Multi-institutional experience of MR-guided stereotactic body radiation therapy for adrenal gland metastases.

Purpose: While dose escalation is associated with improved local control (LC) for adrenal gland metastases (AGMs), the proximity of gastrointestinal (GI) organs-at-risk (OARs) limits the dose that can be safely prescribed via CT-based stereotactic body radiation therapy (SBRT). The advantages of magnetic resonance-guided SBRT (MRgSBRT), including tumor tracking and online plan adaptation, facilitate safe dose escalation. Methods: This is a multi-institutional review of 57 consecutive patients who received MRgSBRT on a 0.35-T MR linac to 61 AGMs from 2019 to 2021. The Kaplan-Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and LC, and the Cox proportional hazards model was utilized for univariate analysis (UVA). Results: Median follow up from MRgSBRT was 16.4 months (range [R]: 1.1-39 months). Median age was 67 years (R: 28-84 years). Primary histologies included non-small cell lung cancer (N = 38), renal cell carcinoma (N = 6), and melanoma (N = 5), amongst others. The median maximum diameter was 2.7 cm (R: 0.6-7.6 cm), and most AGMs were left-sided (N = 32). The median dose was 50 Gy (R: 30-60 Gy) in 5-10 fractions with a median BED10 of 100 Gy (R: 48-132 Gy). 45 cases (74 %) required adaptation for at least 1 fraction (median: 4 fractions, R: 0-10). Left-sided AGMs required adaptation in at least 1 fraction more frequently than right-sided AGMs (88 % vs 59 %, p = 0.018). There were 3 cases of reirradiation, including 60 Gy in 10 fractions (N = 1) and 40 Gy in 5 fractions (N = 2). One-year LC, PFS, and OS were 92 %, 52 %, and 78 %, respectively. On UVA, melanoma histology predicted for inferior 1-year LC (80 % vs 93 %, p = 0.012). There were no instances of grade 3+ toxicity. Conclusions: We demonstrate that MRgSBRT achieves favorable early LC and no grade 3 + toxicity despite prescribing a median BED10 of 100 Gy to targets near GI OARs.

Dosimetric comparison of magnetic resonance-guided radiation therapy, intensity-modulated proton therapy and volumetric-modulated arc therapy for distal esophageal cancer.

Advances in radiotherapy (RT) technologies permit significant decreases in the dose delivered to organs at risk (OARs) for patients with esophageal cancer (EC). Novel RT modalities such as proton beam therapy (PBT) and magnetic resonance-guided radiotherapy (MRgRT), as well as motion management techniques including breath hold (BH) are expected to further improve the therapeutic ratio. However, to our knowledge, the dosimetric benefits of PBT vs MRgRT vs volumetric-modulated arc therapy (VMAT) have not been directly compared for EC. We performed a retrospective in silico evaluation using the images and datasets of nine distal EC patients who were treated at our institution with a 0.35-Tesla MR linac to 50.4 Gy in 28 fractions in mid-inspiration BH (BH-MRgRT). Comparison free-breathing (FB) intensity-modulated PBT (FB-IMPT) and FB-VMAT plans were retrospectively created using the same prescription dose, target volume coverage goals, and OAR constraints. A 5 mm setup margin was used for all plans. BH-IMPT and BH-VMAT plans were not evaluated as they would not reflect our institutional practice. Planners were blinded to the results of the treatment plans created using different radiation modalities. The primary objective was to compare plan quality, target volume coverage, and OAR doses. All treatment plans met pre-defined target volume coverage and OAR constraints. The median conformity and homogeneity indices between FB-IMPT, BH-MRgRT and FB-VMAT were 1.13, 1.25, and 1.43 (PITV) and 1.04, 1.15, 1.04 (HI), respectively. For FB-IMPT, BH-MRgRT and FB-VMAT the median heart dose metrics were 52.8, 79.3, 146.8 (V30Gy, cc), 35.5, 43.8, 77.5 (V40Gy, cc), 16.9, 16.9, 32.5 (V50Gy, cc) and 6.5, 14.9, 17.3 (mean, Gy), respectively. Lung dose metrics were 8.6, 7.9, 18.5 (V20Gy, %), and 4.3, 6.3, 11.2 (mean, Gy), respectively. The mean liver dose (Gy) was 6.5, 19.6, 22.2 respectively. Both FB-IMPT and BH-MRgRT achieve substantial reductions in heart, lung, and liver dose compared to FB-VMAT. We plan to evaluate dosimetric outcomes across these RT modalities assuming consistent use of BH.

