GPVI (Glycoprotein VI) Interaction With Fibrinogen Is Mediated by Avidity and the Fibrinogen αC-Region.

OBJECTIVE: GPVI (glycoprotein VI) is a key molecular player in collagen-induced platelet signaling and aggregation. Recent evidence indicates that it also plays important role in platelet aggregation and thrombus growth through interaction with fibrin(ogen). However, there are discrepancies in the literature regarding whether the monomeric or dimeric form of GPVI binds to fibrinogen at high affinity. The mechanisms of interaction are also not clear, including which region of fibrinogen is responsible for GPVI binding. We aimed to gain further understanding of the mechanisms of interaction at molecular level and to identify the regions on fibrinogen important for GPVI binding. Approach and Results: Using multiple surface- and solution-based protein-protein interaction methods, we observe that dimeric GPVI binds to fibrinogen with much higher affinity and has a slower dissociation rate constant than the monomer due to avidity effects. Moreover, our data show that the highest affinity interaction of GPVI is with the αC-region of fibrinogen. We further show that GPVI interacts with immobilized fibrinogen and fibrin variants at a similar level, including a nonpolymerizing fibrin variant, suggesting that GPVI binding is independent of fibrin polymerization. CONCLUSIONS: Based on the above findings, we conclude that the higher affinity of dimeric GPVI over the monomer for fibrinogen interaction is achieved by avidity. The αC-region of fibrinogen appears essential for GPVI binding. We propose that fibrin polymerization into fibers during coagulation will cluster GPVI through its αC-region, leading to downstream signaling, further activation of platelets, and potentially stimulating clot growth. Graphic Abstract: A graphic abstract is available for this article.

Breast radiology malpractice suits: Characteristics of frequency and outcomes- national and statewide distinctions.

The purpose of this study was to determine the frequency and outcomes of breast malpractice suits among all enrollees in One Call Medical Inc.'s panel of interpreting radiologists nationally and to evaluate state-by-state variations. The 8401 radiologists enrolled had 4764 suits, of which 826 were related to breast disease. In New York and New Jersey, the ratio of breast suits to One Call Radiologists was 0.28 and 0.27, twice as much as in any other state. Breast suits in radiology have a wide variation in frequency across the country with New York and New Jersey far exceeding all others in relative frequency and number of radiologists with multiple breast suits.

Evaluation of internet-based patient education materials from internal medicine subspecialty organizations: will patients understand them?

The majority of Americans use the Internet daily, if not more often, and many search online for health information to better understand a diagnosis they have been given or to research treatment options. The average American reads at an eighth-grade level. The purpose of this study is to evaluate the readability of online patient education materials on the websites of 14 professional organizations representing the major internal medicine subspecialties. We used ten well-established quantitative readability scales to assess written text from patient education materials published on the websites of the major professional organizations representing the following subspecialty groups: allergy and immunology, cardiology, endocrinology, gastroenterology, geriatrics, hematology, hospice and palliative care, infectious disease, nephrology, oncology, pulmonology and critical care, rheumatology, sleep medicine, and sports medicine. Collectively the 540 articles analyzed were written at an 11th-grade level (SD 1.4 grade levels). The sleep medicine and nephrology websites had the most readable materials, written at an academic grade level of 8.5 ± 1.5 and 9.0 ± 0.2, respectively. Material at the infectious disease site was written at the most difficult level, with average readability corresponding to grades 13.9 ± 0.3. None of the patient education materials we reviewed conformed to the American Medical Association (AMA) and the National Institutes of Health (NIH) guidelines requiring that patient education articles be written at a third- to seventh-grade reading level. If these online resources were rewritten, it is likely that more patients would derive benefit from reading them.

Molecular interference of fibrin's divalent polymerization mechanism enables modulation of multiscale material properties.

Protein based polymers provide an exciting and complex landscape for tunable natural biomaterials through modulation of molecular level interactions. Here we demonstrate the ability to modify protein polymer structural and mechanical properties at multiple length scales by molecular 'interference' of fibrin's native polymerization mechanism. We have previously reported that engagement of fibrin's polymerization 'hole b', also known as 'b-pockets', through PEGylated complementary 'knob B' mimics can increase fibrin network porosity but also, somewhat paradoxically, increase network stiffness. Here, we explore the possible mechanistic underpinning of this phenomenon through characterization of the effects of knob B-fibrin interaction at multiple length scales from molecular to bulk polymer. Despite its weak monovalent binding affinity for fibrin, addition of both knob B and PEGylated knob B at concentrations near the binding coefficient, Kd, increased fibrin network porosity, consistent with the reported role of knob B-hole b interactions in promoting lateral growth of fibrin fibers. Addition of PEGylated knob B decreases the extensibility of single fibrin fibers at concentrations near its Kd but increases extensibility of fibers at concentrations above its Kd. The data suggest this bimodal behavior is due to the individual contributions knob B, which decreases fiber extensibility, and PEG, which increase fiber extensibility. Taken together with laser trap-based microrheological and bulk rheological analyses of fibrin polymers, our data strongly suggests that hole b engagement increases in single fiber stiffness that translates to higher storage moduli of fibrin polymers despite their increased porosity. These data point to possible strategies for tuning fibrin polymer mechanical properties through modulation of single fiber mechanics.

