Phase 1 Study of Hypofractionated Proton Beam Radiation Therapy in Adjuvant Pancreatic Cancer (PROTON-PANC).

PURPOSE: Despite improvement in systemic therapy, patients with pancreatic ductal adenocarcinoma (PDAC) frequently experience local recurrence. We sought to determine the safety of hypofractionated proton beam radiation therapy (PBT) during adjuvant chemotherapy. METHODS AND MATERIALS: Nine patients were enrolled in a single-institution phase 1 trial (NCT03885284) between 2019 and 2022. Patients had PDAC of the pancreatic head and underwent R0 or R1 resection and adjuvant modified FOLFIRINOX (mFFX) chemotherapy. The primary endpoint was to determine the dosing schedule of adjuvant PBT (5 Gy × 5 fractions) using limited treatment volumes given between cycles 6 and 7 of mFFX. Patients received PBT on days 15 to 19 in a 28-day cycle before starting cycle 7 (dose level 1, DL1) or on days 8 to 12 in a 21-day cycle before starting cycle 7 (DL2). RESULTS: The median patient age was 66 years (range, 52-78), and the follow-up time from mFFX initiation was 12.5 months (range, 6.2-37.4 months). No patients received preoperative therapy. Four had R1 resections and 5 had node-positive disease. Three patients were enrolled on DL1 and 6 patients on DL2. One dose-limiting toxicity (DLT) occurred at DL2 (prolonged grade 3 neutropenia resulting in discontinuation of mFFX after cycle 7). No other DLTs were observed. Four patients completed 12 cycles of mFFX (range, 7-12; median, 11). No patients have had local recurrence. Five of 9 patients had recurrence: 3 in the liver, 1 in the peritoneum, and 1 in the bone. Six patients are still alive, 4 of whom are recurrence-free. The median time to recurrence was 12 months (95% CI, 4 to not reached [NR]), and median overall survival was NR (95% CI, 6 to NR; 2-year survival rate, 57%). CONCLUSIONS: PBT integrated within adjuvant mFFX was well tolerated, and no local recurrence was observed. These findings warrant further exploration in a phase 2 trial.

Evaluación de la actividad antimicrobiana de extractos de hojas y semillas de Morinda citrifolia L. (noni) / Evaluation of the antimicrobial activity of extracts from leaves and seeds of Morinda citrifolia L. (noni)

INTRODUCCIÓN: reportes científicos han demostrado que la Morinda citrifolia L (noni) presenta actividad antimicrobiana frente a un gran número de bacterias y hongos patógenos, sin embargo estos estudios reportan estas propiedades para el fruto, existiendo poca información sobre las hojas, raíces y semillas de esta planta. OBJETIVOS: evaluar la actividad antimicrobiana in vitro de diferentes extractos de hojas secas y semillas de M. citrifolia L (noni), así como identificar mediante cromatografía de capa fina los principales metabolitos secundarios responsables de la actividad antimicrobiana. MÉTODOS: se evaluó la actividad antimicrobiana in vitro de los extractos alcohólicos, hexánicos, clorofórmicos y de acetato de etilo de las hojas y semillas de la M. citrifolia L. (noni) frente a cepas de E. coli, S. aureus y Candida sppor el método de Bauer-Kirby. Se identificaron mediante cromatografía de capa fina los metabolitos responsables de la actividad antimicrobiana en placas semi-preparativas de sílica gel, y se observaron los perfiles cromatográficos bajo la luz ultravioleta (l=365 nm). RESULTADOS: todos los extractos evaluados de las hojas y semillas de M. citrifolia L (noni) tuvieron actividad antimicrobiana frente a las cepas estudiadas. Los principales metabolitos secundarios detectados fueron, en los extractos de hojas, quinonas, coumarinas y flavonoides; en las semillas, coumarinas y flavonoides respectivamente. CONCLUSIONES: se demostró la actividad antimicrobiana de hojas y semillas del árbol de M. citrifolia L (noni), siendo los metabolitos secundarios quinonas y coumarinas los responsables de ésta.