Surgically targeted radiation therapy (STaRT) for recurrent brain metastases: Initial clinical experience.

PURPOSE: This study evaluates the outcomes of recurrent brain metastasis treated with resection and brachytherapy using a novel Cesium-131 carrier, termed surgically targeted radiation therapy (STaRT), and compares them to the first course of external beam radiotherapy (EBRT). METHODS: Consecutive patients who underwent STaRT between August 2020 and June 2022 were included. All patients underwent maximal safe resection with pathologic confirmation of viable disease prior to STaRT to 60 Gy to a 5-mm depth from the surface of the resection cavity. Complications were assessed using CTCAE version 5.0. RESULTS: Ten patients with 12 recurrent brain metastases after EBRT (median 15.5 months, range: 4.9-44.7) met the inclusion criteria. The median BED10Gy90% and 95% were 132.2 Gy (113.9-265.1 Gy) and 116.0 Gy (96.8-250.6 Gy), respectively. The median maximum point dose BED10Gy for the target was 1076.0 Gy (range: 120.7-1478.3 Gy). The 6-month and 1-year local control rates were 66.7% and 33.3% for the prior EBRT course; these rates were 100% and 100% for STaRT, respectively (p < 0.001). At a median follow-up of 14.5 months, there was one instance of grade two radiation necrosis. Surgery-attributed complications were observed in two patients including pseudomeningocele and minor headache. CONCLUSIONS: STaRT with Cs-131 presents an alternative approach for operable recurrent brain metastases and was associated with superior local control than the first course of EBRT in this series. Our initial clinical experience shows that STaRT is associated with a high local control rate, modest surgical complication rate, and low radiation necrosis risk in the reirradiation setting.

Percutaneous pelvic fixation model: an affordable and realistic simulator for pelvic trauma training.

PURPOSE: To describe the construction and use of a percutaneous pelvic fixation model, evaluate its translational validity among fellowship-trained orthopedic trauma surgeons, and investigate the importance of specific criteria for effective competency-based assessment of pelvic fixation techniques. METHODS: Five orthopedic trauma surgeons were asked to place percutaneous wires on a pelvic fixation model, including anterior column (antegrade/retrograde), posterior column (antegrade/retrograde), supra-acetabular, transsacral, and iliosacral. Evaluation criteria included successful wire placement, redirections, cortical breaches, procedure duration, radiation exposure, and quality of fluoroscopic views. Following completion, participants were provided a survey to rate the model. RESULTS: There were no differences between approaches on successful screw placement, wire redirections, or fluoroscopic quality. Antegrade approaches to the anterior and posterior columns took longer (p = 0.008) and used more radiation (p = 0.02). There was also a trend toward more cortical breaches with the antegrade anterior column approach (p = 0.07). Median ratings among surgeons were 4 out of 5 for their overall impression and its accuracy in tactile response, positioning constraints, and fluoroscopic projections. Learning parameters considered most important to the progression of trainees (most to least important) were successful screw placement, corridor breaches, wire redirections, quality of fluoroscopic views, radiation exposure, and procedure duration. CONCLUSION: In being affordable, accessible, and realistic, this percutaneous pelvic fixation model represents an opportunity to advance orthopedic surgery education globally. Future research is needed to validate the findings of this pilot study and to expand upon how trainees should be evaluated within simulations and the operating room to optimize skill progression.

