Partial resection of native and prosthetic arteriovenous fistula as a treatment of late infections complications - series of case reports.

INTRODUCTION: Infection of arteriovenous fistula (AV) used for hemodialysis (HD) is associated with massive bleeding, sepsis development, formation of metastatic infectious foci, and a high risk of AV loss. Urgent management of an infected AV is crucial for successful treatment and AV salvage. CASE REPORTS: We present the use of partial resection as a successful method of dealing with late AV infection in two cases. In case 1, the resection was performed due to an infection of the native arteriovenous fistula (AVF) with two defects above the drainage vein aneurysms. In case 2, partial resection and replacement of the prosthetic arteriovenous fistula (AVG) were done due to an infection of HD puncture site. The AVs remained patent in both cases, with no further signs of infection postoperatively and, most importantly, without the need to use a temporary HD catheter. CONCLUSION: The establishment of a new AV is limited by the quality of the venous and arterial systems. All surgical, interventional and non-surgical means should be used to safely maintain the created AV patent. Provided that the requirements of an early indication are met, partial resection of the AV is the method of choice for AV infections and allows us to avoid using a permanent dialysis catheter in our patients.

[Neoadjuvant Use of Isolated Limb Perfusion in Large Myxoid Liposarcoma of the Thigh: a Case Report]. / Neoadjuvantní uzití izolované perfuze koncetiny u objemného myxoidního liposarkomu stehna: kazuistika.

Large unresectable STS presents a therapeutic challenge. Several options are being explored to avoid amputation without compromising the oncological outcome. Neoadjuvant chemotherapy delivers inconsistent and rather unsatisfactory results, preoperative radiotherapy compromises healing, hence it can impede adjuvant systemic treatment. We present a case report of neoadjuvant use of isolated limb perfusion with TNF-alfa and Alkeran (Melphalan) in a patient with initially unresectable large myxoid liposarcoma of the thigh. We achieved 55% reduction in size of the tumor that allowed for wide resection with a safe margin. Pathology confirmed 99% tumor necrosis. The patient has a full function of his extremity and is disease-free at one year follow-up. ILP should be considered as a treatment option which, in selected cases, can contribute to limb sparing surgery. Key words: sarcoma, soft tissue, regional perfusion, chemotherapy, surgery, orthopedic, limb salvage.

PD-1, PD-L1 and PD-L2 Expression in Mantle Cell Lymphoma and Healthy Population.

Cell surface expression of PD-1, PD-L1 and PD-L2 immune checkpoints on B and T cells obtained from patients with mantle cell lymphoma shows ambiguous results across many studies and creates obstacles for the implementation of immune checkpoint inhibitors into the therapy of mantle cell lymphoma. Using multiparameter flow cytometry we analysed surface expression of PD-1, PD-L1 and PD-L2 molecules on B and T cells of 31 newly diagnosed mantle cell lymphomas and compared it with the results of 26 newly diagnosed chronic lymphocytic leukaemias and 20 healthy volunteers. To gain insight into the age-dependent changes of surface expression of these immune checkpoints, flow cytometric subanalysis of 30 healthy volunteers of 25-93 years of age was conducted. Overall, we demonstrated weak surface expression of PD-1, PD-L1 and PD-L2 on B and T cells of mantle cell lymphoma patients (< 10 % when compared to healthy individuals). A significant age-dependent increase in the expression of PD-1 and its ligand PD-L2 was observed in healthy volunteers. Our results suggest that neither PD-1 nor its ligands represent relevant druggable targets for the therapy of mantle cell lymphoma. The observed age-dependent changes in healthy population could impact efficiency of immune checkpoint inhibitors and could be at least partly connected with increased incidence of cancer with age.

Visual cortex neurons phase-lock selectively to subsets of LFP oscillations.

