Anne E. Laumann

Inflammation of actinic keratoses subsequent to therapy with sorafenib, a multitargeted tyrosine-kinase inhibitor

The Ras–Raf–MEK–ERK signalling pathway is frequently dysregulated in human malignancies, as is angiogenesis and the vascular endothelial growth factor receptor (VEGF/VEGFR) pathway. These kinases are therefore important anticancer targets. The novel, oral treatment sorafenib (BAY 43–9006), has been shown to be an inhibitor of VEGFR, Raf and platelet‐derived growth factor in clinical trials against a variety of cancers, with the greatest activity to date observed in metastatic renal cancer. Although side‐effects with this targeted therapy are usually not dose‐limiting, they frequently involve the skin, and consist of a maculopapular rash, palmar–plantar dysaesthesia, alopecia and xerosis. In this report, we present two patients in whom treatment with sorafenib resulted in inflammation of actinic keratosis, which in some cases progressed to invasive squamous cell carcinoma. This side‐effect is of clinical importance, as early recognition is critical for early treatment and may represent a source of additional morbidity to these patients.

Nickel hypersensitivity: A clinical review and call to action

Nickel sensitivity is common and increasing in prevalence. This review discusses nickel sensitivity and its association with body piercing and other environmental factors, occupational relevance, and potential implications for implantable metal medical devices. In addition, current European legislation that limits the release of nickel from jewelry is highlighted and an argument for similar legislation elsewhere is presented.

The Tongue Enables Computer and Wheelchair Control for People with Spinal Cord Injury

Individuals with severe spinal cord injury control a computer and powered wheelchair by using a wireless tongue-operated assistive technology called the Tongue Drive System. Tying the Tongue to Motor Control Voluntary tongue motion may help people with limited upper limb mobility, such as those with high-level spinal cord injury, to access computers and to drive wheelchairs. The Tongue Drive System (TDS) is a wireless and wearable assistive technology that allows individuals with severe motor impairments to access their environments using voluntary tongue motion. Kim et al. report on a new study of TDS efficacy in patients with severe spinal cord injury. Two groups of able-bodied participants and a group of patients with spinal cord injury received a magnetic tongue barbell. Participants used the TDS during five to six testing sessions. Comparisons between the TDS and the keypad for the able-bodied groups and a sip-and-puff device (a traditional assistive technology) for those with tetraplegia were based on widely accepted measures of speed and accuracy. A combination of TDS flexibility and inherent human tongue abilities enabled individuals with severe motor impairments to access computers and drive wheelchairs more quickly but just as accurately as when using traditional assistive technologies. The Tongue Drive System (TDS) is a wireless and wearable assistive technology, designed to allow individuals with severe motor impairments such as tetraplegia to access their environment using voluntary tongue motion. Previous TDS trials used a magnetic tracer temporarily attached to the top surface of the tongue with tissue adhesive. We investigated TDS efficacy for controlling a computer and driving a powered wheelchair in two groups of able-bodied subjects and a group of volunteers with spinal cord injury (SCI) at C6 or above. All participants received a magnetic tongue barbell and used the TDS for five to six consecutive sessions. The performance of the group was compared for TDS versus keypad and TDS versus a sip-and-puff device (SnP) using accepted measures of speed and accuracy. All performance measures improved over the course of the trial. The gap between keypad and TDS performance narrowed for able-bodied subjects. Despite participants with SCI already having familiarity with the SnP, their performance measures were up to three times better with the TDS than with the SnP and continued to improve. TDS flexibility and the inherent characteristics of the human tongue enabled individuals with high-level motor impairments to access computers and drive wheelchairs at speeds that were faster than traditional assistive technologies but with comparable accuracy.