INTRODUCTION: scientific studies have shown that Morinda citrifolia L. (noni) has antimicrobial activity against a large number of pathogenic bacteria and fungi. However, those studies report such activity in reference to the fruit, and there is little information about the leaves, roots and seeds of the plant. OBJECTIVES: evaluate the antimicrobial activity in vitro of various extracts from dry leaves and seeds of M. citrifoliaL. (noni) and identify by thin layer chromatography the main secondarymetabolites responsible for such antimicrobial activity. METHODS: an evaluation was conducted of the antimicrobial activity in vitro of alcoholic, hexanic, chloroformic and ethyl acetate extracts from leaves and seeds of M. citrifolia L. (noni) against E. coli, S. aureus and Candida sp. strains using the Bauer-Kirby method. Thin layer chromatography was used to identify the metabolites responsible for antimicrobial activity on semi-preparative silica gel plates. Chromatographic profiles were observed under ultraviolet light (l=365 nm). RESULTS: all the extracts evaluated of leaves and seeds of M. citrifolia L. (noni) had antimicrobial activity against the strains studied. The main secondary metabolites found were quinones, coumarins and flavonoids in the leaf extracts, and coumarins and flavonoids in the seed extracts. CONCLUSIONS: it was demonstrated that leaves and seeds of the M. citrifolia L. tree (noni) have antimicrobial activity, and that quinones and coumarins are the secondary metabolites responsible for such activity.

Evaluación de la actividad antimicrobiana de extractos de hojas y semillas de Morinda citrifolia L. (noni) / Evaluation of the antimicrobial activity of extracts from leaves and seeds of Morinda citrifolia L. (noni)

Introducción: reportes científicos han demostrado que la Morinda citrifolia L (noni) presenta actividad antimicrobiana frente a un gran número de bacterias y hongos patógenos, sin embargo estos estudios reportan estas propiedades para el fruto, existiendo poca información sobre las hojas, raíces y semillas de esta planta. Objetivos: evaluar la actividad antimicrobiana in vitro de diferentes extractos de hojas secas y semillas de M. citrifolia L (noni), así como identificar mediante cromatografía de capa fina los principales metabolitos secundarios responsables de la actividad antimicrobiana. Métodos: se evaluó la actividad antimicrobiana in vitro de los extractos alcohólicos, hexánicos, clorofórmicos y de acetato de etilo de las hojas y semillas de la M. citrifolia L. (noni) frente a cepas de E. coli, S. aureus y Candida sp por el método de Bauer-Kirby. Se identificaron mediante cromatografía de capa fina los metabolitos responsables de la actividad antimicrobiana en placas semi-preparativas de sílica gel, y se observaron los perfiles cromatográficos bajo la luz ultravioleta (l=365 nm). Resultados: todos los extractos evaluados de las hojas y semillas de M. citrifolia L (noni) tuvieron actividad antimicrobiana frente a las cepas estudiadas. Los principales metabolitos secundarios detectados fueron, en los extractos de hojas, quinonas, coumarinas y flavonoides; en las semillas, coumarinas y flavonoides respectivamente. Conclusiones: se demostró la actividad antimicrobiana de hojas y semillas del árbol de M. citrifolia L (noni), siendo los metabolitos secundarios quinonas y coumarinas los responsables de ésta(AU)

Introduction: scientific studies have shown that Morinda citrifolia L. (noni) has antimicrobial activity against a large number of pathogenic bacteria and fungi. However, those studies report such activity in reference to the fruit, and there is little information about the leaves, roots and seeds of the plant. Objectives: evaluate the antimicrobial activity in vitro of various extracts from dry leaves and seeds of M. citrifolia L. (noni) and identify by thin layer chromatography the main secondary metabolites responsible for such antimicrobial activity. Methods: an evaluation was conducted of the antimicrobial activity in vitro of alcoholic, hexanic, chloroformic and ethyl acetate extracts from leaves and seeds of M. citrifolia L. (noni) against E. coli, S. aureus and Candida sp. strains using the Bauer-Kirby method. Thin layer chromatography was used to identify the metabolites responsible for antimicrobial activity on semi-preparative silica gel plates. Chromatographic profiles were observed under ultraviolet light (l=365 nm). Results: all the extracts evaluated of leaves and seeds of M. citrifolia L. (noni) had antimicrobial activity against the strains studied. The main secondary metabolites found were quinones, coumarins and flavonoids in the leaf extracts, and coumarins and flavonoids in the seed extracts. Conclusions: it was demonstrated that leaves and seeds of the M. citrifolia L. tree (noni) have antimicrobial activity, and that quinones and coumarins are the secondary metabolites responsible for such activity(AU)

DTI at 7 and 3 T: systematic comparison of SNR and its influence on quantitative metrics.

