Influence of the calcium and nutrient content of the prelay diet on egg production, egg quality, and tibiae mineralization of brown egg-laying hens from 16 to 63 wk of age.

The influence of the Ca and nutrient content of the diet fed from 16 to 19 wk of age, on egg production, egg quality, and tibiae mineralization, was studied in brown egg-laying hens from 16 to 63 wk of age. The experimental design was completely randomized with 4 prelay diets organized as a 2 × 2 factorial with 2 levels of Ca (2.5 vs. 3.8%) and 2 standardized ileal digestible Lys (g/kg) to AMEn (Mcal/kg) ratios (DLys:ME; 2.84 vs. 3.13) as main effects. From 20 to 63 wk of age, all hens received a common diet with 2.75 Mcal AMEn/kg, 0.75% DLys, and 3.8% Ca. Each treatment was replicated 18 times and the experimental unit was a cage with 10 hens. Hen production and egg quality traits were measured by period (4 wk), feeding phase (prelay and lay), and cumulatively (16-63 wk of age) and tibiae mineralization was measured at 63 wk of age. During the prelay phase, an increase in Ca delayed egg production (P = 0.065), reduced feed intake (P < 0.05), and increased BW gain (P < 0.01) and percentage of shell of the egg (P < 0.05). An increase in the DLys:ME ratio increased feed intake (P < 0.01) and reduced egg size (P < 0.01). Nutrient content of the prelay diets did not affect hen production during the lay phase, except egg weight that increased (P < 0.05) in hens previously fed the low DLys:ME ratio. Eggshell quality (weight, percentage, strength, and thickness) in this phase was better (P < 0.05) in hens previously fed 3.8% Ca. Cumulatively (16-63 wk of age), hens fed the high Ca prelay diets had better shell quality but tibiae mineralization was not affected. In conclusion, an increase in Ca content of the prelay diet from 2.5 to 3.8% improved shell quality for the entire egg cycle without showing any negative effect on hen production.

Influence of the energy concentration and the standardized ileal digestible lysine content of the diet on performance and egg quality of brown-egg laying hens from 18 to 41 weeks of age.

The influence of the energy and the standardized ileal digestible lysine (DLys) content of the diet on egg production and egg quality, was studied in brown-egg laying hens from 18 to 41 wk of age. The experimental design was completely randomized with 10 treatments organized as a 2 × 5 factorial with 2 energy concentrations (2,750 and 2,800 kcal AMEn/kg) and 5 levels of DLys (values varied from 0.66 to 0.78% and 0.67 to 0.79%, for the low and high energy diets, respectively). Each treatment was replicated 10 times (10 hens per replicate). The data were analyzed using the MIXED procedure of SAS with energy concentration and DLys content of the diets as main effects. In addition, the effects of the DLys on the variables studied were partitioned into its lineal and quadratic components. From 18 to 21 wk of age (pre-peak phase), diet composition had limited effects on egg production. From 22 to 41 wk of age (peak phase), however, an increase of 50 kcal AMEn/kg diet increased egg weight (P < 0.05) and tended to improve energy intake (P = 0.083) and feed conversion ratio (P = 0.074). An increase in DLys improved linearly (P < 0.001) egg production, egg weight, egg mass, feed conversion, and energy conversion ratio, and tended to increase BW gain (P = 0.074). Diet composition did not any affect egg quality trait except shell strength that increased linearly (P < 0.05) with increases in the DLys. Cumulatively (18-41 wk of age), egg weight increased (P < 0.05) as the energy and the DLys content of the diet increased. In summary, an increase in energy and DLys content of the diet had limited effects on egg production during the prepeak phase but improved egg production, feed conversion ratio, and BW gain during the peak phase. The data indicate that hens require at least 839 mg DLys/d to maximize egg production in the peak production phase.

Effect of beak trimming at hatch and the inclusion of oat hulls in the diet on growth performance, feed preference, exploratory pecking behavior, and gastrointestinal tract traits of brown-egg pullets from hatch to 15 weeks of age.

