12 research outputs found
Short-course radiotherapy for rectal cancer: real-world evidence in Argentina
No full textLatin America; Rectal cancer; Short-course radiotherapyAmérica Latina; Cáncer de recto; Radioterapia de corta duraciónAmèrica Llatina; Càncer de recte; Radioteràpia de curta duradaBackground: Short-course radiotherapy (SCRT) of 25 Gy in five daily fractions is a recommended strategy in the neoadjuvant setting for resectable locally advanced rectal cancer (LARC), as well as in cases of metastatic disease for local control. There is scarce information regarding the use of SCRT for patients who have received nonoperative management.
Objectives: To describe the characteristics of patients who received treatment with SCRT for LARC and metastatic rectal cancer, toxicity, and the approach after radiation treatment.
Methods: This is a retrospective analysis of all patients who underwent SCRT for rectal cancer at the Alexander Fleming Institute from March 2014 to June 2022.
Results: In total, 44 patients were treated with SCRT. The majority were male (29, 66%), with a median age of 59 years (interquartile range 46–73). Most patients had stage IV disease (26, 59.1%), followed by LARC (18, 40.9%). Most lesions were located in the middle rectum (30, 68%). The majority of LARC patients underwent SCRT followed by consolidation chemotherapy (ChT) (16/18, 89%), while most patients with metastatic disease underwent SCRT followed by consolidation ChT (14/26, 53.8%). A clinical complete response (cCR) was documented in 8/44, 18.2% of patients. Most patients with LARC and cCR were managed by a watch and wait approach (5/18, 27.7%). Local recurrence was observed in LARC cases (2/18, 11.1%). Patients who underwent SCRT following consolidation ChT were more likely to have adverse events (AEs) than those undergoing induction ChT following SCRT (11/30, 36.7% versus 3/12, 25%, p = 0.02)
Conclusion: In a subgroup of patients diagnosed with LARC and treated with SCRT followed by ChT, surgical treatment could be omitted after they achieved a cCR. Local recurrence was similar to that reported in a previous study. SCRT is a reasonable option for local disease control in stage IV disease, yielding low toxicity rates. Therefore, decisions must be made by a multidisciplinary team. Prospective studies are necessary to reach further conclusions
International validation of the Immunoscore-biopsy (IS B ) to guide selection and monitoring of patients treated with watch-and-wait (WW) strategy for rectal cancer.
No full textBackground: The WW strategy for patients with rectal cancer who achieved a clinical complete response (cCR) after neoadjuvant therapy (nT) allows to avoid major resection and the associated morbidity and mortality. Standardized criteria to select and monitor WW patients, including biomarkers predicting recurrence after nT, are lacking. The prognostic impact of the immune infiltrate in colorectal cancers is now demonstrated and has been implemented into clinics through the Immunoscore, the first standardized digital-pathology-based assay, recommended by academic institutions. We evidenced that an Immunoscore adapted to biopsies (IS B ) performed at diagnosis, predicts the response to nT and the risk of recurrence after nT. Its clinical utility was suggested in a test cohort of WW patients (El Sissy et al., Clin Cancer Res 2020). The aim of this study was to confirm the ability of the IS B to predict clinical outcomes, improve patients’ eligibility for the WW strategy, and optimize a follow-up schedule. Methods: A total of 304 WW patients from 10 centers across 7 countries were included. Tumor biopsies before treatment were immunostained for CD3+ and CD8+ T-cells and converted to IS B using the pre-defined cut-off. The primary endpoint was time-to-recurrence (TTR). Secondary endpoint was disease-free-survival (DFS). As immune response originates in draining lymph nodes, signs of immune activation were carried out in lymph nodes of additional patients managed by radical surgery with complete pathological response (pCR; n = 12) or non-pCR (n = 12) by 3' RNA-Seq and immunofluorescence technologies. Results: High-IS B patients presented with the lowest risk of recurrence after WW. 5-year recurrence-free rates were 97% (92%-100%), 61% (49%-76%), and 56% (44%-73%) with IS B High, Intermediate, and Low, respectively (HR [Low-vs-High] = 14.3, 95% CI 1.8-100). In patients with cCR after nT (n = 209), High-IS B showed a significant association with prolonged TTR and DFS (Logrank P = 0.005 and P = 0.006, respectively). When IS B was evaluated as a continuous variable, the risk of recurrence was increasing along with decreasing IS B (Wald tests, all P < 0.005). In multivariate analyses, IS B was independent of age, sex, location, and cTNM stage and was the single parameter correlated with TTR (HR [IS B High-vs-Low] = 0.08, 95% CI 0.01-0.6; P = 0.015) and DFS (P = 0.013). Unlike for patients with cCR, no difference according to IS B was observed for those with incomplete response (n = 41) or treated with brachytherapy (n = 34). Finally, intranodal signs of T-cell and B-cell activation were only evidenced in patients with pCR. Conclusions: IS B provides a reliable biomarker to predict clinical outcomes, improve eligibility, and optimize patients’ follow-up. Intranodal T-cell and B-cell activation further supports the immune benefit of both organ and lymph node preservation
