Imaging of pediatric extragonadal pelvic soft tissue tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

The most common pediatric extragonadal pelvic cancers include germ cell tumors, sacrococcygeal teratomas, and rhabdomyosarcomas (arising from the urinary bladder, prostate, paratesticular tissues, vagina, uterus, and perineum). This paper describes the radiological and nuclear medicine features of these entities and provides consensus-based recommendations for the assessment at diagnosis, during, and after treatment.

Elimination of the Out-of-Pocket Charge for Children's Primary Care Visits: An Application of Value-Based Insurance Design.

OBJECTIVE: To evaluate the impact of a value-based insurance design for primary care among children. STUDY DESIGN: A retrospective analysis of health care claims data on 25 950 children (<18 years of age) was conducted. Individuals were enrolled in a large employer's health plans when zero out-of-pocket cost for primary care physician visits was implemented. A rigorous propensity score matching process was used to generate a control group of equal size from a database of other employer-sponsored insurees. Multivariate difference-in-differences models estimated the effect of zero out-of-pocket cost on 21 health services and cost outcomes 24 months after intervention. RESULTS: Zero out-of-pocket cost for primary care was associated with significant increases (P < .01) in primary care physician visits (+32 per 100 children), as well as decreases in emergency department (-5 per 100 children) and specialist physician visits (-12 per 100 children). The number of prescription drug fills also declined (-20 per 100 children), yet medication adherence for 3 chronic conditions was unaffected. The receipt of well child visits and 4 recommended vaccinations were all significantly (P < .05) greater under the new plan design feature. Employer costs for primary care increased significantly (P < .01) in association with greater utilization ($29 per child), but specialist visit costs declined (-$12 per child) and total health care costs per child did not exhibit a statistically significant increase. CONCLUSION: This novel application of value-based insurance design warrants broader deployment and assessment of its longer term outcomes. As with recommended preventive services, policymakers should consider exempting primary care from health insurance cost-sharing.

Relaxin suppresses atrial fibrillation by reversing fibrosis and myocyte hypertrophy and increasing conduction velocity and sodium current in spontaneously hypertensive rat hearts.

RATIONALE: Atrial fibrillation (AF) contributes significantly to morbidity and mortality in elderly and hypertensive patients and has been correlated to enhanced atrial fibrosis. Despite a lack of direct evidence that fibrosis causes AF, reversal of fibrosis is considered a plausible therapy. OBJECTIVE: To evaluate the efficacy of the antifibrotic hormone relaxin (RLX) in suppressing AF in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: Normotensive Wistar-Kyoto (WKY) and SHR were treated for 2 weeks with vehicle (WKY+V and SHR+V) or RLX (0.4 mg/kg per day, SHR+RLX) using implantable mini-pumps. Hearts were perfused, mapped optically to analyze action potential durations, intracellular Ca²âº transients, and restitution kinetics, and tested for AF vulnerability. SHR hearts had slower conduction velocity (CV; P<0.01 versus WKY), steeper CV restitution kinetics, greater collagen deposition, higher levels of transcripts for transforming growth factor-ß, metalloproteinase-2, metalloproteinase-9, collagen I/III, and reduced connexin 43 phosphorylation (P<0.05 versus WKY). Programmed stimulation triggered sustained AF in SHR (n=5/5) and SHR+V (n=4/4), but not in WKY (n=0/5) and SHR+RLX (n=1/8; P<0.01). RLX treatment reversed the transcripts for fibrosis, flattened CV restitution kinetics, reduced action potential duration at 90% recovery to baseline, increased CV (P<0.01), and reversed atrial hypertrophy (P<0.05). Independent of antifibrotic actions, RLX (0.1 µmol/L) increased Na⁺ current density, INa (≈2-fold in 48 hours) in human cardiomyocytes derived from inducible pluripotent stem cells (n=18/18; P<0.01). CONCLUSIONS: RLX treatment suppressed AF in SHR hearts by increasing CV from a combination of reversal of fibrosis and hypertrophy and by increasing INa. The study provides compelling evidence that RLX may provide a novel therapy to manage AF in humans by reversing fibrosis and hypertrophy and by modulating cardiac ionic currents.

