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Abstract Background Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson’s Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans. Methods In a case–control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n = 159), LBD (n = 110), Alzheimer’s disease dementia (ADD, n = 97), other neurodegenerative disease controls (NDC, n = 19), and immune disease controls (IDC, n = 14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating. Results The model classified LBD from HC with an AUROC of 0.87 ± 0.06 and AUPRC of 0.80 ± 0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes. Conclusions and Relevance Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease.

Abstract Background Electronic health records (EHR) contain large volumes of unstructured free-form text notes that richly describe a patient’s health and medical comorbidities. It is unclear if perioperative risk stratification can be performed directly from these notes without manual data extraction. We conduct a feasibility study using natural language processing (NLP) to predict the American Society of Anesthesiologists Physical Status Classification (ASA-PS) as a surrogate measure for perioperative risk. We explore prediction performance using four different model types and compare the use of different note sections versus the whole note. We use Shapley values to explain model predictions and analyze disagreement between model and human anesthesiologist predictions. Methods Single-center retrospective cohort analysis of EHR notes from patients undergoing procedures with anesthesia care spanning all procedural specialties during a 5 year period who were not assigned ASA VI and also had a preoperative evaluation note filed within 90 days prior to the procedure. NLP models were trained for each combination of 4 models and 8 text snippets from notes. Model performance was compared using area under the receiver operating characteristic curve (AUROC) and area under the precision recall curve (AUPRC). Shapley values were used to explain model predictions. Error analysis and model explanation using Shapley values was conducted for the best performing model. Results Final dataset includes 38,566 patients undergoing 61,503 procedures with anesthesia care. Prevalence of ASA-PS was 8.81% for ASA I, 31.4% for ASA II, 43.25% for ASA III, and 16.54% for ASA IV-V. The best performing models were the BioClinicalBERT model on the truncated note task (macro-average AUROC 0.845) and the fastText model on the full note task (macro-average AUROC 0.865). Shapley values reveal human-interpretable model predictions. Error analysis reveals that some original ASA-PS assignments may be incorrect and the model is making a reasonable prediction in these cases. Conclusions Text classification models can accurately predict a patient’s illness severity using only free-form text descriptions of patients without any manual data extraction. They can be an additional patient safety tool in the perioperative setting and reduce manual chart review for medical billing. Shapley feature attributions produce explanations that logically support model predictions and are understandable to clinicians.

Background: Anesthesiology plays a crucial role in perioperative care, critical care, and pain management, impacting patient experiences and clinical outcomes. However, our understanding of the anesthesiology research landscape is limited. Accordingly, we initiated a data-driven analysis through topic modeling to uncover research trends, enabling informed decision-making and fostering progress within the field. Methods: The easyPubMed R package was used to collect 32,300 PubMed abstracts spanning from 2000 to 2022. These abstracts were authored by 737 Anesthesiology Principal Investigators (PIs) who were recipients of National Institute of Health (NIH) funding from 2010 to 2022. Abstracts were preprocessed, vectorized, and analyzed with the state-of-the-art BERTopic algorithm to identify pillar topics and trending subtopics within anesthesiology research. Temporal trends were assessed using the Mann-Kendall test. Results: The publishing journals with most abstracts in this dataset were Anesthesia & Analgesia 1133, Anesthesiology 992, and Pain 671. Eight pillar topics were identified and categorized as basic or clinical sciences based on a hierarchical clustering analysis. Amongst the pillar topics, “Cells & Proteomics” had both the highest annual and total number of abstracts. Interestingly, there was an overall upward trend for all topics spanning the years 2000–2022. However, when focusing on the period from 2015 to 2022, topics “Cells & Proteomics” and “Pulmonology” exhibit a downward trajectory. Additionally, various subtopics were identified, with notable increasing trends in “Aneurysms”, “Covid 19 Pandemic”, and “Artificial intelligence & Machine Learning”. Conclusion: Our work offers a comprehensive analysis of the anesthesiology research landscape by providing insights into pillar topics, and trending subtopics. These findings contribute to a better understanding of anesthesiology research and can guide future directions.