Perioperative management of aortic stenosis in patients undergoing non-cardiac surgery.

Aortic stenosis is one of the most common cardiac valve pathologies in the world and its prevalence increases with age. Although previously associated with increased perioperative mortality, more recent studies suggest that mortality rates may be decreasing. Recent guidelines suggest that major non-cardiac surgery can be performed safely in asymptomatic severe aortic stenosis patients with close hemodynamic monitoring. Among symptomatic patients, the guidelines recommend aortic valve intervention prior to major non-cardiac surgery because of a reduction in the incidence of postoperative heart failure and improved rates of long-term overall survival. This review provides a comprehensive and contemporary review of the perioperative management of patients with severe aortic valve stenosis.

Treatment of glioblastoma using MRIdian® A3i BrainTx™: Imaging and treatment workflow demonstration.

For patients with newly diagnosed glioblastoma, the current standard-of-care includes maximal safe resection, followed by concurrent chemoradiotherapy and adjuvant temozolomide, with tumor treating fields. Traditionally, diagnostic imaging is performed pre- and post-resection, without additional dedicated longitudinal imaging to evaluate tumor volumes or other treatment-related changes. However, the recent introduction of MR-guided radiotherapy using the ViewRay MRIdian A3i system includes a dedicated BrainTx package to facilitate the treatment of intracranial tumors and provides daily MR images. We present the first reported case of a glioblastoma imaged and treated using this workflow. In this case, a 67-year-old woman underwent adjuvant chemoradiotherapy after gross total resection of a left frontal glioblastoma. The radiotherapy treatment plan consisted of a traditional two-phase design (46 Gy followed by a sequential boost to a total dose of 60 Gy at 2 Gy/fraction). The treatment planning process, institutional workflow, treatment imaging, treatment timelines, and target volume changes visualized during treatment are presented. This case example using our institutional A3i system workflow successfully allows for imaging and treatment of primary brain tumors and has the potential for margin reduction, detection of early disease progression, or to detect the need for dose adaptation due to interfraction tumor volume changes.

Multi-Institutional Outcomes of Patients Aged 75 years and Older With Pancreatic Ductal Adenocarcinoma Treated With 5-Fraction Ablative Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy (A-SMART).

PURPOSE: Treatment options for pancreatic ductal adenocarcinoma (PDAC) are commonly limited for patients with advanced age due to medical comorbidities and/or poor performance status. These patients may not be candidates for more aggressive chemotherapy regimens and/or surgical resection leaving few, if any, other effective treatments. Ablative stereotactic MRI-guided adaptive radiation therapy (A-SMART) is both efficacious and safe for PDAC and can achieve excellent long-term local control, however, the appropriateness of A-SMART for elderly patients with inoperable PDAC is not well understood. METHODS: A retrospective analysis was performed of inoperable non-metastatic PDAC patients aged 75 years or older treated on the MRIdian Linac at 2 institutions. Clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional (LRC). Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE, v5). RESULTS: A total of 49 patients were evaluated with a median age of 81 years (range, 75-91) and a median follow-up of 14 months from diagnosis. PDAC was classified as locally advanced (46.9%), borderline resectable (36.7%), or medically inoperable (16.3%). Neoadjuvant chemotherapy was delivered to 84% of patients and all received A-SMART to a median 50 Gy (range, 40-50 Gy) in 5 fractions. 1 Year LRC, PFS, and OS were 88.9%, 53.8%, and 78.9%, respectively. Nine patients (18%) had resection after A-SMART and benefited from PFS improvement (26 vs 6 months, P = .01). ECOG PS <2 was the only predictor of improved OS on multivariate analysis. Acute and late grade 3 + toxicity rates were 8.2% and 4.1%, respectively. CONCLUSIONS: A-SMART is associated with encouraging LRC and OS in elderly patients with initially inoperable PDAC. This novel non-invasive treatment strategy appears to be well-tolerated in patients with advanced age and should be considered in this population that has limited treatment options.