Evaluation of a Smartphone Platform as a Wireless Interface Between Tongue Drive System and Electric-Powered Wheelchairs

Tongue drive system (TDS) is a new wireless assistive technology (AT) for the mobility impaired population. It provides users with the ability to drive powered wheelchairs (PWC) and access computers using their unconstrained tongue motion. Migration of the TDS processing unit and user interface platform from a bulky personal computer to a smartphone (iPhone) has significantly facilitated its usage by turning it into a true wireless and wearable AT. After implementation of the necessary interfacing hardware and software to allow the smartphone to act as a bridge between the TDS and PWC, the wheelchair navigation performance and associated learning was evaluated in nine able-bodied subjects in five sessions over a 5-week period. Subjects wore magnetic tongue studs over the duration of the study and drove the PWC in an obstacle course with their tongue using three different navigation strategies; namely unlatched, latched, and semiproportional. Qualitative aspects of using the TDS-iPhone-PWC interface were also evaluated via a five-point Likert scale questionnaire. Subjects showed more than 20% improvement in the overall completion time between the first and second sessions, and maintained a modest improvement of ~9% per session over the following three sessions.

Body piercing: complications and prevention of health risks.

Body and earlobe piercing are common practices in the USA today. Minor complications including infection and bleeding occur frequently and, although rare, major complications have been reported. Healthcare professionals should be cognizant of the medical consequences of body piercing.Complications vary depending on the body-piercing site, materials used, experience of the practitioner, hygiene regimens, and aftercare by the recipient. Localized infections are common. Systemic infections such as viral hepatitis and toxic shock syndrome and distant infections such as endocarditis and brain abscesses have been reported. Other general complications include allergic contact dermatitis (e.g. from nickel or latex), bleeding, scarring and keloid formation, nerve damage, and interference with medical procedures such as intubation and blood/organ donation.Site-specific complications have been reported. Oral piercings may lead to difficulty speaking and eating, excessive salivation, and dental problems. Oral and nasal piercings may be aspirated or become embedded, requiring surgical removal. Piercing tracts in the ear, nipple, and navel are prone to tearing. Galactorrhea may be caused by stimulation from a nipple piercing. Genital piercings may lead to infertility secondary to infection, and obstruction of the urethra secondary to scar formation. In men, priapism and fistula formation may occur. Women who are pregnant or breastfeeding and have a piercing or are considering obtaining one need to be aware of the rare complications that may affect them or their child. Though not a ‘complication’ per se, many studies have reported body piercing as a marker for high-risk behavior, psychopathologic symptoms, and anti-social personality traits.When it comes to piercing complications, prevention is the key. Body piercers should take a complete medical and social history to identify conditions that may predispose an individual to complications, and candidates should choose a qualified practitioner to perform their piercing.As body piercing continues to be popular, understanding the risks of the procedures as well as the medical and psychosocial implications of wearing piercing jewelry is important for the medical practitioner.

Pediatric nephrogenic systemic fibrosis is rarely reported: a RADAR report

BackgroundNephrogenic systemic fibrosis is a fibrosing disorder associated with exposure to gadolinium-based contrast agents in people with severely compromised renal function.ObjectiveThe purpose of this study was to determine the reported number of cases of nephrogenic systemic fibrosis in children using three distinct publicly available data sources.Materials and methodsWe conducted systematic searches of the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), the International Center for Nephrogenic Systemic Fibrosis Research (ICNSFR) registry and published literature from January 1997 through September 2012. We contacted authors of individual published cases to obtain follow-up data. Data sets were cross-referenced to eliminate duplicate reporting.ResultsWe identified 23 children with nephrogenic systemic fibrosis. Seventeen had documented exposure to gadolinium-based contrast agents. Six children had been reported in both the FAERS and the literature, four in the FAERS and the ICNSFR registry and five in all three data sources.ConclusionNephrogenic systemic fibrosis has been rarely reported in children. Although rules related to confidentiality limit the ability to reconcile reports, active pharmaco-vigilance using RADAR (Research on Adverse Drug events And Reports) methodology helped in establishing the number of individual pediatric cases within the three major data sources.

