Patients undergoing recurrent CT exams: assessment of patients with non-malignant diseases,reasons for imaging and imaging appropriateness

To determine percent of patients without malignancy and ≤ 40 years of age with high cumulative radiation doses through recurrent CT exams and assess imaging appropriateness. From the cohort of patients who received cumulative effective dose (CED) of ≥ 100 mSv over a 5-year period, a sub-set was identified with non-malignant disease. The top 50 clinical indications leading to multiple CTs were determined. Clinical decision support (CDS) system scores were analyzed using a widely adopted standard of 1–3 (red) as “not usually appropriate,” 4–6 (yellow) “may or may not be appropriate,” and 7–9 (green) “usually appropriate.” Clinicians reviewed patient records to assess compliance with appropriate use criteria (AUC). 9.6% of patients in our series were with non-malignant conditions and 1.4% with age ≤ 40 years. CDS scores (rounded) were 2% red, 38% yellow, 27% green, and 33% unscored CTs. Clinical society guidelines for CT exams, wherever available, were followed in 87.5 to 100% of cases. AUCs were not available for several clinical indications as also referral guidelines for serial CT imaging. More than half of CT exams were unrelated to follow-up of a primary chronic disease. We are faced with a situation wherein patients in age ≤ 40 years require or are thought to require many CT exams over the course of a few years but the radiation risk creates concern. There is a fair number of conditions for which AUC are not available. Suggested solutions include development of CT scanners with lesser radiation dose and further development of appropriateness criteria.     

From altus to parvus: cardiac fatigue in athletes: reply

We would like to thank Professor Erdem Kasikcioglu for his interestin our article. In response to the initial question of why exhaustivephysical activity suppresses diastolic function,     

Neutralizing antibodies to African swine fever virus proteins p30, p54, and p72 are not sufficient for antibody-mediated protection

Although antibody-mediated immune mechanisms have been shown to be important in immunity to ASF, it remains unclear what role virus neutralizing antibodies play in the protective response. Virus neutralizing epitopes have been identified on three viral proteins, p30, p54, and p72. To evaluate the role(s) of these proteins in protective immunity, pigs were immunized with baculovirus-expressed p30, p54, p72, and p22 from the pathogenic African swine fever virus (ASFV) isolate Pr4. ASFV specific neutralizing antibodies were detected in test group animals. Following immunization, animals were challenged with 10(4) TCID(50) of Pr4 virus. In comparison to the control group, test group animals exhibited a 2-day delay to onset of clinical disease and reduced viremia levels at 2 days postinfection (DPI); however, by 4 DPI, there was no significant difference between the two groups and all animals in both groups died between 7 and 10 DPI. These results indicate that neutralizing antibodies to these ASFV proteins are not sufficient for antibody-mediated protection.     

Detection of microcystin synthetase genes in health food supplements containing the freshwater cyanobacterium Aphanizomenon flos-aquae.

In this study we investigated the presence of toxin-producing cyanobacterial contaminants in food supplements manufactured from blooms of the non-toxic freshwater cyanobacterium Aphanizomenon flos-aquae. Previous reports investigating the contamination of health food supplements with toxin-producing cyanobacteria have used chemical and or biochemical methods such as HPLC, ELISA and protein phosphatase assays. Whilst these studies have drawn attention to the presence of hepatotoxic microcystins in some commercially available food supplements, the methods used do not provide any information on the source of the contaminant. Such information would be useful for the quality control of food supplements produced for human consumption. In this study we applied a molecular technique, involving the amplification of the 16s rRNA gene, the phycocyanin operon, and two genes of the microcystin synthetase gene cluster to show that all 12 food supplement samples, sourced from various internet distributors and containing non-toxic A. flos-aquae, also contained toxigenic cyanobacteria. Sequencing of the microcystin synthetase genes detected in all of the food supplements showed that M. aeruginosa was the organism responsible for the production of microcystins in the samples. The presence of microcystins in the food supplements was confirmed by ELISA, with concentrations within the range of 0.1--4.72 microgg(-1) (microcystin-LR equivalents). Given that the molecular methods applied here are highly sensitive, and show good agreement with the results obtained from ELISA, we believe that they could potentially be used as a quality control technique for food products that contain cyanobacteria.     