The influence of infrared beak trimming at hatch (IRBT) and the inclusion of oat hulls (OH) in the diet on growth performance, feed preference, exploratory pecking behavior, and gastrointestinal tract (GIT) development, was studied in brown-egg pullets from 0 to 15 wk of age. The experimental design was completely randomized with 4 treatments arranged as a 2 × 2 factorial with IRBT (sham vs. treated) and OH inclusion (0 vs. 3%) as main effects. Each treatment was replicated 20 times and the experimental unit was a cage with 10 pullets. Feed intake (FI), BW gain, feed conversion ratio (FCR), energy intake (EI, kcal AMEn/d), and energy conversion ratio (ECR, kcal AMEn/g of BW gain) were determined by feeding period (0 to 6, 7 to 10, and 11 to 15 wk of age) and cumulatively. Particle size preference was measured at 7 wk and exploratory pecking behavior of the pullets and at 8 to 14 wk of age. From 0 to 6 wk of age, beak trimming decreased FI (P < 0.01) and increased pullet mortality (P < 0.001) but did not affect BW gain. From 0 to 15 wk of age, OH inclusion improved BW uniformity (P = 0.090) but impaired FCR (P < 0.05) without showing any effect on BW gain or ECR. Preference for coarse particles was greater for the sham than for the treated pullets. Beak trimming and OH feeding reduced (P < 0.05) the exploratory pecking behavior of the pullets from 8 to 12 wk of age but not thereafter. Oat hulls increased the relative weights of the full gizzard and intestines at all ages (P < 0.05). In summary, beak trimming did not affect pullet performance at 15 wk of age or GIT development at any age. Oat hulls improved GIT development at all ages but did not affect BW or ECR. Both beak treatment and OH inclusion affected particle size preference and reduced the exploratory pecking behavior of the birds.

Influence of the energy and digestible lysine contents of the diet on performance and egg quality traits of brown-egg laying hens from 19 to 59 weeks of age.

The influence of nutrient density and standardized ileal digestible lys (DLys) content of the diet on egg production and egg quality traits, was studied in brown-egg laying hens from 19 to 59 wk of age. The experimental design was completely randomized with eight treatments arranged as a 2×4 factorial with two AMEn concentrations (2,680 and 2,780 kcal/kg) and four levels of DLys (0.68, 0.72, 0.76, and 0.80%). Each treatment was replicated nine times and the experimental unit was a cage with nine hens. Hen production, egg components (proportion of albumen, yolk, and shell), egg quality traits (Haugh units, egg shell strength, and incidence of broken, dirty, and shell-less eggs) were measured by period (28 d) and cumulatively. Data were analyzed as a completely randomized design with energy concentration, level of DLys, and their interactions as main effects. In addition, the effects of the level of DLys on the variables studied, were partitioned into its linear and quadratic components. No interactions between AMEn and DLys content of the diet were detected for any of the traits studied and therefore, only main effects are presented. An increase in the AMEn concentration of the diet from 2,680 to 2,780 kcal/kg increased energy intake (P < 0.05) and egg weight (P < 0.001) and improved feed conversion ratio (P < 0.05). An Increase in DLys from 0.68 to 0.80% did not affect the number of eggs produced but increased linearly egg weight (P < 0.01) and egg mass production (P < 0.05). Diet did not affect egg quality. In conclusion, an increase in the AMEn content of the diet from 2,680 to 2,780 kcal/kg increased egg weight and improved feed efficiency. Laying hens require no more than 744 mg DLys/d (corresponding to 0.68% DLys) to optimize egg production. However, when the objective is to maximize egg weight, hens should consume at least 843 mg DLys/d (corresponding to 0.76% D Lys).

The length of the feed restriction period affects eating behavior, growth performance, and the development of the proximal part of the gastrointestinal tract of young broilers.

We studied the effects of restricting the access to feed on the anticipatory eating behavior, growth performance, and the development of the proximal part of the gastrointestinal tract (GIT) in broilers. The experiment consisted in physical restriction of the access of broilers to feed for 0, 4, 6, or 8 h per day from 7 to 19 D of age. At 10, 13, 16, and 19 D of age, immediately before the start of the feed restriction (FR) period, 2 birds per cage were euthanized to evaluate crop and gizzard development. The experimental design was completely randomized, and the linear (L) and quadratic (Q) effects of fasting length on growth performance and GIT traits were determined. In addition, the effect of broiler age on GIT development was studied. From 7 to 19 D of age, ADFI (L, Q; P ≤ 0.05) and BW gain (L; P ≤ 0.01) decreased as the length of the FR period increased, with most of the differences observed with 6 or more hours of fasting. However, feed conversion ratio was not affected by FR length. The relative weight of the crop (% BW) and its fresh content increased (L; P ≤ 0.001) and the moisture of the digesta (%) decreased (L; P ≤ 0.001) as the FR period increased. The DM content (g) of the crop increased with FR, with most of the differences observed with 6 or more hours of fasting (L, Q; P ≤ 0.001). At 19 D of age, the Lactobacillus spp. count in the crop increased (L; P ≤ 0.05) with increase in the FR period. Fasting did not affect any gizzard trait at any age. In summary, physical restriction of the access to feed for 6 h or more reduced BW gain but did not affect feed conversion ratio in broilers from 7 to 19 D of age. Feed restriction for 4 to 8 h stimulated the anticipatory feeding behavior and crop development in broilers.

