Comparison of Tissue Molecular Biomarker Testing Turnaround Times and Concordance Between Standard of Care and the Biocartis Idylla Platform in Patients With Colorectal Cancer.

OBJECTIVES: Management of colorectal cancer warrants mutational analysis of KRAS/NRAS when considering anti-epidermal growth factor receptor therapy and BRAF testing for prognostic stratification. In this multicenter study, we compared a fully integrated, cartridge-based system to standard-of-care assays used by participating laboratories. METHODS: Twenty laboratories enrolled 874 colorectal cancer cases between November 2017 and December 2018. Testing was performed on the Idylla automated system (Biocartis) using the KRAS and NRAS-BRAF cartridges (research use only) and results compared with in-house standard-of-care testing methods. RESULTS: There were sufficient data on 780 cases to measure turnaround time compared with standard assays. In-house polymerase chain reaction (PCR) had an average testing turnaround time of 5.6 days, send-out PCR of 22.5 days, in-house Sanger sequencing of 14.7 days, send-out Sanger of 17.8 days, in-house next-generation sequencing (NGS) of 12.5 days, and send-out NGS of 20.0 days. Standard testing had an average turnaround time of 11 days. Idylla average time to results was 4.9 days with a range of 0.4 to 13.5 days. CONCLUSIONS: The described cartridge-based system offers rapid and reliable testing of clinically actionable mutation in colorectal cancer specimens directly from formalin-fixed, paraffin-embedded tissue sections. Its simplicity and ease of use compared with other molecular techniques make it suitable for routine clinical laboratory testing.

Steroid-Free Over-the-Counter Eczema Skin Care Formulations Reduce Risk of Flare, Prolong Time to Flare, and Reduce Eczema Symptoms in Pediatric Subjects With Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a chronic skin condition associated with decreased barrier function resulting in periodic flare-ups of erythematous and pruritic lesions. Guidelines recommend daily treatment of atopic skin with emollient moisturizers for prevention of flares and maintenance of the flare-free state. This study evaluated the efficacy of 2 steroid-free, nonprescription eczema skin care formulations for reducing the risk of flare and relieving symptoms in infants and children with AD: Body Cream for the daily maintenance treatment of atopic skin and Flare Treatment for the treatment of atopic flares. METHODS: After a 2-week washout period, subjects (N=45; mean age 3.5 years) were randomized to cleanser plus daily moisturizing with Body Cream (moisturizer group) or cleanser only (control group) for 6 months or until flare. Subjects experiencing flare received Flare Treatment for 4 weeks. RESULTS: The incidence of flare was significantly lower in the moisturizer group compared with the control group (21% vs 65%; P=.006), while the median time to flare was shorter in the control group (28 vs >180 days). Risk of flare was reduced by 44.1% after 6 months of Body Cream application. Flare Treatment reduced overall eczema symptom severity at week 2 and week 4; 78.9% of flares had improved or cleared at week 4. CONCLUSIONS: Body Cream reduced the incidence of flare and the time to flare, reinforcing guidelines that daily emollient therapy should be an integral part of the maintenance treatment plan for the prevention of disease flares. Body Cream and Flare Treatment are effective over-the-counter steroid-free options for management of AD in children.

Steroid-free emollient formulations reduce symptoms of eczema and improve quality of life.

Two over-the-counter products have been clinically tested for efficacy and tolerability in the treatment of atopic dermatitis. Study 1 evaluated a daily maintenance Body Cream (Eucerin Eczema Relief Body Crème) applied twice daily for 14 days, followed by treatment withdrawal for 5 days (regression period) in subjects with a history of atopic dermatitis. Study 2 evaluated an acute treatment (Eucerin Eczema Relief Instant Therapy [Instant Therapy]) for active atopic dermatitis lesions administered for 14 days. Skin barrier function, hydration, tolerability, and relief of symptoms were assessed at baseline, day 7, and day 14. Study 2 also measured itch relief and treatment impact on work, social activities, and sleep. Body Cream significantly improved skin hydration and barrier function (P<.001) at 14 days, with improvements persisting through the 5-day regression phase. Itching was significantly improved in 93.8% of subjects (P<.001). Instant Therapy treatment of atopic dermatitis lesions significantly improved skin hydration and barrier function, as well as symptoms of erythema, pruritus, excoriation, and lichenification, with rapid improvement of itch reported within minutes of the first treatment application. Instant Therapy significantly reduced itch intensity and frequency, and demonstrated beneficial improvements in subjects' quality of life. Body Cream and Instant Therapy were both safe and well tolerated.