Abstract Background Due to the role expansion of radiotherapists in dosimetric aspect, radiotherapists have taken up organs at risk (OARs) contouring work in many clinical settings. However, training of newly qualified radiotherapists in OARs contouring can be time consuming, it may also cause extra burden to experienced radiotherapists. As web-based open-source radiotherapy delineation software (WORDS) has become more readily available, it has provided a free and interactive alternative to conventional one-to-one coaching approach during OARs contouring training. The present study aims to evaluate the effectiveness of WORDS in training OARs contouring skills of newly qualified radiotherapists, compared to those trained by conventional one-to-one coaching approach. Methods Nine newly qualified radiotherapists (licensed in 2017 – 2018) were enrolled to the conventional one-to-one coaching group (control group), while 11 newly qualified radiotherapists (licensed in 2019 – 2021) were assigned to WORDS training group (measured group). Ten OARs were selected to be contoured in this 3-phases quantitative study. Participants were required to undergo phase 1 OARs contouring in the beginning of the training session. Afterwards, conventional one-to-one training or WORDS training session was provided to participants according to their assigned group. Then the participants did phase 2 and 3 OARs contouring which were separated 1 week apart. Phase 1 – 3 OARs contouring aimed to demonstrate participants’ pre-training OARs contouring ability, post-training OARs contouring ability and knowledge retention after one-week interval respectively using either training approach. To prevent bias, the computed tomography dataset for OARs contouring in each phase were different. Variations in the contouring scores for the selected OARs were evaluated between 3 phases using Kruskal-Wallis tests with Dunn tests for pairwise comparisons. Variations in the contouring scores between control and measured group in phase 1 – 3 contouring were analyzed using Wilcoxon signed-rank test. A p-value 0.05) were observed in all OARs between both groups. Conclusions The results in this study have demonstrated that the outcome of OARs contouring training using WORDS is comparable to the conventional training approach. In addition, WORDS can offer flexibility to newly qualified radiotherapists to practice OARs contouring at will, as well as reduce staff training burden of experienced radiotherapists.

Summary: Existing techniques for transcriptional profiling of projection neurons could be applied to only one neuronal population per experiment. To increase throughput, we developed VECTORseq, which repurposes retrogradely infecting viruses to deliver multiplexable RNA barcodes, enabling projection anatomy to be read out in single-cell datasets. In this protocol, we describe the delivery of viral barcodes to mouse brain to label different projection neurons. We then detail single-cell or nuclei isolation for sequencing, followed by the analysis of single-cell sequencing data.For complete details on the use and execution of this protocol, please refer to Cheung et al. (2021). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Background Primary splenic cysts are very rarely diagnosed in pregnancy, with only thirteen cases described in the literature. We examine the approach towards diagnosing and managing uniquely large abdominal masses that significantly complicate obstetric care. Case presentation A 37-year-old primigravida woman presented with abdominal distension and discomfort, yet otherwise asymptomatic. On ultrasound, an incidental pregnancy at 25 weeks of gestation and a large pelvic lesion were discovered. MRI defined a 28 × 29 cm lobulated, complex cystic mass in the upper abdomen. The patient underwent two ascitic drainages throughout her pregnancy. At 34 weeks of gestation, she had a classical caesarean section. Then at five-weeks postpartum, she underwent a laparotomy and total splenectomy with 16 L of fluid drained. Histopathological analysis revealed an epithelial cyst of the spleen. Her recovery was complicated by complete portal vein thrombosis. Conclusion This case describes the largest splenic cyst ever reported in pregnancy and explores the diagnostic dilemmas and treatment challenges associated. We introduce the utility of serial ascitic drainages in prolonging the pregnancy and emphasise the reliance on imaging for surveillance of splenic size and fetal wellbeing.