Causes of Death Among Patients With Initially Inoperable Pancreas Cancer After Induction Chemotherapy and Ablative 5-fraction Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy.

Purpose: Nearly all patients with pancreatic ductal adenocarcinoma (PDAC) eventually die of progressive cancer after exhausting treatment options. Although distant metastases (DMs) are a common cause of death, autopsy studies have shown that locoregional progression may be directly responsible for up to one-third of PDAC-related deaths. Ablative stereotactic magnetic resonance-guided adaptive radiation therapy (A-SMART) is a novel treatment strategy that appears to improve locoregional control compared with nonablative radiation therapy, potentially leading to improved overall survival. Methods and Materials: A single-institution retrospective analysis was performed of patients with nonmetastatic inoperable PDAC treated between 2018 to 2020 using the MRIdian Linac with induction chemotherapy, followed by 5-fraction A-SMART. We identified causes of death that occurred after A-SMART. Results: A total of 62 patients were evaluated, of whom 42 (67.7%) had died. The median follow-up time was 18.6 months from diagnosis and 11.0 months from A-SMART. Patients had locally advanced (72.6%), borderline resectable (22.6%), or resectable but medically inoperable PDAC (4.8%). All patients received induction chemotherapy, typically leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin (69.4%) or gemcitabine/nab-paclitaxel (24.2%). The median prescribed dose was 50 Gy (range, 40-50), corresponding to a median biologically effective dose of 100 Gy10. Post-SMART therapy included surgery (22.6%), irreversible electroporation (9.7%), and/or chemotherapy (51.6%). Death was attributed to locoregional progression, DMs, cancer-related cachexia/malnutrition, surgery/irreversible electroporation complications, other reasons not due to cancer progression, or unknown causes in 7.1%, 45.2%, 11.9%, 9.5%, 11.9%, and 14.3% of patients, respectively. Intra-abdominal metastases of the liver and peritoneum were responsible for 84.2% of deaths from DMs. Conclusions: To our knowledge, this is the first contemporary evaluation of causes of death in patients with PDAC receiving dose-escalated radiation therapy. We demonstrated that the predominant cause of PDAC-related death was from liver and peritoneal metastases; therefore novel treatment strategies are indicated to address occult micrometastatic disease at these sites.

Salud y prevención en la preparación del Licenciado en Educación, especialidad Pedagogía-Psicología / Health and prevention in the training of the Bachelor of Education, specialty Pedagogy-Psychology

Fundamento: constituye una necesidad para la educación superior y el sistema cubano de salud fomentar el desarrollo de las habilidades profesionales pedagógicas en los estudiantes universitarios en los diferentes escenarios de la disciplina Educación Física, sustentada en prácticas saludables y estilos de vida sanos. Objetivo: construir un modelo de diseño curricular para la formación de la habilidad profesional de orientación educativa en temas de salud y prevención en los estudiantes de la Licenciatura en Educación, especialidad Pedagogía-Psicología. Métodos: se realizó una investigación con enfoque cualitativo en la sede pedagógica de la Universidad Central "Marta Abreu" de Las Villas durante el periodo 2015-2020 cuyo objeto de estudio fue la formación de las habilidades profesionales pedagógicas en los estudiantes de Pedagogía-Psicología. Para ello se emplearon métodos teóricos y empíricos predominantemente cualitativos. Resultados: se fundamentó el proceso de diseño de un modelo de formación de la habilidad profesional pedagógica de orientación educativa para desarrollar y formar acciones en temas de salud y prevención en los estudiantes universitarios de la carrera Licenciatura en Educación Pedagogía-Psicología. Contiene la determinación de necesidades, un sistema de acciones necesarias para la formación, ofrece recomendaciones metodológicas y finalmente se centra en la evaluación de los resultados una vez ejecutado. Conclusiones: el modelo fue valorado por criterios de expertos con predominio de Muy Adecuado por su pertinencia, factibilidad de aplicación y contribución al objetivo para el cual fue diseñado.