Topical Sodium Thiosulfate Therapy for Leg Ulcers With Dystrophic Calcification

A 41-year-old African American woman with a 14-year history of systemic lupus erythematosus (SLE) presented with exquisitely painful stellate ulcers with surrounding livedo reticularis on both shins in April 2006. In addition to smallvessel involvement, her connective tissue disease was characterized by pulmonary fibrosis, pulmonary hypertension requiring continuous oxygen supplementation, Raynaud phenomenon,andchronicrightpoplitealdeepvenousthrombosis. Her medications included prednisone (5 mg/d), methotrexate (12.5 mg/wk), folic acid, hydroxychloroquine, pentoxyphilline, coumadin, budesonide inhaler, fluticasone inhaler, fexofenadine, erythropoietin, sildenafil, amlodipine, gabapentin, acetaminophen-codeine, tramadol hydrochloride, famciclovir, tolterodine, calcium supplement, vitamin E supplement, alendronate, and esomeprazole. The results of laboratory tests were remarkable for the following values: hemoglobin, 8.8 g/dL (to convert to grams per liter, multiply by 10.0); hematocrit, 27.1% (reference range, 34%-45%); antinuclear antibody, 1:1280 speckled; double-stranded DNA, 52.1 IU/mL (reference value, 5 IU/mL); nRNP/Sm IgG autoantibodies, 118.0 U ( 5.0 U); Sm IgG autoantibodies, 114.0 U (reference value, 5.0 U); SSA IgG autoantibodies, 158.0 U (reference value, 5.0 U); SSB IgG autoantibodies, 167.0 U (reference value, 5.0 U); C3 complement, 49 mg/dL (reference range, 82-235 mg/dL), anticardiolipin antibody IgG, 50 IgG phospholipid units (reference value, 15 IgG phospholipid units); and iron, 13 μg/dL (to convert to micromoles per liter, multiply by 0.179) (reference range, 40170 μg/dL). The findings of urinalysis were normal, as were renal and liver functions. Magnetic resonance imaging of the bilateral lower extremities showed no evidence of osteomyelitis. On examination, the distal portion of the patient’s extremities were cyanotic and cold, with sclerodactyly, finger pad atrophy, and bone resorption. The shin ulcers were 10.0 12.5 cm bilaterally. Initial management included increasing the patient’s immunosuppressive regimen with intravenous solumedrol (3 boluses, 1 g each), raising her dose of erythropoietin, and adding oral iron supplements. Intensive topical therapy with daily aluminum subacetate compresses was initiated, followed by the application of hydrogel (polyethylene oxide with 96% water) dressings for pain relief and triamcinolone acetonide, 0.1%, ointment around the wounds. Within 2 weeks, the wound odor had increased. The compress solution was changed to acetic acid for gram-negative bacterial coverage, and the dressing was changed to a hydrophilic polyurethane membrane matrix (foam) dressing. By late September 2006, the patient’s pain was still incapacitating, and her ulcers had increased in size despite the early appearance of deep granulation tissue. Each ulcer was purulent and foul smelling, despite intermittent use of oral ciprofloxacin and clindamycin. There were many small, hard, yellow granules across the surfaces and penetrating the tissue of the wounds (Figure 1). Several attempts at debridement were made, but they were extremely painful, requiring preprocedure narcotic administration. Histologic examination of the tissue fragments revealed an ulcerated epidermis with dense neutrophilic infiltration and dermal and subcutaneous suppurative and granulomatous inflammation, with calcification, bone formation, a mixed inflammatory infiltrate, and an area of dermal necrosis (Figure 2). A diagnosis of dystrophic calcification in the presence of SLE was made.

Treatment of radiation-relapsing primary cutaneous B-cell lymphoma with an anti-CD20 monoclonal antibody

Primary cutaneous B cell lymphomas have a high recurrence rate after treatment with surgery and/or local radiation therapy. Two men are described in whom radiotherapy‐relapsing cutaneous B‐cell lymphomas were successfully treated with the monoclonal anti‐CD20 antibody rituximab. Both patients had a complete response with no recurrence at follow‐up at 17 and 24 months for the large B‐cell lymphoma of the leg and the follicle centre cell lymphoma, respectively. These are two of the few cases in the literature showing that rituximab is an effective and well‐tolerated treatment for radiotherapy‐relapsing primary cutaneous B cell lymphoma.