SEOM clinical guidelines for cervical cancer (2019).

Cervical cancer (CC) is the fourth most common cancer in women worldwide, strongly linked to high-risk human papilloma virus infection. In high-income countries, the screening programs have dramatically decreased the incidence of CC; however, the lack of accessibility to them in developing countries makes CC an important cause of mortality. Clinical stage is the most relevant prognostic factor in CC. The new FIGO staging system published in 2018 is more accurate than the previous one since it takes into account the lymph node status. In early stages, the primary treatment is surgery-with some concerns recently raised regarding minimally invasive surgery because it might decrease survival-or radiotherapy, whereas concomitant chemo-radiotherapy is the conventional approach in locally advanced stages. For recurrent or metastatic CC, the combination of chemotherapy plus bevacizumab is the preferred therapy. Immunotherapy approach based on checkpoint inhibitors is evolving as the election therapy following failure to platinum therapy.

MALDI imaging mass spectrometry and chemometric tools to discriminate highly similar colorectal cancer tissues.

Intratumour heterogeneity due to cancer cell clonal evolution and microenvironment composition and tumor differences due to genetic variations between patients suffering of the same cancer pathology play a crucial role in patient response to therapies. This study is oriented to show that matrix-assisted laser-desorption ionization-Mass spectrometry imaging (MALDI-MSI), combined with an advanced multivariate data processing pipeline can be used to discriminate subtle variations between highly similar colorectal tumors. To this aim, experimental tumors reproducing the emergence of drug-resistant clones were generated in athymic mice using subcutaneous injection of different mixes of two isogenic cell lines, the irinotecan-resistant HCT116-SN50 (R) and its sibling human colon adenocarcinoma sensitive cell line HCT116 (S). Because irinotecan-resistant and irinotecan-sensitive are derived from the same original parental HCT116 cell line, their genetic characteristics and molecular compositions are closely related. The multivariate data processing pipeline proposed relies on three steps: (a) multiset multivariate curve resolution (MCR) to separate biological contributions from background; (b) multiset K-means segmentation using MCR scores of the biological contributions to separate between tumor and necrotic parts of the tissues; and (c) partial-least squares discriminant analysis (PLS-DA) applied to tumor pixel spectra to discriminate between R and S tumor populations. High levels of correct classification rates (0.85), sensitivity (0.92) and specificity (0.77) for the PLS-DA classification model were obtained. If previously labelled tissue is available, the multistep modeling strategy proposed constitutes a good approach for the identification and characterization of highly similar phenotypic tumor subpopulations that could be potentially applicable to any kind of cancer tissue that exhibits substantial heterogeneity.

Use of physiological information based on grayscale images to improve mass spectrometry imaging data analysis from biological tissues.

The characterization of cancer tissues by matrix-assisted laser desorption ionization-mass spectrometry images (MALDI-MSI) is of great interest because of the power of MALDI-MS to understand the composition of biological samples and the imaging side that allows for setting spatial boundaries among tissues of different nature based on their compositional differences. In tissue-based cancer research, information on the spatial location of necrotic/tumoral cell populations can be approximately known from grayscale images of the scanned tissue slices. This study proposes as a major novelty the introduction of this physiologically-based information to help in the performance of unmixing methods, oriented to extract the MS signatures and distribution maps of the different tissues present in biological samples. Specifically, the information gathered from grayscale images will be used as a local rank constraint in Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) for the analysis of MALDI-MSI of cancer tissues. The use of this constraint, setting absence of certain kind of tissues only in clear zones of the image, will help to improve the performance of MCR-ALS and to provide a more reliable definition of the chemical MS fingerprint and location of the tissues of interest. The general strategy to address the analysis of MALDI-MSI of cancer tissues will involve the study of the MCR-ALS results and the posterior use of MCR-ALS scores as dimensionality reduction for image segmentation based on K-means clustering. The resolution method will provide the MS signatures and their distribution maps for each tissue in the sample. Then, the resolved distribution maps for each biological component (MCR scores) will be submitted as initial information to K-means clustering for image segmentation to obtain information on the boundaries of the different tissular regions in the samples studied. MCR-ALS prior to K-means not only provides the desired dimensionality reduction, but additionally resolved non-biological signal contributions are not used and the weight given to the different biological components in the segmentation process can be modulated by suitable preprocessing methods.

