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Article ; Online: PTPN23 binds the dynein adaptor BICD1 and is required for endocytic sorting of neurotrophin receptors.

Budzinska, Marta I / Villarroel-Campos, David / Golding, Matthew / Weston, Anne / Collinson, Lucy / Snijders, Ambrosius P / Schiavo, Giampietro

Journal of cell science

2020 Volume 133, Issue 6

Abstract: Signalling by target-derived neurotrophins is essential for the correct development of the nervous system and its maintenance throughout life. Several aspects concerning the lifecycle of neurotrophins and their receptors have been characterised over the ... ...

Abstract	Signalling by target-derived neurotrophins is essential for the correct development of the nervous system and its maintenance throughout life. Several aspects concerning the lifecycle of neurotrophins and their receptors have been characterised over the years, including the formation, endocytosis and trafficking of signalling-competent ligand-receptor complexes. However, the molecular mechanisms directing the sorting of activated neurotrophin receptors are still elusive. Previously, our laboratory identified Bicaudal-D1 (BICD1), a dynein motor adaptor, as a key factor for lysosomal degradation of brain-derived neurotrophic factor (BDNF)-activated TrkB (also known as NTRK2) and p75
MeSH term(s)	Animals ; Brain-Derived Neurotrophic Factor/genetics ; Brain-Derived Neurotrophic Factor/metabolism ; Dyneins/genetics ; Mice ; Phosphoric Monoester Hydrolases ; Protein Transport ; Protein Tyrosine Phosphatases, Non-Receptor ; Receptor, trkB/genetics ; Receptor, trkB/metabolism ; Receptors, Nerve Growth Factor/genetics ; Receptors, Nerve Growth Factor/metabolism
Chemical Substances	Brain-Derived Neurotrophic Factor ; Receptors, Nerve Growth Factor ; Receptor, trkB (EC 2.7.10.1) ; Phosphoric Monoester Hydrolases (EC 3.1.3.2) ; PTPN23 protein, mouse (EC 3.1.3.48) ; Protein Tyrosine Phosphatases, Non-Receptor (EC 3.1.3.48) ; Dyneins (EC 3.6.4.2)
Language	English
Publishing date	2020-03-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.242412
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Zs.A 1200: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 14: Show issues

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Article ; Online: Soil and indoor dust as environmental media of human exposure to As, Cd, Cu, and Pb near a copper smelter in central Chile.

Berasaluce, Maite / Mondaca, Pedro / Schuhmacher, Marta / Bravo, Manuel / Sauvé, Sébastien / Navarro-Villarroel, Claudia / Dovletyarova, Elvira A / Neaman, Alexander

Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)

2019 Volume 54, Page(s) 156–162

Abstract: In the present study, we assessed the non-carcinogenic and carcinogenic human health risk due to exposure to trace elements in soil and indoor dust in Puchuncaví valley. We also determined the associations between trace element concentration in hair/ ... ...

