COVID-19 associated coagulopathy: Mechanisms and host-directed treatment.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is associated with specific coagulopathy that frequently occurs during the different phases of coronavirus disease 2019 (COVID-19) and can result in thrombotic complications and/or death. This COVID-19-associated coagulopathy (CAC) exhibits some of the features associated with thrombotic microangiopathy, particularly complement-mediated hemolytic-uremic syndrome. In some cases, due to the anti-phospholipid antibodies, CAC resembles catastrophic anti-phospholipid syndrome. In other patients, it exhibits features of hemophagocytic syndrome. CAC is mainly identified by: increases in fibrinogen, D-dimers, and von Willebrand factor (released from activated endothelial cells), consumption of a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13 (ADAMTS13), over activated and dysregulated complement, and elevated plasma cytokine levels. CAC manifests as both major cardiovascular and/or cerebrovascular events and dysfunctional microcirculation, which leads to multiple organ damage. It is not clear whether the mainstay of COVID-19 is complement overactivation, cytokine/chemokine activation, or a combination of these activities. Available data have suggested that non-critically ill hospitalized patients should be administered full-dose heparin. In critically ill, full dose heparin treatment is discouraged due to higher mortality rate. In addition to anti-coagulation, four different host-directed therapeutic pathways have recently emerged that influence CAC: (1) Anti-von Willebrand factor monoclonal antibodies; (2) activated complement C5a inhibitors; (3) recombinant ADAMTS13; and (4) Interleukin (IL)-1 and IL-6 antibodies. Moreover, neutralizing monoclonal antibodies against the virus surface protein have been tested. However, the role of antiplatelet treatment remains unclear for patients with COVID-19.

Severe thrombotic microangiopathy accompanied by liver rupture and multiorgan failure at week 26 of pregnancy.

OBJECTIVE: Case of a primigravid woman who suffered from severe PTMS (postpartum thrombotic microangiopathy syndrome) in the 26th week of pregnancy. DESIGN: Case report. SETTING: Department of Gynecology and Obstetrics, Hospital Nový Jičín; Department of Gynecology and Obstetrics, University Hospital Ostrava; Department of Hematooncology, University Hospital Ostrava; Department of Anaesthesiology and Resuscitation, University Hospital Ostrava. RESULTS: A thirty-one-year old primigravid woman was admitted to a secondary level institution due to epigastric pain and spontaneous rupture of membranes at 26th week of pregnancy. On admission her blood pressure was 140/90 mm Hg and an intrauterine fetal death was confirmed. The patients condition deteriorated quickly, resulting in a hypertensive crisis (220/120 mm Hg), which did not respond to medication over a two hour period. Emergency caesarean section was performed, but the patients condition progressed to HELLP syndrome class I, DIC and MOF. She was transferred to the intensive care unit (ICU) of the district referral hospital 38 hours postpartum. On admission to ICU, liver rupture was diagnosed which was managed conservatively. Therapeutic plasma exchange (TPEX) was initiated on day 2 postpartum in response to falling platelets and continued for 6 days. Due to acute kidney injury (AKI), the patient required dialysis for 21 days. The patients condition improved gradually and at 28 days after admission to ICU she was transferred back to the referring hospital. The consensus reached by the treating teams was that PTMS was the most likely diagnosis. CONCLUSION: This case demonstrates that PTMS improves (usually rapidly) after TPEX is initiated. It also emphasises the importance of maintaining a high index of suspicion for PTMS so that life-saving TPEX can be initiated, because it does not respond to classical treat-ment used in the management of HELLP syndrome. Other research suggests patients may also require a terminal complement blockade with the anti-C5 monoclonal antibody (eculizumab). Further research could focus on diagnostic tests to distinguish PTMS from HELLP to identify which patients would most benefit from these treatments.

Effect of prostate cancer cell line supernatant on functional polarization in macrophages.