Cannabinoids for the control of experimental multiple sclerosis
No full textPhDThere have been numerous studies reporting that cannabinoids, both exogenous
and endogenous, have a potential beneficial function during incidences of
neurological damage. Using gene knockout mice and cannabinoid-selective agents,
this study demonstrates the diverse actions of cannabinoids with a particular focus
on experimental autoimmune encephalomyelitis, an animal model of multiple
sclerosis. The results presented here report on the action of stimulators of
cannabinoid receptors in the nervous system (CNS) on; immune function, as a
mechanism of suppressing autoimmune attack of the central nervous system, as
agents to suppress neurodegenerative events leading to disease progression and as
agents that can control signs of disease that occur as the consequences of
autoimmune neurodegeneration such as spasticity. Tetrahydrocannabinol the
psychoactive component in cannabis and the CB1 cannabinoid receptor appears to
be central to many of the therapeutic actions of cannabis but also to the side-effect
potential of cannabinoid drugs. This study reports on methods to avoid
psychoactive side-effects of conventional brain-penetrant CB1 receptor agonists
whilst exploiting the therapeutic potential of the cannabinoid system in order to
control spasticity. This was achieved by targeting mechanisms of endocannabinoid
degradation, particularly using fatty acid amide hydrolase inhibitors. Furthermore,
this study also reports the development of novel cannabinoid compounds that are
excluded from the brain and inhibit spasticity and also demonstrates the
mechanism of exclusion of CNS-excluded cannabinoid CB1 receptor agonists. This
study provides further evidence for the efficacy of cannabinoid compounds during
an ongoing CNS disease and also their efficacy for treating the consequences of
CNS autoimmune disease, which hopefully, will give additional impetus for further
clinical investigations of cannabinoid agents in not only multiple sclerosis but also
other neurodegenerative diseases of the CNS
Consenso latinoamericano de hipertensión en pacientes con diabetes tipo 2 y síndrome metabólico
No full textThe present document has been prepared by a group of experts, members of cardiology, endocrinology, internal medicine, nephrology and diabetes societies of Latin American countries, to serve as a guide to physicians taking care of patients with diabetes, hypertension and comorbidities or complications of both conditions. Although the concept of metabolic syndrome is currently disputed, the higher prevalence in Latin America of that cluster of metabolic alterations has suggested that metabolic syndrome is a useful nosography entity in the context of Latin American medicine. Therefore, in the present document, particular attention is paid to this syndrome in order to alert physicians on a particular high-risk population, usually underestimated and undertreated. These recommendations result from presentations and debates by discussion panels during a 2-day conference held in Bucaramanga, in October 2012, and all the participants have approved the final conclusions. The authors acknowledge that the publication and diffusion of guidelines do not suffice to achieve the recommended changes in diagnostic or therapeutic strategies, and plan suitable interventions overcoming knowledge, attitude and behavioural barriers, preventing both physicians and patients from effectively adhering to guideline recommendations.O presente documento foi preparado por um grupo de especialistas, membros das Sociedades de Cardiologia, Endocrinologia, Medicina Interna, Nefrologia e Diabetes dos países da América Latina, para que sirva de diretriz para médicos que cuidam de pacientes com diabetes, hipertensão e fatores de risco concomitantes ou complicações de ambas as condições. Embora o conceito de síndrome metabólica seja atualmente muito discutido, a alta prevalência na América Latina do conjunto de alterações metabólicas que a compõem sugere que a síndrome metabólica é uma entidade nosográfica útil no contexto da medicina latino-americana. Devido a isso, no presente documento presta-se especial atenção a essa síndrome com a finalidade de alertar aos médicos sobre uma população particularmente de alto risco, que, por ser subestimada, não é tratada de forma adequada para os fatores de risco que constituem a síndrome metabólica. As recomendações deste documento são o resultado de apresentações e debates que ocorreram durante um encontro de dois dias em Bucaramanga (Colômbia), em outubro de 2012. Todos os participantes aprovaram as decisões finais. Os autores reconhecem que a publicação e difusão das diretrizes não serão suficientes para alcançar as mudanças recomendadas tanto em estratégias diagnósticas como terapêuticas, por isso programaram intervenções que permitirão identificar as barreiras do conhecimento, as atitudes e comportamento, o que permitirá tanto aos médicos como aos pacientes uma adequada adesão às recomendações sugeridas nestas diretrizes
