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Diagnosis of interstitial lung disease (ILD) requires a multidisciplinary discussion approach that includes clinicians, radiologists, and pathologists. Surgical lung biopsy (SLB) is currently the recommended standard in obtaining pathologic specimens for patients with ILD requiring a tissue diagnosis. The increased diagnostic confidence and accuracy provided by microscopic pathology assessment of SLB specimens must be balanced with the associated risks in patients with ILD. This document was developed by the SLB Working Group of the Pulmonary Fibrosis Foundation, composed of a multidisciplinary group of ILD physicians, including pulmonologists, radiologists, pathologists, and thoracic surgeons. In this document, we present an up-to-date literature review of the indications, contraindications, risks, and alternatives to SLB in the diagnosis of fibrotic ILD; outline an integrated approach to the decision-making around SLB in the diagnosis of fibrotic ILD; and provide practical information to maximize the yield and safety of SLB.

BackgroundAcute exacerbations of interstitial lung diseases (AE-ILD) have a high mortality rate with no effective medical therapies. Lung transplantation is a potentially life-saving option for patients with AE-ILD, but its role is not well established. The aim of this study is to determine if this therapy during AE-ILD significantly affects post-transplant outcomes in comparison to those transplanted with stable disease.MethodsWe conducted a retrospective study of consecutive patients with AE-ILD admitted to our institution from 2015 to 2018. The comparison group included patients with stable ILD listed for lung transplant during the same period. The primary end-points were in-hospital mortality for patients admitted with AE-ILD and 1-year survival for the transplanted patients.ResultsOf 53 patients admitted for AE-ILD, 28 were treated with medical therapy alone and 25 underwent transplantation. All patients with AE-ILD who underwent transplantation survived to hospital discharge, whereas only 43% of the AE-ILD medically treated did. During the same period, 67 patients with stable ILD underwent transplantation. Survival at 1 year for the transplanted patients was not different for the AE-ILD group versus stable ILD group (96% vs 92.5%). The rates of primary graft dysfunction, post-transplant hospital length-of-stay and acute cellular rejection were similar between the groups.ConclusionPatients with ILD transplanted during AE-ILD had no meaningful difference in overall survival, rate of primary graft dysfunction or acute rejection compared with those transplanted with stable disease. Our results suggest that lung transplantation can be considered as a therapeutic option for selected patients with AE-ILD.

It is essential to be aware of widely accepted criteria for grading of treatment response in both high-grade and low-grade gliomas. These criteria primarily take into account responses of measurable and nonmeasurable lesions on T2-weighted, fluid-attenuated inversion recovery, and postcontrast images to determine a final category of response for the patient. The additional role that other advanced imaging techniques, such as diffusion and perfusion imaging, can play in the surveillance of these tumors is discussed in this article.

Pulmonary hypertension in interstitial lung diseases is associated with increased mortality and hospitalizations and reduced exercise capacity. Interstitial pneumonia with autoimmune features (IPAF) is a recently described interstitial lung disease. The characteristics of pulmonary hypertension in IPAF patients are unknown. We sought to characterize patients with IPAF based on their echocardiographic probability of pulmonary hypertension and compare patients with and without pulmonary hypertension identified by right heart catheterization. We conducted a retrospective study of patients seen in the interstitial lung disease clinic from 2015 to 2018. Forty-seven patients with IPAF were identified. Patients were classified into low, intermediate and high echocardiographic pulmonary hypertension probabilities. A sub-group analysis of patients with pulmonary hypertension and without pulmonary hypertension (IPAF-PH vs. IPAF-no PH) identified by right heart catheterization was also performed. Linear regression analysis was performed to study the association between 6-min-walk-distance (6MWD) and pulmonary vascular resistance (PVR) while adjusting for age and body mass index. Right ventricular hypertrophy (>5 mm), right ventricular enlargement (>41 mm) and right ventricular systolic dysfunction defined as fractional area change% ≤35 was present in 76%, 24%, and 39% of patients, respectively. Pulmonary hypertension was identified in 12.7% of patients. IPAF-PH patients had higher mean pulmonary artery pressure and lower cardiac output compared to the IPAF-no PH group (34 mmHg vs. 19 mmHg, p = 0.002 and 4.0 vs. 5.7 L/min, p = 0.023, respectively). Lower 6MWD was associated with higher PVR on regression analysis ( p = 0.002). Pulmonologists should be aware that a significant number of IPAF patients may develop pulmonary hypertension. Reduced 6MWD may suggest the presence of pulmonary hypertension in IPAF patients.

Latinx first-generation college graduates often experience a myriad of structural, emotional, financial and academic barriers while navigating higher education as undergraduate and graduate students and later, if they become faculty members. While many studies have documented these struggles within the field, the political, methodological and pedagogical praxis of testimonio has been used to reflect on and document these struggles in ways that give the authors agency in retelling and reclaiming their experiences of marginalization and resistance. In this paper, the authors build on the metaphor of a labyrinth to describe how higher education can often feel similar to a maze-like path to navigate, yet, the spiritual and reflective practice of labyrinth- walking involves three stages of soul development which can also be experienced through testimonio: releasing, receiving and returning to oneself

Acute acquired comitant esotropia (AACE) is a rare form of esotropia in the older pediatric population. Although the workup for pediatric AACE varies, patients often do not undergo lab testing and imaging, because the overwhelming majority of cases are idiopathic. We describe AACE as the presenting manifestation of multiple sclerosis in a pediatric patient. His only other finding was a horizontal jerk nystagmus isolated to end gaze. Magnetic resonance imaging revealed extensive demyelinating lesions, with a small thalamic lesion possibly accounting for his esotropia. Our case underscores the need for extensive diagnostic workup for any ophthalmic or neurologic findings or symptoms accompanying AACE.

Recurrence of pulmonary sarcoidosis after transplantation of the lung is known to occur and has not been shown to lead to negative outcomes. However, recurrence in a new primary organ is incredibly rare and not an established pattern of clinical presentation. Neurosarcoidosis can present in a variety of ways, one of which is development of acute encephalopathy and diffuse leptomeningeal enhancement on MRI imaging. In the case we present, the MRI findings, the improvement of symptoms and imaging abnormalities with steroid treatment support a diagnosis of probable neurosarcoidosis. Since a minority of patients who undergo lung transplantation have sarcoidosis, it is possible that subsequent development of neurosarcoidosis may be under recognized.

