Uncertainties and correction methods when modeling passive scattering proton therapy treatment heads with Monte Carlo

Nowadays, Monte Carlo models of proton therapy treatment heads are being used to improve beam delivery systems and to calculate the radiation field for patient dose calculations. The achievable accuracy of the model depends on the exact knowledge of the treatment head geometry and time structure, the material characteristics, and the underlying physics. This work aimed at studying the uncertainties in treatment head simulations for passive scattering proton therapy. The sensitivities of spread-out Bragg peak (SOBP) dose distributions on material densities, mean ionization potentials, initial proton beam energy spread and spot size were investigated. An improved understanding of the nature of these parameters may help to improve agreement between calculated and measured SOBP dose distributions and to ensure that the range, modulation width, and uniformity are within clinical tolerance levels. Furthermore, we present a method to make small corrections to the uniformity of spread-out Bragg peaks by utilizing the time structure of the beam delivery. In addition, we re-commissioned the models of the two proton treatment heads located at our facility using the aforementioned correction methods presented in this paper.     

Custom-made angled inserts for tibial coronal malalignment in total knee arthroplasty

Component malalignment continues to be common after knee arthroplasty, with treatment often requiring prosthesis revision. From 1993 to 2005, 9 angled inserts were placed to correct coronal plane deformities due to tibial component malposition. Insert exchange occurred at an average of 67 months (range, 5-149 months) from the index procedure. Two patients died before 2-year follow-up, for an overall average of 60 months (range, 12-157 months) follow-up. Limb alignment improved and Knee Society knee and function scores increased from 68 and 71, respectively, to 92 and 91, postoperatively. All patients reported excellent satisfaction with no revisions at average 5-year follow-up. It is important to be aware that specifically designed angled inserts are available and may provide a conservative method to correct mild to moderate tibial malalignment in rare cases.     

The ability of parents to accurately report concussion occurrence in their bantam-aged minor hockey league children

Objective:

The objective of this study was to assess the ability of hockey parents/guardians to recognize concussion symptoms in their 13–14 year old (Bantam-aged) children.

Outcome Measures:

The outcome measures were the ability to recognize different signs and symptoms listed on the Sport Concussion Assessment Tool (SCAT) as well as 8 detractors consisting of signs and symptoms not associated with post concussive syndrome. Additional questions assessing the parents’ knowledge of concussion management and recognition abilities were also posed.

Participants:

Parents of Bantam-aged minor hockey league athletes volunteered for the study.

Methods:

The study investigators distributed questionnaires during the warm up period or following their children’s games to the study participants. Following questionnaire completion, participants were provided with an information package outlining the correct signs and symptoms of concussion.

Results:

The mean number of correct responses to signs and symptoms of concussion was 21.25/25 for the mothers and 20.41/25 for the fathers. The mean number of detractors identified as not associated with concussion was 5.93/8 for the mothers and 4.85/8 for the fathers, indicating that mothers were more capable of recognizing the signs and symptoms than fathers. An analysis of variance including sporting experience in the model did not strengthen the relationship between parent gender and test outcome.

Conclusion:

This investigation revealed that there is still a disconnect in regards to key components of recognizing a concussion, such as difficulty with sleep, disorientation symptoms, and emotional irritability. Mothers have displayed an ability to better differentiate between true and false signs and symptoms of concussion as compared to fathers. Continued education and awareness of mild traumatic brain injury in athletes should address the misconceptions amongst parents in regards to the true signs and symptoms of a concussion.     

An analysis of disease severity based on SMN2 copy number in adults with spinal muscular atrophy

To evaluate the effect of SMN2 copy number on disease severity in spinal muscular atrophy (SMA), we stratified 45 adult SMA patients based on SMN2 copy number (3 vs. 4 copies). Patients with 3 copies had an earlier age of onset and lower spinal muscular atrophy functional rating scale (SMAFRS) scores and were more likely to be non‐ambulatory. There was, however, no difference between the groups in quantitative muscle strength or pulmonary function testing. Functional scale may be a more discriminating outcome measure for SMA clinical trials. Muscle Nerve, 2009     