OBJECTIVES: We aimed on effect of supernatant derived from prostate cancer cell line PC-3 on M1/M2 functional polarization in macrophages. BACKGROUND: Cytokines play an important role in carcinogenesis. Most of them are produced by macrophages. Macrophages are divided into groups M1 or M2. Classical phenotype macrophages M1 support pro-inflammatory effects and produce pro-inflammatory cytokines, such as interleukin 6 (IL-6), interleukin 12 (IL-12), tumor necrosis factor α (TNF-α). Macrophages exhibiting a phenotype M2 secrete anti-inflammatory cytokines, e. g. interleukin 10 (IL-10), transforming growth factor ß (TGF-ß). METHODS: Peripheral blood monocytes were cultivated for 7 days and during this time went through a differentiation into macrophages. Macrophages were stimulated for 24 hours by lipopolysaccharide (LPS) as a positive control and cultivated with supernatant for another 24 hours. RESULTS: Macrophages cultivated without LPS and without supernatant were used as negative control. Relative expression of IL-6, IL-10, IL-12 and TNF-α was measured by Quantitative real-time PCR. Expression of pro-inflammatory cytokines was lower in macrophages with supernatant compared to positive control. CONCLUSION: Expression of pro-inflammatory cytokines was lower in macrophages with supernatant (MΦ+sup) compared to positive control (MΦ+LPS). Effect of the supernatant on expression of IL-6, IL-10, IL-12 and TNF-α was not confirmed (Tab. 1, Fig. 5, Ref. 15).

[HELLP syndrome requiring therapeutic plasma exchange due to progression to multiple organ dysfunction syndrome with predominant encephalopathy, respiratory and renal insufficiency]. / HELLP syndrom vyzadující plazmaferézu pro rozvoj multiorgánové dysfunkce s dominující encefalopatií, respiracní a renální insuficiencí.

OBJECTIVE: Case report of woman with twin pregnancy complicated by HELLP syndrome which progressed to multiple organ dysfunction syndrome with predominant encephalopathy, renal and respiratory insufficiency with the need to perform repeated therapeutic plasma exchange. DESIGN: Case report. SETTING: Department of gynecology and obstetrics, University Hospital in Ostrava; Departmet of hematooncology, University Hospital in Ostrava; Department of gynecology and obstetrics, Vsetín hospital; Department of hematology and transfusion, Vsetín Hospital. RESULTS: Case of 35-year-old III gravida/II para with previously normal ongoing twin bichorionic biamniotic pregnancy in week 35+0, which was admitted to secondary care delivery room for three days lasting "flu like" symptoms and the right upper quadrant pain. She was icteric, exhausted, but normotensive (120/75 mm Hg). Acute caesarean section was performed for suspected fetal hypoxia and HELLP syndrome. The laboratory exams confirmed coagulopathy and HELLP syndrome second class during the operation. Blood loss was 800 ml. Despite standard treatment of HELLP syndrome, the condition had developed to renal insufficiency, bilateral fluidothorax, alveolar pulmonary edema, encephalopathy and hypertension. In laboratory results dominates markers of coagulopathy, thrombocytopenia and microangiopathic hemolytic anemia with presence of schistocytes. Due to multiple organ dysfunction syndrome with hemolysis of unclear origin, patient was transferred to referral hospital on sixth postoperative day. Therapeutic plasma exchange (TPEX) was promptly begun. Improvement of laboratory parameters occurred already after the first TPEX and after two days there was a significant improvement of neurological status. Nine TPEX procedures were performed. The treatment was terminated after platelet count reached 100×109/l. She was discharged from hospital 21 days after delivery. After exclusion of other clinical entities, the case was closed as postpartum thrombotic microangiopathic syndrome. CONCLUSION: Postpartum thrombotic microangiopathic syndrome includes states, which resemble HELLP syndrome with their laboratory result and clinical expression, but their behavior is different - progressively worsening with signs of disseminated intravascular coagulation and complex microangiopathy with multiple organ dysfunction. It is not responding to classic treatment of HELLP syndrome. In this cases usually improvement of patients condition follow initiation of therapeutic plasma exchange.

Different doxorubicin formulations affect plasma 4-hydroxy-2-nonenal and gene expression of aldehyde dehydrogenase 3A1 and thioredoxin reductase 2 in rat.

