For patients with advanced chronic kidney disease (CKD) appropriately chosen and timely initiated dietary measures, as a complement to drug therapy, may slow the progression of the disease and delay the need for dialysis treatment. According to the results, dietary protein restriction may play a very important in management of such a patient. The effect of low protein diet is given by the early initiation and well cooperation of patients. The low protein diet with supplementation of ketoanalogues of amino acids is an attractive intervention to help maintain good nutritional status of patients and also have a positive role in calcium phosphate metabolism. Depending on the level of CKD´s progression it should not be forgotten either the fluid balance and the limitation of the intake of salt and phosphorus in the diet which may also have an unfortunate effect on the course of the disease.

Therapeutic drug monitoring is a strategy utilized to optimize biological therapy. It consists in the drug level measurement before the next dose is due, when the drug concentration reaches the trough level, and includes the detection of potential antidrug antibodies. The monitoring makes it possible to adjust the therapy accordingly - to intensify or change the biologics applied to secure safe and highly effective therapeutics. Therapeutic optimization is based on the nature of therapy failure, which can be caused by pharmacokinetic or pharmacodynamic factors. Pharmacokinetic monitoring can be currently classified as reactive, measuring the drug level and antidrug antibodies during therapy failure, or adverse reactions to the drug applied, and proactive, monitoring patients in clinical remission to retain remission and prevents development of a secondary failure.

At the Centre for Cardiovascular and Transplantation Surgery, Brno (CKTCH), a total of 638 liver transplantations were performed from the beginning of the transplantation programme on 2/2 1983 to 1/1 2017. Of the overall number of 638 transplantations indicated based on cirrhosis with chronic hepatitis C (HCV), 68 patients (11 %) underwent liver transplantation. Patients with HCV diagnosis were treated both while on the waiting list and after liver transplantation (LT). There was interferon as well as interferon-free therapy used during the treatment. 15 patients received interferon therapy after LT with only 2 of them achieving a sustained virological response 2/15 (13 %). 28 patients received interferon-free therapy after LT. A sustained virological response (SVR 12) was reached by 26/28 (93 %) patients.

Introduction:
Radiofrequency catheter ablation (RFA) has recently become a routine part of atrial fibrillation (AF) treatment. The goal of our study was to determine whether the implementation of RFA of AF under general anesthesia (GA), compared to analgosedation (AS), will affect important characteristics of the ablation procedure, comfort of the patient and whether there is any clinical impact on the complication rate and the overall success of the procedure.
Methods:
50 patients with AF were randomized in a ratio of 1 : 1 into two groups for RFA in AS and in GA. Procedural characteristics, arrhythmia-free survival for the time of 12 months and subjective evaluation of pain tolerability of the procedure were monitored.
Results:
Overall procedural times were comparable in GA and AS groups (111.2 ± 16.3 min vs 104.8 ± 25 min, p = NS). Time needed for preparation of patients was significantly longer in the GA group, while time needed for electrical disconnection of all pulmonary veins (PVs) was significantly shortened. Electrical isolation of the ipsilateral PVs after the last RF application was achieved in 94 % of lesions in GA and in 78 % of lesions in AS, respectively (p = 0.02). Shorter time of RF energy application to achieve electrical isolation of PVs was needed in the group of GA than in the group of AS (1 386 ± 387 s vs 1 745 ± 463 s, p = 0.005). Subjective discomfort evaluation of the procedure was more favorable in patients in the GA group. 88 % of patients in the GA group vs 68 % patients in AS (p = 0.1) had stable sinus rhythm off antiarrhythmic treatment during the 12 month period following the index procedure. While in the GA group all 3 patients with AF recurrence were willing to undergo another procedure in the GA, in the AS group only one patient out of 8 patients with AF recurrences underwent reablation.
Conclusion:
RFA of AF performed under GA provided improved tolerance and positive perception of the procedure, higher final treatment success and improved quality of life.