Radiology medical malpractice suits in gastrointestinal radiology: prevalence, causes, and outcomes.

The purpose of this study is to determine the prevalence, causes, and outcomes of GI malpractice suits in a survey of 8,401 radiologists. The malpractice histories of 8,401 radiologists from 47 states were evaluated from credentialing data of all radiologists participating in the network of One Call Medical Inc. Thirty-two percent of radiologists were defendants in at least one malpractice suit. Of the 4,073 total claims, 346 (8.49 %) were related to the gastrointestinal system. The most frequent primary allegations were failure to diagnose, 65.9 %, and procedural complications, 17.1 %. The commonest missed diagnoses were malignancy, 31.6 %; pneumoperitoneum, 19.3 %; and appendicitis, 14.5 %. Payment to the plaintiff occurred in 75.8 % of claims pertinent to cancer, 73.2 % for missed pneumoperitoneum, and 62.5 % related to appendicitis. Of cases in which a ruling was made in favor of the plaintiff, median payments for pneumoperitoneum was $215,000, for primary cancer $200,000, and for appendicitis $60,000. Among procedurally related errors resulting in judgment against a defending radiologist, 78.6 % of claims regarding retained foreign body, 75 % of barium enema cases, and 62.5 % of liver biopsy resulted in a payment to the plaintiff. Among all resolved cases, the median award was $30,000 for unrecognized foreign body retention, $100,000 for barium enema complications, and $400,000 for liver biopsy complication. Of all GI malpractice claims, failure to diagnose was the most prevalent. Among them, approximately three fourths of claims related to either the diagnosis of primary cancer or for detection of a pneumoperitoneum.

Are we failing to communicate? Internet-based patient education materials and radiation safety.

INTRODUCTION: Patients frequently turn to the Internet when seeking answers to healthcare related inquiries including questions about the effects of radiation when undergoing radiologic studies. We investigate the readability of online patient education materials concerning radiation safety from multiple Internet resources. METHODS: Patient education material regarding radiation safety was downloaded from 8 different websites encompassing: (1) the Centers for Disease Control and Prevention, (2) the Environmental Protection Agency, (3) the European Society of Radiology, (4) the Food and Drug Administration, (5) the Mayo Clinic, (6) MedlinePlus, (7) the Nuclear Regulatory Commission, and (8) the Society of Pediatric Radiology. From these 8 resources, a total of 45 articles were analyzed for their level of readability using 10 different readability scales. RESULTS: The 45 articles had a level of readability ranging from 9.4 to the 17.2 grade level. Only 3/45 (6.7%) were written below the 10th grade level. No statistical difference was seen between the readability level of the 8 different websites. CONCLUSIONS: All 45 articles from all 8 websites failed to meet the recommendations set forth by the National Institutes of Health and American Medical Association that patient education resources be written between the 3rd and 7th grade level. Rewriting the patient education resources on radiation safety from each of these 8 websites would help many consumers of healthcare information adequately comprehend such material.

Malpractice suits in chest radiology: an evaluation of the histories of 8265 radiologists.

PURPOSE: The aim of this study was to present rates of claims, causes of error, percentage of cases resulting in a judgment, and average payments made by radiologists in chest-related malpractice cases in a survey of 8265 radiologists. MATERIALS AND METHODS: The malpractice histories of 8265 radiologists were evaluated from the credentialing files of One-Call Medical Inc., a preferred provider organization for computed tomography/magnetic resonance imaging in workers' compensation cases. RESULTS: Of the 8265 radiologists, 2680 (32.4%) had at least 1 malpractice suit. Of those who were sued, the rate of claims was 55.1 per 1000 person years. The rate of thorax-related suits was 6.6 claims per 1000 radiology practice years (95% confidence interval, 6.0-7.2). There were 496 suits encompassing 48 different causes. Errors in diagnosis comprised 78.0% of the causes. Failure to diagnose lung cancer was by far the most frequent diagnostic error, representing 211 cases or 42.5%. Of the 496 cases, an outcome was known in 417. Sixty-one percent of these were settled in favor of the plaintiff, with a mean payment of $277,230 (95% confidence interval, 226,967-338,614). CONCLUSIONS: Errors in diagnosis, and among them failure to diagnose lung cancer, were by far the most common reasons for initiating a malpractice suit against radiologists related to the thorax and its contents.

