Sickle cell bone disease and response to intravenous bisphosphonates in children.

Children with sickle cell disease (SCD) have the potential for extensive and early-onset bone morbidity. This study reports on the diversity of bone morbidity seen in children with SCD followed at three tertiary centers. IV bisphosphonates were effective for bone pain analgesia and did not trigger sickle cell complications. INTRODUCTION: To evaluate bone morbidity and the response to intravenous (IV) bisphosphonate therapy in children with SCD. METHODS: We conducted a retrospective review of patient records from 2003 to 2019 at three Canadian pediatric tertiary care centers. Radiographs, magnetic resonance images, and computed tomography scans were reviewed for the presence of avascular necrosis (AVN), bone infarcts, and myositis. IV bisphosphonates were offered for bone pain management. Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA). RESULTS: Forty-six children (20 girls, 43%) had bone morbidity at a mean age of 11.8 years (SD 3.9) including AVN of the femoral (17/46, 37%) and humeral (8/46, 17%) heads, H-shaped vertebral body deformities due to endplate infarcts (35/46, 76%), and non-vertebral body skeletal infarcts (15/46, 32%). Five children (5/26, 19%) had myositis overlying areas of AVN or bone infarcts visualized on magnetic resonance imaging. Twenty-three children (8/23 girls) received IV bisphosphonate therapy. They all reported significant or complete resolution of bone pain. There were no reports of sickle cell hemolytic crises, pain crises, or stroke attributed to IV bisphosphonate therapy. CONCLUSION: Children with SCD have the potential for extensive and early-onset bone morbidity. In this series, IV bisphosphonates were effective for bone pain analgesia and did not trigger sickle cell complications.

Hippocampal dysfunction in the pathophysiology of schizophrenia: a selective review and hypothesis for early detection and intervention.

Scientists have long sought to characterize the pathophysiologic basis of schizophrenia and develop biomarkers that could identify the illness. Extensive postmortem and in vivo neuroimaging research has described the early involvement of the hippocampus in the pathophysiology of schizophrenia. In this context, we have developed a hypothesis that describes the evolution of schizophrenia-from the premorbid through the prodromal stages to syndromal psychosis-and posits dysregulation of glutamate neurotransmission beginning in the CA1 region of the hippocampus as inducing attenuated psychotic symptoms and initiating the transition to syndromal psychosis. As the illness progresses, this pathological process expands to other regions of the hippocampal circuit and projection fields in other anatomic areas including the frontal cortex, and induces an atrophic process in which hippocampal neuropil is reduced and interneurons are lost. This paper will describe the studies of our group and other investigators supporting this pathophysiological hypothesis, as well as its implications for early detection and therapeutic intervention.

Baseline demographics, clinical features and predictors of conversion among 200 individuals in a longitudinal prospective psychosis-risk cohort.

BACKGROUND: DSM-5 proposes an Attenuated Psychosis Syndrome (APS) for further investigation, based upon the Attenuated Positive Symptom Syndrome (APSS) in the Structured Interview for Psychosis-Risk Syndromes (SIPS). SIPS Unusual Thought Content, Disorganized Communication and Total Disorganization scores predicted progression to psychosis in a 2015 NAPLS-2 Consortium report. We sought to independently replicate this in a large single-site high-risk cohort, and identify baseline demographic and clinical predictors beyond current APS/APSS criteria. METHOD: We prospectively studied 200 participants meeting criteria for both the SIPS APSS and DSM-5 APS. SIPS scores, demographics, family history of psychosis, DSM Axis-I diagnoses, schizotypy, and social and role functioning were assessed at baseline, with follow-up every 3 months for 2 years. RESULTS: The conversion rate was 30% (n = 60), or 37.7% excluding participants who were followed under 2 years. This rate was stable across time. Conversion time averaged 7.97 months for 60% who developed schizophrenia and 15.68 for other psychoses. Mean conversion age was 20.3 for males and 23.5 for females. Attenuated odd ideas and thought disorder appear to be the positive symptoms which best predict psychosis in a logistic regression. Total negative symptom score, Asian/Pacific Islander and Black/African-American race were also predictive. As no Axis-I diagnosis or schizotypy predicted conversion, the APS is supported as a distinct syndrome. In addition, cannabis use disorder did not increase risk of conversion to psychosis. CONCLUSIONS: NAPLS SIPS findings were replicated while controlling for clinical and demographic factors, strongly supporting the validity of the SIPS APSS and DSM-5 APS diagnosis.