Prothrombotic states related to idiopathic bowel disease (IBD) are typically caused by abnormalities of hemostasis associated with inflammatory processes. The risk of thromboembolic complications in patients with IBD is approximately three times as high as in the general population. A critical role is played by the acquired risk factors including medication, while the proportion of inherited thrombophilia in patients with IBD is the same as in the general population. Many abnormalities can be identified through laboratory testing at the level of coagulation factors, fibrinolysis, thrombocytes and endothelium. Although there are no systematic guidelines for the prevention of thromboembolism in patients with IBD available, valid reasons for prophylactic administration of low-molecular-weight heparin are immobilization, hospitalization for IBD activity and surgery. The treatment of thromboembolism which complicates the course of IBD does not differ from its treatment among the general population, and concern over bleeding into gastrointestinal tract during anticoagulation should not outweigh the risk of possible fatal consequences of untreated thrombosis.

Multiple myeloma has varied manifestations which resemble common patient complaints and that is why this disease is typically not diagnosed until it reaches an advanced stage. Spinal pains can be an expression of deformative and discogenous changes, but also a symptom of multiple myeloma. Pains in the long bones may result from the pain radiating from an arthrotic joint, but also from a large myelomatic osteolytic lesion which makes the bone prone to a spontaneous fracture. Pathological weariness may have many causes, multiple myeloma being one of them. Anemia may have a large number of causes and multiple myeloma is one of them. Raised creatinine levels and renal failure can also be due to many causes and again, multiple myeloma is one of them. Weakened immunity and frequent infections can also have many causes, among them multiple myeloma. Confusion and sleepiness may be due to psychiatric diagnosis, but also may result from hypercalcemia associated with multiple myeloma. The following text which is designed for non-hematology physicians therefore describes in detail the symptoms of multiple myeloma and diagnostic steps leading to establishing the diagnosis and it only briefly outlines the treatment related information. You can also visit www.myeloma.cz for details. This text aims to summarize the symptoms of multiple myeloma for physicians not specializing in hematology in order to facilitate earlier diagnosing of the disease.

We reported the first real data about efficacy of interferon-free therapy of chronic hepatitis C in the Czech Republic. Patients were treated with combined therapy of paritaprevir/ritonavir + ombitasvir + dasabuvir with or without ribavirin. There were 109 patients, predominantly men - 62 (57 %), most of them infected by genotype 1b - 101 patients (93 %), minority infected by genotypes 1a (6/109, 5 %) and 4 (2/109, 2 %). Both treatment-naive (43/109, 39 %), and treatment-experienced patients (66/109, 61 %) were treated. Sustained virological response 12 weeks after therapy termination (SVR12) was 100 %, with exclusion of patients with other reason than virological treatment failure.

Introduction:
A structured care of patients with diabetes is in place in the Czech Republic and the majority of patients are followed up by a diabetologist in outpatient diabetes units. The SPACE project (The Health Records of Patients Accepted by a Diabetologist by way of Export) was initiated to address the lack of the data which would allow for objective evaluation of how the cooperation in the care of patients with diabetes works in the real-life health care practice in the Czech Republic.
Goal:
Gaining the description of anthropometric parameters, presence of complications, the chosen therapy and metabolic state of patients registered for diabetes specialist care. Secondary goals involved identification of the average duration of diabetes at the first patient visit to the outpatient diabetes clinic, prevalence of diabetes-related complications on the registration for diabetes care, the structure of pharmacological therapy for diabetes, hypertension, hyperlipoproteinemia.
Methodology:
Retrospective collection of data for the first 20-25 patients, who were consecutively registered in diabetes outpatient clinics from 1 January 2015 onwards.
Results:
778 complete questionnaires were included in the analysis. The greatest number of patients were referred by the general practitioner (64.5 %). Over 55 % of the patients were aged 50-69, less than 10 % were up to 40 years of age. 95.6 % of all cases involved type 2 diabetes mellitus. In almost 65 % of the cases duration of diabetes before registration for diabetes care is up to 2 years. There were 433 late complications recorded in 272 patients of the total number of 778 patients. 506 patients (65 %) had no late complications. Three most frequently occurring complications were ischemic heart disease (18.6 %), diabetic neuropathy (7.8 %) and stroke (5.5 %). The analysis of pharmacotherapy shows a significant increase in the use of the followed drugs after visiting a diabetologist (74.9 % before the diabetes visit and 96.7 % after the visit). Antidiabetic drugs or insulin were taken by 48.3 % of patients before the diabetologist visit, and they were taken by 92.5 % of patients after the first diabetologist visit.

