Ophthalmic findings associated with Australian tick paralysis (holocyclotoxicity) in hospitalized domestic dogs and cats.

OBJECTIVE: To describe ophthalmic findings in hospitalized canine and feline patients with tick paralysis (TP) and investigate possible predisposing factors. ANIMALS STUDIED: Forty-seven dogs and 28 cats hospitalized with TP assessed with an ophthalmic examination performed by an ABVO resident. METHODS: Dogs and cats were hospitalized with TP from October 2021 to January 2022 and had an ophthalmic examination performed by an ABVO resident. Patient signalment data, information regarding tick number and location, hospitalization duration, medications used, and patient paralysis grades were recorded. Statistical analysis was performed to correlate findings. RESULTS: Corneal ulcers developed in up to 34.8% of dogs and up to 42.9% of cats hospitalized with TP. An absent palpebral reflex ipsilaterally increased the odds of a concurrent corneal ulcer being present by 14.7× in dogs and 20.1× in cats (p < .0001). Palpebral reflexes were absent in 38.3% of dogs and 35.7% of cats hospitalized with TP and were correlated with more severe gait paralysis (p = .01) and respiratory paralysis (p = .005) in dogs, and respiratory paralysis in cats (p = .041). STT-1 findings <10 mm/min were present in 27.7% of dogs and 57.1% of cats examined and were associated with increasing gait paralysis (p = .017) and respiratory paralysis (p = .007) in dogs, and increasing gait paralysis in cats (p = .017). CONCLUSIONS: Simple corneal ulcers, loss of a complete palpebral reflex, and reduced STT-1 scores frequently occurred in dogs and cats hospitalized for TP. The frequency of these findings increased as the degree of patient paralysis increased.

Retrospective assessment of ophthalmic disease development in domestic dogs and cats when hospitalised with tick paralysis caused by Ixodes holocyclus.

OBJECTIVE: To investigate the incidence and predisposing factors leading to the development of corneal ulcers and the loss of a palpebral reflex in hospitalised canine and feline patients with tick paralysis (TP). ANIMALS STUDIED: A total of 102 dogs and 100 cats retrospectively were assessed from previously hospitalised patients. METHODS: A retrospective cohort study was performed on 102 different canine and 100 different feline patients who were hospitalised for TP from October 2020-January 2022. Patient data were collected, and logistic regression was conducted to determine factors affecting the palpebral reflex and the development of corneal ulcers. RESULTS: Corneal ulcers occurred in 23/102 (22.5%) dogs during hospitalisation and were strongly associated with an incomplete palpebral reflex ipsilaterally during hospitalisation (P < 0.001), hospitalisation ≥3 days (P = 0.004), mechanical ventilation ≥3 days (P = 0.015) or a tick location cranial to C1 (P = 0.003). An incomplete palpebral reflex during hospitalisation was observed in 29/102 (28.4%) dogs and was significantly associated with decreasing patient weight (P = 0.018), increasing days hospitalised (P = 0.001), having a tick found cranial to C1 (P = 0.004), highest recorded GP grade (P = 0.01), highest recorded RP grade (P = 0.005), use of amoxycillin-clavulanic acid during hospitalisation (P = 0.002) and use of piperacillin/tazobactam during hospitalisation (P = 0.003). There was a significant association between the loss of a complete palpebral reflex and mortality during hospitalisation in dogs (OR = 4.5, P = 0.029). Corneal ulcers occurred in 10/100 (10.0%) cats during hospitalisation, and was significantly more likely to occur to an eye if an incomplete palpebral reflex was observed ipsilaterally during hospitalisation (OR = 20.1, P < 0.0001) and with increasing patient age (P = 0.019). The absence of a complete palpebral reflex during hospitalisation was observed in 18/10 (18.0%) cats and was significantly associated with increasing days hospitalised (P = 0.034). There was no significant association between the loss of a complete palpebral reflex and mortality during hospitalisation in cats. CONCLUSIONS: The frequency of corneal ulcers and loss of palpebral reflexes were significant in dogs and cats hospitalised by TP, with many factors contributing to the risk of these developing.

