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Background: HER receptor tyrosine kinases (EGFR/HER1; HER2; HER3; HER4) and their soluble ligands represent a robust system involved in the regulation of a diverse array of cellular processes. Deregulation of HER receptors, notably HER2, has been linked to the initiation and progression of breast cancer and other solid tumors. Relatively less is known about the role of HER receptor soluble ligands in tumorigenesis and responsiveness to HER targeted therapies. Here we will discuss the impact of the HER3 ligand heregulin (HRG) on the sensitivity of breast cancers to HER tyrosine kinase inhibitors (TKIs), and identify TKI strategies to treat HRG-driven breast cancers. Methods: The effects of exogenous HRG (50ng/ml) on the antitumor activity of a panel of TKIs with different enzymatic properties e.g. a reversible, selective inhibitor (lapatinib) and irreversible, pan-HER inhibitors (neratinib; CI-1033) were assessed in HER2+ breast cancer (BC) cell lines. The concentration of TKIs used was in the 1--2.5 uM range, and cells were treated over a 72 hr course. Vehicle treatment alone served as controls. The impact of the above mentioned treatments on total HER receptor and specific EGFR, HER2, and HER3 phosphotyrosine sites, in addition to the phosphorylation state of components of downstream MAPK and PI3K signaling pathways was analyzed through western blot. In addition to studying the effects of exogenous HRG, the impact of TKIs on a model of triple negative BC (TNBC) known to produce HRG in an autocrine manner was also evaluated. QRT-PCR was used to assess the effects of TKIs on HER receptor mRNA levels. Results: Lapatinib inhibited proliferation and phosphorylation of EGFR, HER2, HER3, and downstream MAPK and PI3K signaling pathways in HER2+ SKBR3 and BT474 cell lines. Pre-treatment with HRG abrogated the antitumor effects of a therapeutic concentration of lapatinib (1 uM), and reversed the inhibitory effects of lapatinib on the phosphorylation of HER receptors and components of their downstream signaling pathways e.g. Erk1/2 and Akt. Neratinib also blocked proliferation and phosphorylation in HER2+ BC cells. In contrast to lapatinib, the antitumor effects of neratinib were not reversed by exogenous HRG. Interestingly, treatment with neratinib and similar pan-HER irreversible TKIs, but not reversible TKIs, resulted in loss of HER2 and EGFR protein expression. QRT-PCR was used to evaluate if this effect was at the level of transcription. Furthermore, neratinib inhibited cell proliferation and blocked EGFR signaling in a TNBC model driven by autocrine produced HRG. Conclusions: Our findings suggest that HRG is a mediator of therapeutic resistance to lapatinib in HER2+ and TNBC. Neratinib demonstrates profound effects on HER signaling by markedly reducing HER2 and EGFR protein expression and blocking the protumorigenic effects of autocrine or paracrine expression of HRG. In contrast to HRG, we previously showed that EGF, an EGFR specific ligand did not reverse the antitumor effects of lapatinib in breast cancer cells. Thus, the selection of HER targeted therapies in a given tumor should take into account not only the HER receptor expression profile, but also the presence of autocrine or paracrine derived ligands activating HER receptors. [ABSTRACT FROM AUTHOR]

