Sermon panegyrico que en la solemne fiesta ... de San Martin de la Ciudad de Salamanca predicó ... Miguel Geronymo de Ucar, de la Compañía de Jesus ...

Fecha de la licencia: 1716Sign.: [calderón]4, A-C4, D2Apostillas marginalesPort. orladaCopia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 201

Surgery After Neoadjuvant Stereotactic MRI Guided Adaptive Radiation in Pancreatic Cancer: Multi-institutional Toxicity and Survival Outcomes

Background: Favorable toxicity and survival outcomes after dose escalated stereotactic MR guided adaptive radiation therapy (SMART) have been recently published for locally advanced (LA) and borderline resectable (BR) pancreatic cancer. Perioperative morbidity and mortality are not well understood after ablative radiation therapy, which may temper enthusiasm for offering surgery. Objectives: The purpose of this study was to investigate survival and toxicity in resected pancreas cancer patients after neoadjuvant ablative SMART. Methods: In this IRB approved analysis, we retrospectively reviewed 33 consecutive patients with resectable, BR, and LA pancreatic cancer based on NCCN 2.2021 staging criteria who were treated at 2 institutions from 2017-2020 with neoadjuvant SMART 50 Gy in 5 fractions on a 0.35T MR Linac and later underwent definitive surgical resection. Overall survival (OS) and locoregional control (LRC) were evaluated by Kaplan-Meier method. Results: Median follow up was 22.4 months from diagnosis and 17.8 months from last day of RT. Most had BR (55%), otherwise initially resectable (33%) or LA (12%) pancreatic cancer. Median duration of induction chemotherapy was 3.5 (SD 1.6) months with most common regimens being FOLFIRINOX (74%), gemcitabine/abraxane (24%) and FOLFOX (3%). Performance status was ECOG 0, 1, 2 in 16 (48.5%), 12 (36.4%), and 5 (15.2%), respectively. Whipple was performed in 27 (82%) of patients, distal pancreatectomy in 4 (12%), and total pancreatectomy in 2 (6%). The median duration from SMART completion to surgery was 6.9 weeks (4.7-44.1). R0 resections were achieved in 28 (84.8%) of patients with the rest being R1, all in BR patients. Vascular resection/reconstruction was performed of the portal vein (PV) in 8 (24.2%) patients, SMV in 4 (12%), SMA in 1 (3%), and common hepatic artery in 2 (6%). Vascular resection/reconstruction was performed in all LA patients. Median OS, 1-year OS, and 2-year OS from diagnosis were 29.6 months, 93.8%, 81.5%, respectively. Median OS from RT was not yet reached; 1-year OS was 90.9%. LRC at 1 and 2 years was 97% and 93%, respectively. Radiation related acute and late grade 3+ gastrointestinal toxicity was seen in 2 (6%) and 2 (6%) patients. Post-op mortality at 30 and 90 days was seen 2 (6%) and 3 (9%) of patients with 1 death from GI bleed attributed to surgery and 1 death from hepatic ischemia related to PV resection. Conclusions: To the best of our knowledge, this is the first report suggesting that surgery for pancreas cancer after dose escalated 5-fraction SMART is feasible. Further clarification is needed with respect to ideal patient selection and timing for surgery, the safety of arterial versus venous resection/reconstruction, and histopathologic response after delivery of ablative versus non-ablative radiation dose

Surgery After Neoadjuvant Stereotactic MRI Guided Adaptive Radiation in Pancreatic Cancer: Multi-institutional Toxicity and Survival Outcomes

Background: Favorable toxicity and survival outcomes after dose escalated stereotactic MR guided adaptive radiation therapy (SMART) have been recently published for locally advanced (LA) and borderline resectable (BR) pancreatic cancer. Perioperative morbidity and mortality are not well understood after ablative radiation therapy, which may temper enthusiasm for offering surgery. Objectives: The purpose of this study was to investigate survival and toxicity in resected pancreas cancer patients after neoadjuvant ablative SMART. Methods: In this IRB approved analysis, we retrospectively reviewed 33 consecutive patients with resectable, BR, and LA pancreatic cancer based on NCCN 2.2021 staging criteria who were treated at 2 institutions from 2017-2020 with neoadjuvant SMART 50 Gy in 5 fractions on a 0.35T MR Linac and later underwent definitive surgical resection. Overall survival (OS) and locoregional control (LRC) were evaluated by Kaplan-Meier method. Results: Median follow up was 22.4 months from diagnosis and 17.8 months from last day of RT. Most had BR (55%), otherwise initially resectable (33%) or LA (12%) pancreatic cancer. Median duration of induction chemotherapy was 3.5 (SD 1.6) months with most common regimens being FOLFIRINOX (74%), gemcitabine/abraxane (24%) and FOLFOX (3%). Performance status was ECOG 0, 1, 2 in 16 (48.5%), 12 (36.4%), and 5 (15.2%), respectively. Whipple was performed in 27 (82%) of patients, distal pancreatectomy in 4 (12%), and total pancreatectomy in 2 (6%). The median duration from SMART completion to surgery was 6.9 weeks (4.7-44.1). R0 resections were achieved in 28 (84.8%) of patients with the rest being R1, all in BR patients. Vascular resection/reconstruction was performed of the portal vein (PV) in 8 (24.2%) patients, SMV in 4 (12%), SMA in 1 (3%), and common hepatic artery in 2 (6%). Vascular resection/reconstruction was performed in all LA patients. Median OS, 1-year OS, and 2-year OS from diagnosis were 29.6 months, 93.8%, 81.5%, respectively. Median OS from RT was not yet reached; 1-year OS was 90.9%. LRC at 1 and 2 years was 97% and 93%, respectively. Radiation related acute and late grade 3+ gastrointestinal toxicity was seen in 2 (6%) and 2 (6%) patients. Post-op mortality at 30 and 90 days was seen 2 (6%) and 3 (9%) of patients with 1 death from GI bleed attributed to surgery and 1 death from hepatic ischemia related to PV resection. Conclusions: To the best of our knowledge, this is the first report suggesting that surgery for pancreas cancer after dose escalated 5-fraction SMART is feasible. Further clarification is needed with respect to ideal patient selection and timing for surgery, the safety of arterial versus venous resection/reconstruction, and histopathologic response after delivery of ablative versus non-ablative radiation dose