Causes of Death in Endovascularly Treated Patients with Acute Stroke.

BACKGROUND AND PURPOSE: Because stroke therapy has changed with the introduction of endovascular stroke treatment as a standard approach, studies on intrahospital causes of death from stroke are no longer up-to-date. The purpose of this observational study was to present the causes of death during hospitalization of patients with ischemic stroke who received endovascular stroke treatment, with the focus on a differentiation of curative and secondary palliative treatment. MATERIALS AND METHODS: We studied a total cohort of 1342 patients who received endovascular stroke treatment in a tertiary stroke center (Aachen, Germany) between 2010 and 2020 and analyzed the causes of death in all 326 consecutive deceased patients. We distinguished between curative treatment and a secondary palliative approach and analyzed causes of death and treatment numbers across the years. RESULTS: In the entire cohort of 326 deceased patients, the most common cause of death was of a cerebrovascular nature (51.5%), followed by pneumonia and sepsis (25.8%) and cardiovascular causes (8.3%). Neurovascular causes constituted 75.8% of reasons for palliation. In the group with a secondary palliative approach, causes of death were neurovascular in 54.0% of patients and pneumonia and sepsis in 26.0% of patients. CONCLUSIONS: Cerebrovascular causes in patients with stroke play a major role in the intrahospital causes of death and reasons for palliation. Considering the large proportion of secondarily palliative-treated patients, reasons for palliation should be considered instead of causes of death to avoid concealment by, for example, life-terminating measures.

Multi-modality imaging of aggressive submural neoplasia of the hoof in two horses.

This case series presents a 20-year-old Quarter horse gelding and a 10-year-old Thoroughbred gelding with a histologic diagnosis of aggressive submural neoplasia, including an anaplastic sarcoma and a squamous cell carcinoma respectively. The current case series describes these neoplasias with radiography, computed tomography, magnetic resonance imaging and histopathology with immunohistochemistry. The purpose of this case series is to identify the clinical pattern of chronic reoccurring lameness in these cases and highlight the appearance of expansile osteolytic pathology of the distal phalanx with adjacent hoof wall abnormalities. Advanced imaging has the potential to assist with a differential diagnosis list and surgical planning in patients such as these however obtaining a cellular sample for histopathological examination remains necessary for definitive diagnosis.

Performance of cone-beam computed tomography and multidetector computed tomography in diagnostic imaging of the midface: A comparative study on Phantom and cadaver head scans.

PURPOSE: To compare multidetector computed tomography (MDCT) and cone-beam computed tomography (CBCT) regarding radiation, resolution, image noise, and image quality. METHODS: CBCT and 256-MDCT were compared based on three scan protocols: Standard-dose (≈24 mGy), reduced-dose (≈9 mGy), and low-dose (≈4 mGy). MDCT images were acquired in standard- and high-resolution mode (HR-MDCT) and reconstructed using filtered back projection (FBP) and iterative reconstruction (IR). Spatial resolution in linepairs (lp) and objective image noise (OIN) were assessed using dedicated phantoms. Image quality was assessed in scans of 25 cadaver heads using a Likert scale. RESULTS: OIN was markedly higher in FBP-MDCT when compared to CBCT. IR lowered the OIN to comparable values in standard-mode MDCT only. CBCT provided a resolution of 13 lp/cm at standard-dose and 11 lp/cm at reduced-dose vs. 11 lp/cm and 10 lp/cm in HR-MDCT. Resolution of 10 lp/cm was observed for both devices using low-dose settings. Quality scores of MDCT and CBCT did not differ at standard-dose (CBCT, 3.4; MDCT, 3.3-3.5; p > 0.05). Using reduced- and low-dose protocols, CBCT was superior (reduced-dose, 3.2 vs. 2.8; low dose, 3.0 vs. 2.3; p < 0.001). CONCLUSION: Using the low-dose protocol, the assessed CBCT provided better objective and subjective image quality and equality in resolution. Similar image quality, but better resolution using CBCT was observed at higher exposure settings. KEY POINTS: • The assessed CBCT device provided better image quality at lower doses. • Objective and subjective image quality were comparable using higher exposure settings. • CBCT showed superior spatial resolution in standard-dose and reduced-dose settings. • Modern noise-reducing tools are used in CBCT devices currently. • MDCT should be preferred for assessment of soft-tissue injuries and oncologic imaging.