Associations of both hypothyroidism and subclinical hypothyroidism with metabolic syndrome are well established. Nowadays, more attention has been paid to the role of thyroid hormones and thyrotropin (TSH) within the euthyroid range on the development of cardiometabolic health risks. The paper summarizes current knowledge related to the associations of lower free thyroxine (fT₄) level and higher levels of both free triiodothyronine (fT₃) and TSH with body adiposity, metabolic syndrome and insulin resistance in euthyroid subjects. In our recent study of obese euthyroid adolescents, we revealed that fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) positively correlated with fT₃ and TSH and negatively with fT₄. The ratio of fT₃ to fT₄ was also significantly related to HOMA-IR both in girls (r = 0.347, p < 0.001) and boys (r = 0.267, p < 0.001). It is concluded that up-to-date conducted studies mostly confirmed that thyroid hormones and TSH even in euthyroid range may significantly affect the metabolic health and particularly insulin sensitivity.

The present generation of women of childbearing age more frequently suffer from overweight, obesity, initial as well as fully established metabolic syndrome, which together with postponing motherhood until the third decade in life plays an important role in the increasing incidence of gestational diabetes (GDM) that currently affects about 1/5 of pregnant women. However the causal link between diabetes during pregnancy and metabolic diseases in the whole population is mutual. By way of epigenetic changes, maternal diabetes unfavourably programmes metabolism of the offspring, who tend to transfer the disorder to the next generations. Gestational diabetes is therefore an important link fitting into the accumulation curve of the incidence of overweight, obesity, metabolic syndrome and consequently also T2DM among the whole population. Genetic as well as epigenetic factors play a great role in the GDM pathogenesis, which is shown by the fact that this complication also affects women with normal BMI. When it comes to diagnosing GDM, we will need to manage also in future with establishing fasting glycemia and glycemia following glucose challenge (OGTT) that may include a considerable degree of measurement inaccuracy. It is therefore necessary to observe pre-analytical and analytical conditions of measurements in order to obtain a reliable result. It is a positive sign that the Czech professional associations have adopted new international criteria for diagnosing GDM which, as opposed to those valid earlier, better reflect the risk of pregnancy-related and perinatal complications.
The care for gestational patients with diabetes at a low risk (due to satisfactory glycemic control through a diet or small pharmacotherapeutic doses, with an eutrophic fetus and without associated complications) is provided by an outpatient gynecologist and a diabetes specialist, they can give birth in standard maternity hospitals. The care for gestational patients with diabetes at a higher risk is taken over by specialist centres. The early and appropriate treatment of gestational diabetes demonstrably reduces the risk of complications. The base for therapy is formed by regimen-related measures: the therapeutic diet and increased physical activity. The best results of the dietary therapy are achieved with foods low on glycemic index and glycemic load that can also act as efficient prevention of GDM and subsequent development of T2DM. A small number of cases require adding of pharmacological therapy: insulin and newly also metformin. Metformin is the drug of choice primarily in obese patients, however in almost half of the cases insulin must be added. Medication, in particular with insulin, must be introduced carefully, following re-education and elimination of dietary mistakes. The aim of the treatment is not only to achieve normoglycemia, but also to improve, or at least to not further worsen insulin resistance. Insulin resistance alone without diabetes, e.g. due to obesity or a great weight gain, may lead to macrosomia and epigenetic changes. In this regard, the prevention within the whole population of pregnant women needs to be improved and the vicious circle of the causation of metabolic disorders among the population needs to be broken.

Mini review summarizes the results of our studies focused on elucidation of the pathophysiological mechanisms of altered calcium homeostasis in nonexcitable cells from patients with early stages of chronic kidney disease (CKD), as well as on determining the effect of vitamin D₃ supplementation on these mechanisms. The basic mechanisms of calcium entry to and removal of the cell are already changed in early stages of CKD. These disturbances cause an increased the concentration of cytosolic free calcium ([Ca²⁺]_i), which may change a number of cellular processes, and the expression of various signaling molecules. Vitamin D₃ supplementation is a standard procedure of vitamin D insufficiency/ deficiency correction in these patients. The pleiotropic effects of vitamin D may be involved in the modulation of cellular calcium homeostasis. Vitamin D₃ supplementation resulted in a reduction in [Ca²⁺]_i by affecting of specific transport systems of calcium cations entry to and removal of the cell. The normalization [Ca²⁺]_i can have a beneficial effect on intracellular signalling, and thus positively influence the functioning of cells, tissues or organs.