Increased oxidative stress is indisputably an important mechanism of doxorubicin side effects, especially its cardiotoxicity. To prevent impairment of non-tumorous tissue and to improve the specificity in targeting the tumor tissue, new drug nanotransporters are developed. In many cases preclinical therapeutic advantage has been shown when compared with the administration of conventional drug solution. Three forms of doxorubicin--conventional (DOX), encapsulated in liposomes (lipoDOX) and in apoferritin (apoDOX) were applied to Wistar rats. After 24 h exposition, the plasma level of 4-hydroxy-2-nonenal (4-HNE) as a marker of lipoperoxidation and tissue gene expression of thioredoxin reductase 2 (TXNRD2) and aldehyde dehydrogenase 3A1 (ALDH3A1) as an important part of antioxidative system were determined. Only conventional DOX significantly increases the level of 4-HNE; encapsulated forms on the other hand show significant decrease in plasma levels of 4-HNE in comparison with DOX. They also cause significant decrease in gene expression of ALDH3A1 and TXNRD2 in liver as a main detoxification organ, and a mild influence on the expression of these enzymes in left heart ventricle as a potential target of toxicity. Thus, 4-HNE seems to be a good potential biomarker of oxidative stress induced by various forms of doxorubicin.

Early identification of women with HELLP syndrome who need plasma exchange after delivery.

OBJECTIVES: To compare the laboratory course of HELLP syndrome between patients who recover and those who progress to postpartum thrombotic microangiopathic syndrome (PTMS) and require postpartum plasma exchange (PPEX) and to describe maternal characteristics and morbidity in women with PTMS. METHODS: In this retrospective analysis, 81 patients recovered and 5 progressed. Values for aspartate aminotransferase (AST), lactate dehydrogenase (LDH), bilirubin, platelets (Plt), urea, and creatinine at 0, 8, 16, 24, 48, and 72 hours postpartum in both groups were analyzed and compared. We also described maternal characteristics and morbidity of patients who progressed to PTMS. RESULTS: Patient groups differed significantly at 72 hours postpartum for Plt and LDH values and at 24 and 48 hours for bilirubin. Trends for AST and Plt differed significantly between the recovery and progression groups in the first 48 hours. Patients who progressed had acute kidney injury and other severe maternal morbidity, including one case of maternal death. CONCLUSIONS: Women with HELLP syndrome without clear Plt and AST improvement in the first 48 hours and with acute kidney injury, neurological impairment, or respiratory distress syndrome are at risk of progressing to PTMS. They should be administered PPEX between 24 and 72 hours postpartum.

[Thalidomide in the treatment of multiple myeloma: focus on combination with bortezomib]. / Thalidomid v lécbe mnohocetného myelomu se zamerením na kombinaci s bortezomibem.

Thalidomide, the first clinically available immunomodulatory drug, reaches monotherapy treatment response in about 1/ 3 of significantly pretreated patients with multiple myeloma, and in combination with glucocorticoids approximately 50% response rate. After addition of conventional cytostatic into the triple combination, therapeutic response is achieved in 80% of untreated patients or about 60% of pretreated patients. Therapeutic response is achieved even in 1/3 of patients with refractory multiple myeloma resistant to other available treatment. With regard to the frequency of adverse effects, particularly peripheral polyneuropathy, its use as maintenance therapy was nearly abandoned. The combination of thalidomide and bortezomib has a high therapeutic potential that was accompanied by a high frequency of peripheral polyneuropathy in entry studies. After optimizing bortezomib schedule and route of administration, which lead to significant reduction in the frequency of polyneuropathy, this combination is currently a very interesting therapeutic alternative for clinical practice. This is one of the most economically available treatment regimens combining the benefits of two major drug classes in the treatment of multiple myeloma -  proteasome inhibitor and imunumodulatory drugs. There is also a renewed interest in thalidomide following sharp decline in its use in recent years in the Czech Republic. Comprehensive work is focused on summarizing the longterm experience with thalidomide, with special reference to combination with bortezomib.

Prostate cancer, miRNAs, metallothioneins and resistance to cytostatic drugs.

MicroRNAs (miRNAs) translationally repressing their target messenger RNAs due to their gene-regulatory functions play an important but not unexpected role in a tumour development. More surprising are the findings that levels of various miRNAs are well correlated with presence of specific tumours and formation of metastases. Moreover, these small regulatory molecules play a role in the resistance of cancer cells to commonly used anti-cancer drugs, such as cisplatin, anthracyclines, and taxanes. In that respect, miRNAs become very attractive target for potential therapeutic interventions. Improvements in the sensitivity of miRNAs detection techniques led to discovery of circulating miRNAs which became very attractive non-invasive biomarker of cancer with a substantial predictive value. In this review, the authors focus on i) oncogenic and anti-tumour acting miRNAs, ii) function of miRNAs in tumour progression, iii) possible role of miRNAs in resistance to anticancer drugs, and iv) diagnostic potential of miRNAs for identification of cancer from circulating miRNAs with special emphasis on prostate cancer. Moreover, relationship between miRNAs and expression of metallothionein is discussed as a possible explanation of resistance against platinum based drugs.

