Implementation and validation of 2-D-array based tests in routine linac quality assurance.

PURPOSE: In medical linac quality assurance (QA), to replace film dosimetry with low-resolution 2-D ionization chamber array measurements, to validate the procedures, and to perform a comprehensive sensitivity analysis. METHODS: A 2-D ionization chamber array with a spatial resolution of 7.62 mm was deployed to perform the following tests: Junction tests, MLC transmission test, beam profile constancy vs. gantry angle test, beam profile constancy vs. low dose delivery test, and beam energy constancy vs. low dose delivery test. Test validation and sensitivity analyses based on short- and long-term statistics of the test results were performed. RESULTS: All selected mechanical and dosimetry tests could be successfully performed with a 2-D array. Considering the tolerance limits recommended by the AAPM Task Group 142 report (2009), sensitivities of 99.0% or better and specificities ranging from 99.5% to 99.9% could be achieved in all tests when the proper metrics were chosen. CONCLUSIONS: The results showed that a low-resolution 2-D ionization chamber array could replace film dosimetry without having to sacrifice high test sensitivity. Its implementation in the routine clinical linac QA program may involve considerable QA time savings.

Fibrinogenolysis in Venom-Induced Consumption Coagulopathy after Viperidae Snakebites: A Pilot Study.

Envenomations that are caused by Viperidae snakebites are mostly accompanied by venom-induced consumption coagulopathy (VICC) with defibrination. The clinical course of VICC is well described; however, reports about its detailed effects in the hemocoagulation systems of patients are sparse. In this pilot study, we prospectively analyzed the changes in plasma fibrinogen that were caused by the envenomation of six patients by five non-European Viperidae snakes. Western blot analysis was employed and fibrinogen fragments were visualized with the use of specific anti-human fibrinogen antibodies. All of the studied subjects experienced hypo- or afibrinogenemia. The western blot analysis demonstrated fibrinogenolysis of the fibrinogen chains in all of the cases. Fibrinogenolysis was considered to be a predominant cause of defibrination in Crotalus, Echis, and Macrovipera envenomation; while, in the cases of VICC that were caused by Atheris and Calloselasma envenomation, the splitting of the fibrinogen chains was present less significantly.

Splenic Rupture and Massive Hemoperitoneum Due to Coagulopathy after Atheris Viper Snakebite.

Coagulopathy with defibrination is one of symptoms accompanying snakebite envenoming, where life-threatening complications such as massive bleeding and organ hematomas formation can occur. Here, we report a case of hemocoagulation failure due to bite by African Great Lakes bush viper Atheris nitschei with impossibility of specific treatment for absence of antivenom and its life-threatening complication: very rare and unexpected atraumatic splenic rupture with massive hemoperitoneum and necessity of urgent splenectomy.

Activation of QA devices and phantom materials under clinical scanning proton beams-a gamma spectrometry study.

Activation of detectors and phantoms used for commissioning and quality assurance of clinical proton beams may lead to radiation protection issues. Good understanding of the activation nuclide vectors involved is necessary to assess radiation risk for the personnel working with these devices on a daily basis or to fulfill legal requirements regarding transport of radioactive material and its release to the public. 11 devices and material samples were irradiated with a 220 MeV proton pencil beam (PBS, Proton Therapy Center, Prague). This study focuses on devices manufactured by IBA Dosimetry GmbH: MatriXX PT, PPC05, Stingray, Zebra, Lynx, a Blue Phantom rail and samples of RW3, PMMA, titanium, copper and carbon fibre plastic. Monitor units (MU) were monitored during delivery. Gamma spectrometry was then performed for each item using a HPGe detector, with a focus on longer lived gamma emitting radionuclides. Activities were quantified for all found isotopes and compared to relevant legal limits for exemption and clearance of radioactive objects. Activation was found to be significant after long irradiation sessions, as done during commissioning of a proton therapy room. Some of the investigated devices may also cumulate activity in time, depending on the scenario of periodic irradiation in routine clinical practice. However, the levels of activity and resulting beta/gamma doses are more comparable to internationally recommended concentration limits for exemption than to dose limits for radiation workers. Results of this study will help to determine nuclide inventories required by some legal authorities for radiation protection purposes.