Background Sarcoidosis has been well studied in multiple races and ethnic groups. However, there is a paucity of data that describes sarcoidosis in Hispanics. We aimed to determine the prevalence of Hispanic ethnicity, clinical characteristics and impact of sarcoidosis among Hispanics from a US based national registry. Methods We conducted a national registry-based study investigating 3835 respondents to the Sarcoidosis Advanced Registry for Cures questionnaire. This registry is a web-based, self-reported questionnaire that provides data related to demographics, diagnostics, organ involvement, treatment modalities, and the physical and psychosocial impact of sarcoidosis. We compared Hispanic patients to non-Hispanics. We performed multivariate logistic regression analysis adjusting for age, gender, education, income and insurance status and looked at the association between Hispanic ethnicity with depression, chronic pain syndrome, chronic fatigue syndrome, impact on family finances, employment-based disability and job termination. Results Nine percent of the patients reported a Hispanic ethnicity and the majority of these patients self-identified as white women. The most common organs involved were the lungs (74.9%), central lymph nodes (53.8%), and peripheral lymph nodes (37.1%). Hispanics reported more peripheral nerves and peripheral lymph nodes involvement than non-Hispanics. Hispanics experienced more depression, sleep apnea, and chronic pain syndrome than non-Hispanics. The use of mobility assistive devices was more common among Hispanics, as well as employment-based disability, and disease-related job termination compared to non-Hispanics. The majority of Hispanics reported significantly more pain that interfered with the enjoyment of life than non-Hispanics. On multivariate logistic regression analysis, Hispanic ethnicity was associated with depression (adjusted odds ratio (aOR) = 1.5; 95% CI: 1.01–2.2), chronic pain syndrome (aOR = 1.7; 1.1–2.6), job termination due to sarcoidosis (aOR = 1.7; 1.1–2.7) and higher impact on family finances (aOR = 1.7; 1.1–2.5). Conclusion The clinical presentation of sarcoidosis in Hispanic patients differs from that in non-Hispanic patients living in the United States. These differences should be considered when managing Hispanic patients with sarcoidosis. We encourage more studies that investigate phenotyping among Hispanics with sarcoidosis.

Objectives In this retrospective study, we evaluated the diagnostic accuracy of molecular tests (MT) for the detection of DR-TB, compared to the gold standard liquid-based drug susceptibility testing (DST) in Karakalpakstan. Methods A total of 6670 specimens received in the Republican TB No 1 Hospital Laboratory of Karakalpakstan between January and July 2017 from new and retreatment patients were analysed. Samples were tested using Xpert MTB/RIF and line probe assays (LPA) for the detection of mutations associated with resistance. The sensitivity and specificity of MTs were calculated relative to results based on DST. Results The accuracy of MT for detection of rifampicin resistance was high, with sensitivity and specificity over 98%. However, we observed reduced sensitivity of LPA for detection of resistance; 86% for isoniazid (95% CI 82-90%), 86% for fluoroquinolones (95% CI 68-96%), 70% for capreomycin (95% CI 46-88%) and 23% for kanamycin (95% CI 13-35%). Conclusions We show that MTs are a useful tool for rapid and safe diagnosis of DR-TB; however, clinicians should be aware of their limitations. Although detection of rifampicin resistance was highly accurate, our data suggest that resistance mutations circulating in the Republic of Karakalpakstan for other drugs were not detected by the methods used here. This merits further investigation.

Contains fulltext : 244043.pdf (Publisher’s version ) (Open Access) Pediatric community-acquired bloodstream infections (CA-BSIs) in sub Saharan African humanitarian contexts are rarely documented. Effective treatment of these infections is additionally complicated by increasing rates of antimicrobial resistance. We describe the findings from epidemiological and microbiological surveillance implemented in pediatric patients with suspected CA-BSIs presenting for care at a secondary hospital in the conflict affected area of Zamfara state, Nigeria. Any child (> 2 months of age) presenting to Anka General Hospital from November 2018 to August 2020 with clinical severe sepsis at admission had clinical and epidemiological information and a blood culture collected at admission. Bacterial isolates were tested for antibiotic susceptibility. We calculated frequencies of epidemiological, microbiological and clinical parameters. We explored risk factors for death amongst severe sepsis cases using univariable and multivariable Poisson regression, adjusting for time between admission and hospital exit. We included 234 severe sepsis patients with 195 blood culture results. There were 39 positive blood cultures. Of the bacterial isolates, 14 were Gram positive and 18 were Gram negative; 5 were resistant to empiric antibiotics: methicillin-resistant Staphylococcus aureus (MRSA; n = 2) and Extended Spectrum Beta-Lactamase positive enterobacterales (n = 3). We identified no significant association between sex, age-group, ward, CA-BSI, appropriate intravenous antibiotic, malaria positivity at admission, suspected focus of sepsis, clinical severity and death in the multivariable regression. There is an urgent need for access to good clinical microbiological services, including point of care methods, and awareness and practice around rational antibiotic in healthcare staff in humanitarian settings to reduce morbidity and mortality from sepsis in children.

Background Autoimmunity is a common cause of pulmonary fibrosis and can present either as a manifestation of an established connective tissue disease or as the recently described entity of interstitial pneumonia with autoimmune features. The rate of progression and responsiveness to immunosuppression in these illnesses are difficult to predict. Circulating fibrocytes are bone marrow-derived progenitor cells that home to injured tissues and contribute to lung fibrogenesis. We sought to test the hypothesis that the blood fibrocyte concentration predicts outcome and treatment responsiveness in autoimmune interstitial lung diseases. Methods We compared the concentration of circulating fibrocytes in 50 subjects with autoimmune interstitial lung disease and 26 matched healthy controls and assessed the relationship between serial peripheral blood fibrocyte concentrations and clinical outcomes over a median of 6.25 years. Results As compared to controls, subjects with autoimmune interstitial lung disease had higher circulating concentrations of total fibrocytes, the subset of activated fibrocytes, and fibrocytes with activation of PI3K/AKT/mTOR, transforming growth factor-β (TGF-β) receptor and interleukin (IL)-4/IL-13 receptor signalling pathways. Over the follow-up period, there were episodes of marked elevation in the concentration of circulating fibrocytes in subjects with autoimmune interstitial lung disease but not controls. Initiation of immunosuppressive therapy was associated with a decline in the concentration of circulating fibrocytes. For each 100 000 cells·mL−1 increase in peak concentration of circulating fibrocytes, we found a 5% increase in odds of death or lung function decline. Conclusion In patients with autoimmune interstitial lung disease, circulating fibrocytes may represent a biomarker of outcome and treatment response., Autoimmune diseases are common causes of pulmonary fibrosis. The blood concentration of fibrocytes, cells involved in formation of scar tissue, predicts outcomes and response to immunosuppression in these patients. https://bit.ly/35bel62

Little is known about the prevalence, clinical characteristics and impact of hypothyroidism in patients with sarcoidosis. We aimed to determine the prevalence and clinical features of hypothyroidism and its relation to organ involvement and other clinical manifestations in patients with sarcoidosis. We conducted a national registry-based study investigating 3835 respondents to the Sarcoidosis Advanced Registry for Cures Questionnaire between June 2014 and August 2019. This registry is based on a self-reported, web-based questionnaire that provides data related to demographics, diagnostics, sarcoidosis manifestations and treatment. We compared sarcoidosis patients with and without self-reported hypothyroidism. We used multivariable logistic regression and adjusted for potential confounders to determine the association of hypothyroidism with nonorgan-specific manifestations. 14% of the sarcoidosis patients self-reported hypothyroidism and were generally middle-aged white women. Hypothyroid patients had more comorbid conditions and were more likely to have multiorgan sarcoidosis involvement, especially with cutaneous, ocular, joints, liver and lacrimal gland involvement. Self-reported hypothyroidism was associated with depression (adjusted odds ratio (aOR) 1.3, 95% CI 1.01–1.6), antidepressant use (aOR 1.3, 95% CI 1.1–1.7), obesity (aOR 1.7, 95% CI 1.4–2.1), sleep apnoea (aOR 1.7, 95% CI 1.3–2.2), chronic fatigue syndrome (aOR 1.5, 95% CI 1.2–2) and was borderline associated with fibromyalgia (aOR 1.3, 95% CI 1–1.8). Physical impairment was more common in patients with hypothyroidism. Hypothyroidism is a frequent comorbidity in sarcoidosis patients that might be a potentially reversible contributor to fatigue, depression and physical impairment in this population. We recommend considering routine screening for hypothyroidism in sarcoidosis patients especially in those with multiorgan sarcoidosis, fatigue and depression., Hypothyroidism is a frequent comorbidity in sarcoidosis patients, is often associated with sarcoidosis multiorgan involvement, and might be a potentially reversible contributor to fatigue, depression and physical impairment in this population https://bit.ly/2XGdjKg

