Myeloproliferative neoplasms (MPN) are uncommon in children/young adults. Here we present data on unselected patients diagnosed before 25 years of age included from 38 centres in 15 countries. Sequential patients were included. We identified 444 patients, with median follow up 9.7 years (0-47.8). Forty-nine (11.1%) had a history of thrombosis at diagnosis, 49 new thrombotic events were recorded (1.16 % pt/year), peri-hepatic vein thromboses were most frequent (47.6% venous events) and logistic regression identified JAK2V617F mutation (p=0.016) and hyperviscosity symptoms (visual disturbances, dizziness, vertigo, headache) as risk factors (p=0.040). New hemorrhagic events occurred in 44 patients (9.9%, 1.04 % pt/y). Disease transformation occurred in 48 patients (10.9%, 1.13 % pt/year), usually to myelofibrosis (7.5%) with splenomegaly as a novel risk factor for transformation in ET (p= 0.000) in logistical regression. Eight deaths (1.8%) were recorded, three after allogeneic stem cell transplantation. Concerning conventional risk scores: IPSET-T and IPSET-NT differentiated ET patients in terms of thrombotic risk. Both scores identified high-risk patients with the same median thrombosis-free survival of 28.5y. No contemporary scores were able to predict survival for young ET or PV patients. Our data represents the largest real-world study of MPN patients age <25 years at diagnosis). Rates of thrombotic events and transformation were higher than expected compared with the previous literature. Our study provides new and reliable information as a basis for prospective studies, trials, and development of harmonized international guidelines for the specific management of young patients with MPN.

In our opinion, a detailed evaluation and appropriate interpretation of clinical and laboratory data in such a category of patients seem to be extremely important, especially when a decision about the TKI change due to therapy failure is considered.

The present study aimed to assess the fibrinolytic and metabolic system parameters in obese patients with polycystic ovary syndrome (PCOS) and to compare them in obese PCOS patients and women with simple obesity. We studied 19 obese women with PCOS (age: 25.1 +/- 4.6 years, body mass index (BMI): 34.7 +/- 3.9 kg/m2; mean +/- standard deviation) and 20 age- and BMI-matched ovulatory controls. We measured blood levels of 17beta-estradiol, testosterone, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEAS), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucose and insulin. The following fibrinolytic tests were also performed: euglobulin clot lysis time, plasminogen level, alpha2-antiplasmin activity, plasminogen activator inhibitor-1 activity, fibrinogen concentration and estimated fibrinolytic activity. Testosterone and LH levels were significantly higher in obese women with PCOS (p < 0.01 and p < 0.001, respectively). The groups did not differ with regard to 17beta-estradiol, prolactin, FSH, DHEAS, TC, TG, HDL-C, LDL-C, glucose and insulin. All of the fibrinolysis parameters with the exception of plasminogen were comparable between the two groups. Serum plasminogen level was lower in obese PCOS patients than in women with simple obesity (p < 0.05). Euglobulin clot lysis time was positively correlated with insulin (r = 0.88, p < 0.05) in both groups. Our results show that fibrinolysis is not suppressed in women with PCOS and that there is no difference in fibrinolytic activity between obese patients with PCOS and women with simple obesity.

The expression of apoptosis-related BCL2 family genes, fine-tuned in normal cells, is dysregulated in many neoplasms. In acute myeloid leukemia (AML), this problem has not been studied comprehensively. To address this issue, RNA-seq data were used to analyze the expression of 26 BCL2 family members in 27 AML FAB M1 and M2 patients, divided into subgroups differently responding to chemotherapy. A correlation analysis, analysis of variance, and Kaplan-Meier analysis were applied to associate the expression of particular genes with other gene expression, clinical features, and the presence of mutations detected by exome sequencing. The expression of BCL2 family genes was dysregulated in AML, as compared to healthy controls. An upregulation of anti-apoptotic and downregulation of pro-apoptotic genes was observed, though only a decrease in BMF, BNIP1, and HRK was statistically significant. In a group of patients resistant to chemotherapy, overexpression of BCL2L1 was manifested. In agreement with the literature data, our results reveal that BCL2L1 is one of the key players in apoptosis regulation in different types of tumors. An exome sequencing data analysis indicates that BCL2 family genes are not mutated in AML, but their expression is correlated with the mutational status of other genes, including those recurrently mutated in AML and splicing-related. High levels of some BCL2 family members, in particular BIK and BCL2L13, were associated with poor outcome.

