Rationale and design of ENDEAVOR: A sequential phase 2b-3 randomized clinical trial to evaluate the effect of myeloperoxidase inhibition on symptoms and exercise capacity in heart failure with preserved or mildly reduced ejection fraction.

AIMS: Mitiperstat (formerly AZD4831) is a novel selective myeloperoxidase inhibitor. Currently, no effective therapies target comorbidity-induced systemic inflammation, which may be a key mechanism underlying heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). Circulating neutrophils secrete myeloperoxidase, causing oxidative stress, microvascular endothelial dysfunction, interstitial fibrosis, cardiomyocyte remodelling and diastolic dysfunction. Mitiperstat may therefore improve function of the heart and other organs, and ameliorate heart failure symptoms and exercise intolerance. ENDEAVOR is a combined, seamless phase 2b-3 study of the efficacy and safety of mitiperstat in patients with HFpEF/HFmrEF. METHODS: In phase 2b, approximately 660 patients with heart failure and ejection fraction >40% are being randomized 1:1:1 to mitiperstat 2.5 mg, 5 mg or placebo for 48 weeks. Eligible patients have baseline 6-min walk distance (6MWD) of 30-400 m with a <50 m difference between screening and randomization and Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) ≤90 points at screening and randomization. The dual primary endpoints are change from baseline to week 16 in 6MWD and KCCQ-TSS. The sample size provides 85% power to detect placebo-adjusted improvements of 21 m in 6MWD and 6.0 points in KCCQ-TSS at overall two-sided alpha of 0.05. Safety is monitored throughout treatment, with a focus on maculopapular rash. In phase 3 of ENDEAVOR, approximately 820 patients will be randomized 1:1 to mitiperstat or placebo. CONCLUSION: ENDEAVOR is the first phase 2b-3 study to evaluate whether myeloperoxidase inhibition can improve symptoms and exercise capacity in patients with HFpEF/HFmrEF.

[MR imaging late changes of brain after carbon monoxide poisoning--case report]. / Odlegle zmiany w obrazie MR mózgowia po zatruciu tlenkiem wegla--opis przypadku.

We present the case of 28 years old patient hospitalized at the Regional Center of Clinical Toxicology in Lublin after carbon monoxide poisoning. The level of carboxyhemoglobin was 33.3%. Because of neurological symptoms MR of brain was performed with normal result. During hospitalization the progression of clinical symptoms was observed and the patient underwent control MR of brain. The result was abnormal and show changes bilaterally in white matter.

[MR imaging in patients with carbon monoxide poisoning]. / Obrazowanie MR u pacjentów po zatruciu tlenkiem wegla.

UNLABELLED: The aim of the study was to describe MR imaging findings in patients after acute carbon monoxide poisoning. MATERIAL AND METHOD: In the period of 7 months (from October 2011 to April in 2012), 72 patients were hospitalized at the Center of Clinical Toxicology after acute carbon monoxide poisoning. In all patients the level of carboxyhemoglobin (COHb) was determined. Brain MR examination was performed in 14 patients of this group due to persistent neurological symptoms. RESULTS: In 72 patients the mean value of COHb was 21.52%. In 14 patients with persistent neurological symptoms mean value of COHb was 26.14%. In 14 patients who underwent MRI of the brain, in 4 there was no MR change and their COHb average value was 20.45%. In the remaining 10 patients MR brain abnormalities were diagnosed, including changes of basal ganglia, white matter or cortex, and their COHb average value was 26.56%. CONCLUSIONS: In patients with persistent neurological symptoms after acute carbon monoxide poisoning are changes in brain MRI. These changes correlate with the concentration of COHb. MRI seems to be the method of choice for imaging the brain in patients after acute carbon monoxide poisoning.

[Three-fold ethylene glycol poisoning over 3 years--a case report]. / Trzykrotne zatrucie glikolem etylenowym na przestrzeni 3 lat--opis przypadku.

This paper describes a case of now 49-year-old patient with alcohol dependence syndrome, hospitalized three times in the Center of Clinical Toxicology in 2009-2012 due to ethylene glycol poisoning. Twice, the course of poisoning was defined as severe. It was complicated by respiratory failure, severe metabolic acidosis, renal failure, disorders of the central nervous system; once referred to it as a medium, complicated by renal failure. He was treated with ethyl alcohol as an inhibitor of alcohol dehydrogenase, hemodialysess and intensive symptomatic and supportive therapy. This paper shows the great effectiveness of early hemodialysis and intensive therapy even in case of multiple and severe intoxication with toxic alcohols.