The impact of emotion awareness and regulation on social functioning in individuals at clinical high risk for psychosis.

BACKGROUND: Social functioning (SF) difficulties are ubiquitous among individuals at clinical high risk for psychosis (CHR), but it is not yet clear why. One possibility is suggested by the observation that effective SF requires adaptive emotion awareness and regulation. Previous reports have documented deficits in emotion awareness and regulation in individuals with schizophrenia, and have shown that such deficits predicted SF. However, it is unknown whether these deficits are present prior to the onset of psychosis or whether they are linked to SF in CHR individuals. METHOD: We conducted a cross-sectional comparison of emotion awareness and regulation in 54 individuals at CHR, 87 with schizophrenia and 50 healthy controls (HC). Then, within the CHR group, we examined links between emotion awareness, emotion regulation and SF as indexed by the Global Functioning Scale: Social (Cornblatt et al. 2007). RESULTS: Group comparisons indicated significant differences between HC and the two clinical groups in their ability to identify and describe feelings, as well as the use of suppression and reappraisal emotion-regulation strategies. Specifically, the CHR and schizophrenia groups displayed comparable deficits in all domains of emotion awareness and emotion regulation. A hierarchical multiple regression analysis indicated that difficulties describing feelings accounted for 23.2% of the SF variance. CONCLUSIONS: The results indicate that CHR individuals display substantial emotion awareness and emotion-regulation deficits, at severity comparable with those observed in individuals with schizophrenia. Such deficits, in particular difficulties describing feelings, predate the onset of psychosis and contribute significantly to poor SF in this population.

Imaging glutamate in schizophrenia: review of findings and implications for drug discovery.

Currently, all treatments for schizophrenia (SCZ) function primarily by blocking D(2)-type dopamine receptors. Given the limitations of these medications, substantial efforts have been made to identify alternative neurochemical targets for treatment development in SCZ. One such target is brain glutamate. The objective of this article is to review and synthesize the proton magnetic resonance spectroscopy ((1)H MRS) and positron emission tomography (PET)/single-photon emission computed tomography (SPECT) investigations that have examined glutamatergic indices in SCZ, including those of modulatory compounds such as glutathione (GSH) and glycine, as well as data from ketamine challenge studies. The reviewed (1)H MRS and PET/SPECT studies support the theory of hypofunction of the N-methyl-D-aspartate receptor (NMDAR) in SCZ, as well as the convergence between the dopamine and glutamate models of SCZ. We also review several advances in MRS and PET technologies that have opened the door for new opportunities to investigate the glutamate system in SCZ and discuss some ways in which these imaging tools can be used to facilitate a greater understanding of the glutamate system in SCZ and the successful and efficient development of new glutamate-based treatments for SCZ.

Striatal dopamine release in schizophrenia comorbid with substance dependence.

Dopamine (DA) has a role in the pathophysiology of schizophrenia and addiction. Imaging studies have indicated that striatal DA release is increased in schizophrenia, predominantly in the precommissural caudate (preDCA), and blunted in addiction, mostly in the ventral striatum (VST). Therefore, we aimed to measure striatal DA release in patients with comorbid schizophrenia and substance dependence. We used [(11)C]raclopride positron emission tomography and an amphetamine challenge to measure baseline DA D2-receptor availability (BPND) and its percent change post-amphetamine (ΔBPND, to index amphetamine-induced DA release) in striatal subregions in 11 unmedicated, drug-free patients with both schizophrenia and substance dependence, and 15 healthy controls. There were no significant group differences in baseline BPND. Linear mixed modeling using ΔBPND as the dependent variable and striatal region of interest as a repeated measure indicated a significant main effect of diagnosis, F(1,24)=8.38, P=0.008, with significantly smaller ΔBPND in patients in all striatal subregions (all P ≤ 0.04) except VST. Among patients, change in positive symptoms after amphetamine was significantly associated with ΔBPND in the preDCA (rs=0.69, P=0.03) and VST (rs=0.64, P=0.05). In conclusion, patients with comorbid schizophrenia and substance dependence showed significant blunting of striatal DA release, in contrast to what has been found in schizophrenia without substance dependence. Despite this blunting, DA release was associated with the transient amphetamine-induced positive-symptom change, as observed in schizophrenia. This is the first description of a group of patients with schizophrenia who display low presynaptic DA release, yet show a psychotic reaction to increases in D2 stimulation, suggesting abnormal postsynaptic D2 function.

