[First Experience with Diaphragm Pacing System in the Czech Republic]. / První zkusenosti se stimulacním systémem bránice v Ceské republice.

Patients with impaired diaphragm function are dependent on long-term mechanical ventilation. It is associated with numerous health complications as well as significant economic burden. Intramuscular diaphragm stimulation through laparoscopic implantation of pacing electrodes is a safe method which enables restoring breathing using diaphragm in a considerable number of patients. The first implantation of diaphragm pacing system in the Czech Republic was performed in a thirty-four-year-old patient suffering from a high-level cervical spinal cord lesion. After eight years of mechanical ventilation support, just five months from initiation of stimulation, the patient is able to breathe spontaneously for ten hours per day on average, with expected total weaning. Once the insurance companies decide to reimburse the pacing system, a widespread use of the method even in patients with other diagnoses, including children, is expected. Key words: electrical stimulation, diaphragm, spinal cord injury, laparoscopic surgery.

Finding Eden - alternative transplantation sites for pancreatic islets.

Pancreatic islets transplantation is an established treatment method for type 1 diabetic patients with the hypoglycemia unawareness syndrome in whom a therapy with modern technologies fails. Islet transplantation is most commonly done using an interventional radiology method: a tissue suspension of pancreatic islets is applied into a branch of the portal vein through a percutaneously installed catheter. Although being minimally invasive unlike pancreas organ transplant, this method is associated with many technical difficulties. Possible complications of the procedure include hemorrhage and portal vein thrombosis. Unlike their natural dispersed localization in exocrine pancreas, isolated pancreatic islets are exposed to hypoxia, toxins and immunosuppressive drugs in the liver parenchyma. Direct contact with the recipients blood causes an instant blood mediated inflammatory reaction (IBMIR) resulting in the death of more than half of the pancreatic islets shortly after their application. Therefore the size of the islet graft is often insufficient and a number of transplanted patients require administration of exogenous insulin. All of these are reasons for seeking an alternative transplantation site with more hospitable conditions for long-term islet survival. Various transplantation sites have been tested in experimental and clinical research. The advantages and disadvantages of some of them are summarized in this paper. Currently, transplantation into the greater omentum seems most promising, which has already been used in clinical practice at several institutions.

[Hemicorporectomy as the Highest Grade of En Bloc Sacrectomy]. / Hemikorporektomie jako nejvyssí stupen en bloc resekce sakra.

Hemicorporectomy or translumbar amputation is an extensive surgical procedure consisting in removing the lower portion of the body. Thakur et al. found a total of 71 hemicorporectomies described in literature before 2017. In the form of a case study we present the case of our patient with terminal pelvic osteomyelitis, in whom hemicorporectomy was subsequently performed, namely from the spine surgery perspective. The man, 19 years old, was exposed to high-voltage electricity and fell down from a height of 4 meters. He suffered an instable comminuted fracture of T10 (AO A3.3.) with paraplegia (Frankel A) and multiple third-degree burns affecting 25% of his total body surface area. Subsequently, the patient underwent a total of 16 surgical procedures performed by medical experts in various specialties (orthopaedic surgery, general surgery, plastic surgery, urology, vascular surgery), but in spite of that the extensive pelvic osteomyelitis has not been successfully managed. At first, urine and stool diversion were performed. After 3 weeks, i.e. 18 months after the injury, the removal of the lower portion of the body was scheduled. The hemicorporectomy was divided into 4 stages. The surgery started by posterior transecting the spine at L4-L5 segment with nerve root and dural sac ligation and treating the bleeding venous plexus in the spinal canal. After turning the patient to the supine position, the second stage of the operation followed, consisting in transecting large vessels and harvesting a musculocutaneous flap from the right thigh. During the third stage of the surgery the separation of the L4-L5 motion segment was completed by the transaction of the anterior longitudinal ligament and m. psoas major, subsequently followed by the amputation of the lower portion of the body. During the last stage of the surgery, the wound was closed by musculocutaneous flap from the fight thigh with preserved a. femoralis. The patient was discharged to home in a generally good condition 127 days after the amputation of the lower portion of the body. Now, 1 year after the surgery, the patient enjoys good physical as well as mental health. Hemicorporectomy is an extensive surgical technique, which can despite multiple complications be offered to patients with otherwise unmanageable condition. Terminal pelvic osteomyelitis is currently the most frequent diagnostic indication and the resulting condition makes possible a long-term survival of the patient in a satisfactory condition. The spinal surgeon is an irreplaceable member of the multidisciplinary team performing the surgical procedure, the primary treatment of the spinal column considerably limits blood losses. Key words: hemicorporectomy, en bloc sacrectomy, terminal pelvic osteomyelitis, sacral tumors.