An exploratory study investigating the metabolic activity and local cytokine profile in patients with melanoma treated with pazopanib and paclitaxel.

BACKGROUND: There is a medical need for new drugs in patients with BRAF wild-type metastatic melanoma. Pazopanib is a multitarget tyrosine kinase inhibitor with antitumour and antiangiogenic activity. OBJECTIVES: The primary aim was to investigate the metabolic response to pazopanib monotherapy and pazopanib plus paclitaxel in patients with BRAF wild-type melanoma. Secondary end points were the early cytokine and chemokine profiles and histological findings. METHODS: Pazopanib (400 mg twice daily) was administered orally from days 1 to 10 and from days 14 to 70. An intravenous infusion with paclitaxel (150 mg m-2 body surface) was administered on days 14, 35 and 56. Metabolic response evaluation was performed before treatment, after treatment with pazopanib (day 10) and after treatment with pazopanib and paclitaxel (day 70). Skin biopsy of metastatic tissue for chemokine and cytokine expression analysis and histology and immunohistochemistry (CD68, CD163) evaluation, and blood samples were taken at the same time points. RESULTS: Two patients failed screening and 17 were dosed. Of 67 adverse events, nine (13%) were grade 3 or 4. Five of 14 evaluable patients had a partial metabolic response at day 10 under pazopanib monotherapy. The response rate at day 70 under combined pazopanib-paclitaxel treatment was 0%. Immunohistochemistry revealed an increase of M2-like macrophages in nonresponders compared with responders. We observed a significant upregulation of five cytokines (CXCL1, CXCL2, CXCL13, CCL22 and SPP1) in responding vs. nonresponding lesions. Overall, the median progression-free survival was 70 days (range 5-331), which did not differ significantly between responders (148 days) and nonresponders (70 days, P = 0·17). CONCLUSIONS: In this patient population pazopanib efficacy was limited. Response is associated with low M2-like macrophage density and increased expression of several chemokines.

Impact of increasing levels of advanced iterative reconstruction on image quality in low-dose cardiac CT angiography.

PURPOSE: To investigate the effects of an advanced iterative reconstruction (IR) technique on subjective and objective image quality (IQ) in low-dose cardiac CT angiography (CCTA). MATERIALS AND METHODS: 30 datasets of prospectively triggered "step-and-shoot" CCTA scans acquired on a 256-slice CT scanner with optimized exposure settings were processed on a prototype IR system using filtered back-projection (FBP) and 4 levels of advanced IR (iDose4, Philips) providing incremental rates of IR (level 2, 4, 6, 7). In addition, the effects of different reconstruction kernels (semi-smooth [CB], standard with edge-enhancement [XCB]) and a "multi-resolution" feature [MR] to preserve the noise power spectrum were evaluated resulting in a total of n = 480 image sets. Contrast-to-noise ratios (CNR) were computed from regions of interest at 9 coronary locations. The subjective IQ was rated on a 4-point-scale with "classic" image appearance and noise-related artifacts as main criteria. RESULTS: At an effective dose of 1.7 ±â€Š0.7 mSv, the CNR significantly improved with every increasing level of IR (range: 14.2 - 27.8; p < 0.001) with the best objective IQ at the highest level of IR (level 7). The subjective IQ, however, was rated best at the medium level of IR (level 4) with minimal artifacts and a more "classic" image appearance when compared to higher IR levels. The XCB kernel provided better subjective ratings than CB (p < 0.05) and the MR feature further increased the IQ at a high level of IR. CONCLUSION: The objective IQ of low-dose CCTA progressively improves with an increasing level of IR. The best subjective IQ, however, is reached at medium levels of IR combined with an edge-enhancing kernel allowing for preservation of a "classic" image appearance suggesting application in the clinical routine. KEY POINTS: • iterative reconstruction (IR) improves image quality in low-dose coronary CTA• objective image quality (CNR) enhances with increasing level of IR• best subjective image quality is reached at medium level of IR• "multi-resolution" algorithm further improves image quality at a higher level of IR.

