BACKGROUND: Hospital-based studies recently have shown increases in colorectal cancer survival, and better survival for women, young people, and patients diagnosed at an early disease stage. OBJECTIVE: To describe the overall survival and analyze the prognostic factors of patients treated for colorectal cancer at an oncology center. METHODS: The analysis included patients diagnosed with colon and rectal adenocarcinoma between 2000 and 2013 and identified in the Hospital Cancer Registry at A.C.Camargo Cancer Center. Overall 5-year survival was estimated using the Kaplan-Meier method, and prognostic factors were evaluated in a Cox regression model. Hazard ratios (HR) are reported with 95% confidence intervals (CI). RESULTS: Of 2,279 colorectal cancer cases analyzed, 58.4% were in the colon. The 5-year overall survival rate for colorectal cancer patients was 63.5% (65.6% and 60.6% for colonic and rectal malignancies, respectively). The risk of death was elevated for patients in the 50-74-year (HR=1.24, 95%CI =1.02-1.51) and ≥75-year (HR=3.02, 95%CI =2.42-3.78) age groups, for patients with rectal cancer (HR=1.37, 95%CI =1.11-1.69) and for those whose treatment was started >60 days after diagnosis (HR=1.22, 95%CI =1.04-1.43). The risk decreased for patients diagnosed in recent time periods (2005-2009 HR=0.76, 95%CI =0.63-0.91; 2010-2013 HR=0.69, 95%CI =0.57-0.83). CONCLUSION: Better survival of patients with colorectal cancer improves with early stage and started treatment within 60 days of diagnosis. Age over 70 years old was an independent factor predictive of a poor prognosis. The overall survival increased to all patients treated in the period 2000-2004 to 2010-2013.

Loss of the Y chromosome (LOY) in peripheral blood mononuclear cells (PBMCs) is the most common somatic alteration in men and is associated with higher mortality from epithelial cancers^1,2,3. In tumours, epithelial LOY is also associated with poor survival^4,5,6,7. This raises several fundamental questions, such as why LOY in PBMCs drives cancer mortality and whether there is a relationship between LOY in PBMCs, PBMC-derived immune cells and cancer cells (and, if so, what its consequences are). We sought to answer these questions through a comprehensive pan-cancer analysis of bulk and single-cell RNA sequencing data from 29 human tumour types, along with autochthonous and syngeneic mouse models. In human and mouse tumours, malignant epithelial cells had the highest LOY prevalence, yet LOY was also present in tumour stromal and immune cells, with LOY in malignant epithelial cells predicting LOY in benign cells. LOY also correlated between paired tumour and PBMC samples from patients. Among benign cells, LOY induced the strongest shift in CD4⁺ and CD8⁺ T cells, with both showing transcriptomic signatures of immunosuppression. Furthermore, the magnitude of LOY in epithelial cells, CD4⁺ T cells and CD8⁺ T cells independently predicts survival, with tumours exhibiting concurrent epithelial and T cell LOY having the worst outcomes. Here we establish a model that links LOY in immune cells to LOY in malignant cells, which may explain in part why LOY in PBMCs is associated with increased cancer mortality.

Spared regions of the damaged central nervous system undergo dynamic remodelling and exhibit a remarkable potential for therapeutic exploitation¹. Lesion-remote astrocytes (LRAs), which interact with viable neurons and glia, undergo reactive transformations whose molecular and functional properties are poorly understood². Here, using multiple transcriptional profiling methods, we investigated LRAs from spared regions of mouse spinal cord following traumatic spinal cord injury. We show that LRAs acquire a spectrum of molecularly distinct, neuroanatomically restricted reactivity states that evolve after spinal cord injury. We identify transcriptionally unique reactive LRAs in degenerating white matter that direct the specification and function of local microglia that clear lipid-rich myelin debris to promote tissue repair. Fuelling this LRA functional adaptation is the secreted matricellular protein CCN1. Loss of astrocyte-derived CCN1 results in excessive, aberrant activation of local microglia, characterized by abnormal molecular specification, impaired debris processing reflected by the intracellular accumulation of myelin and axon debris, and dysregulated lipid metabolism with distinctive attenuation in lipid droplet accumulation. Mechanistically, we find that CCN1 binds microglial SDC4 to augment lipid storage, linking this signalling axis to a vital repair-associated lipid buffering response in debris-clearing microglia. Accordingly, microglial deficits resulting from astrocyte CCN1 depletion culminate in blunted clearance of white matter debris and impaired neurological recovery from spinal cord injury. Ccn1-expressing white matter astrocytes are induced by local myelin damage and are generated in diverse demyelinating disorders in mice and humans, pointing to their fundamental, evolutionarily conserved role in white matter repair. Our findings show that context-specific cues shape regionally distinct LRA reactivity states with functional adaptations that orchestrate multicellular processes underlying neural repair and influence disease outcome.

In this paper, we propose a defective model induced by a frailty term for modeling the proportion of cured. Unlike most of the cure rate models, defective models have advantage of modeling the cure rate without adding any extra parameter in model. The introduction of an unobserved heterogeneity among individuals has bring advantages for the estimated model. The influence of unobserved covariates is incorporated using a proportional hazard model. The frailty term assumed to follow a gamma distribution is introduced on the hazard rate to control the unobservable heterogeneity of the patients. We assume that the baseline distribution follows a Gompertz and inverse Gaussian defective distributions. Thus we propose and discuss two defective distributions: the defective gamma-Gompertz and gamma-inverse Gaussian regression models. Simulation studies are performed to verify the asymptotic properties of the maximum likelihood estimator. Lastly, in order to illustrate the proposed model, we present three applications in real data sets, in which one of them we are using for the first time, related to a study about breast cancer in the A.C.Camargo Cancer Center, São Paulo, Brazil.

Final oocyte maturation with Human Chorionic Gonadotropin (hCG) and ovarian stimulation with Follicle Stimulation Hormone (FSH) combined with Gonadotrophin-releasing Hormone (GnRH) antagonist to block Luteinizing hormone (LH) surge is a standard procedure of in vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI). However, GnRH agonist has been replacing the use of hCG in certain situations, especially in patients at risk of Ovarian Hyperstimulation Syndrome (OHSS). Some studies have also shown advantages in the combined use of GnRH agonist concurrently with hCG in inducing final oocyte maturation, a treatment known as "Dual Trigger". In theory, this method combines the advantages of both induction regimens, and it has brought promising results. The objective of this study is to compare Dual Trigger with the use of hCG alone or the use of GnRH agonist alone. A systematic review of articles on Dual Trigger and a retrospective cohort study comparing the three methods of induction of final oocyte maturation have been conducted. It has been found that Dual Triggering for poor responder patients had a statistically significant increase in the number of retrieved oocytes, mature oocytes, and fertilized embryos in the positive beta hCG rate, implantation rate, and newborn/transferred embryo (TE) rate.