CT perfusion imaging of lung cancer: benefit of motion correction for blood flow estimates.

PURPOSE: CT perfusion (CTP) imaging assessment of treatment response in advanced lung cancer can be compromised by respiratory motion. Our purpose was to determine whether an original motion correction method could improve the reproducibility of such measurements. MATERIALS AND METHODS: The institutional review board approved this prospective study. Twenty-one adult patients with non-resectable non-small-cell lung cancer provided written informed consent to undergo CTP imaging. A motion correction method that consisted of manually outlining the tumor margins and then applying a rigid manual landmark registration algorithm followed by the non-rigid diffeomorphic demons algorithm was applied. The non-motion-corrected and motion-corrected images were analyzed with dual blood supply perfusion analysis software. Two observers performed the analysis twice, and the intra- and inter-observer variability of each method was assessed with Bland-Altman statistics. RESULTS: The 95% limits of agreement of intra-observer reproducibility for observer 1 improved from -84.4%, 65.3% before motion correction to -33.8%, 30.3% after motion correction (r = 0.86 and 0.97, before and after motion correction, p < 0.0001 for both) and for observer 2 from -151%, 96% to -49 %, 36 % (r = 0.87 and 0.95, p < 0.0001 for both). The 95% limits of agreement of inter-observer reproducibility improved from -168%, 154% to -17%, 25%. CONCLUSION: The use of a motion correction method significantly improves the reproducibility of CTP estimates of tumor blood flow in lung cancer. KEY POINTS: • Tumor blood flow estimates in advanced lung cancer show significant variability. • Motion correction improves the reproducibility of CT blood flow estimates in advanced lung cancer. • Reproducibility of blood flow measurements is critical to characterize lung tumor biology and the success of treatment in lung cancer.

Regulatory T cell frequencies are increased in preterm infants with clinical early-onset sepsis.

The predisposition of preterm neonates to invasive infection is, as yet, incompletely understood. Regulatory T cells (Tregs ) are potential candidates for the ontogenetic control of immune activation and tissue damage in preterm infants. It was the aim of our study to characterize lymphocyte subsets and in particular CD4(+) CD25(+) forkhead box protein 3 (FoxP3)(+) Tregs in peripheral blood of well-phenotyped preterm infants (n = 117; 23 + 0 - 36 + 6 weeks of gestational age) in the first 3 days of life in comparison to term infants and adults. We demonstrated a negative correlation of Treg frequencies and gestational age. Tregs were increased in blood samples of preterm infants compared to term infants and adults. Notably, we found an increased Treg frequency in preterm infants with clinical early-onset sepsis while cause of preterm delivery, e.g. chorioamnionitis, did not affect Treg frequencies. Our data suggest that Tregs apparently play an important role in maintaining maternal-fetal tolerance, which turns into an increased sepsis risk after preterm delivery. Functional analyses are needed in order to elucidate whether Tregs have potential as future target for diagnostics and therapeutics.

[Robot-assisted surgery in the head and neck region]. / Robotergestützte Chirurgie im Kopf-Hals-Bereich.

Robot-assisted surgery (RAS) in the head and neck region is believed to have a large potential for the improvement of patient care. Several systems with a master-slave setup are already in routine clinical use, particularly for oncologic surgery. Although specific patient groups may benefit from RAS, there is a lack of randomized clinical studies validating the advantages of these new technological systems in comparison to the existing standard procedures. On the other hand, RAS in the head and neck region is being constantly developed. Currently, the main limitations are the technical miniaturization of the tools and the loss of haptic feedback, as well as the high costs for acquisition and maintenance without financial reimbursement. In any case, the current generation of head and neck surgeons will face the technical, scientific, and ethical challenges of RAS.

Consistency of spectral results in cardiac dual-source photon-counting CT.