A Trimodal Imaging Platform for Tracking Viable Transplanted Pancreatic Islets In Vivo: F-19 MR, Fluorescence, and Bioluminescence Imaging.

PURPOSE: Combining specific and quantitative F-19 magnetic resonance imaging (MRI) with sensitive and convenient optical imaging provides complementary information about the distribution and viability of transplanted pancreatic islet grafts. In this study, pancreatic islets (PIs) were labeled with positively charged multimodal nanoparticles based on poly(lactic-co-glycolic acid) (PLGA-NPs) with encapsulated perfluoro-15-crown-5-ether and the near-infrared fluorescent dye indocyanine green. PROCEDURES: One thousand and three thousand bioluminescent PIs were transplanted into subcutaneous artificial scaffolds, which served as an alternative transplant site. The grafts were monitored using in vivo F-19 MR, fluorescence, and bioluminescence imaging in healthy rats for 2 weeks. RESULTS: Transplanted PIs were unambiguously localized in the scaffolds by F-19 MRI throughout the whole experiment. Fluorescence was detected in the first 4 days after transplantation only. Importantly, in vivo bioluminescence correlated with the F-19 MRI signal. CONCLUSIONS: We developed a trimodal imaging platform for in vivo examination of transplanted PIs. Fluorescence imaging revealed instability of the fluorescent dye and its limited applicability for longitudinal in vivo studies. A correlation between the bioluminescence signal and the F-19 MRI signal indicated the fast clearance of PLGA-NPs from the transplantation site after cell death, which addresses a major issue with intracellular imaging labels. Therefore, the proposed PLGA-NP platform is reliable for reflecting the status of transplanted PIs in vivo.

Incidence of acute spinal cord injury in the Czech Republic: a prospective epidemiological study 2006-2015.

STUDY DESIGN: A prospective study. OBJECTIVES: Analysis of epidemiological data about acute spinal cord injury (SCI) in the Czech Republic over a period of 10 years (2006-2015). METHODS: A data collection system was implemented in the rehabilitation centres which provides care to patients with acute SCI in the Czech Republic. The recorded variables are as follows: age at time of SCI; gender; cause of injury; neurological level of injury (NLI); and its severity (ASIA Impairment Scale (AIS)). Data from 2006 to 2015 were analysed and trends were determined. RESULTS: The overall number of acute SCI ranges between 250 and 300 cases annually. Two-third of the affected population are males. The average age at time of SCI is 49.1 years. The average incidence of traumatic SCI is 15.5 cases per year and is gradually decreasing. The leading cause of SCI are falls (44.5%), followed by traffic accidents (28.2%) and sports injuries including diving into water (19.7%). The incidence of non-traumatic SCI is 8.6 cases per year on average and has an upward trend. Inflammatory lesions account for 26.7% of cases, tumours account for 20.9%, and vascular related injuries make up 17.7%. The NLI occurs most often in the cervical segments (45.3%). The most frequently occurring lesions are motor incomplete: AIS D (33.3%). CONCLUSION: This study shows a stable occurrence of SCI in the Czech Republic, with cervical and motor incomplete cases being the leading ones. Epidemiological data are needed to improve the care of SCI patients and to promote an active life following it.

New quality assurance program integrating "modern radiotherapy" within the German Hodgkin Study Group.