Background: it is a necessity for higher education and the Cuban health system to promote the development of professional pedagogical skills in university students in the different scenarios of the Physical Education discipline, supported by healthy practices and healthy lifestyles. Objective: to build a model of curricular design for the training of the professional skill of educational orientation in health and prevention issues in the students of the Bachelor of Education, specialty Pedagogy-Psychology. Methods: a research within the qualitative approach was carried out at the pedagogical university site of "Marta Abreu" Central University of Las Villas from 2015 to 2020 whose object of study was the training of professional pedagogical skills in Pedagogy-Psychology students. For this, predominantly qualitative theoretical and empirical methods were used. Results: the process of designing a training model for the professional pedagogical skill of educational orientation was based to develop and train actions on health and prevention issues in university students of the Bachelor of Education Pedagogy-Psychology degree. It contains the determination of needs, a system of actions necessary for training, it offers methodological recommendations and finally focuses on the evaluation of the results once implemented. Conclusions: the model was valued by expert criteria with a predominance of Very Adequate for its relevance, feasibility of application and contribution to the objective for which it was designed.

Vigilancia epidemiológica del dengue en la provincia Camagüey, Cuba

Introducción: La vigilancia es un componente esencial en el trabajo cotidiano en todos los niveles del Sistema Nacional de Salud en Cuba. El dengue una enfermedad reemergente, de estricta vigilancia y control en el país. Objetivo: Caracterizar la vigilancia epidemiológica del dengue en Camagüey durante el año 2021. Métodos: Investigación observacional, descriptiva, transversal realizada desde el 1 de enero hasta el 31 de diciembre de 2021. El universo de estudio estuvo constituido por 13 961 pacientes con síndrome febril inespecífico notificados por el departamento de estadística provincial en ese año y que cumplieron con los criterios de inclusión y exclusión. Resultados: Se ingresaron el 99,9 % de los pacientes con síndrome febril inespecífico informados, 50,2 % ingresó en las primeras 24 horas, el 19 % en las 48 y 30,8 % en 72 horas y más. El 97,7 % de las inmunoglobulinas M reactivas correspondientes a pacientes en la provincia, se comportaron como dengue sin signos de alarma, 2,1 % como dengue con signos de alarma y solo 0,2 % manifestaron formas grave de la enfermedad. Conclusiones: Se ingresa un alto porcentaje de enfermos con síndrome febril inespecífico detectados por los sistemas de vigilancia. La mitad de los pacientes febriles registrados ingresaron oportunamente. El uso de la clasificación operacional del dengue propuesto por la Organización Mundial de la Salud permitió que un porcentaje muy bajo de los pacientes manifestaran formas graves de la enfermedad.

Introduction: Surveillance is an essential component in the daily work at all levels of the National Health System in Cuba. Dengue is a re-emerging disease, under strict surveillance and control in the country. Objective: To characterize the epidemiological surveillance of dengue in Camagüey during 2021. Methods: An observational, descriptive, cross-sectional research was carried out from January 1 to December 31, 2021. The study universe consisted of 13,961 patients with nonspecific febrile syndrome notified by the provincial statistics department in that year and who met the inclusion and exclusion criteria. Results: 99.9% of the reported patients with nonspecific febrile syndrome were admitted, 50.2% admitted in the first 24 hours, 19% in 48 and 30.8% in 72 hours and more. 97.7% of the reactive immunoglobulins M corresponding to patients in the province behaved like dengue without alarm signs, 2.1% like dengue with alarm signs and only 0.2% manifested severe forms of the disease. Conclusions: High percentage of patients with non-specific febrile syndrome detected by surveillance systems are admitted. Half of the registered febrile patients were admitted timely. The use of the operational classification of dengue proposed by the World Health Organization allowed a very low percentage of patients to manifest severe forms of the disease.