Diagnostic and prognostic value of presepsin vs. established biomarkers in critically ill patients with sepsis or systemic inflammatory response syndrome.

BACKGROUND: Inflammatory biomarkers may aid to distinguish between systemic inflammatory response syndrome (SIRS) vs. sepsis. We tested the hypotheses that (1) presepsin, a novel biomarker, can distinguish between SIRS and sepsis, and (2) higher presepsin levels will be associated with increased severity of illness and (3) with 28-day mortality, outperforming traditional biomarkers. METHODS: Procalcitonin (PCT), C-reactive protein (CRP), presepsin, and lactate were analyzed in 60 consecutive patients (sepsis and SIRS, n=30 per group) on day 1 (D1) to D3 (onset sepsis, or after cardiac surgery). The systemic organ failure assessment (SOFA) score was determined daily. RESULTS: There was no difference in mortality in sepsis vs. SIRS (12/30 vs. 8/30). Patients with sepsis had higher SOFA score vs. patients with SIRS (11±4 vs. 8±5; p=0.023), higher presepsin (AUC=0.674; p<0.021), PCT (AUC=0.791; p<0.001), CRP (AUC=0.903; p<0.0001), but not lactate (AUC=0.506; p=0.941). Unlike other biomarkers, presepsin did not correlate with SOFA on D1. All biomarkers were associated with mortality on D1: presepsin (AUC=0.734; p=0.0006; best cutoff=1843 pg/mL), PCT (AUC=0.844; p<0.0001), CRP (AUC=0.701; p=0.0048), and lactate (AUC=0.778; p<0.0001). Multiple regression analyses showed independent associations of CRP with diagnosis of sepsis, and CRP and lactate with mortality. Increased neutrophils (p=0.002) and decreased lymphocytes (p=0.007) and monocytes (p=0.046) were also associated with mortality. CONCLUSIONS: Presepsin did not outperform traditional sepsis biomarkers in diagnosing sepsis from SIRS and in prognostication of mortality in critically ill patients. Presepsin may have a limited adjunct value for both diagnosis and an early risk stratification, performing independently of clinical illness severity.

Severe Snakebite Envenoming in Intensive Care.

Snakebites by exotic venomous snakes can cause serious or even life-threatening envenoming. In Europe and North America most victims are breeders, with a few snakebites from wild native American rattlesnakes. The envenomed victims may present in organ and/or system failure with muscle paralysis, respiratory failure, circulatory instability, acute kidney injury, severe coagulation disorder, and local disability - compartment syndrome and necrosis. Best managed by close collaboration between clinical toxicology and intensive care, most severe envenomings are managed primarily by intensive care physicians. Due to the low incidence of severe envenoming, the clinical course and correct management of these cases are not intrinsically familiar to most physicians. This review article summarizes the clinical syndromes caused by severe envenoming and the therapeutic options available in the intensive care setting.

The descending branch of the lateral circumflex femoral artery as an alternative conduit for coronary artery bypass grafting: Experience from an anatomical, radiological and histological study.