A 50-year-old male presented with atrial flutter 25 days after heart and kidney transplantation. Rejection was excluded, however, he developed severe COVID-19 with cardiac allograft dysfunction. Despite continued corticosteroids and tacrolimus, he remained aviremic. Respiratory and myocardial function recovered after a week of mechanical ventilation. The cardiomyopathy was stress induced., Graphical abstract

IntroductionAfghanistan is affected by one of the world's longest protracted armed conflicts, frequent natural disasters, disease outbreaks and large population movements and it suffers from a high burden of tuberculosis (TB), including rifampicin-resistant TB (RR-TB). The study shows Médecins Sans Frontières' experiences with care for patients with RR-TB in Kandahar Province. We describe the uptake of RR-TB treatment, how World Health Organisation criteria for the choice between the short and an individualized regimen were implemented, and treatment outcomes.MethodsThis is a retrospective cohort analysis of routinely collected data from RR-TB patients enrolled in care from 2016 until 2019. Descriptive analysis was performed to present characteristics of patients and treatment outcomes. Multivariable Cox analysis was performed to identify risk factors for having an unfavourable treatment outcome.ResultsOut of 146 enrolled RR-TB patients, 112 (76.7%) started treatment: 41 (36.6%) and 71 (63.4%) with the short and individualized treatment regimen, respectively. Of 82 with results for fluoroquinolone susceptibility, 39 (47.6%) had fluoroquinolone-resistant TB. Seven patients with initially fluoroquinolone-resistant TB and three pregnant women started the short regimen and 18 patients eligible for the short regimen started the injectable-free individualized regimen. Overall, six-month smear and culture conversion were 98.7% and 97.1%, respectively; treatment success was 70.1%. Known initial fluoroquinolone resistance (aHR 3.77, 95%CI:1.53-9.27) but not choice of regimen predicted having an unfavourable outcome.ConclusionEven though criteria for the choice of treatment regimen were not applied strictly, we have achieved acceptable outcomes in this cohort. To expand RR-TB care, treatment regimens should fit provision at primary health care level and take patient preferences into account.

Pomalidomide is an immunomodulatory drug and the dosage of 4 mg per day taken orally on days 1‐21 of repeated 28‐day cycles has been approved in the European Union and United States to treat patients with relapsed/refractory multiple myeloma. Because pomalidomide is extensively metabolized prior to excretion, a total of 32 subjects (8 healthy subjects in group 1; 8 subjects with severe hepatic impairment in group 2; 8 subjects with moderate hepatic impairment in group 3; and 8 subjects with mild hepatic impairment in group 4) were enrolled in a multicenter, open‐label, single‐dose study to assess the impact of hepatic impairment on pomalidomide exposure. Following administration of a single oral dose of 4‐mg pomalidomide, the geometric mean ratios of pomalidomide total plasma exposures (AUC) were 171.5%, 157.5%, and 151.2% and the geometric mean ratios of pomalidomide plasma peak exposures (Cmax) were 75.8%, 94.8%, and 94.2% for subjects with severe, moderate, or mild hepatic impairment, respectively, versus healthy subjects. Pomalidomide administered as a single oral 4‐mg dose was safe and well tolerated by healthy subjects and subjects with severe, moderate, or mild hepatic impairment. Based on the pharmacokinetic results from this study, the pomalidomide prescribing information approved by the US Food and Drug Administration recommends for patients with mild or moderate hepatic impairment (Child‐Pugh classes A or B), a 3‐mg starting daily dose (25% dose reduction) and for patients with severe hepatic impairment (Child‐Pugh class C), a 2‐mg starting daily dose (50% dose reduction).

BACKGROUND: Image-guided biopsy is routinely conducted in patients with suspected discitis, though the sensitivity reported in the literature ranges widely. PURPOSE: We applied a systematic review and meta-analysis to estimate the yield of image-guided biopsy for infectious discitis. DATA SOURCES: We performed a literature search of 4 data bases: PubMed, Cochrane CENTRAL Register of Controlled Trials, Embase.com, and Scopus from data base inception to March 2016. STUDY SELECTION: A screen of 1814 articles identified 88 potentially relevant articles. Data were extracted for 33 articles, which were eligible if they were peer-reviewed publications of patients with clinical suspicion of discitis who underwent image-guided biopsy. DATA ANALYSIS: Patients with positive cultures out of total image-guided biopsy procedures were pooled to estimate yield with 95% confidence intervals. Hypothesis testing was performed with an inverse variance method after logit transformation. DATA SYNTHESIS: Image-guided biopsy has a yield of approximately 48% (793/1763), which is significantly lower than the open surgical biopsy yield of 76% (152/201; P < .01). Biopsy in patients with prior antibiotic exposure had a yield of 32% (106/346), which was not significantly different from the yield of 43% (336/813; P = .08) in patients without prior antibiotic exposure. LIMITATIONS: The conclusions of this meta-analysis are primarily limited by the heterogeneity of the included studies. CONCLUSIONS: Image-guided biopsy has a moderate yield for the diagnosis of infectious discitis, which is significantly lower than the yield of open surgical biopsy. This yield is not significantly affected by prior antibiotic use.

Objectives: The worldwide spread of Parkinson's disease (PD) calls for sensitive and specific measures enabling its early (or, ideally, preclinical) detection. Here, we use language measures revealing deficits in PD to explore whether similar disturbances are present in asymptomatic individuals at risk for the disease. Methods: We administered executive, semantic, verb-production, and syntactic tasks to sporadic PD patients, genetic PD patients with PARK2 (parkin) or LRRK2 (dardarin) mutation, asymptomatic first-degree relatives of the latter with similar mutations, and socio-demographically matched controls. Moreover, to detect sui generis language disturbances, we ran analysis of covariance tests using executive functions as covariate. Results: The two clinical groups showed impairments in all measures, most of which survived covariation with executive functions. However, the key finding concerned asymptomatic mutation carriers. While these subjects showed intact executive, semantic, and action-verb production skills, they evinced deficits in a syntactic test with minimal working memory load. Conclusions: We propose that this sui generis disturbance may constitute a prodromal sign anticipating eventual development of PD. Moreover, our results suggest that mutations on specific genes (PARK2 and LRRK2) compromising basal ganglia functioning may be subtly related to language-processing mechanisms. Fil: García, Adolfo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina. Universidad Nacional de Cuyo. Facultad de Educación Elemental y Especial; Argentina Fil: Sedeño, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina Fil: Trujillo, Natalia. Universidad de Antioquia; Colombia Fil: Bocanegra, Yamile. Universidad de Antioquia; Colombia Fil: Gomez, Diana. Universidad de Antioquia; Colombia Fil: Pineda, David. Universidad de Antioquia; Colombia Fil: Villegas, Andrés. Universidad de Antioquia; Colombia Fil: Muñoz, Edinson. Universidad de Santiago de Chile; Chile Fil: Arias, William. Universidad de Antioquia; Colombia Fil: Ibáñez Barassi, Agustín Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina. Universidad Autónoma del Caribe; Colombia. Universidad Adolfo Ibañez; Chile. Macquarie University; Australia

