ECG findings in professional rugby players using international screening recommendations.

BackgroundWhile World Rugby guidelines do not mandate the inclusion of an electrocardiogram (ECG) for all players, this is required for entry into international rugby competitions. We, therefore, sought to describe sport-specific normative ECG values and evaluate the performance of contemporary athlete ECG guidelines in male and female professional rugby players.MethodsWe retrospectively analysed professional rugby players' ECGs (n=356, male 79%) obtained during preparticipation screening (2010-2022), comparing by sex and playing position (forwards vs backs). ECGs were categorised as normal 'training-related', borderline and abnormal findings, as defined by the 2017 International Recommendations.Results84% of players had one or more normal, 'training-related' findings, with males having a higher prevalence than females (91% vs 60%, pConclusionsThe application of contemporary ECG interpretation criteria resulted in a low positivity rate isolated to male players. These results help inform the logistic feasibility of ECG-inclusive screening, which is already required to enter major tournaments

Long-Term Corticosteroid-Sparing Immunosuppression for Cardiac Sarcoidosis.

Background Long-term corticosteroid therapy is the standard of care for treatment of cardiac sarcoidosis (CS). The efficacy of long-term corticosteroid-sparing immunosuppression in CS is unknown. The goal of this study was to assess the efficacy of methotrexate with or without adalimumab for long-term disease suppression in CS, and to assess recurrence and adverse event rates after immunosuppression discontinuation. Methods and Results Retrospective chart review identified treatment-naive CS patients at a single academic medical center who received corticosteroid-sparing maintenance therapy. Demographics, cardiac uptake of 18-fluorodeoxyglucose, and adverse cardiac events were compared before and during treatment and between those with persistent or interrupted immunosuppression. Twenty-eight CS patients were followed for a mean 4.1 (SD 1.5) years. Twenty-five patients received 4 to 8 weeks of high-dose prednisone (>30 mg/day), followed by taper and maintenance therapy with methotrexate±low-dose prednisone (low-dose prednisone, <10 mg/day). Adalimumab was added in 19 patients with persistently active CS or in those with intolerance to methotrexate. Methotrexate±low-dose prednisone resulted in initial reduction (88%) or elimination (60%) of 18-fluorodeoxyglucose uptake, and patients receiving adalimumab-containing regimens experienced improved (84%) or resolved (63%) 18-fluorodeoxyglucose uptake. Radiologic relapse occurred in 8 of 9 patients after immunosuppression cessation, 4 patients on methotrexate-containing regimens, and in no patients on adalimumab-containing regimens. Conclusions Corticosteroid-sparing regimens containing methotrexate with or without adalimumab is an effective maintenance therapy in patients after an initial response is confirmed. Disease recurrence in patients on and off immunosuppression support need for ongoing radiologic surveillance regardless of immunosuppression regimen

Relative Burden of Large CNVs on a Range of Neurodevelopmental Phenotypes

While numerous studies have implicated copy number variants (CNVs) in a range of neurological phenotypes, the impact relative to disease severity has been difficult to ascertain due to small sample sizes, lack of phenotypic details, and heterogeneity in platforms used for discovery. Using a customized microarray enriched for genomic hotspots, we assayed for large CNVs among 1,227 individuals with various neurological deficits including dyslexia (376), sporadic autism (350), and intellectual disability (ID) (501), as well as 337 controls. We show that the frequency of large CNVs (>1 Mbp) is significantly greater for ID–associated phenotypes compared to autism (p = 9.58×10−11, odds ratio = 4.59), dyslexia (p = 3.81×10−18, odds ratio = 14.45), or controls (p = 2.75×10−17, odds ratio = 13.71). There is a striking difference in the frequency of rare CNVs (>50 kbp) in autism (10%, p = 2.4×10−6, odds ratio = 6) or ID (16%, p = 3.55×10−12, odds ratio = 10) compared to dyslexia (2%) with essentially no difference in large CNV burden among dyslexia patients compared to controls. Rare CNVs were more likely to arise de novo (64%) in ID when compared to autism (40%) or dyslexia (0%). We observed a significantly increased large CNV burden in individuals with ID and multiple congenital anomalies (MCA) compared to ID alone (p = 0.001, odds ratio = 2.54). Our data suggest that large CNV burden positively correlates with the severity of childhood disability: ID with MCA being most severely affected and dyslexics being indistinguishable from controls. When autism without ID was considered separately, the increase in CNV burden was modest compared to controls (p = 0.07, odds ratio = 2.33)

PM00104 (Zalypsis®): A Marine Derived Alkylating Agent

PM00104 (Zalypsis®) is a synthethic tetrahydroisoquinolone alkaloid, which is structurally similar to many marine organisms. The compound has been proposed as a potential chemotherapeutic agent in the treatment of solid human tumors and hematological malignancies. PM00104 is a DNA binding agent, causing inhibition of the cell cycle and transcription, which can lead to double stranded DNA breaks. After rigorous pre-clinical testing, the drug has been evaluated in a number of phase II clinical trials. This manuscript provides a review of current trials and appraises the efficacy of PM00104 as a future cancer treatment