[Transnasal endoscopic skull base surgery: analysis of complications in the first 120 procedures]. / Cirugía endoscópica transnasal de base de cráneo: Análisis de las complicaciones en los primeros 120 procedimientos.

Background: The endonasal endoscopic approach (EEA) has potential advantages over traditional open approaches. However, complications such as cerebrospinal fluid (CFS) leak, visual disturbances, and postoperative meningitis have been described. The aim was to present the experience accumulated in 120 cases of skull base EEA performed by the same surgical team and describe and analyze the main postoperative complications according to the complexity of the cases. Methods: Retrospective study on our database of patients undergoing skull base EEA for various pathologies between July 2011 and March 2022. Results: 120 skull base EEA surgeries were analyzed. 57.14% were performed on women. The median age was 44 years. 26.66% were reinterventions. The most frequent pathology was pituitary adenoma (49.17%) followed by CSF leak (8.33%). The most used EEA was the transelar 65.83%. 26 complications were recorded, with no differences according to complexity. There were 13 cases of diabetes insipidus (DI) and 8 of CSF leak. This was more frequent in patients with intraoperative CSF leak. The median hospital stay was 5.5 days. Conclusion: Skull base EEA has become increasingly common for the surgical management of skull base pathology, with a low frequency of immediate postoperative complications and low mortality. The improvement of the technique and the improvement in postoperative care are associated with a shorter hospital stay.

Induction Chemotherapy and Ablative Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy for Inoperable Pancreas Cancer.

Background: Radiation therapy (RT) dose for inoperable pancreatic ductal adenocarcinoma (PDAC) has historically been non-ablative to avoid injuring gastrointestinal (GI) organs at risk (OARs). Accruing data suggest that dose escalation, in select patients, may significantly improve clinical outcomes. Early results of ablative stereotactic magnetic resonance image-guided adaptive radiation therapy (A-SMART) have been encouraging, although long-term outcomes are not well understood. Methods: A single institution retrospective analysis was performed of inoperable non-metastatic PDAC patients who received induction chemotherapy then 5-fraction A-SMART on a 0.35T-MR Linac from 2018-2021. Results: Sixty-two patients were evaluated with a median age of 66 years (range 35-91) and nearly all achieved Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (96.8%). Locally advanced disease was common (72.6%), otherwise borderline resectable (22.6%), or medically inoperable (4.8%). All received induction chemotherapy for a median 4.2 months (range, 0.2-13.3) most commonly FOLFIRINOX (n=43; 69.4%). Median prescribed dose was 50 Gy (range 40-50); median biologically effective dose (BED10) was 100 Gy10. The median local control (LC), progression-free survival (PFS), and overall survival (OS) from diagnosis were not reached, 20 months, and 23 months, respectively. Also, 2-year LC, PFS, and OS were 68.8%, 40.0%, and 45.5%, respectively. Acute and late grade 3+ toxicity rates were 4.8% and 4.8%, respectively. Conclusions: To our knowledge, this is the largest series of induction chemotherapy followed by ablative 5-fraction SMART delivered on an MR Linac for inoperable PDAC. The potential for this novel treatment strategy is to achieve long-term LC and OS, compared to chemotherapy alone, and warrants prospective evaluation.

Rectovaginal Colonization with Serotypes of Group B Streptococci with Reduced Penicillin Susceptibility among Pregnant Women in León, Nicaragua.