International Validation of the Immunoscore Biopsy in Patients With Rectal Cancer Managed by a Watch-and-Wait Strategy
No full textPURPOSE: No biomarker capable of improving selection and monitoring of patients with rectal cancer managed by watch-and-wait (W&W) strategy is currently available. Prognostic performance of the Immunoscore biopsy (IS ) was recently suggested in a preliminary study. METHODS: This international validation study included 249 patients with clinical complete response (cCR) managed by W&W strategy. Intratumoral CD3+ and CD8+ T cells were quantified on pretreatment rectal biopsies by digital pathology and converted to IS . The primary end point was time to recurrence (TTR; the time from the end of neoadjuvant treatment to the date of local regrowth or distant metastasis). Associations between IS and outcomes were analyzed by stratified Cox regression adjusted for confounders. Immune status of tumor-draining lymph nodes (n = 161) of 17 additional patients treated by neoadjuvant chemoradiotherapy and surgery was investigated by 3'RNA-Seq and immunofluorescence. RESULTS: Recurrence-free rates at 5 years were 91.3% (82.4%-100.0%), 62.5% (53.2%-73.3%), and 53.1% (42.4%-66.5%) with IS High, IS Intermediate, and IS Low, respectively (hazard ratio [HR; Low High], 6.51; 95% CI, 1.99 to 21.28; log-rank = .0004). IS was also significantly associated with disease-free survival (log-rank = .0002), and predicted both local regrowth and distant metastasis. In multivariate analysis, IS was independent of patient age, sex, tumor location, cT stage (T, primary tumor; c, clinical), cN stage (N, regional lymph node; c, clinical), and was the strongest predictor for TTR (HR [IS High Low], 6.93; 95% CI, 2.08 to 23.15; = .0017). The addition of IS to a clinical-based model significantly improved the prediction of recurrence. Finally, B-cell proliferation and memory in draining lymph nodes was evidenced in the draining lymph nodes of patients with cCR. CONCLUSION: The IS is validated as a biomarker to predict both local regrowth and distant metastasis, with a gradual scaling of the risk of pejorative outcome
Epigenetic mechanisms and posttranslational Modifications in systemic lupus erythematosus
No full textThe complex physiology of eukaryotic cells is regulated through numerous mechanisms,
including epigenetic changes and posttranslational modifications. The wide-ranging diversity of these mechanisms constitutes a way of dynamic regulation of the functionality of proteins, their activity, and their subcellular localization as well as modulation of the di erential expression of genes in response to external and internal stimuli that allow an organism to respond or adapt to accordingly. However, alterations in these mechanisms have been evidenced in several autoimmune diseases, including systemic lupus erythematosus (SLE). The present review aims to provide an approach to the current knowledge of the implications of these mechanisms in SLE pathophysiology.Navarro Quiroz, Elkin-will be generated-orcid-0000-0001-7567-6409-600Chavez-Estrada, ValeriaMacias-Ochoa, KarimeAyala-Navarro, María FernandaFlores-Aguilar, Aniyensy SaraiMorales Navarrete, Francisco-will be generated-orcid-0000-0002-3461-7186-600de la Cruz Lopez, FernandoGOMEZ ESCORCIA, LORENA-will be generated-orcid-0000-0002-9736-6417-600Musso, Carlos-will be generated-orcid-0000-0003-4928-1280-600Aroca Martínez, GustavoGonzales Torres, HenryDíaz Pérez, AndersonCadena Bonfanti, Andres Angélo-will be generated-orcid-0000-0003-3903-1915-600Sarmiento Gutiérrez, JoanyMeza, JainyDiaz Arroyo, Esperanza-will be generated-orcid-0000-0002-3286-022X-600Bello-Lemus, Yesit-will be generated-orcid-0000-0003-1006-0042-600Ahmad, Mostapha-will be generated-orcid-0000-0002-3825-9478-600Navarro Quiroz, Robert
Global disparities in surgeons' workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study
No full text: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI
Global disparities in surgeons' workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study
No full textThe workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI
Diversity of fungi and bacteria present in tropical forest soils of the western range - Valle del Cauca in response to an altitudinal gradient.
