BACKGROUND: Anamorelin, a drug to treat cancer cachexia, binds to ghrelin receptors and improves body weight and appetite. In clinical trials in Japan, patients experienced a 10.7% frequency of stimulant conduction system depression as a severe side effect. Although rare, anamorelin sometimes causes fatal arrhythmias. Because patients with cancer cachexia are often underweight, data on the safety of anamorelin in obese patients are lacking. We report a case of QT interval prolongation after anamorelin administration to an obese patient with non-small cell lung cancer.
METHODS: A female patient with a body mass index of 30 kg/m2 underwent immunotherapy for lung adenocarcinoma. She presented with severe weight loss, anorexia, and fatigue. She had no history of heart disease. On day 12, after administration of anamorelin 100 mg once daily, the patient developed nausea, diarrhea, and anorexia, which were considered cancer immunotherapy-induced immune-related adverse events, and she was admitted to the hospital. An electrocardiogram (ECG) on admission showed a QTc interval of 502 ms. On admission, her hepatic function was Child-Pugh class B, and anamorelin was discontinued the next day. On day 3 after anamorelin discontinuation, the QTc interval was prolonged by up to 557 ms, then decreased to 490 ms on day 6, and improved to 450 ms on day 16. Re-administration of anamorelin was avoided.
CONCLUSIONS: When administering anamorelin to obese patients, we should be aware of the potential for stimulatory conduction system depression, as in underweight patients. Therefore, we should monitor patients by ECG from the early stages of anamorelin administration. Anamorelin is lipophilic, and its volume of distribution is increased in obese patients. Consequently, obese patients may continue to have QT interval prolongation after discontinuation of anamorelin, requiring long-term side-effect monitoring.

OBJECTIVE: To analyze the clinical and genetic characteristics of a patient with long QT syndrome type 14 (long QT syndrome-14, LQT14, OMIM # 616247) caused by a de novo CALM1 mutation.
METHODS: The clinical data of the patient were collected, next-generation sequencing technology was used to determine the exome gene sequence of the patient, and the suspected pathogenic locus was verified by Sanger sequencing.
RESULTS: A 5-year and 9-month-old girl was admitted to the hospital due to a syncopal episode. During the attack, the main symptoms were loss of consciousness, cyanosis of the face and lips, and weakness of limbs. The child had multiple seizures in the past, all of which occurred after emotional excitement and activity. She was diagnosed with epilepsy for more than 3 years, but the effect of antiepileptic treatment was not satisfactory. The electrocardiogram was normal in the past. A month ago, convulsions occurred again after exercise, and the electrocardiogram showed QTc 496 ms. The treadmill test showed a significant prolongation of QTc after exercise, and the genetic results suggested a new heterozygous variant of CALM1, c.395A>G; p. (Asp132Gly). Consequently, she was diagnosed with LQT14 and treated with propranolol. During a follow-up of 15 months, there were no seizures or syncope.
CONCLUSIONS: This patient had multiple episodes of convulsions or syncope after emotional stimulation or activity, with intermittent prolongation of the QTc on routine ECG, marked prolongation of the QTc after exercise, and T-wave alternans, which differed from the LQT14 phenotype caused by the previous CALM1 mutation.

We report the case of an 8-year-old boy with left ventricular noncompaction cardiomyopathy (LVNC) and QT prolongation who experienced further prolongation of the QTc during general anesthesia for extraction of a maxillary mesiodens. Pronounced prolongation of the QTc was observed after induction of general anesthesia with thiamylal and during emergence. No notable fluctuations in blood pressure, heart rate, and estimated continuous cardiac output were observed. We considered it likely that the QT prolongation was triggered by thiamylal and increased sympathetic nervous system activity. During general anesthesia for children with LVNC and QT prolongation, it is necessary to monitor intraoperative hemodynamic fluctuations and prepare for the possible occurrence of arrhythmias.

In this paper, we explore the use of the Static Qualitative Trajectory Calculus (QTCS), a qualitative spatiotemporal method based on the QTC, for the analysis of team formations in football. While methods for team formation analysis in sports are predominantly quantitative in nature, QTCS enables the comparison of team formations by describing the relative positions between players in a qualitative manner, which is more related to the way players position themselves on the field. QTCS has the potential to allow to monitor to what extent a football team plays according to a coach\'s predetermined formation. When applied to multiple matches of one team, the method can contribute to the definition of the playing style of a team. We present an experiment aimed at identifying the team formation played by Belgian national football team during the 2018 FIFA World Cup held in France.

The circadian rhythm of cardiac electrophysiology is dependent on many physiological and biochemical factors. Provided, that models describing the circadian patterns of cardiac activity and/or electrophysiology which have been verified to the acceptable level, modeling and simulation can give answers to many of heart chronotherapy questions. The aim of the study was to assess the performance of the circadian models implemented in Cardiac Safety Simulator v 2.2 (Certara, Sheffield, UK) (CSS), as well as investigate the influence ofcircadian rhythms on the simulation results in terms of cardiac safety. The simulations which were run in CSS accounted for inter-individual and intra-individual variability. Firstly, the diurnal variations in QT interval length in a healthy population were simulated accounting for heart rate (HR) circadian changes alone, or with concomitant diurnal variations of plasma ion concentrations. Next, tolterodine was chosen as an exemplary drug for PKPD modelling exercise to assess the role of circadian rhythmicity in the prediction of drug effects on QT interval. The results of the simulations were in line with clinical observations, what can serve as a verification of the circadian models implemented in CSS. Moreover, the results have suggested that the circadian variability of the electrolytes balance is the main factor influencing QT circadian pattern. The fluctuation of ion concentration increases the intra-subject variability of predicted drug-triggered QT corrected for HR (QTc) prolongation effect and, in case of modest drug effect on QTc interval length, allows to capture this effect.

