15 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
A tool box for operational mosquito larval control: preliminary results and early lessons from the Urban Malaria Control Programme in Dar es Salaam, Tanzania.
No full textBACKGROUND\ud
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As the population of Africa rapidly urbanizes, large populations could be protected from malaria by controlling aquatic stages of mosquitoes if cost-effective and scalable implementation systems can be designed.\ud
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METHODS\ud
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A recently initiated Urban Malaria Control Programme in Dar es Salaam delegates responsibility for routine mosquito control and surveillance to modestly-paid community members, known as Community-Owned Resource Persons (CORPs). New vector surveillance, larviciding and management systems were designed and evaluated in 15 city wards to allow timely collection, interpretation and reaction to entomologic monitoring data using practical procedures that rely on minimal technology. After one year of baseline data collection, operational larviciding with Bacillus thuringiensis var. israelensis commenced in March 2006 in three selected wards.\ud
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RESULTS\ud
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The procedures and staff management systems described greatly improved standards of larval surveillance relative to that reported at the outset of this programme. In the first year of the programme, over 65,000 potential Anopheles habitats were surveyed by 90 CORPs on a weekly basis. Reaction times to vector surveillance at observations were one day, week and month at ward, municipal and city levels, respectively. One year of community-based larviciding reduced transmission by the primary malaria vector, Anopheles gambiae s.l., by 31% (95% C.I. = 21.6-37.6%; p = 0.04).\ud
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CONCLUSION\ud
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This novel management, monitoring and evaluation system for implementing routine larviciding of malaria vectors in African cities has shown considerable potential for sustained, rapidly responsive, data-driven and affordable application. Nevertheless, the true programmatic value of larviciding in urban Africa can only be established through longer-term programmes which are stably financed and allow the operational teams and management infrastructures to mature by learning from experience
Signatures of adaptation to plant parasitism in nematode genomes
No full textEach author is, or was, at the time of the work, a paid employee of their affiliated organization. The James Hutton Institute receives funding from the Scottish Government. TK is funded by JSPS KAKENHI Grant Numbers 20353659 and 23248024 Date of Acceptance: 27/11/2013Plant-parasitic nematodes cause considerable damage to global agriculture. The ability to parasitize plants is a derived character that appears to have independently emerged several times in the phylum Nematoda. Morphological convergence to feeding style has been observed, but whether this is emergent from molecular convergence is less obvious. To address this, we assess whether genomic signatures can be associated with plant parasitism by nematodes. In this review, we report genomic features and characteristics that appear to be common in plant-parasitic nematodes while absent or rare in animal parasites, predators or free-living species. Candidate horizontal acquisitions of parasitism genes have systematically been found in all plant-parasitic species investigated at the sequence level. Presence of peptides that mimic plant hormones also appears to be a trait of plant-parasitic species. Annotations of the few genomes of plant-parasitic nematodes available to date have revealed a set of apparently species-specific genes on every occasion. Effector genes, important for parasitism are frequently found among those species-specific genes, indicating poor overlap. Overall, nematodes appear to have developed convergent genomic solutions to adapt to plant parasitism.Peer reviewe
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
Machine learning and dengue forecasting: Comparing random forests and artificial neural networks for predicting dengue burden at national and sub-national scales in Colombia.
No full textThe robust estimate and forecast capability of random forests (RF) has been widely recognized, however this ensemble machine learning method has not been widely used in mosquito-borne disease forecasting. In this study, two sets of RF models were developed at the national (pooled department-level data) and department level in Colombia to predict weekly dengue cases for 12-weeks ahead. A pooled national model based on artificial neural networks (ANN) was also developed and used as a comparator to the RF models. The various predictors included historic dengue cases, satellite-derived estimates for vegetation, precipitation, and air temperature, as well as population counts, income inequality, and education. Our RF model trained on the pooled national data was more accurate for department-specific weekly dengue cases estimation compared to a local model trained only on the department's data. Additionally, the forecast errors of the national RF model were smaller to those of the national pooled ANN model and were increased with the forecast horizon increasing from one-week-ahead (mean absolute error, MAE: 9.32) to 12-weeks ahead (MAE: 24.56). There was considerable variation in the relative importance of predictors dependent on forecast horizon. The environmental and meteorological predictors were relatively important for short-term dengue forecast horizons while socio-demographic predictors were relevant for longer-term forecast horizons. This study demonstrates the potential of RF in dengue forecasting with a feasible approach of using a national pooled model to forecast at finer spatial scales. Furthermore, including sociodemographic predictors is likely to be helpful in capturing longer-term dengue trends
