Citations

Abstract Objectives To adapt and evaluate a deep learning language model for answering why-questions based on patient-specific clinical text. Materials and Methods Bidirectional encoder representations from transformers (BERT) models were trained with varying data sources to perform SQuAD 2.0 style why-question answering (why-QA) on clinical notes. The evaluation focused on: (1) comparing the merits from different training data and (2) error analysis. Results The best model achieved an accuracy of 0.707 (or 0.760 by partial match). Training toward customization for the clinical language helped increase 6% in accuracy. Discussion The error analysis suggested that the model did not really perform deep reasoning and that clinical why-QA might warrant more sophisticated solutions. Conclusion The BERT model achieved moderate accuracy in clinical why-QA and should benefit from the rapidly evolving technology. Despite the identified limitations, it could serve as a competent proxy for question-driven clinical information extraction.

Background Although rituximab‐based high‐dose therapy is frequently used in diffuse large B cell lymphoma (DLBCL) patients undergoing autologous hematopoietic cell transplantation (auto‐HCT), data supporting the benefits are not available. Herein, we report the impact of rituximab‐based conditioning on auto‐HCT outcomes in patients who have DLBCL. Methods Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, 862 adult DLBCL patients undergoing auto‐HCT between 2003 and 2017 using BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning regimen were included. All patients received frontline rituximab‐containing chemoimmunotherapy and had chemosensitive disease pre‐HCT. Early chemoimmunotherapy failure was defined as not achieving complete remission (CR) after frontline chemoimmunotherapy or relapse within 1 year of initial diagnosis. The primary outcome was overall survival (OS). Results The study cohort was divided into 2 groups: BEAM (n = 667) and R‐BEAM (n = 195). On multivariate analysis, no significant difference was seen in OS ( P = .83) or progression‐free survival (PFS) ( P = .61) across the 2 cohorts. No significant association between the use of rituximab and risk of relapse ( P = .15) or nonrelapse mortality ( P = .12) was observed. Variables independently associated with lower OS included older age at auto‐HCT ( P < .001), absence of CR at auto‐HCT ( P < .001) and early chemoimmunotherapy failure ( P < .001). Older age ( P < .0002) and non‐CR pre‐HCT ( P < .0001) were also associated with inferior PFS. There was no significant difference in early infectious complications between the 2 cohorts. Conclusion In this large registry analysis of DLBCL patients undergoing auto‐HCT, the addition of rituximab to the BEAM conditioning regimen had no impact on transplantation outcomes. Older age, absence of CR pre auto‐HCT, and early chemoimmunotherapy failure were associated with inferior survival.

PURPOSETo compare the outcomes of patients with Hodgkin or non-Hodgkin lymphoma undergoing nonmyeloablative haploidentical or unrelated cord blood (UCB) hematopoietic cell transplantation.PATIENTS AND METHODSWe retrospectively studied 740 patients with Hodgkin lymphoma (n = 283, 38%) and non-Hodgkin lymphoma (n = 457, 62%) age 18-75 years who received transplantations from 2009 to 2016. Data were reported to the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation, Eurocord, or Center for International Blood and Marrow Transplant Research. Of the 526 patients who received haploidentical transplantation, 68% received bone marrow and 32% received peripheral blood. All patients received a uniform transplantation conditioning regimen (2 Gy of total-body irradiation, cyclophosphamide, and fludarabine) and graft-versus-host disease prophylaxis (calcineurin inhibitor and mycophenolate). In addition, patients who received a haploidentical transplantation received posttransplantation cyclophosphamide.RESULTSCompared with haploidentical bone marrow and peripheral-blood transplantations and adjusted for age, lymphoma subtype, and disease status, survival was lower after UCB transplantation (hazard ratio [HR], 1.55; P = .001; and HR, 1.59; P = .005, respectively). Similarly, progression-free survival was lower after UCB transplantations compared with haploidentical bone marrow and peripheral-blood transplantations (HR, 1.44; P = .002; and HR, 1.86; P < .0001), respectively. The 4-year overall and progression-free survival rates after UCB transplantation were 49% and 36%, respectively, compared with 58% and 46% after haploidentical bone marrow transplantation and 59% and 52% after peripheral-blood transplantation, respectively. Lower survival was attributed to higher transplantation-related mortality after UCB transplantation compared with haploidentical bone marrow and peripheral-blood transplantation (HR, 1.91; P = .0001; and HR, 2.27; P = .0002, respectively).CONCLUSIONWhen considering HLA-mismatched transplantation for Hodgkin or non-Hodgkin lymphoma, the data support haploidentical related donor transplantation over UCB transplantation.

Adverse childhood experiences (ACE) have been associated with a greater prevalence of risky behaviors and chronic health conditions, such as diabetes in adulthood. While adolescents with risk taking behaviors experience worsening of diabetic metabolic control, it is yet to be determined whether glycemic management in children and adolescents is negatively and independently influenced by ACEs. This study examines the relationship between ACEs in children and adolescents with type 1 diabetes (T1DM) and glycemic control, BMI and lipids. For such children, we hypothesized that hemoglobin A1c (HbA1c) is positively correlated with ACE scores. Parents of children (age 2–18 years) with T1DM completed a validated ACE questionnaire. The associations between parent and child ACE score and HbA1c, lipids and BMI z-scores were assessed using linear regression. The prevalence of any ACE was 27.9% among children and 49.0% among parents. HbA1c was significantly higher in children who had exposure to three or more ACEs (β:0.63 (4.5 mmol/mol); p = 0.02), in those who had a parent exposed to four or more ACEs (β:0.87 (7.2 mmol/mol); p = 0.03), in children who had exposure to household incarceration (β:0.62 (4.4 mmol/mol); p = 0.05) and children who witnessed or had been victim of violence in the neighborhood (β:0.71 (5.4 mmol/mol); p = 0.02). ACEs were highly prevalent among children with T1DM and had a positive association with glycemic control.