Administration of succinylcholine to normal individuals results in alterations in muscle membrane integrity expressed as a slight increase in the concentrations of creatine phosphokinase (CK) in serum and appearance of small amounts of myoglobin in the urine, but without clinical symptoms. Subjects with strabismus due to congenital muscular dystrophy may develop more significant rhabdomyolysis expressed as muscle stiffness and weakness, massive myoglobinuria, marked elevation of serum CK and other enzymes, metabolic acidosis, tachycardia and moderate elevation of body temperature. In some cases grave malignant hyperthermia with significant hypoxia, metabolic acidosis, tachycardia and marked abnormalities in serum electrolyte concentrations may cause irreversible damage to the central nervous system and other vital organs and death.A case of difficult anaesthesia for a six year old boy belonging to family affected with muscular dystrophy is presented. More attention must be given to preoperative exarmnation (anamnesis, serum enzymes) of ophthalmological patients and more careful monitoring during anaesthesia and in the early postoperative period must be instituted to prevent and treat complications induced by suecinylcholine and volatile anaesthetic agents.KEY WORDS: COMVLICArtONS, muscular dystrophy, strabismus, rhabdomyolysis, myoglobinuria, malignant hyperthermia.A PREVIOUSLY HEALTHY six year old boy was presented for correction of divergent strabismus of the right eye. The child had been anaesthetized uneventfully six months earlier for the same operation on his left eye. He had no allergies and was considered a minor anaesthetic risk (group 1). On the morning of the operation his blood pressure, pulse, body temperature, haemoglobin and blood leueocytes were normal. Forty-five minutes before anaesthesia, the patient received meperidine 17.5 mg and atropine 0.25rag intramuscularly (weight 17.5 kg). The patient arrived in the operating room well sedated and cooperative. Ten minutes before the start of the anaesthetic methohexitone 120rag was given by rectum. Anaesthesia was started by a junior member of staff with nitrous oxide and oxygen, four litres per minute of each, and halothane 0.5-2.0 per cent given by mask from a Jaekson-Rees system. After the patient had reached the surgical level of anaesthesia, suecinyleholine chloride 25 mg was injected intravenously. The muscle fasciculation was unusually strong and tracheal intubation could not be

Rhabdomyolysis, myoglobinuria, hyperpyrexia, muscle weakness and stiffness occurred in a 4-yr-old boy after halothane anaesthesia and a single dose of suxamethonium. Neurological examination of the patient and his mother revealed no physical abnormality although in both the serum creatine kinase and lactic dehydrogenase concentrations were increased. McArdle's disease was excluded by a normal response to an ischaemic work test.Apparently normal individuals may show minimal signs of muscle destruction following the administration of suxamethonium or halothane or both, as demonstrated by slight increases in serum concentrations of creatine phosphokinase (CK), but without clinical manifestation. Subjects with an increase in their resting serum CK concentration may develop significant destruction of striated muscles with clinical signs varying from muscle weakness, hyperaesthesia, myoglobinuria, mild increase in body temperature, mild metabolic acidosis, and marked increases in concentrations of their serum enzyme, to fulminating hyperpyrexia, grave hypoxia, marked disorder of serum electrolyte concentrations and death.A case of anaesthesia complicated by rhabdomyolysis, myoglobinuria, muscle rigidity and a moderate increase in body temperature is presented. CASE REPORTA previously healthy, 4-yr-old boy presented for tonsillectomy. He had never been anaesthetized before, had no allergies and was considered a good anaesthesia risk. Before operation the arterial pressure, heart rate, body temperature, haemoglobin concentration and packed cell volume were normal. Forty-five minutes before induction anaesthesia, pethidine 20mg and atropine 0.25 mg were given i.m. (body weight 19 kg). Anaesthesia was induced with nitrous oxide 41itremin~', oxygen 41itremin~' and 1.5% halothane given by mask. Breathing was spontaneous. Suxamethonium 25 mg was injected i.v.; muscle fasciculation was unusually strong and the jaw was not relaxed. Intubation of the trachea was performed with difficulty, although no additional neuromuscular blocker was given. There was no cyanosis. Anaesthesia was continued with a mixture of nitrous oxide and halothane in oxygen with spontaneous breathing. At the beginning of the operation the patient received thiopentone 25 mg because his limbs were stiff and the level of anaesthesia was considered inadequate. The later course of anaesthesia was judged to be normal except for slight stiffness of the upper limbs and a heart rate of 140-160 beat min" 1 Breathing was satisfactory and there was no cyanosis. Body temperature was not monitored. The operation lasted 30min. The trachea was extubated, oxygen administered via a face mask and the patient regained consciousness normally.Five hours later dark brown urine was voided and rhabdomyolysis and myoglobinuria were suspected. The rectal temperature was 38 °C; measurements were now made at frequent intervals. Oxygen 6 litre min" 1 was given via a mask. The rectal temperature never exceeded 38.2 °C. Body temperature was decreased to normal with electric fans. The po...

This article collects several published cases in which immune thrombocytopenic purpura (ITP) is followed by essential thrombocythemia (ET) and vice versa. This surprising clinical condition is possible, but very rare and difficult to diagnose and manage. We have made an attempt to analyse the possible causes of the sequential appearance of ITP and ET taking into consideration the following: alteration of the thrombopoietin (TPO) receptor, the role of autoimmunity and inflammation, and cytokine modulation. A better understanding of these interactions may provide opportunities to determine predisposing factors and aid in finding new treatment modalities both for ITP and ET patients.

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