Abstract Background Although whole brain radiation therapy (WBRT) provides palliation and prophylaxis, reduces local recurrence probability and improves overall survival, it is evident that WBRT is associated with neurocognitive deficits due to radiation induced damage of the hippocampus. Therefore, minimizing hippocampal dose to the least possible level is of high clinical relevance. In dual-arc conventional volumetric modulated arc therapy (dac-VMAT), the large irradiation field for whole brain planned target volume (PTV) requires a wide jaw opening in which substantial low dose volume to the hippocampus may be produced due to suboptimal multi-leaf collimator (MLC) movements. The present study investigates the potential of a radiation therapy technique with split-arc and reduced field size, namely split-arc partial-field volumetric modulated arc therapy (sapf-VMAT) to spare the hippocampus during WBRT. Methods Computed tomography and magnetic resonance images of 20 patients with brain metastases were retrieved in this retrospective planning study. The hippocampus was manually delineated by single radiation oncologist strictly following the RTOG 0933 atlas definition. Plans delivering 30 Gy in 10 fractions were generated for each patient using dac-VMAT and sapf-VMAT. Dosimetric parameters from both techniques were compared by paired t-test. Results The results demonstrated that radiation dose to the hippocampus was significantly reduced using sapf-VMAT relative to dac-VMAT plans. sapf-VMAT (7.86Gy, p = 0.001) had significantly lowered average D100% compared to dac-VMAT (9.23 Gy). Decrease in hippocampus Dmax using sapf-VMAT (13.23 Gy, p = 0.001) was statistically significant when compared to dac-VMAT (16.33 Gy). The resulting mean dose to the hippocampus was 9.16 Gy for the for sapf-VMAT. Mean dose of sapf-VMAT was significantly lower than dac-VMAT (10.85 Gy, p

Background: Medical tourism is increasingly popular for elective cosmetic surgical procedures. However, medical tourism has been accompanied by reports of post-surgical infections due to rapidly growing mycobacteria (RGM). The authors’ experience working with patients with RGM infections who have returned to the USA after traveling abroad for cosmetic surgical procedures is described here. Methods: Patients who developed RGM infections after undergoing cosmetic surgeries abroad and who presented at the Montefiore Medical Center (Bronx, New York, USA) between August 2015 and June 2016 were identified. A review of patient medical records was performed. Results: Four patients who presented with culture-proven RGM infections at the sites of recent cosmetic procedures were identified. All patients were treated with a combination of antibiotics and aggressive surgical treatment. Conclusions: This case series of RGM infections following recent cosmetic surgeries abroad highlights the risks of medical tourism. Close monitoring of affected patients by surgical and infectious disease specialties is necessary, as aggressive surgical debridement combined with appropriate antibiotic regimens is needed to achieve cure. Given the increasing reports of post-surgical RGM infections, consultants should have a low threshold for suspecting RGM, as rapid diagnosis may accelerate the initiation of targeted treatment and minimize morbidity.

Introduction: Nasopharyngeal carcinoma (NPC) is a prevalent disease in Southern China. Radiation therapy remains the primary treatment modality for NPC due to its high radiation sensitivity. Conventional volumetric-modulated arc therapy (VMAT) can achieve excellent target volume coverage and superior conformal dose distributions while sparing organs at risk (OARs). However, VMAT may also produce substantial volume of low-dose region in the surrounding normal tissue. Our oncology centre has incorporated the concept of anterior cervical field with VMAT in clinical practice of NPC treatment planning. The purpose of this treatment-comparison case study is to demonstrate the lower neck OARs sparing ability of hybrid volumetric-modulated arc therapy (hybrid-VMAT) over conventional VMAT for NPC. Methods: Four patients diagnosed with NPC of different clinical lymph node staging (N staging) were enrolled for this treatment-comparison case study. Planning target volumes and OARs were delineated with reference to Radiation Therapy Oncology Group (RTOG) 0225/0615. Additional OARs from lower neck region, including thyroid, trachea, cervical spine and pharyngeal constrictor muscles (PCMs), were also delineated. Two treatment techniques, hybrid-VMAT and VMAT, were created for each patient's dataset. Results and findings: Both treatment techniques produced adequate target coverage and reduced radiation dose to the OARs as suggested in RTOG 0225/0615. Hybrid-VMAT plans achieved superior dose reduction in larynx, oesophagus, middle PCM, inferior PCM, cervical spine and trachea comparing with VMAT plans. Hence, the clinical usability and functional outcome of hybrid-VMAT should be further investigated for NPC radiation therapy. [ABSTRACT FROM AUTHOR]