Noninvasive imaging methods are sought to objectively predict early response to therapy for high-grade glioma tumors. Quantitative metrics derived from diffusion-weighted imaging, such as apparent diffusion coefficient (ADC), have previously shown promise when used in combination with voxel-based analysis reflecting regional changes. The functional diffusion mapping (fDM) metric is hypothesized to be associated with volume of tumor exhibiting an increasing ADC owing to effective therapeutic action. In this work, the reference fDM-predicted survival (from previous study) for 3 weeks from treatment initiation (midtreatment) is compared to multiple histogram-based metrics using Kaplan–Meier estimator for 80 glioma patients stratified to responders and nonresponders based on the population median value for the given metric. The ADC histogram metric reflecting reduction in midtreatment volume of solid tumor (ADC &lt, 1.25 × 10−3 mm2/s) by &gt, 8% population-median with respect to pretreatment is found to have the same predictive power as the reference fDM of increasing midtreatment ADC volume above 4%. This study establishes the level of correlation between fDM increase and low-ADC tumor volume shrinkage for prediction of early response to radiation therapy in patients with glioma malignancies.

Dengue is an acute febrile illness caused by any of four dengue virus types (DENV-1-4). DENVs are transmitted by mosquitos of the genus Aedes (1) and are endemic throughout the tropics (2). In 2010, an estimated 390 million DENV infections occurred worldwide (2). During 2007-2013, a total of three to 10 dengue cases were reported annually in Arizona and all were travel-associated. During September-December 2014, coincident with a dengue outbreak in Sonora, Mexico, 93 travel-associated dengue cases were reported in Arizona residents; 70 (75%) cases were among residents of Yuma County, which borders San Luis Río Colorado, Sonora, Mexico. San Luis Río Colorado reported its first case of locally acquired dengue in September 2014. To investigate the temporal relationship of the dengue outbreaks in Yuma County and San Luis Río Colorado and compare patient characteristics and signs and symptoms, passive surveillance data from both locations were analyzed. In addition, household-based cluster investigations were conducted near the residences of reported dengue cases in Yuma County to identify unreported cases and assess risk for local transmission. Surveillance data identified 52 locally acquired cases (21% hospitalized) in San Luis Río Colorado and 70 travel-associated cases (66% hospitalized) in Yuma County with illness onset during September-December 2014. Among 194 persons who participated in the cluster investigations in Yuma County, 152 (78%) traveled to Mexico at least monthly during the preceding 3 months. Four (2%) of 161 Yuma County residents who provided serum samples for diagnostic testing during cluster investigations had detectable DENV immunoglobulin M (IgM); one reported a recent febrile illness, and all four had traveled to Mexico during the preceding 3 months. Entomologic assessments among 105 households revealed 24 water containers per 100 houses colonized by Ae. aegypti. Frequent travel to Mexico and Ae. aegypti colonization indicate risk for local transmission of DENV in Yuma County. Public health officials in Sonora and Arizona should continue to collaborate on dengue surveillance and educate the public regarding mosquito abatement and avoidance practices. Clinicians evaluating patients from the U.S.-Mexico border region should consider dengue in patients with acute febrile illness and report suspected cases to public health authorities.

PROBLEM/CONDITION Aquatic facility-associated illness and injury in the United States include disease outbreaks of infectious or chemical etiology, drowning, and pool chemical-associated health events (e.g., respiratory distress or burns). These conditions affect persons of all ages, particularly young children, and can lead to disability or even death. A total of 650 aquatic facility-associated outbreaks have been reported to CDC for 1978-2012. During 1999-2010, drownings resulted in approximately 4,000 deaths each year in the United States. Drowning is the leading cause of injury deaths in children aged 1-4 years, and approximately half of fatal drownings in this age group occur in swimming pools. During 2003-2012, pool chemical-associated health events resulted in an estimated 3,000-5,000 visits to U.S. emergency departments each year, and approximately half of the patients were aged

PURPOSE The aim was to evaluate the interobserver agreement in the assessment of cerebellar tonsil position on sagittal magnetic resonance imaging using 3 different osseous landmarks. MATERIALS AND METHODS This retrospective study consisted of brain magnetic resonance imagings performed at our institution in patients with and without Chiari I malformation between January 2010 and 2012. Sagittal T1-weighted images were reviewed by 2 senior board-certified neuroradiologists (blinded to underlying clinical diagnosis) with measurement of both cerebellar tonsillar positions based on lines drawn perpendicular from the tonsillar tip to the foramen magnum [FM] line, C1 line, and C2 line. Spearman correlation coefficients were calculated. Interobserver variation between the readers was assessed using Bland-Altman analysis and intraclass correlation coefficient. RESULTS A total of 320 cerebellar tonsils on 160 patients, 50 with Chiari I malformations, and 110 control subjects without Chiari I malformation were evaluated. The Spearman correlation coefficients for the entire cohort were 0.86 (FM), 0.94 (C1), and 0.90 (C2). Bland-Altman analysis for the entire cohort showed the best interobserver agreement for C1 line (-0.3 mm bias) and the least for C2 line (4.6 mm bias). The Intraclass correlation coefficients for all patients were 0.84 (FM), 0.92 (C1), and 0.54 (C2). The least bias and highest correlation coefficients were also seen individually in the Chiari and non-Chiari cohorts with the C1 technique. CONCLUSIONS Determination of cerebellar tonsillar position using a C1 arch landmark may be superior to the currently more commonly used FM-based landmark with lesser interobserver variability and higher interobserver correlation.

Introduction Pericardial involvement of sarcoidosis is a rare cause for acute heart failure, and usually occurs as a result of the development of a pericardial effusion leading to cardiac tamponade. Even rarer still, is the manifestation of constrictive pericarditis. We report a case of sarcoidosis with lung, pleural, and pericardial involvement with effusive-constrictive pericarditis leading to cardiac tamponade. Case presentation A 34-year-old Caucasian man presented for evaluation of a history of worsening exertional dyspnea, edema, and weight loss. A high-resolution chest computed tomography showed diffuse pulmonary nodules with upper lobe predominance and in a perilymphatic distribution; large right pleural effusion; and large pericardial effusion with pericardial thickening. A transthoracic echocardiogram demonstrated early tamponade physiology for which a pericardial drain was placed. After removal of the drain he developed cardiogenic shock from cardiac tamponade attributed to the reaccumulation of a pericardial effusion and urgent pericardial window was performed. Serial echocardiography was concerning for organization and localization of the pericardial fluid. Cardiac magnetic resonance imaging demonstrated a significant reduction in pericardial slippage between the parietal and visceral layers around the heart collectively suggestive of constrictive pericarditis. Confirmation of effusive-constrictive pericarditis was noted on right heart catheterization. He then underwent pericardiectomy, which on histopathologic evaluation demonstrated non-necrotizing granulomas, thus confirming pericardial involvement of sarcoidosis. Conclusions We report a case demonstrating unique manifestations of sarcoidosis; effusive-constrictive pericarditis presenting with acute congestive heart failure.