Large-Scale SARS-CoV-2 Antigen Testing With Real-World Specimens.

Real-world data are needed to establish SARS-CoV-2 rapid antigen testing (RAT) as an effective and reliable approach for SARS-CoV-2 screening. This study included 1,952,931 individuals who provided upper respiratory specimens during SARS-CoV-2 screening at CityMD urgent care locations in the New York metropolitan area from October 2020 to March 2021. Positive and negative results, as determined by the BD Veritor™ System for Rapid Detection of SARS-CoV-2 antigen (Veritor), were obtained for all individuals, with reflex reverse transcriptase-polymerase chain reaction (RT-PCR) testing performed on a case-by-case basis, per standard of care. Using verification bias adjustment, two alternative model assumptions were utilized for RAT results with missing reflex RT-PCR results. The worst antigen diagnostic performance estimates asserted that missing RT-PCR results would show a distribution similar to those RT-PCR results actually obtained, based on symptom category. The best antigen diagnostic performance estimates asserted that individuals without RT-PCR results had a clinical presentation consistent with RAT results, and, therefore, missing RT-PCR results would agree with RAT results. For patients with symptoms or high-risk exposure, 25.3% (n = 86,811/343,253) of RAT results were positive; vs. 3.4% (n = 53,046/1,559,733) positive for asymptomatic individuals without high-risk exposure. Reflex RT-PCR results were obtained from 46.3% (n = 158,836/343,253) and 13.8% (n = 215,708/1,559,733) of symptomatic and asymptomatic individuals, respectively. RT-PCR confirmed 94.4% (4,265/4,518) of positive and 90.6% (139,759/154,318) of negative RAT results in symptomatic individuals; and confirmed 83.4% (6,693/8,024) of positive and 95.3% (197,955/207,684) of negative RAT results in asymptomatic individuals. Applied assumptions for missing reflex RT-PCR results led to worst performance sensitivity estimates of 77.2 and 38.5% in the symptomatic and asymptomatic populations, respectively; assumptions for best performance estimates led to sensitivity values of 85.6 and 84.2%, respectively. Specificity values, regardless of assumptions or symptom category, ranged from 97.9-99.9%. At 10% SARS-CoV-2 prevalence, RAT positive predictive value was 86.9 and 99.0% for worst and best performance estimates across the total population, respectively; negative predictive values were >95% regardless of the applied assumption. Veritor test performance was consistent with that listed in the manufacturer instructions for use for symptomatic individuals. Real-world evidence should be gathered on RATs to support their efficacy as SARS-CoV-2 persists.

SARS-CoV-2 pandemic in New York metropolitan area: the view from a major urgent care provider.

PURPOSE: Tracking severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing and positivity trends is crucial for understanding the trajectory of the pandemic. We describe demographic and clinical characteristics, testing, and positivity rates for SARS-CoV-2 among 2.8 million patients evaluated at an urgent care provider. METHODS: We conducted a retrospective study of patients receiving a diagnostic or serologic test for SARS-CoV-2 between March 1, 2020 and July 20, 2021 at 115 CityMD locations in the New York metropolitan area. Temporal trends in SARS-CoV-2 positivity by diagnostic and serologic tests stratified by age, sex, race/ethnicity, and borough of residence were assessed. RESULTS: During the study period, 6.1 million COVID diagnostic and serological tests were performed on 2.8 million individuals. Testing levels were higher among 20-29-year-old, non-Hispanic White, and female patients compared with other groups. About 35% were repeat testers. Reverse transcriptase polymerase chain reaction positivity was higher in non-Hispanic Black (7.9%), Hispanic (8.2%), and Native American (8.2%) compared to non-Hispanic White (5.7%) patients. Overall seropositivity was estimated to be 22.1% (95% confidence interval: 22.0-22.2) and was highest among 10-14 year olds (27.9%), and non-Hispanic Black (26.0%) and Hispanic (31.0%) testers. CONCLUSION: Urgent care centers can provide broad access to diagnostic testing and critical evaluation for ambulatory patients during pandemics, especially in population-dense, urban epicenters.  Urgent care center electronic medical records data can provide in-depth surveillance during pandemics complementary to citywide health department data sources.