Outcomes of hospitalisation for right heart failure in pulmonary arterial hypertension.

The aim of this study was to examine the causes and outcomes of hospitalisation in patients with pulmonary arterial hypertension (PAH). 205 consecutive hospitalisations occurring between 2000 and 2009 in 90 PAH patients were studied. The leading causes for hospitalisation were right heart failure (RHF; 56%), infection (16%) and bleeding disorders (8%). For patients with RHF, in-hospital mortality was 14% overall, 46% for patients receiving inotropes and 48% for those admitted to the intensive care unit. The predictors for in-hospital mortality were the presence of connective tissue disease (CTD) (OR 4.92), systolic blood pressure <100 mmHg (OR 4.32) and Na ≤ 136 mEq · L(-1) (OR 4.29). Mortality after discharge was 13, 26 and 35% at 3, 6 and 12 months, respectively. World Health Organization functional class prior to admission, renal dysfunction, Charlson comorbidity index, and the presence of CTD were all predictors of mortality after discharge. Hyponatraemia and low systolic blood pressure upon admission and underlying CTD are the main prognostic factors for in-hospital mortality in patients with PAH admitted for RHF. The short-term outcomes after discharge are poor and remarkably worse in patients with underlying CTD or renal impairment. Early recognition of these factors may guide decisions regarding more aggressive therapy, including consideration for lung transplantation.

Disproportionate elevation of N-terminal pro-brain natriuretic peptide in scleroderma-related pulmonary hypertension.

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of neurohormonal activation that is useful in the diagnosis and prognosis of various forms of pulmonary arterial hypertension (PAH). We sought to characterise and compare NT-proBNP in a cohort of PAH related to systemic sclerosis (PAH-SSc) and idiopathic PAH (IPAH) patients. NT-proBNP levels, collected from PAH-SSc and IPAH patients followed prospectively, were compared and correlated with haemodynamic variables. Cox proportional hazard models were created to assess the predictive value of NT-proBNP. 98 patients (55 PAH-SSc, 43 IPAH) were included. Haemodynamics were similar, except for lower mean pulmonary arterial pressure in PAH-SSc. NT-proBNP levels were significantly higher in PAH-SSc (3,419+/-3,784 versus 1,393+/-1,633 pg x mL(-1); p<0.01) and were more closely related to haemodynamics in PAH-SSc than IPAH. 28 patients died. NT-proBNP predicted survival (hazard ratio (HR) 3.18; p<0.01) in the overall cohort; however, when stratified by group, predicted survival only in PAH-SSc (HR 3.07, p<0.01 versus 2.02, p = 0.29 in IPAH). This is the first description showing NT-proBNP levels are 1) significantly higher in PAH-SSc than IPAH despite less severe haemodynamic perturbations, and 2) stronger predictors of survival in PAH-SSc, suggesting that neurohormonal regulation may differ between PAH-SSc and IPAH. Future studies to define pertinent mechanisms are warranted.

Exercise as an end-point in pulmonary hypertension trials.

With recent advances in our understanding of pulmonary hypertension and with ever increasing therapeutic options at our disposal, it remains disappointing that clinical markers of disease progression remain dated. There has long been a search for a more robust clinical correlate than the 6 minute walk test. Resting right heart pressures do not increase linearly with worsening disease, limiting their use as primary endpoints. Some progress has been made however, with 'time to clinical worsening' a composite endpoint of several markers of disease severity. Trials have also been undertaken to evaluate the merits of echocardiographic indices, cardio pulmonary exercise testing and cardiac MRI, with mixed results. With the lack of a sensitive and specific biomarker for pulmonary hypertension, the goal of finding a reproducible endpoint that accurately reflects disease severity and prognosis remains elusive. In this article we discuss relevant endpoints and focus on exercise haemodynamics as a primary endpoint for clinical trials.

Antipsychotic drug mechanisms: links between therapeutic effects, metabolic side effects and the insulin signaling pathway.

