fibrotic diseases were developed. Centers for Disease Control, “Fibrosing skin condition among patients with renal disease–United States and Europe, 1997–2002,” 51 MMWR Morbidity and Mortality Weekly Report 25 (2002). Physicians identified the condition among patients with renal insufficiency who had received MRI with a gadolinium-based contrast agent (GBCA). Given the rarity of both the exposure (GBCA and renal insufficiency) and the outcome (NSF), the relationship between NSF and the use of gadolinium-containing contrast agents for magnetic resonance imaging (MRI) was discovered largely from case reports. A case registry is maintained at Yale University, and has identified 380 cases to date. Shawn E. Cowper, “Nephrogenic Systemic Fibrosis” at the website for The International Center for Nephrogenic Systemic Fibrosis Research (ICNSFR) [last updated June 15, 2013).

The little epidemiology that exists on the subject generally has found that all “cases” had exposure to Gd[1]. Or almost all. There have been occasional cases found without reported exposure to GBCA. Indeed, one case of NSF without prior GBCA was reported last month in the dermatological literature. C. Ross, N. De Rosa, G. Marshman, D. Astill, Nephrogenic systemic fibrosis in a gadolinium-naïve patient: Successful treatment with oral sirolimus,” Australas. J. Dermatol. (2014); doi: 10.1111/ajd.12176. [Epub ahead of print].

In litigation, the usual scenario is that plaintiffs and their counsel and expert witnesses want to offer case reports or case series as probative of a causal association between an exposure and a particular disease outcome. In the silicone gel breast implant litigation, women, who self-characterized themselves “victims,” shouted outside courtrooms, “We are the evidence.”

When the outcome in question has a baseline rate, and the exposure is widespread, this strategy is usually illegitimate and most courts have limited or prohibited the obvious attempt to prejudice the jury by the use of evidence that has little or no probative value.

The causal connection between NSF and GBCA, described above, was postulated on the basis of case reports, but this is not really a rejection of the general rule about case reports. NSF is an extremely rare outcome, and GBCA administered to patients with serious kidney insufficiency is a fairly rare exposure. In addition, gadolinium ion has a known human toxicity, and the connection between renal insufficiency and Gd toxicity is rather straightforward. The insufficiency of the kidney function results in longer “in residence” times for the GBCA, with the consequence that the gadolinium disassociates from its chelating agent, and the free Gd ion does its damage. Furthermore, biopsies of affected tissues show an uptake of gadolinium in NSF patients.

   *   *   *   *   *   *   *   *

GE Healthcare manufactures Omniscan, a GBCA, for use as an MRI-contrast medium. Given the recently discovered dangers of GBCAs in vulnerable patients, Omniscan has been a magnet for lawsuits, with the peak intensity of the litigation field in the MDL courtroom of federal district courtroom of Judge Dan Polster. Judge Polster tried the first Omniscan case, which resulted in a verdict for the plaintiff. GE appealed, complaining about several of Judge Polster’s rulings, including the uneven handling of case reports. Last month, the Sixth Circuit affirmed. Decker v. GE Healthcare Inc., ___ F.3d ___, 2014 FED App. 0258P, 2014 U.S. App. LEXIS 20049 (6th Cir. Oct. 20, 2014).

General causation between GBCAs and NSF was apparently not disputed in Decker. Although plaintiffs in the GBCA litigation established the causality of GABC in producing NSF, by case reports, Judge Polster refused to permit GEHC’s expert witnesses to testify about their reliance upon case reports of gadolinium-naïve cases of NSF; that is, the court disallowed testimony about reported cases that occurred in the absence of GBCA exposure[2]. Id. at *9. Judge Polster found that the reported gadolinium-naïve case reports were “methodologically flawed” because they did not adequately show that the NSF patients in question lacked Gd exposure, with tissue biopsy or other means. Id. at * 10. The district court speculated that there may have Gd exposure from a non-MRI procedure, but never explained what non-MRI procedure would involve internal administration of GBCA. Nor did the district court address the temporal relationship between this undocumented, conjectured non-MRI gadolinium-based imaging procedure and the onset of the reported patient’s NSF.

Before trial defendant GEHC moved for reconsideration of the district court’s previous decision on defensive use of gadolinium-naïve case reports, based upon on a then recent publication of a “purported” case of gadolinium-naïve NSF. Id. at *8. A quick read of the late-breaking case study shows that it was more than a “purported” case. A.A. Lemy, et al., “Revisiting nephrogenic systemic fibrosis in 6 kidney transplant recipients: a single-center experience,” 63 J. Am. Acad. Dermatol. 389 (2010). The cited paper by Lemy had diagnosed NSF in a patient without GBCA exposure, and mass spectrometry testing of affected tissue revealed no Gd. The district court, however, dismissed the Lemy case as irrelevant unless GEHC’s expert witnesses could demonstrate that Lemy’s patient number 5 and the plaintiff were so clinical similar that “it was probable that Mr. Decker’s NSF was not caused by his 2005 Omniscan [exposure].”