BACKGROUND: Resistance to lapatinib generally develops in approximately half of patients within one year of initiating treatment. When lapatinib is withdrawn, there is often a rapid progression of disease which is associated with high mortality rates. This "flare" phenomenon has also been observed upon discontinuation of other tyrosine kinase inhibitors (TKIs) in lung cancer, renal cell carcinoma, and gastrointestinal stromal tumors. METHODS: Using the HER2+ cell lines SKBR3 and BT474, we developed both in vitro and in vivo models demonstrating lapatinib resistance and the tumor "flare" phenomenon. Parental HER2+ cell lines were gradually exposed to increasing doses of lapatinib (100nM to 5uM) to develop a lapatinib-resistant form which was ultimately maintained in 1uM of lapatinib. Lapatinib-"released" cell lines were developed by removing lapatinib exposure from resistant cell lines and allowing the cells to grow for at least two weeks. Cell lines were grown in vitro using traditional monolayer cell culturing techniques and mammosphere technology. A comprehensive analysis of parental, lapatinib-resistant, and lapatinib-released cell lines was performed using microscopy, protein/phosphoprotein analysis, cell cycle, cancer stem cell markers by FACS, and invasion assays. Parental cells served as the control in all experiments. In vivo models were performed by injecting 10,000 cells of parental, resistant, and released cell lines in the mammary fat pads of SCID mice. Tumors were surgically resected after approximately sixty days and volume recorded. All experiments were repeated three times and calculated for statistical significance. RESULTS: Cell cycle analysis and proliferation assays demonstrate that lapatinib-resistant and released cell lines continue to proliferate despite the addition of 1uM lapatinib. Released cells also demonstrate less of a response to retreatment with lapatinib. Tumor volume of lapatinib-released cell lines were significantly larger than parental and resistant counterparts [parental: 39.9mm³, SD 9.48; resistant: 71.8mm³, SD 62.33; released: 943.4mm³, SD 100.1] and this difference was statistically significant (p < 0.01). After three series of passages, mammosphere forming efficiency (MFE) was higher among lapatinib-released cell lines [parental: 1.03%; resistant: 1.93% released: 7.23%] and was statistically significant (p <0.01). Lapatinib-released mammosphere phenotypes appeared larger and less organized than the parental and resistant counterparts. MFE did not correlate with ALDH expression by FACS, and expression varied based on cell line. Western blot analysis revealed loss of E-cadherin among lapatinib-released cells which was not demonstrated in parental or resistant counterparts. Invasion assays demonstrated increased migration among resistant and released cell lines. CONCLUSIONS: We demonstrate the first in vitro and in vivo models of the tumor "flare" phenomenon using HER2+ breast cancer cell lines. This model demonstrates that lapatinib -resistant cells released from the exposure to lapatinib are propelled into a unique and more aggressive phenotype. This model has potential to elucidate new mechanisms of resistance to TKI therapy and provide novel preclinical data that may help in the understanding of disease progression. [ABSTRACT FROM AUTHOR]

Focuses on a study on autologous peripheral blood proginetor cell transplantations performed between March 1996 and March 1998. Underlying diseases; Conclusion on the use of granulocyte-colony stimulating factor in patients infused with lower counts of precursor cells.

Academics in medicine are frequently asked to serve on panels to discuss their clinical, research, education, administrative or personal expertise. While panel discussions are often the highlight of a conference or event, in the medical literature, there is very little published on how an individual can effectively prepare and present as an expert panelist. This paper offers guidelines that will enable academics to prepare, deliver, and engage in active dialogue during a panel discussion. Specific tactics include how to accept invitations to serve on a panel, conducting pre-panel conference meetings and background research, preparing concise opening statements and new insights, connecting with the audience, answering questions in a collaborative spirit, and debriefing after the panel. These guidelines will be valuable to any individual invited to serve on a panel discussion and will promote future panelists in engaging in constructive and fulfilling dialogue, with the ultimate goal of leaving the audience with a greater understanding of the topic of discourse.

The Hodgkin lymphoma International Study for Individual Care (HoLISTIC) Consortium's A-HIPI model, developed in 2022 for advanced-stage classical Hodgkin lymphoma (cHL), predicts survival within 5 years amongst newly diagnosed patients. This study validates its performance in the Brazilian Hodgkin lymphoma registry. By 2022, the Brazilian HL registry included 1357 cHL patients, with a median 5-year follow-up. Probabilities for 5-year progression-free survival (PFS) and overall survival (OS) were calculated using A-HIPI-model equations. Discrimination (Harrell C-statistic/Uno C-statistic) and calibration measures assessed external validation and calibration. Lab values beyond the allowed range were excluded, mirroring the initial A-HIPI analysis. A total of 694 advanced-stage cHL patients met the original inclusion criteria (age 18-65 years, Stage IIB-IV). Median age was 31 years; 46.3% were females. Stage distribution was IIB (33.1%), III (27.4%), IV (39.5%). Bulky disease in 32.6%. Five-year PFS and OS were 68.4% and 86.0%, respectively. Harrell C-statistics were 0.60 for PFS and 0.69 for OS, and Uno C-statistics were 0.63 for PFS and 0.72 for OS. Calibration plots demonstrated well-calibrated predictions with calibration slopes of 0.91 and 1.03 for 5-year OS and PFS, respectively. Despite differing patient, clinical characteristics, and socioeconomic factors, the baseline prediction tool performed well in the Brazilian cohort, demonstrating adequate discrimination and calibration. This supports its reliability in diverse settings., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background: The U.S. Boards of Nursing (BONs) collect annual report data from their nursing programs as part of their approval process. This paper highlights the 2020 and 2021 annual report data on the effect of coronavirus disease 2019 (COVID-19) on all nursing programs in 17 BONs in 2020 and 19 in 2021., Method: Nursing programs answered 16 questions on the effect of COVID-19 on their programs. Because BONs require annual report data, all programs in the participating states answered the questions, which included 798 programs in 2020 and 929 in 2021., Results: Major disruptions in nursing education occurred during the pandemic. Clinical experiences and didactic classes were greatly affected, though alternative strategies were used. Student and faculty attrition rates were particularly high in 2021., Conclusion: The authors call for a national forum where nurse leaders analyze what happened and make recommendations for future crisis events. [ J Nurs Educ . 2024;63(5):312-319.] .