Diffusion tensor imaging (DTI) and advanced related methods such as diffusion spectrum and kurtosis imaging are limited by low signal-to-noise ratio (SNR) at conventional field strengths. DTI at 7 T can provide increased SNR; however, B0 and B1 inhomogeneity and shorter T2⁎ still pose formidable challenges. The purpose of this study was to quantify and compare SNR at 7 and 3 T for different parallel imaging reduction factors, R, and TE, and to evaluate SNRs influences on fractional anisotropy (FA) and apparent diffusion coefficient (ADC). We found that R>4 at 7 T and R≥2 at 3 T were needed to reduce geometric distortions due to B0 inhomogeneity. For these R at 7 T, SNR was 70-90 for b=0 s/mm(2) and 22-28 for b=1000s/mm(2) in central brain regions. SNR was lower at 3 T (40 for b=0 s/mm(2) and 15 for b=1000 s/mm(2)) and in lateral brain regions at 7 T due to B1 inhomogeneity. FA and ADC did not change with MRI field strength, SENSE factor or TE in the tested range. However, the coefficient of variation for FA increased for SNR <15 and for SNR <10 in ADC, consistent with published theoretical studies. Our study demonstrates that 7 T is advantageous for DTI and lays the groundwork for further development. Foremost, future work should further address challenges with B0 and B1 inhomogeneity to take full advantage for the increased SNR at 7 T.

Qualitative and quantitative radio-anatomical variation of the posterior clinoid process.

This study was conducted to investigate the radiological anatomy of the posterior clinoid process (PCP) to highlight preoperative awareness of its variations and its relationships to other skull base landmarks. The PCPs of 36, three-dimensional computed tomographic cadaveric heads were evaluated by studying the gross anatomy of the PCP and by measuring the distances between the PCP and other skull base anatomical landmarks relevant to transnasal or transcranial skull base approaches. PCP variations were found in five specimens (14%): in two the dorsum sellae was absent, in one the PCP and the anterior clinoid process (ACP) were connected unilaterally and in two bilaterally. The mean distance between the right/left PCP and the crista galli was 45.14 ± 4.0 standard deviation (SD_/46.24 ± 4.5 SD, respectively, while the distance to the middle point of the basion at the level of the foramen magnum was 40.41 ± 5.1 SD/41.0 ± 5.2 SD, respectively. The mean distance between the PCP and the ACP was 12.03 ± 3.18 SD on the right side and 12.11 ± 2.77 SD on the left. The data provided highlights the importance of careful preoperative evaluation of the PCP and of its relationships to other commonly encountered skull base landmarks. This information may give an idea of the exposure achievable through different transcranial and transnasal approaches. This is especially relevant when neuronavigation is not available.

Residual magnetism in an MRI suite after field-rampdown: what are the issues and experiences?

PURPOSE: To investigate residual magnetization at different locations in the MRI suite at several time points prior, during and after field-rampdown with the goal to determine if the MRI suites could be reused in a clinical environment after the field-rampdown of MR scanners of different field strengths. MATERIALS AND METHODS: Residual magnetism was measured with two gaussmeters in the MRI suites of an 8 Tesla (T) and a 0.7T whole body magnet at several time points prior, during and after field-rampdown. RESULTS: Residual magnetism, in the MRI suite after controlled rampdown of an 8T superconducting magnet, was not significantly elevated compared with magnetic fields in the environment. Through 40 days, no significant changes in magnetism could be seen compared with initial measurements directly after rampdown, as both gaussmeters consistently measured. Similar findings were also observed after the quenched shutdown of a 0.7T system but a remanence was observed. CONCLUSION: A controlled rampdown of even an ultrahigh field MR system does not lead to retained magnetic contamination, while forced quenched rampdown of a mid-field system revealed temporary remanence. There is no need to degauss an MRI suite when an appropriate steel composition has been used in the iron shield.