It is generally thought that apart from receptive field differences, such as preferred orientation and spatial frequency selectivity, primary visual cortex neurons are functionally similar to each other. However, the genetic diversity of cortical neurons plus the existence of inputs additional to those required to explain known receptive field properties might suggest otherwise. Here we report the existence of desynchronized states in anesthetized cat area 17 lasting up to 45 min, characterized by variable narrow-band local field potential (LFP) oscillations in the range 2-100 Hz and the absence of a synchronized 1/f frequency spectrum. During these periods, spontaneously active neurons phase-locked to variable subsets of LFP oscillations. Individual neurons often ignored frequencies that others phase-locked to. We suggest that these desynchronized periods may correspond to REM sleep-like episodes occurring under anesthesia. Frequency-selective codes may be used for signaling during these periods. Hence frequency-selective combination and frequency-labeled pathways may represent a previously unsuspected dimension of cortical organization. NEW & NOTEWORTHY We investigated spontaneous neuronal firing during periods of desynchronized local field potential (LFP) activity, resembling REM sleep, in anesthetized cats. During these periods, neurons synchronized their spikes to specific phases of multiple LFP frequency components, with some neurons ignoring frequencies that others were synchronized to. Some neurons fired at phase alignments of frequency pairs, thereby acting as phase coincidence detectors. These results suggest that internal brain signaling may use frequency combination codes to generate temporally structured spike trains.

Development of vascular substitutes for low-flow peripheral bypass grafting - a review.

The development of a low-flow vascular prosthesis is a very topical issue. The authors present a pathway for the development of a prosthesis with optimal properties based on the idea of mimicking the characteristics of a biological model (saphenous vein graft) and programming these properties in the model of the prosthetic substitute. The vascular prosthesis presented consists of three layers - a non-absorbable scaffold representing vascular “media”, and two absorbable collagen layers - pseudointima and pseudoadventitia. The basic methods of physical testing are presented - the single axis stretch test and inflation-extension test, as well as other procedures that affect the final properties. These include collagen curing, antithrombotic treatment of the inner layer and the use of sterilization methods. The designed new graft was successfully implanted in an ovine model.

Concomitant embolism in the subclavian and pulmonary artery.

INTRODUCTION: Pulmonary embolism is a life-threatening condition that causes obstruction of the pulmonary arteries by an embolus, most often originating from the venous system of the lower limbs or pelvic veins. Depending on the extent of the embolism, an acute right-sided heart failure may result, with subsequent death. Paradoxical embolism is a condition in which a venous thrombus is embolized into the systemic circulation arteries by a right-to-left heart shunt. This condition most commonly occurs in the interatrial septum. The aim of treatment for pulmonary embolism is to remove the obstruction of the lung. Depending on the extent of the embolism and the patients hemodynamic status, thrombolytic or surgical treatment can be chosen. Thrombolytic therapy has become the basis of treatment for all types of acute pulmonary embolism. Currently, open surgery is indicated in hemodynamically unstable patients with massive pulmonary embolism, and increasingly frequently in submassive embolism where thrombolytic therapy is not effective or contraindicated. CASE REPORT: The case report describes a less common condition of pulmonary and concurrently systemic embolization in the subclavian artery. Thrombolytic therapy was contraindicated in this case due to the high risk of secondary embolism to the brain. Surgical embolectomy was performed from the pulmonary arteries simultaneously with direct embolectomy from the subclavian and brachiocephalic artery. The surgical management of acute pulmonary embolism is a suitable method of treatment for both massive pulmonary embolism where the procedure is performed as a life-saving indication, and submassive embolism where less invasive treatment would not be effective. CONCLUSION: Direct embolectomy of subclavian and brachiocephalic artery is associated with minimal risk of iatrogenic embolism into the arteries supplying the brain compared to indirect embolectomy performed from the cubital or brachial artery. Key words: embolism paradoxical embolization - embolectomy foramen ovale stroke.

[Isolated Perfusion of the Upper Extremity with TNF-α - Double Venous Cannulation]. / Izolovaná perfuze horní koncetiny s TNF-α - dvojitá kanylace zilního systému.

BACKGROUND: The authors present a technical variation of the standard cannulation for cardiopulmonary bypass perfusion during hyperthermic isolated limb perfusion (ILP) procedures in selected patients with unresectable soft tissue sarcoma or malignant melanoma. PATIENTS: Of 55 ILP procedures performed at our institution since the procedure was established in 2009, nine were performed at the upper extremity. Standard single venous cannulation was used in five cases, and extended, double venous cannulation in the last four. The standard technique for brachial vein cannulation in a small compartment of the upper extremity entails a problematic and longer perfusion of the upper extremity. This is due to the lower flow rate in the venous system and relatively large surface area with respect to weight. We present a simple technique based on a "Y" cannulation of the venous system via the deep brachial vein and superficial venous system via the basilic vein, delivering a 20% increase in flow rate in the extracorporeal circulation. Faster heating of the upper extremity and a stable thermal environment throughout upper-extremity ILP are essential for successful treatment. CONCLUSION: Extended technique of venous cannulation for extracorporeal circulation setting, due to their advantages, became standard in the upper limb ILP procedure at our institution.Key words: isolated limb perfusion - malignant melanoma - soft tissue sarcoma - upper limb - extracorporeal circulation The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 8. 1. 2017Accepted: 15. 1. 2017.