Abstract	In the present study, we assessed the non-carcinogenic and carcinogenic human health risk due to exposure to trace elements in soil and indoor dust in Puchuncaví valley. We also determined the associations between trace element concentration in hair/toenails and the estimated chronic daily intake of trace elements in soil and indoor dust. We found statistically significant association between the trace element concentration in hair/toenails and the estimated chronic daily intake of soil and indoor dust. Indoor dust was more important than soil in terms of human exposure to trace elements in Puchuncaví, due to the high concentration of trace elements on this environmental media and long periods of time that the population spends at their households. With regards to non-carcinogenic risk, we found that there was no health risk associated to soil and indoor dust exposure in the Puchuncaví valley, because none of the hazard quotient values surpassed 1.0. However, carcinogenic risk due to arsenic exposure was above the threshold value of 1.0E-04 in the population of young children (from 1 to 5 years old) in all studied areas, including the control, and in the population of children (from 6 to <18 years old) in the exposed area. Such risk values are classified as unacceptable (US EPA, 2001), requiring some target intervention from the Chilean government.
MeSH term(s)	Adolescent ; Air Pollution, Indoor/analysis ; Arsenic/analysis ; Cadmium/analysis ; Child ; Child, Preschool ; Chile ; Copper/analysis ; Dust/analysis ; Environmental Exposure/adverse effects ; Environmental Monitoring ; Female ; Humans ; Infant ; Lead/analysis ; Male ; Soil/chemistry
Chemical Substances	Dust ; Soil ; Cadmium (00BH33GNGH) ; Lead (2P299V784P) ; Copper (789U1901C5) ; Arsenic (N712M78A8G)
Language	English
Publishing date	2019-04-29
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1236267-0
ISSN	1878-3252 ; 1611-602X ; 0946-672X
ISSN (online)	1878-3252 ; 1611-602X
ISSN	0946-672X
DOI	10.1016/j.jtemb.2019.04.006
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Article: Do Clinical Trials Meet Current Care Needs? Views of Digestive Oncology Specialists in Galicia (Spain) Using the Delphi Method.

Fernández Montes, Ana / Martinez-Lago, Nieves / de la Cámara Gomez, Juan / Brozos Vázquez, Elena María / Candamio Folgar, Sonia / Carmona Campos, Marta / Cousillas Castiñeiras, Antía / Covela Rúa, Marta / Gallardo Martín, Elena / González Villarroel, Paula / Graña Suarez, Begoña / Jorge Fernández, Mónica / Pellón Augusto, María Luz / Quintero Aldana, Guillermo / Romero Reinoso, Carlos / Salgado Fernández, Mercedes / Vázquez Rivera, Francisca / Ayuso Álvarez, Ana / Culqui, Dante R /

Méndez Méndez, José Carlos / RIGhT-Sens Working Group

Healthcare (Basel, Switzerland)

2021 Volume 9, Issue 6

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2021-06-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2721009-1
ISSN	2227-9032
ISSN	2227-9032
DOI	10.3390/healthcare9060665
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Article: Sustained Energy Deficit Following Perinatal Asphyxia: A Shift towards the Fructose-2,6-bisphosphatase (TIGAR)-Dependent Pentose Phosphate Pathway and Postnatal Development.

Lespay-Rebolledo, Carolyne / Tapia-Bustos, Andrea / Perez-Lobos, Ronald / Vio, Valentina / Casanova-Ortiz, Emmanuel / Farfan-Troncoso, Nancy / Zamorano-Cataldo, Marta / Redel-Villarroel, Martina / Ezquer, Fernando / Quintanilla, Maria Elena / Israel, Yedy / Morales, Paola / Herrera-Marschitz, Mario

Antioxidants (Basel, Switzerland)

2021 Volume 11, Issue 1

Abstract: Labor and delivery entail a complex and sequential metabolic and physiologic cascade, culminating in most circumstances in successful childbirth, although delivery can be a risky episode if oxygen supply is interrupted, resulting in perinatal asphyxia ( ... ...

Abstract	Labor and delivery entail a complex and sequential metabolic and physiologic cascade, culminating in most circumstances in successful childbirth, although delivery can be a risky episode if oxygen supply is interrupted, resulting in perinatal asphyxia (PA). PA causes an energy failure, leading to cell dysfunction and death if re-oxygenation is not promptly restored. PA is associated with long-term effects, challenging the ability of the brain to cope with stressors occurring along with life. We review here relevant targets responsible for metabolic cascades linked to neurodevelopmental impairments, that we have identified with a model of global PA in rats. Severe PA induces a sustained effect on redox homeostasis, increasing oxidative stress, decreasing metabolic and tissue antioxidant capacity in vulnerable brain regions, which remains weeks after the insult. Catalase activity is decreased in mesencephalon and hippocampus from PA-exposed (AS), compared to control neonates (CS), in parallel with increased cleaved caspase-3 levels, associated with decreased glutathione reductase and glutathione peroxidase activity, a shift towards the TIGAR-dependent pentose phosphate pathway, and delayed calpain-dependent cell death. The brain damage continues long after the re-oxygenation period, extending for weeks after PA, affecting neurons and glial cells, including myelination in grey and white matter. The resulting vulnerability was investigated with organotypic cultures built from AS and CS rat newborns, showing that substantia nigra TH-dopamine-positive cells from AS were more vulnerable to 1 mM of H
Language	English
Publishing date	2021-12-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox11010074
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Article ; Online: The role of endoscopic ultrasound guidance for biliary and pancreatic duct access and drainage to overcome the limitations of ERCP: a retrospective evaluation.