[Tako-tsubo cardiomyopathy in the course of carbon monoxide poisoning]. / Kardiomiopatia tako-tsubo w przebiegu zatrucia tlenkiem wegla.

Tako-tsubo cardiomyopathy is a clinical syndrome induced by a strong mental or physical stress, characterized by a transient hypokinesia, akinesia or dyskinesia middle segments of the left ventricle and apical, with associated electrocardiographic changes of ST-T segment like in acute coronary syndrome, with no significant changes in coronary arteries in coronary angiography. Tako-tsubo cardiomyopathy is mainly found in women in the sixth and seventh decade of life and represents 1-2% of cases originally diagnosed as acute coronary syndrome. We present a case of tako-tsubo syndrome in the course of carbon monoxide poisoning in a 56-year-old patient, with a positive history of ischemic heart disease and hypertension. Moreover, the reasons for its occurrence were considered based on clinical course, laboratory tests and imaging, and available literature.

[Noncardiogenic pulmonary edema in the course of poisoning with clozapine, ketoprofen and thiethylperazine]. / Niekardiogenny obrzek pluc w przebiegu zatrucia klozapina, ketoprofenem i tietylperazyna.

Pulmonary edema is a severe, potentially fatal clinical condition. It happens, when interstitial fluid is accumulating in the alveoli, impeding proper gas exchange. Typically we distinguish cardiogenic and noncardiogenic pulmonary edema. The article describes the case of severe pulmonary edema, which occurred in a young woman, free of cardiac diseases, about 30 hours after a suicidal drug poisoning (clozapine, ketoprofen, thiethylperazine). Both clozapine and ketoprofen intoxication, may be severe. Complications in these poisonings affect not only the central nervous system, but also the circulatory or respiratory system and may even occur several hours after the overdose of these drugs. The study considered the causes and possible mechanisms of pulmonary edema in poisoning with these drugs.

[Impact of internet on poisoning with psychoactive substances in young people]. / Wplyw internetu na zatrucia substancjami psychoaktywnymi u ludzi mlodych.

These days young people use internet as a source of information. Internet offers knowledge that can be used not only for school education but also to obtain information about usage and effects of psychoactive substances. Recent research shows that young people more often use internet websites and chat rooms to exchange knowledge and experience with chemicals and everyday products used as intoxicants, for example: nutmeg, nonprescription medications, metal cleaning liquid or feminine hygiene products. This article shows the extend of knowledge young people can gain from popular internet websites. Information on the web is presented as appealing, attractive and encouraging. From a toxicologist point of view it is extremely important to be familiar with those new threats because more and more often we have to treat young patients with a serious poisoning from usage of experimental intoxicating substances.

[Severe digoxin poisoning a case study]. / Ciezkie zatrucie digoksyna--opis przypadku.

Digitalis glycosides are among the oldest drugs used in cardiology. Nowadays, due to the limited indications for their use (advanced heart failure, usually concomitant with atrial fibrillation), cases of poisoning induced by this class of drugs are rarely observed. Digoxin produces a positive inotropic and bathmotropic effect on the heart, but has a negative chronotropic and dromotropic effect. Cardiac glycosides have a narrow therapeutic window, so digitalis treatment can easily lead to symptoms of overdose. In patients taking digoxin, the drug therapeutic level should be maintained at 1-2 ng/ml; the toxic effects occur at concentrations > 2.8 ng/ml and are mainly related to disturbances of cardiac function and of the circulatory system, as well as gastrointestinal symptoms and CNS disturbances. We present, a 45-years-old patient who was hospitalized following the ingestion with suicidal intent of 100 0.25 mg tablets of digoxin. In spite of rapidly applied gastric irrigation and administration of activated charcoal, the drug level in the patient's blood was estimated at 12.0 ng/ml. During her stay on the ward, typical symptoms of severe poisoning were observed: from gastric symptoms (severe nausea, vomiting) to numerous severe arrhythmias and conduction disturbances. Type I, II and III AV blocks were detected, as well as numerous ventricular and supraventricular extrasystoles. These conduction disorders required the use of temporary endocardial pacing. Due to the unavailability of specific antidotes (antidigitalis antibodies) and lack of efficient methods of extracorporeal elimination of the drug, symptomatic treatment comprising the correction of electrolyte disturbances and heart rate control remains the most effective.

[Is it possible to survive metabolic acidosis with pH measure below 6.8? A study of two cases of inedible alcohol intoxication]. / Czy mozliwe jest przezycie kwasicy metabolicznej o wartosci pH ponizej 6,8? Opis 2 przypadków klinicznych zatrucia alkoholami niespozywczymi.