MAGNETIC ROTATION SPECTROSCOPY OF SINGLET METHYLENE

Author Institution: Department of Chemistry, University of California BerkeleyThe Doppler-limited spectra of singlet methylene $(\tilde{b} ^{l}B_{1}\leftarrow\tilde{a} ^{1}A_{1})$,have been observed by direct absorption and magnetic rotation spectroscopy (MRS). Since magnetic rotation is exhibited only by singlet methylene states that are coupled to the triplet manifold, this technique is extremely sensitive to even weak singlet-triplet perturbations. The magnetic activity is observed in greater than 80\% of transitions (studied between $16000 cm^{-1}$ and $17000 cm^{-1})$) indicating strong coupling between singlet and triplet manifolds. Large magnetic effects are observed in vibronic transitions originating from $7_{16}$, $4_{31}$, and $4_{32}$ levels, in good agreement with perturbation analysis of triplet methylene rotational LMR $spectra.^{1}$ This work will lead to a better understanding of electronic structure of methylene and a more accurate determination of the singlet-triplet splitting, as well as a re-evaluation of the $\tilde{b} ^{1}B_{1}\leftarrow\tilde{a} ^{1}A_{1}$ spectrum. $^{1}$T. J. Sears, private communication

Trabectedin in Soft Tissue Sarcomas

Soft tissue sarcomas are a group of rare tumors derived from mesenchymal tissue, accounting for about 1% of adult cancers. There are over 60 different histological subtypes, each with their own unique biological behavior and response to systemic therapy. The outcome for patients with metastatic soft tissue sarcoma is poor with few available systemic treatment options. For decades, the mainstay of management has consisted of doxorubicin with or without ifosfamide. Trabectedin is a synthetic agent derived from the Caribbean tunicate, Ecteinascidia turbinata. This drug has a number of potential mechanisms of action, including binding the DNA minor groove, interfering with DNA repair pathways and the cell cycle, as well as interacting with transcription factors. Several phase II trials have shown that trabectedin has activity in anthracycline and alkylating agent-resistant soft tissue sarcoma and suggest use in the second- and third-line setting. More recently, trabectedin has shown similar progression-free survival to doxorubicin in the first-line setting and significant activity in liposarcoma and leiomyosarcoma subtypes. Trabectedin has shown a favorable toxicity profile and has been approved in over 70 countries for the treatment of metastatic soft tissue sarcoma. This manuscript will review the development of trabectedin in soft tissue sarcomas

ULTRA SENSITIVE IR LASER ABSORPTION SPECTROSCOPY OF TRANSIENT RADICALS AND IONS

Author Institution: Department of Chemistry, University of California; Department of Chemistry, University of New MexicoIn this work, a tunable difference frequency laser system is employed to obtain high quality, Doppler-limited infrared spectra of transient molecular radicals generated by excimer laser photolysis, and molecular ions produced in an AC glow discharge. The response time of the high resolution, flash-kinetic ir spectrometer is $\lesssim 100$ nsec, with an absorption sensitivity of $\lesssim 0.5\%$ over a 100 cm pathlength, permitting detailed spectroscopic, kinetic, and photofragmentation studies of a wide variety of transient radicals. Data and analysis are presented on the $\nu_{1}$ and $\nu_{3}$ CH stretching spectra of singlet methylene over the region $2600 - 3050 cm^{-1}$. Strong interaction between the singlet and ground state triplet manifold is indicated by significant perturbations in the spectrum, and can be sensitively observed by magnetic modulation of the triplet coupled states. For obtaining molecular ion absorption spectra in an AC glow discharge, velocity modulation techniques are employed. By dual beam subtraction of laser amplitude noise, near shot noise sensitivity limits of $\lesssim 10^{-6} absorbance/Hz^{1/2}$ have been achieved. Data is presented on the $\nu_{1}$ DN stretching mode in $DNN^{+}$; transitions out to $J = 20$ in both P and R branch are observed for $(10^{0}0) \leftarrow (00^{0}0)$ and the hot band $(11^{1}0) \leftarrow (01^{1}0)$. Rotational constants for ground ground and excited states, vibrational frequencies, and $\ell$-type doubling constants for the $\nu_{2}$ excited states are reported. Rotational state distributions appear equilibrated in the liquid nitrogen cooled discharge and correspond to a 190 K temperature

The Cardiac Effects of COVID-19 on Young Competitive Athletes : Results from the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA)

The Outcomes Registry for Cardiac Conditions in Athletes (ORCCA) study is a large-scale prospective investigation evaluating the cardiovascular effects and outcomes of SARS-CoV-2 infection on young competitive athletes. This review provides an overview of the key results from the ORCCA study. Results from the ORCCA study have provided important insights into the clinical impact of SARS-CoV-2 infection on the cardiovascular health of young competitive athletes and informed contemporary screening and return to sport practices. Key results include defining a low prevalence of both cardiac involvement and adverse cardiovascular outcomes after SARS-CoV-2 infection and evaluating the utility of a return-to-play cardiac evaluation. Future aims of the ORCCA study include the longer-term evaluation of cardiovascular outcomes among athletes post-SARS-CoV-2 infection and the transition to investigating outcomes in young athletes with potentially high-risk genetic or structural cardiac diagnoses.Medicine, Faculty ofNon UBCReviewedFacultyResearche

The Cardiac Effects of COVID-19 on Young Competitive Athletes: Results from the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA)

The Outcomes Registry for Cardiac Conditions in Athletes (ORCCA) study is a large-scale prospective investigation evaluating the cardiovascular effects and outcomes of SARS-CoV-2 infection on young competitive athletes. This review provides an overview of the key results from the ORCCA study. Results from the ORCCA study have provided important insights into the clinical impact of SARS-CoV-2 infection on the cardiovascular health of young competitive athletes and informed contemporary screening and return to sport practices. Key results include defining a low prevalence of both cardiac involvement and adverse cardiovascular outcomes after SARS-CoV-2 infection and evaluating the utility of a return-to-play cardiac evaluation. Future aims of the ORCCA study include the longer-term evaluation of cardiovascular outcomes among athletes post-SARS-CoV-2 infection and the transition to investigating outcomes in young athletes with potentially high-risk genetic or structural cardiac diagnoses