Patient Preferences for Coronary CT Angiography with Stress Perfusion, SPECT, or Invasive Coronary Angiography.

Background Patient preference is pivotal for widespread adoption of tests in clinical practice. Patient preferences for invasive versus other noninvasive tests for coronary artery disease are not known. Purpose To compare patient acceptance and preferences for noninvasive and invasive cardiac imaging in North and South America, Asia, and Europe. Materials and Methods This was a prospective 16-center trial in 381 study participants undergoing coronary CT angiography with stress perfusion, SPECT, and invasive coronary angiography (ICA). Patient preferences were collected by using a previously validated questionnaire translated into eight languages. Responses were converted to ordinal scales and were modeled with generalized linear mixed models. Results In patients in whom at least one test was associated with pain, CT and SPECT showed reduced median pain levels, reported on 0-100 visual analog scales, from 20 for ICA (interquartile range [IQR], 4-50) to 6 for CT (IQR, 0-27.5) and 5 for SPECT (IQR, 0-25) (P < .001). Patients from Asia reported significantly more pain than patients from other continents for ICA (median, 25; IQR, 10-50; P = .01), CT (median, 10; IQR, 0-30; P = .02), and SPECT (median, 7; IQR, 0-28; P = .03). Satisfaction with preparation differed by continent and test (P = .01), with patients from Asia reporting generally lower ratings. Patients from North America had greater percentages of "very high" or "high" satisfaction than patients from other continents for ICA (96% vs 82%, respectively; P < .001) and SPECT (95% vs 79%, respectively; P = .04) but not for CT (89% vs 86%, respectively; P = .70). Among all patients, CT was preferred by 54% of patients, compared with 18% for SPECT and 28% for ICA (P < .001). Conclusion For cardiac imaging, patients generally favored CT angiography with stress perfusion, while study participants from Asia generally reported lowest satisfaction. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Woodard and Nguyen in this issue.

Developing a risk-based composite neurologic outcome for a trial of hydroxyurea in young children with sickle cell disease.

BACKGROUND: Studies of interventions to prevent the many neurological complications of sickle cell disease must take into account multiple outcomes of variable severity, with limited sample size. The goals of the studies presented were to use investigator preferences across outcomes to determine an attitude-based weighting of relevant clinical outcomes and to establish a valid composite outcome for a clinical trial. METHODS: In Study 1, investigators were surveyed about their practice regarding hydroxyurea therapy and opinions about outcomes for the "Hydroxyurea to Prevent the Central Nervous System Complications of Sickle Cell Disease Trial" (HU Prevent), and their minimally acceptable relative risk reduction for the two outcome components, motor and neurocognitive deficits. In Study 2, HU Prevent investigators provided overall weights for these two components. In Study 3, they provided more granular rankings, ratings, and maximum number acceptable to harm. A weighted composite outcome, the Stroke Consequences Risk Score, was constructed that incorporates the major neurologic complications of sickle cell disease. The Stroke Consequences Risk Score represents the 3-year risk of suffering the adverse consequences of stroke. In Study 4, the results of the Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP2) and Silent Infarct Transfusion Trials were reanalyzed in light of the composite outcome. RESULTS: In total, 22 to 27 investigators participated per study. In Study 1, across three samplings between 2009 and 2015, the average minimally acceptable relative risk reduction ranged from 0.36 to 0.50, at or below the target effect size of 0.50. In 2015, 21 (91%) reported that a placebo-controlled trial is reasonable; 23 (100%), that it is ethical; and 22 (96%), that they would change their practice, if the results of the trial were positive. In Studies 2 and 3, the weight elicited for a cognitive decline (of 10 IQ points) from the overall assessment was 0.67 (and for motor deficit, the complementary 0.33); from ranking, 0.6; from rating, 0.58; and from maximal number acceptable to harm, 0.5. Using data from two major clinical trials, Study 4 demonstrated the same conclusions as the original trials using the Stroke Consequences Risk Score, with smaller p-values for both reanalyses. An assessment of acceptability was performed as well. CONCLUSION: This set of studies provides the rationale, justification, and validation for the use of a weighted composite outcome and confirms the need for the phase III HU Prevent study. Surveys of investigators in multi-center studies can provide the basis of clinically meaningful outcomes that foster the translation of study results into practice while increasing the efficiency of a study.