We evaluate stability of spectral results at different heart rates, acquisition modes, and cardiac phases in first-generation clinical dual-source photon-counting CT (PCCT). A cardiac motion simulator with a coronary stenosis mimicking a 50% eccentric calcium plaque was scanned at five different heart rates (0, 60-100 bpm) with the three available cardiac scan modes (high pitch prospectively ECG-triggered spiral, prospectively ECG-triggered axial, retrospectively ECG-gated spiral). Subsequently, full width half max (FWHM) of the stenosis, Dice score (DSC) for the stenosed region, and eccentricity of the non-stenosed region were calculated for virtual monoenergetic images (VMI) at 50, 70, and 150 keV and iodine density maps at both diastole and systole. FWHM averaged differences of - 0.20, - 0.28, and - 0.15 mm relative to static FWHM at VMI 150 keV across acquisition parameters for high pitch prospectively ECG-triggered spiral, prospectively ECG-triggered axial, and retrospectively ECG-gated spiral scans, respectively. Additionally, there was no effect of heart rate and acquisition mode on FWHM at diastole (p-values < 0.001). DSC demonstrated similarity among parameters with standard deviations of 0.08, 0.09, 0.11, and 0.08 for VMI 50, 70, and 150 keV, and iodine density maps, respectively, with insignificant differences at diastole (p-values < 0.01). Similarly, eccentricity illustrated small differences across heart rate and acquisition mode for each spectral result. Consistency of spectral results at different heart rates and acquisition modes for different cardiac phase demonstrates the added benefit of spectral results from PCCT to dual-source CT to further increase confidence in quantification and advance cardiovascular diagnostics.

Translational, rotational, and vibrational coupling into phase in diffractively coupled optical cavities.

All-reflective optical systems are under consideration for future gravitational wave detector topologies. A key feature of these all-reflective systems is the use of Fabry-Perot cavities with diffraction gratings as input couplers; however, theory predicts and experiment has shown that translation of the grating surface across the incident laser light will introduce additional phase into the system. This translation can be induced through simple side-to-side motion of the coupler, yaw motion of the coupler around a central point (i.e., rotation about a vertical axis), and even via internal resonances (i.e., vibration) of the optical element. In this Letter we demonstrate on a prototype-scale suspended cavity that conventional cavity length-sensing techniques used to detect longitudinal changes along the cavity axis will also be sensitive to translational, rotational, and vibrational motion of the diffractive input coupler. We also experimentally verify the amplitude response and frequency dependency of the noise coupling as given by theory.

Angiotensin II receptor blocker induced fetopathy: 7 cases.

BACKGROUND: During a period of 12 months 7 newborns with a partially severe fetopathy caused most probably by maternal sartan-intake in pregnancy were treated in 5 German teaching hospitals. Sartans antagonize the effect of angiotensin II at the AT1-receptor and are used to treat arterial hypertension. METHOD: We presented 2 cases at the yearly GNPI meeting 2010 and we were informed about similar cases in other German teaching hospitals which we brought together in this publication. RESULTS: In the presented cases, maternal sartan intake was noticed at different times in pregnancy and was in part discontinued some weeks before delivery. In all pregnancies oligohydramnios was present and fetal kidneys displayed a hyperechogenic structure on ultrasound. The newborns' postnatal course varied: oligohydramnios sequence with lung hypoplasia, arterial hypotension and renal insufficiency were the predominant problems of the first days of life. The majority (4/7) of infants did not survive this period, in other cases there was a complete (1/7) recovery of renal function whereas others survived with renal impairment (2/7), in part requiring chronic dialysis. Further distinctive features seen frequently were disturbances of cranial ossification and flaccid paralysis of hands and feet with deviations as well as sensorineural hearing loss. CONCLUSION: These case reports again underline the hazardousness of maternal sartan intake with potential fatal outcome for the newborn. Though the use of sartans in pregnancy is contraindicated and several case reports of sartan induced fetopathies exist, the risk of sartan treatment generally seems to be underestimated.

Preclinical Performance Evaluation of a Robotic Endoscope for Non-Contact Laser Surgery.

