Real-World Outcomes of Adolescents and Young Adults with Diffuse Large B-Cell Lymphoma: A Multicenter Retrospective Cohort Study.

Purpose: Patients with diffuse large B-cell lymphoma (DLBCL) are typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, a standard of care for managing adolescents and young adults (AYAs) with DLBCL is lacking. We examine treatment approaches and outcomes of this population. Methods: We included 90 AYAs (15-39 years) diagnosed with DLBCL between 2008 and 2018 in three tertiary centers in Peru. Overall response rates (ORR) were available for all patients. Overall survival (OS) and progression-free survival (PFS) rates were estimated using the Kaplan-Meier method. Results: The median age at diagnosis was 33 years, 57% were males, 57% had good performance status (Lansky/Karnofsky ≥90), and 61% were diagnosed with early-stage disease (Ann Arbor stages I-II). R-CHOP (n = 69, 77%) was the most frequently used first-line regimen, with an ORR of 91%. With a median follow-up of 83 months, the 5-year OS and PFS among all patients were 79% and 67%, respectively. Among the patients who received R-CHOP, the 5-year OS and PFS were 77% and 66%, respectively. Of the 29 (32%) patients with relapsed/refractory (R/R) disease, 83% received second-line treatment and only 14% underwent consolidation therapy with autologous transplantation. The 3-year OS for R/R DLBCL was 36%. Conclusion: Our data show that AYAs with DLBCL who received conventional therapy had comparable outcomes to those observed in studies conducted among the adult population. However, the prognosis for AYAs with R/R disease was dismal, indicating the unmet need for developing and increasing access to novel treatment modalities in AYAs.

Impact of hospital characteristics on implementation of a Pediatric Early Warning System in resource-limited cancer hospitals.

Background: Pediatric Early Warning Systems (PEWS) aid in identification of deterioration in hospitalized children with cancer but are underutilized in resource-limited settings. Proyecto EVAT is a multicenter quality improvement (QI) collaborative in Latin America to implement PEWS. This study investigates the relationship between hospital characteristics and time required for PEWS implementation. Methods: This convergent mixed-methods study included 23 Proyecto EVAT childhood cancer centers; 5 hospitals representing quick and slow implementers were selected for qualitative analysis. Semi-structured interviews were conducted with 71 stakeholders involved in PEWS implementation. Interviews were recorded, transcribed and translated to English, then coded using a priori and novel codes. Thematic content analysis explored the impact of hospital characteristics and QI experience on time required for PEWS implementation and was supplemented by quantitative analysis exploring the relationship between hospital characteristics and implementation time. Results: In both quantitative and qualitative analysis, material and human resources to support PEWS significantly impacted time to implementation. Lack of resources produced various obstacles that extended time necessary for centers to achieve successful implementation. Hospital characteristics, such as funding structure and type, influenced PEWS implementation time by determining their resource-availability. Prior hospital or implementation leader experience with QI, however, helped facilitate implementation by assisting implementers predict and overcome resource-related challenges. Conclusions: Hospital characteristics impact time required to implement PEWS in resource-limited childhood cancer centers; however, prior QI experience helps anticipate and adapt to resource challenges and more quickly implement PEWS. QI training should be a component of strategies to scale-up use of evidence-based interventions like PEWS in resource-limited settings.

Transcriptomics Provides a Genetic Signature of Vineyard Site and Offers Insight into Vintage-Independent Inoculated Fermentation Outcomes.

Ribosomal DNA amplicon sequencing of grape musts has demonstrated that microorganisms occur nonrandomly and are associated with the vineyard of origin, suggesting a role for the vineyard, grape, and wine microbiome in shaping wine fermentation outcomes. Here, ribosomal DNA amplicon sequencing from grape musts and RNA sequencing of eukaryotic transcripts from primary fermentations inoculated with the wine yeast Saccharomyces cerevisiae RC212 were used to profile fermentations from 15 vineyards in California and Oregon across two vintages. These data demonstrate that the relative abundance of fungal organisms detected by ribosomal DNA amplicon sequencing correlated with neither transcript abundance from those same organisms within the RNA sequencing data nor gene expression of the inoculated RC212 yeast strain. These data suggest that the majority of the fungi detected in must by ribosomal DNA amplicon sequencing were not active during the primary stage of these inoculated fermentations and were not a major factor in determining RC212 gene expression. However, unique genetic signatures were detected within the ribosomal DNA amplicon and eukaryotic transcriptomic sequencing that were predictive of vineyard site and region. These signatures included S. cerevisiae gene expression patterns linked to nitrogen, sulfur, and thiamine metabolism. These genetic signatures of site offer insight into specific environmental factors to consider with respect to fermentation outcomes and vineyard site and regional wine characteristics.IMPORTANCE The wine industry generates billions of dollars of revenue annually, and economic productivity is in part associated with regional distinctiveness of wine sensory attributes. Microorganisms associated with grapes and wineries are influenced by region of origin, and given that some microorganisms play a role in fermentation, it is thought that microbes may contribute to the regional distinctiveness of wine. In this work, as in previous studies, it is demonstrated that specific bacteria and fungi are associated with individual wine regions and vineyard sites. However, this work further shows that their presence is not associated with detectable fungal gene expression during the primary fermentation or the expression of specific genes by the inoculate Saccharomyces cerevisiae strain RC212. The detected RC212 gene expression signatures associated with region and vineyard site also allowed the identification of flavor-associated metabolic processes and environmental factors that could impact primary fermentation outcomes. These data offer novel insights into the complexities and subtleties of vineyard-specific inoculated wine fermentation and starting points for future investigations into factors that contribute to regional wine distinctiveness.