The causes of medical malpractice suits against radiologists in the United States.

PURPOSE: To determine the most frequent causes of malpractice suits as derived from credentialing data of 8401 radiologists. MATERIALS AND METHODS: This study was approved by the Institutional Review Board of New Jersey Medical School. A total of 8401 radiologists in 47 states participating in the network of One-Call Medical, a broker for computed tomographic/magnetic resonance studies in workers' compensation cases, were required to provide their malpractice history as part of their credentialing application. Of these, 2624 (31%) radiologists had at least one claim in their career. In each enrollee's credentialing file, if there was a claim against the enrollee there was a narrative regarding each malpractice case from which, in most instances, a primary allegation could be discerned. Among the 4793 cases, an alleged cause could be derived from the narrative in 4043 (84%). Statistical analysis was performed with Stata 12 (2011; Stata, College Station, Tex) software. RESULTS: The most common general cause was error in diagnosis (14.83 claims per 1000 person-years [95% confidence interval {CI}: 14.19, 15.51]). In this category, breast cancer was the most frequently missed diagnosis (3.57 claims per 1000 person-years [95% CI: 3.26, 3.91]), followed by nonspinal fractures (2.49 claims per 1000 person-years [95% CI: 2.28, 2.72]), spinal fractures (1.32 claims per 1000 person-years [95% CI: 1.16, 1.49]), lung cancer (1.26 claims per 1000 person-years [95% CI: 1.11, 1.42]), and vascular disease (1.08 claims per 1000 person-years [95% CI: 0.93, 1.24]). The category next in frequency was procedural complications (1.76 claims per 1000 person-years [95% CI: 1.58, 1.96]), followed by inadequate communication with either patient (0.40 claim per 1000 person-years [95% CI: 0.32, 0.50]) or referrer (0.71 claim per 1000 person-years [95% CI: 0.60, 0.84]). Radiologists had only a peripheral role in 0.92 claim per 1000 person-years (95% CI: 0.77, 1.10). Failure to recommend additional testing was a rare cause (0.41 claim per 1000 person-years [95% CI: 0.34, 0.50]). CONCLUSION: Errors in diagnosis are, by far, the most common generic cause of malpractice suits against radiologists. In this category, breast cancer was the most frequently missed diagnosis, followed by nonvertebral fractures and spinal fractures. Failure to communicate and failure to recommend additional testing are both uncommon reasons for initiating a suit.

Relative importance of metaphor in radiology versus other medical specialties.

The acquisition of competence in radiology often entails referring to other realms of knowledge, by which insights are acquired through the use of metaphor. One way in which compelling associations are made and retained is by linking anatomic structures and pathologic conditions with objects, places, and concepts, and codifying these relationships as metaphoric signs. An aggregate of specialty-specific signs were obtained from two general medical dictionaries and from encyclopedic texts in radiology and six other specialties: internal medicine, dermatology, pathology, general surgery, orthopedics, and pediatrics. The signs were then separated into two categories: eponymous (bearing the name of an individual or place) and metaphoric (extending meaning from one context to another). A total of 375 metaphoric signs were collected from citations in the researched dictionaries and texts, the overwhelming majority (66%) of which were radiologic in reference. In every other specialty, eponymous signs outnumbered metaphoric signs. In contrast, eponymous signs were comparatively infrequent in radiology. The striking difference observed in the data highlights the importance of metaphors for discourse and instruction in radiology. In image interpretation, the meaning of perceptual input is often discerned through associations with pictures previously encountered and understood both concretely and metaphorically. The inherent nature of radiologic images as simulacra of both normal anatomy and disease entities makes imaging findings well suited to explanation by means of named patterns borrowed from other realms of knowledge.

Overuse of concomitant foot radiographic series in patients sustaining minor ankle injuries.