[Diagnosis of heparin-induced thrombocytopenia in the Czech Republic]. / Moznosti diagnostiky heparinem indukované trombocytopenie v Ceské republice.

Heparin-induced thrombocytopenia is a prothrombotic adverse effect induced by platelet-activating antibodies against complexes of platelet factor 4 and heparin. Diagnosis rests on a clinical assessment of disease probability and laboratory testing. In this review, I describe some approaches to the evaluation of patients with suspected heparin-induced thrombocytopenia. In conclusion I draw attention to some of the reserves in the diagnostic approaches to this potentially fatal disorder in the Czech Republic.

[Guidelines for alemtuzumab treatment in chronic lymphocytic leukaemia (CLL)]. / Doporucení pro lécbu alemtuzumabem u chronické lymfocytární leukemie (CLL).

UNLABELLED: Alemtuzumab, the humanized monoclonal anti-CD52 antibody, is an effective agent in the treatment of fludarabine-refractory chronic lymphocytic leukemia (CLL). Due to many specific issues associated with alemtuzumab treatment, the Working Committee of Czech CLL Study Group developed these guidelines. SUMMARY OF RECOMMENDATIONS: (1) The main indication of alemtuzumab is fludarabine-refractory CLL. (2) Further possible indications include first-line treatment (in patients who cannot be treated by fludarabine-containing regimens), therapy of patients with del 17p, treatment of refractory autoimmune cytopenias and management of patients with severe cytopenias due to bone marrow infiltration. (3) The treatment should last 12 weeks and should not be terminated prematurely if there are no signs of CLL progression; bone marrow aspirate/biopsy can be performed after 12 weeks of treatment. (4) Subcutaneous administration of alemtuzumab seems to be equally effective with advantageous reduction of infusion-related adverse events. (5) Patients treated with alemtuzumab must receive combined antimicrobial prophylaxis against Pneumocystis jiroveci and herpetic viruses. Cytomegalovirus viremia should be monitored using weekly PCR from peripheral blood. (6) Use of alemtuzumab in combinations and consolidation/maintenance protocols must be considered experimental and needs optimization within prospective clinical trials. (7) Alemtuzumab treatment should be conducted by an experienced hematologist within a center of intensive hematology care.

Evaluation of alpha-methylacyl-CoA racemase, metallothionein and prostate specific antigen as prostate cancer prognostic markers.

Current diagnostic techniques are inefficient in distinguishing latent and low-risk forms of prostate cancer from high-risk forms. The present study is focused on determination of putative tumor markers of aggressive high-grade forms of prostate cancer. Potential markers were determined in blood sera of 133 patients (82 cases and 51 controls) and in cell lines (Gleason score 9-derived 22Rv1 and normal tissue derived PNT1A) on mRNA and protein levels. Alpha-methylacyl-CoA racemase (AMACR), metallothionein classes 1A and 2A (MT1A and MT2A) were determined and compared to prostate specific antigen (PSA) levels. On mRNA level, significantly increased expression of MT2A (2.4-fold), PSA (2.6-fold) and AMACR (8.4-fold) and insignificantly (1.9-fold) elevated MT1A in 22Rv1 compared to non-tumor PNT1A were determined. On protein level, significant enhancement of free PSA and total PSA in tumor cell line was evident. AMACR protein was 1.5-fold elevated in tumor line (below the level of significance). Contrary to mRNA, significantly (p = 0.01) reduced level of MT protein in tumor lines was determined. In the case of serum level, significantly enhanced MT level (4.5-fold) in patients' sera was found. No significant changes were observed in the case of AMACR. These findings indicate possible alternative role of MT to PSA prostate cancer marker. In addition, level of AMACR is distinctly higher in the Gleason score 9 in serum of patients and MT shows a descending trend in relation to Gleason score.

Insight to physiology and pathology of zinc(II) ions and their actions in breast and prostate carcinoma.