The antibiofilm activity of a hydrogen peroxide-generating electrochemical scaffold (e-scaffold) was determined against mono- and trispecies biofilms of methicillin-resistant Staphylococcus aureus , multidrug-resistant Pseudomonas aeruginosa , and Candida albicans . Significant time-dependent decreases were found in the overall CFU of biofilms of all three monospecies and the trispecies forms. Confocal laser scanning microscopy showed dramatic reductions in fluorescence intensities of biofilm matrix protein and polysaccharide components of e-scaffold-treated biofilms.

AbstractBackgroundOptimal sequencing of systemic therapy in the management for metastatic castration resistant prostate cancer (mCRPC) remains poorly elucidated. The CHAARTED and STAMPEDE studies have proven that early chemotherapy in the hormone‐sensitive setting yields a greater net survival advantage than docetaxel for mCRPC. In a retrospective study, we attempt to investigate the two most common treatment sequences for mCRPC and investigate whether earlier chemotherapy for mCRPC is consequential to survival outcomes.MethodsWe identified 112 patients with mCRPC treated at the Mayo Clinic between 2011 and 2017. We identified two cohorts, 80 patients (group A) received full course docetaxel chemotherapy followed by second generation hormone therapy (2nd gen androgen deprivation therapy [ADT]; Abiraterone or Enzalutamide) and 32 patients (group B) treated with 2nd gen ADT followed by docetaxel. The primary endpoint evaluated was 3‐year cancer‐specific survival.ResultsMean prostate specific antigen at initiation of first treatment was 32.0 in group A and 21.7 in group B (P = .4). Bone metastases were more prevalent in group B (87% vs 58%, P = .01). All other clinicopathologic variables were statistically similar between group A and group B. Three‐year cancer‐specific survival was 87.4% vs 64.1% for group A and group B, respectively (P = .016). We report a univariate hazard ratio of 3.61 (95% CI, 1.74‐9.5, 0 P = .01). Three‐year overall survival was 82.4% and 60.8% for group A and group B, P = .01. These results held true when excluding patients with lymph node only metastasi.ConclusionOur data indicates that sequence of systemic therapy may influence outcomes for mCRPC and that docetaxel should be considered before 2nd generation ADT. Our results support the importance of earlier chemotherapy in the castration resistant state.

Background The epidemiological transition of non-communicable diseases replacing infectious diseases as the main contributors to disease burden has been well documented in global health literature. Less focus, however, has been given to the relationship between sociodemographic changes and injury. The aim of this study was to examine the association between disability-adjusted life years (DALYs) from injury for 195 countries and territories at different levels along the development spectrum between 1990 and 2017 based on the Global Burden of Disease (GBD) 2017 estimates. Methods Injury mortality was estimated using the GBD mortality database, corrections for garbage coding and CODEm—the cause of death ensemble modelling tool. Morbidity estimation was based on surveys and inpatient and outpatient data sets for 30 cause-of-injury with 47 nature-of-injury categories each. The Socio-demographic Index (SDI) is a composite indicator that includes lagged income per capita, average educational attainment over age 15 years and total fertility rate. Results For many causes of injury, age-standardised DALY rates declined with increasing SDI, although road injury, interpersonal violence and self-harm did not follow this pattern. Particularly for self-harm opposing patterns were observed in regions with similar SDI levels. For road injuries, this effect was less pronounced. Conclusions The overall global pattern is that of declining injury burden with increasing SDI. However, not all injuries follow this pattern, which suggests multiple underlying mechanisms influencing injury DALYs. There is a need for a detailed understanding of these patterns to help to inform national and global efforts to address injury-related health outcomes across the development spectrum.

Abstract Several subsets of regulatory CD4+ T cells (CD4+ Tregs) have been described in peripheral blood and tumor microenvironment and blood of breast cancer (BC) patients and may play a key role in the progression of BC. High-risk human papilloma virus (HPV) have a causal role in a significant proportion of cervical, and head, and neck tumors and may play an important role in evoking neoplasia in BC. In this study we assessed the prevalence of CD4+Tregs (CD4+CD25+ FOXP3+ cells) and CD3+ CD8+ T cells by flow cytometry in peripheral blood from a total of 55 Egyptian women, including 20 treatment-naïve BC, 15 with breast benign lesions (BBL) and 20 healthy volunteers (HV). High-risk HPV genotype type 16, 18, and 31 was investigated in breast tissue from all BC and BBL patients using Real-Time PCR. HPV was detected in 4 BC, but in none of BBL patients. The frequency of CD4+ Tregs was significantly higher in BC compared to BBL and HV, (p < 0.001). In addition, we observed a significantly higher frequency of CD3+ CD8+ T cells in peripheral blood of patients with late stage III compared to early stage I and II BC (p = 0.011). However, there was no significant association between the ratio of CD8+ T cell to CD4+ Tregs frequencies and the expression of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). In conclusion, CD4+ Tregs may contribute to progression BC in Egyptian women with HPV infection. The potential role CD4+ Tregs as a prognostic or predictive parameter should be analyzed in a larger longitudinal study with sufficient follow-up time.