Evaluation and recommendations of the oral health, oral function, and orofacial aesthetics-related measures of the ICHOM Standard Set for Cleft Lip and Palate.

This study was performed to evaluate the efficacy of outcome measures for the orofacial domain included in the International Consortium for Health Outcomes Measurement Standard Set for Cleft Lip and Palate (ICHOM-SCS). In this multicentre study involving two cleft centres, suggestions to optimize the type and timing of outcome measures were made based on data and clinical experience. Patient-reported outcome measures (PROMs) (CLEFT-Q Jaw, Teeth, Eating/Drinking; Child Oral Health Impact Profile-Oral Symptoms Scale (COHIP-OSS)) and clinical outcome measures (caries experience and dental occlusion) data were collected retrospectively for age 5, 8, 10, 12, 19, and 22 years. The data were categorized by cleft type and analysed within and between age groups using Spearman correlation, the distribution of responses per item, a two-sample test for equality of proportions, and effect plots. Most correlations between PROMs and clinical outcome measures were weak (r < 0.5), suggesting PROMs and clinical outcome measures complement each other. The COHIP-OSS and CLEFT-Q Eating/Drinking barely detected problems in any patient category and are no longer recommended. A suitable alternative appears complex to find; outcomes of this study and the recent literature doubt an added value. Similar problems were found in the CLEFT-Q Jaw at time-point 12 years. Therefore, time-points 15 and 17 years are currently suggested.

External control cohorts for the single-arm LIBRETTO-001 trial of selpercatinib in RET+ non-small-cell lung cancer.

BACKGROUND: Data for selpercatinib [a selective REarranged during Transfection (RET) inhibitor] from a single-arm trial (LIBRETTO-001, NCT03157128) in RET-fusion-positive advanced/metastatic non-small-cell lung cancer (NSCLC) were used in combination with external data sources to estimate comparative efficacy [objective response rate (ORR), progression-free survival, and overall survival (OS)] in first- and second-line treatment settings. METHODS: Patient-level data were obtained from a de-identified real-world database. Patients diagnosed with advanced/metastatic NSCLC with no prior exposure to a RET inhibitor and one or more prior line of therapy were eligible. Additionally, individual patient-level data (IPD) were obtained from the pemetrexed + platinum arm of KEYNOTE-189 (NCT03950674, first line) and the docetaxel arm of REVEL (NCT01168973, post-progression). Patients were matched using entropy balancing, doubly robust method, and propensity score approaches. For patients with unknown/negative RET status, adjustment was made using a model fitted to IPD from a real-world database. RESULTS: In first-line unadjusted analyses of the real-world control, ORR was 87.2% for LIBRETTO-001 versus 66.7% for those with RET-positive NSCLC (P = 0.06). After adjustment for unknown RET status and other patient characteristics, selpercatinib remained significantly superior versus the real-world control for all outcomes (all P < 0.001 except unadjusted RET-fusion-positive cohort). Similarly, outcomes were significantly improved versus clinical trial controls (all P < 0.05). CONCLUSIONS: Findings suggest improvement in outcomes associated with selpercatinib treatment versus the multiple external control cohorts, but should be interpreted with caution. Data were limited by the rarity of RET, lack of mature OS data, and uncertainty from assumptions to create control arms from external data.

Patient Perspectives on the Risk-Based NLST Outcomes Tool for Lung Cancer Screening.

Researchers at the NCI have developed the Risk-Based NLST Outcomes Tool (RNOT), an online tool that calculates risk of lung cancer diagnosis and death with and without lung cancer screening, and false-positive risk estimates. This tool has the potential to facilitate shared decision making for screening. The objective of this study was to examine how current heavy and former smokers understand and respond to personalized risk estimates from the RNOT. Individuals who were eligible for lung cancer screening and were visiting Walter Reed National Military Medical Center were invited to participate in a semi-structured interview to assess their experiences with and perceptions of the RNOT. Results were analyzed using template analysis. Participants found their risk of lung cancer death to be lower than anticipated and were confused by changes in risk for lung cancer diagnosis with and without screening. Most participants indicated that the RNOT would be helpful in making screening decisions, despite reporting that there was no maximum risk for a false positive that would lead them to forgo lung cancer screening. Participants provided actionable needs and recommendations to optimize this tool. Risk-based screening tools may enhance shared decision making. The RNOT is being updated to incorporate these findings.