The descending branch of the lateral circumflex femoral artery (DBLCFA) has been suggested as an option for use in coronary artery bypass grafting (CABG). Our aim was to combine radiological examination, surgical and anatomical preparation, and histological assessment of the DBLCFA to map its variability and to assess the benefits of this conduit in cardiac surgery. The pelvic and femoral arteries were examined by CT angiography (CTA) in 100 patients (aged 68.3 ± 9.3 years) to assess the variability of the DBLCFA. Anatomical dissections were performed on 20 cadavers. In 15 patients, an autologous DBLCFA was implanted during CABG. In 35 samples, possible atherosclerotic lesions were examined histologically. The length of the potential DBLCFA conduits measured by CTA was 9.3 ± 2.9 cm, without correlating with the length of the thigh. Anatomical variations that would prevent the DBLCFA from being used in CABG were found in 27 out of 100 patients. Except for focal thickening of the intima, eccentric hypertrophy of the intima was found in three out of 35 samples. No inflammatory infiltration, foam cells, atheroma, or calcifications were found histologically. The DBLCFA is not to be used routinely or in preference to other grafts of choice. However, owing to its moderate variability, sufficient length, caliber, and rare atherosclerosis, it can be used in the absence of other suitable grafts as an alternative conduit implanted as a composite Y-graft end-to-side to the internal thoracic artery in patients without diabetic angiopathy, neuropathy or peripheral artery disease who are undergoing extensive or repeat coronary revascularization. Clin. Anat. 29:779-788, 2016. © 2016 Wiley Periodicals, Inc.

Snakebite Envenoming by Sochurek's Saw-scaled Viper Echis Carinatus Sochureki.

A snake breeder, 47-years-old man, was bitten by the saw-scaled viper (Echis carinatus sochureki). After admission to Toxinology Centre, within 1.5 h, laboratory evaluation showed clotting times prolonged to non-measurable values, afibrinogenaemia, significantly elevated D-dimers, haemolysis and myoglobin elevation. Currently unavailable antivenom was urgently imported and administered within 10 hours. In 24 hours, oligoanuric acute kidney injury (AKI) and mild acute respiratory distress syndrome (ARDS) developed. Despite administration of 10 vials of urgently imported Polyvalent Snake Antivenom Saudi Arabia, the venom-induced consumption coagulopathy (VICC) and AKI persisted. Another ten vials of antivenom were imported from abroad. VICC slowly subsided during the antivenom treatment and disappeared after administration of total 20 vials during 5 day period. No signs of haemorrhage were present during treatment. After resolving VICC, patient was transferred to Department of Nephrology for persisting AKI and requirement for haemodialysis. AKI completely resolved after 20 days. Despite rather timed administration of appropriate antivenom, VICC and AKI developed and the quantity of 20 vials was needed to cease acute symptoms of systemic envenoming. The course illustrates low immunogenicity of the venom haemocoagulation components and thus higher requirements of the antivenom in similar cases.

Envenoming by Crotalid Snake Chinese Moccasin Agkistrodon Acutus Bite - A Case Report.

Although the bites caused by snakes from former Agkistrodon family in the areas of occurrence are not rare and even have certain epidemiologic importance, in case of envenoming by Deinagkistrodon acutus the clinical studies and case reports are very sporadic. This case report describes the envenoming of a private snake breeder bitten by young Chinese moccasin Deinagkistrodon acutus to the thumb of his left hand. He sought for a medical help immediately after snakebite. Patient presented with a local oedema on the affected limb, extending up to the half of the forearm. Laboratory examinations showed serious haemostatic disturbance with defibrination syndrome, immeasurably prolonged clotting times and extreme elevation of D-dimers. No other obvious clinical symptoms were present. Fibrinogen and fresh frozen plasma were administered because the antivenom was not available immediately. The specific antivenom was urgently imported 22 hours after the bite and administered at a dose of two vials three times until laboratory haemocoagulation parameters returned back to physiological values.

Biomarkers in critically ill patients with systemic inflammatory response syndrome or sepsis supplemented with high-dose selenium.