Technique, pitfalls, quality, radiation dose and findings of dynamic 4-dimensional computed tomography for airway imaging in infants and children.

This retrospective review of 33 children's dynamic 4-dimensional (4-D) computed tomography (CT) images of the airways, performed using volume scanning on a 320-detector array without anaesthesia (free-breathing) and 1.4-s continuous scanning, was undertaken to report technique, pitfalls, quality, radiation doses and findings. Tracheobronchomalacia (airway diameter collapse >28%) was recorded. Age-matched routine chest CT scans and bronchograms acted as benchmarks for comparing effective dose. Pitfalls included failure to administer intravenous contrast, pull back endotracheal tubes and/or remove nasogastric tubes. Twenty-two studies (67%) were diagnostic. Motion artefact was present in 16 (48%). Mean effective dose: dynamic 4-D CT 1.0 mSv; routine CT chest, 1.0 mSv, and bronchograms, 1.4 mSv. Dynamic 4-D CT showed tracheobronchomalacia in 20 patients (61%) and cardiovascular abnormalities in 12 (36%). Fourteen children (70%) with tracheobronchomalacia were managed successfully by optimising conservative management, 5 (25%) underwent surgical interventions and 1 (5%) died from the presenting disorder.

Diagnosis, treatment and long-term outcome of autoimmune pancreatitis in Sweden.

INTRODUCTION: Autoimmune pancreatitis (AIP) is a pancreatic inflammatory process characterized by a strong inflammatory cell infiltration and two histopathologically distinct subtypes: type 1 and type 2. Diagnosis is often challenging and requires a combination of clinical, laboratory and imaging data. AIP can mimic pancreatic tumours leading to unnecessary resections if not correctly diagnosed. Short- and long-term outcomes of AIP have been poorly investigated so far and no large series have been previously reported from Sweden. METHODS: A single-centre, retrospective, cohort study of patients with histologically confirmed or highly probable diagnosis of AIP according to ICDC criteria. Demographic, clinical and radiological characteristics, type of treatment and its outcomes were collected and analysed. RESULTS: Seventy-one patients with AIP (87% with type 1), were evaluated at Karolinska University Hospital between 2004 and 2018; 49% males, mean age 49 years (range 44-53). Among them, 28% were histologically confirmed, 35% presented with jaundice, 22% with acute pancreatitis, 39% had non-specific symptoms such as weight loss or abdominal pain, 84% showed other organ involvement (OOI). Radiologically, 76% showed a focal pancreatic enlargement, 27% diffuse enlargement, 27% signs of acute pancreatitis and 10% of chronic pancreatitis. Overall, 58 patients (81%) underwent treatment with different medications: 46 (79%) cortisone, 7 (12%) azathioprine, 5 (8%) other immunosuppressive drugs. Twenty-six (36%) underwent biliary stenting and 12 (16%) were given surgery. In total, 47% of patients developed pancreatic exocrine insufficiency (PEI), of whom 76% had a severe form (faecal elastase-1 < 100 µg/g) and 21% of patients developed diabetes mellitus (pancreatic endocrine insufficiency), of whom 73% required insulin. CONCLUSIONS: AIP is a challenging disease for diagnosis and treatment. Cortisone treatment is generally successful and provides clinical remission in the large majority of patients (>90%). In the further course of the disease, a considerable number of patients develop PEI and diabetes. Only one-quarter of patients exhibit on imaging the characteristic "sausage-like" pancreas (diffuse enlargement), approximately three-quarters had a focal mass that could be misdiagnosed as pancreatic malignancy.

Allergies - A T cells perspective in the era beyond the TH1/TH2 paradigm.