The Sixth Circuit affirmed this “tails they win; heads you lose” approach to gatekeeping as all within the scope of the district court’s exercise of discretion. Lemy’s case number 5 and Mr. Decker both had NSF, and yet the courts do not describe clinical varieties among NSF, which vary based upon their relatedness to gadolinium exposure. It would seem that the courts were imposing an extremely heavy burden on the defense to show that the gadolinium-naïve cases were absolutely free of Gd exposure, and that they resembled the particular plaintiff’s NSF diagnosis in every respect. Without any evidence of diagnostic disease criteria sensitivity and specificity, and positive predictive value for the criteria, the district and the appellate courts seem to have accepted glib demands for absolute identity between the plaintiff’s NSF manifestation and any candidate Gd-free NSF case. Given that there is clinical heterogeneity among Gd-NSF cases, and that causality was basically inferred from cases and case series, the courts’ reasoning seems strained.

The appellate court also seemed blithely unaware of the fallacious circularity of permitting a diagnostic entity to be defined based upon exposure, thereby preventing any fair test of the hypothesis that all NSF cases are caused by gadolinium. This fallacy was advanced in the silicone gel breast implant litigation, where the litigation industry shrank from claims that silicone caused classic connective tissue diseases, in the face of exculpatory epidemiologic studies. The claimants retreated to a claim that silicone caused a “new” disease that was defined by mostly vague, self-reported symptoms [so very different from NSF in this respect], in conjunction with silicone exposure. The court-appointed expert witnesses, however, would have none of these shenanigans:

“The National Science Panel concluded that they do not yet support the inclusion of SSRD [systemic silicone-related disease] in the list of accepted diseases, for 4 reasons. First, the requirement of the inclusion of the putative cause (silicone exposure) as one of the criteria does not allow the criteria set to be tested objectively without knowledge of the presence of implants, thus incurring incorporation bias (27).”

Peter Tugwell, George Wells, Joan Peterson, Vivian Welch, Jacqueline Page, Carolyn Davison, Jessie McGowan, David Ramroth, and Beverley Shea, “Do Silicone Breast Implants Cause Rheumatologic Disorders? A Systematic Review for a Court-Appointed National Science Panel,” 44 Arthritis & Rheumatism 2477, 2479 (2001) (citing David Sackett, “Bias in analytic research,” 32 J. Chronic Dis. 51 (1979)).

Of course, NSF does not share the dubious provenance of SSRD, or SAD [silicone-associated disorder] as it was sometimes known. Still, the analytic studies that have shown that NSF cases all, or mostly, had GBCA exposure, explicitly refrained from defining the NSF case as including gadolinium exposure.

Decker is thus a curious case. The trial and appellate court talked about preventing the defense expert witnesses from relying upon case reports that were “methodologically flawed,” but the courts never mentioned Federal Rule of Evidence 703, which should have been the basis for such selective pruning of the expert witnesses’ reliance materials. And then there is the matter that even if GEHC were correct about Gd-free NSF cases, the attributable risk for NSF to prior Gd exposure is almost certainly very high, and the debate over whether NSF is a “signature” disease was not likely going to affect the case outcome.

Decker can perhaps best be understood as a dispute about specific causation, with established general causation, in which the relative risk of NSF from GBCA exposure is extraordinarily high among patients with renal insufficiency. If there are other causes of NSF, they are considerably more rare than GBCA/renal insufficiency exposed cases. In the face of this very high attributable risk, GE’s expert witnesses’ discussions of an idiopathic or other cause was too speculative to pass muster under Rule 702.

[1] Elana J. Bernstein, Tamara Isakova, Mary E. Sullivan, Lori B. Chibnik, Myles Wolf & Jonathan Kay, “Nephrogenic systemic fibrosis is associated with hypophosphataemia: a case–control study,” 53 Rheumatology 1613 (2014); T.R. Elmholdt, M. Pedersen, B. Jørgensen, K. Søndergaard, J.D. Jensen, M. Ramsing, and A.B. Olesen, “Nephrogenic systemic fibrosis is found only among gadolinium-exposed patients with renal insufficiency: a case-control study from Denmark,” 165 Br. J. Dermatol. 828 (2011); P. Marckmann, “An epidemic outbreak of nephrogenic systemic fibrosis in a Danish hospital,” 66 Eur. J. Radiol. 187 (2008) (reporting all patients had gadodiamide-enhanced magnetic resonance imaging and severe renal insufficiency before onset of NSF); P. Marckmann, L. Skov, K. Rossen, J.G. Heaf, and H.S. Thomsen, “Case-control study of gadodiamide-related nephrogenic systemic fibrosis,” 22 Nephrol. Dialysis &Transplant. 3174 (2007) (all 19 cases in case-control study had prior exposure to gadolinium (Gd)-containing magnetic resonance imaging contrast agents); Centers for Disease Control, “Nephrogenic Fibrosing Dermopathy Associated with Exposure to Gadolinium-Containing Contrast Agents — St. Louis, Missouri, 2002–2006,” 56 MMWR Morbidity and Mortality Weekly Report (Feb. 23, 2007).

[2] T.A. Collidge, P.C. Thomson, P.B. Mark, et al., “Gadolinium-Enhanced MR Imaging and Nephrogenic Systemic Fibrosis: Retrospective Study of a Renal Replacement Therapy Cohort,” 245 Radiology 168-175 (2007); I.M. Wahba, E.L. Simpson, and K. White, “Gadolinium Is Not The Only Trigger For Nephrogenic Systemic Fibrosis: Insights From Two Cases And Review Of The Recent Literature,” 7 Am. J. Transplant. 1 (2007); A. Deng, D.B. Martin, et al., “Nephrogenic Systemic Fibrosis with a Spectrum of Clinical and Histopathological Presentation: A Disorder of Aberrant Dermal Remodeling,” 37 J. Cutan. Pathol. 204 (2009).