[Urogenital Injury in Polytrauma Patients: a Five-year Epidemiological Study]. / Urogenitální poranení u pacientu u polytraumatu: petiletá epidemiologická studie.

INTRODUCTION The authors present an overview of polytrauma patients with urinary tract injuries managed in the Level I trauma centre. The purpose of this study was to evaluate the frequency of injuries to the urinary system, the mechanism of their injury and the method of treatment in the cohort of polytrauma patients treated in the trauma centre. MATERIAL AND METHODS Between 2012 and 2016, a total of 231 polytrauma patients were treated, of whom 47 (20.3%) also suffered a urotrauma. The renal trauma, ureteral trauma, bladder trauma and urethral trauma were classified according to the American Association for the Surgery of Trauma (AAST) scoring scale. RESULTS The non-operative treatment was opted for in 24 patients (86%) with Grade I and II kidney injury, whereas a surgical revision was indicated in line with the European Association of Urology (EAU) Guidelines in 9 patients (100%) with Grade III renal trauma or higher. The bladder trauma was treated non-operatively in two patients (22.2%) with Grade I and II bladder injury and operatively in 7 patients (77.7%) with Grade III injury or higher. After the operative management of urogenital injuries in 18 patients (38%), complications occurred in 7 patients (39%). A total of 7 patients (14.9%) died as a consequence of polytrauma with urinary tract injuries and in 5 of them the death occurred within 30 days of polytrauma, but no urinary tract injury led directly to death of the patient. DISCUSSION Kidneys are the most frequently injured uropoietic organ. A civilian kidney trauma is present in up to 5% of trauma patients and accounts for 24% of abdominal injuries. The computed tomography scanning with intravenous contrast (CT IVU) remains the Gold Standard. In recent decades there was a shift in treating the prevailing majority of patients with a kidney trauma, namely from surgical revision to non-operative treatment. This trend was also observed by the authors in their own cohort. CONCLUSIONS Based on the evaluation of their own cohort of patients, the authors state that the diagnostic algorithm including CT IVU and also UCG in indicated patients are adequate to timely diagnose the urinary tract injuries, including polytraumas. The study confirmed that the most frequent injury to the urinary tract in polytrauma patients is the kidney trauma and that the urinary tract injury is not usually the cause of death in polytraumatized patients. Key words: polytrauma, urotrauma, urogenital organ injury, kidney, urinary bladder, AAST.

Driving performance and psychomotor function in depressed patients treated with agomelatine or venlafaxine.

OBJECTIVE: We conducted a randomized case-control study in depressive inpatients to assess the effects of agomelatine and venlafaxine on psychomotor functions related to driving skills and on driving performance in an on-road driving test. METHOD: 40 depressed inpatients treated with agomelatine (n = 20) or venlafaxine (n = 20) were tested before pharmacological treatment (t0), and on days 14 (t1) and 28 (t2). 20 healthy subjects were examined in the same time schedule to control for retest effects in psychomotor measures. Additionally, participants were rated in a standardized on-road driving test on day 28 by a licensed driving instructor, who was blind with respect to treatment, diagnosis and test results. RESULTS: After 4 weeks of treatment (t2) with agomelatine or venlafaxine, patients showed a significant reduction in depressive symptoms, and a distinct improvement in psychomotor functions. Controlling for retest effects in psychomotor measures, data indicate, that both patient groups significantly improved in tests measuring reactivity and stress-tolerance. Furthermore, prior discharge to outpatient treatment (day 28), 72.5% of patients were labeled abundantly fit to drive in the on-road driving test by a licensed driving instructor. However, patients did not reach the performance level of healthy controls in functional domains tested. Significant differences between treatment groups were not observed. CONCLUSION: Our results indicate that depressed inpatients treated with agomelatine or venlafaxine show a better test performance on tasks related to driving skills than do untreated depressives and could predominantly be rated as fit to drive on an actual driving test prior discharge to outpatient treatment.

Early improvement and serum concentrations of citalopram to predict antidepressant drug response of patients with major depression.