Utilizing Participatory Research to Engage Underserved Populations to Improve Health-Related Outcomes in Delaware.

Cooperative Extension is a community outreach program. Despite its large reach, there is a need for the evaluation of changes in health-related outcomes for individuals engaged with Cooperative Extension. A team-based challenge was developed using community-engaged participatory research integrated with Cooperative Extension to encourage healthy eating and physical activity behaviors through Cooperative Extension programming. Thus, the primary purpose of this secondary analysis was to (1) evaluate changes in anthropometric outcomes and (2) evaluate changes in health behavior outcomes. Associations of anthropometric changes and health behavior changes with engagement in the three-month team-based challenge were explored. Anthropometrics were measured using standard procedures, and intake of fruits and vegetables and physical activity were self-reported. Of the 145 participants in the community-engaged participatory research portion of the study, 52.4% (n = 76) had complete anthropometrics before and after the team-based challenge and were included in this study. At 3 months, there was a significant reduction in body mass index (-0.3 kg/m2, p = 0.024) and no significant change in waist circumference (p = 0.781). Fruit and vegetable intake significantly increased (+0.44 servings/day, p = 0.018). Physical activity did not significantly change based on (1) the number of days 30 or more minutes of physical activity was conducted (p = 0.765) and (2) Godin Leisure-Time Exercise Questionnaire scores (p = 0.612). Changes in anthropometrics and health behaviors were not associated with engagement in the team-based challenge. Using community-engaged participatory research with community outreach programs, such as Cooperative Extension, can improve health-related outcomes in underserved populations. However, despite a participatory approach, changes in anthropometrics and health behaviors were not associated with engagement in the developed team-based challenge.

Cardiac MRI for Patients with Increased Cardiometabolic Risk.

Cardiac MRI (CMR) has rich potential for future cardiovascular screening even though not approved clinically for routine screening for cardiovascular disease among patients with increased cardiometabolic risk. Patients with increased cardiometabolic risk include those with abnormal blood pressure, body mass, cholesterol level, or fasting glucose level, which may be related to dietary and exercise habits. However, CMR does accurately evaluate cardiac structure and function. CMR allows for effective tissue characterization with a variety of sequences that provide unique insights as to fibrosis, infiltration, inflammation, edema, presence of fat, strain, and other potential pathologic features that influence future cardiovascular risk. Ongoing epidemiologic and clinical research may demonstrate clinical benefit leading to increased future use. © RSNA, 2021.

Thymic Epithelial Neoplasms: Radiologic-Pathologic Correlation.

Thymic epithelial neoplasms, as classified by the World Health Organization, include thymoma, thymic carcinoma, and thymic carcinoid. They are a rare group of tumors and are often diagnosed incidentally in the work-up of parathymic syndrome, such as myasthenia gravis, or when mass effect or local invasion causes other symptoms. In each of these scenarios, understanding the radiologic-pathologic relationship of these tumors allows clinical imagers to contribute meaningfully to management decisions and overall patient care. Integrating important imaging features, such as local invasion, and pathologic features, such as necrosis and immunohistochemistry, ensures a meaningful contribution by clinical imagers to the care team.

Diffuse Lung Metastases in EGFR-Mutant Non-Small Cell Lung Cancer.

Diffuse lung metastases have been reported in non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The purpose of our study was to compare the incidence of diffuse lung metastases in EGFR-mutant NSCLC and EGFR-wild type NSCLC and to assess other imaging features that may be associated with diffuse lung metastases in EGFR-mutant NSCLC. Two radiologists retrospectively reviewed pre-treatment imaging of metastatic NSCLC cases with known EGFR mutation status. We assessed the imaging features of the primary tumor and patterns of metastases. The cohort consisted of 217 patients (117 EGFR-mutant, 100 EGFR wild-type). Diffuse lung metastasis was significantly more common in EGFR-mutant NSCLC compared with wild-type (18% vs. 3%, p < 0.01). Among the EGFR-mutant group, diffuse lung metastases were inversely correlated with the presence of a nodule greater than 6 mm other than the primary lung lesion (OR: 0.13, 95% CI: 0.04-0.41, p < 0.01). EGFR mutations in NSCLC are associated with increased frequency of diffuse lung metastases. The presence of diffuse lung metastases in EGFR-mutant NSCLC is also associated with a decreased presence of other larger discrete lung metastases. EGFR mutations in NSCLC should be suspected in the setting of a dominant primary lung mass associated with diffuse lung metastases.