SEOM clinical guidelines in gestational trophoblastic disease (2017).

Gestational trophoblastic disease (GTD) is a rare but curable disease. Recent improvements in diagnosis and molecular biology have resulted in changes in staging and treatment. These guidelines provide evidence-based recommendation on how to manage GTD.

Human sperm motility, capacitation and acrosome reaction are impaired by 2-arachidonoylglycerol endocannabinoid.

The endocannabinoids are cannabinoids synthesized by mammalian tissues. These compounds are closely related to the regulation of the male reproductive system. However, little is known about the effects produced by 2-arachidonoylglycerol (2AG) on in vitro human sperm functions. This study was undertaken to determine the effects produced by 2AG on fresh human sperm and in the capacitation technique. Semen samples from healthy young men were exposed to different concentrations of 2AG before and during capacitation technique. In this work, we have demonstrated that 2AG induces the spontaneous acrosome reaction and reduces progressive motility in fresh human sperm. During the capacitation technique, sperm becomes more sensitive to low concentrations of 2AG, triggering the acrosome reaction and inhibiting protein phosphorylation. In summary, 2AG affects the in vitro functionality of human sperm by reducing motility, inhibiting capacitation and triggering the acrosome reaction.

SEOM guidelines for cervical cancer.

Cervical cancer (CC) is the second most common cancer worldwide, strongly linked to high-risk human papilloma virus infection. Although screening programs have led to a relevant reduction in the incidence and mortality due to CC in developed countries, it is still an important cause of mortality in undeveloped countries. Clinical stage is still the most relevant prognostic factor. In early stages, the primary treatment is surgery or radiotherapy, whereas concomitant chemo-radiotherapy is the conventional approach in locally advanced stages. In the setting of recurrent or metastatic CC, for the first time ever, the combination of chemotherapy plus bevacizumab prolongs the overall survival beyond 12 months. Therefore, this regimen is considered by most of the oncologist a new standard of care for metastatic/recurrent CC.

Combining multiset resolution and segmentation for hyperspectral image analysis of biological tissues.

Hyperspectral images can provide useful biochemical information about tissue samples. Often, Fourier transform infrared (FTIR) images have been used to distinguish different tissue elements and changes caused by pathological causes. The spectral variation between tissue types and pathological states is very small and multivariate analysis methods are required to describe adequately these subtle changes. In this work, a strategy combining multivariate curve resolution-alternating least squares (MCR-ALS), a resolution (unmixing) method, which recovers distribution maps and pure spectra of image constituents, and K-means clustering, a segmentation method, which identifies groups of similar pixels in an image, is used to provide efficient information on tissue samples. First, multiset MCR-ALS analysis is performed on the set of images related to a particular pathology status to provide basic spectral signatures and distribution maps of the biological contributions needed to describe the tissues. Later on, multiset segmentation analysis is applied to the obtained MCR scores (concentration profiles), used as compressed initial information for segmentation purposes. The multiset idea is transferred to perform image segmentation of different tissue samples. Doing so, a difference can be made between clusters associated with relevant biological parts common to all images, linked to general trends of the type of samples analyzed, and sample-specific clusters, that reflect the natural biological sample-to-sample variability. The last step consists of performing separate multiset MCR-ALS analyses on the pixels of each of the relevant segmentation clusters for the pathology studied to obtain a finer description of the related tissue parts. The potential of the strategy combining multiset resolution on complete images, multiset segmentation and multiset local resolution analysis will be shown on a study focused on FTIR images of tissue sections recorded on inflamed and non-inflamed palatine tonsils.

Monitoring polymorphic transformations by using in situ Raman hyperspectral imaging and image multiset analysis.