Zinc(II) ions contribute to a number of biological processes e.g. DNA synthesis, gene expression, enzymatic catalysis, neurotransmission, and apoptosis. Zinc(II) dysregulation, deficiency and over-supply are connected with various diseases, particularly cancer. 98 % of human body zinc(II) is localized in the intracellular compartment, where zinc(II) is bound with low affinity to metallothionein (MT). Zinc transporters ZIP and ZnT maintain transmembrane transport from/to cells or organelles. Imbalance of their regulation is described in cancers, particularly prostate (down-regulated zinc transporters ZIP1, 2, 3 and ZnT-2) and breast, notably its high-risk variant (up-regulated ZIP6, 7, 10). As a result, intracellular and even blood plasma zinc(II) levels are altered. MT protects cells against oxidative stress, because it cooperates with reduced glutathione (GSH). Recent studies indicate elevated serum level of MT in a number of malignancies, among others in breast, and prostate. MT together with zinc(II) affect apoptosis and proliferation, thus together with its antioxidative effects it may affect cancer. To date, only little is known about the influence of zinc(II) and MT on cancer, while these compounds may play an important role in pathogenesis. This review concludes current data regarding the impact of zinc(II) on the pathogenesis of breast and prostate cancers with potential outlines of new, targeted therapy and prevention. Moreover, blood plasma zinc(II) and MT levels and dietary zinc(II) intake are discussed in relation to breast and prostate cancer risk.

[Molecular mechanisms of zinc in prostate cancer]. / Zinek--molekulární mechanizmy u karcinomu prostaty.

In many developed countries, prostate cancer is the most common male tumour disease. The high incidence and mortality requires early diagnosis, differentiation of aggressive, highly malignant forms from clinically silent forms and understanding of the pathogenesis with its typical metabolic aberrancies (if any) in order to develop new targeted therapies. Prostate cells (including prostate cancer cells) are unique in their relation to zinc ions. Prostate tissue can accumulate these ions in up to tenfold higher concentration than other body cells. These ions influence many cellular processes incl. proliferation, differentiation and apoptosis. Prostate cancer cells lack ability to accumulate zinc. Therefore, zinc ions may be expected to play an important role in the disease pathogenesis, in its propagation and metastatic potential of tumour cells. Intracellular zinc levels are regulated by zinc-binding proteins, especially metallothioneins, and zinc transporters. Zinc level regulation dysfunction has been identified in prostate cancer cells and may thus play an important role in the prostate cancer pathogenesis. Moreover, due to its overproduction by prostate tissue, metallothionein serum levels are elevated and can be used as an important tumour marker.

Low molecular weight heparins for thromboprophylaxis during induction chemotherapy in patients with multiple myeloma.

BACKGROUNDS: Patients with multiple myeloma have a high risk of venous thromboembolism (VTE), especially during the induction chemotherapy. The aim of our observational study was to determine the impact of prophylaxis with low molecular weight heparin (LMWH) on the incidence of thromboembolic complications. PATIENTS AND METHODS: We analyzed the incidence of thromboembolic events in 258 patients treated with induction chemotherapy containing vincristin, doxorubicin or idarubicin, and dexamethasone, followed by stimulation chemotherapy with cyclophosphamide and G-CSF, and high-dose chemotherapy with melphalan. Two groups of these patients were compared based on the practice of thromboprophylaxis. Patients in the first group (Control, n = 140) were either not treated or treated with a short duration of anticoagulation therapy while the patients in the second group (Prophylactic, n = 118) underwent standard prophylaxis with LMWH throughout the entire period of induction chemotherapy. A total of 102 patients were selected for a close monitoring of the prophylactic effect of different LMWH doses and to be compared to patients without treatment. RESULTS: Standard prophylaxis with LMWH significantly (p < 0.007) lowered a risk of VTE when compared to patients without such prophylaxis (3.4% versus 12.9%, respectively). Furthermore, analysis of the subgroup of 102 patients revealed that higher LMWH doses (> 70 IU/kg per day) achieved full prophylaxis in 28 patients while lower doses were less effective leading to DVT in 3 (7.7%) out of 39 patients. In contrast, VTE was diagnosed in 5 (14.3%) out of 35 patients without any LMWH prophylaxis. CONCLUSION: Prophylaxis with LMWH leads to a significant reduction of the risk of thromboembolic complications during the induction chemotherapy in patients suffering from MM. The prophylactic effect of LMWH is dose-dependent.

Cell therapy, a new standard in management of chronic critical limb ischemia and foot ulcer.