Myocardial tissue remodeling after orthotopic heart transplantation: a pilot cardiac magnetic resonance study

After orthotopic heart transplantation (OHT), the allograft undergoes characteristic alterations in myocardial structure, including hypertrophy, increased ventricular stiffness, ischemia, and inflammation, all of which may decrease overall graft survival. Methods to quantify these phenotypes may clarify the pathophysiology of progressive graft dysfunction post-OHT. We performed cardiac magnetic resonance (CMR) with T1 mapping in 26 OHT recipients (mean age 47?±?7 years, 30?% female, median follow-up post-OHT 6 months) and 30 age-matched healthy volunteers (mean age 50.5?±?15 years; LVEF 63.5?±?7?%). OHT recipients had a normal left ventricular ejection fraction (LVEF 65.3?±?11?%) with higher LV mass relative to age-matched healthy volunteers (114?±?27 vs. 85.8?±?18 g; p?<?0.001). There was no late gadolinium enhancement in either group. Both myocardial extracellular volume fraction (ECV) and intracellular lifetime of water (τ_ic), a measure of cardiomyocyte hypertrophy, were higher in patients post-OHT (ECV: 0.39?±?0.06 vs. 0.28?±?0.03, p?<?0.0001; τ_ic: 0.12?±?0.08 vs. 0.08?±?0.03, p?<?0.001). ECV was associated with LV mass (r?=?0.74, p?<?0.001). In follow-up, OHT recipients with normal biopsies by pathology (ISHLT grade 0R) in the first year post-OHT exhibited a lower ECV relative to patients with any rejection ≥2R (0.35?±?0.02 for 0R vs. 0.45?±?0, p?<?0.001). Higher ECV but not LVEF was significantly associated with a reduced rejection-free survival. After OHT, markers of tissue remodeling by CMR (ECV and τ_ic) are elevated and associated with myocardial hypertrophy. Interstitial myocardial remodeling (by ECV) is associated with cellular rejection. Further research on the impact of graft preservation and early immunosuppression on tissue-level remodeling of the allograft is necessary to delineate the clinical implications of these findings.     

Persistent and reversible cardiac dysfunction among amateur marathon runners.

AIMS: Transient systolic and diastolic abnormalities in ventricular function have previously been documented during endurance sports. However, these described alterations may be limited by the techniques applied. We sought, using less load-dependent methods, to characterize both the extent and the chronology of the cardiac changes associated with endurance events. METHODS AND RESULTS: Transthoracic echocardiography (TTE) was performed prior to, immediately after, and approximately 1 month after completion of the 2003 Boston Marathon in 20 amateur athletes. TTE included two-dimensional, spectral and tissue Doppler (TD) and flow propagation velocity (V(p)). After completion of the marathon, global measures of left ventricular (LV) systolic function were unchanged (EF 59 +/- 6 vs. 61 +/- 4% post, P = 0.14), whereas TD-derived measures of LV systolic function [septal strain -23 +/- 5 vs. -17 +/- 4%, P = 0.007; septal strain rate (SR) -1.5 +/- 0.3 vs. -1.1+/- 0.2 s(-1), P = 0.007] and right ventricular (RV) systolic function (RV apical strain -33 +/- 4 vs. -27 +/- 5%, P = 0.001; RV apical SR -2.4 +/- 0.7 vs. -1.8 +/- 0.5, P = 0.002) were reduced. Significant changes in transmitral velocity (E/A ratio 2.0 +/- 0.5 vs.1.3 +/- 0.3, P = 0.005) and TD indices of LV and RV diastolic function (E(a) septal 9.5 +/- 1.8 vs. 8.1 +/- 1.2 cm/s post-marathon, P = 0.01) were also observed, indicating an inherent alteration in LV relaxation. Although all indices of LV and RV systolic function had returned to normal on follow-up, there were persistent diastolic abnormalities (RV E(a), 11.5 +/- 1.5 cm/s pre-marathon vs. 10.0 +/- 1.6 cm/s follow-up, P = 0.01). CONCLUSION: Marathon running leads to transient systolic and more persistent diastolic dysfunction of both the LV and the RV.     

Consider Myocarditis When Patients Treated with Immune Checkpoint Inhibitors Present with Ocular Symptoms

Immune checkpoint inhibitors (ICIs) have been associated with neurological immune related adverse events (irAE-N) and patients with ICI toxicity may present with neurological or ocular symptoms. Furthermore, patients on ICI may initially present to oncology or neurology. We report a case series of 3 patients treated with ICIs presenting with diplopia or ptosis, found to have concurrent myocarditis in addition to immune-related myopathy (irMyopathy) or myasthenia gravis (irMG). None of the patients described cardiac symptoms, underscoring the importance of screening for myocarditis in patients presenting with diplopia and/or other neuromuscular symptoms which may suggest either irMyopathy or irMG.     

Differential sensitivities of mouse strains to morphine and [Dmt1]DALDA analgesia

[Dmt(1)]DALDA (H-Dmt-D-Arg-Phe-Lys-NH(2)), is a highly potent and selective mu-opioid agonist. Nevertheless, systemic [Dmt(1)]DALDA retained its analgesic actions in MOR-1 knockout animals and CXBK mice despite the inactivity of morphine in these mice. [Dmt(1)]DALDA was 6-fold less potent in C57BL/6J mice than in CD-1 mice, whereas morphine potency did not differ between the two strains. Thus, [Dmt(1)]DALDA is a highly selective mu-opioid analgesic with significant pharmacological differences with the prototypic mu-opioid morphine.