Despite great efforts, transoral robotic laser surgery has not been established clinically. Patient benefits are yet to be proven to accept shortcomings of robotic systems. In particular, laryngeal reachability and transition from microscope to accurate endoscopic laser ablation have not been achieved. We have addressed those challenges with a highly integrated robotic endoscope for non-contact endolaryngeal laser surgery. The current performance status has been assessed in multi-level user studies. In addition, the system was deployed to an ex vivo porcine larynx. The robotic design comprises an extensible continuum manipulator with multifunctional tip. The latter features laser optics, stereo vision, and illumination. Vision-based performance assessment is derived from depth estimation and scene tracking. Novices and experts (n = 20) conducted teleoperated delineation tasks to mimic laser ablation of delicate anatomy. Delineation with motion-compensated and raw endoscopic visualisation was carried out on planar and non-planar nominal patterns. Root mean square tracing errors of less than 0.75 mm were feasible with task completion times below 45 s. Relevant anatomy in the porcine larynx was exposed successfully. Accuracy and usability of the integrated platform bear potential for dexterous laser manipulation in clinical settings. Cadaver and in vivo animal studies may translate ex vivo findings.

WITHDRAWN: Radiology Extenders: Impact on Throughput and Accuracy for Routine Chest Radiographs.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

[The ulm emergency algorithm for the acute treatment of drug-induced, bradykinin-mediated angioedema]. / Ulmer Notfallalgorithmus: die Akuttherapie von medikamenteninduzierten bradykininvermittelten Angioödemen.

BACKGROUND: Bradykinin-mediated, drug-induced edema like ACE-inhibitor-induced angioedema (ACEi AE) is almost exclusively located in the head and neck region and is potentially life threatening. To date, there are no guidelines or officially-approved treatments available for this pathology. OBJECTIVES: We sought to provide a structured therapeutic algorithm for the acute treatment of drug-induced bradykinin-mediated angioedema. MATERIALS AND METHODS: We analyzed data (especially the course of disease and therapy) of all patients with acute angioedema, who presented to the Department of Otorhinolaryngology, Head and Neck Surgery at the University of Ulm (2010-2015). We also conducted a literature review on PubMed with the terms "acute angioedema", "angioedema emergency", "ACE angioedema", "bradykinin angioedema" and "angioedema therapy". Other fundamental references were the recent German guidelines "hereditary angioedema", "anaphylaxis" and "airway management". RESULTS: An emergency algorithm was generated as a flowchart for the acute therapy of bradykinin-mediated drug-induced angioedema was generated. We focused on the decision criteria for intubation/airway management and pharmacological therapy: antihistamines and glucocorticoids versus anti-bradykinin treatment. Furthermore, recommendations for inpatient monitoring have been derived. CONCLUSION/DISCUSSION: To date, therapy of drug-induced bradykinin-mediated angioedema is performed according to an "off-label" use and without officially-approved guidelines. The presented emergency algorithm provides a first approach for a structured therapeutic concept for a potentially life-threatening pathology.

Sexual and demographic determinants for herpes simplex virus type 2 among fishermen along Lake Victoria, Kenya.

OBJECTIVES: To determine the prevalence and correlates of herpes simplex virus type 2 (HSV-2) seropositivity among fishermen along the shores of Lake Victoria in Kisumu district, Kenya. METHODS: Sera from a random sample of 250 fishermen from 18 beaches were collected after a detailed sociodemographic interview. HSV-2 infection was tested by Kalon HSV-2 ELISA. RESULTS: The HSV-2 seroprevalence was 63.9%. In multivariate analysis, fishermen were more likely to be infected with HSV-2 if they were HIV positive (prevalence ratio (PR) 1.27; 95% CI 1.06 to 1.52) compared with those testing HIV negative, were aged 18-20 (PR 0.49; 95% CI 0.24 to 0.99) and older than 40 (PR 1.66; 95% CI 1.30 to 2.14) years compared with those aged 21-25 years, perceived their last two sexual partners to have a sexually transmitted infection (STI; PR 1.27; 95% CI 1.06 to 1.52) compared with those who did not and were more likely to be circumcised (PR 1.49; 95% CI 1.19 to 1.86). CONCLUSIONS: HSV-2 seroprevalence is high among this population and is associated with HIV serostatus, age, perception about partner's STI status and circumcision.