During the past 50 years the molecular mechanisms of renal reabsorption of sodium and water have been described and molecules specifically interfering with these mechanisms have been developed (diuretics, vasopressin receptor antagonists). Chronic hyponatremia is caused by relative excess of free water, it occurs within a broad spectrum of diseases associated with hypervolemia (heart failure, liver cirrhosis), normovolemia and hypovolemia and it is a negative prognostic factor for patients with chronic heart failure and cirrhotic ascites. Vaptans (vasopressin antagonists, vasopressin V2-receptor inhibitors) reduce reabsorption of water in the distal nephron, they increase free water excretion and normalize serum concentrations of sodium in normovolemic and hypervolemic conditions associated with hyponatremia. Hyponatremia can be corrected (depending on cause, severity and speed of development) through the reduction of fluid intake, administration of a hypertonic solution NaCl, diuretics, oral administration of urea and by vaptans. The role of vaptans in the treatment of hyponatremia should be defined even better, in Europe vaptans can be used to treat the syndrome of inadequate antidiuretic hormone secretion (SIADH).

Hypoglycemia is a side effect of the therapy primarily with insulin, sulphonylurea derivates and glinides. Its therapy is based on the immediate ingestion of sacharides, preferably glucose. Amount of 15-20 g is recommended as its optimal dose, although several recent studies are suggesting amount related to the patient's weight. The therapy of severe hypoglycemia in the non-professional settings is based on glucagon injection, in the professional ones intravenous administration of glucose is preferable option.

Recent research of nutrition in the acute phase has brought up important findings regarding high protein and energy administration in critical illness with suggested adverse outcomes in catabolic patients. On the other hand, refeeding hypophosphatemia and refeeding syndrome may also be common during acute illness especially in chronically malnourished patients. Moreover, enteral nutrition is no longer superior to parenteral nutrition in recent studies as signals of harm using the enteral route in shock have been suggested. A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale has been proposed. Nutrition screening, assessment and intervention guidelines in intensive care and in chronic polymorbid internal patients has recently been published. These new findings and guidelines will probably change the practice of metabolic and nutrition therapy in acute illness and subsequent recovery.

Adenosintriphosphate is basic unit of cellular energetics, although during situations of high energy demand, cell had developed metabolic inert molecules - phosphagens - including phosphocreatine. Nowadays there are not so many recent publications describing positive effect of phosphocreatine supplementation., its potential benefit in supplementation is mainly in cardiology - acute myocardial infarction, acute or chronic heart failure. Another field of medicine with potential use of phosphocreatine is nephrology - in dialysis patients, or in psotemnopausal women in prevention of osteoporosis. In following article, we present review of studies describing positive effect of using phosphocreatine in specific group of patients in internal medicine.

Introduction:
GLP1 receptor agonist lixisenatide has demonstrated its efficacy in numerous clinical trials, nevertheless its real-life effectiveness data is limited.
Aim:
To describe effectiveness and safety of lixisenatide in routine clinical practice in the Czech Republic and the Slovak Republic, as recorded by the Registry-Based Observational Study.
Methods:
Multinational, multicenter, observational, non-interventional, 6-month prospective product registry of patients with type 2 diabetes mellitus aged > 18 years who were initiating therapy with lixisenatide. Patients were enrolled into this registry, provided written informed consent, between 1 May 2013 and 31 December 2015. Evaluations were performed at baseline and after 3 and 6 months of lixisenatide treatment. The primary objective of the study was the absolute change in glycated hemoglobin (HbA_1c) from baseline to month 6 after lixisenatide initiation. The study was approved by responsible ethics committees and performed in accordance with the Helsinki Declaration. Informed consent was obtained from all patients before enrolment in the study.
Results:
Overall 772 eligible patients (51.4 % males), mean age 56.7 (± 9.3) years, with mean diabetes duration 7.7 (± 5.5) years, mean duration of treatment with oral antidiabetic drugs 6.8 (± 4.9) years, and body mass index 37.6 (± 5.9) kg/m² were enrolled in the study. Overall, 93.6 % were obese, 86.3 % subject were treated for hypertension, and 76.0 % for dyslipidemia. In total 96.1 % of patients completed the 6 months' therapy. Lixisenatide significantly reduced HbA_1c (decrease by 9.7 ± 14.4 mmol/mol [3.1 ± 0.2 % DCCT] after 6 months in per protocol population), and body weight (decrease by 3.5 ± 5.4 kg). The best responders to the treatment were younger patients with higher BMI, who had a shorter duration of diabetes. Overall safety profile of lixisenatide was satisfactory in the study. The most frequent adverse events were functional disorders affecting the gastrointestinal system. There was no episode of severe hypoglycemia reported throughout the study.
Conclusion:
In a real-life practice cohort of patients with type 2 diabetes mellitus 6 months treatment with once-daily GLP1 receptor agonist lixisenatide significantly improved glucose control and decreased body weight without increasing the risk of symptomatic and/or severe hypoglycemia risk.
Funding:
Sanofi Czech Republic.

