Evaluation of precalibrated implantable MOSFET radiation dosimeters for megavoltage photon beams

We have studied the response of factory calibrated implantable MOSFET detectors to absorbed doses from 100 to 400 cGy. The average measured dose is quite close to the true delivered dose, with the standard deviation falling between 1.4 and 3.6%. The measured dose tends to be slightly underestimated for smaller doses, while it tends to be slightly overestimated for larger doses. Thus, although the calibration of the detector is most accurate for doses close to the calibration dose of 200 cGy, it may be used over the range of commonly used doses in fractionated radiotherapy.     

Meta-analyses using real-world data to generate clinical and epidemiological evidence: a systematic literature review of existing recommendations

Objectives: To identify existing guidelines, key recommendations, and existing limitations regarding the evaluation and use of real-world evidence (RWE) in meta-analyses (MAs) to generate clinical and epidemiological evidence: a systematic review of existing recommendations.

Methods: A literature search was performed in April 2017 in MEDLINE and Embase using the Ovid platform, the Cochrane Library, and other sources. No specific inclusion and exclusion criteria were applied, and no restrictions in timeframe, language, or geographical scope were imposed.

Results: The search strategy identified 1681 citations; 12 references were included in this review. Recommendations within the literature regarding the use of RWE in MAs are: (1) it may be useful to extract and analyze adjusted results because confounding is expected; (2) testing heterogeneity in the MA of RWE is important as it may minimize the potential for bias and generate hypotheses for future research; (3) limiting a search ≤2 bibliographic databases when conducting MAs of RWE will not provide a thorough summary of existing literature; and (4) the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) checklist is a 35-item checklist developed to allow for more standardized reporting of MAs of RWE and address their limitations.

Limitations: (1) No formal guidelines were found regarding the use of RWE in MAs; (2) no consensus was found on a preferred instrument for the assessment of RWE; and (3) critical appraisal of RWE is often omitted from Health Technology Assessment submissions.

Conclusions: The inclusion of RWE in MAs may facilitate the confirmation of conclusions drawn from randomized controlled trials and, thus, reassure decision-makers that findings can be extrapolated to real-world populations. However, qualitative and quantitative bias may co-exist in MAs of RWE. Reviewers should select the most appropriate tools that match the study designs identified in a particular systematic review.     

Proto-oncogene c-mpl is involved in spontaneous megakaryocytopoiesis in myeloproliferative disorders

Spontaneous megakaryocytic colonies (CFU-MK) formation without the addition of Meg-CSA in myeloproliferative disorders (MPD) has been reported by many laboratories. The mechanism by which this occurs is still unknown. In our previous work we have found that the spontaneous colonies persisted in serum-free agar culture although the colony cells were smaller and the colony numbers fewer than in plasma clot culture and that monoclonal antibodies against IL3, IL6 and GM-CSF had no inhibitory effect on spontaneous CFU-MK in both semi-solid cultures. Recently, proto-oncogene c-mpl and c-mpl ligand, thrombopoietin (TPO), have been shown to specifically participate in the regulation of normal human megakaryocytopoiesis. In order to test the hypothesis that c-mplc-mpl ligand pathway is involved in the spontaneous growth of megakaryocyte progenitors, we investigated mRNA expressions of c-mpl and TPO in cells grown in serum-free liquid culture using RT-PCR. The c-mpl expression was detected in the cultured cells from all nine patients (six with ET, two with PV, one with PMF) who had spontaneous CFU-MK in clonal assays. However, none of the patients expressed TPO mRNA in these cells. Pre-incubation of nonadherent mononuclear cells with thioester-modified antisense oligodeoxynucleotide to c-mpl at a concentration of 6μM significantly decreased the cloning efficiency of spontaneous megakaryocyte growth by 42.5% (P<0.05) in plasma clot assay (seven with ET, one with PV) and 69.6% (P<0.05) in serum-free agar culture (six with ET, one with PV). In control experiments the introduction of a scrambled oligomer to antisense oligodeoxynucleotide had no such effect on spontaneous colony formation. These results indicate that c-mpl exerts an important effect in the growth of spontaneous megakaryocytopoiesis in MPD.     

Dose escalation with proton or photon radiation treatment for pancreatic cancer

Purpose

The purpose was to determine the optimal radiation therapy modality (three-dimensional conformal photon-radiation therapy [3DCRT], intensity-modulated photon-radiation therapy [IMRT], or passive-scattering proton therapy [PT]) for safe dose escalation (72 Gy) in pancreatic tumors in different positions relative to organs at risk (OAR) anatomy.

Methods and materials

A 3-cm pancreatic tumor was virtually translated every 5 mm over 5 cm laterally. We generated two plans for each of the three techniques (3DCRT, IMRT, and PT), one that adhered to target coverage objectives and another to meet OAR sparing constraints with best coverage. We evaluated distances between gross tumor volumes and isodoses and compared dose-volume histograms.

Results

IMRT was more conformal in higher gradient dose regions circumferentially, but tumor positions with anteriorly located small bowel benefited more from PT. 3DCRT plans resulted in inadequate target coverage. The V_15Gy (mean ± SD) were as follows for the IMRT and PT plans, respectively: stomach, 48% ± 4% vs 5% ± 3% (p < 0.0001); and small bowel, 61% ± 8% vs 9% ± 4% (p < 0.0001).

Conclusions

Our study showed that the optimal radiation therapy modality for safe dose escalation depends on pancreatic tumor position in relation to OAR anatomy.     

Functional specializations of human epidermal Langerhans cells and CD14+ dermal dendritic cells

Little is known about the functional differences between the human skin myeloid dendritic cell (DC) subsets, epidermal CD207(+) Langerhans cells (LCs) and dermal CD14(+) DCs. We showed that CD14(+) DCs primed CD4(+) T cells into cells that induce naive B cells to switch isotype and become plasma cells. In contrast, LCs preferentially induced the differentiation of CD4(+) T cells secreting T helper 2 (Th2) cell cytokines and were efficient at priming and crosspriming naive CD8(+) T cells. A third DC population, CD14(-)CD207(-)CD1a(+) DC, which resides in the dermis, could activate CD8(+) T cells better than CD14(+) DCs but less efficiently than LCs. Thus, the human skin displays three DC subsets, two of which, i.e., CD14(+) DCs and LCs, display functional specializations, the preferential activation of humoral and cellular immunity, respectively.     

<Emphasis Type="Italic">Francisella tularensis</Emphasis> aortitis

Francisella tularensis, the agent of tularemia, is a Gram-negative coccobacillus primarily pathogen for animals and occasionally for humans. The clinical manifestations of tularemia include pneumonia, ulceroglandular, oropharyngeal, or typhoidal disease. Rare manifestations are also described, but to our knowledge, we describe here the first case of F. tularensis aortitis in a human. Diagnosis was confirmed by the presence of F. tularensis in blood culture, by the presence of F. tularensis DNA in the aortic biopsy and by specific IgG and IgM responses against the bacteria. The outcome was favorable after surgery and specific antimicrobial therapy.