OBJECTIVE: Low levels of selenium (Se) and glutathione peroxidase (GSHPx), a key selenoenzyme, were documented in systemic inflammatory response syndrome (SIRS) and sepsis, both associated with high mortality. Se supplementation had mixed effects on outcome. We hypothesized that Se supplementation could have a different impact on biomarkers and 28-day mortality in patients with SIRS vs. sepsis. METHODS: Adult patients with SIRS or sepsis were randomized to either high-dose (Se+, n = 75) or standard-dose (Se-, n = 75) Se supplementation. Plasma Se, whole blood GSHPx activity, C-reactive protein (CRP), procalcitonin (PCT), prealbumin, albumin and cholesterol levels were measured serially up to day 14. RESULTS: There was no difference in mortality between Se- (24/75) vs. Se+ group (19/75; p = 0.367) or between SIRS and septic patients (8/26 vs. 35/124; p = 0.794). There was a trend to reduced mortality in SIRS patients in the Se+ vs. Se- group (p = 0.084). Plasma Se levels increased in the Se+ group only in patients with sepsis but not in patients with SIRS. Plasma Se levels correlated with GSHPx. In SIRS/Se+ group, Se correlated only with GSHPx. In SIRS/Se- group, Se correlated with cholesterol but not with other biomarkers. In sepsis patients, Se levels correlated with cholesterol, GSHPx and prealbumin. Cholesterol levels were higher in survivors in the Se- group. CONCLUSIONS: Se levels correlated with GSHPx activity and other nutritional biomarkers with significant differences between SIRS and sepsis groups. High-dose Se supplementation did not affect mortality but a strong trend to decreased mortality in SIRS patients warrants further studies in this population.

Exotic snake bites in the Czech Republic--Epidemiological and clinical aspects during 15-year period (1999-2013).

UNLABELLED: Only one natural venomous snake-the adder viper-lives in the central European region and its bite is usually associated only with mild course of envenoming. Cases of envenoming caused by exotic snakes among their breeders are clinically more important. OBJECTIVE: The aim of this study was to analyze the epidemiological and clinical aspects of registered venomous bites caused by exotic snakes in the Czech Republic over a period of 15 years (1999-2013). MATERIALS AND METHODS: This is an observational case series. Data have been collected retrospectively from a database and medical charts of the Toxinology Center belonging to the General University Hospital in Prague. RESULTS: In total, 87 cases of exotic snakebites caused by 34 venomous snake species were registered during the study period, coming from 18 genera of Elapinae, Viperinae, and Crotalinae subfamilies. In the cohort, 29 patients (33.3%) developed systemic envenoming and 17 (19.5%) were treated with antivenom. Ten cases of envenoming (11.5%) were considered as potentially life threatening. No patient died due to envenoming caused by exotic snake bites during the study period. Four illustrative cases of envenoming (Echis pyramidum, Dendroaspis polylepis, Protobothrops mangshanensis, and Proatheris superciliaris) are described in detail. CONCLUSION: Bites caused by exotic snakes resulted in serious and life-threatening envenomings in some patients. Early transfer to the Center, antivenom administration, and support of failing organ functions contributed to favorable outcome of victims.

Common viper bites in the Czech Republic - epidemiological and clinical aspects during 15 year period (1999-2013).

The aim of this study was to analyse most important epidemiological and clinical aspects of registered snakebites caused by a native common European viper Vipera berus in the Czech Republic over a period of 15 years (1999–2013). Data have been collected retrospectively from a database of the Toxinology Centre belonging to the General University Hospital in Prague. In total, 191 cases of snakebites caused by common viper were registered during the study period. Systemic envenoming occurred in 49 (25.7%) patients, local envenoming without systemic symptoms was recorded in 91 (47.6%) and asymptomatic dry bites were seen in 51 (26.7%) cases, respectively. Twenty-four patients (12.6% of all bites) were treated with administration of antivenom. None of the victims died as a result of snakebite during the observation period. Native viper snakes usually did not cause serious harm to the patients, with the exception of children. Antivenom should be administered in all cases with systemic manifestations, in children even with serious local affection and administered as soon as possible. Envenomed patients should be admitted to the hospital and treated at least under supervision of specialists with experience in snakebite treatment, who can indicate and provide administration of the antivenom.

Soluble receptor for advanced glycation end products predicts 28-day mortality in critically ill patients with sepsis.