The exact therapeutic mechanism of action of antipsychotic drugs remains unclear. Recent evidence has shown that second-generation antipsychotic drugs (SGAs) are differentially associated with metabolic side effects compared to first-generation antipsychotic drugs (FGAs). Their proclivity to cause metabolic disturbances correlates, to some degree, with their comparative efficacy. This is particularly the case for clozapine and olanzapine. In addition, the insulin signaling pathway is vital for normal brain development and function. Abnormalities of this pathway have been found in persons with schizophrenia and antipsychotic drugs may ameliorate some of these alterations. This prompted us to hypothesize that the therapeutic antipsychotic and adverse metabolic effects of antipsychotic drugs might be related to a common pharmacologic mechanism. This article reviews insulin metabolism in the brain and related abnormalities associated with schizophrenia with the goals of gaining insight into antipsychotic drug effects and possibly also into the pathophysiology of schizophrenia. Finally, we speculate about one potential mechanism of action (that is, functional selectivity) that would be consistent with the data reviewed herein and make suggestions for the future investigation that is required before a therapeutic agent based on these data can be realized.

HIV-associated pulmonary arterial hypertension: a clinical problem that is here to stay?

HIV-associated pulmonary arterial hypertension (PAH) is a serious complication of HIV infection and associated with high patient mortality. There are multiple similarities between HIV-associated PAH and idiopathic PAH and standard PAH medications have been used to treat the condition with reported success. Prior to the advent of highly active antiretroviral treatments (HAART), the prevalence of the condition in the HIV-infected population was estimated at 0.5%. In a recently published, large, prospective, multi-centre study performed in the HIV-population across France, the prevalence of HIV-associated PAH was estimated at 0.46%. In this article, we provide an overview of HIV-associated PAH and summarise the methodology, pertinent findings and implications of this important paper.

The Early Psychosis Screener for Internet (EPSI)-SR: Predicting 12 month psychotic conversion using machine learning.

INTRODUCTION: A faster and more accurate self-report screener for early psychosis is needed to promote early identification and intervention. METHODS: Self-report Likert-scale survey items were administered to individuals being screened with the Structured Interview for Psychosis-risk Syndromes (SIPS) and followed at eight early psychosis clinics. An a priori analytic plan included Spectral Clustering Analysis to reduce the item pool, followed by development of Support Vector Machine (SVM) classifiers. RESULTS: The cross-validated positive predictive value (PPV) of the EPSI at the default cut-off (76.5%) exceeded that of the clinician-administered SIPS (68.5%) at separating individuals who would not convert to psychosis within 12 months from those who either would convert within 12 months or who had already experienced a first episode psychosis (FEP). When used in tandem with the SIPS on clinical high risk participants, the EPSI increased the combined PPV to 86.6%. The SVM classified as FEP/converters only 1% of individuals in non-clinical and 4% of clinical low risk populations. Sensitivity of the EPSI, however, was 51% at the default cut-off. DISCUSSION: The EPSI identifies, comparably to the SIPS but in less time and with fewer resources, individuals who are either at very high risk to develop a psychotic disorder within 12 months or who are already psychotic. At its default cut-off, EPSI misses 49% of current or future psychotic cases. The cut-off can, however, be adjusted based on purpose. The EPSI is the first validated assessment to predict 12-month psychotic conversion. An online screening system, www.eps.telesage.org, is under development.

The Early Psychosis Screener (EPS): Quantitative validation against the SIPS using machine learning.

Machine learning techniques were used to identify highly informative early psychosis self-report items and to validate an early psychosis screener (EPS) against the Structured Interview for Psychosis-risk Syndromes (SIPS). The Prodromal Questionnaire-Brief Version (PQ-B) and 148 additional items were administered to 229 individuals being screened with the SIPS at 7 North American Prodrome Longitudinal Study sites and at Columbia University. Fifty individuals were found to have SIPS scores of 0, 1, or 2, making them clinically low risk (CLR) controls; 144 were classified as clinically high risk (CHR) (SIPS 3-5) and 35 were found to have first episode psychosis (FEP) (SIPS 6). Spectral clustering analysis, performed on 124 of the items, yielded two cohesive item groups, the first mostly related to psychosis and mania, the second mostly related to depression, anxiety, and social and general work/school functioning. Items within each group were sorted according to their usefulness in distinguishing between CLR and CHR individuals using the Minimum Redundancy Maximum Relevance procedure. A receiver operating characteristic area under the curve (AUC) analysis indicated that maximal differentiation of CLR and CHR participants was achieved with a 26-item solution (AUC=0.899±0.001). The EPS-26 outperformed the PQ-B (AUC=0.834±0.001). For screening purposes, the self-report EPS-26 appeared to differentiate individuals who are either CLR or CHR approximately as well as the clinician-administered SIPS. The EPS-26 may prove useful as a self-report screener and may lead to a decrease in the duration of untreated psychosis. A validation of the EPS-26 against actual conversion is underway.

Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplantation in Patients Over Age 70 Years: A Case Report.

Extracorporeal membrane oxygenation (ECMO) may be used safely as a bridge to lung transplantation in carefully selected elderly patients. We report the case of a 70-year-old patient bridged on ECMO before transplantation. A brief discussion on improving outcomes for the elderly and patients bridged on ECMO in general is presented.

The Novel Compound Sul-121 Preserves Endothelial Function and Inhibits Progression of Kidney Damage in Type 2 Diabetes Mellitus in Mice.

Diabetic nephropathy is still a common complication of type 2 diabetes mellitus (T2DM) and improvement of endothelial dysfunction (ED) and inhibition of reactive oxygen species (ROS) are considered important targets for new therapies. Recently, we developed a new class of compounds (Sul compounds) which inhibit mitochondrial ROS production. Here, we tested the therapeutic effects of Sul-121 on ED and kidney damage in experimental T2DM. Diabetic db/db and lean mice were implanted with osmotic pumps delivering Sul-121 (2.2 mg/kg/day) or vehicle from age 10 to 18 weeks. Albuminuria, blood pressure, endothelial mediated relaxation, renal histology, plasma creatinine, and H2O2 levels were assessed. Sul-121 prevented progression of albuminuria and attenuated kidney damage in db/db, as evidenced by lower glomerular fibronectin expression (~50%), decreased focal glomerular sclerosis score (~40%) and normalization of glomerular size and kidney weight. Further, Sul-121 restored endothelium mediated vasorelaxation through increased production of Nitric Oxide production and normalized plasma H2O2 levels. Sul-121 treatment in lean mice demonstrated no observable major side-effects, indicating that Sul-121 is well tolerated. Our data show that Sul-121 inhibits progression of diabetic kidney damage via a mechanism that involves restoration of endothelial function and attenuation of oxidative stress.

The effects of glucocorticoid replacement therapy on growth, bone mineral density, and bone turnover markers in children with congenital adrenal hyperplasia.

Even with current so called physiologic doses of glucocorticoid replacement therapy, children with congenital adrenal hyperplasia (CAH) often show relative short stature and delayed bone maturation, an observation that suggests possible long-term effects on bone metabolism of daily transient post-absorptive hypercortisolemia. In 28 patients with 21-hydroxylase or 17 alpha-hydroxylase deficiency (16 females and 12 males, ages 4.9-22 yr) who had received oral cortisol 10-15 mg/M2/day for 4.7-22 yr, we studied cortisol bioavailability, growth, bone maturation, vertebral bone mineral density, and various markers of bone formation and resorption. Patients were grouped according to mean on-therapy serum 170H-progesterone or progesterone levels as tight control (170HP < 10 nmol/L), fair control (170HP 10-40 nmol/L or progesterone 1.0-1.5 nmol/L), or poor control (170HP > 40 nmol/L). There was no difference in peak post-absorptive serum cortisol or area under the concentration-time curve, and only three patients had a peak serum cortisol of more than 700 nmol/L. There was no difference in present height Z-score (-0.96; -0.24; -0.6), height Z-score at age 2 yr (-1.5; +0.4; -1.3), or current growth velocity Z-score (-0.1; +1.2; -2.2) between the groups, but bone maturation Z-score was significantly delayed (-1.63) in the tight control group and advanced (+0.8) in the poor control group. Present height was highly correlated (r = 0.8) with height at age 2 yr. Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25OH-vitamin D levels were all normal. There was no difference between the groups in age-corrected vertebral bone mineral density, and no difference in serum osteocalcin, procollagen peptide, or collagen C-terminal telopeptide, nor in urinary amino-terminal telopeptide. The data suggest that current methods of cortisol replacement do not significantly influence bone formation, resorption or density during childhood and therefore should not contribute to adult osteoporosis. The possibility remains that hypercortisolemia during infancy produces the short stature and delayed bone maturation that are present by the age 2 yr.