The emergence, surge and subsequent wave of the SARS-CoV-2 pandemic in New York metropolitan area: The view from a major region-wide urgent care provider.

BACKGROUND: Describing SARS-CoV-2 testing and positivity trends among urgent care users is crucial for understanding the trajectory of the pandemic. OBJECTIVE: To describe demographic and clinical characteristics, positivity rates, and repeat testing patterns among patients tested for SARS-CoV-2 at CityMD, an urgent care provider in the New York City metropolitan area. DESIGN: Retrospective study of all persons testing for SARS-CoV-2 between March 1, 2020 and January 8, 2021 at 115 CityMD locations in the New York metropolitan area. PATIENTS: Individuals receiving a SARS-CoV-2 diagnostic or serologic test. MEASUREMENTS: Test and individual level SARS-CoV-2 positivity by PCR, rapid antigen, or serologic tests. RESULTS: During the study period, 3.4 million COVID tests were performed on 1.8 million individuals. In New York City, CityMD diagnosed 268,298 individuals, including 17% of all reported cases. Testing levels were higher among 20-29 year olds, non-Hispanic Whites, and females compared with other groups. About 24.8% (n=464,902) were repeat testers. Test positivity was higher in non-Hispanic Black (6.4%), Hispanic (8.0%), and Native American (8.0%) patients compared to non-Hispanic White (5.4%) patients. Overall seropositivity was estimated to be 21.7% (95% Confidence Interval [CI]: 21.6-21.8) and was highest among 10-14 year olds (27.3%). Seropositivity was also high among non-Hispanic Black (24.5%) and Hispanic (30.6%) testers, and residents of the Bronx (31.3%) and Queens (30.5%). Using PCR as the gold standard, SARS-CoV-2 rapid tests had a false positive rate of 5.4% (95%CI 5.3-5.5). CONCLUSION: Urgent care centers can provide broad access to critical evaluation, diagnostic testing and treatment of a substantial number of ambulatory patients during pandemics, especially in population-dense, urban epicenters.

Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling.

Ventricular tachycardia (VT) is the most common and potentially lethal complication following myocardial infarction (MI). Biological correction of the conduction inhomogeneity that underlies re-entry could be a major advance in infarction therapy. As minimal increases in conduction of infarcted tissue markedly influence VT susceptibility, we reasoned that enhanced propagation of the electrical signal between non-excitable cells within a resolving infarct might comprise a simple means to decrease post-infarction arrhythmia risk. We therefore tested lentivirus-mediated delivery of the gap-junction protein Connexin 43 (Cx43) into acute myocardial lesions. Cx43 was expressed in (myo)fibroblasts and CD45+ cells within the scar and provided prominent and long lasting arrhythmia protection in vivo. Optical mapping of Cx43 injected hearts revealed enhanced conduction velocity within the scar, indicating Cx43-mediated electrical coupling between myocytes and (myo)fibroblasts. Thus, Cx43 gene therapy, by direct in vivo transduction of non-cardiomyocytes, comprises a simple and clinically applicable biological therapy that markedly reduces post-infarction VT.

Relaxin suppresses atrial fibrillation in aged rats by reversing fibrosis and upregulating Na+ channels.

