Explore the vast range of titles available.

Examines a potential ethnic disparity in the phenotype of polycythaemia vera (PV) between New Zealand European and Polynesian patients. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

The addition of the oral proteasome inhibitor ixazomib to a regimen of lenalidomide plus dexamethasone led to a significant prolongation of progression-free survival of almost 6 months, as compared with placebo, with a small increase in the risk of thrombocytopenia. Outcomes of multiple myeloma have improved substantially over the past 15 years with the introduction of proteasome inhibitors and immunomodulatory drugs, 1 , 2 and these agents now form the backbone of therapy for multiple myeloma. 3 In phase 3 studies, triplet regimens based on these agents were shown to be more efficacious than doublet regimens when these regimens were used as a first-line treatment 4 – 6 and in relapsed disease. 7 , 8 In addition, there has been a shift in treatment patterns toward the use of extended treatment to further improve long-term outcomes, 9 and this shift highlights the need for additional effective agents with . . .

Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries. Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies. In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75–84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I2=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28–4·7) and 7·0% (1·2–13·0). Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control. Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network.

Phosphorus is one of the essential nutrients for plant growth, but it may be relatively unavailable to plants because of its chemistry. In soil, the majority of phosphorus is present in the form of a phosphate, usually as metal complexes making it bound to minerals or organic matter. Therefore, inorganic phosphate solubilization is an important process of plant growth promotion by plant associated bacteria and fungi. Non-nodulating plant species have been shown to thrive in low-nutrient environments, in some instances by relying on plant associated microorganisms called endophytes. These microorganisms live within the plant and help supply nutrients for the plant. Despite their potential enormous environmental importance, there are a limited number of studies looking at the direct molecular impact of phosphate solubilizing endophytic bacteria on the host plant. In this work, we studied the impact of two endophyte strains of wild poplar ( Populus trichocarpa ) that solubilize phosphate. Using a combination of x-ray imaging, spectroscopy methods, and proteomics, we report direct evidence of endophyte-promoted phosphorus uptake in poplar. We found that the solubilized phosphate may react and become insoluble once inside plant tissue, suggesting that endophytes may aid in the re-release of phosphate. Using synchrotron x-ray fluorescence spectromicroscopy, we visualized the nutrient phosphorus inside poplar roots inoculated by the selected endophytes and found the phosphorus in both forms of organic and inorganic phosphates inside the root. Tomography-based root imaging revealed a markedly different root biomass and root architecture for poplar samples inoculated with the phosphate solubilizing bacteria strains. Proteomics characterization on poplar roots coupled with protein network analysis revealed novel proteins and metabolic pathways with possible involvement in endophyte enriched phosphorus uptake. These findings suggest an important role of endophytes for phosphorus acquisition and provide a deeper understanding of the critical symbiotic associations between poplar and the endophytic bacteria.

Abstract Coronavirus disease 2019 (COVID-19) can become complicated by secondary invasive fungal infections (IFIs), stemming primarily from severe lung damage and immunologic deficits associated with the virus or immunomodulatory therapy. Other risk factors include poorly controlled diabetes, structural lung disease and/or other comorbidities, and fungal colonization. Opportunistic IFI following severe respiratory viral illness has been increasingly recognized, most notably with severe influenza. There have been many reports of fungal infections associated with COVID-19, initially predominated by pulmonary aspergillosis, but with recent emergence of mucormycosis, candidiasis, and endemic mycoses. These infections can be challenging to diagnose and are associated with poor outcomes. The reported incidence of IFI has varied, often related to heterogeneity in patient populations, surveillance protocols, and definitions used for classification of fungal infections. Herein, we review IFI complicating COVID-19 and address knowledge gaps related to epidemiology, diagnosis, and management of COVID-19–associated fungal infections.

Candida auris is an emerging, multidrug-resistant yeast that can spread in healthcare settings. It can cause invasive infections with high mortality and is difficult to identify using traditional yeast identification methods. Candida auris has been reported in more than a dozen countries, and as of August 2017, 112 clinical cases have been reported in the United States. Candida auris can colonize skin and persist in the healthcare environment, allowing for transmission between patients. Prompt investigation and aggressive interventions, including notification to public health agencies, implementation of contact precautions, thorough environmental cleaning and disinfection, infection control assessments, contact tracing and screening of contacts to assess for colonization, and retrospective review of microbiology records and prospective surveillance for cases at laboratories are all needed to limit the spread of C. auris. This review summarizes the current recommended approach to manage cases and control transmission of C. auris in healthcare facilities.