[Hyperthermic Isolated Limb Perfusion Combined with Tasonermin - a Perfusion Leakage Monitoring Technique]. / Hypertermická izolovaná perfuze koncetin v kombinaci s tasonerminem - technika monitorování úniku perfuzátu.

BACKGROUND: Hyperthermic isolated limb perfusion is used to treat irresectable extremity malignancies. It is based on the following principle - the perfusion of the extremity is isolated from systemic circulation and connected to an extra-corporal circuit via which a very high concentration of a chemotherapeutic agent is administered into the blood compartment of the extremity. In some cases, treatment efficiency can be improved using tasonermin (a TNF-α agent). By itself, tasonermin can cause severe health complications in patients if leakage into systemic circulation results in a level that exceeds the maximally tolerated dose. Therefore, it is important to monitor for leakage during the whole operation. METHOD: Leakage monitoring was performed by a nuclear medicine method based on the measurement of activity of a gamma-emitting radiotracer detected by a scintillation probe located over the heart. An amount of radiotracer that resulted in a basal level of measured signal was first administered into the systemic circuit followed by the administration of a second, one order of magnitude higher amount of radiotracer into the perfusion circuit. Leakage, when it occurred, increased the count rate detected over the heart, and the mathematical relation between leakage level and count rate increase was derived. RESULTS: In our department, the method was tested and optimized during isolated limb perfusion without using a TNF-α agent. Then, accreditation for the use of TNF-α was granted. Since then, the method has been used to monitor leakage in all cases of isolated limb perfusion with TNF-α. All isolated limb perfusion operations with TNF-α passed without complications. The radiation burden was almost negligible for both the patient and medical staff. CONCLUSION: The method described in this report represents a reliable method for perfusion leakage monitoring when using TNF-α in our department.Key words: perfusion - isolated limb - TNF-α - leakage - monitoring - nuclear medicine - radiopharmaceuticalsThe authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 16. 6. 2016Accepted: 21. 6. 2016.

Transcranial Doppler Ultrasound in the Current Era of Carotid Artery Stenting.

Since its introduction in 1982, transcranial Doppler ultrasound (TCD) has become an important diagnostic and monitoring tool and its usefulness has been well established in many clinical applications. In carotid artery stenting (CAS), TCD has mostly been reserved for the optimization of emboli protection devices. Currently, with increasing use of proximal protection systems resembling surgical clamps, TCD has become invaluable in providing the operator an insight into a patient's cerebral hemodynamic status. Additionally, in selected patients, adverse peri- or post-procedural cerebral outcomes may even be predicted allowing the operator to adjust the therapeutic strategy. This review summarizes the current knowledge regarding the use of TCD in patients undergoing CAS and suggests potential directions of future research.

[Small Molecules in the Treatment of Chronic Lymphocytic Leukemia in 2015 and in the Near Future]. / Malé molekuly v lécbe chronické lymfocytární leukemie v roce 2015 a v blízké budoucnosti.

Chronic lymphocytic leukemia is one of the most common lymphoid malignancies and is characterized by a highly heterogeneous clinical course. Combined regimens, such as fludarabine, cyclophosphamide, and rituximab have led to improvements in survival in younger patients with chronic lymphocytic leukemia and have become the standard of care in fit patients. However, the majority of chronic lymphocytic leukemia patients are elderly and not all patients are eligible for aggressive chemoimmunotherapy. In addition, patients with poor- risk cytogenetics have inferior responses to standard treatments with often shorter durations of response. Furthermore, the treatment outcomes of refractory disease are dismal. Nevertheless, there has been a dramatic change in therapeutic paradigms in the past year. Several new drugs have been approved for the treatment of chronic lymphocytic leukemia, including ibrutinib and idelalisib. These new molecules are orally active agents and both target the B -cell receptor associated kinases. Ibrutinib is a selective, irreversible inhibitor of Bruton tyrosine kinase, whereas idelalisib selectively targets phosphatidylinositol 3- kinase (PI3K) δ isoform. These agents have demonstrated remarkable activity in patients with relapsed/ refractory chronic lymphocytic leukemia, as well as patients with high-risk deletion of the 17p chromosome and/ or TP53 mutation. This review focuses on some of the novel small molecules that are currently approved or in advanced clinical development.