INTRODUCTION: Field design changed substantially from extended-field RT (EF-RT) to involved-field RT (IF-RT) and now to involved-node RT (IN-RT) and involved-site RT (IS-RT) as well as treatment techniques in radiotherapy (RT) of Hodgkin's lymphoma (HL). The purpose of this article is to demonstrate the establishment of a quality assurance program (QAP) including modern RT techniques and field designs within the German Hodgkin Study Group (GHSG). METHODS: In the era of modern conformal RT, this QAP had to be fundamentally adapted and a new evaluation process has been intensively discussed by the radiotherapeutic expert panel of the GHSG. RESULTS: The expert panel developed guidelines and criteria to analyse "modern" field designs and treatment techniques. This work is based on a dataset of 11 patients treated within the sixth study generation (HD16-17). CONCLUSION: To develop a QAP of "modern RT", the expert panel defined criteria for analysing current RT procedures. The consensus of a modified QAP in ongoing and future trials is presented. With this schedule, the QAP of the GHSG could serve as a model for other study groups.

Quality control of involved field radiotherapy in the HD 13 and HD 14 trials : Report of the radiotherapy panel of the German Hodgkin Study Group (GHSG).

INTRODUCTION: As part of the foundation of the German Hodgkin Study Group (GHSG) in 1978, a central radiotherapy (RT) reference centre was established to evaluate and to improve the quality of treatment. During the study generations, the quality assurance programs (QAP) were continued and adapted to the demands of each study. The purpose of this article is to demonstrate the results of the fifth study generation and to compare them to the previous findings. METHODS: With the start of the fourth GHSG study generation (HD10-12), a central prospective review of all diagnostic images was established to create an individual treatment plan for each early stage study patient. The quality of involved field RT was retrospectively evaluated by an expert panel of radiation oncologists. In the fifth study generation (HD13-15), the retrospective review of radiotherapy performed was refined and the results were compared with the findings of the fourth generation. RESULTS: The expert panel analyzed the RT planning and application of 1037 (28 %) patients (HD13 n = 465, HD14 n = 572). Simulation films were available in 85 % of cases and verification films in 87 %. RT was assessed as major violation in 46 % (HD13 = 38 %, HD14 = 52 %), minor violation in 9 % (HD13 = 9 %, HD14 = 9 %) and according to the protocol in 45 % (HD13 = 52 %, HD14 = 38 %). CONCLUSION: The value for QAP of RT within the GHSG trials is well known. Still there were several protocol violations. In the future, the QAP program has to be adapted to the requirements of "modern RT" in malignant lymphoma.

Formation of Cholangiogenic Cysts Following Intrahepatic Islet Transplantation in Streptozotocin Diabetic Rats.

Permanent hyperinsulinemia and the resulting overstimulation of the insulin receptor signaling pathway is suspected as a trigger of cancer genesis in the livers of type 2 diabetic patients. Liver tissue (LT) surrounding transplanted pancreatic islets (PI) can be permanently exposed to insulin in even higher concentrations than in type 2 diabetic patients. Therefore, this study examines the effect of PI transplantation (Tx) on LT in animals with streptozotocin (STZ)-induced diabetes mellitus. The suboptimal mass (400 or 1000) of isogeneic PI was transplanted into either the portal vein or under the kidney capsule of diabetic Brown Norway (BN) rats. Healthy BN rats treated with 400 isogeneic PI transplanted in the portal vein served as a control group. During the first 6 months after PI Tx, small and infrequent cystic lesions developed in animals with STZ diabetes, irrespective of the Tx site. In 10 months, frequent and complex cystic lesions appeared in these animals. In the control group, several small lesions were detected but not until 10 months after the PI Tx. In summary, STZ is the likely main inductor of hepatic cystic lesions, but the contribution of PI was not confirmed.

In vivo vascularization of anisotropic channeled porous polylactide-based capsules for islet transplantation: the effects of scaffold architecture and implantation site.