Characterization of atherosclerotic plaques in human coronary arteries with 16-slice multidetector row computed tomography by analysis of attenuation profiles.

RATIONALE AND OBJECTIVES: We investigated if 16-slice multidetector row computed tomography (MDCT) allows correct classification of coronary plaques into calcified or noncalcified and further subclassification of noncalcified plaques into either lipid-rich with a necrotic core or fibrous. MATERIALS AND METHODS: Coronary arteries of 30 isolated hearts were filled postmortem with a contrast medium and scanned with a 16-slice MDCT imager (Light Speed 16 pro, GEMS, Milwaukee, WI). Imaging parameters: collimation 16 x 0.625 mm, pitch 0.325, tube voltage 120 kV, tube current 250 mA, and gantry rotation time 500 milliseconds. The images were reformatted perpendicular to the axis of the coronary arteries (AW 4.2 software, GEMS) and analyzed by establishing attenuation profiles of the coronary cross sections (ImageJ 1.33n software, NIH, Bethesda, MD). Results were compared with the correlating histopathologic sections of the arteries. RESULTS: Analysis of 195 CT cross-sections showed a sensitivity and specificity for the correct classification of calcified plaques of 100% and 97.3% and for noncalcified plaques of 80.8% and 95.1%, respectively. The attenuation of epicardial fat ranged from -119 Hounsfield units (HU) to 23 HU (median -71 HU), and from 93 HU to 625 HU (308 HU) for the contrast medium. Calcified plaques showed an attenuation between 333 HU and 1944 HU (1,089 HU), noncalcified plaques between 26 HU and 124 HU (52 HU). Further subclassification of noncalcified plaques showed attenuation values between 26 HU and 67 HU (median 44 HU) for lipid-rich plaques with a necrotic core and from 37 HU to 124 HU (median 67 HU) for fibrous plaques. CONCLUSIONS: Coronary atherosclerotic plaques can be reliably identified and classified as either calcified or noncalcified by 16-slice MDCT in postmortem studies. Further differentiation of noncalcified plaques in either lipid-rich or fibrous is not reliably feasible because of substantial overlap of the attenuation.

Teleoperated tubular continuum robots for transoral surgery - feasibility in a porcine larynx model.

BACKGROUND: Evidence suggests that transoral robot-assisted surgery is becoming increasingly common, yet current systems are incapable of sufficiently reaching the glottis or subglottic areas. This paper presents a teleoperated tubular continuum robot prototype for laryngeal surgery in a feasibility study. METHODS: A tubular continuum robot prototype is used to perform basic surgical examination in five ex vivo porcine laryngeal specimens. Standard imaging and tooling were integrated and evaluated to improve the system for future application in humans. RESULTS: Access to and application of the tubular continuum robot in the porcine larynx is feasible. Visualization of and accessibility to all structures of interest were successfully achieved, and minor surgical procedures such as biopsies could be performed. CONCLUSIONS: Despite proven feasibility, there is a need for further improvements. A version with dual robot arms would be essential to realize a pre-market prototype for further investigation in a human model.

Efficacy of waiting periods and topical fluoride treatment on toothbrush abrasion of eroded enamel in situ.

