Citations

Abstract Eosinophils are multifunctional cells of the innate immune system linked to allergic inflammation. Asthmatics were more likely to be hospitalized but less likely to suffer severe morbidity and mortality during the 2009 influenza pandemic. These epidemiologic findings were recapitulated in a mouse model of fungal asthma wherein infection during heightened allergic inflammation was protective against influenza A virus (IAV) infection and disease. Our goal was to delineate a mechanism(s) by which allergic asthma may alleviate influenza disease outcome, focused on the hypothesis that pulmonary eosinophilia linked with allergic respiratory disease is able to promote antiviral host defenses against the influenza virus. The transfer of eosinophils from the lungs of allergen-sensitized and challenged mice into influenza virus–infected mice resulted in reduced morbidity and viral burden, improved lung compliance, and increased CD8+ T cell numbers in the airways. In vitro assays with primary or bone marrow–derived eosinophils were used to determine eosinophil responses to the virus using the laboratory strain (A/PR/08/1934) or the pandemic strain (A/CA/04/2009) of IAV. Eosinophils were susceptible to IAV infection and responded by activation, piecemeal degranulation, and upregulation of Ag presentation markers. Virus- or viral peptide–exposed eosinophils induced CD8+ T cell proliferation, activation, and effector functions. Our data suggest that eosinophils promote host cellular immunity to reduce influenza virus replication in lungs, thereby providing a novel mechanism by which hosts with allergic asthma may be protected from influenza morbidity.

Abstract Rationale Patients with malignant pleural effusions have significant dyspnea and shortened life expectancy. Indwelling pleural catheters allow patients to drain pleural fluid at home and can lead to autopleurodesis. The optimal drainage frequency to achieve autopleurodesis and freedom from catheter has not been determined. Objectives To determine whether an aggressive daily drainage strategy is superior to the current standard every other day drainage of pleural fluid in achieving autopleurodesis. Methods Patients were randomized to either an aggressive drainage (daily drainage; n = 73) or standard drainage (every other day drainage; n = 76) of pleural fluid via a tunneled pleural catheter. Measurements and Main Results The primary outcome was the incidence of autopleurodesis following the placement of the indwelling pleural catheters. The rate of autopleurodesis, defined as complete or partial response based on symptomatic and radiographic changes, was greater in the aggressive drainage arm than the standard drainage arm (47% vs. 24%, respectively; P = 0.003). Median time to autopleurodesis was shorter in the aggressive arm (54 d; 95% confidence interval, 34–83) as compared with the standard arm (90 d; 95% confidence interval, 70 to nonestimable). Rate of adverse events, quality of life, and patient satisfaction were not significantly different between the two arms. Conclusions Among patients with malignant pleural effusion, daily drainage of pleural fluid via an indwelling pleural catheter led to a higher rate of autopleurodesis and faster time to liberty from catheter. Clinical trial registered with www.clinicaltrials.gov (NCT 00978939).

Abstract Introduction A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. Methods Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web‐based quantitative survey regarding symptom frequency and the conceptualization of PCA. Results A three‐level classification framework for PCA is described comprising both syndrome‐ and disease‐level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico‐radiological syndrome. Classification level 2 (PCA‐pure, PCA‐plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA‐AD], Lewy body disease [PCA‐LBD], corticobasal degeneration [PCA‐CBD], prion disease [PCA‐prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome‐level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. Discussion There was strong agreement regarding the definition of the core clinico‐radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single‐center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work.

The purpose of this study is to investigate changes in lung tumor internal target volume during stereotactic body radiotherapy treatment (SBRT) using magnetic resonance imaging (MRI). Ten lung cancer patients (13 tumors) undergoing SBRT (48 Gy over four consecutive days) were evaluated. Each patient underwent three lung MRI evaluations: before SBRT (MRI‐1), after fraction 3 of SBRT (MRI‐3), and three months after completion of SBRT (MRI‐3m). Each MRI consisted of T1‐weighted images in axial plane through the entire lung. A cone‐beam CT (CBCT) was taken before each fraction. On MRI and CBCT taken before fractions 1 and 3, gross tumor volume (GTV) was contoured and differences between the two volumes were compared. Median tumor size on CBCT before fractions 1 (CBCT‐1) and 3 (CBCT‐3) was 8.68 and 11.10 cm3, respectively. In 12 tumors, the GTV was larger on CBCT‐3 compared to CBCT‐1 (median enlargement, 1.56 cm3). Median tumor size on MRI‐1, MRI‐3, and MRI‐3m was 7.91, 11.60, and 3.33 cm3, respectively. In all patients, the GTV was larger on MRI‐3 compared to MRI‐1 (median enlargement, 1.54 cm3). In all patients, GTV was smaller on MRI‐3m compared to MRI‐1 (median shrinkage, 5.44 cm3). On CBCT and MRI, all patients showed enlargement of the GTV during the treatment week of SBRT, except for one patient who showed minimal shrinkage (0.86 cm3). Changes in tumor volume are unpredictable; therefore, motion and breathing must be taken into account during treatment planning, and image‐guided methods should be used, when treating with large fraction sizes.PACS number: 87.53.Ly

The main purpose of this work was to quantify patient organ doses from the two kilovoltage cone beam computed tomography (CBCT) systems currently available on medical linear accelerators, namely the X‐ray Volumetric Imager (XVI, Elekta Oncology Systems) and the On‐Board Imager (OBI, Varian Medical Systems). Organ dose measurements were performed using a fiber‐optic coupled (FOC) dosimetry system along with an adult male anthropomorphic phantom for three different clinically relevant scan sites: head, chest, and pelvis. The FOC dosimeter was previously characterized at diagnostic energies by Hyer et al. [Med Phys 2009;36(5):1711–16] and a total uncertainty of approximately 4% was found for in‐phantom dose measurements. All scans were performed using current manufacturer‐installed clinical protocols and appropriate bow‐tie filters. A comparison of image quality between these manufacturer‐installed protocols was also performed using a Catphan 440 image quality phantom. Results indicated that for the XVI, the dose to the lens of the eye (1.07 mGy) was highest in a head scan, thyroid dose (19.24 mGy) was highest in a chest scan, and gonad dose (29 mGy) was highest in a pelvis scan. For the OBI, brain dose (3.01 mGy) was highest in a head scan, breast dose (5.34 mGy) was highest in a chest scan, and gonad dose (34.61 mGy) was highest in a pelvis scan. Image quality measurements demonstrated that the OBI provided superior image quality for all protocols, with both better spatial resolution and low‐contrast detectability. The measured organ doses were also used to calculate a reference male effective dose to allow further comparison of the two machines and imaging protocols. The head, chest, and pelvis scans yielded effective doses of 0.04, 7.15, and 3.73 mSv for the XVI, and 0.12, 1.82, and 4.34 mSv for the OBI, respectively.PACS number: 87.57.uq