Group B Streptococci (GBS) are important causes of neonatal sepsis and meningitis globally. To elucidate the potential benefits of maternal GBS vaccines, data is needed on the epidemiology of maternal GBS rectovaginal colonization, distribution of serotypes, and resistance to intrapartum antibiotic prophylaxis (IAP). We collected rectal and vaginal samples from 305 pregnant women in León, Nicaragua between 35 and 40 weeks gestation. Samples were cultured for GBS and confirmed using latex agglutination. GBS isolates underwent serotyping by quantitative polymerase chain reaction, and antimicrobial susceptibility testing by disk diffusion and microdilution following Clinical Laboratory Standard Institute guidelines. Sixty-three women (20.7%) were colonized with GBS in either the rectum or the vagina. Of 91 GBS isolates collected from positive cultures, most were serotypes II (28.6%), Ia (27.5%), and III (20.9%). Most GBS isolates (52.9%) were resistant to penicillin, the first-line prophylactic antibiotic. Penicillin resistance was highly correlated with resistance to vancomycin, ceftriaxone, and meropenem. The results of our study suggest that one-fifth of pregnant women in the urban area of León, Nicaragua are colonized with GBS and risk transmitting GBS to their offspring during labor. High resistance to commonly available antibiotics in the region suggests that prophylactic maternal GBS vaccination would be an effective alternative to IAP.

Diversification of Amidyl Radical Intermediates Derived from C-H Aminopyridylation.

The N-activating substituents typically encountered in C-H amination chemistry are challenging to remove and have limited scope for synthetic elaboration. Here, we demonstrate that N-benzylaminopyridinium species provide a platform for synthetic elaboration via reductive N-N bond activation to unveil electrophilic N-centered radicals. These reactive intermediates can be trapped either via anti-Markovnikov olefin carboamination to provide access to tetrahydroisoquinolines or via aza-Rubottom chemistry with silyl enol ethers to provide α-amino ketones.

Traceless Benzylic C-H Amination via Bifunctional N-Aminopyridinium Intermediates.

C-H amination reactions provide the opportunity to streamline the synthesis of nitrogen-containing organic small molecules. The impact of intermolecular C-H amination methods, however, is currently limited the frequent requirement for the amine precursors to bear activating groups, such as N-sulfonyl substituents, that are both challenging to remove and not useful synthetic handles for subsequent derivatization. Here, we introduce traceless nitrogen activation for C-H amination-which enables application of selective C-H amination chemistry to the preparation of diverse N-functionalized products-via sequential benzylic C-H N-aminopyridylation followed by Ni-catalyzed C-N cross-coupling with aryl boronic acids. Unlike many C-H amination reactions that provide access to protected amines, the current method installs an easily diversifiable synthetic handle that serves as a lynchpin for C-H amination, deaminative N-N functionalization sequences.

Dose-Escalated Magnetic Resonance Image-Guided Abdominopelvic Reirradiation With Continuous Intrafraction Visualization, Soft Tissue Tracking, and Automatic Beam Gating.

PURPOSE: Compared with computed tomography, magnetic resonance (MR) image guidance offers significant advantages for radiation therapy (RT) that may be particularly beneficial for reirradiation (reRT). However, clinical outcomes of MR-guided reRT are not well described in the published literature. METHODS AND MATERIALS: We performed a single-institution retrospective safety and efficacy analysis of reRT patients treated on the MRIdian Linac to targets within the abdomen or pelvis using continuous intrafraction MR-based motion management with automatic beam triggering. Fiducial markers were not used. RESULTS: We evaluated 11 patients who received prior RT to a median of 50 Gy (range, 30-58.8 Gy) in 25 fractions (range, 5-28 fractions). The median interval to reRT was 26.8 months. The most frequently retreated sites were nodal metastases (36.4%) and pancreatic cancer (27.3%). The median reRT dose was 40 Gy (range, 25-54 Gy) in 6 fractions (range, 5-36 fractions); ultrahypofractionation (63.6%) was more common than hyperfractionation (36.4%). Daily on-table adaptive replanning was used for 3 patients (27.3%). With a median of 14 months' follow-up from reRT completion (range, 6-32 months), the median and 1-year freedom from local progression were 29 months and 88.9%, respectively, and the median and 1-year overall survival were 17.5 months and 70.0%, respectively. One patient (9.1%) experienced acute grade 2 toxic effects; there were no acute or late treatment-related toxic effects of grade 3 or greater. CONCLUSIONS: Magnetic resonance-guided reRT appeared to be feasible and may facilitate safe dose escalation. Additional follow-up is needed to better assess long-term efficacy and late toxic effects. Prospective evaluation of this novel treatment strategy is warranted.