Citrin deficiency,a perplexing global disorder

Citrin deficiency, caused by mutations in SLC25A13, can present with neonatal intrahepatic cholestasis or with adult onset neuropsychiatric, hepatic and pancreatic disease. Until recently, it had been thought to be found mostly in individuals of East Asian ancestry. A key diagnostic feature has been the deficient argininosuccinate synthetase (ASS) activity (E.C. 6.3.4.5) in liver, with normal activity in skin fibroblasts. In this series we describe the clinical presentation of 10 patients referred to our laboratories for sequence analysis of the SCL25A13 gene, including several patients who presented with elevated citrulline on newborn screening. In addition to sequence analysis performed on all patients, ASS enzyme activity, citrulline incorporation and Western blot analysis for ASS and citrin were performed on skin fibroblasts if available. We have found 5 unreported mutations including two apparent founder mutations in three unrelated French-Canadian patients. In marked contrast to previous cases, these patients have a markedly reduced ASS activity in skin fibroblasts. The presence of citrin protein on Western blot in three of our cases reduces the sensitivity of a screening test based on protein immunoblotting. The finding of citrin mutations in patients of Arabic, Pakistani, French Canadian and Northern European origins supports the concept that citrin deficiency is a panethnic disease.     

Prostaglandin E1 and misoprostol increase epidermal growth factor production in 3D-cultured human annulus cells

Background contextEpidermal growth factor (EGF) is a peptide known to modulate a number of cellular responses including embryogenesis, cell proliferation, and cell survival. Little is known about EGF and its regulation in human annulus cells. Previous work has identified EGF and its receptor in control outer annulus disc tissue, but not in herniated tissue.PurposeTo determine if human annulus cells express EGF in vitro, to determine if the epidermal growth factor-receptor (EGF-r) was expressed in vivo and in vitro in disc cells, to test the effect of EGF on annulus cell proliferation and proteoglycan production in vitro, and to test the effect of prostaglandin E1 (PGE1) and misoprostol on disc cell production of EGF in vitro.Study design/settingStudies were approved by the authors' Human Subjects Institutional review Board. Human disc tissue was used for immunocytochemistry, and human annulus cells were tested in vitro.Patient sampleThirty-four disc specimens were used for studies of proteoglycan production, cell proliferation, and EGF production in vitro. An additional nine discs were used for EGF-r immunolocalization.MethodsDisc tissue was used for immunocytochemical studies for the localization of EGF-r and as a source for cultured annulus cells. Monolayer culture was used to test proliferation responses to 0, 25, 50, or 75 ng/mL EGF over a 2-day culture period. Three-dimensional (3D) culture in a collagen sponge was used to test 100,000 cells cultured in a paired experimental design over 14 days for production of EGF and proteoglycans. Cells were exposed to control conditions, or to either misoprostol at 8 ng/mL or PGE1 at 10^?7 M. Conditioned media was harvested and assayed using an enzyme-linked immunosorbent assay (ELISA) assay with the Human Protein Cytokine Antibody Array I kit. Replicate EGF relative intensity values were averaged and normalized to controls assayed on the same membrane. 3D-cultured cells were also used to confirm EGF gene expression using microarray analysis. Standard statistical methods were used to analyze results.ResultsMicroarray analysis of mRNA from annulus cells in 3D culture confirmed expression of EGF, and immunocytochemistry verified the presence of EGF-r in vitro and in vivo. PGE1, at a dose of 10^?7 M, and misoprostol (a synthetic PGE1 analog) at a dose of 8 ng/mL, both significantly increased EGF levels in annulus cells cultured in 3D compared with control levels (p=.031 and .034, respectively). No significant difference, however, was seen in cell proliferation or in total sulfated proteoglycan production in EGF-exposed annulus cells.ConclusionsData showed that EGF is expressed and produced by annulus cells in vivo and in 3D culture, with significantly greater in vitro EGF produced in the presence of PGE1 or the PGE1 analog misoprostol. Misoprostol, developed for prevention/treatment of nonsteroidal anti-inflammatory-induced gastropathy, has now been reported to have some interesting anabolic effects stimulating osteoblasts during fracture healing and during ovariectomy in animal models. Exogenous EGF did not increase cell proliferation in monolayer, or total production of proteoglycans in 3D culture. Additional work is needed to further delineate the role of EGF in the human disc.     

Percutaneous retrieval of a biliary stent after migration and ileal perforation

We present a case of a migrated biliary stent that resulted in a distal small bowel perforation, abscess formation and high grade partial small bowel obstruction in a medically stable patient without signs of sepsis or diffuse peritonitis. We performed a percutaneous drainage of the abscess followed by percutaneous retrieval of the stent. The entero-peritoneal fistula closed spontaneously with a drain in place. We conclude, migrated biliary stents associated with perforation distal to the Ligament of Trietz (LOT), may be treated by percutaneous drainage of the abscess and retrieval of the stent from the peritoneal cavity, even when associated with a large intra-abdominal abscess.