Saccharomyces cerevisiae Gene Expression during Fermentation of Pinot Noir Wines at an Industrially Relevant Scale.

Saccharomyces cerevisiae metabolism produces ethanol and other compounds during the fermentation of grape must into wine. Thousands of genes change expression over the course of a wine fermentation, allowing S. cerevisiae to adapt to and dominate the fermentation environment. Investigations into these gene expression patterns previously revealed genes that underlie cellular adaptation to the grape must and wine environments, involving metabolic specialization and ethanol tolerance. However, the majority of studies detailing gene expression patterns have occurred in controlled environments that may not recapitulate the biological and chemical complexity of fermentations performed at production scale. Here, an analysis of the S. cerevisiae RC212 gene expression program is presented, drawing from 40 pilot-scale fermentations (150 liters) using Pinot noir grapes from 10 California vineyards across two vintages. A core gene expression program was observed across all fermentations irrespective of vintage, similar to that of laboratory fermentations, in addition to novel gene expression patterns likely related to the presence of non-Saccharomyces microorganisms and oxygen availability during fermentation. These gene expression patterns, both common and diverse, provide insight into Saccharomyces cerevisiae biology critical to fermentation outcomes under industry-relevant conditions.IMPORTANCE This study characterized Saccharomyces cerevisiae RC212 gene expression during Pinot noir fermentation at pilot scale (150 liters) using industry-relevant conditions. The reported gene expression patterns of RC212 are generally similar to those observed under laboratory fermentation conditions but also contain gene expression signatures related to yeast-environment interactions found in a production setting (e.g., the presence of non-Saccharomyces microorganisms). Key genes and pathways highlighted by this work remain undercharacterized, indicating the need for further research to understand the roles of these genes and their impact on industrial wine fermentation outcomes.

ONCOPEDS: A mobile application to improve early diagnosis and timely referral in childhood cancer in a low- and middle-income country-A pilot study.

BACKGROUND: Diagnosis delay in children and adolescents with cancer is a public health problem in Peru that leads to high rates of advanced disease and mortality. We aimed to assess the implementation feasibility and potential utility of ONCOpeds®, a mobile application that provides consultations with pediatric oncologists, in reducing the latency to diagnosis (LD) and referral time (RT) among children and adolescents in Peru diagnosed with cancer. MATERIAL AND METHODS: A prospective pilot study was conducted in the region of Callao between November 2017 and April 2018. Primary and secondary care providers were trained on the use of ONCOpeds in five educational sessions. Patients younger than 18 years who resided in Callao and were diagnosed with cancer at four pediatric cancer units in Lima were analyzed by referral type: ONCOpeds facilitated or conventional. RESULTS: ONCOpeds was successfully installed in the smartphones of 78 primary and secondary care providers of Callao. During the study period, 23 new cases of cancer in children and adolescents from the region were diagnosed. Ten patients received ONCOpeds-facilitated referrals and 13 received conventional referrals. The RT decreased among those who received ONCOpeds-facilitated referrals by 66% (P = 0.02); however, the LD did not significantly decrease with the use of ONCOpeds. CONCLUSIONS: The implementation of ONCOpeds was found to be feasible in this pilot study, having a potential utility in improving early diagnosis and referral in children and adolescents newly diagnosed with cancer. Directions for future research include multicenter studies with a larger population to further test the application's effectiveness.

Pretreatment Neutrophil-to-Lymphocyte Ratio and Lymphocyte Recovery: Independent Prognostic Factors for Survival in Pediatric Sarcomas.

