Comparing Flaxseed and Perindopril in the Prevention of Doxorubicin and Trastuzumab-Induced Cardiotoxicity in C57Bl/6 Mice.

BACKGROUND: Two anti-cancer agents, doxorubicin (DOX) and trastuzumab (TRZ), are commonly used in the management of breast cancer in women. Despite their efficacy in reducing the morbidity and mortality of individuals with breast cancer, the use of these agents is limited by adverse cardiotoxic side effects. Both the nutraceutical agent flaxseed (FLX) and the pharmaceutical drug perindopril (PER) have been studied individually in the prevention of chemotherapy-mediated cardiac dysfunction. The objective of this study was to determine whether the prophylactic administration of FLX is comparable and/or synergistic with PER in preventing DOX + TRZ-induced cardiotoxicity. METHODS: Over a six-week period, 81 wild-type C57Bl/6 female mice (8-12 weeks old) were randomized to receive regular chow (RC) or 10% FLX-supplemented diets with or without PER (3 mg/kg/week; oral gavage). Starting at week 4, mice were randomized to receive a weekly injection of saline or DOX (8 mg/kg) + TRZ (3 mg/kg). Serial echocardiography was conducted weekly and histological and biochemical analyses were performed at the end of the study. RESULTS: In mice treated with RC + DOX + TRZ, left ventricular ejection (LVEF) decreased from 75 ± 2% at baseline to 37 ± 3% at week 6. However, prophylactic treatment with either FLX, PER, or FLX + PER partially preserved left ventricular systolic function with LVEF values of 61 ± 2%, 62 ± 2%, and 64 ± 2%, respectively. The administration of FLX, PER, or FLX + PER was also partially cardioprotective in preserving cardiomyocyte integrity and attenuating the expression of the inflammatory biomarker NF-κB due to DOX + TRZ administration. CONCLUSION: FLX was equivalent to PER at preventing DOX + TRZ-induced cardiotoxicity in a chronic in vivo murine model.

Prevalence and Functional Implication of Silent Coronary Artery Disease in Marathon Runners Over 40 Years of Age: The MATCH-40 Study.

BACKGROUND: Marathon participation is becoming increasingly popular among individuals ≥40 years of age. Little is known about the prevalence of subclinical coronary artery disease (CAD) and corresponding ischemia in this patient population. The study objectives are: (1) to characterize the prevalence of silent CAD in marathoners ≥ 40 years old using cardiac computed tomography angiography (CCT); and (2) if subclinical CAD was detected, to determine the functional significance of occult lesions by stress echocardiography (SE). METHODS: Marathoners aged ≥ 40 years who completed a full marathon between 2018 and 2019 were recruited to undergo a prospective CCT. Coronary artery stenosis was graded as zero, mild (1%-49%), moderate (50%-69%), or severe (> 70%). All study participants diagnosed with mild-to-severe atherosclerotic CAD on CCT further underwent functional imaging with exercise treadmill SE. RESULTS: A total of 65 individuals (53 ± 7 years, 65% males, 24 ± 3 kg/m2) underwent a prospective CCT within 12 months of marathon completion. Of the total study population, 13 participants (20%) were diagnosed with CAD, of whom 10 (77%) had mild disease, 1 (8%) had moderate disease, and 2 (15%) had severe disease by CCT. Despite the identification of subclinical CAD on CCT, none of the 13 patients had any evidence of inducible ischemia on SE. CONCLUSIONS: This is the first study to incorporate both CCT and SE in the evaluation of subclinical CAD in marathoners ≥40 years old. Although the overall prevalence of anatomic CAD was 20%, there was no evidence of functional ischemia in this highly competitive cohort.