Conventional antimicrobial discovery relies on targeting essential enzymes in pathogenic organisms, contributing to a paucity of new antibiotics to address resistant strains. Here, by targeting a non-essential enzyme, Borrelia burgdorferi HtpG, to deliver lethal payloads, we expand what can be considered druggable within any pathogen. We synthesized HS-291, an HtpG inhibitor tethered to the photoactive toxin verteporfin. Reactive oxygen species, generated by light, enables HS-291 to sterilize Borrelia cultures by causing oxidation of HtpG, and a discrete subset of proteins in proximity to the chaperone. This caused irreversible nucleoid collapse and membrane blebbing. Tethering verteporfin to the HtpG inhibitor was essential, since free verteporfin was not retained by Borrelia in contrast to HS-291. For this reason, we liken HS-291 to a berserker, wreaking havoc upon the pathogen's biology once selectively absorbed and activated. This strategy expands the druggable pathogenic genome and offsets antibiotic resistance by targeting non-essential proteins., Competing Interests: Declaration of interests T.A.J.H. and P.F.H. have multiple patents issued or disclosed with Duke University around the tethering technology described in this study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Adolescents living with type 1 diabetes (T1D) often experience diabetes distress (DD), a construct distinct from depression or anxiety that refers to the negative emotions that arise from living with and managing diabetes. Self-compassion, which involves being open to one's own suffering and treating oneself with the same care one would show to loved ones, is associated with better psychological and clinical outcomes among individuals with T1D. Self-compassion is a skill that can be taught and therefore represents an opportunity for intervention., Objective: The overall aim of this study is to assess the effectiveness of a web-based mindful self-compassion for teens (MSC-T) intervention on improving DD, anxiety, depression, diabetes-related disordered eating, and suicidal ideation experienced by youth with T1D (aged between 12 and 17 years) compared with a waitlist control group (standard of care). We will also explore (1) if the effect of the MSC-T intervention changes over time, (2) if the MSC-T intervention has a positive impact on measures of glycemic control, and (3) if the effect of the MSC-T intervention differs based on self-reported gender., Methods: We will conduct a single-center, parallel-group randomized controlled trial of 140 adolescents with T1D followed for 12 months. Participants will be randomly allocated (using hidden allocation) in a 1:1 ratio to either the MSC-T intervention or the waitlist control group. Our primary outcome is DD, as measured by the Problem Areas in Diabetes-Teen (PAID-T) version at 3 months. Secondary outcomes, assessed at 3 and 12 months, include anxiety (Generalized Anxiety Disorder 7-item [GAD-7] scale), depression (Patient Health Questionnaire-9 [PHQ-9]), diabetes-related disordered eating (Diabetes Eating Problem Survey-Revised [DEPS-R] version), and suicidal ideation (using 1 question from the PHQ-9)., Results: Study recruitment began in October 2022 and was completed in March 2023, with a total of 141 participants enrolling. Data collection will be ongoing until March 2024. The first results are expected in June 2024., Conclusions: This study will be the first randomized trial to assess the effectiveness of the web-based MSC-T intervention on adolescents with T1D. Given that adolescence is a period where individuals are typically required to assume more responsibility for their diabetes care, providing adolescents with the tools they need to better manage the stress that often accompanies T1D management is paramount., Trial Registration: ClinicalTrials.gov NCT05463874; https://clinicaltrials.gov/study/NCT05463874., International Registered Report Identifier (irrid): DERR1-10.2196/53935., (©Saunya Dover, Alexandra Ahmet, Karen Bluth, Brian M Feldman, Ellen B Goldbloom, Gary S Goldfield, Sarah Hamilton, Omar Imran, Adam Khalif, Karine Khatchadourian, Sarah Lawrence, Andrew Leonard, Kuan Liu, Yongdong Ouyang, Corien Peeters, Jai Shah, Noah Spector, Caroline Zuijdwijk, Marie-Eve Robinson. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 26.12.2023.)