Radiographic series of the foot are often obtained in conjunction with ankle X-rays when the clinical presentation is limited to trauma to the ankle. The Ottawa Ankle and Foot Rules were established in 1992 and serve as reliable guidelines to determine when an ankle or foot series is warranted in patients who have sustained minor ankle and/or foot injury. We retrospectively reviewed radiographic studies of all patients over a period of 18 months who simultaneously had ankle and foot plain radiographs performed for acute complaints limited to the ankle alone. Of the 243 patients who met our inclusion criteria, 55 patients had fractures, 46 in or near the ankle joint, and nine which were located at the base of the fifth metatarsal bone. No fractures or dislocations were noted elsewhere in the foot. All of the fifth metatarsal fractures were evident on adequately performed ankle series. Our findings suggest that films of the foot are not necessary when trauma is limited to the ankle and when an appropriately performed ankle series has been completed.

Inadvertent thyroid irradiation in protocol-driven trauma CT: a survey of hospital ERs.

Given the well-recognized association of radiation and thyroid cancer, the objective of this study was to assess the frequency of radiation overlap at the level of the thyroid gland as part of standard protocols for computed tomography (CT) assessment of trauma, incorporating both cervical spine and chest images. A survey was sent to physician members of the American Society of Emergency Radiology. Among other questions, the respondents were asked to indicate their CT protocol with respect to the lower boundary of their cervical spine series and the upper boundary of their chest CT series. Forty-one surveys were returned. Of these, 83% reported overlap of the contiguous margins of the two CT studies resulting in partial or total double radiation deposition to the thyroid gland, which typically extends from vertebral levels C5 to T1. Sixty-one percent reported overlapping at T1 only, 15% at C7 to T1, 4.9% at C6 to T1, and 2.4% at C5 to T1. These data reveal that the predominant practice among the respondents is to include the thyroid gland in coincident CT studies of the cervical spine and chest in trauma protocols.

The value of the internship for radiation oncology training: results of a survey of current and recent trainees.

PURPOSE: Although a 12-month clinical internship is the traditional precursor to a radiation oncology residency, the continuance of this mandated training sequence has been questioned. This study was performed to evaluate the perceptions of current radiation oncology residents with respect to the value of their internship experience. METHODS AND MATERIALS: A survey was sent to all US radiation oncology residents. Each was queried about whether they considered the internship to be a necessary prerequisite for a career as a radiation oncologist and as a physician. Preferences were listed on a Likert scale (1 = not at all necessary to 5 = absolutely necessary). RESULTS: Seventy-one percent considered the internship year mostly (Likert Scale 4) or absolutely necessary (Likert Scale 5) for their development as a radiation oncologist, whereas 19.1% answered hardly or not at all (Likert Scale 2 and 1, respectively). With respect to their collective considerations about the impact of the internship year on their development as a physician, 89% had a positive response, 5.8% had a negative response, and 4.7% had no opinion. Although both deemed the preliminary year favorably, affirmative answers were more frequent among erstwhile internal medicine interns than former transitional program interns. CONCLUSIONS: A majority of radiation oncology residents positively acknowledged their internship for their development as a specialist and an even greater majority valued it for their development as a physician. This affirmative opinion was registered more frequently by those completing an internal medicine internship compared with a transitional internship.

The value of the internship year for radiologists: a retrospective analysis as assessed by current residents and fellows.

RATIONALE AND OBJECTIVES: The purposes of the study were to determine (a) if radiology residents and fellows view their internship year as a valued prerequisite for their career as a radiologist and as a physician, (b) how their postgraduate year (PGY)-1 was perceived with regard to a specific type of internship (i.e., internal medicine, transitional year, or surgery), and (c) how their internship is considered from the vantage point of their current year of training and subspecialty career choice. MATERIALS AND METHODS: A survey was sent to all current U.S. radiology residents and fellows from a list derived from the American College of Radiology database. They were polled regarding their experiences in their preliminary year (PGY-1). Responses were coded on a 5-point Likert scale. RESULTS: Response rate for the study was 35%. Although 70% of respondents maintained that their internship year was necessary for their development as a physician, only 49% indicated that it was necessary for their development as a radiologist. Of respondents who graduated from surgical internships, 72% claimed that their PGY-1 was important for their development as a radiologist, compared to 44% of former transitional year interns and 49% of internal medicine interns (P<.001). When disaggregated by subspecialty career choice, participants were evenly divided about their perceptions of their intern year. However, among those considering interventional radiology, 67% of respondents considered their internship important to their development as a radiologist (P<.001). CONCLUSION: Overall, these data suggest that although the internship year was believed to have merit, the transitional year was least liked by radiology trainees. Efforts should be made to determine why the transitional year does not fare so well in the hope that structural improvements in it can be undertaken to make the year seem more worthwhile and more highly regarded.

Critique of the transitional year internship and its relationship to radiology residency.