INTRODUCTION: Post hoc analyses of clinical trials have shown that early improvement around day 14 is highly predictive for later response. More-over, evidence has been given that sufficiently high concentrations of antidepressant drugs in blood are required to attain response. In this study, we determined cut-off levels for citalopram serum concentrations and clinical improvement during the early phase of treatment to predict later response and the predictive power of these measures either alone or in combination. METHODS: Inpatients with depressive disorder according to ICD-10 who received citalopram were included. Psychopathology was assessed by the 17-item Hamilton Depression (HAMD-17) rating scale, and serum concentrations of citalopram were measured in weekly intervals. RESULTS: The analysis included 55 inpatients. Receiver operating characteristics analysis revealed for citalopram a serum concentration of 53 ng/ml on day 7 and a clinical improvement of 24% on the HAMD-17 scale on day 14 as significant cut-off values to predict response after 5 weeks of treatment. Both measures taken together predicted response on week 5 with 73% sensitivity and 85% specificity with an odds ratio of 14.6. DISCUSSION: It is concluded that treatment with citalopram should be guided by symptom rating at baseline and on day 14 and serum concentration determination on day 7.

Lack of involvement of type 7 phosphodiesterase in an experimental model of asthma.

Type 7 phosphodiesterases (PDE7) are responsible for the decrease of intracellular cyclic AMP (cAMP) in many cells involved in allergic asthma by suppressing their potential to respond to many activating stimuli. The elevation of intracellular cAMP has been associated with immunosuppressive and anti-inflammatory activities and represents a potential treatment of asthma. Our aim was to evaluate the impact of the deletion of the murine phosphodiesterase (PDE)7B gene and then to evaluate the efficacy of a newly described selective PDE7A and -B inhibitor on an ovalbumin (OVA)-induced airway inflammation and airway hyperreactivity (AHR) model in mice. Inflammation was determined 72 h after single OVA challenge or 24 h after multiple challenges by the relative cell influx and cytokine content in bronchoalveolar lavage fluid. AHR and immunoglobulin E levels in serum were determined after multiple challenges. For the first time, we have demonstrated that the deletion of the PDE7B gene or the pharmacological inhibition of PDE7A and -B had no effect on all the parameters looked at in this model. These results highlight the absence of any implication of the PDE7 enzyme in our model.

AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011.

Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from "strongly recommended" to "potentially useful". Evidence-based "therapeutic reference ranges" and "dose related reference ranges" were elaborated after an extensive literature search and a structured internal review process. A "laboratory alert level" was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate- and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint effort.

AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011.

Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from "strongly recommended" to "potentially useful". Evidence-based "therapeutic reference ranges" and "dose related reference ranges" were elaborated after an extensive literature search and a structured internal review process. A "laboratory alert level" was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint eff ort.

[Mortality risk in polytrauma patients with pelvic injury]. / Riziko umrtí u polytraumatizovaných pacientu s poranením pánve.

The aim of the study is to present results showing whether a pelvic injury in polytrauma patients means a high risk of mortality. The retrospective study (January 2001 - December 2006) included 453 polytrauma patients (130 women, 323 men) with ISS exceeding 16 points, hospitalized at the authors' department (Traumacentre Level I). The age of patients ranged between 13-93 years, the mean age of the whole group was 41 years (43 years in women, 40 years in men). The highest percentage of the deceased was recorded in the subgroup with abdominal injury (35%) and in the subgroup with pelvic injury (31%), the lowest in the subgroup without abdominal injury (20%). A significant difference was recorded between the numbers of deceased patients with and without abdominal trauma (p < 0.001), and between the numbers of patients with and without pelvic injury (p = 0.046). The results of the study have demonstrated a significantly higher rate of mortality in polytrauma patients with ISS > 16 points, with a simultaneous pelvic injury as compared to the patients without pelvic injury.

[Infectious complications of surgically treatment pelvic fractures]. / Infekcní komplikace operacní lécby zlomenin pánve.

Based on case histories, the authors draw attention to important infectious complications in patients surgically treated for pelvic injuries. These complications were recorded in four out of 75 patients (5.3%) undergoing surgery for pelvic fracture in the period from 2001 to 2005. The chief risk factors for the development of infection included the poor state of health of a polytraumatized patient in combination with a long stay in an acute care unit, and severe trauma and bleeding of soft tissue structures in B and C types of pelvic injury. Bacteriological findings showed the presence of several pathogenic species (Enterobacter cloacae, Citrobacter koseri, Pseudomonas aeruginosa and Klebsiella oxytoca) or multi-resistant bacteria (methicillin-resistant Staphylococcus aureus).

[Polytraumas in injured patients over 65 years of age]. / Polytrauma u zranených starsích 65 let.