García-Alonso, Francisco Javier / Peñas-Herrero, Irene / Sanchez-Ocana, Ramon / Villarroel, Mariano / Cimavilla, Marta / Bazaga, Sergio / De Benito Sanz, Marina / Gil-Simon, Paula / de la Serna-Higuera, Carlos / Perez-Miranda, Manuel

Endoscopy

2020 Volume 53, Issue 7, Page(s) 691–699

Abstract: Background: Endoscopic ultrasound (EUS)-guided ductal access and drainage (EUS-DAD) of biliary/pancreatic ducts after failed endoscopic retrograde cholangiopancreatography (ERCP) is less invasive than percutaneous transhepatic biliary drainage (PTBD). ... ...

Abstract	Background: Endoscopic ultrasound (EUS)-guided ductal access and drainage (EUS-DAD) of biliary/pancreatic ducts after failed endoscopic retrograde cholangiopancreatography (ERCP) is less invasive than percutaneous transhepatic biliary drainage (PTBD). The actual need for EUS-DAD remains unknown. We aimed to determine how often EUS-DAD is needed to overcome ERCP failure. Methods: Consecutive duct access procedures (n = 2205; 95 % biliary) performed between June 2013 and November 2015 at a tertiary-care center were reviewed. ERCP was used first line, EUS-DAD as salvage after ERCP, and PTBD when both had failed. Procedures were defined as "index" in patients without prior endoscopic duct access and "combined" when EUS-DAD followed successful ERCP. The main outcomes were the EUS-DAD and PTBD rates. Results: EUS-DAD was performed in 7.7 % (170/2205) of overall procedures: 9.1 % (116/1274) index and 5.8 % (54/931) follow-up. Most index EUS-DADs were performed following (46 %) or anticipating (39 %) ERCP failure, whereas 15 % followed successful ERCP (combined procedures). Among index procedures, the EUS-DAD rate was higher in surgically altered anatomy (58.2 % [39 /67)] vs. 6.4 % [77/1207]); PTBD was required in 0.2 % (3/1274). Among follow-up procedures, ERCP represented 85.7 %, cholangiopancreatography through mature transmural fistulas 8.5 %, and EUS-DAD 5.8 %; no patient required PTBD. The secondary PTBD rate was 0.1 % (3/2205). Six primary PTBDs were performed (overall PTBD rate 0.4 % [9/2205]). Conclusions: EUS-DAD was required in 7.7 % of ERCPs for benign and malignant biliary/pancreatic duct indications. Salvage PTBD was required in 0.1 %. This high EUS-DAD rate reflects disease complexity, a wide definition of ERCP failure, and restrictive PTBD use, not poor ERCP skills. EUS-DAD effectively overcomes the limitations of ERCP eliminating the need for primary and salvage PTBD in most cases.
MeSH term(s)	Cholangiopancreatography, Endoscopic Retrograde ; Drainage ; Endosonography ; Humans ; Pancreatic Ducts/diagnostic imaging ; Retrospective Studies
Language	English
Publishing date	2020-12-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	80120-3
ISSN	1438-8812 ; 0013-726X
ISSN (online)	1438-8812
ISSN	0013-726X
DOI	10.1055/a-1266-7592
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Zs.A 669: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 162: Show issues

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Article ; Online: Experiencia en COVID-19 en pacientes hospitalizados en unidades de paciente crítico pediátrico durante el periodo pandémico.