Present knowledge on pathogenic mechanisms in type 1 and type 2 diabetes mellitus may offer the identical scheme of the cascade steps disturbing B-cell and its organells. The only one difference is based in the initiation of the whole cascade by cytokines activated in previous infection (Type 1 DM) or by increased concentration of free fatty acids (Type 2 DM) in the individuals with different genetic background for both types of diabetes. Impaired function and structure of mitochondria causes cell failure and its following apoptosis. The elucidation of the cause of changes in developed diabetes enables to suggest some perspective therapeutic approaches and/or preventive ways.

Venous thromboembolic disease which includes both venous thrombosis and pulmonary embolism, is a frequent and potentially fatal disease. Based on the introduction of low-molecular-weight heparins (LMWH) into practice it has been proved that outpatient treatment of venous thrombosis is effective and safe for a large number of patients with VTE. The growing volume of data on LMWH outpatient treatment in recent years shows that up to 50 % of patients with clinically stable pulmonary embolism can be treated at home. In spite of these facts home treatment of pulmonary embolism has not been established as part of common practice as yet. If we were to summarize the conditions for home treatment, we would consider outpatient care for patients at low risk based on auxiliary criteria, free from hemodynamic instability (primarily without a shock state), free from right ventricular failure, prior chronic heart or lung disease, serious comorbidities (gastrointestinal tract disease, kidney disease, blood diseases, advanced cancers), at low risk of early thromboembolism recurrence, free from other indications for hospitalization (pain requiring parenteral analgesics, infections etc.), at low risk of bleeding and with guaranteed patient's cooperation and well-organized home care.

The prevalence of obesity continues to be increasing in all age groups in most countries of the European Union (EU). Many obese people have a history of several successful weight losses, but very few are able to maintain the weight loss over a longer period of time. Initiation of the GLP1 RA administration during weight loss maintenance would inhibit weight loss-induced increases in soluble leptin receptor plasma concentrations resulting in higher level of free leptin thereby preventing weight regain. In contrast initiation of insulin treatment in type 2 diabetes patients is frequently accompanied with weight gain. The GLP1 administration results in HbA_1c decrease accompanied with weight loss, presents attractive alternative to basal insulin. The question remains to be answered in the future, if the GLP1 RA administration is generally more frequently started in antiobese than antidiabetes implication.

Our report describes the case of patient with hypersensitive reaction regularly arising early after initiation of haemodialysis. This characteristic reaction with pletoric face coloration, bronchospasm, increase of blood pressure, anxiety and decrease of blood oxygen saturation at the consequence and central cyanosis was regularly present without dependence on type of dialysis membrane, drug premedication or prophylactic flushing haemodialysis system by isotonic natrium chloride solution. Low platelet value and trouble-free haemodialysis realized without heparin showed real cause of patients problem. Resolution of this state was regional citrate anticoagulation during intermitent haemodialysis.