Ultra-high field magnetic resonance imaging parameter mapping in the posterior horn of ex vivo human menisci.

OBJECTIVE: To investigate the relationship between meniscus magnetic resonance (MR) relaxation parameters and meniscus degradation through quantitative imaging of ex vivo posterior horns of menisci from subjects with and without knee osteoarthritis (OA). DESIGN: We sampled medial and lateral menisci from ten medial compartment knee OA patients (mean age 63 years) undergoing total knee replacement and from ten deceased donors (references, mean age 51 years). MR relaxation parameters T2*, T2 and T1 of the posterior horn were measured at a 9.4 T scanner. Comparisons were made between OA patients and references (with adjustment for age) as well as between medial and lateral menisci from the same knees. RESULTS: Mean values (standard deviation) of mean T2* were 13 (3.8), 6.9 (2.3), 7.2 (1.9) and 7.2 (1.7) ms for the medial and lateral patient menisci and the medial and lateral reference menisci, respectively. Corresponding values were 17 (3.7), 9.0 (2.2), 12 (4) and 9.0 (1.3) ms for T2 and 1810 (150), 1630 (30), 1580 (90) and 1560 (50) ms for T1. All three relaxation times were significantly longer in medial OA menisci compared to the other groups. Among medial reference menisci, relaxation times (mainly T1) tended to increase with age. CONCLUSIONS: MR relaxation times T2*, T2 and T1 in the posterior horn are longer in the medial menisci of patients with end-stage medial compartment knee OA compared to the corresponding lateral menisci and to reference menisci. The meniscus seems to undergo intrasubstance alterations related to both OA and ageing.

Imaging of Combat-Related Thoracic Trauma - Review of Penetrating Trauma.

Introduction: Combat-related thoracic trauma is a significant contributor to morbidity and mortality of the casualties from Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF). Penetrating, blunt, and blast injuries were the most common mechanisms of trauma. Imaging plays a key role in the management of combat-related thoracic trauma casualties. This review discusses the imaging manifestations of thoracic injuries from penetrating trauma, emphasizing epidemiology and diagnostic clues seen during OEF and OIF. Materials and Methods: The assessment of radiologic findings in patients who suffer from combat-related thoracic trauma is the basis of this review article. The imaging modalities for this study include multi-detector computed tomography and chest radiography. Results: High-velocity penetrating projectile injuries appear as hemorrhage and re-expansion pulmonary edema from the temporary cavity and a linear, blood-filled track from the permanent cavity. In cases where the projectile passes totally through the body, entrance wounds at the skin surface and tracks through the subcutaneous tissues may be the only indications of penetrating trauma. When assessing vascular injury, special attention should be paid to the right hilum in contrast-enhanced multi-detector computed tomography, as contrast is concentrated in the superior vena cava and superior cavoatrial junction may obscure small fragments. Additionally, CT angiography may show vessel disruption or extravasation of contrast distal to normal vessel location in addition to intraluminal filling defects and pseudo-aneurysms. Tension pneumopericardium may rarely complicate penetrating or blunt chest trauma. On imaging, distension of the pericardial sack by pneumopericardium and compression of the heart support the diagnosis of tension. On multi-detector computed tomography in the acute trauma setting, fluid in the pleural space should be considered hemothorax, particularly when Hounsfield units are above 35. Acutely, extravasated blood will have similar attenuation to the thoracic vasculature, whereas clotted blood will have higher values of 50-90 Hounsfield units. Conclusion: Combat-related thoracic trauma continues to be a significant contributor to the morbidity and mortality of those injured during OEF and OIF. This review of the imaging manifestations of penetrating thoracic injury during OEF and OIF focuses on key diagnostic findings for clinicians caring for combat casualties. The distinct injury pattern and atypical imaging manifestations of penetrating trauma are important to recognize early due to the acuity of this patient population and the influence of accurate diagnosis on clinical management.