BACKGROUND: Pretreatment neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) recovery have been shown to be associated with prognosis in several types of cancer in adults. However, evidence in pediatric cancer is scarce. The aim of our study was to evaluate whether pretreatment NLR and lymphocyte recovery are prognostic factors in pediatric sarcomas. MATERIALS AND METHODS: Study participants were identified from a retrospective cohort of 100 children with osteosarcoma (n=55), rhabdomyosarcoma (n=22), and Ewing sarcoma (n=23). Data for the hematological variables were obtained from medical records and analyzed with other known prognostic factors in univariate and multivariate analyses. RESULTS: In multivariate analysis, NLR>2 was an independent prognostic factor for OS in patients with osteosarcoma (hazard ratio [HR], 2.27, 95% confidence interval [CI], 1.07-5.30; P=0.046) along with metastatic disease and poor histologic response; as well as in patients with rhabdomyosarcoma (HR, 4.76, 95% CI, 1.01-22.24; P=0.0237) along with metastatic disease and risk group. ALC recovery correlated for inferior OS in osteosarcoma (HR, 3.34, 95% CI, 1.37-8.12; P=0.008) and rhabdomyosarcoma (HR, 3.89; 95% CI, 1.01-14.89; P=0.0338). CONCLUSIONS: Our study confirms that NLR and ALC recovery are independent prognostic factors for pediatric sarcomas, implying an important role of immune system in survival. Clinical utility of these prognostic biomarkers should be validated in larger pediatric studies.

Timeliness, frequency and content of antenatal care: which is most important to reducing indigenous disparities in birth weight in Mexico?

This article examines the role of components of adequate antenatal care (ANC) in disparities in birth weight between indigenous and non-indigenous women in Mexico. We estimate the potential for added weight gain among indigenous infants if their mothers received timely, frequent ( ≥4 visits) and complete ANC (≥75% of recommended processes of care). We used population-based survey data (2012;N= 6612 women 12-49). We applied quantile regression to examine heterogeneity of the association between adequate ANC, indigenous ethnicity and birth weight across quantiles of the birth weight distribution. A greater proportion of indigenous women reported a low-birth weight infant (<2.5 kg) at last delivery (14 vs 8% among non-indigenous women). Coverage of adequate ANC (timely, frequent and complete care) is lower among indigenous (59%, CI:53;65) than non-indigenous (68%, CI:66;70) women. Indigenous ethnicity is associated with a lower birth weight across quantiles of the observed birth weight distribution: between 300 g in the 0.05, 0.10 and 0.25 quantiles. Among indigenous women, greater newborn weight gains are achieved in the lowest quantiles if they have access to ≥75% of the content of ANC compared with those that did not have access: ∼180 and 260 g are gained in both quantiles 0.05 and 0.10, respectively. This means that the smallest indigenous newborns could potentially reach 2.36 kg (from 1.86 kg), close to the normal weight threshold. The frequency of ANC was positively associated with birth weight for all women but complete ANC appears to differentially affect indigenous women at the bottom of the birth weight distribution. The marginal gains obtained among indigenous newborns that received complete ANC compared with indigenous/non-indigenous newborns did not receive it, is particularly important in low-birth weight quantiles. Delivering basic processes of ANC may therefore have the potential to impact the highest risk women and help them to overcome the low-birth weight threshold.

Fecal ESBL Escherichia coli carriage as a risk factor for bacteremia in patients with hematological malignancies.

PURPOSE: The purpose of this study is to evaluate the impact of fecal extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) colonization for bloodstream infection (BSI), clinical outcome, and costs in patients with hematologic malignancies (HM) and severe neutropenia. METHODS: This is a cohort study, carried out at a cancer-referral hospital. The study population comprises patients with HM, hospitalized prior to administration of the first chemotherapy cycle. A stool culture was taken during the first 48 h; they were grouped as colonized by ESBL-EC or non-ESBL-EC. Patients were followed upon completion of chemotherapy or death. The sum of the days of antibiotics and the length of stay of all hospitalizations in the different cycles of chemotherapy were recorded. RESULTS: We included 126 patients with a recent diagnosis of HM, grouped as 63 patients colonized by ESBL-EC and 63 colonized by non-ESBL-EC, aged 42 ± 16 years old, 78 males (62%). BSI by ESBL-EC developed in 14 patients (22.2%) colonized by the same strain and in 5 (7.9%) in the group colonized with non-ESBL-EC. BSI by non-ESBL-EC was observed in 3 patients (4.7%) colonized by ESBL-EC and in 17 (26.9%) patients colonized by non-ESBL-EC. Colonization with ESBL-EC increased the risk of BSI by the same strain (relative risk (RR) = 3.4, 95% confidence interval (95% CI) 1.5-7.8, p = 0.001), shorter time to death (74 ± 62 vs. 95 ± 83 days, p < 0.001), longer hospital stay (64 ± 39 vs. 48 ± 32 days, p = 0.01), and higher infection-related costs ($6528 ± $4348 vs. $4722 ± $3173, p = 0.01). There was no difference in overall mortality between both groups. CONCLUSIONS: Fecal colonization by ESBL-EC is associated with increased risk of BSI by this strain, longer hospital stay, and higher related costs.