[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.

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.

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.

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.

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.

Quality control of involved-field radiotherapy for patients with early stage Hodgkin's lymphoma based on a central prospective review. Comparison of the results between two study generations of the German Hodgkin Study Group.

PURPOSE: Based on experience in trials HD10 and HD11 (1998-2003), the radiotherapy reference center of the German Hodgkin Study Group (GHSG) continued their central prospective radiation oncological review in trials HD13 and HD14. The purpose of this analysis was to identify the impact of this procedure on radiotherapeutic management and to compare findings with former trials. METHODS: Between 2003 and 2009, 1,710 patients were enrolled in the HD13 trial (early favorable stages) and 2,039 patients in the HD14 trial (early unfavorable stages). All patients received a total of 30 Gy involved-field (IF) radiotherapy within a combined modality approach. RESULTS: For patients in HD13, there was a correction of disease involvement in 847/1,518 patients (56%), and for patients in HD14 in 1,370/1,905 patients (72%). Most discrepancies were observed in the lower mediastinum (19.2%), infraclavicular (31.7%), upper cervical (12.7%), and supraclavicular (10.8%) lymph nodes. This resulted in a change of disease stage in 241 (7%) patients and a shift into another study protocol in 66 (2%) patients. Due to the incorrect lymph node documentation of the participating study centers, the IF radiotherapy volume had to be enlarged in 1,063/3,423 patients (31%) and reduced in 244/3,423 patients (7.1%). These findings are comparable to the results of the quality control in the trials HD10 and HD11 (2,611 patients reviewed). CONCLUSION: Central review of the diagnostic imaging and clinical findings of Hodgkin's lymphoma patients shows a considerable number of discrepancies compared with the local evaluation. Thus, meticulous evaluation of all imaging information in close collaboration between the radiation oncologist and diagnostic radiologist is mandatory.

Clinical relevance of different dose calculation strategies for mediastinal IMRT in Hodgkin's disease.

BACKGROUND AND PURPOSE: Conventional algorithms show uncertainties in dose calculation already for three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) might even increase these. We wanted to assess differences in dose distribution for pencil beam (PB), collapsed cone (CC), and Monte Carlo (MC) algorithm for both 3D-CRT and IMRT in patients with mediastinal Hodgkin lymphoma. PATIENTS AND METHODS: Based on 20 computed tomograph (CT) datasets of patients with mediastinal Hodgkin lymphoma, we created treatment plans according to the guidelines of the German Hodgkin Study Group (GHSG) with PB and CC algorithm for 3D-CRT and with PB and MC algorithm for IMRT. Doses were compared for planning target volume (PTV) and organs at risk. RESULTS: For 3D-CRT, PB overestimated PTV(95) and V(20) of the lung by 6.9% and 3.3% and underestimated V(10) of the lung by 5.8%, compared to the CC algorithm. For IMRT, PB overestimated PTV(95), V(20) of the lung, V(25) of the heart and V(10) of the female left/right breast by 8.1%, 25.8%, 14.0% and 43.6%/189.1%, and underestimated V(10) of the lung, V(4) of the heart and V(4) of the female left/right breast by 6.3%, 6.8% and 23.2%/15.6%, compared to MC. CONCLUSION: The PB algorithm underestimates low doses to the organs at risk and overestimates dose to PTV and high doses to the organs at risk. For 3D-CRT, a well-modeled PB algorithm is clinically acceptable; for IMRT planning, however, an advanced algorithm such as CC or MC should be used at least for part of the plan optimization.

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.

Detection of pancreatic islet allograft impairment in advance of functional failure using magnetic resonance imaging.