Competing Interests: The authors declare they have no conflicts of interest.

The treatment of older patients with Hodgkin lymphoma (HL) remains a challenge. We sought to identify the treatment patterns and outcomes in older HL patients included in the Brazilian HL registry (NCT02589548). A total of 136 patients with HIV-negative classic HL, aged ≥ 60 years, diagnosed between 2009 and 2018, were analyzed. The median age was 66 years old (60-90), 72% had advanced disease, 62% had a high IPS, and 49% had a nodular sclerosis subtype. Median follow-up was 64 months for alive patients. ABVD was the front-line treatment in 96% of patients. Twenty-one patients (15%) died during front-line treatment. The 5-year PFS and 5-year OS rates were 55% and 59%, respectively. The 5-year OS rates in localized and advanced disease were 81% and 51% (p=0.013). Lung toxicity developed in 11% of the patients treated with ABVD. Bleomycin was administered for > 2 cycles in 65% of patients. Compared with 2009-2014, there was a decrease in the use of bleomycin for > 2 cycles in 2015-2018 (88% × 45%, p<0.0001). The impact of socioeconomic status (SES) on outcomes was studied in patients treated with ABVD. After adjusting for potential confounders, lower SES remained independently associated with poorer survival (HR 2.22 [1.14-4.31] for OS and HR 2.84 [1.48-5.45] for PFS). Treatment outcomes were inferior to those observed in developed countries. These inferior outcomes were due to an excess of deaths during front-line treatment and the excessive use of bleomycin. SES was an independent factor for shorter survival., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The COVID-19 pandemic has had a profound impact on prelicensure nursing education, leading to widespread disruptions that may have implications for nursing students' learning and engagement outcomes. Understanding how the rapid shift to online and simulation-based teaching methods has affected new graduates' clinical preparedness is critical to ensure patient safety moving forward., Purpose: To assess the impact of institutional, academic, and demographic characteristics on prelicensure nursing students' academic, initial postgraduation, and early career outcomes during the COVID-19 pandemic., Methods: We conducted a mixed-methods longitudinal study focused on prelicensure registered nurse (RN) students entering the core of their didactic and clinical nursing coursework during the pandemic. This study uses a combination of real-time student and faculty self-report data, including externally validated instruments, within and end-of-program standardized test scores, and focus group findings. Various statistical methods, ranging from simpler descriptive and non-parametric methods to Generalized Estimating Equation (GEE) models and detailed textual analysis, are applied to assess student, faculty, and institution-level data., Results: The final sample includes more than 1,100 student and faculty participants affiliated with 51 prelicensure RN programs located across 27 states. Leveraging more than 4,000 course observations collected from fall 2020 to spring 2022 and supplemented by the rich personal narratives of over 60 focus group participants, this study illuminates the breadth, scale, and ever-evolving nature of prelicensure RN programs' efforts to maintain the continuity of nursing students' education during the public health crisis. In doing so, it captures the many ways in which nursing administrators, faculty, and students sought to address the unparalleled challenges they confronted on a day-to-day basis. In particular, the findings provide critical insights into the efficacy of the changes nursing programs made to their course delivery formats to adjust to the confluence of rapidly evolving federal, state, and private restrictions to stem the spread of COVID-19., Conclusion: This study stands as the most comprehensive assessment of prelicensure nursing education in the United States since the onset of COVID-19. It extends knowledge by linking potential deficiencies in students' didactic and clinical education during the pandemic and their early career preparedness, clinical competence, and the patient safety implications therein., (© 2023 National Council of State Boards of Nursing.)