Alterations in classical and nonclassical HLA expression in recurrent and progressive HPV-induced usual vulvar intraepithelial neoplasia and implications for immunotherapy.

Immunotherapy of usual vulvar intraepithelial neoplasia (uVIN) is promising; however, many patients still fail to show clinical responses, which could be explained by an immune escape through alterations in human leukocyte antigen (HLA) expression. Therefore, we analyzed a cohort of patients with a primary (n = 43) and subsequent recurrent uVIN lesion (n = 20), vaccine-treated uVIN patients (n = 12), patients with human papillomavirus (HPV)-induced vulvar carcinoma (n = 21) and healthy controls (n = 26) for the expression of classical HLA-class I/II and nonclassical HLA-E/-G and MHC class I chain-related molecule A (MICA). HLA-class I was downregulated in 70% of uVIN patients, including patients with a clinical response to immunotherapy. Downregulation of HLA-class I is probably reversible, as only 15% of the uVIN cases displayed loss of heterozygosity (LOH) and HLA-class I could be upregulated in uVIN keratinocyte cultures by interferon γ. HLA-class I downregulation is more frequently associated with LOH in vulvar carcinomas (25-55.5%). HLA-class II was found to be focally expressed in 65% of uVIN patients. Of the nonclassical molecules, MICA was downregulated in 80% of uVIN whereas HLA-E and -G were expressed in a minority of cases. Their expression was more prominent in vulvar carcinoma. No differences were found between the alterations observed in paired primary and recurrent uVIN. Importantly, downregulation of HLA-B/C in primary uVIN lesions was associated with the development of recurrences and progression to cancer. We conclude that downregulation of HLA is frequently observed in premalignant HPV-induced lesions, including clinical responders to immunotherapy, and is associated with worse clinical outcome. However, in the majority of cases downregulation may still be reversible.

Intraindividual evaluation of the influence of iterative reconstruction and filter kernel on subjective and objective image quality in computed tomography of the brain.

OBJECTIVES: To intraindividually evaluate the potential of 4th generation iterative reconstruction (IR) on brain CT with regard to subjective and objective image quality. METHODS: 31 consecutive raw data sets of clinical routine native sequential brain CT scans were reconstructed with IR level 0 (= filtered back projection), 1, 3 and 4; 3 different brain filter kernels (smooth/standard/sharp) were applied respectively. Five independent radiologists with different levels of experience performed subjective image rating. Detailed ROI analysis of image contrast and noise was performed. Statistical analysis was carried out by applying a random intercept model. RESULTS: Subjective scores for the smooth and the standard kernels were best at low IR levels, but both, in particular the smooth kernel, scored inferior with an increasing IR level. The sharp kernel scored lowest at IR 0, while the scores substantially increased at high IR levels, reaching significantly best scores at IR 4. Objective measurements revealed an overall increase in contrast-to-noise ratio at higher IR levels, which was highest when applying the soft filter kernel. The absolute grey-white contrast decreased with an increasing IR level and was highest when applying the sharp filter kernel. All subjective effects were independent of the raters' experience and the patients' age and sex. CONCLUSION: Different combinations of IR level and filter kernel substantially influence subjective and objective image quality of brain CT.

Impact of a 4th generation iterative reconstruction technique on image quality in low-dose computed tomography of the chest in immunocompromised patients.