Wegner Araya, Adriana / Céspedes Fernández, Pamela / Astudillo Paredes, Patricio / Diettes González, Adriana / Diaz Rubio, Franco / Scheu Gonçalves, Christian / Chauriye Kuncar, Verónica / Gaete Amenábar, Tomás / Zamora Astudillo, Marta / Acuña Aguirre, Carlos / Drago Thibaut, Michele / Monreal Eloaiza, Víctor / Lapadula Amelina, Michelangelo / Pietroboni Fuster, Pietro / Varela Ortiz, Javier / Gallardo Martínez, Alena / Scheuch Ruiz, Karin / Manen Chinchón, Andrés / Villarroel Carreño, María-José

Andes pediatrica : revista Chilena de pediatria

2023 Volume 94, Issue 5, Page(s) 616–627

Abstract: Objectives: To characterize the COVID-19 disease profile in Chilean children hospitalized in pediatric intensive care units (PICU) and to evaluate risk factors associated with severe COVID-19.: Patients and method: A multicenter prospective cohort ... ...

Title translation	Experience in COVID-19 in hospitalized patients in pediatric critical units during pandemic period.
Abstract	Objectives: To characterize the COVID-19 disease profile in Chilean children hospitalized in pediatric intensive care units (PICU) and to evaluate risk factors associated with severe COVID-19. Patients and method: A multicenter prospective cohort study with patients 0-18 years of age with confirmed SARS-CoV-2 hospitalized in PICU. Clinical, laboratory, imaging, and therapeutic variables were recorded. We compared "mild/moderate COVID-19" with ''severe COVID-19" using median with interquartile range (IQR), Mann-Whitney U test, two-tailed Fisher's test, and forward binary multivariate analysis to adjust variables for "severe COVID-19". A p < 0.05 was considered significant. Results: From 16 PICUs, 219 patients were recruited, 55.3% were male, with a median age of 86 months (IQR: 13.5-156). The most frequent comorbidities were obesity and respiratory diseases. Overall mortality was 3.6%. "Severe COVID-19" (26.5%) showed more leukopenia, lymphopenia, increased inflammatory parameters, and altered organ function (p < 0.05). It also developed more sepsis/shock, ARDS, and organ dysfunction, requiring more hemodynamic, anti-inflammatory, anticoagulation, and antibiotic therapy, with a longer stay in the PICU/hospital (p < 0.05), and 13.8% of mortality. Risk factors associated with "severe COVID-19" were shock on admission to the PICU [aOR 28.44 (95%CI 10.45-77.4)], obesity [aOR 3.55 (95%CI 1.3-9.6)], consolidation [aOR 3.1 (95%CI 1.1 -8.7)], atelectasis [aOR: 8.7 (95%CI 1.17-64.3)], stress dose of corticosteroids [aOR 7.7 (95%CI 1.9-30.6)], early antibiotic therapy [aOR: 12.02 (95%CI 1.11-130.02)], acquired/congenital immunodeficiency [aOR: 19.2 (95%CI: 1.19-321)], and oncological pathology [aOR 10.7 (95%CI 2.14-47.8)]. Conclusion: In this Chilean pediatric cohort, most patients with COVID-19 admitted to de PICU were male, of school age, with associated comorbidity. Risk factors for developing severe COVID-19 were the presence of comorbidities such as acquired/congenital immunodeficiency, oncological pathology, and obesity, in addition to shock on admission and consolidations on X-rays.
MeSH term(s)	Humans ; Child ; Male ; Female ; COVID-19/epidemiology ; SARS-CoV-2 ; Pandemics ; Prospective Studies ; Obesity ; Thrombocytopenia ; Anti-Bacterial Agents/therapeutic use
Chemical Substances	Anti-Bacterial Agents
Language	Spanish
Publishing date	2023-11-17
Publishing country	Chile
Document type	Multicenter Study ; English Abstract ; Journal Article
ISSN	2452-6053
ISSN (online)	2452-6053
DOI	10.32641/andespediatr.v94i5.4527
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Article ; Online: Efficacy and safety of FOLFIRI/aflibercept (FA) in an elderly population with metastatic colorectal cancer (mCRC) after failure of an oxaliplatin-based regimen.

