This study investigated the potential of single nucleotide polymorphisms as predictors of survival in two cohorts comprising 417 metastatic colorectal cancer (mCRC) patients treated with the FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) regimen. The rs4806668G > T of the ribosomal protein gene RPL28 was associated with shorter progression-free survival and overall survival by 5 and 9 months (P = 0.002), with hazard ratios of 3.36 (P < 0.001) and 3.07 (P = 0.002), respectively. The rs4806668T allele was associated with an increased RPL28 expression in transverse normal colon tissues (n = 246, P = 0.007). RPL28 expression was higher in colorectal tumors compared to paired normal tissues by up to 124% (P < 0.001) in three independent datasets. Metastatic cases with highest RPL28 tumor expression had a reduced survival in two datasets (n = 88, P = 0.009 and n = 56, P = 0.009). High RPL28 was further associated with changes in immunoglobulin and extracellular matrix pathways. Repression of RPL28 reduced proliferation by 1.4-fold to 5.6-fold (P < 0.05) in colon cancer HCT116 and HT-29 cells. Our findings suggest that the ribosomal RPL28 protein may influence mCRC outcome.

Background: The identification of factors involved in the postnatal growth of preterm infants will help achieve growth similar to that of term infants. Objectives: As per protocol: to compare body composition in very preterm infants at term-corrected age (TCA) with that in term infants, and to explore relationships between neonatal characteristics and body composition in preterm infants. Methods: Anthropometry, nutritional characteristics, and neonatal outcomes were prospectively collected in 26 preterm (<29 weeks) and 33 term (37-40 weeks) infants. Body composition using dual-energy X-ray absorptiometry (DXA) was measured at TCA in preterm infants and between days 7 and 10 in term infants. Results: Parenteral nutrition in preterm infants provided a mean of 2.9 ± 0.2 and 2.1 ± 0.5 g/kg/day of intravenous amino acids and lipids, respectively, during the first week of life. The mean weight gain velocity from birth to DXA assessment was 12.1 ± 1.4 g/kg/day. Compared with term infants, preterm infants at TCA were shorter and lighter, with a smaller head circumference, a lower weight estimated by DXA (2,960 ± 552 vs. 3,843 ± 377 g), and increased skinfold thicknesses. Fat mass percent (13.9 ± 5.4%) and lean mass percent (84.7 ± 5.6%) in preterm infants were similar to those in term infants (14.7 ± 3.5 and 83.5 ± 3.6%, respectively). Neonatal weight gain velocity in preterm infants was positively associated with lean mass (grams). Conclusion: Subcutaneous fat is increased in preterm infants. Higher protein intake in preterm infants might increase weight gain velocity and achieve a lean mass comparable to that of term infants.

Background: The interdependence of cytokines and appetite‐modifying hormones implicated in cancer anorexia‐cachexia syndrome (CACS) remains unclear. This study aimed to regroup these cytokines and hormones into distinct inflammatory (or non‐inflammatory) pathways and determine whether these pathways can classify patients with CACS phenotypes.Methods: Clinical characteristics of 133 patients [61.7% male; mean age = 63.4 (SD: 13.1) years] with advanced cancer prior to oncology treatments were documented, including weight loss history. Patients completed the Functional Assessment of Anorexia‐Cachexia Therapy (FAACT) questionnaire and Timed Up and Go test and had their sex‐standardized skeletal muscle index (z‐SMI) and fat mass index (z‐FMI) derived using computed tomography scans. Their plasma levels of cytokines and appetite‐modifying hormones were also determined. Date of death was recorded. Exploratory factor analysis (EFA) was used to regroup 15 cytokines and hormone into distinct inflammatory pathways (factors). For each patient, regression factor scores (RFS), which tell how strongly the patient associates with each factor, were derived. Two‐step cluster analysis on the RFS was used to classify patients into groups. CACS phenotypes were correlated with RFS and compared between groups. Groups' survival was estimated using Kaplan–Meier analysis.Results: Patients had low z‐SMI (mean = −3.78 cm²/m²; SD: 8.88) and z‐FMI (mean = 0.08 kg²/m²; SD: 56.25), and 62 (46.6%) had cachexia. EFA identified three factors: (F‐1) IFN‐γ, IL‐1β, Il‐4, IL‐6, IL‐10, IL‐12, TGFβ1 (positive contribution), and IL‐18 (negative); (F‐2) IL‐8, IL‐18, MCP‐1, TGFβ1, TNF‐α (positive), and ghrelin (negative); and (F‐3) TRAIL and leptin (positive), and TGFβ1 and adiponectin (negative). RFS‐1 was associated with cachexia (P = 0.002); RFS‐2, with higher CRP (P < 0.0001) and decreased physical function (P = 0.01); and RFS‐3 with better appetite (P = 0.04), lower CRP (P = 0.002), higher z‐SMI (P = 0.04) and z‐FMI (P < 0.0001), and less cachexia characteristics (all P < 0.001). Four patient groups were identified with specific RFS clusters aligning with the CACS continuum from no cachexia to pre‐cachexia, cachexia, and terminal cachexia. Compared to the other two groups, groups 1 and 2 had higher plasma levels of IL‐18 and TRAIL. Group 1 also had lower inflammatory cytokines, adiponectin, and CRP compared to the other three groups. Group 3 had inflammatory cytokine levels similar to group 2, except for TNF‐α and leptin which were lower. Group 4 had very high inflammatory cytokines, adiponectin, and CRP compared to the other 3 groups (all P < 0.0001). Groups 3 and 4 had worse cachexia characteristics (P < 0.05) and shorter survival (log rank: P = 0.0009) than the other two groups.Conclusions: This exploratory study identified three distinct pathways of inflammation, or lack thereof, characterizing different CACS phenotypes.