No full textIlstraciones, tablasSe realizó una caracterización taxonómica bacteriana (16S) y fúngica (ITS) utilizando
metabarcoding sobre un gradiente altitudinal en la cordillera occidental del Valle del Cauca,
Colombia, que incluyó ecosistemas de Bosques Andino, Seco Tropical y Páramo en las
localidades de Laguna de Sonso (LS) (900 msnm), Yotoco (Yt) (1800 msnm), Bosque del
Duende (BD) (2400 msnm) y páramo del Duende (PDU) (3200 msnm). Los análisis
fisicoquímicos mostraron suelos con materia orgánica alta (>10%), sin problemas de
compactación, pHs extremadamente ácidos (4,4) para zonas con mayor altitud, ligera y
fuertemente ácidos en zonas bajas (5,5-6,1). Se identificaron 59 familias de plantas en las
zonas de muestreo, siendo las más abundantes Araceae, Lauraceae y Fabaceae. Las
asignaciones taxonómicas bacterianas fueron dominadas por los phyla Acidobacteriota
(33,1%) y Proteobacteria (23,9%), para hongos dominaron Ascomycota (38,6%,) y
Basidiomycota (11,3%). En general los análisis diversidad alfa mostraron alta diversidad,
riqueza y baja dominancia, demostrando que las comunidades son altamente diversas,
mientras la diversidad beta reflejó las diferencias de la composición en las localidades y la
heterogeneidad de estas. Las predicciones funcionales reflejaron que la abundancia
absoluta más alta para bacterias presentó actividad quimioheterotrofa y se relaciona con
diferentes componentes del ciclo del nitrógeno mientras en hongos se clasifica por gremios
ecológicos, donde los relacionados con actividad patogénica tanto en animales como en
plantas, endofitismo, saprofitismo y epifitos fueron más representativos. Los resultados
encontrados demuestran una variabilidad genética ecológica de los microorganismos entre
las zonas de muestreo, además, respondieron a los cambios fisicoquímicos y de
vegetación propios del gradiente altitudinal. (Texto tomado de la fuente)A bacterial (16S) and fungal (ITS) taxonomic characterization was carried out using
metabarcoding over an altitudinal gradient in the western mountain range of Valle del
Cauca, Colombia, which included ecosystems of Andean, Tropical Dry and Paramo Forests
in the localities of Laguna de Sonso (LS) (900 masl), Yotoco (Yt) (1800 masl), Bosque del
Duende (BD) (2400 masl) and paramo of Duende (PDU) (3200 masl). The physicochemical
analyses showed soils with high organic matter (>10%), no compaction problems,
extremely acidic pHs (4.4) for higher altitude zones, and slightly and strongly acidic in lower
zones (5.5-6.1). Fifty-nine plant families were identified in the sampling areas, the most
abundant being Araceae, Lauraceae, and Fabaceae. Bacterial taxonomic assignments
were dominated by the phyla Acidobacteriota (33.1%) and Proteobacteria (23.9%), for fungi
Ascomycota (38.6%) and Basidiomycota (11.3%). In general, alpha diversity analyses
showed high diversity, richness, and low dominance, demonstrating that the communities
are highly diverse. In contrast, beta diversity reflected the differences in the composition of
the localities and their heterogeneity. Functional predictions reflected that the highest
absolute abundance for bacteria presented chemoheterotrophic activity and was related to
different components of the nitrogen cycle. At the same time, fungi were classified by
ecological guilds, where those related to pathogenic activity in animals and plants,
endophytes, saprophytes, and epiphytes were more representative. The results show an
ecological genetic variability of the microorganisms among the sampling zones, in addition,
they responded to the physicochemical and vegetation changes characteristic of the
altitudinal gradient.MaestríaMagíster en Ciencias BiológicasEn 3 de las 4 localidades evaluadas, se establecieron 3 parcelas de 100 m2
respectivamente, de cada una se tomaron 3 cilindros (submuestras) obteniendo 27
muestras, en el PDU, donde por ser una zona agreste se pudo establecer 2 parcelas con
5 submuestras donde finalmente se recolectaron 10 muestras, en total se recolectaron 37
muestras Las muestras de suelo fueron tomadas de una fracción entre 0 a 25 cm de
profundidad del suelo, homogenizadas y almacenadas en tubos Falcon de 25 ml que
posteriormente se preservaron a temperatura de -80°C para para preservar la integridad y
estabilidad del ADN hasta la realización de extracción del mismo. Así mismo, dentro de las
zonas se realizó una caracterización de la abundancia de la flora presente en cada una de
las parcelas.Ecología microbianaCiencias Agropecuarias.Sede Palmir