Imaging of Combat-Related Thoracic Trauma - Blunt Trauma and Blast Lung Injury.

Introduction: Combat-related thoracic trauma (CRTT) is a significant contributor to morbidity and mortality of the casualties from Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF). Penetrating, blunt, and blast injuries are the most common mechanisms of trauma to the chest. Imaging plays a key role in the battlefield management of CRTT casualties. This work discusses the imaging manifestations of thoracic injuries from blunt trauma and blast injury, emphasizing epidemiology and diagnostic clues seen during OEF and OIF. Materials and Methods: The assessment of radiologic findings in patients who suffer from combat-related blunt thoracic trauma and blast injury is the basis of this work. The imaging modalities for this work include multi-detector computed tomography (MDCT) and chest radiography. Results: Multiple imaging modalities are available to imagers on or near the battlefront, including radiography, fluoroscopy, and MDCT. MDCT with multi-planar reconstructions is the most sensitive imaging modality available in combat hospitals for the evaluation of CRTT. In modern combat, blunt and blast injuries account for a significant portion of CRTT. Individual body armor converts penetrating trauma to blunt trauma, leading to pulmonary contusion that accounted for 50.2% of thoracic injuries during OIF and OEF. Flail chest, a subset of blunt chest injury, is caused by significant blunt force to the chest and occurs four times as frequently in combat casualties when compared with the civilian population. Imaging features of CRTT have significant diagnostic and prognostic value. Pulmonary contusions on chest radiography appear as patchy consolidations in the acute setting with ill-defined and non-segmental borders. MDCT of the chest is a superior imaging modality in diagnosing and evaluating pulmonary contusion. Contusions on MDCT appear as crescentic ground-glass opacities (opacities through which lung interstitium and vasculature are still visible) and areas of consolidation that often do not respect the anatomic boundaries of the affected lobes. Additionally, small pulmonary contusions may exhibit sub-pleural sparing and may distinguish contusion from pneumonia or other lung pathology. Although pulmonary laceration is typically the result of penetrating trauma, laceration may also be caused by displaced rib fractures or significant shearing forces on the lung without penetrating injury. Because of elastic recoil of the normal pulmonary parenchyma surrounding the injury, pulmonary lacerations may present as late as 48-72 h after injury. Pulmonary lacerations may appear similar to pulmonary contusions on chest radiography initially and will require MDCT for definitive diagnosis. Blast injury is a defining injury of modern combat. Blast lung injury is initially diagnosed with chest radiography, where the pattern of lung opacities has previously been described by clinicians as "batwing" or "butterfly" because of its central appearance in the lung. "Peribronchovascular" may be a more accurate description of primary blast lung based on its appearance on MDCT. This pattern may differentiate primary blast lung injury from other causes of thoracic trauma. Conclusion: CRTT continues to be a significant contributor to the morbidity and mortality of those injured during OEF and OIF. The distinct injury patterns and atypical imaging manifestations of blunt trauma and blast lung injury are important to recognize early because of the acuity of this patient population and the influence of accurate diagnosis on clinical management.

Persisting CAM deformity is associated with early cartilage degeneration after Slipped Capital Femoral Epiphysis: 11-year follow-up including dGEMRIC.