PURPOSE: To determine the image quality of an iterative reconstruction (IR) technique in low-dose MDCT (LDCT) of the chest of immunocompromised patients in an intraindividual comparison to filtered back projection (FBP) and to evaluate the dose reduction capability. MATERIALS AND METHODS: 30 chest LDCT scans were performed in immunocompromised patients (Brilliance iCT; 20-40 mAs; mean CTDIvol: 1.7 mGy). The raw data were reconstructed using FBP and the IR technique (iDose4™, Philips, Best, The Netherlands) set to seven iteration levels. 30 routine-dose MDCT (RDCT) reconstructed with FBP served as controls (mean exposure: 116 mAs; mean CDTIvol: 7.6 mGy). Three blinded radiologists scored subjective image quality and lesion conspicuity. Quantitative parameters including CT attenuation and objective image noise (OIN) were determined. RESULTS: In LDCT high iDose4™ levels lead to a significant decrease in OIN (FBP vs. iDose7: subscapular muscle 139.4 vs. 40.6 HU). The high iDose4™ levels provided significant improvements in image quality and artifact and noise reduction compared to LDCT FBP images. The conspicuity of subtle lesions was limited in LDCT FBP images. It significantly improved with high iDose4™ levels (> iDose4). LDCT with iDose4™ level 6 was determined to be of equivalent image quality as RDCT with FBP. CONCLUSION: iDose4™ substantially improves image quality and lesion conspicuity and reduces noise in low-dose chest CT. Compared to RDCT, high iDose4™ levels provide equivalent image quality in LDCT, hence suggesting a potential dose reduction of almost 80%.

Performance of an automatic dose control system for CT: patient studies.

PURPOSE: To study the effect of an automatic dose control (ADC) system with adequate noise characteristic on the individual perception of image noise and diagnostic acceptance compared to objectively measured image noise and the dose reductions achieved in a representative group of patients. MATERIALS AND METHODS: In a retrospective study two matched cohorts of 20 patients each were identified: a manual cohort with exposure settings according to body size (small - regular - large) and an ADC cohort with exposure settings calculated by the ADC system (DoseRight 2.0™, Philips Healthcare). For each patient, 12 images from 6 defined anatomic levels from contrast-enhanced scans of chest and abdomen/pelvis were analyzed by 4 independent readers concerning image noise and diagnostic acceptance on a five-point Likert scale and evaluated for objectively measured image noise. Radiation exposure was calculated from recorded exposure data. RESULTS: Use of the ADC system reduced the average effective dose for patients by 36 % in chest scans (3.2 vs. 4.9 mSv) and by 17 % in abdomen/pelvis scans (7.6 vs. 8.3 mSv). Average objective noise was slightly lower in the manual cohort (11.1 vs. 12.8 HU), correlating with a slightly better rating in subjective noise score (4.4 vs. 4.2). However, diagnostic acceptance was rated almost equal in both cohorts with excellent image quality (4.6 vs. 4.5). CONCLUSION: Use of an ADC system with adequate noise characteristic leads to significant reductions in radiation exposure for patients while maintaining excellent image quality.

256-MSCT image acquisition with sequential axial scans: evaluation of image quality and resolution in a phantom study.

PURPOSE: Evaluation of image quality and resolution of varying sequential axial scan protocols utilizing two resolution phantoms with a 256-MSCT scanner. MATERIALS AND METHODS: Sequential axial scans were performed on a z-axis and an axial-plane resolution phantom with varying acquisition and reconstruction parameters. Two independent observers evaluated the image quality and resolution, and analyzed quantitative image quality parameters and radiation doses. RESULTS: The best image quality and resolution were achieved with an activated z-flying focal spot (zFFS) and overlapping reconstruction. With an activated zFFS, image degradation was significantly minimized in marginal or overlapping zones of the beam, but the maximum effective detector width was reduced to 82 % and 75 %, respectively depending on the field of view. With a deactivated zFFS, the effective detector width was not restricted, but the image quality decreased and the artifacts increased as the collimation increased. CONCLUSION: For sequential axial CT data acquisition with multi-planar image reformation, the zFFS technique is crucial to achieve the best image quality and resolution. Major advantages are minimized image degradation and increased spatial resolution along the z-axis, but the zFFS reduces the maximum effective detector width.

Performance of an automatic dose control system for CT: specifications and basic phantom tests.