The incidence and prevalence of food allergy (FA) is increasing. While several studies have established the safety and efficacy of early introduction of single allergens in infants for the prevention of FA, the exact dose, frequency, and number of allergens that can be safely introduced to infants, particularly in those at high or low risk of atopy, are still unclear. This 1-year pilot study evaluated the safety of the early introduction of single foods (milk, egg, or peanut) vs. two foods (milk/egg, egg/peanut, milk/peanut) vs. multiple foods (milk/egg/peanut/cashew/almond/shrimp/walnut/wheat/salmon/hazelnut at low, medium, or high doses) vs. no early introduction in 180 infants between 4–6 months of age. At the end of the study, they were evaluated for plasma biomarkers associated with food reactivity via standardized blood tests. Two to four years after the start of the study, participants were evaluated by standardized food challenges. The serving sizes for the single, double, and low dose mixtures were 300 mg total protein per day. The serving sizes for the medium and high dose mixtures were 900 mg and 3000 mg total protein, respectively. Equal parts of each protein were used for double or mixture foods. All infants were breastfed until at least six months of age. The results demonstrate that infants at either high or low risk for atopy were able to tolerate the early introduction of multiple allergenic foods with no increases in any safety issues, including eczema, FA, or food protein induced enterocolitis. The mixtures of foods at either low, medium, or high doses demonstrated trends for improvement in food challenge reactivity and plasma biomarkers compared to single and double food introductions. The results of this study suggest that the early introduction of foods, particularly simultaneous mixtures of many allergenic foods, may be safe and efficacious for preventing FA and can occur safely. These results need to be confirmed by larger randomized controlled studies.

Since the discovery of the fusion between EML4 (echinoderm microtubule associated protein-like 4) and ALK (anaplastic lymphoma kinase), EML4-ALK, in lung adenocarcinomas in 2007, and the subsequent identification of at least 15 different variants in lung cancers, there has been a revolution in molecular-targeted therapy that has transformed the outlook for these patients. Our recent focus has been on understanding how and why the expression of particular variants can affect biological and molecular properties of cancer cells, as well as identifying the key signalling pathways triggered, as a result. In the clinical setting, this understanding led to the discovery that the type of variant influences the response of patients to ALK therapy. Here, we discuss what we know so far about the EML4-ALK variants in molecular signalling pathways and what questions remain to be answered. In the longer term, this analysis may uncover ways to specifically treat patients for a better outcome.

Chile has high incidence rates of gallbladder cancer globally, particularly among Amerindian women, who also have a high prevalence of gallstones. We examined differences in inflammatory biomarkers between Mapuche and non-Mapuche women from the Chile Biliary Longitudinal Study, a cohort of women with ultrasound-detected gallstones. We randomly selected 200 Mapuche women frequency matched to non-Mapuche women on age and statin use Inflammatory biomarkers were analyzed using a multiplex assay and linear regression to assess associations of a priori markers (CCL20, CXCL10, IL-6, and IL-8) with ethnicity. Novel biomarkers were analyzed using exploratory factor analysis (EFA) and sufficient dimension reduction (SDR) to identify correlated marker groups, followed by linear regression to examine their association with ethnicity. The mean values of IL-8 were higher in Mapuche than non-Mapuche women ( P  = 0.04), while CCL20, CXCL10, and IL-6 did not differ significantly by ethnicity. EFA revealed two marker groups associated with ethnicity ( P  = 0.03 and P  < 0.001). SDR analysis confirmed correlation between the biomarkers and ethnicity. We found higher IL-8 levels among Mapuche than non-Mapuche women. Novel inflammatory biomarkers were correlated with ethnicity and should be studied further for their role in gallbladder disease. These findings may elucidate underlying ethnic disparities in gallstones and carcinogenesis among Amerindians.

Studies have shown that reducing sedation of critically ill patients shortens time on the ventilator and in the intensive care unit (ICU). Little is known, however, of how such strategies affect long-term cognitive, psychological, and functional outcomes. To determine the long-term effects of a wake up and breathe protocol that interrupts and reduces sedative exposure in the ICU. In this a priori planned substudy conducted at one tertiary care hospital during the Awakening and Breathing Controlled Trial, a multicenter randomized controlled trial, we assessed cognitive, psychological, and functional/quality-of-life outcomes 3 and 12 months postdischarge among 180 medical ICU patients randomized to paired daily spontaneous awakening trials with spontaneous breathing trials (SBTs) or to sedation per usual care plus daily SBTs. Cognitive impairment was less common in the intervention group at 3-month follow-up (absolute risk reduction, 20.2%; 95% confidence interval, 1.5-36.1%; P = 0.03) but not at 12-month follow-up (absolute risk reduction, -1.9%; 95% CI, -21.3 to 27.1%; P = 0.89). Composite cognitive scores, alternatively, were similar in the two groups at 3-month and 12-month follow-up (P = 0.80 and 0.61, respectively), as were symptoms of depression (P = 0.59 and 0.82) and posttraumatic stress disorder (P = 0.59 and 0.97). Activities of daily living, functional status, and mental and physical quality of life were similar between groups throughout follow-up. In this trial, management of mechanically ventilated medical ICU patients with a wake up and breathe protocol resulted in similar cognitive, psychological, and functional outcomes among patients tested 3 and 12 months post-ICU. The proven benefits of this protocol, including improved 1-year survival, were not offset by adverse long-term outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT 00097630).