Introduction As we previously reported (Leuk Res. 2018; 72:74-78) hypercholesterolemia in the recipients, donors, or both, prior allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with increased frequency of acute graft-versus-host disease (aGVHD). This could be explained by the pro-inflammatory response caused by high levels of cholesterol. On the other hand, it is known that depletion of regulatory T cells (Tregs) is associated with worsening of GVHD, thus, Tregs are essential for the induction of tolerance to allo-antigens. Objective To correlate Tregs in donor bone marrow (BM) samples with their levels of cholesterol and associate these results with recipients who developed aGVHD and those who did not. Materials and Methods A prospective analysis was performed in 39 donor BM samples. Mononuclear cells were counted and viability was evaluated. A 24 hour resting with RPMI, and posterior activation with PMA (50 ng/ml) for 48 hours was performed. Cells were harvested and from each sample, one million mononuclear cells were permeabilized, fixed, and stained for their posterior phenotipication by flow cytometry. The samples were obtained in a BD LSR Fortessa cytometry, and analyzed with the Flow-Jo software. Total cholesterol in the donor was documented as part of the pre-transplant workup. High cholesterol was considered ≥ 200mg/dL. NIH criteria was used to diagnose aGVHD. Recipient information was analyzed using SPSS v.21. Results From the 39 donors, 11 (28%) had hypercholesterolemia. Acute GVHD was observed in 8 recipients (21%): 4 recipients (36%) from the 11 donors with hypercholesterolemia versus 4 recipients (14%) from the group of donors with normal levels of cholesterol (n=28). As shown in Figure 1, donor samples with hypercholesterolemia were characterized by diminished Tregs compared to donors with normal levels of cholesterol (30.1 cells/µL vs 78.6 cells/µL, p=0.03). Conclusions Acute GVHD was higher in patients whose donors had hypercholesterolemia and we demonstrated that BM samples of the latter showed a less favorable immunologic profile characterized by diminished Tregs. Further, as aGVHD can contribute to the morbidity and mortality after allo-HSCT, more effective prevention strategies are needed, thus, our results might suggest that normalizing the levels of total cholesterol in the donor, prior performing allo-HSCT, might be an effective approach to diminish the risk of the receptor to develop aGVHD, especially among Mexican or American populations where dyslipidemia is prevalent.

The study of seizures and status epilepticus (SE) has seen tremendous advances over the last few decades, particularly in neuroimaging. Modern neuroimaging has made it possible to demonstrate structural etiologies for seizures and epilepsy that would have been considered “cryptogenic” previously. Similarly, nuclear imaging studies have demonstrated complementary metabolic or functional correlates of ictal, interictal, and post-ictal activity. During SE, neuroimaging has practical limitations. SE is typically a medical emergency requiring prompt therapeutic intervention, and prolonged comprehensive imaging studies should not delay appropriate medical care. It is also challenging to choose among the many types of imaging modalities in order to obtain the best information, while maintaining patient safety. There are practical, financial, and therapeutic considerations in choosing the most appropriate imaging modality for a particular clinical situation.

Objectives: The aim of this study was to describe the patterns and trends of autochthonous leprosy in the Valencia Region (Spain). Methods: We included all new leprosy cases originating from the Valencia Region between the years 1940 and 2015. Patients originating from other countries or other Spanish regions were excluded. New cases were analysed by age, sex, clinical type, occupation, and geographic distribution. Results: A total of 442 patients with presumably autochthonous leprosy were included. Incidence rates consistently declined over the study period. Mean age at onset gradually increased from 34.2 years during the period 1940-1949 to 59.5 years during 2000-2015. There were no cases with clinical onset after 2006 and no cases born after 1973. Patients were predominantly males (57.7%) and 85.4% had multibacillary leprosy. The proportion of multibacillary cases increased gradually after 1970. The majority of male patients (67.9%) worked in agriculture. Most of the cases, especially during the later periods, were concentrated in the coastal regions. Conclusions: Our findings are consistent with trends described in other regions with declining leprosy incidence rates and suggest that the transmission of M. leprae infection in this area may well have now stopped. Autochthonous leprosy in this region has had a male predominance and a high proportion of multibacillary cases. The geographic distribution and the high incidence in agricultural workers suggest that environmental factors should be further explored.

Significant heterogeneity of computed tomography (CT) presentation exists within chronic hypersensitivity pneumonitis (HP). There are limited data aimed at delineating the prognostic value of specific CT features, distribution, and patterns in chronic HP.To examine whether the presence of CT mosaic attenuation (MA) and air trapping (AT), and the distribution or patterns of fibrosis impact survival in subjects with chronic HP.We retrospectively identified 110 consecutively enrolled, well-characterized, biopsy-proven adult subjects with chronic HP between 1982 and 2015 from the National Jewish Health interstitial lung disease research database. The first available CT scan of diagnostic quality from each subject was formally evaluated for specific CT findings associated with chronic HP and for overall CT pattern. A Cox proportional hazards model was used to identify independent predictors in time-to-death analysis, and bootstrap analysis was performed for internal model validation.Fibrotic HP (65%; 72/110) was most often peripheral in the axial plane and lower lung preponderant. The distribution of lung disease in those without fibrosis was most often axially and zonally diffuse. There was no association between survival and CT distribution or CT pattern in the whole cohort or within the fibrotic subset of subjects. After multivariate adjustment, AT/MA was independently associated with survival in the whole cohort (HR = 0.26; 95% confidence interval = 0.07-0.97). Results were similar after restricting the analyses to fibrotic HP cases.Among subjects with chronic HP, the presence of CT AT/MA may identify subjects with better prognosis.

BACKGROUND: The differential diagnosis of benign-appearing posterior element lesions is complex. OBJECTIVE: To explore the etiology of an unusual benign lesion found on the lamina of L5 described in a case report. METHODS: Case report. The patient’s medical, surgical and imaging histories as well as medical literature were reviewed. RESULTS: A 35-year old male complained of low back pain radiating to both legs for 5 months. Abdominal CT scan 1 year prior as well as post symptom-onset CT and MRI showed a well-corticated lesion lateral to the spinous process of L5. After failed rehabilitation and injection, operation revealed normal cortical bone. Pain was not markedly relieved post-operatively. CONCLUSION: The pre-surgical differential diagnosis of this lesion included osteosarcoma and osteoid osteoma, however benign pathological results suggest the possibility of atypical spina bifida occulta, Baastrup changes, atypical sacralization of L5, or a resolved fracture with heterotopic ossification.