Fifty percent of diabetics (7% of general population) suffer from peripheral arterial occlusive disease, which may lead to amputation due to critical limb ischemia (CLI). The aim of our study was to prevent major limb amputation (MLA) in this group of patients using a local application of autologous bone marrow stem cells (ABMSC) concentrate. A total of 96 patients with CLI and foot ulcer (FU) were randomized into groups I and II. Patients in group I (n = 42, 36 males, 6 females, 66.2 ± 10.6 years) underwent local treatment with ABMSC while those in group II (n = 54, control, 42 males, 12 females, 64.1 ± 8.6 years) received standard medical care. The frequency of major limb amputation in groups I and II was 21% and 44% within the 120 days of follow up, respectively (p < 0.05). Only in salvaged limbs of group I both toe pressure and toe brachial index increased (from 22.66 ± 5.32 to 25.63 ± 4.75 mmHg and from 0.14 ± 0.03 to 0.17 ± 0.03, respectively, mean ± SEM). The CD34(+) cell counts in bone marrow concentrate (BMC) decreased (correlation, p = 0.024) with age, even though there was no correlation between age and healing. An unexpected finding was made of relative, bone marrow lymphopenia in the initial bone marrow concentrates in patients who failed ABMSC therapy (21% of MLA). This difference was statistically significant (p < 0.040). We conclude ABMSC therapy results in 79% limb salvage in patients suffering from CLI and FU. In the remaining 21% lymphopenia and thrombocytopenia were identified as potential causative factors, suggesting that at least a partial correction with platelet supplementation may be beneficial.

Thrombolysis and cardiac arrest.

Cardiac arrest (CA) is a serious clinical condition that might be responsible in many cases for death, in other at least for development of irreversible multiple organ dysfunctions. During and after the CA a significant coagulopathy develops causing a decrease in proper tissue perfusion even if an early return of spontaneous circulation (ROSC) is achieved (no-reflow phenomenon). Administration of thrombolytics can solve the problem by destructing the blood clot in both macrocirculation and microcirculation. Results of some clinical trials proving an effectiveness of thrombolysis were published in the literature. Generally, it was done by describing its positive influence on some important clinical outcome measures (24hour survival, number of hospital admissions, better neurological status etc.) without significant increase in the number of bleeding complications. However, recent pivotal evidence based medicine (EBM) trial represented by TROICA study did not confirm the expected positive results. Because of that and also for other reasons (cost, fear of adverse effects, little practice etc.) thrombolysis, although theoretically promising therapeutical intervention, is not overly recommended and used in routine clinical practice in both out-of-hospital and in-hospital settings (Fig. 2, Tab. 4, Ref. 24). Full Text in free PDF www.bmj.sk.

Autologous bone marrow stem cell transplantation in patients with end-stage chronical critical limb ischemia and diabetic foot.

A total 37 patients suffering from end stage-IV Fontaine (CLI and diabetic foot) with an ulcerated limb in whom all previous therapeutic strategies failed (e.g. surgical revascularization and endovascular repair) were selected and underwent local transplantation of Autologous Bone Marrow Stem Cells (ABMSCs). The efficacy/safety ofthis therapy was assessed by using several endpoints such as (a) prevention of amputation, (b) wound healing and (c) degree of angiogenesis. In order to assess the limb ischemia and hypoxia the several tests and measurements were performed pre- and post transplantation at a variety of time intervals. The measurements include: TP-toe pressure measurements (by Periflux 5000 Laser Doppler and Oxymetry system), SPP-skin perfusion pressure, ABI-ankle brachial index, LDP-Laser Doppler baseline and heat perfusion assessment, TcpO2 without and with O2 provocation inhalation test. In addition, a battery of biochemical and hematological tests of peripheral venous blood samples and bone marrow analysis were performed. Limb salvage was 81% in 30 patients, 7 patients (19%) were amputated for terminal severe ischemia and gangrene progression. In the group of limb salvage patients initial Toe pressure 23.119 (std. error 5.358) increased in 90 days follow-up into 29.888 (std. error 5.99), Toe brachial index increased from 0.1469 (std. 0.0326) to 0.1991(std. 0.401). In LASER doppler and TcpO2, TcpCO2 tissue perfusion examination TcpO2% Increase after O2 provocation inhalation test was elevated from 162.95 (%) to 229.86% which confirmed a very good tissue vasoreactivity after BMSC transplantation.