Allergic diseases have emerged as a major health care burden, especially in the western hemisphere. They are defined by overshooting reactions of an aberrant immune system to harmless exogenous stimuli. The TH1/TH2 paradigm assumes that a dominance of TH2 cell activation and an inadequate TH1 cell response are responsible for the development of allergies. However, the characterization of additional T helper cell subpopulations such as TH9, TH17, TH22, THGM-CSF and their interplay with regulatory T cells suggest further layers of complexity. This review summarizes state-of-the-art knowledge on T cell diversity and their induction, while revisiting the TH1/TH2 paradigm. With respect to these numerous contributors, it offers a new perspective on the pathogenesis of asthma, allergic rhinitis (AR) and atopic dermatitis (AD) incorporating recent discoveries in the field of T cell plasticity.

Differential effects of oxytocin on mouse hippocampal oscillations in vitro.

The hypothalamic neuropeptide oxytocin (OT) controls childbirth and lactation, is involved in social behaviors, plays a role in various psychiatric disorders, and has effects on learning and memory. Although behavioral effects of OT have been extensively studied, much less is known about its effects on neuronal and network activity patterns. Here, we investigate the effect of OT on two major patterns of hippocampal network activity in mouse hippocampal slices. We studied different in vitro models of gamma-frequency oscillations and sharp wave-ripple complexes (SPW-R), two patterns implicated in spatial memory formation and memory consolidation respectively. Strikingly, we found a profound difference of OT on these distinct, mutually exclusive activity patterns. While gamma oscillations where not affected by the activation of hippocampal OT receptors, SPW-R were potently and rapidly suppressed. Interestingly, the temporal precision of oscillation-coupled spikes was enhanced at the same time. Thus, OT exerts strongly different modulatory effects on different network patterns, most likely by inhibition of different sets of inhibitory interneurons. The observed dichotomy between gamma and SPW-R oscillations may have profound effects on the behavioral and cognitive effects of OT which are relevant to cognitive processes and to psychiatric diseases.

Influence of Season, Storage Temperature and Time of Sample Collection in Pancreatitis-Associated Protein-Based Algorithms for Newborn Screening for Cystic Fibrosis.

Newborn screening (NBS) for cystic fibrosis (CF) based on pancreatitis-associated protein (PAP) has been performed for several years. While some influencing factors are known, there is currently a lack of information on the influence of seasonal temperature on PAP determination or on the course of PAP blood concentration in infants during the first year of life. Using data from two PAP studies at the Heidelberg NBS centre and storage experiments, we compared PAP determinations in summer and winter and determined the direct influence of temperature. In addition, PAP concentrations measured in CF-NBS, between days 21-35 and 36-365, were compared. Over a 7-year period, we found no significant differences between PAP concentrations determined in summer or winter. We also found no differences in PAP determination after 8 days of storage at 4 °C, room temperature or 37 °C. When stored for up to 3 months, PAP samples remained stable at 4 °C, but not at room temperature (p = 0.007). After birth, PAP in neonatal blood showed a significant increasing trend up to the 96th hour of life (p < 0.0001). During the first year of life, blood PAP concentrations continued to increase in both CF- (36-72 h vs. 36-365 d p < 0.0001) and non-CF infants (36-72 h vs. 36-365 d p < 0.0001). Seasonal effects in central Europe appear to have a limited impact on PAP determination. The impact of the increase in blood PAP during the critical period for CF-NBS and beyond on the applicability and performance of PAP-based CF-NBS algorithms needs to be re-discussed.

Three-dimensional printed realistic pediatric static and dynamic airway models for bronchoscopy and foreign body removal training.