The utility of annual surveillance bronchoscopy in heart-lung transplant recipients.

Bronchoscopy with transbronchial biopsy (TBBx) and bronchoalveolar lavage (BAL) has an appreciable yield in detecting asymptomatic abnormalities in heart-lung transplant recipients (HLTR) during the early postoperative period. The utility of annual surveillance procedures has not been critically evaluated. We reviewed all annual bronchoscopies performed on 29 HLTR to determine the frequency of asymptomatic abnormalities. Surveillance bronchoscopies (SB) were performed on asymptomatic subjects with unchanged lung function compared with baseline. Surveillance/clinical bronchoscopies (SCB) were those performed in patients with stable decrements in lung function. Nineteen patients underwent 48 SB and 8 had 18 SCB. Five of 15 (33%) SB performed at one year yielded an abnormal TBBx (1 grade 2 acute rejection [AR], 1 grade 1 AR, 1 grade 1 AR with obliterative bronchiolitis [OB] and 2 Pneumocystis carinii pneumonia). At 2 or more years, TBBx was abnormal in 2 of 33 (6%, p = 0.024 compared with first year TBBx) (1 grade 1 AR, 1 lymphocytic bronchiolitis). Pathogens were identified in BAL in 19 (40%) SB. Fourteen (78%) SCB were abnormal. Nine (50%) revealed an abnormal TBBx (all OB), but only 2 (11%) of these altered patient management. Seven (39%) demonstrated pathogens in BAL. We conclude that in HLTR (1) surveillance TBBx rarely yields positive findings 2 or more years posttransplant, (2) surveillance TBBx seldom alters management in patients with stable decrements in lung function, and (3) BAL is useful to screen for potential pathogens.

Actinomyces odontolyticus thoracopulmonary infections. Two cases in lung and heart-lung transplant recipients and a review of the literature.

We present the first case of mediastinitis and the third case of pneumonia attributed to Actinomyces odontolyticus. The first patient presented 10 months after single-lung transplant with a subacute apical infiltrate in the native lung and responded to therapy with oral penicillin. The second patient developed pyogenic mediastinitis 25 days after a heart-lung transplant and required sternal debridement and intravenous penicillin. We also review the literature on thoracopulmonary infections due to A odontolyticus.

Detection of small airway dysfunction using specific airway conductance.

STUDY OBJECTIVE: To assess the potential utility of specific airway conductance (sGaw) in detecting small airways dysfunction, the postlung-transplant bronchiolitis obliterans syndrome (BOS) was used as a model of small airways dysfunction. BOS is defined as an otherwise unexplained 20% reduction in FEV1. We hypothesized that if sGaw is sensitive to small airways dysfunction, it should decrease before the decline in FEV1. DESIGN/METHODS: The pulmonary function test and sGaw measurements of patients who underwent heart-lung or bilateral lung transplantation between May 1981 and January 1993 were reviewed. Patients with and without BOS were identified. A significant decrease in sGaw was defined as a 20% fall from baseline. RESULTS: Twenty-six BOS and 15 non-BOS patients had at least three sGaw measurements such that trends could be examined. Eleven of the 26 BOS patients (42%) had a significant decrease in sGaw before a 20% decrease in FEV1, as compared to 2 of the 15 non-BOS patients (13%) (p=0.08). In comparison, 12 of the 26 BOS patients (46%) and 4 of the 15 non-BOS patients (27%) had a significant decrease in forced expiratory flow at 25 to 75% of the forced lung volume (FEF(25-75)) (p=0.32), an accepted test of small airways dysfunction. CONCLUSION: sGaw tended to decrease before FEV1 in BOS. The trend in sGaw was similar to the trend in FEF(25-75). We conclude that (1) small airways may contribute more to airway conductance than previously thought, and (2) further prospective studies are warranted to better define the relative contribution of small and large airways to sGaw.

Bilateral proximal pulmonary artery aneurysms simulating hilar adenopathy.

Proximal pulmonary artery aneurysms (PAAs) are rare. Most are associated with secondary pulmonary hypertension or a variety of rare systemic disorders. An asymptomatic adult patient presented with bilateral hilar enlargement on a routine chest roentgenogram. Computed tomography of the chest revealed 5 cm bilateral proximal PAAs with a normal pulmonary trunk. The clinician should consider proximal PAA in the differential diagnosis of hilar enlargement.