Candidates for transcatheter aortic valve replacement: fitting the PARTNERS criteria.

OBJECTIVES: To determine an estimate patient volume with severe AS meeting PARTNER-B criteria, with the objective of providing insights into the annual volume needed to sustain a TAVR program. BACKGROUND: While the prevalence of AS is well documented, potential TAVR candidates remains less established. A better understanding of this population is critical for the development of TAVR programs. Though no clear volume has been determined, societies suggest a minimum of 20-24 annual cases to establish a TAVR program. METHODS: A total of 21,652 patients were screened from a single center echocardiography registry over a 3-year period. From them, 833 patients with AS were identified representing our study population. Severity was stratified by echocardiographic criteria. Those identified to have moderate-to-severe and severe AS were further investigated to determine clinical status and surgical candidacy. Nonsurgical candidates were cross referenced with the PARTNER-B exclusion criteria to determine eligibility for TAVR. RESULTS: Symptomatic AS was present in 133 patients (16%). Fifty (38%) were considered nonsurgical candidates. Nonsurgical patients had higher STS score (11.1 ± 10.8 vs. 4.0 ± 3.3, P < 0.001). After applying PARTNERS-B exclusion criteria, only 18 patients (14%) were considered TAVR candidates. These findings indicate that to meet the recommended annual volume of 20-24 TAVR cases, a minimum of 150-170 symptomatic severe AS patients are required. CONCLUSION: In real world clinical practice, the prevalence of AS meeting PARTNERS-B criteria for TAVR can be low. These findings suggest that either high volume valvular centers or regional referral centers will need to be considered as part of the strategy to incorporate this new technology into clinical practice.

Persistent erythema with niacin is not attributable to aspirin resistance.

BACKGROUND: Niacin is suboptimally used in patients because it causes flushing and erythema. These side effects have been attributed to release of the vasodilating prostaglandin D2, generated in a reaction catalyzed by cyclooxygenase-1. Aspirin reduces but does not completely eliminate these side effects. Because some patients are resistant to its antiplatelet effects, we hypothesized that patients with persistent niacin-induced erythema might be aspirin resistant. METHODS: Platelet function studies (via the use of a whole-blood platelet function aggregometer [VerifyNow; Accumetrics, San Diego, CA] with end points of aspirin reaction unit [ARUs] and P2Y12 reaction units [PRUs]) were performed on 32 healthy, drug-free subjects before and after 324 mg of aspirin. A niacin skin test with the use of topical methylnicotinate was also performed before and after the administration of aspirin. Responses to methyl nicotinate were assessed by a reaction score and by counting the time to first visible redness (TTR). RESULTS: All subjects had an expected decrease in arachidonic acid induced platelet response (ARU 642.8 ± 47.20 before to 431.5 ± 41.1 after aspirin, P < .0001) without a significant change in the PRU. The reaction score and TTR were prolonged by aspirin at methylnicotinate concentrations ≥ 0.001 M. Although no subject had aspirin resistance (defined as ARU > 550), there was considerable variability in skin responses with erythema elicited in all subjects at the greatest concentrations. There was no difference in the ARU for subjects with TTR values above and below the mean, indicating that aspirin resistance does not explain the variation in skin responses to a topical niacin derivative. CONCLUSION: Aspirin resistance is unlikely to be a significant contributor to the persistent erythema and flushing in niacin-treated patients.

Pericardial fat and atrial conduction abnormalities in the Multiethnic Study of Atherosclerosis (MESA).