BACKGROUND: Atrial fibrillation (AF) contributes significantly to morbidity and mortality in elderly patients and has been correlated with enhanced age-dependent atrial fibrosis. Reversal of atrial fibrosis has been proposed as therapeutic strategy to suppress AF. OBJECTIVE: To test the ability of relaxin to reverse age-dependent atrial fibrosis and suppress AF. METHODS: Aged F-344 rats (24 months old) were treated with subcutaneous infusion of vehicle or relaxin (0.4 mg/kg/day) for 2 weeks. Rat hearts were excised, perfused on a Langendorff apparatus, and stained with voltage and Ca(2+) indicator dyes. Optical mapping and programmed electrical stimulation was used to test arrhythmia vulnerability and changes in electrophysiological characteristics. Changes in protein expression and Na(+) current density (INa) were measured by tissue immunofluorescence and whole-cell patch clamp technique. RESULTS: In aged rats, sustained AF was readily induced with a premature pulse (n = 7/8) and relaxin treatment suppressed sustained AF by a premature impulse or burst pacing (n = 1/6) (P < .01). Relaxin significantly increased atrial action potential conduction velocity and decreased atrial fibrosis. Relaxin treatment increased Nav1.5 expression (n = 6; 36% ± 10%) and decreased total collagen and collagen I (n = 5-6; 55%-66% ± 15%) in aged atria (P < .05) and decreased collagen I and III and TGF-ß1 mRNA (P < .05). Voltage-clamp experiments demonstrated that relaxin treatment (100 nM for 2 days) increased atrial INa by 46% ± 4% (n = 12-13/group, P < .02). CONCLUSION: Relaxin suppresses AF through an increase in atrial conduction velocity by decreasing atrial fibrosis and increasing INa. These data provide compelling evidence that relaxin may serve as an effective therapy to manage AF in geriatric patients by reversing fibrosis and modulating cardiac ionic currents.

Ranolazine stabilizes cardiac ryanodine receptors: a novel mechanism for the suppression of early afterdepolarization and torsades de pointes in long QT type 2.

BACKGROUND: Ranolazine (Ran) is known to inhibit multiple targets, including the late Na(+)current, the rapid delayed rectifying K(+)current, the L-type Ca(2+)current, and fatty acid metabolism. Functionally, Ran suppresses early afterdepolarization (EADs) and torsades de pointes (TdP) in drug-induced long QT type 2 (LQT2) presumably by decreasing intracellular [Na(+)](i) and Ca(2+)overload. However, simulations of EADs in LQT2 failed to predict their suppression by Ran. OBJECTIVE: To elucidate the mechanism(s) whereby Ran alters cardiac action potentials (APs) and cytosolic Ca(2+)transients and suppresses EADs and TdP in LQT2. METHODS: The known effects of Ran were included in simulations (Shannon and Mahajan models) of rabbit ventricular APs and Ca(2+)transients in control and LQT2 models and compared with experimental optical mapping data from Langendorff rabbit hearts treated with E4031 (0.5 µM) to block the rapid delayed rectifying K(+)current. Direct effects of Ran on cardiac ryanodine receptors (RyR2) were investigated in single channels and changes in Ca(2+)-dependent high-affinity ryanodine binding. RESULTS: Ran (10 µM) alone prolonged action potential durations (206 ± 4.6 to 240 ± 7.8 ms; P <0.05); E4031 prolonged action potential durations (204 ± 6 to 546 ± 35 ms; P <0.05) and elicited EADs and TdP that were suppressed by Ran (10 µM; n = 7 of 7 hearts). Simulations (Shannon but not Mahajan model) closely reproduced experimental data except for EAD suppression by Ran. Ran reduced open probability (P(o)) of RyR2 (half maximal inhibitory concentration = 10 ± 3 µM; n = 7) in bilayers and shifted half maximal effective concentration for Ca(2+)-dependent ryanodine binding from 0.42 ± 0.02 to 0.64 ± 0.02 µM with 30 µM Ran. CONCLUSIONS: Ran reduces P(o) of RyR2, desensitizes Ca(2+)-dependent RyR2 activation, and inhibits Ca(i) oscillations, which represents a novel mechanism for its suppression of EADs and TdP.