RATIONALE AND OBJECTIVES: The purpose of the study is to determine if transitional year program (TYP) requirements foster realization of standards of excellence and clinical relevance for future radiologists and to explore demographic and economic factors pertinent to TYPs. MATERIALS AND METHODS: A list of accredited TYPs were obtained from the American Medical Association's Graduate Medical Education (ACGME) Directory 2006-2007. Specialty distribution of TYP graduates was examined from statistics provided by the ACGME, and data from the 2007 Main Residency Match was analyzed. Data derived from a concurrent survey of the perception of the value of internship sent to all current radiology residents and fellows was assessed. The institutional costs of employing TYP interns versus physician assistants were also calculated. RESULTS: Forty-one of the 125 TYPs lack residencies in internal medicine (IM), general surgery (GS), or both, and approximately two-third of these lack full medical school affiliation. The interns who will graduate from these 41 programs account for 103 of the 1,128 radiology residents in their post-graduate year 2. Despite the longest elective time offered in TYPs compared to conventional preliminary programs, current radiology trainees who had participated in preliminary IM or GS internships were more satisfied compared to trainees completing TYPs. CONCLUSIONS: The requirements of the transitional internship and compliance with them need to be carefully assessed to determine their efficacy. Despite the strong economic impetus for hiring TYP interns, the availability of open slots in existing preliminary programs in IM and GS, coupled with radiology residents' greater level of satisfaction with traditional over transitional internships, makes the existence of TYPs less compelling.

Open surgical treatment of aneurysmal sac expansion following endovascular abdominal aneurysm repair: solution for an unresolved clinical dilemma.

The advantages of endovascular aneurysm repair (EVAR) are probably related to the avoidance of the three major physiological insults associated with open abdominal aortic aneurysm (AAA) repair: laparotomy, aortic cross-clamping and ischemia reperfusion injury. Continuing aneurysm expansion indicates a failure to exclude the AAA from the circulation. We describe our experience with open surgery of post-EVAR sac expansion. A consecutive series of 68 EVAR patients was followed up. Endovascular and minimally invasive procedures were the initial treatment option. Failure of these attempts to curtail AAA sac expansion or type 2 large endoleaks (EL) resulted in opening of the aneurysm sac. The procedure includes positioning of a deflated occlusion balloon proximal to the stent graft (SG). Laparotomy with opening of the eneurysm sac was then performed. The thrombus was removed and backbleeding vessels oversewn. The aneurysm sac was then plicated over the SG. Four patients (5.9%) were diagnosed as having either persistent large type 2 EL or sac enlargement. In all patients the procedure was accomplished successfully. One patient died from acute myocardial infarction perioperatively. Three patients recovered uneventfully and follow-up computed tomography confirmed the absence of endoleak and a disappearance of the AAA. We believe that whenever EVAR fails to exclude the aneurysm from the circulation, open exploration without graft replacement should be considered.

The thyroid cancer epidemic: is it the dark side of the CT revolution?

The rapid increase in CT use since 1990 and especially in the past 10 years has been accompanied by a coterminous worldwide increase in incidence of thyroid cancer especially in women. Are the two trends independent or related? Specific information from many countries and seven American states suggest that the relationship is real as no other cause can account fully for the temporal change in the frequency of this malignancy. Moreover, newer techniques of CT performance with or without the administration of iodinated contrast material favor the likelihood of a contingent association of image test utilization and thyroid cancer induction.

Histopathologic evaluation of tissue extracted on the radiofrequency probe after ablation of liver tumors: preliminary findings.

OBJECTIVE: Our aim was to evaluate the histologic characteristics of tissue extracted on the probe immediately after radiofrequency ablation of malignant tumors in the liver. MATERIALS AND METHODS: From April to December 2001, 20 radiofrequency ablations were performed in 19 patients with primary (n = 17) and metastatic (n = 2) liver masses. Track ablation according to device protocol was performed after each ablation. Tissue was adherent to the probe after all radiofrequency probe passes. All pieces of tissue found on the probe were collected and preserved in formalin. RESULTS: Tissue was examined by the study pathologist. In eight (40%) of 20 specimens, coagulation necrosis was present. In five (25%) of 20 specimens, possibly nonviable tissue was extracted, although some cell characteristics were identified. In seven (35%) of 20 specimens with hepatocellular carcinoma, possibly viable tissue was found. Five specimens were identified as hepatocellular carcinoma, and two, as cirrhotic nodules. CONCLUSION: Histopathologic evaluation of the tissue extracted on the radiofrequency probe after ablation is feasible. This study showed that coagulation necrosis was clearly present in at least 40% of the patients, which proves that nonviable tissue can be seen immediately after ablation. Whether this pathologic finding has prognostic value is not known.