Abstract Background: This technical note aims to verify the hippocampus and adjacent organs at risk (OARs) sparing ability of an improved beam arrangement, namely hybrid split-arc partial-field volumetric modulated arc therapy (VMAT) (Hsapf-VMAT) during whole brain radiation therapy (WBRT). Materials and methods: Computed tomography simulation images of 22 patients with brain metastases were retrieved in this retrospective planning study. The hippocampus was manually delineated according to the criterion of RTOG 0933. Plans delivering 30 Gy in 10 fractions were generated for each patient using split-arc partial-field VMAT (sapf-VMAT) and Hsapf-VMAT. The sapf-VMAT plans consisted of 4 arc fields of 179.9° each with reduced field size. The Hsapf-VMAT consisted of 4 arc fields similar to sapf-VMAT in addition to 2 lateral opposing static fields. Statistical comparisons between treatment plans of both techniques were performed using the paired t-test at 5% level significance. Results: The results demonstrated that Hsapf-VMAT can achieve superior dose sparing in hippocampus which is comparable to sapf-VMAT (p > 0.05). In both eyes, Hsapf-VMAT had significantly lower Dmean and Dmax compared to sapf-VMAT (p < 0.005). Decrease in Dmax of both lenses using Hsapf-VMAT (p < 0.005) were statistically significant when compared to sapf-VMAT. Hsapf-VMAT demonstrated significant reduction of Dmean and Dmedian to the optic nerves (p < 0.05). Whole brain planning target volume (PTV) coverage was not compromised in both techniques. Conclusion: The present study adopts a hybrid technique, namely Hsapf-VMAT, for hippocampal sparing WBRT. Hsapf-VMAT can achieve promising dose reduction to the hippocampus, both eyes and lenses. Therefore, Hsapf-VMAT can be considered an improved version of sapf-VMAT. [ABSTRACT FROM AUTHOR]

Background: Due to the role expansion of radiotherapists in dosimetric aspect, radiotherapists have taken up organs at risk (OARs) contouring work in many clinical settings. However, training of newly qualified radiotherapists in OARs contouring can be time consuming, it may also cause extra burden to experienced radiotherapists. As web-based open-source radiotherapy delineation software (WORDS) has become more readily available, it has provided a free and interactive alternative to conventional one-to-one coaching approach during OARs contouring training. The present study aims to evaluate the effectiveness of WORDS in training OARs contouring skills of newly qualified radiotherapists, compared to those trained by conventional one-to-one coaching approach. Methods: Nine newly qualified radiotherapists (licensed in 2017 – 2018) were enrolled to the conventional one-to-one coaching group (control group), while 11 newly qualified radiotherapists (licensed in 2019 – 2021) were assigned to WORDS training group (measured group). Ten OARs were selected to be contoured in this 3-phases quantitative study. Participants were required to undergo phase 1 OARs contouring in the beginning of the training session. Afterwards, conventional one-to-one training or WORDS training session was provided to participants according to their assigned group. Then the participants did phase 2 and 3 OARs contouring which were separated 1 week apart. Phase 1 – 3 OARs contouring aimed to demonstrate participants' pre-training OARs contouring ability, post-training OARs contouring ability and knowledge retention after one-week interval respectively using either training approach. To prevent bias, the computed tomography dataset for OARs contouring in each phase were different. Variations in the contouring scores for the selected OARs were evaluated between 3 phases using Kruskal-Wallis tests with Dunn tests for pairwise comparisons. Variations in the contouring scores between control and measured group in phase 1 – 3 contouring were analyzed using Wilcoxon signed-rank test. A p-value < 0.05 was considered to be statistically significant. Results: In both control group and measured group, significant improvement (p < 0.05) in phase 2 and 3 contouring scores have been observed comparing to phase 1 contouring scores. In comparison of contouring scores between control group and measured group, no significant differences (p > 0.05) were observed in all OARs between both groups. Conclusions: The results in this study have demonstrated that the outcome of OARs contouring training using WORDS is comparable to the conventional training approach. In addition, WORDS can offer flexibility to newly qualified radiotherapists to practice OARs contouring at will, as well as reduce staff training burden of experienced radiotherapists. [ABSTRACT FROM AUTHOR]