The aim of this study was to investigate the effectiveness of both waiting periods between acid exposure and tooth brushing and fluoride applications in preventing toothbrush abrasion of acid-softened enamel surfaces. The study, on 5 subjects, had an in situ crossover design with experimental periods of 5 days each. Human enamel samples were recessed in mouth appliances and at the end of each experimental period, enamel loss was determined profilometrically. Specimens were eroded extraorally (2 x 20 min per day; 0.05 M citric acid), standardized brushing (2 x 30 s per sample per day; powered toothbrush) was performed in situ. The groups were: (1) erosion only, (2) brushing with fluoride-free toothpaste directly after, (3) 2 h after, or (4) before erosion; fluoride application was either (5) brushing with a fluoride toothpaste or (6) brushing with a fluoride toothpaste or gel, and rinsing with a fluoride mouth rinse. Enamel loss was (1) 45.2 +/- 10.8, (2) 79.3 +/- 7.8, (3) 81.7 +/- 9.5, (4) 69.7 +/- 13.8, (5) 51.5 +/- 13.0, and (6) 41.2 +/- 1.8 microm. Brushing without fluoride increased the enamel loss significantly (p < or = 0.001), waiting for 2 h had no protective effect, and brushing before erosion decreased enamel loss values only by 12% (n.s.). In the fluoride groups, enamel loss was significantly lower than after brushing with the fluoride-free toothpaste and comparable to values after erosion only (n.s.). Waiting periods had only a minor effect, whilst the application of fluoride appeared promising.

An Innovate Robotic Endoscope Guidance System for Transnasal Sinus and Skull Base Surgery: Proof of Concept.

Objective Advanced transnasal sinus and skull base surgery remains a challenging discipline for head and neck surgeons. Restricted access and space for instrumentation can impede advanced interventions. Thus, we present the combination of an innovative robotic endoscope guidance system and a specific endoscope with adjustable viewing angle to facilitate transnasal surgery in a human cadaver model. Materials and Methods The applicability of the robotic endoscope guidance system with custom foot pedal controller was tested for advanced transnasal surgery on a fresh frozen human cadaver head. Visualization was enabled using a commercially available endoscope with adjustable viewing angle (15-90 degrees). Results Visualization and instrumentation of all paranasal sinuses, including the anterior and middle skull base, were feasible with the presented setup. Controlling the robotic endoscope guidance system was effectively precise, and the adjustable endoscope lens extended the view in the surgical field without the common change of fixed viewing angle endoscopes. Conclusion The combination of a robotic endoscope guidance system and an advanced endoscope with adjustable viewing angle enables bimanual surgery in transnasal interventions of the paranasal sinuses and the anterior skull base in a human cadaver model. The adjustable lens allows for the abandonment of fixed-angle endoscopes, saving time and resources, without reducing the quality of imaging.

Performance of a novel test for IgM and IgG antibodies in subjects with culture-documented genital herpes simplex virus-1 or -2 infection.

Novel tests (BioPlex) for herpes simplex virus-1 (HSV-1) and HSV-2 IgG were compared with HerpeSelect HSV-1 and HSV-2 ELISAs for type-specific IgG. The sensitivity and specificity of BioPlex HSV-1 IgG were 94% (84/89) and 96% (119/124), respectively, with unselected sera, while the sensitivity and specificity of BioPlex HSV-2 IgG were 92% (109/118) and 98% (95/97), respectively. BioPlex IgM was compared with Diamedix IgM against sera from patients with culture-documented genital herpes. The test results were concordant in 81% of sera from HSV-1 patients and in 90% of sera from HSV-2 patients. Use of BioPlex IgM in addition to BioPlex IgG tests increased HSV-2 seroconversion detection from 47% of subjects to 70%. Use of Diamedix IgM in addition to Focus IgG ELISA increased HSV-2 detection from 40% of subjects to 70%. IgM was detected by BioPlex in 63% of sera from patients with early HSV-2 infection (< 30 days) and in 59% of sera by Diamedix. IgM was also detected in a large proportion of sera from subjects with established HSV-2 infection (33% by BioPlex and 29% by Diamedix). Addition of IgM testing substantially increased the ability to detect seroconversion early in infection. IgM is an indicator of recent infection only in subjects who lack detectable IgG.

Design, synthesis, and conformational analysis of a novel macrocyclic HIV-protease inhibitor.