CONTEXTE: Les marathons ont gagné en popularité auprès des individus âgés de 40 ans ou plus. On en sait toutefois peu sur la prévalence de la coronaropathie subclinique et de l'ischémie qui lui est associée dans cette population de patients. L'étude visait à 1) caractériser la prévalence de la coronaropathie silencieuse chez les marathoniens âgés de 40 ans ou plus à l'aide d'une angiographie cardiaque par tomodensitométrie (ACTDM) si une coronaropathie subclinique était détectée, à déterminer l'importance fonctionnelle des lésions occultes par une échocardiographie d'effort (EE). MÉTHODOLOGIE: Des marathoniens âgés de 40 ans ou plus ayant réalisé un marathon entre 2018 et 2019 ont été recrutés et soumis à une ACTDM prospective. Les sténoses des artères coronaires étaient classées selon une échelle allant de zéro, légère (1 à 49 %), modérée (50 à 69 %) à sévère (> 70 %). Tous les participants à l'étude ayant reçu un diagnostic de coronaropathie athéroscléreuse légère à sévère à la suite de l'ACTDM ont été soumis à une imagerie fonctionnelle avec EE sur tapis roulant. RÉSULTATS: Au total, 65 sujets (53 ± 7 ans, 65 % d'hommes, 24 ± 3 kg/m2) ont été soumis à une ACTDM prospective dans un délai de 12 mois à la suite de leur dernier marathon. Dans l'ensemble de la population à l'étude, 13 participants (20 %) ont reçu un diagnostic de coronaropathie; 10 (77 %) présentaient une maladie bénigne, 1 (8 %) présentait une maladie modérée et 2 (15 %) présentaient une maladie sévère selon l'ACTDM. Même si une coronaropathie subclinique a été diagnostiquée lors de l'ACTDM, aucun des 13 patients ne présentait de signe d'ischémie inductible à l'EE. CONCLUSIONS: Il s'agit de la première étude à utiliser l'ACTDM et l'EE pour évaluer la présence d'une coronaropathie chez des marathoniens âgés de 40 ou plus. Même si la prévalence globale de la coronaropathie anatomique était de 20 %, il n'y avait aucun signe d'ischémie fonctionnelle au sein de cette cohorte hautement compétitive.

Earlier radiosurgery leads to better pain relief and less medication usage for trigeminal neuralgia patients: an international multicenter study.

OBJECTIVE: Trigeminal neuralgia (TN) is a chronic pain condition that is difficult to control with conservative management. Furthermore, disabling medication-related side effects are common. This study examined how stereotactic radiosurgery (SRS) affects pain outcomes and medication dependence based on the latency period between diagnosis and radiosurgery. METHODS: The authors conducted a retrospective analysis of patients with type I TN at 12 Gamma Knife treatment centers. SRS was the primary surgical intervention in all patients. Patient demographics, disease characteristics, treatment plans, medication histories, and outcomes were reviewed. RESULTS: Overall, 404 patients were included. The mean patient age at SRS was 70 years, and 60% of the population was female. The most common indication for SRS was pain refractory to medications (81%). The median maximum radiation dose was 80 Gy (range 50-95 Gy), and the mean follow-up duration was 32 months. The mean number of medications between baseline (pre-SRS) and the last follow-up decreased from 1.98 to 0.90 (p < 0.0001), respectively, and this significant reduction was observed across all medication categories. Patients who received SRS within 4 years of their initial diagnosis achieved significantly faster pain relief than those who underwent treatment after 4 years (median 21 vs 30 days, p = 0.041). The 90-day pain relief rate for those who received SRS ≤ 4 years after their diagnosis was 83.8% compared with 73.7% in patients who received SRS > 4 years after their diagnosis. The maximum radiation dose was the strongest predictor of a durable pain response (OR 1.091, p = 0.003). Early intervention (OR 1.785, p = 0.007) and higher maximum radiation dose (OR 1.150, p < 0.0001) were also significant predictors of being pain free (a Barrow Neurological Institute pain intensity score of I-IIIA) at the last follow-up visit. New sensory symptoms of any kind were seen in 98 patients (24.3%) after SRS. Higher maximum radiation dose trended toward predicting new sensory deficits but was nonsignificant (p = 0.075). CONCLUSIONS: TN patients managed with SRS within 4 years of diagnosis experienced a shorter interval to pain relief with low risk. SRS also yielded significant decreases in adjunct medication utilization. Radiosurgery should be considered earlier in the course of treatment for TN.