Browsing by Author "Hamilton, Robert"

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    Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry
    (Oxford University Press, 2023) Crotti, Lia; Spazzolini, Carla; Nyegaard, Mette; Overgaard, Michael T.; Kotta, Maria-Christina; Dagradi, Federica; Sala, Luca; Aiba, Takeshi; Ayers, Mark D.; Baban, Anwar; Barc, Julien; Beach, Cheyenne M.; Behr, Elijah R.; Bos, J. Martijn; Cerrone, Marina; Covi, Peter; Cuneo, Bettina; Denjoy, Isabelle; Donner, Birgit; Elbert, Adrienne; Eliasson, Håkan; Etheridge, Susan P.; Fukuyama, Megumi; Girolami, Francesca; Hamilton, Robert; Horie, Minoru; Iascone, Maria; Jiménez-Jaimez, Juan; Jensen, Henrik Kjærulf; Kannankeril, Prince J.; Kaski, Juan P.; Makita, Naomasa; Muñoz-Esparza, Carmen; Odland, Hans H.; Ohno, Seiko; Papagiannis, John; Porretta, Alessandra Pia; Prandstetter, Christopher; Probst, Vincent; Robyns, Tomas; Rosenthal, Eric; Rosés-Noguer, Ferran; Sekarski, Nicole; Singh, Anoop; Spentzou, Georgia; Stute, Fridrike; Tfelt-Hansen, Jacob; Till, Jan; Tobert, Kathryn E.; Vinocur, Jeffrey M.; Webster, Gregory; Wilde, Arthur A. M.; Wolf, Cordula M.; Ackerman, Michael J.; Schwartz, Peter J.; Pediatrics, School of Medicine
    Aims: Calmodulinopathy due to mutations in any of the three CALM genes (CALM1-3) causes life-threatening arrhythmia syndromes, especially in young individuals. The International Calmodulinopathy Registry (ICalmR) aims to define and link the increasing complexity of the clinical presentation to the underlying molecular mechanisms. Methods and results: The ICalmR is an international, collaborative, observational study, assembling and analysing clinical and genetic data on CALM-positive patients. The ICalmR has enrolled 140 subjects (median age 10.8 years [interquartile range 5-19]), 97 index cases and 43 family members. CALM-LQTS and CALM-CPVT are the prevalent phenotypes. Primary neurological manifestations, unrelated to post-anoxic sequelae, manifested in 20 patients. Calmodulinopathy remains associated with a high arrhythmic event rate (symptomatic patients, n = 103, 74%). However, compared with the original 2019 cohort, there was a reduced frequency and severity of all cardiac events (61% vs. 85%; P = .001) and sudden death (9% vs. 27%; P = .008). Data on therapy do not allow definitive recommendations. Cardiac structural abnormalities, either cardiomyopathy or congenital heart defects, are present in 30% of patients, mainly CALM-LQTS, and lethal cases of heart failure have occurred. The number of familial cases and of families with strikingly different phenotypes is increasing. Conclusion: Calmodulinopathy has pleiotropic presentations, from channelopathy to syndromic forms. Clinical severity ranges from the early onset of life-threatening arrhythmias to the absence of symptoms, and the percentage of milder and familial forms is increasing. There are no hard data to guide therapy, and current management includes pharmacological and surgical antiadrenergic interventions with sodium channel blockers often accompanied by an implantable cardioverter-defibrillator.
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    Comprehensive Audiometric Analysis of Hearing Impairment and Tinnitus After Cisplatin-Based Chemotherapy in Survivors of Adult-Onset Cancer
    (ASCO Journals, 2016-08-10) Frisina, Robert D.; Wheeler, Heather E.; Fossa, Sophie D.; Kerns, Sarah L.; Fung, Chunkit; Sesso, Howard D.; Monahan, Patrick O.; Feldman, Darren R.; Hamilton, Robert; Vaughn, David J.; Beard, Clair J.; Budnick, Amy; Johnson, Eileen M.; Ardeshir-Rouhani-Fard, Shirin; Einhorn, Lawrence H.; Lipshultz, Steven E.; Dolan, M. Eileen; Travis, Lois B.; Medicine, School of Medicine
    Purpose Cisplatin is widely used but highly ototoxic. Effects of cumulative cisplatin dose on hearing loss have not been comprehensively evaluated in survivors of adult-onset cancer. Patients and Methods Comprehensive audiological measures were conducted on 488 North American male germ cell tumor (GCT) survivors in relation to cumulative cisplatin dose, including audiograms (0.25 to 12 kHz), tests of middle ear function, and tinnitus. American Speech-Language-Hearing Association criteria defined hearing loss severity. The geometric mean of hearing thresholds (0.25 to 12 kHz) summarized overall hearing status consistent with audiometric guidelines. Patients were sorted into quartiles of hearing thresholds of age- and sex-matched controls. Results Increasing cumulative cisplatin dose (median, 400 mg/m2; range, 200 to 800 mg/m2) was significantly related to hearing loss at 4, 6, 8, 10, and 12 kHz (P trends, .021 to < .001): every 100 mg/m2 increase resulted in a 3.2-dB impairment in age-adjusted overall hearing threshold (4 to 12 kHz; P < .001). Cumulative cisplatin doses > 300 mg/m2 were associated with greater American Speech-Language-Hearing Association–defined hearing loss severity (odds ratio, 1.59; P = .0066) and worse normative-matched quartiles (odds ratio, 1.33; P = .093) compared with smaller doses. Almost one in five (18%) patients had severe to profound hearing loss. Tinnitus (40% patients) was significantly correlated with reduced hearing at each frequency (P < .001). Noise-induced damage (10% patients) was unaffected by cisplatin dose (P = .59). Hypertension was significantly related (P = .0066) to overall hearing threshold (4 to 12 kHz) in age- and cisplatin dose–adjusted analyses. Middle ear deficits occurred in 22.3% of patients but, as expected, were not related to cytotoxic drug dosage. Conclusion Follow-up of adult-onset cancer survivors given cisplatin should include routine inquiry for hearing status and tinnitus, referral to audiologists as clinically indicated, and hypertension control. Patients should be urged to avoid noise exposure, ototoxic drugs, and other factors that further damage hearing.