PURPOSE: To assess the performance and to provide more detailed insight into the characteristics and limitations of devices for automatic dose control (ADC) in CT. MATERIALS AND METHODS: A comprehensive study on DoseRight 2.0, the ADC system provided by Philips for its Brilliance CT scanners, was conducted. Phantom tests were carried out on a 64-slice scanner (Brilliance 64) using assorted quality control (QC) phantoms that allowed verification of the basic specifications. If feasible, the findings were verified by model calculations based on known specifications. RESULTS: For all tests, the dose reductions and modulation characteristics fully met the values expected from the specifications. Adverse effects due to increased image noise were only moderate as a result of the "adequate noise system" design that employs comparatively gentle modulation, and the additional use of adaptive filtration. CONCLUSION: Simple tests with QC phantoms allow evaluation of the most relevant characteristics of devices for ADC in CT.

Performance of an automatic dose control system for CT: anthropomorphic phantom studies.

PURPOSE: To assess the performance and to provide more detailed insight into characteristics and limitations of devices for automatic dose control (ADC) in CT. MATERIALS AND METHODS: A comprehensive study on DoseRight 2.0, the ADC system provided by Philips for its Brilliance CT scanners, was conducted with assorted tests using an anthropomorphic phantom that allowed simulation of the operation of the system under almost realistic conditions. The scan protocol settings for the neck, chest and abdomen with pelvis were identical to those applied in the clinical routine. RESULTS: Using the appropriate ADC functionalities, dose reductions equal 40% for the neck, 20% for the chest and 10% for the abdomen with pelvis. Larger dose reductions can be expected for average patients, since their attenuating properties differ significantly from the anthropomorphic phantom. Adverse effects due to increased image noise were only moderate as a consequence of the "adequate noise system" design and the complementary use of adaptive filtration. The results of specific tests also provided deeper insight into the operation of the ADC system that helps to identify the causes of suspected malfunctions and to prevent potential pitfalls. CONCLUSION: Tests with anthropomorphic phantoms allow verification of the characteristics of devices for ADC in CT under almost realistic conditions. However, differences in phantom shape and material composition require supplementary patient studies on representative patient groups.

Quantification of radiation dose savings in cardiac computed tomography using prospectively triggered mode and ECG pulsing: a phantom study.

OBJECTIVE: To quantify radiation dose reduction in cardiac computed tomography (CT) using a prospectively triggered mode compared with a retrospective ECG-gated helical mode. METHODS: Absorbed organ doses in cardiac 64-row multidetector CT were quantified using an anthropomorphic male Alderson phantom with 74 thermoluminescence dosimeters. Three different imaging protocols were applied: retrospective ECG-gating, retrospective ECG-gating with additional ECG-pulsing, and a prospectively triggered mode. The measured organ doses were compared with dose estimation by a mathematical phantom. RESULTS: Compared with the retrospective ECG-gating mode, the mean relative organ doses were reduced by 44% using ECG pulsing and by 76% using the prospectively triggered mode. The range of dose savings varied from 34% to 49% using ECG pulsing and from 65% to 87% using the prospectively triggered mode. The effective dose was 16.5 mSv using retrospective gating, 9.2 mSv using retrospective gating with ECG pulsing and 4.0 mSv using the prospectively triggered mode. CONCLUSIONS: Our measurements confirm the high dose-saving potential of the prospectively triggered technique in cardiac CT. The reduction in the organ doses measured corresponds to estimates determined by the mathematical phantom. The effective dose calculated by the mathematical phantom was, in some cases, significantly lower than that calculated using the anthropomorphic phantom.

Simulated low-dose computed tomography in oncological patients: a feasibility study.