Martínez-Lago, Nieves / Cameselle García, Soledad / Alonso de Castro, Beatriz / Gómez-Randulfe Rodríguez, Martín I / Carmona Campos, Marta / González Villarroel, Paula / Salgado Fernández, Mercedes / De la Cámara Gómez, Juan C / Romero Reinoso, Carlos / Cousillas Castiñeiras, Antía / Méndez Méndez, José Carlos / Vidal Insua, Yolanda / Fernández-Montes, Ana

PloS one

2022 Volume 17, Issue 6, Page(s) e0269399

Abstract: Background: The VELOUR study showed the benefit of FOLFIRI-Aflibercept (FA) versus FOLFIRI in patients with metastatic colorectal cancer (mCRC) in second-line treatment. However, only 36% of the included patients were ≥65 years. Thus, we seek to ... ...

Abstract	Background: The VELOUR study showed the benefit of FOLFIRI-Aflibercept (FA) versus FOLFIRI in patients with metastatic colorectal cancer (mCRC) in second-line treatment. However, only 36% of the included patients were ≥65 years. Thus, we seek to evaluate the efficacy and safety of FA in the elderly population in the context of routine practice. Materials and methods: We conducted an observational, retrospective, multicenter, observational study of patients ≥70 years with mCRC treated with FA after progression to oxaliplatin chemotherapy in routine clinical practice in 9 hospitals of the GITuD group. Results: Of 388 patients treated with FA between June 2013 and November 2018, 75 patients ≥70 years were included. The median number of cycles was 10 and the objective response (ORR) and disease control rates (DCR) were 33.8% and 72.0%, respectively. With a median follow-up of 27.1 months, median Progression-free survival (PFS) was 6.6 months and median Overall Survival (OS) was 15.1 months. One third fewer metastasectomies were performed in the ≥75 years' subgroup (24 vs. 52%, p = 0.024) and more initial FOLFIRI dose reductions (68 vs. 36%, p = 0.014). ORR (23.8% vs. 38.3%), DCR (42.8% vs. 85.1%), and PFS (4 vs. 7.8 months; p = 0.017) were significantly less, without difference in OS (9.9 vs. 17.1 months; p = 0.129). The presence of prior hypertension (HT) (PFS 7.9 vs. 5.7 months, p = 0.049) and HT ≥ grade 3 during treatment (PFS 7.6 vs. 6.6 months, p = 0.024) were associated with longer PFS. The most frequent grade 3/4 adverse events were: asthenia (21.3%), neutropenia (14.7%), and diarrhea (14.7%). 57.3% required FOLFIRI dose reduction; 34.7% of aflibercept, including discontinuation (5.3% and 18.7%, respectively). Conclusions: FA combination is effective in patients ≥70 years. The occurrence of HT is predictive of efficacy. Close monitoring of toxicity and initial dose adjustment is recommended.
MeSH term(s)	Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Camptothecin/adverse effects ; Colonic Neoplasms/drug therapy ; Colorectal Neoplasms/pathology ; Fluorouracil/adverse effects ; Humans ; Leucovorin/adverse effects ; Oxaliplatin ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/adverse effects ; Rectal Neoplasms/drug therapy ; Retrospective Studies
Chemical Substances	Recombinant Fusion Proteins ; Oxaliplatin (04ZR38536J) ; aflibercept (15C2VL427D) ; Receptors, Vascular Endothelial Growth Factor (EC 2.7.10.1) ; Leucovorin (Q573I9DVLP) ; Fluorouracil (U3P01618RT) ; Camptothecin (XT3Z54Z28A)
Language	English
Publishing date	2022-06-03
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Observational Study
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0269399
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Article: Aortic Valvular Disease in Elderly Subjects with Heterozygous Familial Hypercholesterolemia: Impact of Lipid-Lowering Therapy.