Largest neurosurgical social media group and its impact on communication and research.

BACKGROUND: The use of social media to communicate and disseminate knowledge has increased exponentially, especially in the field of neurosurgery. 'Neurosurgery cocktail' (NC) was developed by a group of young neurosurgeons as a means of sharing didactic materials and clinical experiences via social media. It connects 35.000 neurosurgeons worldwide on multiple platforms, primarily Facebook and Twitter. Given the rising utilization of social media in neurosurgery, the popularity of NC has also increased since its inception. In this study, the authors surveyed the social media analytics of NC for both Facebook and Twitter. Besides, we reviewed the literature on the use of social media in neurosurgery. METHODS: Facebook and Twitter metrics were extracted through each respective platform's analytics tools from December 2020 (earliest available date for data analysis) through January 2021. A literature search was conducted using PubMed (MEDLINE) and Scopus databases. RESULTS: On Facebook, as of January 2021, the group had a total of 25.590 members (87.6% male), most commonly (29%) between 35 and 44 years of age with over 100 countries were represented. As of January 2021, they had amassed 6457 followers on Twitter. During the last 28 d between December 2020 and January 2021, the account published 65 tweets that garnered a total of 196,900 impressions. Twelve articles were identified in our literature review on the use of social media within the neurosurgical community. CONCLUSIONS: NC is one of the most widely utilized neurosurgical social media resources available. Sharing knowledge has been broadened thanks to the recent social media evolution, and NC has become a leading player in disseminating neurosurgical knowledge.

Initial clinical experience with magnetic resonance-guided radiotherapy in pediatric patients: Lessons learned from a single institution with proton therapy.

Purpose/Objectives: Magnetic resonance-guided radiotherapy (MRgRT) is increasingly used in a variety of adult cancers. To date, published experience regarding the use of MRgRT in pediatric patients is limited to two case reports. We report on the use of MRgRT for pediatric patients at our institution during a four-year period and describe important considerations in the selection and application of this technology in children. Materials/Methods: All patients treated with MRgRT since inception at our institution between 4/2018 and 4/2022 were retrospectively reviewed. We also evaluated all pediatric patients treated at our institution during the same period who received either imaging or treatment using our magnetic resonance-guided linear accelerator (MR Linac). We summarize four clinical cases where MRgRT was selected for treatment in our clinic, including disease outcomes and toxicities and describe our experience using the MR Linac for imaging before and during treatment for image fusion and tumor assessments. Results: Between 4/2018 and 4/2022, 535 patients received MRgRT at our center, including 405 (75.7%) with stereotactic ablative radiotherapy (SABR). During this period, 347 distinct radiotherapy courses were delivered to pediatric patients, including 217 (62.5%) with proton therapy. Four pediatric patients received MRgRT. One received SABR for lung metastasis with daily adaptive replanning and a second was treated for liver metastasis using a non-adaptive workflow. Two patients received fractionated MRgRT for an ALK-rearranged non-small cell lung cancer and neuroblastoma. No Grade 2 or higher toxicities were observed or reported during MRgRT or subsequent follow-up. Twelve patients underwent MR imaging without contrast during treatment for brain tumors to assess for tumor/cystic changes. Two patients treated with other modalities underwent MR simulation for target volume delineation and organ at risk sparing due to anatomic changes during treatment or unexpected delays in obtaining diagnostic MR appointments. Conclusions: In four pediatric patients treated with MRgRT, treatment was well tolerated with no severe acute effects. At our center, most pediatric patients are treated with proton therapy, but the cases selected for MRgRT demonstrated significant organ at risk sparing compared to alternative modalities. In particular, MRgRT may provide advantages for thoracic/abdominal/pelvic targets using gated delivery and adaptive replanning, but selected patients treated with fractionated radiotherapy may also benefit MRgRT through superior organ at risk sparing.