OBJECTIVE: Slipped capital femoral epiphysis (SCFE) in adolescence is associated with increased risk of future osteoarthritis (OA). The purpose of this study was to study clinical and radiographic risk factors for early cartilage degeneration after SCFE. DESIGN: 22 patients (44 hips) (mean age 24 years, range 18-27) treated with in situ fixation (The Hansson hook-pin) for stable SCFE on average 11 years previously were investigated. Cartilage status was assessed with delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC). The alpha angle, reflecting femoroacetabular impingement (FAI), and the original slip angle were measured. Clinical outcome was assessed with the Copenhagen hip and groin outcome score (HAGOS) and clinical examination. RESULTS: The dGEMRIC index was lower in SCFE hips than unaffected hips 456 ms (CI 419-493) vs 521 ms (CI 476-567) (P = 0.03). The difference was larger (mean 21 ms) in anterior than posterior regions of the hip (P = 0.038). The alpha angle was higher in SCFE hips, 61.5° (CI 53.9-69.1) vs 45.6° (CI 43.6-47.6), (P < 0.001). The alpha angle, but not the original slip angle, correlated negatively with the dGEMRIC index (R = -0.40, P = 0.046). There was a positive correlation between HAGOS and the dGEMRIC-index (R = 0.41, P = 0.012). CONCLUSIONS: Early cartilage degeneration after SCFE seems related to persisting FAI in adulthood, rather than the initial slip severity. The correlation between dGEMRIC and HAGOS indicates a clinical relevance of the MRI findings. Our results suggest that FAI after SCFE should be evaluated already after physeal closure in order to predict and possibly prevent future OA development.

The Association Between Fruit and Vegetable Consumption and Fruit and Vegetable Stage of Change in Underserved Communities Engaging With Cooperative Extension Services.

OBJECTIVE: To compare differences in fruit and vegetable (FV) intake and FV stage of change in 2 diverse communities engaging with cooperative extension services (Extension). METHODS: Cross-sectional study of FV behaviors of community members enrolled in a team-based challenge offered by Extension. t test and chi-square analyses examined differences in FV intake and FV stage of change. Linear regression examined the relationship between FV stage of change and FV intake, adjusting for demographics. RESULTS: There was a significant (P = .01) difference in staging between the African American and Hispanic communities. Of individuals in the African American community, 60% were in the preparation stage; in the Hispanic community, 55% were in the precontemplation/contemplation stage. The FV stage of change was significantly associated with daily FV intake (ß = .53; P < .001). CONCLUSIONS AND IMPLICATIONS: To promote consumption of FVs better, nutrition education programs such as Extension should differentiate based on stages of change among subpopulations.

Immune Reactivity and Pseudoprogression or Tumor Flare in a Serially Biopsied Neuroendocrine Patient Treated with the Epigenetic Agent RRx-001.

Neuroendocrine tumors (NETs) are grouped together as a single class on the basis of histologic appearance, immunoreactivity for the neuroendocrine markers chromogranin A and synaptophysin, and potential secretion of hormones, neurotransmitters, neuromodulators and neuropeptides. Nevertheless, despite these common characteristics, NETs differ widely in terms of their natural histories: high-grade NETs are clinically aggressive and, like small cell lung cancer, which they most closely resemble, tend to respond to cisplatin and etoposide. In contrast, low-grade NETs, which as a rule progress and behave indolently, do not. In either case, the treatment strategy, apart from potentially curative surgical resection, is very poorly defined. This report describes the case of a 28-year-old white male with a diagnosis of high-grade NET of undetermined primary site metastatic to the lymph nodes, skin and paraspinal soft tissues, treated with the experimental anticancer agent RRx-001, in the context of a phase II clinical trial called TRIPLE THREAT (NCT02489903); serial sampling of tumor material through repeat biopsies demonstrated an intratumoral inflammatory response, including the amplification of infiltrating T cells, which correlated with clinical and symptomatic benefit. This case suggests that pseudoprogression or RRx-001-induced enlargement of tumor lesions, which has been previously described for several RRx-001-treated patients, is the result of tumoral lymphocyte infiltration.

Pancreas volume and fat fraction in children with Type 1 diabetes.

AIMS: People with Type 1 diabetes have smaller pancreases than healthy individuals. Several diseases causing pancreatic atrophy are associated with pancreatic steatosis, but pancreatic fat in Type 1 diabetes has not been measured. This cross-sectional study aimed to compare pancreas size and fat fraction in children with Type 1 diabetes and controls. METHODS: The volume and fat fraction of the pancreases of 22 children with Type 1 diabetes and 29 controls were determined using magnetic resonance imaging. RESULTS: Pancreas volume was 27% smaller in children with diabetes (median 34.9 cm(3) ) than in controls (47.8 cm(3) ; P < 0.001). Pancreas volume correlated positively with age in controls (P = 0.033), but not in children with diabetes (P = 0.649). Pancreas volume did not correlate with diabetes duration, but it did correlate positively with units of insulin/kg body weight/day (P = 0.048). A linear model of pancreas volume as influenced by age, body surface area and insulin units/kg body weight/day found that insulin dosage correlated with pancreas volume after controlling for both age and body surface area (P = 0.009). Pancreatic fat fraction was not significantly different between the two groups (1.34% vs. 1.57%; P = 0.891). CONCLUSIONS: Our findings do not indicate that pancreatic atrophy in Type 1 diabetes is associated with an increased pancreatic fat fraction, unlike some other diseases featuring reduced pancreatic volume. We speculate that our results may support the hypotheses that much of pancreatic atrophy in Type 1 diabetes occurs before the clinical onset of the disease and that exogenous insulin administration decelerates pancreatic atrophy after diabetes onset.