The replacement of pancreatic islets for the possible treatment of type 1 diabetes is limited by the extremely high oxygen demand of the islets. To this end, here we hypothesize to create a novel extra-hepatic highly-vascularized bioartificial cavity using a porous scaffold as a template and using the host body as a living bioreactor for subsequent islet transplantation. Polylactide-based capsular-shaped anisotropic channeled porous scaffolds were prepared by following the unidirectional thermally-induced phase separation technique, and were implanted under the skin and in the greater omentum of Brown Norway rats. Polyamide mesh-based isotropic regular porous capsules were used as the controls. After 4weeks, the implants were excised and analyzed by histology. The hematoxylin and eosin, as well as Masson's trichrome staining, revealed a) low or no infiltration of giant inflammatory cells in the implant, b) minor but insignificant fibrosis around the implant, c) guided infiltration of host cells in the test capsule in contrast to random cell infiltration in the control capsule, and d) relatively superior cell infiltration in the capsules implanted in the greater omentum than in the capsules implanted under the skin. Furthermore, the anti-CD31 immunohistochemistry staining revealed numerous vessels at the implant site, but mostly on the external surface of the capsules. Taken together, the current study, the first of its kind, is a significant step-forward towards engineering a bioartificial microenvironment for the transplantation of islets.

Concordance in the interpretation of PET after chemotherapy in advanced stage Hodgkin lymphoma.

UNLABELLED: The aim was to analyze the degree of agreement between the central review panel and the local PET interpretation within the HD15 trial and its impact on subsequent treatment and progression free survival. PATIENTS, METHODS: The analysis set consisted of 739 patients with residues ≥ 2.5 cm after 6 or 8 cycles of BEACOPPesc from the HD15 trial performed by the German Hodgkin Study Group. The recommendation for or against further radiotherapy was based on the central [(18)F]FDG-PET interpretation. Central PET interpretation was compared to the local PET interpretation and concordance was measured using Cohen's Kappa coefficient. Prognostic impact of the analysis of concordance between local and central PET interpretations was evaluated using progression free survival (PFS); groups were compared with the log rank test. RESULTS: The central panel rated 548 of 739 patients (74%) as PET negative. Of these, 513 were also rated as PET negative in the local PET interpretation. PET positivity was seen by central reviewers in the remaining 191 patients (26%), in concordance with local reviewers in 155 cases. Even though substantial agreement was found (Cohen's Kappa 0.81), the interpretation of the central PET review panel led to a different therapeutic recommendation in 71/739 (10%) patients. PFS was equally high in groups in which the therapeutic regime had been changed on the basis of the central panel decision. CONCLUSION: High concordance is found between local and central reviewers with regard to PET interpretation in residual tissue after intense chemotherapy. The existence of the central PET review panel allows the identification of additional patients as PET negative so that radiotherapy can be safely omitted (35 of 548 patients = 4.7%).

Hyponatremia in spinal cord injury patients: new insight into differentiating between the dilution and depletion forms.

STUDY DESIGN: This is a retrospective study. OBJECTIVES: The objectives of this study were to present a new model for differentiating between the dilution and depletion forms of hyponatremia in patients in the postacute phase after spinal cord injury (SCI), and to identify possible etiological factors contributing to hyponatremia in these patients. SETTING: University Hospital Motol, Prague, Czech Republic. METHODS: Eighty-seven of 352 patients hospitalized in 2008-2012 in the Spinal Cord Unit were hyponatremic. Seventy-four patients had SNa+=130-135 mmol l(-1) and 13 patients had SNa+ below 130 mmol l(-1). We propose a simple model of an electrolyte solution in which the Na(+) concentration is higher than the Cl(-) concentration, making it possible to compare the effects of dilution and depletion of Na(+) and Cl(-) on the Na(+) concentration. The depletion of Na(+) and Cl(-) leads to a significant increase in the Na(+)/Cl(-) ratio, with the Na(+)-Cl(-) value remaining unchanged. Dilution with water results in a decrease of Na(+)-Cl(-) with the Na(+)/Cl(-) ratio remaining unchanged. RESULTS: In patients with SNa+ below 130 mmol l(-1), hyponatremia was consistent with the depletion model in 46% and with the dilution model in 32%. In patients with SNa+ ranging between 130 and 135 mmol l(-1), the respective rates were 34 and 12%. CONCLUSION: Examination of SNa+-SCl- and SNa+/SCl- in patients with SCI could be helpful in considering whether hyponatremia is consistent either with the NaCl dilution model or with the NaCl depletion model. Further studies are needed for more accurate interpretation of the results, particularly with respect to volume and acid-base disorders.

