Purpose Patients with inoperable pancreatic adenocarcinoma have limited options, with traditional chemoradiation providing modest clinical benefit and an otherwise poor prognosis. Stereotactic body radiation therapy for pancreatic cancer is limited by proximity to organs-at-risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has shown promise in delivering ablative doses safely. We sought to demonstrate the benefits of SMART using a 5-fraction approach with daily on-table adaptation. Methods and Materials Patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were treated with 50 Gy in 5 fractions (biologically effective dose 10 100 Gy) with a prescribed goal of 95% planning target volume coverage by 95% of prescription, prioritizing hard OAR constraints. Daily online adaptation was performed using magnetic resonance-guidance and on-table reoptimization. Patient outcomes, treatment factors, and daily adaptation were evaluated. Results Forty-four patients were treated with SMART at our institution from 2014 to 2019. Median follow-up from date of diagnosis was 16 months (range, 6.7-51.6). Late toxicity was limited to 2 (4.6%) grade 3 (gastrointestinal ulcers) and 3 (6.8%) grade 2 toxicities (duodenal perforation, antral ulcer, and gastric bleed). Tumor abutted OARs in 35 patients (79.5%) and tumor invaded OARs in 5 patients (11.1%). Reoptimization was performed for 93% of all fractions. Median overall survival was 15.7 months (95% confidence interval, 10.2-21.2), while 1-year and 2-year overall survival rates were 68.2% and 37.9%, respectively. One-year local control was 84.3%. Conclusions This is the first reported experience using 50 Gy in 5 fractions for inoperable pancreatic cancer. SMART allows this ablative dose with promising outcomes while minimizing toxicity. Additional prospective trials evaluating efficacy and safety are warranted.
Recombinant bovine viral diarrhea virus (BVDV) nonstructural protein 5B (NS5B) produced in insect cellshas been shown to possess an RNA-dependent RNA polymerase (RdRp) activity. Our initial attempt to produce the full-length BVDV NS5B with a C-terminal hexahistidine tag in Escherichia coli failed due to the expression of insoluble products. Prompted by a recent report that removal of the C-terminal hydrophobic domain significantly improved the solubility of hepatitis C virus (HCV) NS5B, we constructed a similar deletion of 24 amino acids at the C terminus of BVDV NS5B. The resulting fusion protein, NS5B⌬CT24-His, was purified to homogeneity and demonstrated to direct RNA replication via both primer-dependent (elongative) and primerindependent (de novo) mechanisms. Furthermore, BVDV RdRp was found to utilize a circular single-stranded DNA as a template for RNA synthesis, suggesting that synthesis does not require ends in the template. In addition to the previously described polymerase motifs A, B, C, and D, alignments with other flavivirus sequences revealed two additional motifs, one N-terminal to motif A and one C-terminal to motif D. Extensive alanine substitutions showed that while most mutations had similar effects on both elongative and de novo RNA syntheses, some had selective effects. Finally, deletions of up to 90 amino acids from the N terminus did not significantly affect RdRp activities, whereas deletions of more than 24 amino acids at the C terminus resulted in either insoluble products or soluble proteins (⌬CT179 and ⌬CT218) that lacked RdRp activities.
Purpose ChatGPT is a large language model trained on a large dataset covering a broad range of topics, including the medical literature. We aim to examine its accuracy and reproducibility in answering patient questions regarding bariatric surgery. Materials and methods Questions were gathered from nationally regarded professional societies and health institutions as well as Facebook support groups. Board-certified bariatric surgeons graded the accuracy and reproducibility of responses. The grading scale included the following: (1) comprehensive, (2) correct but inadequate, (3) some correct and some incorrect, and (4) completely incorrect. Reproducibility was determined by asking the model each question twice and examining difference in grading category between the two responses. Results In total, 151 questions related to bariatric surgery were included. The model provided “comprehensive” responses to 131/151 (86.8%) of questions. When examined by category, the model provided “comprehensive” responses to 93.8% of questions related to “efficacy, eligibility and procedure options”; 93.3% related to “preoperative preparation”; 85.3% related to “recovery, risks, and complications”; 88.2% related to “lifestyle changes”; and 66.7% related to “other”. The model provided reproducible answers to 137 (90.7%) of questions. Conclusion The large language model ChatGPT often provided accurate and reproducible responses to common questions related to bariatric surgery. ChatGPT may serve as a helpful adjunct information resource for patients regarding bariatric surgery in addition to standard of care provided by licensed healthcare professionals. We encourage future studies to examine how to leverage this disruptive technology to improve patient outcomes and quality of life. Graphical Abstract
Purpose To demonstrate the versatility and performance of a compact Bayer filter snapshot hyperspectral fundus camera for in-vivo clinical applications including retinal oximetry and macular pigment optical density measurements. Methods 12 healthy volunteers were recruited under an Institutional Review Board (IRB) approved protocol. Fundus images were taken with a custom hyperspectral camera with a spectral range of 460–630 nm. We determined retinal vascular oxygen saturation (sO2) for the healthy population using the captured spectra by least squares curve fitting. Additionally, macular pigment optical density was localized and visualized using multispectral reflectometry from selected wavelengths. Results We successfully determined the mean sO2 of arteries and veins of each subject (ages 21–80) with excellent intrasubject repeatability (1.4% standard deviation). The mean arterial sO2 for all subjects was 90.9% ± 2.5%, whereas the mean venous sO2 for all subjects was 64.5% ± 3.5%. The mean artery–vein (A–V) difference in sO2 varied between 20.5% and 31.9%. In addition, we were able to reveal and quantify macular pigment optical density. Conclusions We demonstrated a single imaging tool capable of oxygen saturation and macular pigment density measurements in vivo. The unique combination of broad spectral range, high spectral–spatial resolution, rapid and robust imaging capability, and compact design make this system a valuable tool for multifunction spectral imaging that can be easily performed in a clinic setting.
Continuing perioperative administration of antibiotics for the entire duration that a drain is in place after spinal surgery did not decrease the rate of surgical site infections.
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