Efficacy and safety of maintenance pemetrexed in patients with advanced nonsquamous non-small cell lung cancer following pemetrexed plus cisplatin induction treatment: A cross-trial comparison of two phase III trials.

OBJECTIVES: Two phase III trials of advanced NSCLC patients were compared to examine relative efficacy and safety of differing treatment regimens. The JMDB trial investigated first-line pemetrexed-cisplatin (pemetrexed 500mg/m(2) plus cisplatin 75mg/m(2) every 21 days; maximum: 6 cycles). The PARAMOUNT phase III trial compared maintenance pemetrexed versus placebo after patients with nonsquamous NSCLC completed 4 cycles of first-line pemetrexed-cisplatin without disease progression. METHODS: Overall survival (OS) and progression-free survival (PFS), analyzed by Kaplan-Meier and Cox methods, and toxicity rates were compared between the PARAMOUNT arms and a selected homogeneous population from JMDB: 346 patients with disease and prior treatment characteristics matching the PARAMOUNT population. RESULTS: Outcomes for the PARAMOUNT placebo arm were similar to the JMDB homogeneous group (median PFS: 5.6 versus 6.2 months, p=0.117, HR=1.16; median OS: 14.0 versus 14.2 months, p=0.979, HR=1.00). The PARAMOUNT maintenance pemetrexed group had statistically superior efficacy compared with the JMDB homogeneous group (median PFS: 7.5 versus 6.2 months, p<0.00001, HR=0.66; median OS: 16.9 versus 14.2 months, p=0.003, HR=0.75). Patients who received pemetrexed maintenance (median 4 cycles, range 1-44) following 4 cycles of pemetrexed-cisplatin exhibited a higher incidence of drug-related serious adverse events compared with JMDB patients (median 6 cycles of pemetrexed-cisplatin) (10.6% versus 2.9%); grade 3/4 fatigue and renal toxicity were also higher in the pemetrexed arm of PARAMOUNT. CONCLUSIONS: The across-trial comparison of a relevant JMDB study population with the two arms of the PARAMOUNT study supported the efficacy of the pemetrexed continuation maintenance strategy and suggested the results are not influenced by limiting the pemetrexed-cisplatin induction treatment to four cycles. Although longer exposure to pemetrexed-cisplatin or maintenance pemetrexed increased some toxicities, the overall incidence remained low, underscoring the relative safety of these treatment regimens.

On the encapsulation of hydrocarbon components of natural gas within molecular baskets in water. The role of C-H···π interactions and the host's conformational dynamics in the process of encapsulation.

We examined the encapsulation of CH4, C2H6, C3H8 and iso-C4H10 in water, using four molecular baskets [1]-[4]. The baskets were shown to bind to hydrocarbon gases by forming favourable C-H···π contacts and, concurrently, adjusting the size of their cup-shaped platform.

Anti-cytokine autoantibodies preceding onset of autoimmune polyendocrine syndrome type I features in early childhood.