[The EDEC curriculum-the path to advanced echocardiography in the intensive care unit]. / Das EDEC-Curriculum ­ der Weg zur fortgeschrittenen Echokardiographie auf der Intensivstation.

Good knowledge of echocardiography is essential for modern intensive care medicine. A standardized curriculum for acquiring the expertise to perform TTE and TEE is a good way to strengthen one's own diagnostic skills.The EDEC curriculum from ESICM, which has been established for years, offers a good opportunity for structural further training at the advanced level in combination with gaining a high level of professional competence.

Viability of Human Arterial Grafts Monitored by Comet Assay.

An analytical method for studying DNA degradation by electrophoresis after cell lysis and visualization of DNA fragments with fluorescent dye, comet assay, was used to evaluate the viability of the endothelial layer of human arterial grafts with the aim of identifying the procedure that will least damage the tissue before cryopreservation. Four groups of samples were studied: cryopreserved arterial grafts that were thawed in two different ways, slowly lasting 2 hours or rapidly for approx. 7 minutes. Arterial grafts that were collected as part of multiorgan procurement with minimal warm ischemia time. Cadaveric grafts were taken as part of the autopsy, so they have a more extended period of warm ischemia. The HeadDNA (%) parameter and others commonly used parameters like TailDNA (%). TailMoment, TailLength, OliveMoment, TailMoment to characterize the comet were used to assess viability in this study. The ratio of non-decayed to decayed nuclei was determined from the values found. This ratio for cadaveric grafts was 0.63, for slowly thawed cryopreserved grafts 2.9, for rapidly thawed cryopreserved grafts 1.9, and for multi-organ procurement grafts 0.68. The results of the study confirmed the assumption that the allografts obtained from cadaveric donors are the least suitable. On the other hand, grafts obtained from multiorgan donors are better in terms of viability monitored by comet assay. Keywords: Arterial grafts, Cryopreservation, Cadaveric, Multiorgan procurement, Viability, Comet assay.

[Positive effects of training curriculum using the example of the interdisciplinary intensive care unit]. / Positive Effekte eines Einarbeitungs- und Weiterbildungscurriculums am Beispiel der interdisziplinären Intensivstation.

The training of new medical colleagues in hospitals is due to various aspects such as for instance staff shortages and time pressure often very challenging for everyone involved. Using the example of the interdisciplinary intensive care unit, the positive effects of a structured training curriculum have been scientifically proven in regular employee surveys. There was a statistically significant increase in satisfaction in the quality of induction (p < 0.0001), quality of training (p < 0.0001),  preparation for night shifts in the intensive care unit (p < 0.0001) and an improvement in general satisfaction in the clinic (p < 0.003) can also be shown. For these reasons, such curriculum contributes to increasing the quality of care and patient safety as well as the safety of medical staff in the medical work.

Endovascular treatment of infected aortic aneurysms.

OBJECTIVE: To report on the short- and long-term outcomes of patients with primary infected aortic aneurysm (IAA) treated by stent graft (SG) in two centers. MATERIAL AND METHOD: Over a period of 15 years, 32 patients with IAA underwent endovascular treatment. None had undergone previous aortic surgery. The causal relationship was gastrointestinal infection in 9 patients (28%), endovascular diagnostic/therapeutic procedures/resuscitation in 6 (19%), wound infection after previous surgeries in 5 (16%), urinary infection in 4 (13%), urology or gastroenterology procedures in 3 (9%), pancreatitis in 2 (6%), endocarditis in 1 (3%) and phlebitis in 1 (3%) patient. We implanted 11 bifurcated, 10 tubular thoracic, 4 aorto-uni-iliac, 4 tubular abdominal and 1 iliac SG. Two other surgeries were hybrid procedures. RESULTS: The etiological agent was identified in 28 (88%) patients. Twenty-six (81%) patients survived the 30-day postoperative period. Sixteen (50%) survived to 1-year follow-up and 13 (40.6%) survived to 3-year follow-up. Three patients have survived for less than 1 year and a further 3 for less than 3 years, so far. Among patients with aneurysms situated in central parts of the thoracic and infrarenal aorta there was a better death/survival ratio than among patients with a proximal or distal aneurysm location. CONCLUSION: The implantation of a SG may be an alternative to open surgery in selected groups of patients with primary IAA. Aneurysms of the central part of the thoracic or abdominal aorta have a more favorable prognosis with endovascular treatment.