We describe a case of an untreated female patient monitored over 8 years for chronic B-lymphocytic leukaemia (B-CLL). Over the 8 years, the patient has gradually developed severe kidney failure, even though the criteria for B-CLL treatment had not been fulfilled. Kidney biopsy revealed renal damage due to λ free light chains cast nephropathy as well as an infiltration of renal parenchyma with B-CLL cells. It was not before this biopsy that the presence of monoclonal immunoglobulins has been investigated. Immunofixation identified free monoclonal λ light chains in the serum and urine. Their serum concentration, quantified by densitometry, was 2.6 g/ l and urine concentration was 0.5 g/ l. A specific evaluation of free light chains in the serum revealed an extremely high concentration of free λ light chains, over 4,500 mg/ l, and normal concentration of κ free light chains, 10 mg/ l. The aim of this report is to emphasise that monoclonal immunoglobulin may be present in B-CLL as well as other lymphoprolipherative diseases and that it may cause damage to organs, similar to multiple myeloma or monoclonal gammopathy of undetermined significance. The described case confirms poor prognostic value of monoclonal immunoglobulin free light chains in patients with B-CLL and usefulness of an evaluation of their presence in patients with B-CLL, particularly if the patients have increased creatinine level. The described case also highlights the need for evaluation of the presence of free light chains in the serum of all patients with unclear cause of renal failure.

Cirrhosis of the liver is the final morphological stage of most liver diseases with subsequent risk of decompensation and complications (portal hypertension, HCC). At present it is apparent, however, that a dynamic two-way process is involved with a possibility of further progression, but also regression of fibrosis/cirrhosis provided that causal treatment of the basic hepatologic disease is possible. Determining the stage and level of fibrosis progression is absolutely key to further care of the patient, establishment of the prognosis and possibly the treatment indication. At present non-invasive methods of liver fibrosis are the preferred option already, (serum, elastography), which for this indication gradually replace a liver biopsy. These methods allow for an exact estimate of the patient's prognosis and first of all long-term non-invasive following of the liver disease development. Chronic hepatitis C is one of the most frequent causes of liver cirrhosis. The healing of hepatitis C is essential for the improvement of patients' prognosis and reduction of the risk of complications development. In the field of treatment of this disease a pharmacological revolution has taken place in recent years, unprecedented in the other fields of internal medicine. Due to the exact description and understanding of the cycle of virus replication, a number of direct-acting antiviral drugs have been introduced to the clinical practice, which made it possible to remove interferon preparations (numerous adverse effects) from the treatment after 20 years, but first of all they increased the effect of HCV treatment, reaching approx. 95-100 % healed patients after 12 weeks of the combined therapy. These preparations are essentially free from adverse effects and the treatment lasts 12-24 weeks (with an option of its shortening to 8 weeks). Their main disadvantage is their extremely high cost at the present time.

The article reviews history, indication and follow-up after heart transplantation, including the mechanical assist devices. Various complications of posttransplant follow-up are mentioned, e.g. rejection, infection, vasculopathy, meta-bolic disorders, hypertension or malignities. Pharmacotherapy used for immunosuppression is discussed. Heart transplantation improves the prognosis of patients with previous heart failure and also their quality of life.

Disturbance of haemostasis and bleeding are rather frequent complications of AL amyloidosis. These are frequently caused by increased fragility of capillaries, thrombocyte function disorders and coagulation cascade defects. The most frequent coagulation disorder is decreased factor X activity. We describe a 34-year old female after hysterectomy for myomatous uterus and metrorhagia. Before the surgery, the attending physicians did not identify any pathological changes suggesting a need for further investigations or presence of AL amyloidosis. Post-surgery development was complicated by life-threatening diffuse haemorrhage. Extended investigations of coagulation cascade revealed reduction of factor X activity to 16%. Targeted histological examination of the resected uterus confirmed AL amyloid deposits consisting of κ chains. The patient's bone marrow contained certain small level of multiplied κ chains-expressing plasma cells (< 10%); monoclonal immunoglobulins IgG κ and free κ chains were identified in serum. At that time, the patient did not satisfy the then valid Durie-Salmon criteria for multiple myeloma and thus the patient was diagnosed with primary systemic AL amyloidosis. The patient's condition gradually improved following substitution therapy (Prothromplex, fresh frozen plasma and erythrocyte transfusion) and bleeding slowly ceased so that chemotherapy with VAD (vincristine, adriamycin and dexamethasone) was initiated 6 weeks after the surgery. A total of 8 chemotherapy cycles were administered and complete haematological remission was achieved after the 5th cycle. Administration of the 8 VAD chemotherapy cycles resulted in increased factor X activity; bleeding complications subsided completely, thereby decreasing the risk of life-threatening mucositis-associated haemorrhage. Consequently, tandem high-dose chemotherapy (melphalan 100 mg/m²) with autologous haematopoietic stem cells transplantation was added to the treatment plan. Treatment was completed at the beginning of 2003 and, from that time, the patient is on continuous maintenance therapy with interferon α. Seven years from the diagnosis and 6 years from the completion of treatment the patient is in complete haematological remission, with no signs of organic damage caused by AL amyloid and with normal factor X activity. Factor X activity increased at the time when complete haematological remission was achieved after 8 cycles of VAD chemotherapy to 42%, it reached 68% the second year following high-dose chemotherapy, 77% after 5 years and 85% after 7 years. We had considered administration of high-dose chemotherapy in the standard regimen, i.e. following 4 cycles of VAD chemotherapy, as too high risk in the described young female patient. Therefore, we administered 8 cycles of conventional chemotherapy and only after complete haematological remission and partial organ response (factor X activity increased to 42%) were achieved, we added tandem high-dose chemotherapy to the treatment. We thus achieved long-term (7-years so far) complete haematological and organ remission. Increase in factor X activity is explicit over the entire 7-year observational period. We recommend starting treatment of high-risk transplant patients with AL amyloidosis with traditional chemoth