Advancing pharmacovigilance through academic–legal collaboration: the case of gadolinium-based contrast agents and nephrogenic systemic fibrosis—a research on adverse drug events and reports (RADAR) report

OBJECTIVE To compare and contrast three databases, that is, The International Centre for Nephrogenic Systemic Fibrosis Registry (ICNSFR), the Food and Drug Administration Adverse Event Reporting System (FAERS) and a legal data set, through pharmacovigilance and to evaluate international nephrogenic systemic fibrosis (NSF) safety efforts. METHODS The Research on Adverse Drug events And Reports methodology was used for assessment-the FAERS (through June 2009), ICNSFR and the legal data set (January 2002 to December 2010). Safety information was obtained from the European Medicines Agency, the Danish Medicine Agency and the Food and Drug Administration. RESULTS The FAERS encompassed the largest number (n = 1395) of NSF reports. The ICNSFR contained the most complete (n = 335, 100%) histopathological data. A total of 382 individual biopsy-proven, product-specific NSF cases were analysed from the legal data set. 76.2% (291/382) identified exposure to gadodiamide, of which 67.7% (197/291) were unconfounded. Additionally, 40.1% (153/382) of cases involved gadopentetate dimeglumine, of which 48.4% (74/153) were unconfounded, while gadoversetamide was identified in 7.3% (28/382) of which 28.6% (8/28) were unconfounded. Some cases involved gadobenate dimeglumine or gadoteridol, 5.8% (22/382), all of which were confounded. The mean number of exposures to gadolinium-based contrast agents (GBCAs) was gadodiamide (3), gadopentetate dimeglumine (5) and gadoversetamide (2). Of the 279 unconfounded cases, all involved a linear-structured GBCA. 205 (73.5%) were a non-ionic GBCA while 74 (26.5%) were an ionic GBCA. CONCLUSION Clinical and legal databases exhibit unique characteristics that prove complementary in safety evaluations. Use of the legal data set allowed the identification of the most commonly implicated GBCA. ADVANCES IN KNOWLEDGE This article is the first to demonstrate explicitly the utility of a legal data set to pharmacovigilance research.

Melanoma and Non-Melanoma Skin Cancer Associated with Angiotensin-Converting-Enzyme Inhibitors, Angiotensin-Receptor Blockers and Thiazides: A Matched Cohort Study

IntroductionControversy exists about an association between angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), and thiazides (TZs) and the risk of malignant melanoma (MM), and non-melanoma skin cancer—basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).ObjectiveThe aim of this study was to determine if an association exists for ACEI, ARB, or TZ exposure and skin cancers.MethodsThis was a matched cohort study using a large electronic medical records repository, the Northwestern Medicine Enterprise Data Warehouse (NMEDW). The exposed population consisted of patients with a documented order for an ACEI, ARB, or TZ with no prior history of skin cancer. The control population consisted of matched patients without documented exposure to ACEI, ARB, or TZ and no previous skin cancer. Incident MM, BCC, or SCC diagnosis by ICD-9 codes was recorded. Odds ratios (ORs) were obtained by using logistic regression analyses.ResultsAmong the 27,134 patients exposed to an ACEI, 87 MM, 533 BCC, and 182 SCC were detected. Among the 13,818 patients exposed to an ARB, 96 MM, 283 BCC, and 106 SCC were detected. Among the 15,166 patients exposed to a TZ, 99 MM, 262 BCC, and 130 SCC were detected. Significant associations using ORs from logistic regression were found for MM and TZs (OR 1.82; 95% confidence interval [CI] 1.01–3.82); BCC and ARBs (OR 2.86; 95% CI 2.13–3.83), ACEIs (OR 2.23; 95% CI 1.78–2.81) and TZs (OR 2.11; 95% CI 1.60–2.79); SCC and ARBs (OR 2.22; 95% CI 1.37–3.61), ACEIs (OR 1.94; 95% CI 1.37–2.76), and TZs (OR 4.11; 95% CI 2.66–6.35).ConclusionsA safety signal for ACEIs, ARBs, and TZs and BCC and SCC, as well as for TZs and MM, was detected. An increased awareness and education, especially for those who are at high risk for skin cancer, are warranted for patients and healthcare providers. Further exploration of such associations for these commonly used drug classes is warranted.