Background: In men with localized prostate cancer who are undergoing radical prostatectomy (RP), it is uncertain whether their systemic hormonal environment is associated with outcomes. The objective of the study was to examine the association between the circulating steroid metabolome with prognostic factors and progression. Methods: The prospective PROCURE cohort was recruited from 2007 to 2012, and comprises 1,766 patients with localized prostate cancer who provided blood samples prior to RP. The levels of 15 steroids were measured in plasma using mass spectrometry, and their association with prognostic factors and disease-free survival (DFS) was established with logistic regression and multivariable Cox proportional hazard models. Results: The median follow-up time after surgery was 73.2 months. Overall, 524 patients experienced biochemical failure and 75 developed metastatic disease. Testosterone and androsterone levels were higher in low-risk disease. Associations were observed between adrenal precursors and risk of cancer progression. In high-risk patients, a one-unit increment in log-transformed androstenediol (A5diol) and dehydroepiandrosterone-sulfate (DHEA-S) levels were linked to DFS with HR of 1.47 (P = 0.0017; q = 0.026) and 1.24 (P = 0.043; q = 0.323), respectively. Although the number of metastatic events was limited, trends with metastasis-free survival were observed for A5diol (HR = 1.51; P = 0.057) and DHEA-S levels (HR = 1.43; P = 0.054). Conclusions: In men with localized prostate cancer, our data suggest that the preoperative steroid metabolome is associated with the risk of recurrence of high-risk disease. Impact: The associations of adrenal androgens with progression of localized high-risk disease could help refine hormonal strategies for these patients.

Background: In Canada, 30%-60% of patients presenting to emergency departments are ambulatory. This category has been labeled as a source of emergency department overuse. Acting on the presumption that primary care practices and walk-in clinics offer equivalent care at a lower cost, governments have invested massively in improving access to these alternative settings in the hope that patients would present there instead when possible, thereby reducing the load on emergency departments. Data in support of this approach remain scarce and equivocal. Objective: The aim of this study is to compare the value of care received in emergency departments, walk-in clinics, and primary care practices by ambulatory patients with upper respiratory tract infection, sinusitis, otitis media, tonsillitis, pharyngitis, bronchitis, influenza-like illness, pneumonia, acute asthma, or acute exacerbation of chronic obstructive pulmonary disease. Methods: A multicenter prospective cohort study will be performed in Ontario and Québec. In phase 1, a time-driven activity-based costing method will be applied at each of the 15 study sites. This method uses time as a cost driver to allocate direct costs (eg, medication), consumable expenditures (eg, needles), overhead costs (eg, building maintenance), and physician charges to patient care. Thus, the cost of a care episode will be proportional to the time spent receiving the care. At the end of this phase, a list of care process costs will be generated and used to calculate the cost of each consultation during phase 2, in which a prospective cohort of patients will be monitored to compare the care received in each setting. Patients aged 18 years and older, ambulatory throughout the care episode, and discharged to home with one of the aforementioned targeted diagnoses will be considered. The estimated sample size is 1485 patients. The 3 types of care settings will be compared on the basis of primary outcomes in terms of the proportion of return visits to any site 3 and 7 days after the initial visit and the mean cost of care. The secondary outcomes measured will include scores on patient-reported outcome and experience measures and mean costs borne wholly by patients. We will use multilevel generalized linear models to compare the care settings and an overlap weights approach to adjust for confounding factors related to age, sex, gender, ethnicity, comorbidities, registration with a family physician, socioeconomic status, and severity of illness. Results: Phase 1 will begin in 2021 and phase 2, in 2023. The results will be available in 2025. Conclusions: The end point of our program will be for deciders, patients, and care providers to be able to determine the most appropriate care setting for the management of ambulatory emergency respiratory conditions, based on the quality and cost of care associated with each alternative. International Registered Report Identifier (IRRID): PRR1-10.2196/25619