26 of serious inedible alcohol (ethylene glycol and methanol) intoxications have been observed in Lublin Regional Center of Clinical Toxicology during 2010/2011 (18 mounths). As a result of such intoxications, metabolic acidosis and acute renal failure and other organs injury develop. The writings inform that it is possible to survive a pH spectrum between 6.8 and 7.8, whereas beyond these values protein denaturation and death proceed. The paper presents two cases of intoxication with ethylene glycol and ethylene glycol, methanol together where the lowest pH values in capillary blood were recorded below 6.8. The first case is of a male, 45, who was diagnosed glycol concentration at 283.3 mg/dl, with the lowest pH value obtained in the gasometric examination of capillary blood at 6.712. The other case is of another male, 54, who had probably drunk condenser liquid. Ethylene glycol and methanol's concentration were 535 mg/dl and 37.5 mg/dl correspondingly, whereas the lowest capillary blood pH value was recorded at 6.745. Both men had been addicted to alcohol for many years. The treatment demanded multiple hemodialyses, respiratory therapy, catecholamine intravenous injections as well as intensive pharmacological treatment resulting from multi-organ complications. The intoxication in either case was non-lethal.

[Methanol poisoning in a 61-year old male with recently diagnosed diabetes--a case report]. / Zatrucie metanolem u 61-letniego mezczyzny ze swiezo wykryta cukrzyca--opis przypadku.

The aim of this paper is to present a case of a 61-year-old male transferred to the Regional Center of Clinical Toxicology from the Department of Endocrinology with suspected methanol poisoning. The patient presented symptoms of diabetes with extreme hyperglycemia >1600 mg/dl and nonketotic hyperosmolar coma. Laboratory tests showed metabolic/respiratory acidosis, methanol 80 mg/dl, ethanol 0.47 g/l, creatinine 3.5 mg/dl, urea 140 mg/dl, lactic acid 4.11 mmol/l, myoglobin >1000 ng/ml, HbA1C >14.5%. During a few days prior to the hospitalization the patient was drinking a great amount of fruit juices and milk (a dozen or so litres per twenty four hours). The eventuality of metabolizing glucose and aspartame into methanol is known from professional literature. The possibility of excessive consumption of aspartame and its metabolites causing methanol poisoning in the presented patient was considered.

[Myocardial infarction secondary to carbon monoxide poisoning--a study of two cases]. / Zawal serca w przebiegu zatrucia tlenkiem wegla--opis dwóch przypadków klinicznych.

The carbon monoxide poisoning still remains a main cause of fatal poisoning. The carbon monoxide poisoning occurs after inhalation of carbon monoxide. Carbon monoxide binds strongly to molecules, such as cytochrome oxidase, myoglobin, hemoglobin, causing hypoxia of tissues and organs. Carbon monoxide converts hemoglobin to carboxyhemoglobin and makes transport of oxygen through the body impossible and causes severe hypoxia. The only treatment is administering 100% oxygen or providing hyperbaric oxygen therapy. The central nervous system and heart are the most sensitive to hypoxia. We present the cases of two young people with no history of chronic diseases (a 24-year-old man and a 39-year-old woman) who were diagnosed NSTEMI in the course of severe carbon monoxide poisoning. Both poisoning cases were severe, both patients were unconscious when they were admitted to our hospital. We observed elevation of serum troponin level and changes in ECG (e.g. atrial fibrillation) significant for myocardial infarction.

[Imbalance of oxidoreductive status in suicidal antidepressant drugs poisoning]. / Zachwianie równowagi oksydoredukcyjnej w samobójczych zatruciach lekami przeciwdepresyjnymi.

The aim of this study was to examine the association between suicidal poisoning with antidepressants and the oxidoreductive balance by evaluation of changes in activity of glutathione reductase (GR) and total antioxidative status (TAS) in serum. GR activity and TAS were determined in 29 patients hospitalized after suicidal poisoning with antidepressants and compared with the results of the control group consisting of 16 healthy people. For this purpose, RANDOX diagnostic sets were used. The GR activity and TAS were significantly lower in the examined group, compared with the control group. The results obtained show a significant reduction of GR activity and TAS level in patients with suicidal antidepressants poisoning. It seems, that the oxidoreductive balance is shift towards the oxidative potential and leads to the decrease of the organism's antioxidative potential, which is manifested by the increase of oxygen free radicals and the intensification of the oxidative stress.