Current trends in the diagnosis of vascular prosthesis infection.

Early diagnosis of an infected vascular prosthesis, a potentially life-threatening disease, is a precondition of adequate treatment. The most frequently used diagnostic imaging method is computer tomography. Non-acute infections caused by low grade agents may pose a challenge with ambiguous CT-images and other ancillary imaging methods are used for these cases, each offering different levels of diagnostic sensitivity. These methods come from the fields of radiology (magnetic resonance imaging - MRI) and nuclear medicine studies using labelled leukocytes (111In or 99mTc HMPAO), 99mTc labelled antigranulocyte antibodies, 67Ga-citrate or labelled antibiotics (99mTc-ciprofloxacin) or avidin in combination with 111In-biotin. Positron emission tomography (PET) or hybrid PET/CT using 18F-FDG are becoming increasingly popular. The authors of this review article point out the diagnostic potential of the different methods and current trends, including the possibilities of microbiological demonstration of the agent, as well as their potential position in the diagnostic algorithm.

[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.

Alterations of CHEK2 forkhead-associated domain increase the risk of Hodgkin lymphoma.

Checkpoint kinase 2 gene (CHEK2) codes for an important mediator of DNA damage response pathway. Mutations in the CHEK2 gene increase the risk of several cancer types, however, their role in Hodgkin lymphoma (HL) has not been studied so far. The most frequent CHEK2 alterations (including c.470T>C; p.I157T) cluster into the forkhead-associated (FHA) domain-coding region of the CHEK2 gene. We performed mutation analysis of the CHEK2 gene segment coding for FHA domain using denaturing high-performance liquid chromatography in 298 HL patients and analyzed the impact of characterized CHEK2 gene variants on the risk of HL development and progression-free survival (PFS). The overall frequency of CHEK2 alterations was significantly higher in HL patients (17/298; 5.7%) compared to the previously analyzed non-cancer controls (19/683; 2.8%; p= 0.04). Presence of any alteration within the analyzed region of the CHEK2 gene was associated with increased risk of HL development (OR = 2.11; 95% CI = 1.08 - 4.13; p= 0.04). The most frequent I157T mutation was found in 4.0% of HL patients and 2.5% of controls (p = 0.22), however, the frequency of 5 other alterations (excluding I157T) was significantly higher in HL cases and associated with increased risk of HL development (OR = 5.81; 95% CI = 1.12 - 30.12; p= 0.03). PFS in HL patients did not differ between CHEK2 mutation carriers and non-carriers. The predominant I157T mutation together with other alterations in its proximity represent moderate genetic predisposition factor increasing the risk of HL development.

[Cytostatic hyperthermic isolated limb perfusion (HILP) in VFN (General Faculty Hospital in Prague)]. / Cytostatická hypertermická perfuze izolované koncetiny (HILP) ve VFN.

Hyperthermic isolated limb perfusion (HILP) is a standardized method of treatment in selected patients with in-transient locoregional recurrence/methastasis of melanoma or, some other soft tissue tumors (incl. sarcoma etc.) Authors present history and current status of this treatment modality in General University Hospital in Prague. During one year period (7/2009-6/2010) 10 patients were indicated for this procedure. We performed 13 procedures (3x redo), 11 in lower extremity and 2 in upper extremity. There was no serious complication in this cohort of patiens. Multidisciplinar approach is indicated in melanoma patients care.

Contribution to FDG-PET/CT diagnostics and post-operative monitoring of patients with mycotic aneurysm of the thoracic aorta.

Bacterial infection of the aorta is a life threatening condition calling for timely diagnostics and therapy. In the short communication presented here, the authors offer a case report on a patient of 70 years of age with aneurysm of the descending aorta caused by salmonella. The advantages of a new diagnostic hybrid modality are demonstrated and also the possibility of using it in the course of long-term monitoring of patients.

[Contribution to diagnostics of vascular prosthesis infections]. / Príspevek k diagnostice infekce cévní protézy.

Vascular prosthesis infection is a life-threatening complication in 0.5-5% of cases. Early and reliable diagnosis is a necessity for adequate treatment. Computed tomography (CT) is the gold standard diagnostic method used world-wide with excellent results, but in cases of advanced graft infection. Low grade infections in non-acute patients are a diagnostic challenge requiring a new method with good diagnostic accuracy. The authors describe diagnostic accuracy of currently available methods.