Polymorphism is often encountered in many crystalline compounds. To control the quality of the products, it is relevant knowing the potential presence of polymorph transformations induced by different agents, such as light exposure or temperature changes. Raman images offer a great potential to identify polymorphs involved in a process and to accurately describe this kind of solid-state transformation in the surface scanned. As a way of example, this work proposes the use of multiset analysis on the series of Raman hyperspectral images acquired during a thermal induced transformation of carbamazepine as the optimal way to extract useful information about polymorphic or any other kind of dynamic transformation among process compounds. Image multiset analysis, performed by using Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS), will furnish pure spectra and distribution maps of the compounds involved in the process and, hence, will allow the identification of polymorphs and, more important, the description of the process evolution at a global and local (pixel) level. Thus, process will be defined from a spatial point of view and by means of a set of global process profiles dependent on the process control variable. The results obtained confirm the power of this methodology and show the crucial role of the spatial information contained in the image (absent in conventional spectroscopy) for a correct process description.

Breast cancer management in the elderly.

The increase in life expectancy in the western world means that we are faced with patients diagnosed with breast cancer in old age with increasing frequency. The management of these cases is a challenge for the oncologist, who must take into account the conditions associated with advanced age and the lack of trials in this population. In this review, we addressed the incorporation of geriatric assessment methods that may be useful in making decisions, the particular biological characteristics of breast cancer in elderly patients and their treatment in both localized and advanced disease. Finally, we collected recommendations based on scientific evidence regarding the monitoring and life-style after finishing treatment.

Blending process modeling and control by multivariate curve resolution.

The application of the Multivariate Curve Resolution by Alternating Least Squares (MCR-ALS) method to model and control blend processes of pharmaceutical formulations is assessed. Within the MCR-ALS framework, different data analysis approaches have been tested depending on the objective of the study, i.e., knowing the effect of different factors in the evolution of the blending process (modeling) or detecting the blend end-point and monitoring the concentration of the different species during and at the end of the process (control). Data analysis has been carried out studying multiple blending runs simultaneously taking advantage of the multiset mode of the MCR-ALS method. During the ALS optimization, natural constraints, such as non-negativity (spectral and concentration directions) have been applied for blend modeling. When blending control is the main purpose, a variant of the MCR-ALS algorithm with correlation constraint in the concentration direction has been additionally used. This constraint incorporates an internal calibration procedure, which relates resolved concentration values (in arbitrary units) with the real reference concentration values in the calibration samples (known references) providing values in real concentration scale in the final MCR-ALS results. Two systems consisting of pharmaceutical mixtures of an active principle (acetaminophen) with two or four excipients have been investigated. In the first case, MCR results allowed the description of the evolution of the individual compounds and the assessment of some physical effects in the blending process. In the second case, MCR analysis allowed the detection of the end-point of the process and the assessment of the effects linked to variations in the concentration level of the compounds.

Chemometric strategies to unmix information and increase the spatial description of hyperspectral images: a single-cell case study.

Hyperspectral images are analytical measurements that provide spatial and structural information. The spatial description of the samples is the specific asset of these measurements and the reason why they have become so important in (bio)chemical fields, where the microdistribution of sample constituents or the morphology or spatial pattern of sample elements constitute very relevant information. Often, because of the small size of the samples, the spatial detail provided by the image acquisition systems is insufficient. This work proposes a data processing strategy to overcome this instrumental limitation and increase the natural spatial detail present in the acquired raw images. The approach works by combining the information of a set of images, slightly shifted from each other with a motion step among them lower than the pixel size of the raw images. The data treatment includes the application of multivariate curve resolution (unmixing) multiset analysis to the set of collected images to obtain the distribution maps and spectral signatures of the sample constituents. These sets of maps are noise-filtered and compound-specific representations of all the relevant information in the pixel space and decrease the dimensionality of the original image from hundreds of spectral channels to few sets of maps, one per sample constituent or element. The information in each compound-specific set of maps is combined via a super-resolution post-processing algorithm, which takes into account the shifting, decimation, and point spread function of the instrument to reconstruct a single map per sample constituent with much higher spatial detail than that of the original image measurement.

GEICO (Spanish Group for Investigation on Ovarian Cancer) treatment guidelines in ovarian cancer 2012.