The study compares treatment results in two groups of patients with critical limb ischaemia:
the group A - 21 patients treated only with the pedal bypass is compared with the group B - 17 patients treated with the pedal bypass and free microsurgical muscular transfer covered with dermoepidermal graft. Primary/secondary one-year patency in the first group was 64.7/82.4% and 54.5/81.8% in the second group, respectively. Evaluation of the patency at the end of the study by means of the survival analysis together with construction of Kaplan-Meier survival curves and long-rank test did not prove significantly relevant difference between the two groups (p = 0.14). No statistically significant differences were found even in the number of relapses, amputations and deaths. Even though combined surgery is incomparably more demanding for surgical team, it represents substantially higher stress for a patient and it is performed in conditions of more extensive peripheral affection of the limb than pedal bypass only, it is not related with the higher number of relapses, amputations nor higher mortality. It is unjustifiable to deny this surgery to the patients in higher age groups with associated diseases and to use possible risks of this demanding surgery as a reasoning of the denial. Pedal bypass and muscular transfer represent the last possibility of saving a limb and keeping bipedal walking for these patients.

Background and Aims:
Rituximab in combination with chemotherapy is an effective treatment of patients (pts) with chronic lymphocytic leukemia (CLL). The most frequent adverse event of rituximab is infusion-related toxicity, e.g. cytokine-release syndrome that occurs usually during the first infusion. However, there is scarce data on feasibility and tolerability of rituximab infusions in CLL outside clinical trials. Therefore, we performed a single-center retrospective analysis of the frequency of rituximab infusion-related adverse events during the first- and the second line CLL treatment administered in the routine practice. We also analyzed its relation to parameters of tumor load and possible association with treatment efficacy. The safety of rapid infusion of rituximab in CLL pts was also evaluated.
Patients and Methods:
We analyzed 108 pts with CLL treated with rituximab-containing regimens between March 2005 and May 2011 at our institution. The most common first-line regimens (n = 66, 47 males, median age 63 years) were FCR (43 pts) and low-dose FCR (13 pts); 10 pts were treated by other protocols. Forty-two pts (32 males, median age, 65 years) underwent second line treatment: 18 pts rituximab-dexamethasone, 7 pts FCR, 7 pts low-dose FCR and 10 pts other regimens. Intravenous hydration (2 000 ml daily on days 0 and 1 of cycle), allopurinol 300-600 mg p. o. daily and premedication with methylprednisolone 80 mg i. v., acetaminophen 1 000 mg p. o. and bisulepine 1 mg i. v. were administered before rituximab infusion. Rituximab was given by fractionated infusion (100 mg for 2 hours, then if tolerated well, the rest of the dose with infusion rate escalation from 100 mg/hour up to 400 mg/hour) at the dose of 375 mg/m² in the first cycle. Subsequent doses (500 mg/m²) were administered by rapid-infusion protocol.
Results:
Rituximab infusion-related toxicity occurred in 32 % pts (n = 21) during the first line treatment and 19% pts (n = 8) during the second line treatment. Adverse events were predominantly mild and NCI CTCAE grade III/IV occurred rarely (3% in the first line, 2% in the second line). Infusion toxicity manifested predominantly as rigors, chills, fever and hypotension. All patients with adverse events could finish rituximab infusion as initially planned on the same day. Treatment response analysis did not demonstrate statistically significant differences between patients with and without rituximab infusion toxicity. Patients who developed rituximab infusion toxicity had higher absolute lymphocyte count (first line, 87 vs 56 × 10⁹/l, p = 0.21; second line, 101 vs 14 × 10⁹/l, p = 0.043). At the median follow-up of 36 months, there were no statistically significant differences in PFS or OS in both cohorts.
Conclusions:
Rituximab infusion-related toxicity in pts with CLL is relatively frequent (32%). However, occurrence of infusion-related symptoms can be reduced by proper premedication and severe adverse events are uncommon. In our experience, all patients were able to receive the planned dose of rituximab. Subsequent doses of rituximab could be safely administered by rapid-infusion protocol. We did not find statistically significant association between rituximab infusion