Background: This article reviews national efforts toward promoting fair and just cultures in schools of nursing. A real-life vignette in which a nursing student made a medication error is presented, and the nursing program contacted the nursing regulatory body for advice on how to handle the situation., Method: A framework was used to analyze the causes of the error. Commentary is offered regarding how applying the principles of a fair and just culture could improve student performance and advance the school's culture to reflect one that was fair and just., Results: A fair and just culture requires a commitment of all leaders and faculty within a school of nursing. Administrators and faculty must recognize that errors are part of the learning process, that errors can be minimized but not eliminated, and that learning can occur from each incident to prevent similar occurrences in the future., Conclusion: Academic leaders must engage faculty, staff, and students in a dialogue about the principles of a fair and just culture to develop a tailored plan of action. [ J Nurs Educ . 2023;62(3):139-145.] .

Background: Understanding the magnitude of errors and near misses in all health care situations is crucial to preventing them from occurring in the future. However, little research is available on the type or extent of nursing student errors in the United States., Method: Nursing student error and near miss data were submitted by more than 200 participating prelicensure nursing programs via a secured online repository., Results: Medication errors represented more than half (58.8%, n = 613) of the total error and near-miss data ( n = 1,042) submitted. Errors and near misses were attributed to students not adhering to three major patient safety procedures: checking the patient's identification, checking the patient's allergy status, and following the rights of medication administration., Conclusion: Results indicate collecting data on nursing students' errors and near misses can help nursing programs identify system issues, promote transparency, and make quality improvements. [ J Nurs Educ . 2023;62(1):12-19.] .

Importance: Children of parents expressing limited comfort with English (LCE) or limited English proficiency may be at increased risk of adverse events (harms due to medical care). No prior studies have examined, in a multicenter fashion, the association between language comfort or language proficiency and systematically, actively collected adverse events that include family safety reporting., Objective: To examine the association between parent LCE and adverse events in a cohort of hospitalized children., Design, Setting, and Participants: This multicenter prospective cohort study was conducted from December 2014 to January 2017, concurrent with data collection from the Patient and Family Centered I-PASS Study, a clinician-family communication and patient safety intervention study. The study included 1666 Arabic-, Chinese-, English-, and Spanish-speaking parents of general pediatric and subspecialty patients 17 years and younger in the pediatric units of 7 North American hospitals. Data were analyzed from January 2018 to May 2020., Exposures: Language-comfort data were collected through parent self-reporting. LCE was defined as reporting any language besides English as the language in which parents were most comfortable speaking to physicians or nurses., Main Outcomes and Measures: The primary outcome was adverse events; the secondary outcome was preventable adverse events. Adverse events were collected using a systematic 2-step methodology. First, clinician abstractors reviewed patient medical records, solicited clinician reports, hospital incident reports, and family safety interviews. Then, review and consensus classification were completed by physician pairs. To examine the association of LCE with adverse events, a multivariable logistic regression was conducted with random intercepts to adjust for clustering by site., Results: Of 1666 parents providing language-comfort data, 1341 (80.5%) were female, and the mean (SD) age of parents was 35.4 (10.0) years. A total of 147 parents (8.8%) expressed LCE, most of whom (105 [71.4%]) preferred Spanish. Children of parents who expressed LCE had higher odds of having 1 or more adverse events compared with children whose parents expressed comfort with English (26 of 147 [17.7%] vs 146 of 1519 [9.6%]; adjusted odds ratio, 2.1; 95% CI, 1.2-3.7), after adjustment for parent race and education, complex chronic conditions, length of stay, site, and the intervention period. Similarly, children whose parents expressed LCE were more likely to experience 1 or more preventable adverse events (adjusted odds ratio, 2.3; 95% CI, 1.2-4.2)., Conclusions and Relevance: Hospitalized children of parents expressing LCE were twice as likely to experience harms due to medical care. Targeted strategies are needed to improve communication and safety for this vulnerable group of children.