Pericardial fat (Pfat) overlies the cardiac surface including atria and their inter- and intra-conduction system. Through its local inflammatory effects, Pfat may predispose to atrial abnormalities that could be detected as changes in P-wave morphology in the 12-lead electrocardiogram (ECG). We evaluated the association between Pfat and ECG measurements of P wave and PR interval (referred to as P-wave indexes): PR duration (PR-dur), P-wave duration (P-dur), and P-wave terminal force (P-term), in the Multiethnic Study of Atherosclerosis (MESA). Participants with available Pfat measured by computed tomography (CT) and P-wave indexes measured by ECG were included (N = 996). Differences in P-wave indexes per 1 standard deviation difference in Pfat were tested in unadjusted linear regression analysis first, then adjusted for demographics (age, sex, and ethnicity), and further adjusted for measures of adiposity (BMI or waist circumference (WC)), or cardiovascular risk factors (hypertension (HTN), diabetes, and smoking). All P-wave indexes were significantly associated with Pfat in unadjusted analyses (regression-coefficient (ß) (95% CI): PR-dur (ms) 2.53 (1.02, 4.04), P-dur (ms) 2.59 (1.84, 3.35), P-term (µV·s) 0.25 (0.13, 0.36)). After demographics adjustment, P-dur (1.68 (0.87, 2.49)) and P-term (0.16 (0.04,0.28)), but not PR-dur (1.11 (-0.52, 2.74)) were associated with Pfat. No associations were significant after adjustment for BMI, WC, or cardiovascular disease (CVD) risk factors. BMI and WC, separately, were significantly associated with P-wave indexes in all models, including those that included Pfat as a covariate. BMI, but not WC, was associated with P-wave indexes when the two were entered into the same model. In conclusion, Pfat is associated with P-wave indexes, but not after adjusting for measures of adiposity or CVD risk factors. Among Pfat, BMI and WC, BMI had the most robust association with P-wave indexes. These findings raise doubts about potential local effects of Pfat on atrial electrophysiology and morphology.

Ablative fractionated erbium:YAG laser for the treatment of ice pick alar scars due to neodymium:YAG laser burns.

The authors present a case of ice pick scars forming in the nasal alar grooves of a patient who was treated with a 1064-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser for facial telangiectasias. Treatment options for these types of scars are reviewed and specifically we report the success of an ablative fractionated 2940-nm erbium:yttrium-aluminum-garnet (Er:YAG) laser.

Structural and kinetic characterization of myoglobins from eurythermal and stenothermal fish species.

Teleost myoglobin (Mb) proteins from four fish species inhabiting different temperature environments were used to investigate the relationship between protein function and thermal stability. Mb was isolated from yellowfin tuna (homeothermal warm), mackerel (eurythermal warm), and the Antarctic teleost Notothenia coriiceps (stenothermal cold). Zebrafish (stenothermal tropical) myoglobin was expressed from cloned cDNA. These proteins differed in oxygen affinity, as measured by O2 dissociation rates and P50 values, and thermal stability as measured by autooxidation rates. Mackerel Mb had the highest P50 value at 25 degrees C (3.7 mmHg), corresponding to the lowest O2 affinity, followed by zebrafish (1.0 mmHg), yellowfin tuna (1.0 mmHg), and N. coriiceps (0.6 mmHg). Oxygen dissociation rates and Arrhenius plots were similar between all teleost species in this study, with the exception of mackerel myoglobin, which was two-fold faster at all temperatures tested. Myoglobin from the Antarctic teleost had the highest autooxidation rate (0.44 h(-1)), followed by mackerel (0.26 h(-1)), zebrafish (0.22 h(-1)), and yellowfin tuna (0.088 h(-1)). Primary structural analysis revealed residue differences distributed throughout the polypeptide sequences, making it difficult to identify, which, if any, residues contribute to structural flexibility. However, analysis of molecular dynamics trajectories indicates that Mb from the eurythermal mackerel is predicted to be the most flexible protein within the D loop and FG turn. At the same time, it has the lowest O2 affinity and the highest O2 dissociation rates when compared to myoglobins from teleosts that appear to be less flexible in our dynamics simulations.