[Destruction of the Humeral Head in Sensory Deficit due to the Spinal Hemorhagia. Case Report]. / Destrukce hlavice humeru pri senzitivním deficitu po mísní hemoragii - kazuistika.

Degenerative changes of the shoulder are a common complication in patients after spinal cord injury. The main cause is chronic overload to the shoulder joint due to manual wheelchair propulsion and transfers. Reduced shoulder function has a significant impact on all aspects of daily life. Shoulder arthroplasty in this group of patients is a challenging procedure because of the unique demand on the shoulder. This report presents the case of a wheelchair user who additionally experienced a complete loss of sensation around her shoulder. As a result of a repetitive strain during transfers from the wheelchair to the ground, the humeral head was destroyed.

Effect of mesenchymal stem cells on the vascularization of the artificial site for islet transplantation in rats.

An adequate vascularization of the artificially created cavity is crucial for subsequent transplantation of isolated pancreatic islets. In a reported study, dynamic contrast-enhanced magnetic resonance imaging was used to assess the effect of mesenchymal stem cells on neoangiogenesis within connective tissue surrounding an implantable biocompatible device. The signal increase detected after injection of magnetic resonance contrast agent in each target region was considered to be an effect of contrast agent, which was related to the blood supply. To minimize the influence of variability in contrast agent application, all outcomes measured in the implanted devices were normalized to the signal intensity of kidney tissue. When supported by mesenchymal stem cells, the mean signal increase intra-abdominally was 42%, 41%, and 64% and within subcutaneously implanted devices was 23%, 54%, and 52% of that measured in kidney.

Intermittent self-catheterization in tetraplegic patients: a 6-year experience gained in the spinal cord unit in Prague.

OBJECTIVES: To present a system of urological care for patients with cervical spinal cord injury (SCI) in the Spinal Cord Unit in Prague. METHODS: Forty-one out of 412 patients hospitalized with acute SCI between 2007 and 2012 with motor complete SCI (AIS A,B) at the C4-C7 motor level and with sufficient follow-up duration were selected. Patients were trained using a male bladder catheterization model (37 with a transurethral catheter and 4 with a suprapubic catheter) to perform intermittent catheterization (IC) using an ergohand device, and were later encouraged to perform self-catheterization. RESULTS: On the basis of the motor level of the SCI, 8 out of the 41 study patients were assigned to group 1 (C4), 11 to group 2 (C5), 15 to group 3 (C6) and 7 to group 4 (C7). All patients in group 1 had an indwelling urinary catheter. In group 2, 6 patients (54.6%) learned to perform IC, with 2 of them needing another person's assistance. In 5 patients (45.5%), suprapubic cystostomy was maintained (insufficient functional grip, severe autonomic dysreflexia, prompt reflex erection). Group 3 included 12 patients (80%) performing intermittent catheterization and 3 patients (20%) with suprapubic cystostomy (insufficient functional grip, post-bladder-surgery condition, cognitive impairment). In group 4, only 1 patient (14.3%) had an indwelling catheter due to severe abductor spasticity, whereas the remaining 6 (85.7%) learned to perform IC. CONCLUSIONS: These findings suggest that patients with cervical SCI below the C5 motor level are able to learn self-catheterization, which increases independence and decreases the risk of urinary infection and stone formation.

The German evidence-based guidelines for Hodgkin's lymphoma. Aspects for radiation oncologists.

This report reviews aspects of the German evidence-based guidelines for Hodgkin's lymphoma relevant to radiation oncologists. Stage-adapted treatment is discussed with the focus on radiotherapy. Up-to-date literature citations provide an overview of current recommendations.