PURPOSE: Almost all patients with autoimmune polyendocrine syndrome (APS)-I have high titer neutralizing autoantibodies to type I interferons (IFN), especially IFN-ω and IFN-α2, whatever their clinical features and onset-ages. About 90 % also have antibodies to interleukin (IL)-17A, IL-17F and/or IL-22; they correlate with the chronic mucocutaneous candidiasis (CMC) that affects ~90 % of patients. Our aim was to explore how early the manifestations and endocrine and cytokine autoantibodies appear in young APS-I patients. That may hold clues to very early events in the autoimmunization process in these patients. METHODS: Clinical investigations and autoantibody measurements in 13 APS-I patients sampled before age 7 years, and 3 pre-symptomatic siblings with AIRE-mutations in both alleles. RESULTS: Antibody titers were already high against IFN-α2 and IFN-ω at age 6 months in one sibling-8 months before onset of APS-I-and also against IL-22 at 7 months in another (still unaffected at age 5 years). In 12 of the 13 APS-I patients, antibody levels were high against IFN-ω and/or IL-22 when first tested, but only modestly positive against IFN-ω in one patient who had only hypo-parathyroidism. Endocrine organ-specific antibodies were present at age 6 months in one sibling, and as early as 36 and 48 months in two of the six informative subjects. CONCLUSION: This is the first study to collate the onset of clinical features, cytokine and endocrine autoantibodies in APS-I infants and siblings. The highly restricted early autoantibody responses and clinical features they show are not easily explained by mere loss of broad-specific self-tolerance inducing mechanisms, but hint at some more sharply focused early event(s) in autoimmunization.

Anti-cytokine autoantibodies suggest pathogenetic links with autoimmune regulator deficiency in humans and mice.

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a recessive disorder resulting from mutations in the autoimmune regulator (AIRE). The patients' autoantibodies recognize not only multiple organ-specific targets, but also many type I interferons (IFNs) and most T helper type 17 (Th17) cell-associated cytokines, whose biological actions they neutralize in vitro. These anti-cytokine autoantibodies are highly disease-specific: otherwise, they have been found only in patients with thymomas, tumours of thymic epithelial cells that fail to express AIRE. Moreover, autoantibodies against Th17 cell-associated cytokines correlate with chronic mucocutaneous candidiasis in both syndromes. Here, we demonstrate that the immunoglobulin (Ig)Gs but not the IgAs in APECED sera are responsible for neutralizing IFN-ω, IFN-α2a, interleukin (IL)-17A and IL-22. Their dominant subclasses proved to be IgG1 and, surprisingly, IgG4 without IgE, possibly implicating regulatory T cell responses and/or epithelia in their initiation in these AIRE-deficiency states. The epitopes on IL-22 and IFN-α2a appeared mainly conformational. We also found mainly IgG1 neutralizing autoantibodies to IL-17A in aged AIRE-deficient BALB/c mice - the first report of any target shared by these human and murine AIRE-deficiency states. We conclude that autoimmunization against cytokines in AIRE deficiency is not simply a mere side effect of chronic mucosal Candida infection, but appears to be related more closely to disease initiation.

Extreme compression for extreme conditions: pilot study to identify optimal compression of CT images using MPEG-4 video compression.

This study aims to evaluate the utility of compressed computed tomography (CT) studies (to expedite transmission) using Motion Pictures Experts Group, Layer 4 (MPEG-4) movie formatting in combat hospitals when guiding major treatment regimens. This retrospective analysis was approved by Walter Reed Army Medical Center institutional review board with a waiver for the informed consent requirement. Twenty-five CT chest, abdomen, and pelvis exams were converted from Digital Imaging and Communications in Medicine to MPEG-4 movie format at various compression ratios. Three board-certified radiologists reviewed various levels of compression on emergent CT findings on 25 combat casualties and compared with the interpretation of the original series. A Universal Trauma Window was selected at -200 HU level and 1,500 HU width, then compressed at three lossy levels. Sensitivities and specificities for each reviewer were calculated along with 95 % confidence intervals using the method of general estimating equations. The compression ratios compared were 171:1, 86:1, and 41:1 with combined sensitivities of 90 % (95 % confidence interval, 79-95), 94 % (87-97), and 100 % (93-100), respectively. Combined specificities were 100 % (85-100), 100 % (85-100), and 96 % (78-99), respectively. The introduction of CT in combat hospitals with increasing detectors and image data in recent military operations has increased the need for effective teleradiology; mandating compression technology. Image compression is currently used to transmit images from combat hospital to tertiary care centers with subspecialists and our study demonstrates MPEG-4 technology as a reasonable means of achieving such compression.