OBJECTIVE: Multiple biomarkers are used to assess sepsis severity and prognosis. Increased levels of the soluble receptor for advanced glycation end products (sRAGE) were previously observed in sepsis but also in end-organ injury without sepsis. We evaluated associations between sRAGE and (i) 28-day mortality, (ii) sepsis severity, and (iii) individual organ failure. Traditional biomarkers procalcitonin (PCT), C-reactive protein (CRP) and lactate served as controls. METHODS: sRAGE, PCT, CRP, and lactate levels were observed on days 1 (D1) and 3 (D3) in 54 septic patients. We also assessed the correlation between the biomarkers and acute respiratory distress syndrome (ARDS), acute kidney injury (AKI) and acute heart failure. RESULTS: There were 38 survivors and 16 non-survivors. On D1, non-survivors had higher sRAGE levels than survivors (p = 0.027). On D3, sRAGE further increased only in non-survivors (p < 0.0001) but remained unchanged in survivors. Unadjusted odds ratio (OR) for 28-day mortality was 8.2 (95% CI: 1.02-60.64) for sRAGE, p = 0.048. Receiver operating characteristic analysis determined strong correlation with outcome on D3 (AUC = 0.906, p < 0.001), superior to other studied biomarkers. sRAGE correlated with sepsis severity (p < 0.00001). sRAGE showed a significant positive correlation with PCT and CRP on D3. In patients without ARDS, sRAGE was significantly higher in non-survivors (p < 0.0001) on D3. CONCLUSION: Increased sRAGE was associated with 28-day mortality in patients with sepsis, and was superior compared to PCT, CRP and lactate. sRAGE correlated with sepsis severity. sRAGE was increased in patients with individual organ failure. sRAGE could be used as an early biomarker in prognostication of outcome in septic patients.

Asymptomatic abdominal aortic aneurysms show histological signs of progression: a quantitative histochemical analysis.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a serious disease due to its covert nature, relatively high prevalence and fatal prognosis in the case of rupture. To obtain new insights into AAA pathogenesis, we examined the relationships between histopathology, multiplex in vitro immunoassay data, diameter and symptomatology. METHODS: In a prospective, non-randomised study, we evaluated samples from 6 normal infrarenal aortae and 65 AAA patients (65 walls, 55 thrombi). The AAA patients were either asymptomatic (n = 44), symptomatic (n = 7) or with ruptured AAA (n = 14). The AAA diameter was classified as small (<5 cm, n = 18), medium (5-7 cm, n = 26) and large (>7 cm, n = 21). We quantified the histopathology of the AAA wall and the adjacent thrombus. We assessed the expression of proteins in the same samples. RESULTS: Asymptomatic AAAs had walls with more abundant inflammatory infiltrates, lower amounts of PAI-1, a higher number of tPA-positive elements, a tendency towards decreased collagen content, whereas the adjacent thrombi had a greater concentration of VCAM-1 and MMP-2 when compared with symptomatic AAAs. Compared with the aneurysmatic aorta, the normal aorta contained less collagen and more elastin, actin, desmin and PAI-1-positive elements; in addition, it was more vascular. Medium-sized AAAs were the most actin and vimentin rich, and large AAAs were the most vascular. CONCLUSION: Our results show that asymptomatic AAA walls often have more potentially deleterious histopathological alterations than symptomatic AAA walls. This result indicates that a progression from an asymptomatic AAA to rupture can be expected and screening patients who are at risk of rupture could be beneficial.

Protobothrops mangshanensis bite: first clinical report of envenoming and its treatment.