Expression analysis of genes involved in TLR2-related signaling pathway: Inflammation and apoptosis after ischemic brain injury.

Toll-like receptor 2 (TLR2) is involved in innate immunity in the brain and in the cascade of events after ischemic stroke. The aim of this study was to get an insight into the expression of genes related to TLR2 signaling pathway and associated with inflammation and apoptosis in the later stages of brain response after ischemic injury. Middle cerebral artery occlusion was performed on both wild-type and TLR2(-/-) mice followed by real-time PCR to measure the relative expression of selected genes. In TLR2(-/-) mice expression of genes involved in proinflammatory response was decreased after cerebral ischemia. Tnf was the most prominent cytokine active in the late phase of recovery. Contrary to proinflammatory genes, the expression of Casp8, as a hallmark of apoptosis, was increased in TLR2(-/-) mice, in particular in the late phase of recovery.

Large mediastinal tumor mass as a prognostic factor in Hodgkin's lymphoma. Is the definition on the basis of a chest radiograph in the era of CT obsolete?

PURPOSE: The risk factor "large mediastinal tumor mass" is an internationally accepted unfavorable prognostic factor in the staging of Hodgkin's lymphoma (HL). The definition of this risk factor varies considerably between large cooperative study groups. The purpose of the present analysis was to determine to which degree data obtained from chest radiograph (CRX) give the same results as those from CT scans (CT). METHODS: A total of 145 de novo HL patients in early unfavorable and advanced stages were included in this study. A total of 94 patients had a large mediastinal tumor mass according to the guidelines of the German Hodgkin Study Group (GHSG), while 51 had mediastinal lymph node involvement only. The size of mediastinal involvement and the thoracic diameter were measured on CRX and CT. Agreement between CRX and CT was determined by sensitivity and specificity analysis as well as descriptive statistics and correlations. RESULTS: The correlation of the diameters on CRX with those of CT was 0.95 for the tumor size and 0.77 for the thoracic diameter. The diagnostic decision-large mediastinal mass or not-correlated with 0.81 between CRX and CT and was identical in 90.3% of cases. The sensitivity was 0.87 and the specificity 0.96 for CRX, which is considered the current standard. CONCLUSION: The results show that there is a high agreement between the measurements of CRX and CT. Diagnosis of a large mediastinal mass disagreed in 10% of patients. Since the correct diagnosis of this risk factor is decisive for the adequate multimodal treatment choice, CRX should not be omitted.

Activation of the Jak/Stat signalling pathway by leukaemia inhibitory factor stimulates trans-differentiation of human non-endocrine pancreatic cells into insulin-producing cells.

Differentiation of pancreatic ß-cells is regulated by a wide range of signalling pathways. The aim of our current work was to evaluate the effect of the Jak/Stat signalling pathway on the differentiation of human non-endocrine pancreatic cells into insulin-producing cells. Activation of the Jak/Stat signalling pathway by leukaemia inhibitory factor (LIF) stimulated differentiation of C-peptide-negative human non-endocrine pancreatic cells into insulin-producing cells in 6.3 ± 2.0 % cells (N = 5) and induced expression of pro-endocrine transcription factor neurogenin 3, Notch signalling pathway suppressor HES6 and stimulator of ß-cell neogenesis REG3A. The expression of the REG3A gene and increased rate of differentiation into insulin-producing cells (10.2 ± 2.1 %) were further stimulated by a combination of LIF with nicotinamide and dexamethasone. Glucose-stimulated (5 vs. 20 mM) C-peptide secretion confirmed proper insulin secretory function of trans-differentiated insulin-producing cells (0.51 vs. 2.03 pmol C-peptide/µg DNA, P < 0.05). Our results indicate that Jak/Stat signalling critically contributes to trans-differentiation of non-endocrine pancreatic cells into functional insulin-producing cells. The positive effect of the Jak/Stat signalling pathway on trans-differentiation is mediated by the key genes that activate differentiation of pancreatic ß-cells.