OBJECTIVE: Image quality of chest and abdominal computed tomographic (CT) scans was evaluated at different doses to assess the lowest value of x-ray dose at which the image quality was not being affected. MATERIALS AND METHODS: Using multislice CT (MSCT), 29 patients who submitted to follow-up examinations were examined using a combined MSCT protocol of the chest and the abdomen on 4-raw MSCT (Siemens, Erlangen, Germany). For each examination, approximately 120 mL of contrast agent (Bracco-Altana, Konstanz, Germany) was applied intravenously. The raw data were transferred to an external personal computer equipped with an image reconstruction software (CardioRecon 6; Siemens, Forchheim, Germany) to simulate 5 different dose levels. To simulate them correctly, a milliampere second-dependent noise was added to every image, so that the changes in a current-time product could be imitated. The images were compared in consensus by 2 radiologists who were not informed about the technical scanning parameters, that is, dose parameters, and were graded in 4 different subcategories on a 1-to-5-point scale. For statistical analysis, the Friedman test was used. Additional evaluations for lesions smaller than 1.0 cm were performed and analyzed separately. RESULTS: For image noise, there was a significant change between 40 and 60 mA s. For lesion detection, there was no significant change. The contour of the small objects did not differ between 90, 60, and 40 mA s. However, a dose reduction to 30 mA s had a significant effect. The contrast did not differ between 90, 60, 40, and even down to 30 mA s. Only a maximal dose reduction to 20 mA s had a significant effect on the contrast. The level of noise was most sensitive to the current. Whereas a dose reduction to 60 mA s did not yet have a significant effect, there was a significant increase of noise at 40 mA s. CONCLUSIONS: The MSCT can be applied with a lower dose than that usually selected in examinations at present to follow-up and stage the oncological patients adequately.

Sacroplasty in a cadaveric trial: comparison of CT and fluoroscopic guidance with and without balloon assistance.

Sacral insufficiency fractures can cause severe, debilitating pain to patients concerned. The incidence of this fracture type correlates with the appearance of osteoporosis in the elderly population. A polymethylmethacrylate (PMMA) cement injection procedure called sacroplasty has been recently described as an optional method for the treatment of this fracture type. However, the correct cement placement in the complex anatomical structure of the sacrum is a surgical challenge. The aim of the study is to compare the precision, safety, and radiation exposure of standard multiplanar fluoroscopy and computed tomography (CT) guidance for PMMA application to the sacrum using both balloon-assisted sacroplasty and conventional sacroplasty. A controlled experimental investigation in a human cadaver trial has been performed. Two imaging and two application modalities to monitor percutaneous PMMA injection to the sacrum were examined. The application forms were randomized from side to side of the pelvis. We found less cement extravasation in the CT-guided groups, but also a significant higher radiation exposure (P < 0.05) by using CT guidance. The conventional fluoroscopy-guided sacroplasty revealed the shortest procedure time (incision to closure time) of all treatment groups (P < 0.01). These findings show no difference regarding cement extravasation between ballon-assisted and conventional sacroplasty. Further, in comparison to fluoroscopy-assisted technique, the CT-guided cement injection seems to decrease the risk of cement extravasation, irrespective of the use of an additional balloon assistance. However, we have to consider a greater radiation exposure using CT guidance. Further investigations will proof the suitability in the normal course of clinical life.

[Dose reduction in high-resolution MSCT examinations of the chest for early detection of pneumonia in immunocompromised patients]. / High-Resolution-MSCT-Thoraxuntersuchungen zur Infiltratsuche: Untersuchung einer Dosisreduktion bei immunsupprimierten Patienten.

PURPOSE: The purpose of this study was to optimize high-resolution MSCT chest protocols for the evaluation of symptomatic immunosuppressed patients with suspected pneumonia using a dose-simulating program. MATERIALS AND METHODS: Using the MSCT (Siemens, Erlangen, Germany), 30 immunosuppressed patients with suspected pneumonia were examined with a low-dose HRCT of the chest (120 kV, 100 eff.mAs and collimation of 4 x 1 mm). A dose-simulating program was used to reconstruct the raw data at four different dose levels (70, 50, 35 und 25 mAs). For dose simulation for each mAs product, the correspondent noise level was added to the data. Images were generated with a slice thickness of 1 mm and 5 mm in the lung window. The images were then evaluated independently by two radiologists and graded on a scale of 1 to 3 points: 1 = no pneumonia, 2 = unclear, 3 = pneumonia. A receiver operating curve (ROC) analysis was performed to calculate the area under the curve (AUC). The actual dosage in mSv was calculated. The sensitivity and specificity were evaluated. RESULTS: Out of 30 patients, 7 had a normal chest finding and 23 had pneumonia. The area under the ROC curve (AUC) was 1.0 for every dosage and slice thickness. Infiltrates were detected correctly for all dosage levels. The sensitivity was 100 % for all dose levels and slice thicknesses. There was one false positive finding at 35 mAs and 1 mm slice thickness. At this dose level the specificity was reduced to 93 %. A reduction to 25 mAs had no influence on the detection of pneumonia. Thus, MSCT examinations of the chest can be performed with 25 mAs without missing the right diagnosis, resulting in an effective dose of 1.15 mSv (men), 1.5 mSv (women) and a CTDIvol of 2.5 mGy. CONCLUSION: For the evaluation of pneumonia in immunocompromised patients, MSCT examination of the chest can be performed with 25 mAs. Thus, radiation exposure was reduced to a quarter compared to the standard protocol.