For mastering bronchoscope handling, positioning, and directing of the bronchoscope in response to the intraluminal view provided by the bronchoscope camera, sufficient training is necessary, especially in infants and toddlers who have smaller airways, faster respiratory rates, and higher airway collapsibility. With the use of three-dimensional printing, we aimed to develop a set of anatomically accurate and low-cost airway models for teaching and training of bronchoscopy technique and foreign body removal: a translucent airway box model, a static airway model, and a dynamic airway model consisting of a flexible tree model connected to a pump that allows simulation of airway collapsibility during breathing. Computed tomography (CT) patient data of three different ages (1, 5, and 18 years of age) was imported into Materialise Mimics, segmented, and printed using VisoClear and soft Tango+ material. The models were evaluated by three pediatric pulmonology attendings for anatomical accuracy and usefulness for teaching and training. The translucent airway box model was preferred for the initial presentation of bronchoscope handling and learning anatomy in three dimensions. The static and flexible tree models were used to train bronchoscope handling and foreign body removal. The dynamic model provided the most realistic representation of a pediatric airway throughout the respiratory cycle with increased patency during inspiration and relative collapse during exhalation. Objective verification of anatomical accuracy and physiology of breathing motion was obtained by comparing CT scans of the model with original images and by application of 4D dynamic CT airway imaging protocols, respectively.

Immunoglobulin G subtypes-1 and 2 differentiate immunoglobulin G4-associated sclerosing cholangitis from primary sclerosing cholangitis.

BACKGROUND: Autoimmune pancreatitis is a special form of chronic pancreatitis with strong lymphocytic infiltration and two histopathological distinct subtypes, a lymphoplasmacytic sclerosing pancreatitis and idiopathic duct centric pancreatitis. Immunoglobulin G4-associated cholangitis may be present at the time of autoimmune pancreatitis type 1 diagnosis or occur later over the course of the disease. Immunoglobulin G4 is considered reliable but not an ideal marker for diagnosis of autoimmune pancreatitis type 1 with reported sensitivity between 71-81%. It is essential to differentiate sclerosing cholangitis with autoimmune pancreatitis from primary sclerosing cholangitis as the treatment and prognosis of the two diseases are totally different. It was the aim of the study to find a marker for immunoglobulin G4-associated cholangitis that would distinguish it from primary sclerosing cholangitis. PATIENTS AND METHODS: We performed a retrospective analysis of patients with autoimmune pancreatitis at our outpatient clinic. Patients from the primary sclerosing cholangitis registry were taken as a control group. Blood samples for the measurement of immunoglobulin subclasses were analysed at the time of diagnosis. RESULTS: Patients with autoimmune pancreatitis and immunoglobulin G4-associated cholangitis had higher values of immunoglobulin G2 when compared to autoimmune pancreatitis alone or primary sclerosing cholangitis with a high specificity (97%) and high positive predictive value (91%). In patients with normal or low immunoglobulin G2 or immunoglobulin G4, a high level of immunoglobulin G1 indicated primary sclerosing cholangitis. CONCLUSION: Immunoglobulin G1 and immunoglobulin G2 can distinguish patients with immunoglobulin G4-associated cholangitis from those with primary sclerosing cholangitis.

MR imaging of the shoulder in youth baseball players: Anatomy, pathophysiology, and treatment.

With an increasing participation in youth sports and a growing popularity of overhead sports, shoulder pain and injuries are common in pediatric baseball players. In contrast to traumatic and collision injuries, which are more frequent with high-impact sports, many of the shoulder injuries are the result of repetitive overuse. Undiagnosed and untreated injury to the growth plates of skeletally immature athletes can lead to remodeling, which can negatively impact the biomechanics of the shoulder and produce long-term morbidity. Recently, there is an increasing emphasis on the association between skeletal maturation and injury patterns. The increasing use of magnetic resonance (MR) imaging has led to a better characterization of the traditionally radiographically-diagnosed growth plate injuries and awareness of other soft tissue and cartilaginous injuries that were previously thought to predominately occur in adult baseball players. The goal of this review is to: 1) highlight the normal anatomic changes that occur in the shoulder girdle during development and maturation; 2) discuss the biomechanical forces that are applied to the shoulder during a pitch; and 3) highlight the various injury patterns and adaptive remodeling that can occur in the shoulders of youth baseball athletes along with the current treatment options. These topics include growth plate injury, osteochondral injury, labral tear, capsular remodeling and rotator cuff tendinopathy.