[Our first experiences with autologous transplantation of bone marrow stem cells to treat pseudarthrosis, delayed fracture healing and long bone defects fracture]. / Nase první zkusenosti s transplantatí autologních kmenových bunek kostní drene v lécbe pakloubu, opozdeného hojení zlomenin a defektních zlomenin dlouhých kostí.

Traumatology and orthopaedics have undergone substantial progress in the use of new, sophisticated techniques, implants and navigation methods. Nevertheless, these new methods continue to fail in some instances. Regenerative medicine using the growth potential of stem cells that posses the ability to regenerate damaged tissues represent one of the possible ways forward. There is a potential for more comprehensive utilization of bone marrow stem cells that had for many years been used in transplant medicine. Traumatology and orthopaedics could utilise stem cells in the treatment of bone defects, i.e. in the treatment of pseudarthrosis, delayed fracture healing, defect fractures and aseptic bone necroses. Bone formation and growth is a complex, predominantly anabolic, process with a range of feedbacks. Nevertheless, it is the bone marrow where the necessary progenitors of bone growth are located. These are mesenchymal stem cells (MSCs), haematopoietic stem cells (HSCs) as well as thrombocytes containing a range of necessary growth factors. A number of studies showed positive results for stem cells treatment of pseudarthrosis, with only a fraction, however, being statistically significant in human medicine. This method was used in 11 patients of the Traumatology Centre of the Faculty Hospital in Ostrava, Czech Republic in 2008. The researched patients were treated for pseudarthrosis of long bones, delayed multifragmentary fracture haling and defect fractures of long bones. Autologous concentrate of bone marrow stem cells was applied in one session into the area of bone defect in a patient lightly anaesthetised with propofol. The results from this small sample of patients are not yet available. However, we are sharing our first experiences with this treatment option.

[Prevention of venous thromboembolism in surgery, laparoscopic surgery and urology]. / Prevence zilního tromboembolizmu v chirurgii, laparoskopické chirurgii, urologii.

Deep venous thrombosis and pulmonary embolism are major health problems with potential serious outcomes. Acutely, pulmonary embolism may be fatal. In the long term, pulmonary hypertension can develop from recurrent pulmonary embolism. Often overlooked is post-thrombotic chronic venous insufficiency occurring as a result of deep venous thrombosis causing deep venous reflux or obstruction with skin changes and ulceration with adverse impact on quality of life and escalation of health care costs. Almost all hospitalized patients have at least one risk factor for venous thrombosis and approximately 40% have three or more risk factors. Without thromboprophylaxis, the incidence of objectively confirmed, hospital-acquired deep venous thrombosis is approximately 10 to 40% among medical or general surgical patients and 40 to 60% following major orthopedic surgery. Abundant data from metaanalysis and blinded, randomized clinical trials have demonstrated strong evidence that primary thromboprophylaxis reduces deep venous thrombosis and pulmonary embolism and little or no increase in the rates of clinically important bleeding with prophylactic doses of low-dose unfractionated heparin, low-molecular-weight heparin or fondaparinuxem.

[Pre-operative care for cardiac surgery patients with cold antibody disorder, cryoglobulinaemia and cryofibrinogenemia]. / Péce a pacienty s nemocí chladovych protilátek, kryoglobulinemií a kryofibrinogenemií pred kardiochirurgickými zákroky.

We present an example of a patient with confirmed cold agglutinin disease who underwent cardiac surgery in hypothermia to illustrate a known fact that, when exposed to cold, cold agglutinins induce haemolysis of erythrocytes and that cryoglobulins and cryofibrinogens may, upon exposition to cold during a surgery under hypothermia, precipitate or gelify and thus increase plasma viscosity and damage microcirculation. Detailed immunological and haematological investigations in all patients awaiting cardiac surgery with a risk of developing hypothermia is not advantageous considering the low number of patients with clinical and laboratory signs of cold agglutinin disease, autoimmune haemolytic anaemia or paroxysmal cold haemoglobinuria and considering that these investigations, in addition, might not detect cryoglobulinaemia and cryofibrinogenemia. Identification of in-risk patients from the warning signs in the medical history, physical or basal laboratory testing who would subsequently undergo confirmatory investigations to verify the presence of these entities and define them accurately might be a potential solution to this clinical issue. Cardiac surgery strategy and peri-operative care should be tailored to the results of these investigations. Well-structured, practiced and functional cooperation between clinicians and laboratory personnel is a prerequisite for success in these circumstances.