In 2006, under the auspices of The Spanish Research Group for Ovarian Cancer (Spanish initials GEICO), the first "Treatment Guidelines in Ovarian Cancer" were developed and then published in Clinical and Translational Oncology by Poveda Velasco et al. (Clin Transl Oncol 9(5):308-316, 2007). Almost 6 years have elapsed and over this time, we have seen some important developments in the treatment of ovarian cancer. Significant changes were also introduced after the GCIG-sponsored 4th Consensus Conference on Ovarian Cancer by Stuart et al. (Int J Gynecol Cancer 21:750-755, 2011). So we decided to update the treatment guidelines in ovarian cancer and, with this objective, a group of investigators of the GEICO group met in February 2012. This study summarizes the presentations, discussions and evidence that were reviewed during the meeting and during further discussions of the manuscript.

The pudendal thigh flap as YV advanced flap for the release of perineum burns contractures.

Contractures secondary to burns affecting the perineum often cause severe functional, aesthetic and psychological harm. Many different surgical techniques are used to treat such conditions ranging from grafts, to triangular plasty transposition or advancement flaps of local tissue. It is usually advisable to use a flap or local perineoplasty because the quality of reconstruction tends to be better and the risk of reoccurrence of the contracture is lower. The pudendal thigh fasciocutaneous (PTF) flap is an axial patterned and sensate flap based on the groin crease. It has frequently been used for perineal and vaginal reconstructions. Technically, it is not difficult to perform, with a well tolerated scar located in the inguinal crease, and it is characterized by its thinness and its ready adaptation to the defects, and because it maintains sensitivity. To the best of our knowledge, no previous case of perineal contracture treatment has been reported with the use of a PTF flap harvested as an YV advanced flap. Here we report the case of a patient with a severe contracture who was treated using the flap described above, a satisfactory result being achieved.

Resolution and segmentation of hyperspectral biomedical images by multivariate curve resolution-alternating least squares.

MCR-ALS is a resolution method that has been applied in many different fields, such as process analysis, environmental data and, recently, hyperspectral image analysis. In this context, the algorithm provides the distribution maps and the pure spectra of the image constituents from the sole information in the raw image measurement. Based on the distribution maps and spectra obtained, additional information can be easily derived, such as identification of constituents when libraries are available or quantitation within the image, expressed as constituent signal contribution. This work summarizes first the protocol followed for the resolution on two examples of kidney calculi, taken as representations of images with major and minor compounds, respectively. Image segmentation allows separating regions of images according to their pixel similarity and is also relevant in the biomedical field to differentiate healthy from non-healthy regions in tissues or to identify sample regions with distinct properties. Information on pixel similarity is enclosed not only in pixel spectra, but also in other smaller pixel representations, such as PCA scores. In this paper, we propose the use of MCR scores (concentration profiles) for segmentation purposes. K-means results obtained from different pixel representations of the data set are compared. The main advantages of the use of MCR scores are the interpretability of the class centroids and the compound-wise selection and preprocessing of the input information in the segmentation scheme.

Prognostic time dependence of deletions affecting codons 557 and/or 558 of KIT gene for relapse-free survival (RFS) in localized GIST: a Spanish Group for Sarcoma Research (GEIS) Study.

BACKGROUND: To assess whether deletions involving codons 557 and/or 558 (critical deletions) of exon 11 of KIT are relevant in the prognosis of relapse-free survival (RFS) in gastrointestinal stromal tumor (GIST) patients with a long follow-up. PATIENTS AND METHODS: A univariate and multivariate analysis for RFS were carried out on 162 localized GIST patients over the entire follow-up period and over the intervals 0-4 years and >4 years. Factors assessed among others were Fletcher/National Institutes of Health and Miettinen-Lasota/Armed Forces Institute of Pathology (M-L/AFIP) risk categories, critical deletions and non-deletion-type mutation (NDTM) within exon 11 of KIT. RESULTS: Multivariate analyses revealed that M-L/AFIP [relative risk (RR) 11.45, confidence interval (CI) 4.40-29.76, for the high-risk subgroup and RR 5.97, CI 2.09-17.06, for the intermediate subgroup] and critical deletions (RR 3.05, CI 1.59-5.85) were independent prognostic factors for RFS for the first 4 years and for the entire follow-up period. Beyond 4 years, the high-risk M-L/AFIP subgroup (RR 8.12, CI 1.48-44.4) and NDTM (RR 6.42, CI 1.17-35.12) were independent prognostic factors for RFS. The median follow-up was 84 months. CONCLUSION: Critical deletions represent a time-dependent prognostic factor limited to the first 4 years after surgery, which could help identify a subset with higher and earlier risk for relapse in GIST patients.