Identification, pharmacologic considerations, and management of prostatitis.

BACKGROUND: Prostatitis is a collection of signs and symptoms that occur as a result of inflammation or swelling of the prostate gland. There are many different causes for prostatitis, including infection; occasionally no clear etiology for the inflammation is found. Effective treatment often depends on identification of the cause, but a microbiologic organism is not always detectable, especially in cases of chronic prostatitis. OBJECTIVE: The aim of this article was to review identification and treatment options for prostatitis, including pharmacologic and nonpharmacologic interventions. METHODS: Relevant information was identified through a search of MEDLINE (1966-June 2010), International Pharmaceutical Abstracts (1970-June 2010), and EMBASE (1947-June 2010). Randomized, controlled trials that examined prostate cancer, benign prostatic hypertrophy, or procedures related to the prostate (ie, biopsies) were excluded. RESULTS: A working classification system for prostatitis was developed in 1999, but there are few randomized controlled trials that distinguish between the various treatment options. Bacterial prostatitis can be acute or chronic but always requires some degree of antimicrobial therapy. Pharmacologic features of fluoroquinolones make them the preferred agents for most patients. These antibiotics can become trapped in a chronically inflamed prostate due to pH differences between prostatic tissue and serum. Many fluoroquinolones have penetration ratios (prostate level:serum level) of up to 4:1. A study in European men (N = 117) who received levofloxacin 500 mg/d with a diagnosis of chronic bacterial prostatitis demonstrated clinical success rates of 92% (95% CI 84.8%-96.5%), 77.4% (95% CI, 68.2-84.9%), 66.0% (95% CI, 56.2%-75.0%), and 61.9% (95% CI, 51.9%-71.2%) at 5-12 days, 1 month, 3 months, and 6 months after treatment. Additionally, there have been numerous randomized, placebo-controlled trials in patients with chronic prostatitis that have studied α-blockers, steroid inhibitors, anti-inflammatory agents, and bioflavonoids. Treatment responses to α-blockers appear to be greater with longer durations of therapy in α-blocker-naïve patients (National Institutes of Health-Chronic Prostatitis Symptom Index [NIH-CPSI] score reduction of at least 3.6 points after 6 weeks of tamsulosin therapy [P = 0.04] and up to 14.3 and 9.9 point NIH-CPSI score reductions with 14 weeks of terazosin and 24 weeks of alfuzosin therapy, respectively [P = 0.01 for both]). Combination therapy with an α-blocker, an anti-inflammatory, and a muscle relaxant does not appear to offer significant advantages over monotherapy (12.7 vs 12.4 point reduction in NIH-CPSI scores) and a stepwise approach to therapy involving antibiotics followed by bioflavonoids and then α-blockers appears to effectively reduce symptoms for up to 1 year in patients with chronic prostatitis (mean NIH-CPSI point reduction of 9.5 points compared with baseline, P < 0.0001). Patients who have had multiple unsuccessful treatment regimens may benefit from direct stimulation of the pelvic muscles through electromagnetic or electroacupuncture therapy. CONCLUSIONS: Prostatitis can resemble various other medical conditions but proper classification and an understanding of the pharmacologic features and expectations of the medications used to treat it can help identify effective treatment strategies. Fluoroquinolones are the preferred agents for treating bacterial causes of prostatitis and have demonstrated efficacy in some cases of chronic prostatitis when an organism has not been identified. However, the use of agents with anti-inflammatory or antiadrenergic properties may be necessary in combination with or after trying antimicrobial agents.

Simultaneous dual coronary very late stent thrombosis following noncardiac surgery.

Challenges arise in the care of patients with drug-eluting stents (DES) undergoing noncardiac surgery. The risk of bleeding during surgery must be balanced with the risk of stent thrombosis from interrupted dual antiplatelet therapy. We report a case of a patient with simultaneous stent thrombosis in two coronary arteries following discontinuation of clopidogrel for an elective noncardiac surgery 3 years after DES placement.