INTRODUCTION: Geriatric trauma is most commonly defined as a trauma in patients of 65 years of age and over. These patients represent a specific problem due to their vulnerability, limited physiological response to the traumatic stress and high frequency of associated disorders, complicating the treatment. The aim of this report is to assess polytrauma patients of 65 years of age and older, compared to a group of younger patients. PATIENTS, METHODOLOGY AND RESULTS: 198 polytrauma patients, hospitalized from 2005 to 2006 were included in the retrospective study. Out of the total, 27 subjects (13.6%) were 65+ years old. Upon their admission, the difference in APACHE II between the groups was highly statistically significant (19-27.2, p = 0.0001). The ISS (the mean value) score was higher in the elderly patients (29-38). Traffic injuries, including pedestrian-vehicle collisions (61-73%), were the commonest mechanism of injuries in the both groups. There was a significant difference in the rates of craniocerebral injuries (80-96%, p = 0.041). During the early posttraumatic period, 99 (57%) urgent surgical procedures were performed in younger patients, compared to 11 (79%) procedures in the elderly. The difference in death rates was statistically significant (25-44%, p = 0.031). CONCLUSION: Polytraumas in the elderly (65 years of age and over) injured is characterized by higher severity scores and higher rates of craniocerebral injuries. Traffic injury was the commonest mechanism of injury. The death rate was higher in the elderly patients.

Ultrasound estimation of volume of pleural fluid in mechanically ventilated patients.

OBJECTIVE: The aim was to develop a practical method for estimation of the volume of pleural effusion using ultrasonography in mechanically ventilated patients. DESIGN: Prospective observational study. SETTING: 20-bed general intensive care unit in the university hospital. PATIENTS AND PARTICIPANTS: 81 patients were included after initial suspicion of pleural fluid on chest supine X-ray and pre-puncture ultrasound confirming effusion. Patients with thoracic deformities, post-lung surgery, with diaphragm pathology, haemothorax, empyema and with incomplete aspiration of pleural fluid on post-puncture ultrasound were excluded. INTERVENTIONS: Patients were supine with mild trunk elevation at 15 degrees . Probe was moved upwards in posterior axillary line, and transverse section perpendicular to the body axis was obtained with pleural separation visible at lung base. The maximal distance between parietal and visceral pleura (Sep) in end-expiration was recorded. Thoracentesis was performed at previous probe position and volume of pleural fluid (V) recorded. MEASUREMENTS AND RESULTS: 92 effusions were evaluated and drained; 11 (12%) were excluded for incomplete aspiration. Success rate of obtaining fluid under ultrasound guidance was 100%; the incidence of pneumothorax or bleeding was zero. Mean Sep was 35+/-13 mm. Mean V was 658+/-320 ml. Significant positive correlation between both Sep and V was found: r=0.72; r(2)=0.52; p<0.001. The amount of pleural fluid volume can be estimated with the simplified formula: V (ml)=20 x Sep (mm). Mean prediction error of V using Sep was 158.4+/-160.6 ml. CONCLUSIONS: Easy quantification of pleural fluid may help to decide about performing thoracentesis in high-risk patients, although thoracentesis under ultrasound guidance appears to be a safe procedure.

Normocapnic high-frequency oscillatory ventilation affects differently extrapulmonary and pulmonary forms of acute respiratory distress syndrome in adults.

The recently reported differences between pulmonary and extrapulmonary acute respiratory distress syndromes (ARDS(p), ARDS(exp)) are the main reasons of scientific discussion on potential differences in the effects of current ventilatory strategies. The aim of this study is to assess whether the presence of ARDS(p) or ARDS(exp) can differently affect the beneficial effects of high-frequency oscillatory ventilation (HFOV) upon physiological and clinical parameters. Thirty adults fulfilling the ARDS criteria were indicated for HFOV in case of failure of conventional ventilation strategy. According to the ARDS type, each patient was included either in the group of patients with ARDS(p) or ARDS(exp). Six hours after normocapnic HFOV introduction, there was no significant increase in PaO2/F(I)O2 in ARDS(p) group (from 129+/-47 to 133+/-50 Torr), but a significant improvement was found in ARDS(exp) (from 114+/-54 to 200+/-65 Torr, p<0.01). Despite the insignificant difference in the latest mean airway pressure (MAP) on conventional mechanical ventilation (CMV) between both groups, initial optimal continuous distension pressure (CDP) for the best PaO2/F(I)O2 during HFOV was 2.0+/-0.6 kPa in ARDS(p) and 2.8+/-0.6 kPa in ARDS(exp) (p<0.01). HFOV recruits and thus it is more effective in ARDS(exp). ARDS(exp) patients require higher CDP levels than ARDS(p) patients. The testing period for positive effect of HFOV is recommended not to be longer than 24 hours.

Apoptosis as an early event in the development of multiple organ failure?