Protein profiling of non-malignant and malignant ascites by SELDI-TOF MS: proof of principle.

Ascites is a common clinical symptom in liver cirrhosis, inflammatory disorders of the abdomen and a major late manifestation of metastatic malignancies. Standard cytopathological techniques and immunocytochemistry have specificities and sensitivities of approximately 95 and 60%, respectively for the presence of tumor cells. Development of faster and more accurate screening methods would be of great clinical utility. In this work we examined differential analysis of the unbound proteins in the supernatant of ascites fluid by Protein-Chip SELDI mass spectrometry. There were 21 tumor cell-positive and 34 tumor cell-negative samples. We used principal component analysis coupled with linear regression applied to the mass spectra of the samples to distinguish between the sample groups. Two sample sets for statistical analysis were created after randomization, a training set with 37 samples and a validation set with 18 samples resulting in a specificity of 93% and a sensitivity of 83% on the training set. The validation set yielded a specificity and sensitivity of 75%. This study suggests that SELDI-TOF mass spectrometry appears to have great potential as a surrogate diagnostic tool to evaluate effusion specimens.

Effects of neuron-specific ADAM10 modulation in an in vivo model of acute excitotoxic stress.

A disintegrin and metalloprotease (ADAM) 10 is the main candidate enzyme for the alpha-secretase processing of the amyloid precursor protein (APP). Neuron-specific ADAM10 overexpression proved beneficial in the APP[V717I] mutant Alzheimer mouse model [Postina R, Schroeder A, Dewachter I, Bohl J, Schmitt U, Kojro E, Prinzen C, Endres K, Hiemke C, Blessing M, Flamez P, Dequenne A, Godaux E, van Leuven F, Fahrenholz F (2004) A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J Clin Invest 113:1456-1464]. Since Alzheimer patients have a high prevalence for epileptic seizures, we investigated the effects of ADAM10 modulation under conditions of experimentally induced epileptic seizures. In this context we also examined whether ADAM10 effects were influenced by APP levels. Therefore we compared severity of kainate-induced seizures, neurodegeneration and inflammation in double transgenic mice overexpressing functional ADAM10 or a dominant negative ADAM10 mutant in the APP[V717I] background with single transgenic ADAM10 modulated mice. Double transgenic dominant negative ADAM10dn/APP[V717I] mice suffered from stronger epileptic seizures, had a longer recovery period and showed more neurodegeneration and glial activation in the hippocampal region than double transgenic mice moderately overexpressing functional ADAM10 (ADAM10mo/APP[V717I]) and APP[V717I] mice with endogenous ADAM10 levels. This suggests that ADAM10 activity is necessary to provide neuroprotection against excitotoxicity in the APP[V717I] mouse model. Interestingly, increased expression of functional ADAM10 above the endogenous level did not correlate with a better protection against seizures and neurodegeneration. Furthermore, ADAM10 dominant negative mice without transgenic APP overexpression (ADAM10dn) were seizing for a shorter time and showed less neuronal cell death and neuroinflammation after kainate injection than wild-type mice, which shows beneficial effects of ADAM10 inhibition in context with neurodegeneration. In contrast, mice with a high ADAM10 overexpression showed more seizures and stronger neuronal damage and inflammation than wild-type mice and mice with moderate ADAM10 overexpression. Hence, additional cleavage products of ADAM10 may counterbalance the neuroprotective effect of alpha-secretase-cleaved APP in the defense against excitotoxicity. Our findings highlight the need of a careful modulation of ADAM10 activity for neuroprotection depending on substrate availability and on neurotoxic stress conditions.