Diffusion-weighted (DW) MRI has been shown to be an imaging biomarker for assessing tumor aggressiveness and early response to therapy in various cancers.1 The DW-MRI acquisition is rapid and noninvasive and uses neither exogenous contrast agent nor ionizing radiation. The apparent diffusion coefficient (ADC), quantified from DW-MRI, measures water mobility in tissue and is sensitive to cellular density, extracellular space tortuosity, and intactness of cellular membranes.1,2 However, quantification of an ADC change in the tumor is still a challenge and affects sensitivity and specificity of diffusion indices for early prediction of tumor response to therapy, mainly because the ADCs in a tumor manifest a heterogeneous distribution pattern,3,4 due to spatial variation in cellular density, cell structure, and water content. In a high cellular region, mobility of water molecules is restricted, and thus the ADC is low, while in a region with necrosis or edema, water molecules move more freely and hence the ADC is high. Animal studies have shown that the ADC in a tumor is inversely correlated with tumor cellularity.3 When a tumor responds to treatment, the ADC in the high cellular region could increase due to cell shrinkage followed by phagocytosis or necrosis.4 Also, the ADC in the edema region could decrease due to drainage of water as cells move into the region.4 Hence, the direction of the change depends upon where the ADC is measured and what the original value of the ADC is. Therefore, the heterogeneity in the tumor ADCs and the complex changes that occur after treatment suggest that a change in the mean ADC of a tumor may be a poor indicator for therapy response. So far, several methodologies have been proposed to quantify the ADC changes in tumors, beyond a change in the mean ADC of a tumor, for response assessment. Functional diffusion mapping (fDM),3–7 probably the most common approach, measures the voxel-to-voxel interval changes in a pair of the coregistered ADC images acquired before and after the start of therapy. The voxels with an ADC change above a threshold are considered as a measure of response. Despite the promising results of the fDM-based approach and its modifications,8 the issue of voxel-to-voxel misregistration, particularly in the region where a tumor volume shrinks or grows during the interval of measurements, is not solved yet. Also, since the decrease/increase in regions of high cellularity or edema could have different interpretations, it is important to consider the initial ADC values to interpret subsequent changes correctly. Alternatively, analysis of the tumor ADC histogram has been proposed. A binormal distribution mixture model has shown that the mean value of the low-ADC distribution can predict therapy response in gliomas.9–11 Also, changes in mean, skewness, and kurtosis of the ADC histogram or the minimum value of the ADC in tumors have been related to survival and treatment outcome.12–20 However, these methods have not considered changes in the whole ADC histogram, including both regions with high cellularity and edema, in each of which a change could reflect a part of the process of a tumor response to therapy and therefore may lead to losing information from the analyses. Hence, it is highly desirable to develop a new methodology for quantifying the tumor ADCs to improve the performance of DW-MRI for therapy assessment. In this study, we aim to develop a diffusion abnormality index (DAI) to quantify the extent of diffusion abnormality of brain metastases compared with normal tissue for early prediction of tumor response to radiation therapy (RT). Brain metastases are the most prevalent form of intracranial cancer, exceeding the number of primary brain tumors and occurring in approximately 25% of all cancer patients.21 In our proposed approach, we assigned an abnormal diffusion probability to each voxel of the tumor based upon its ADC value relating to the normal tissue ADC distribution. Then, a DAI of the tumor is obtained by summing all the abnormal probabilities within the lesion. We tested whether an early change in the DAI could predict response of brain metastases in the patients who were treated by either whole brain radiation therapy (WBRT) alone or in combination with bortezomib as a radiation sensitizer.

The aim of this study was to assess and compare the pharmacokinetics (PK) and safety of Enasidenib in healthy adult male Japanese subjects to healthy adult male Caucasian subjects. This was a phase 1, single dose study to evaluate the PK and safety of Enasidenib in healthy adult male Japanese subjects relative to healthy adult male Caucasian subjects. A total of 62 subjects (31 Japanese and 31 Caucasian) were enrolled into three dose cohorts (single doses of 50 mg, 100 mg, or 300 mg Enasidenib). Blood samples for PK assessment were collected up to 672 hours postdose. Safety was evaluated throughout the study. In the present study, we found that PK exposures of Enasidenib and its metabolite AGI‐16903 for Caucasian and Japanese subjects were comparable at the 50, 100, and 300 mg dose levels, demonstrated by that the 90% confidence intervals (CIs) of geometric mean ratios for AUCs and C max between these two populations generally contained 100% from all three treatment cohorts. In conclusion, PK exposures of Enasidenib and its metabolite AGI‐16903 for Caucasians and Japanese subjects were comparable and Enasidenib was safe and well tolerated with no apparent differences between Japanese and Caucasian subjects when administered as single oral doses of 50 mg, 100 mg, and 300 mg.

The purpose of our study was to explore the feasibility and utility of 2D chemical shift imaging (CSI) MR spectroscopy in the evaluation of new areas of contrast enhancement at the site of a previously treated brain neoplasm.Two-dimensional CSI (point-resolved spectroscopy sequence [PRESS]; TR/TE, 1,500/144) was performed in 29 consecutive patients (4-54 years old; mean age, 34 years) who had a new contrast-enhancing lesion in the vicinity of a previously diagnosed and treated brain neoplasm. Clinical and imaging follow-up, and histopathology in 16 patients, were used as indicators of the identity of a lesion.Diagnostic-quality spectra were obtained in 97% of the patients. The Cho/Cr (choline/creatine) and Cho/NAA (choline/N-acetyl aspartate) ratios were significantly higher, and the NAA/Cr ratios significantly lower, in tumor than in radiation injury (all three differences, p0.0001). The Cho/Cr and Cho/NAA ratios were significantly higher in radiation injury than in normal-appearing white matter (p0.0003 and p0.0001, respectively), whereas NAA/Cr ratios were not different (p = 0.075). Mean Cho/Cr ratios were 2.52 for tumor, 1.57 for radiation injury, and 1.14 for normal-appearing white matter. Mean Cho/NAA ratios were 3.48, 1.31, 0.79, and mean NAA/Cr ratios were 0.79, 1.22, and 1.38, respectively. When values greater than 1.8 for either Cho/Cr or Cho/NAA ratios were considered evidence of tumor, 27 of 28 patients could be correctly classified.Two-dimensional CSI MR spectroscopy can differentiate tumor from radiation injury in patients with recurrent contrast-enhancing intracranial lesions. In these lesions, the Cho/NAA and Cho/Cr ratios may be the best numeric discriminators.