AIM: This case report presents envenoming by the Chinese pit viper Protobothrops mangshanensis (formerly Zhaoermia) and its treatment. METHODS: A 38 year old snake breeder suffered two-fang bites to elbow by a Chinese pit viper Protobothrops mangshanensis resulting in local edema of the affected arm. No other signs of envenoming appeared. On the 5(th) day following the bite a hematoma developed on the other arm which had been mechanically injured 14 days before. Laboratory testing revealed severe coagulopathy with hypofibrinogenemia and immeasurably prolonged coagulation times. RESULTS: As substitution therapy with fibrinogen and fresh frozen plasma was unsuccessful and specific antivenom is not produced, antivenin against some other Asian pit vipers GREEN PIT VIPER ANTIVENIN, Thai Red Cross, Thailand was applied. Three doses of antivenom reversed the course of the hemocoagulation disorder. CONCLUSION: The case confirms the persistence of active venom components affecting coagulation, difficulty in ameliorating the hemocoagulatin disorder caused by snake venom through substitution therapy and the effectiveness of delayed treatment using antivenin. It points out the potential risk of a clinically asymptomatic progress of envenoming by snake venoms containing hemocoagulation acting components, if the hemocoagulation disorder is not investigated and suitably treated. Therapy using the GREEN PIT VIPER ANTIVENIN, Thai Red Cross, Thailand in this case of envenomation by a Protobothrops mangshanensis bite proved to be applicable and the antivenom could be characterised as a paraspecific active.

[Morphology and etiopathogenesis of the abdominal aortic aneurysm]. / Morfologie a etiopatogeneze aneuryzmatu brisní aorty.

The paper summarizes the latest research on the abdominal aorta aneurysm etiopathogenesis and compares normal aorta morphology with changes in the aortic aneurysm wall. The role of risk factors, especially hemodynamic and genetic, is discussed in detail. Special attention is paid to inflammatory processes including cytokines and matrix degrading proteases that contribute to the development of aneurysm. The role of thrombus and the current results of research into biomarkers indicating the risks and progression of the disease are analysed. Finally, a review of pharmacomodulation of the aortic aneurysm using statins, antibiotics, antihypertensive and nonsteroidal antiinflammatory drugs is presented.

[Variability of the deep femoral venous system]. / Variabilita hlubokých zil stehna.

Deep venous system is known for its extreme variability but in anatomy it receives only marginal interest. Although a few previous anatomical studies have already pointed out the fact of a significant discrepancy between the autopsy findings and the literary description, it has not had any particular output so far. Our findings confirmed the deep femoral vein to be an alternative collateral vein connecting the popliteal with the femoral vein.

High-dose selenium substitution in sepsis: a prospective randomized clinical trial.

OBJECTIVE: Systemic inflammatory response syndrome (SIRS) and sepsis remain the leading cause of death in the critically ill. A reduction in the antioxidant capacity, including selenoenzymes that are dependent on selenium (Se), could be a contributing factor. Se supplementation in septic patients have yielded conflicting results. We hypothesized that a high-dose Se supplementation would (1) improve markers of inflammation, nutrition and antioxidant defence, and (2) decrease mortality. METHODS: This prospective, randomized, open-label, single-centre clinical trial included 150 patients with SIRS/sepsis and a SOFA score of >5. Patients in the Se+ group (n = 75) received Se for 14 days (1,000 µg on day 1,500 µg/day on days 2-14). Patients in both the control (Se-) group (n = 75) and the Se+ group received a standard Se dose (<75 µg/day). Plasma Se, whole-blood glutathione peroxidase (GPx) activity, C-reactive protein (CRP), procalcitonin (PCT), albumin, prealbumin and cholesterol levels, along with APACHE II and SOFA scores, were determined at baseline and on days 1-7 and day 14. Mortality was assessed at day 28. RESULTS: Plasma Se and GPx activity were increased in the Se+ group from day 1 onwards. Negative correlations were demonstrated between plasma Se, CRP (P = 0.035), PCT (P = 0.022) and SOFA (P = 0.001) at admission but not on days 7 or 14. Prealbumin and cholesterol increased in the Se+ group versus the respective baselines. Mortality was similar between groups, with no gender differences. CONCLUSION: High-dose Se substitution in patients with SIRS/sepsis increased plasma Se and GPx levels, but did not reduce mortality. Markers of inflammation were reduced similarly in both groups.