Marco-Benedí, Victoria / Laclaustra, Martin / Casado-Dominguez, Juan M / Villa-Pobo, Rosa / Mateo-Gallego, Rocío / Sánchez-Hernández, Rosa M / Blanco Nuez, Marta / Ortega-Martínez de Victoria, Emilio / Sitges, Marta / Pedro-Botet, Juan / Puzo, Jose / Villarroel, Teresa / Civeira, Fernando

Journal of clinical medicine

2019 Volume 8, Issue 12

Abstract: Hypercholesterolemia and statins are risk factors for aortic stenosis (AS) and vascular calcification, respectively. Whether heterozygous subjects with familial hypercholesterolemia (HeFH) treated with statins are at risk of AS is unknown. We study the ... ...

Abstract	Hypercholesterolemia and statins are risk factors for aortic stenosis (AS) and vascular calcification, respectively. Whether heterozygous subjects with familial hypercholesterolemia (HeFH) treated with statins are at risk of AS is unknown. We study the prevalence of AS, aortic valve calcification (AoVC), and aortic sclerosis (ASc) in elderly subjects with HeFH in a prolonged statin treatment. Case-control study, cases were adults ≥65 years of age with a genetic diagnosis of HeFH, LDLc >220 mg/dl, and statin treatment ≥5 years. Controls were relatives of HeFH patients, with LDLc <190 mg/dl. Participants underwent a cardiac ultrasound for aortic valve analysis. We studied 205 subjects, 112 HeFH and 93 controls, with mean age 71.8(6.5) years and 70.0(7.3) years, respectively. HeHF, with respect to controls, presented greater gradients of aortic transvalvular pressure, 7.4(7.3) mmHg versus 5.0(2.8) mmHg, and maximum aortic velocity, 1.7(0.7) m/s versus 1.5(0.4) m/s, and lower aortic valve opening area, 2.0(0.7) cm
Language	English
Publishing date	2019-12-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm8122209
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Article ; Online: Prediction of survival in patients with advanced, refractory colorectal cancer in treatment with trifluridine/tipiracil: real-world vs clinical trial data.

Fernández Montes, Ana / Carmona-Bayonas, Alberto / Jimenez-Fonseca, Paula / Vázquez Rivera, Francisca / Martinez Lago, Nieves / Covela Rúa, Marta / Cousillas Castiñeiras, Antía / Gonzalez Villarroel, Paula / De la Cámara Gómez, Juan / Méndez, José Carlos Méndez / Carriles Fernández, Carmen / Sanchez Cánovas, Manuel / Garcia García, Teresa

Scientific reports

2021 Volume 11, Issue 1, Page(s) 14321

Abstract: Trifluridine/tipiracil increases overall survival (OS) in patients with refractory, metastatic colorectal cancer (mCRC). A post hoc exploratory analysis of the RECOURSE randomized clinical trial (RCT) established two categories, a good prognosis ... ...