Acute brain dysfunction (ABD) is a frequent and severe syndrome occurring in critically ill patients and early identification of high-risk patients is paramount. In the present analysis, we propose a clinically applicable model for early phenotype identification of ABD at the bedside in mechanically ventilated patients, improving the recognition of patients with prolonged ABD.Prospective cohort with 629 mechanically ventilated patients in two medical-surgical intensive care units at academic centers. We applied cluster analysis to identify phenotypes using clinical and biological data. We then tested the association of phenotypes and its respective clinical outcomes. We performed a validation on a new cohort of patients select on subsequent patients admitted to the participants intensive care units.A model with 3 phenotypes best described the study population. A 4-variable model including medical admission, sepsis diagnosis, simplified acute physiologic score II and basal serum C-reactive protein (CRP) accurately classified each phenotype (area under curve 0.82; 95% CI, 0.79-0.86). Phenotype A had the shorter duration of ABD (median, 1 day), while phenotypes B and C had progressively longer duration of ABD (median, 3 and 6 days, respectively; P < .0001). There was an association between the duration of ABD and the baseline CRP levels and simplified acute physiology score II score (sensitivity and specificity of 80%). To increase the sensitivity of the model, we added CRP kinetics. By day 1, a CRP < 1.0 times the initial level was associated with a shorter duration of ABD (specificity 0.98).A model based on widely available clinical variables could provide phenotypes associated with the duration of ABD. Phenotypes with longer duration of ABD (phenotypes B and C) are characterized by more severe inflammation and by significantly worse clinical outcomes.

Inflammatory breast cancer (IBC) is an understudied and aggressive form of breast cancer with a poor prognosis, accounting for 2-6% of new breast cancer diagnoses but 10% of all breast cancer-related deaths in the United States. Currently there are no therapeutic regimens developed specifically for IBC, and it is critical to recognize that all aspects of treating IBC - including staging, diagnosis, and therapy - are vastly different than other breast cancers. In December 2014, under the umbrella of an interdisciplinary initiative supported by the Duke School of Medicine, researchers, clinicians, research administrators, and patient advocates formed the Duke Consortium for IBC to address the needs of patients in North Carolina (an ethnically and economically diverse state with 100 counties) and across the Southeastern United States. The primary goal of this group is to translate research into action and improve both awareness and patient care through collaborations with local, national and international IBC programs. The consortium held its inaugural meeting on Feb 28, 2018, which also marked Rare Disease Day and convened national research experts, clinicians, patients, advocates, government representatives, foundation leaders, staff, and trainees. The meeting focused on new developments and challenges in the clinical management of IBC, research challenges and opportunities, and an interactive session to garner input from patients, advocates, and community partners that would inform a strategic plan toward continuing improvements in IBC patient care, research, and education., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Upregulation of human epidermal growth factor receptor 3 (HER3) is a major mechanism of acquired resistance to therapies targeting its heterodimerization partners epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), but also exposes HER3 as a target for immune attack. We generated an adenovirus encoding full length human HER3 (Ad-HER3) to serve as a cancer vaccine. Previously we reported the anti-tumor efficacy and function of the T cell response to this vaccine. We now provide a detailed assessment of the antitumor efficacy and functional mechanisms of the HER3 vaccine-induced antibodies (HER3-VIAs) in serum from mice immunized with Ad-HER3., Methods: Serum containing HER3-VIA was tested in complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) assays and for its effect on HER3 internalization and degradation, downstream signaling of HER3 heterodimers and growth of metastatic HER2+ (BT474M1), HER2 therapy-resistant (rBT474), and triple negative (MDA-MB-468) breast cancers., Results: HER3-VIAs mediated CDC and ADCC, HER3 internalization, interruption of HER3 heterodimer-driven tumor signaling pathways, and anti-proliferative effects against HER2+ tumor cells in vitro and significant antitumor effects against metastatic HER2+ BT474M1, treatment refractory HER2+ rBT474 and triple negative MDA-MB-468 in vivo., Conclusions: In addition to the T cell anti-tumor response induced by Ad-HER3, the HER3-VIAs provide additional functions to eliminate tumors in which HER3 signaling mediates aggressive behavior or acquired resistance to HER2-targeted therapy. These data support clinical studies of vaccination against HER3 prior to or concomitantly with other therapies to prevent outgrowth of therapy-resistant HER2+ and triple negative clones.