Objective: To determine whether changes in tumor volume occur during the course of conformal 3D radiotherapy of high-grade gliomas by use of magnetic resonance imaging (MRI) during treatment and whether these changes had an impact on tumor coverage. Methods and Materials: Between December 2000 and January 2004, 21 patients with WHO Grades 3 to 4 supratentorial malignant gliomas treated with 3D conformal radiotherapy (median dose, 70 Gy) were enrolled in a prospective clinical study. All patients underwent T1-weighted contrast-enhancing and T2-weighted and fluid-attenuated inversion recovery (FLAIR) imaging at approximately 1 to 2 weeks before radiotherapy, during radiotherapy (Weeks 1 and 3), and at routine intervals thereafter. All MRI scans were coregistered to the treatment-planning CT. Gross tumor volume (GTV Pre-Rx) was defined from a postoperative T1-weighted contrast-enhancing MRI performed 1 to 2 weeks before start of radiotherapy. A second GTV (GTV Week 3) was defined by use of an MRI performed during Week 3 of radiotherapy. A uniform 0.5 cm expansion of the respective GTV, PTV (Pre-Rx), and PTV (Week 3) was applied to the final boost plan. Dose-volume histograms (DVH) were used to analyze any potential adverse changes in tumor coverage based on Week 3 MRI. Results: All MRI scans were reviewed independently by a neuroradiologist (DGH). Two patients were noted to have multifocal disease at presentation and were excluded from analysis. In 19 cases, changes in the GTV based on MRI at Week 3 during radiotherapy were as follows: 2 cases had an objective decrease in GTV (≥50%); 12 cases revealed a slight decrease in the rim enhancement or changes in cystic appearance of the GTV; 2 cases showed no change in GTV; and 3 cases demonstrated an increase in tumor volume. Both cases with objective decreases in GTV during treatment were Grade 3 tumors. No cases of tumor progression were noted in Grade 3 tumors during treatment. In comparison, three of 12 Grade 4 tumors had tumor progression, based on MRI obtained during Week 3 of radiotherapy. Median increase in GTV (Week 3) was 11.7 cc (range, 9.8–21.3). Retrospective DVH analysis of PTV (Pre-Rx) and PTV (Week 3) demonstrated a decrease in V95%(PTV volume receiving 95% of the prescribed dose) in those 3 cases. Conclusions: Routine MR imaging during radiotherapy may be essential in ensuring tumor coverage if highly conformal radiotherapy techniques such as stereotactic boost and intensity-modulated radiotherapy are used in dose-escalation trials that utilize smaller treatment margins.

Background Graft versus host disease (GVHD) is the major complication of allogeneic hematopoietic stem cell transplantation. It is characterized by an imbalance between the effector and regulatory arms of the immune system which results in the over production of inflammatory cytokines. Regulatory T (T regs) cells and T helper 17 (Th17) cells are two recently described lymphocyte subsets with opposing actions. Both can develop from naïve CD4+ T cell precursors under the influence of TGFβ1. Th17 lymphocytes, are key effector cells in rodent models of human diseases including GVHD. The other subset, T regs, is essential for dominant immunologic tolerance. At our institution, patients transplanted using G-CSF primed bone marrow (G-BM), have a lower incidence of acute and chronic GVHD when compared to those transplanted with peripheral blood and not primed bone marrow. Some microenvironment characteristics of this hematopoietic stem cells (HSC) source remain unknown, as well as the difference between Tregs, Th17 and cytokine levels in patients who develop GVHD and those who do not. Objective To analyze the characteristics of thirty-eight G-BM donor samples, identifying lymphocytes subsets and associated cytokines, and comparing patients who developed chronic GVHD (cGVHD) and those who did not. Materials and Methods A prospective analysis was performed in 38 G-BM samples from donors from 1999 to 2016. Mononuclear cells were defrosted, counted, and viability was evaluated. A 24 hour resting with RPMI, and posterior activation with PMA (50 ng/ml) for 48 hours was performed. Cells were harvested and cytokines were evaluated by flow cytometry (CBA assay). From each sample, one million mononuclear cells were permeabilized, fixed, and stained with CD4-FITC, IL17A-PE, IFN-γ APC, and IL-4 PECy7, for their posterior phenotipication by flow cytometry. The samples were obtained in a BD LSR Fortessa cytometry, and analyzed with the Flow-Jo software. Patients (recipients) information was analyzed using SPSS v.21. Results GVHD incidence was reported as following: Three (8%) patients developed acute GVHD (2 grade II, and 1 grade IV), 11 patients (29%) developed chronic GVHD (9% extensive, and 91% limited), and 24 patients did not present either. Mononuclear cells from G-BM from donors of patients who developed cGVHD showed a pro inflammatory response, characterized by an increased concentration of IL-17A (15.5 vs 0.71 pg/mL, p=0.013), TNF-α (80.27 vs 0.13 pg/mL, p=0.001), and IL-6 (4953.6 vs 11.75 pg/mL, p=0.025), after a mitogenic stimulation, compared to cells from donors of patients who did not developed GVHD. On the other hand, a decreased IL-10 production (2.62 vs 52.81 pg/mL, p=0.001) was documented in mononuclear cells from donors of patients who developed chronic GVHD, compared to donor cells of patients who did not. No significant difference in the production of IL-2, IL-4, and IFN-γ was observed. There was no difference in Th1 and Th2 between both groups, but mononuclear cells from donors of patients who developed chronic GVHD had a higher percentage of Th17 (1.02% vs 0.46%, p Conclusions Patients who develop cGVHD (29%) are characterized by a pro inflammatory response with an increased production of IL-17A, IL-6, and IFN-γ, and also a major percentage of Th17 cells. Also, a decreased suppressive response was documented with reduced IL-10 and Tregs levels. The low incidence of cGVHD show that G-CSF primed bone marrow is an excellent source for allogeneic HSC transplantations, and would be useful to compare these results with other HSC sources. Disclosures No relevant conflicts of interest to declare.

To develop an image analysis framework to delineate the physiological imaging-defined subvolumes of a tumor in relating to treatment response and outcome.Our proposed approach delineates the subvolumes of a tumor based on its heterogeneous distributions of physiological imaging parameters. The method assigns each voxel a probabilistic membership function belonging to the physiological parameter classes defined in a sample of tumors, and then calculates the related subvolumes in each tumor. We applied our approach to regional cerebral blood volume (rCBV) and Gd-DTPA transfer constant (K(trans)) images of patients who had brain metastases and were treated by whole-brain radiation therapy (WBRT). A total of 45 lesions were included in the analysis. Changes in the rCBV (or K(trans))-defined subvolumes of the tumors from pre-RT to 2 weeks after the start of WBRT (2W) were evaluated for differentiation of responsive, stable, and progressive tumors using the Mann-Whitney U test. Performance of the newly developed metrics for predicting tumor response to WBRT was evaluated by receiver operating characteristic (ROC) curve analysis.The percentage decrease in the high-CBV-defined subvolumes of the tumors from pre-RT to 2W was significantly greater in the group of responsive tumors than in the group of stable and progressive tumors (P.007). The change in the high-CBV-defined subvolumes of the tumors from pre-RT to 2W was a predictor for post-RT response significantly better than change in the gross tumor volume observed during the same time interval (P=.012), suggesting that the physiological change occurs before the volumetric change. Also, K(trans) did not add significant discriminatory information for assessing response with respect to rCBV.The physiological imaging-defined subvolumes of the tumors delineated by our method could be candidates for boost target, for which further development and evaluation is warranted.

