Evaluation of skin dose associated with different frequencies of bolus applications in post-mastectomy three-dimensional conformal radiotherapy

<p>Abstract</p> <p>Background</p> <p>The study aimed to calculate chest-wall skin dose associated with different frequencies of bolus applications in post-mastectomy three-dimensional conformal radiotherapy (3D-CRT) and to provide detailed information in the selection of an appropriate bolus regimen in this clinical setting.</p> <p>Methods</p> <p>CT-Simulation scans of 22 post-mastectomy patients were used. Chest wall for clinical target volume (CTV) and a volume including 2-mm surface thickness of the chest wall for skin structures were delineated. Precise PLAN 2.11 treatment planning system (TPS) was used for 3D-CRT planning. 50 Gy in 25 fractions were prescribed using tangential fields and 6-MV photons. Six different frequencies of bolus applications (0, 5, 10, 15, 20, and 25) were administered. Cumulative dose-volume histograms were generated for each bolus regimen. The minimum, maximum and mean skin doses associated with the bolus regimens were compared. To test the accuracy of TPS dose calculations, experimental measurements were performed using EBT gafchromic films.</p> <p>Results</p> <p>The mean, minimum and maximum skin doses were significantly increased with increasing days of bolus applications (p < 0.001). The minimum skin doses for 0, 5, 10, 15, 20, and 25 days of bolus applications were 73.0% ± 2.0%, 78.2% ± 2.0%, 83.3% ± 1.7%, 88.3% ± 1.6%, 92.2% ± 1.7%, and 93.8% ± 1.8%, respectively. The minimum skin dose increments between 20 and 25 (1.6% ± 1.0%), and 15 and 20 (4.0% ± 1.0%) days of bolus applications were significantly lower than the dose increments between 0 and 5 (5.2% ± 0.6%), 5 and 10 (5.1% ± 0.8%), and 10 and 15 (4.9% ± 0.8%) days of bolus applications (p < 0.001). The maximum skin doses for 0, 5, 10, 15, 20, and 25 days of bolus applications were 110.1% ± 1.1%, 110.3% ± 1.1%, 110.5% ± 1.2%, 110.8% ± 1.3%, 111.2% ± 1.5%, and 112.2% ± 1.7%, respectively. The maximum skin dose increments between 20 and 25 (1.0% ± 0.6%), and 15 and 20 (0.4% ± 0.3%) days of bolus applications were significantly higher than the dose increments between 0 and 5 (0.2% ± 0.2%), 5 and 10 (0.2% ± 0.2%), and 10 and 15 (0.2% ± 0.2%) days of bolus applications (p ≤ 0.003). The TPS overestimated the near-surface dose 10.8% at 2-mm below the skin surface.</p> <p>Conclusion</p> <p>In post-mastectomy 3D-CRT, using a 1-cm thick bolus in up to 15 of the total 25 fractions increased minimum skin doses with a tolerable increase in maximum doses.</p

A Quantitative RNAi Screen for JNK Modifiers Identifies Pvr as a Novel Regulator of Drosophila Immune Signaling

Drosophila melanogaster responds to gram-negative bacterial challenges through the IMD pathway, a signal transduction cassette that is driven by the coordinated activities of JNK, NF-κB and caspase modules. While many modifiers of NF-κB activity were identified in cell culture and in vivo assays, the regulatory apparatus that determines JNK inputs into the IMD pathway is relatively unexplored. In this manuscript, we present the first quantitative screen of the entire genome of Drosophila for novel regulators of JNK activity in the IMD pathway. We identified a large number of gene products that negatively or positively impact on JNK activation in the IMD pathway. In particular, we identified the Pvr receptor tyrosine kinase as a potent inhibitor of JNK activation. In a series of in vivo and cell culture assays, we demonstrated that activation of the IMD pathway drives JNK-dependent expression of the Pvr ligands, Pvf2 and Pvf3, which in turn act through the Pvr/ERK MAP kinase pathway to attenuate the JNK and NF-κB arms of the IMD pathway. Our data illuminate a poorly understood arm of a critical and evolutionarily conserved innate immune response. Furthermore, given the pleiotropic involvement of JNK in eukaryotic cell biology, we believe that many of the novel regulators identified in this screen are of interest beyond immune signaling

The Drosophila melanogaster host model

The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen–host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial–host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis–host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Analysis of clinicopathological prognostic parameters in adenocarcinoma of the gastric cardia

Background : The optimal extent of resection for carcinoma of gastric cardia remains a subject of controversy. Although both total gastrectomy (TG) and proximal gastrectomy (PG) have their own advantages, similar survival rates were given for both. The main aim of this study is to investigate whether the extent, of resection is an important prognostic factor in carcinoma of the gastric cardia

Wkly Abstr Sanit Rep

19316859PMCnul

Chorio-retinal thickness measurements in patients with acromegaly

Purpose To compare choroidal, foveal, and peripapillary retinal thickness between patients with acromegaly and healthy adults.Methods This prospective, cross-sectional, and comparative study included 30 patients with acromegaly (study group) and 30 healthy subjects (control group). The subfoveal choroidal thickness (SFCT), foveal thickness, and peripapillary retinal nerve fibre layer thickness were measured with spectral domain optical coherence tomography.Results The mean SFCT in the study group and in the control eyes was 374.4 +/- 98.1 and 308.6 +/- 77.3 mu m, respectively (P<0.001). The mean thinnest foveal thickness value was 233.2 +/- 22.4 mu m in the acromegaly group and 222.8 +/- 13.9 mu m in the control group (P = 0.003). The mean peripapillary retinal nerve fibre layer thickness did not differ significantly between the groups (P = 0.34).Conclusion The SFCT and foveal thickness were significantly higher in patients with acromegaly, whereas peripapillary retinal nerve fibre layer thickness was similar between the groups