A vital aspect of the drug discovery and development process is the identification and filtering of drugs with high risk of dangerous adverse events. Torsade de Pointes (TdP) is one example of an adverse event that requires thorough in vitro and in vivo drug screening. This is because TdP, a tachycardic ventricular arrhythmia, can develop into fatal cardiac events if left unresolved and has been missed during drug development with profound consequences. These factors led to the development of pre-clinical screening guidelines based on the presence of drug induced QT prolongation (QTp), which has been linked to TdP. These guidelines have high sensitivity, but low specificity, as they tend to predict QTp, which precedes TdP events but does not always lead to TdP. Computational models have the potential to improve these prediction methods by bridging the gaps between preclinical and clinical data. This study proposes the use of adverse event reports obtained from the FDA Adverse Event Reporting System as a representation of clinical TdP risk. By incorporating these reports into computational models, a more accurate risk prediction may be developed.

The Qualitative Trajectory Calculus (QTC) is a qualitative spatio-temporal calculus for describing interactions between moving point objects. So far, it remained unclear whether QTC is useful for describing subtle differences, such as between the movements of different parts of a human body. We tested the applicability of QTC to detect differences in the gait patterns of children with or without Developmental Coordination Disorder (DCD). We found that using a combination of three markers (i.e. ankle, toe and trochanter), QTC can achieve a high classification accuracy (i.e. 83.3%) of classifying subjects correctly to either the DCD group or the control group.

We report that sevoflurane not only caused marked QTc interval prolongation but also increased transmural dispersion of repolarization in a patient with long QT syndrome 3 (LQT3). A 16-year-old male with LQT3 underwent a shoulder operation. He experienced no episode of syncope or cardiac arrest, but his preoperative electrocardiography (ECG) showed marked QTc interval prolongation (631 ms) and Tp-e interval prolongation (126 ms). Anesthesia was induced with propofol and maintained with 2% sevoflurane and remifentanil. Although no lethal arrhythmias occurred in the perioperative period, not only the QTc interval but also Tp-e interval was further prolonged by sevoflurane. While sevoflurane has been recognized as a safe anesthetic in terms of QT interval prolongation, even in patients with long QT syndromes, we believe that sevoflurane might be avoided for poorly controlled LQT3 patients.

Long QT values have been reported in patients with anorexia nervosa of the restricting type (ANr) potentially increasing the risk of fatal arrhythmia, especially if psychotropic drug treatment is required. Nevertheless, the previous studies on this topic are biased by drug exposure, long disease durations, and small sample sizes. This study is aimed at assessing QTc and QTcd values in ANr adolescents with recent onset and drug free, as compared to subjects affected by psychiatric disorders other than ANr. We evaluated QTc and its dispersion (QTcd) in a population of 77 drug-free ANr female adolescents and compared to an equal number of healthy controls (H-CTRL) and pathological controls (P-CTRL, mixed psychiatric disorders). The QT determination was performed on a standard simultaneous 12-lead ECG in blind by a single experienced investigator. QTc was calculated by the Bazett\'s formula and QTcd was determined as the difference between the maximum and minimum QTc intervals in different leads. Only for ANr patients, clinico-demographic data, hormones, and electrolytes were obtained. QTc was slightly reduced in ANr patients (27.7 ms, < 10%, p < 0.0003) vs. controls, while QTcd was increased in P-CTRL (30%, p < 0.0003). Heart rate was significantly lower in ANr patients vs. controls (25%; p < 0.003). Tyroid hormones and serum potassium showed weak although significant positive correlations with QTc in ANr patients. QTcd displayed a weak negative correlation with the BMI percentile (r = - 0.262, p = 0.03). We reject the hypothesis that QTc and QTcd are increased in drug-free ANr adolescents with a relatively short-disease duration. Further studies are needed to understand if the previously reported increase might be related to other associated chronic disorders, such as hormonal or electrolyte imbalance.

BACKGROUND: Iloperidone is a recently introduced antipsychotic medication. It is approved for the treatment of schizophrenia. There are no published reports of iloperidone overdosage, but there are eight cases that have been reported to the US Food and Drug Administration.
METHODS: A case of a 27-year-old man who took 84 mg of iloperidone while also smoking cocaine is described. He developed a prolonged QTc (527 ms) without arrhythmias and respiratory failure with mandated respiratory support. He ultimately recovered without sequelae.
CONCLUSIONS: The information regarding previous cases of toxicity on the US Food and Drug Administration website is incomplete. However, there were no fatalities due to iloperidone over-ingestion. Prolongation of the QTc may be a common feature.