Purpose: To determine the maximum-tolerated dose (MTD) of radiation (RT) with concurrent temozolomide in patients with newly diagnosed glioblastoma (GBM), to estimate their progression-free (PFS) and overall survival (OS), and to assess the role of 11C methionine PET (MET-PET) imaging in predicting recurrence. Experimental Design: Intensity-modulated RT (IMRT) doses of 66 to 81 Gy, assigned to patients by the time-to-event continual reassessment method, were delivered over 6 weeks with concurrent daily temozolomide (75 mg/m2) followed by adjuvant cyclic temozolomide (200 mg/m2 d1-5 q28d ×6 cycles). Treatment was based on gadolinium-enhanced MRI. Pretreatment MET-PET scans were obtained for correlation with eventual sites of failure. Results: A total of 38 patients were analyzed with a median follow-up of 54 months for patients who remain alive. Late CNS grade ≥III toxicity was observed at 78 (2 of 7 patients) and 81 Gy (1 of 9 patients). None of 22 patients receiving 75 or less Gy developed RT necrosis. Median OS and PFS were 20.1 (14.0–32.5) and 9.0 (6.0–11.7) months, respectively. Twenty-two of 32 patients with pretreatment MET-PET uptake showed uptake beyond the contrast-enhanced MRI. Patients whose treatment did not include the region of increased MET-PET uptake showed an increased risk of noncentral failure (P < 0.001). Conclusions: Patients with GBM can safely receive standard temozolomide with 75 Gy in 30 fractions, delivered using IMRT. The median OS of 20.1 months is promising. Furthermore, MET-PET appears to predict regions of high risk of recurrence not defined by MRI, suggesting that further improvements may be possible by targeting metabolically active regions. Clin Cancer Res; 18(1); 273–9. ©2011 AACR.

The traffic operations academy has been conducted in-house at the California Department of Transportation (Caltrans) for more than 20 years to give junior engineers working knowledge on fundamental traffic operations. In the past two years, the academy was revamped to emphasize the Caltrans system management philosophy, refresh the course material, and most importantly, improve the way it was delivered. The revamped academy was very well received by the students and won an award from management. In this paper, the experience and lessons learned from the revamp of the academy are presented, with special focus on course design and course delivery strategies and tips. It is hoped that such experience will benefit all DOT in-house training programs in other states.

The purpose of this study was to implement and evaluate a program for obese school children. A pretest-posttest design was utilized. Data was collected related to weight status, skinfold measurements, self-esteem, and nutritional knowledge. A convenience sample of 26 children, in the fourth to sixth grades, completed this 9-week program. The results indicate that self-esteem increased significantly (p less than .001) between the pretest and posttest interval. Weight status and nutritional knowledge showed no improvement. Exercise was difficult to assess on self-report, therefore no conclusions were were drawn in relation to this variable. Future research will be directed toward refining this intervention program.

The aim of this study was to analyze the MRI findings and assess the prevalence of different associated structural abnormalities in children with scoliosis and to determine if the age of onset is a possible indicator of intraspinal pathology. This is a retrospective analysis of 663 consecutive MR examinations (319 patients). Thirteen patients with known intraspinal tumors were excluded and a total of 306 patients aged 2–18 years with scoliosis were subjected for analysis. The scoliosis was regarded as idiopathic in 62% of patients. Among the remaining 38% the most commonly seen abnormality was syrinx and Chiari malformations. There was no statistically significant difference in the occurrence of syrinx only or syrinx associated with Chiari I malformation in patients younger than ten years and those older than ten years. MRI examination is an essential part of the work up of scoliosis in the pediatric population especially before any corrective surgery. This study and a review of the current literature suggest there is no clinical marker that would definitely serve as an indicator of the presence of intraspinal pathology in these patients.

TPS9079 Background: Despite recent advances in the treatment of metastatic melanoma, survival remains poor in patients who develop brain metastases. Radiation therapy continues to be the backbone o...

Purpose: The aim of this study was to test the hypothesis that measuring quantitative changes in signal intensity early after radiotherapy (RT) in the contrast-enhancing tumor rim and nonenhancing core may be a noninvasive marker of early treatment response in patients with high-grade gliomas. Methods and Materials: Twenty patients with high-grade gliomas had magnetic resonance imaging (MRI) performed 1 week before RT, during Weeks 1 and 3 of RT, and every 1 to 3 months after RT as part of a clinical prospective study. Regions of interest (ROI) including contrast-enhancing rim, and the nonenhancing core were defined automatically based on a calculated image of post- to precontrast T1-weighted MRI. Pretreatment T1-weighted MRI signal intensity changes were compared with Weeks 1 and 3 RT and 1 and 3 months post-RT MRI. Clinical and MRI parameters were then tested for prediction of overall survival. Results: Regional T1-weighted signal intensity changes in both the contrast-enhancing rim and the nonenhancing core were observed in all patients during Week 1 and Week 3 of RT. Imaging parameters including signal intensity change within the nonenhancing core after Weeks 1 to 2 RT ( p = 0.004), Weeks 3 to 4 RT ( p = 0.002) and 1 month after completion of RT ( p = 0.002) were predictive of overall survival. Using multivariate analysis including RTOG recursive partitioning analysis (RPA) and signal intensity change, only the signal intensity change in the nonenhancing core at 1 month after RT ( p = 0.01) retained significance. Conclusion: Quantitative measurements of T1-weighted MRI signal intensity changes in the nonenhancing tumor core (using ratios of pre–post values) may provide valuable information regarding early response during treatment and improve our ability to predict posttreatment outcome.

We describe a patient with genetically- and biochemically-proven mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) who was initially misdiagnosed as having had multiple ischemic strokes in part because the clinical presentation appeared to be acute, the MRI of lesions showed restricted diffusion, and the brain biopsy showed features suggestive of stroke. This report emphasizes the pitfalls in the diagnosis of MELAS and points out the similarities and differences between MELAS and ischemic stroke.

Purpose: To investigate the impact of combining image‐based measurements related to alterations of vascular and cellularity properties of brain metastases for early prediction of tumor response to radiation therapy (RT). Methods: 24 patients undergoing treatment for metastases had perfusion (DCE) and diffusion MRI scans. Tumor subvolumes with high regional cerebral blood volume (rCBV) and high Gd‐DTAP transfer constant (Ktrans) were extracted. The apparent diffusion coefficient (ADC) histograms of the tumor volume were categorized into low, normal and high ADC subvolumes. Changes in different tumor subvolumes and their combination from pre‐RT to week 2 after start of radiation were evaluated in differentiation of responsive, stable and progressive tumors for patients treated by either whole brain radiation therapy (WBRT, 28 lesions) alone or combined with Bortezomib as a radiation sensitizer (39 lesions). Receiver Operating Characteristic (ROC) analysis compared a combined perfusion/diffusion prediction model with changes in gross tumor volume (GTV) within the same time interval. Results: For lesions treated with WBRT alone, a decrease in both high cellularity and edema subvolumes were associated with response. A decrease in the tumor subvolumes with high cellularity and vascularity was associated with response in lesions treated with RT combined with Bortezomib. In ROC analysis, areas under curve (AUCs) of 0.96 (WBRT alone) and 0.96 (WBRT + Bortezomib) were seen in prediction of non‐responsive lesions when changes in different subvolumes were combined. Also, GTV changes could predict the non‐responsive lesions treated with WBRT alone (AUC = 0.91) but failed to predict the response in lesions treated with WBRT combined with Bortezomib (AUC = 0.57). Conclusion: Combining the changes in tumor cellularity and vascularity could be used for early prediction of brain metastases response to RT and perform better than the GTV changes, suggesting that physiological changes could occur earlier than the morphological changes. (Support: NIH RO1NS064973) NIH grant ROl NS064973