Socioeconomic status (SES) is a well-known determinant of outcomes in cancer. The purpose of this study was to analyze the impact of the SES on the outcomes of Hodgkin lymphoma (HL) patients from the Brazilian Prospective HL Registry. SES stratification was done using an individual asset/education-based household index. A total of 624 classical HL patients with diagnosis from January/2009 to December/2014, and treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine), were analyzed. The median follow-up was 35.6 months, and 33% were classified as lower SES. The 3-year progression- free survival (PFS) in higher and lower SES were 78 and 64% (p < 0.0001), respectively. The 3-year overall survival (OS) in higher and lower SES were 94 and 82% (p < 0.0001), respectively. Lower SES patients were more likely to be ≥ 60 years (16 vs. 8%, p = 0.003), and to present higher risk International Prognostic score (IPS) (44 vs. 31%, p = 0.004) and advanced disease (71 vs. 58%, p = 0.003). After adjustments for potential confounders, lower SES remained independently associated with poorer survival (HR = 3.12 [1.86-5.22] for OS and HR = 1.66 [1.19-2.32] for PFS). The fatality ratio during treatment was 7.5 and 1.3% for lower and higher SES (p = 0.0001). Infections and treatment toxicity accounted for 81% of these deaths. SES is an independent factor associated with shorter survival in HL in Brazil. Potential underlying mechanisms associated with the impact of SES are delayed diagnosis and poorer education. Educational and socio-economic support interventions must be tested in this vulnerable population., (© 2017 UICC.)

Data about Hodgkin lymphoma (HL) in developing countries are scarce and suggest the existence of substantial disparities in healthcare and outcomes in large areas of the world. In 2009, a prospective registry of HL was implemented in Brazil. Web-based data were contributed by 20 institutions across the country participating in the Brazilian Prospective Hodgkin's Lymphoma Registry. The aim of this study was to present the clinical features and outcomes of newly diagnosed patients with HL aged 13 to 90 years. Multivariate Cox regression models were used to estimate progression-free (PFS) and overall survival (OS) by clinical factors. A total of 674 patients with classical HL were analysed, with a median follow-up of 37 months. Median age was 30 years (13-90). The median time from the onset of symptoms to diagnosis was 6 months (0-60). Only 6% of patients had early favourable disease, while 65% had advanced disease. Stage IVB was present in 26% and a high-risk International Prognostic Score in 38%. Doxorubicin, bleomycin, vinblastine, and dacarbazine was used in 93%. The median dose of radiotherapy was 36 Gy for localized disease and 32 Gy for advanced disease. The 3 year PFS in early favourable, early unfavourable, and advanced disease were 95%, 88%, and 66%, respectively. High-risk International Prognostic Score, advanced disease, and age greater than or equal to 60 were independently associated with poorer PFS and OS; performance status greater than or equal to 2 was also associated with a poorer OS. Poor-risk patients predominated. Radiation doses for localized disease appear higher than current recommendations. Outcomes appear inferior in developing countries than in developed countries. Delayed diagnosis is probably a major factor underlying these findings. Scattered reports from developing nations suggest that many aspects of standard care in developed countries remain unmet needs for populations living in developing countries. The present report contributes to this body of data, with a proper description of what is currently achieved in urban areas in Brazil., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objectives: The aims of this study were to examine the relationship between 1-year retention of newly licensed RNs (NLRNs) employed in hospitals and personal and hospital characteristics, and determine which characteristics had the most influence., Methods: A secondary analysis of data collected in a study of transition to practice was used to describe the retention of 1464 NLRNs employed by 97 hospitals in 3 states. Hospitals varied in size, location (urban and rural), Magnet® designation, and university affiliation. The NLRNs also varied in education, age, race, gender, and experience., Results: The overall retention rate at 1 year was 83%. Retention of NLRNs was higher in urban areas and in Magnet hospitals. The only personal characteristic that affected retention was age, with younger nurses more likely to stay., Conclusion: Hospital characteristics had a larger effect on NLRN retention than personal characteristics. Hospitals in rural areas have a particular challenge in retaining NLRNs.