We have recently developed a simple method of plasma free DNA detection, which enables us to distinguish between apoptotic and genomic (necrotic) DNA. After applying this method to the critically ill, we revealed apoptotic DNA on the day of admission to be higher than later when multiple-organ failure developed. Moreover, apoptotic DNA contributed to total plasma DNA much more than DNA from necrotic cells and its increase predicted future development of multiple-organ failure and death.

[1H-MR spectroscopic imaging in patients with clinically diagnosed Alzheimer's disease]. / 1H-MR-spektroskopische Bildgebung bei Patienten mit klinisch gesichertem Morbus Alzheimer.

PURPOSE: To detect regional differences in accompanying metabolic changes, 1H-Magnetic Resonance Spectroscopic Imaging (MRSI) was performed in 16 patients with Alzheimer's disease (AD); the clinical diagnosis was based upon DSM-III-R and NINCDS-ADRDA guidelines. METHODS: In the hippocampal region metabolic maps of the local distribution of N-acetylaspartate (NAA), choline (Cho), creatine compounds (P(Cr)) and lactate were determined. Ratios of Cho/NAA, (P)Cr/NAA and Cho/(P)Cr calculated from selected hippocampal spectra were compared to those from healthy volunteers (n = 17). RESULTS: AD patients demonstrated an increase of Cho/NAA and (P)Cr/NAA ratios caused by increased choline compounds and decreased NAA. These alterations were observed in 11/12 cases in the hippocampal and in 7/12 in the temporo-occipital region. Hippocampal Cho/NAA ratios (0.56 +/- 0.19) were significantly elevated compared with controls (0.33 +/- 0.04; p < 0.0001). CONCLUSION: The observed elevation of choline compounds in the hippocampus supports the hypothesis that alterations in the cholinergic system play an important role in Alzheimer's disease. The observed reduction of NAA is due to neuronal degeneration.

The influence of smoking on the serum level of duloxetine.

Duloxetine is a dual acting antidepressant (selective serotonin and norepinephrine reuptake inhibitor). Existing data suggest that the advisable therapeutic serum level of duloxetine ranges between 20 and 80 ng/mL. In a naturalistic setting we determined duloxetine serum levels within a steady state in a sample of depressive inpatients by high performance liquid chromatography (HPLC). The mean serum levels in 28 patients at the time of the first TDM analysis were 52.0+/-67 ng/mL. Eight of the patients were smokers and showed a considerably lower serum level of 24.3+/-18.8 ng/mL. In the further course of treatment the difference was compensated by application of higher doses in smokers. These findings suggest that smoking is associated with lower duloxetine serum levels due to an induction of CYP1A2 by polycylic hydrocarbons which are contained in tobacco smoke. Therefore in smokers higher doses of duloxetine (about 15%) seem to be necessary to reach adequate serum levels.

Atrophy of hippocampus in patients with Alzheimer's disease and other diseases with memory impairment.

In clinical practice, Alzheimer's disease (AD), multi-infarct Dementia (MID) and depression are often difficult to differentiate and may coexist. This study reports the findings of CT and MRI focused on hippocampal atrophy (HA). Quantitative volumetric MRI measurements of the hippocampus showed a reduced volume in AD patients compared to normal controls with no overlap. CT studies reported a significant widening of the hippocampal fissure in AD patients. Because volumetric measurements are not available for routine examinations, so far we are required to use the finding of hippocampal lucency in CT and dilatation of the directly visible hippocampal fissure in coronal MRI scans as criteria for HA. These findings were visually classified on a 4-point scale by 2 neuroradiologists, who had no knowledge of the clinical diagnosis. The examinations of 80 patients (42 with AD, 22 with major depression, 3 with MID, 6 classified as age-associated memory impairment (AAMI) and 8 'normals' with only subjective memory impairment) showed that the HA strongly supports the diagnosis of AD, by correctly identifying 95% of the AD patients and 47.8% of the patients without AD. These results suggest that CT and MRI examinations of the hippocampus are capable of demonstrating HA in clinical practice, which is strongly correlated with the diagnosis of AD.

[Regression of cerebral post-transplantation lymphoma under cyclosporin A reduction]. / Regression zerebraler Posttransplantationslymphome unter Cyclosporin-A-Reduktion.

4.5 months after successful kidney transplantation a Non-Hodgkin-lymphoma with polymorph centroblastic appearance of the tonsillar gland developed in a 21 years old male patient during immunosuppressive therapy with cyclosporine A and prednisone parallel to infection with Epstein Barr virus. Focal epileptic seizures occurred and were due to cerebral posttransplantation lymphomas as proven by brain biopsy. Reduction of immunosuppressive therapy led to complete remission as shown by CCT and MRI.