Light chain deposition disease (LCDD) is a rare systemic condition caused by monoclonal proliferation of terminally differentiated B-lymphocytes with production of free light chains and their deposition in kidneys or other organs. The aim of our study is to show the pitfalls of the diagnostics, and to demonstrate the effect of bortezomib-based therapy on a series of 4 patients with LCDD, from the point of hematological and organ therapeutic response. We include that bortezomib based treatment provides rapid and effective hematological response. It is, however, often accompanied by adverse events, especially within intensive treatment schedules. The most serious adverse effects includes peripheral neuropathy, which might be dose or treatment-limiting. Less intensive regimens ("bortezomib weekly") suggest an alternative with expectation of lower incidence of adverse effects. Autologous stem cell transplantation is a recommended and relatively safe approach in convenient candidates. Organ response is significantly delayed after hematological response, and organ damage by light chain deposits might not be fully reversible.

Paraneoplastic hypoglycaemia is relatively rare. The most common cause is insulinoma, tumour from pancreatic beta cells with insulin production. Fasting glycaemia together with hyperinsulinaemia during 24 hours of fasting is characteristically present. Endoscopic ultrasonography is the most sensitive method for localization of insulinoma, scintigraphy with labelled GLP-1 analogs and modified positron emission tomography are new perspective methods. Non-beta-cells tumours are mesenchymal or epithelial tumours with huge size, slow growth and increased production of insulin like growth factor IGF-2 (IGF-2oma). Fasting hypoglycaemia in this case is associated with increased levels of total and free IGF-2 as well as big IGF-2 form. Due to suppression effect there are decreased levels of insulin, growth hormone and IGF-1 and ratio IGF-2/IGF-1 is typically increased. In opposite to insulinoma diagnosis of non-beta-cells tumour mostly precedes the occurrence of hypoglycaemia.

Insulin resistance (IR) is defined as a condition where normal plasma free insuconcentrations induce a reduced response of the body. In the narrower sense we understand IR as the impairment of insulin action in the target structure which may arise at any level of the insulin signalling cascade. In the clinical conditions we usually define it as the impairment of insulin action in glucose metabolism, although it is true that the impairment may concern different effects of insulin and different cell structures. The characteristic feature of IR linked to the metabolic syndrome or Type 2 diabetes is defective signalling which affects PI3-kinase branch of insulin signalling cascade. Other insulin actions depending on the signalling through the Ras complex and MAP-kinase, may not be affected. Due to compensatory hyperinsulinemia they may be even increased. The article summarizes some recent findings regarding the structure and regulation of insulin signalling cascade and analyses selected primary and secondary causes of IR which include genetic and epigenetic factors, the microRNA regulation role, metabolic, humoral and immunological factors. The detailed knowledge of the causes of IR opens possibilities of its rational treatment. This is currently based on the treatment of curable causes of IR, i.e. consistent compensation of diabetes, weight reduction, regimen arrangements (diet, physical activity), re-assessment of the need to use corticosteroids in therapy, treatment of coexisting conditions and possibly administration of metformin or pioglitazone.