Design modifications to the lead HIV-PR inhibitor 1 (MDL 73,669, Ki = 5 nM) have been postulated based on a computational model of the 1/HIV-PR complex. A novel macrocyclic inhibitor 8 (MDL 104,168) wherein the P1 and P3 side chains of the original acyclic inhibitor have been joined retains good biological activity (Ki = 20 nM). NMR analysis of the precursor alcohol (S)-7 shows the conformation of the cyclic region to be very similar to that observed in the enzyme-bound 8 as determined by the computational model. Consistency of the computational model with NMR data and in vacuo molecular dynamics simulations provide the basis for postulating further modifications of the cyclic inhibitor expected to optimize its interactions with HIV-PR.

Cyclic nitrone free radical traps: isolation, identification, and synthesis of 3,3-dimethyl-3,4-dihydroisoquinolin-4-ol N-oxide, a metabolite with reduced side effects.

A C-4 hydroxylated metabolite (2, 3,3-dimethyl-3,4-dihydroisoquinolin-4-ol N-oxide) of the previously described cyclic nitrone free radical trap 1 (3,3-dimethyl-3,4-dihydroisoquinoline N-oxide, a cyclic analog of phenyl-tert-butylnitrone (PBN)) was isolated, identified, and synthesized. The metabolite (2), though a less potent antioxidant than 1 in an in vitro lipid peroxidation assay, showed greatly reduced acute toxicity and sedative properties. Several analogs of 2 were prepared in attempts to improve on its weak antioxidant activity while retaining the desirable side effect profile. Effective structural changes included replacement of the gem-dimethyl moiety with spirocycloalkane groups and/or oxidation of the alcohols to the corresponding ketones. All of the analogs were more lipophilic (log k'(w)) and more active in the standard lipid peroxidation assay than 2. In addition, some of the compounds were able to protect cerebellar granule cells against oxidative damage (an in vitro model of oxidative brain injury) with IC50 values well below the value of the lead compound 1. The ketones, as predicted, were much more potent than 2 (and 1) in both of the above assays (up to ca. 200-fold). However, only compounds with a hydroxyl or an acetate group at C-4 displayed significantly reduced acute toxicity and sedative properties relative to those of 1. Importantly, the diminishment of toxicity and sedation were not the result of a lack of brain penetration as both 2 and the corresponding ketone (3,3-dimethyl-3,4-dihydro-3H-isoquinolin-4-one N-oxide) achieved equal or greater brain levels than those of 1 when administered to rats i.p.

Dynamic high-resolution electron-beam CT scanning for the diagnosis of bronchiolitis obliterans syndrome after lung transplantation.

PURPOSES: To determine the diagnostic capabilities of dynamic high-resolution electron-beam (HREB) CT scanning for diagnosing bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. MATERIALS AND METHODS: At the time of follow-up examinations after lung transplantation, 52 patients were examined by dynamic HREB CT scan. Visual signs of small airway disease were assessed and compared with lung function. For numerical analysis, the mean lung attenuation and its SD were determined and compared with the course of lung function tests. RESULTS: On visual analysis, significant parenchymal attenuation inhomogeneities were present in eight of nine patients with manifest BOS, and in two of four patients who developed BOS during follow-up. Thirteen of 20 patients with persistent normal lung function displayed homogeneous lung attenuation. On numerical analysis, mean lung attenuation was significantly lower in patients who developed BOS during follow-up than in patients with persistent normal lung function (both in expiration and inspiration, p < 0.0001). With an optimal threshold, the sensitivity was 100% (4 of 4 patients) and the specificity was 90% (19 of 20 patients). In patients with BOS at the time of the CT scan examination, parenchymal attenuation was less homogeneous than in patients with persistent normal lung function (p < 0.0001). With an optimal threshold, the sensitivity was 78% (7 of 9 patients) and the specificity was 85% (17 of 20 patients). CONCLUSIONS: Dynamic HREB CT of lung transplant recipients correlates well with lung function criteria of BOS at the time of the CT examination and with the subsequent progression to BOS.