Abstract	Trifluridine/tipiracil increases overall survival (OS) in patients with refractory, metastatic colorectal cancer (mCRC). A post hoc exploratory analysis of the RECOURSE randomized clinical trial (RCT) established two categories, a good prognosis corresponding to subjects having a low tumor burden and indolent disease. Other models in refractory mCRC are the FAS-CORRECT and Colon Life nomogram. The main objective was to externally validate the prognostic factors of the RECOURSE and FAS-CORRECT trials, and the Colon Life nomogram in a multicenter, real-world series of mCRC treated in 3rd and successive lines with trifluridine/tipiracil. The secondary aim was to develop an OS predictive model, TAS-RECOSMO. Between 2016 and 2019, 244 patients were recruited. Median OS was 8.15 vs 8.12 months for the poor (85% of the subjects) and good (15%) prognosis groups from the RESOURCE trial, respectively, log-rank p = 0.9. The most common grade 3-4 toxicities were neutropenia (17%), asthenia (6%), and anemia (5%). The AFT lognormal model TAS-RECOSMO included six variables: ECOG-PS, KRAS/NRAS/BRAF mutation status, time between diagnosis of metastasis and beginning of trifluridine/tipiracil, NLR, CEA, and alkaline phosphatase. The model's bootstrapped bias-corrected c-index was 0.682 (95% CI, 0.636-0.722). The factors from the Colon Life model, FAS-CORRECT, and RECOURSE displayed a c-index of 0.690, 0.630, and 0.507, respectively. TAS-RECOSMO, FAS-CORRECT, and the Colon Life nomogram appear to predict OS in patients with refractory mCCR who begin trifluridine/tipiracil treatment in the real world. The prognostic groups of the RECOURCE RCT were unable to capture the situation of real-world subjects treated with trifluridine/tipiracil in this series.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asthenia/drug therapy ; Colorectal Neoplasms/drug therapy ; Drug Combinations ; Female ; Humans ; Male ; Middle Aged ; Multicenter Studies as Topic ; Neutropenia/drug therapy ; Pyrrolidines/therapeutic use ; Thymine/therapeutic use ; Trifluridine/therapeutic use ; Young Adult
Chemical Substances	Drug Combinations ; Pyrrolidines ; trifluridine tipiracil drug combination ; Thymine (QR26YLT7LT) ; Trifluridine (RMW9V5RW38)
Language	English
Publishing date	2021-07-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-93732-5
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Article ; Online: Neurodegeneration: An early event of diabetic retinopathy.

Villarroel, Marta / Ciudin, Andreea / Hernández, Cristina / Simó, Rafael

World journal of diabetes

2011 Volume 1, Issue 2, Page(s) 57–64

Abstract: Diabetic retinopathy (DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyperglycemia. However, retinal ... ...

Abstract	Diabetic retinopathy (DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyperglycemia. However, retinal neurodegeneration is already present before any microcirculatory abnormalities can be detected in ophthalmoscopic examination. In other words, retinal neurodegeneration is an early event in the pathogenesis of DR which predates and participates in the microcirculatory abnormalities that occur in DR. Therefore, the study of the mechanisms that lead to neurodegeneration will be essential to identify new therapeutic targets in the early stages of DR. Elevated levels of glutamate and the overexpression of the renin- angiotensin-system play an essential role in the neurodegenerative process that occurs in diabetic retina. Among neuroprotective factors, pigment epithelial derived factor, somatostatin and erythropoietin seem to be the most relevant and these will be considered in this review. Nevertheless, it should be noted that the balance between neurotoxic and neuroprotective factors rather than levels of neurotoxic factors alone will determine the presence or absence of retinal neurodegeneration in the diabetic eye. New strategies, based on either the delivery of neuroprotective agents or the blockade of neurotoxic factors, are currently being tested in experimental models and in clinical pilot studies. Whether these novel therapies will eventually supplement or prevent the need for laser photocoagulation or vitrectomy awaits the results of additional clinical research.
Language	English
Publishing date	2011-02-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2583471-X
ISSN	1948-9358 ; 1948-9358
ISSN (online)	1948-9358
ISSN	1948-9358
DOI	10.4239/wjd.v1.i2.57
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In stock of ZB MED Cologne/Königswinter

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Inter-library loan at ZB MED

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Full text online

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