Sermon, que predico a la eleccion del señor Don Luis Gomez de Parada, en Rector de la ... Universidad de Salamanca, el dia del glorioso S. Nicolas Obispo ...

Copia digital. Madrid : Ministerio de Cultura. Dirección General del Libro, Archivos y Bibliotecas, 2010Sign.: [calderón]\p4\s, A-C\p4\sPort. con orla tip

Sestrins induce natural killer function in senescent-like CD8(+) T cells

Aging is associated with remodeling of the immune system to enable the maintenance of life-long immunity. In the CD8⁺ T cell compartment, aging results in the expansion of highly differentiated cells that exhibit characteristics of cellular senescence. Here we found that CD27⁻CD28⁻CD8⁺ T cells lost the signaling activity of the T cell antigen receptor (TCR) and expressed a protein complex containing the agonistic natural killer (NK) receptor NKG2D and the NK adaptor molecule DAP12, which promoted cytotoxicity against cells that expressed NKG2D ligands. Immunoprecipitation and imaging cytometry indicated that the NKG2D-DAP12 complex was associated with sestrin 2. The genetic inhibition of sestrin 2 resulted in decreased expression of NKG2D and DAP12 and restored TCR signaling in senescent-like CD27⁻CD28⁻CD8⁺ T cells. Therefore, during aging, sestrins induce the reprogramming of non-proliferative senescent-like CD27⁻CD28⁻CD8⁺ T cells to acquire a broad-spectrum, innate-like killing activity

Estimating a threshold price for CO2 emissions of buildings to improve their energy performance level. Case study of a new Spanish home

Energy consumption in homes produces CO2. In many countries, building regulations are being set to enable energy efficiency performance levels to be issued. In Spain, there is a regulated procedure to certify the energy performance of buildings according to their CO2 emissions. Consequently, some software tools have been design to simulate buildings and to obtain their energy consumption and CO2 emissions. In this paper the investment, maintenance and energy consumption costs are calculated for different energy performance levels and for various climatic zones, in a single-family home. According to the results, more energy efficient buildings imply higher construction and maintenance costs, which are not compensated by lower energy costs. Therefore, under current conditions, economic criteria do not support the improvement of the energy efficiency of a dwelling. 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Carglumic acid enhances rapid ammonia detoxification in classical organic acidurias with a favourable risk-benefit profile: A retrospective observational study

BACKGROUND: Isovaleric aciduria (IVA), propionic aciduria (PA) and methylmalonic aciduria (MMA) are inherited organic acidurias (OAs) in which impaired organic acid metabolism induces hyperammonaemia arising partly from secondary deficiency of N-acetylglutamate (NAG) synthase. Rapid reduction in plasma ammonia is required to prevent neurological complications. This retrospective, multicentre, open-label, uncontrolled, phase IIIb study evaluated the efficacy and safety of carglumic acid, a synthetic structural analogue of NAG, for treating hyperammonaemia during OA decompensation. METHODS: Eligible patients had confirmed OA and hyperammonaemia (plasma NH3 > 60 μmol/L) in ≥1 decompensation episode treated with carglumic acid (dose discretionary, mean (SD) first dose 96.3 (73.8) mg/kg). The primary outcome was change in plasma ammonia from baseline to endpoint (last available ammonia measurement at ≤18 hours after the last carglumic acid administration, or on Day 15) for each episode. Secondary outcomes included clinical response and safety. RESULTS: The efficacy population (received ≥1 dose of study drug and had post-baseline measurements) comprised 41 patients (MMA: 21, PA: 16, IVA: 4) with 48 decompensation episodes (MMA: 25, PA: 19, IVA: 4). Mean baseline plasma ammonia concentration was 468.3 (±365.3) μmol/L in neonates (29 episodes) and 171.3 (±75.7) μmol/L in non-neonates (19 episodes). At endpoint the mean plasma NH3 concentration was 60.7 (±36.5) μmol/L in neonates and 55.2 (±21.8) μmol/L in non-neonates. Median time to normalise ammonaemia was 38.4 hours in neonates vs 28.3 hours in non-neonates and was similar between OA subgroups (MMA: 37.5 hours, PA: 36.0 hours, IVA: 40.5 hours). Median time to ammonia normalisation was 1.5 and 1.6 days in patients receiving and not receiving concomitant scavenger therapy, respectively. Although patients receiving carglumic acid with scavengers had a greater reduction in plasma ammonia, the endpoint ammonia levels were similar with or without scavenger therapy. Clinical symptoms improved with therapy. Twenty-five of 57 patients in the safety population (67 episodes) experienced AEs, most of which were not drug-related. Overall, carglumic acid seems to have a good safety profile for treating hyperammonaemia during OA decompensation. CONCLUSION: Carglumic acid when used with or without ammonia scavengers, is an effective treatment for restoration of normal plasma ammonia concentrations in hyperammonaemic episodes in OA patients