Background: Although whole brain radiation therapy (WBRT) provides palliation and prophylaxis, reduces local recurrence probability and improves overall survival, it is evident that WBRT is associated with neurocognitive deficits due to radiation induced damage of the hippocampus. Therefore, minimizing hippocampal dose to the least possible level is of high clinical relevance. In dual-arc conventional volumetric modulated arc therapy (dac-VMAT), the large irradiation field for whole brain planned target volume (PTV) requires a wide jaw opening in which substantial low dose volume to the hippocampus may be produced due to suboptimal multi-leaf collimator (MLC) movements. The present study investigates the potential of a radiation therapy technique with split-arc and reduced field size, namely split-arc partial-field volumetric modulated arc therapy (sapf-VMAT) to spare the hippocampus during WBRT.Methods: Computed tomography and magnetic resonance images of 20 patients with brain metastases were retrieved in this retrospective planning study. The hippocampus was manually delineated by single radiation oncologist strictly following the RTOG 0933 atlas definition. Plans delivering 30 Gy in 10 fractions were generated for each patient using dac-VMAT and sapf-VMAT. Dosimetric parameters from both techniques were compared by paired t-test.Results: The results demonstrated that radiation dose to the hippocampus was significantly reduced using sapf-VMAT relative to dac-VMAT plans. sapf-VMAT (7.86Gy, p = 0.001) had significantly lowered average D100% compared to dac-VMAT (9.23 Gy). Decrease in hippocampus Dmax using sapf-VMAT (13.23 Gy, p = 0.001) was statistically significant when compared to dac-VMAT (16.33 Gy). The resulting mean dose to the hippocampus was 9.16 Gy for the for sapf-VMAT. Mean dose of sapf-VMAT was significantly lower than dac-VMAT (10.85 Gy, p < 0.05). In both eyes, sapf-VMAT demonstrated significantly lower Dmean compared to dac-VMAT (p < 0.05). Whole brain PTV coverage was not compromised in both techniques.Conclusion: sapf-VMAT has demonstrated significant dose reduction to the hippocampus and both eyes compared to dac-VMAT. [ABSTRACT FROM AUTHOR]

Background: This technical note aims to verify the hippocampus and adjacent organs at risk (OARs) sparing ability of an improved beam arrangement, namely hybrid split-arc partial-field volumetric modulated arc therapy (VMAT) (Hsapf-VMAT) during whole brain radiation therapy (WBRT)., Materials and Methods: Computed tomography simulation images of 22 patients with brain metastases were retrieved in this retrospective planning study. The hippocampus was manually delineated according to the criterion of RTOG 0933. Plans delivering 30 Gy in 10 fractions were generated for each patient using split-arc partial-field VMAT (sapf-VMAT) and Hsapf-VMAT. The sapf-VMAT plans consisted of 4 arc fields of 179.9° each with reduced field size. The Hsapf-VMAT consisted of 4 arc fields similar to sapf-VMAT in addition to 2 lateral opposing static fields. Statistical comparisons between treatment plans of both techniques were performed using the paired t-test at 5% level significance., Results: The results demonstrated that Hsapf-VMAT can achieve superior dose sparing in hippocampus which is comparable to sapf-VMAT (p > 0.05). In both eyes, Hsapf-VMAT had significantly lower D mean and D max compared to sapf-VMAT (p < 0.005). Decrease in D max of both lenses using Hsapf-VMAT (p < 0.005) were statistically significant when compared to sapf-VMAT. Hsapf-VMAT demonstrated significant reduction of D mean and D median to the optic nerves (p < 0.05). Whole brain planning target volume (PTV) coverage was not compromised in both techniques., Conclusion: The present study adopts a hybrid technique, namely Hsapf-VMAT, for hippocampal sparing WBRT. Hsapf-VMAT can achieve promising dose reduction to the hippocampus, both eyes and lenses. Therefore, Hsapf-VMAT can be considered an improved version of sapf-VMAT., Competing Interests: Conflict of interests None declared. Funding The authors declare no competing financial interests., (© 2022 Greater Poland Cancer Centre.)