This study evaluated the ability of magnetic resonance imaging (MRI) to predict failure of pancreatic islets (PI) transplanted into the hepatic portal vein. Brown-Norway (n = 18) and Lewis (n = 6) rats received islets isolated from Lewis donors. The rejection process in Brown-Norway recipients was mitigated by two different immunosuppressive regimens [tacrolimus + hydrocortisone for 3 months (n = 6) or tacrolimus for 12 days (n = 12)]. Longitudinal MRI monitoring of recipients at post-transplantation weeks 1, 2, 3, 4, 6, 8, 10, and 12 confirmed the ability to detect SPIO labeled PI after transplantation into the liver. The relative number of MRI signals related to PI isografts remained stable up to study completion. Recipients of PI allografts were normoglycemic until the end of study; signals declined gradually to 44 ± 17% in these animals. In animals with islets failure during post-transplant week 12, the number of signals decreased to 25 ± 10% of initial values. The difference between groups (islet function/failed) became significant post-transplant week 3. Our data demonstrate that the MRI changes attributable to rejection become apparent within 3 weeks after transplantation, i.e. at least 8 weeks before functional allograft failure.

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.

[Simultaneous transplantation of the kidney and the islets of Langerhans]. / Simultánní transplantace ledviny a Langerhansových ostruvku.

Simultaneous kidney and islet transplantation is recent therapeutic alternative for diabetics with end-stage kidney disease, who are not acceptable for simultaneous pancreas-kidney transplantation. Islet transplantation has less complications but still worse long-term function compared to whole pancreas transplantation.

Live imaging of Toll-like receptor 2 response in cerebral ischaemia reveals a role of olfactory bulb microglia as modulators of inflammation.

Activation of microglial cells in response to ischaemic injury, inflammatory and/or immune stimuli is associated with the marked induction of Toll-like receptor 2 (TLR2). At present, little is known about the spatial and temporal sequence of events, micro-regional specificities and the potential long term role of the TLR2 response to brain injuries. To investigate microglial activation/TLR2 response in real time, we generated a transgenic mouse model bearing the dual reporter system luciferase/green fluorescent protein under transcriptional control of a murine TLR2 promoter. In this model, transcriptional activation of TLR2 was visualized in the brains of live animals using biophotonic/bioluminescence molecular imaging and a high resolution/sensitivity charged coupled device camera. It was found that TLR2 induction/microglial activation has a marked chronic component after ischaemic injury and may last several months after the initial attack. The pro-inflammatory response was not restricted to the site of ischaemic injury but was also evident in the olfactory bulb. A significant TLR2 response was first seen in the olfactory bulb 6 h after stroke and several hours before the increase in photon emission over the site of infarction. This sequence of events was further confirmed by immunohistochemistry. A similar early TLR2 response from olfactory bulb microglia was observed in the brain's immune response to pathogens. We therefore propose that, owing to their unique situation, receiving and translating numerous inputs from the brain as well as from the environment, olfactory bulb microglia may serve as sensors and/or modulators of brain inflammation.

Diagnostic criteria of traumatic central cord syndrome. Part 2: a questionnaire survey among spine specialists.

STUDY DESIGN: A questionnaire survey. OBJECTIVES: To evaluate the need for the introduction of quantitative diagnostic criteria for the traumatic central cord syndrome (TCCS). SETTING: An online questionnaire survey with participants from all over the world. METHODS: An invitation to participate in an eight-item online survey questionnaire was sent to surgeon members of AOSpine International. RESULTS: Out of 3340 invited professionals, 157 surgeons (5%) from 41 countries completed the survey. Whereas most of the respondents (75%) described greater impairment of the upper extremities than of the lower extremities in their own TCCS definitions, symptoms such as sensory deficit (39%) and bladder dysfunctions (24%) were reported less frequently. Initially, any difference in motor strength between the upper and lower extremities was considered most frequently (23%) as a 'disproportionate' difference in power. However, after presenting literature review findings, the majority of surgeons (61%) considered a proposed difference of at least 10 points of power (based on the Medical Research Council scale) in favor of the lower extremities as an acceptable cutoff criterion for a diagnosis of TCCS. Most of the participants (40%) felt that applying a single criterion to the diagnosis of TCCS is insufficient for research purposes. CONCLUSION: Various definitions of TCCS were used by physicians involved in the spinal trauma care. The authors consider a difference of at least 10 motor score points between upper and lower extremity power a clear diagnostic criterion. For clinical research purposes, this diagnostic criterion can be considered as a face valid addendum to the commonly applied TCCS definition as introduced by Schneider et al.