bluuebunny/crossref_metadata_2025_split huggingface dataset:
The EBV Oncogene LMP1 Protects Lymphoma Cells From Cell Death Through The Collagen-Mediated Activation Of Discoidin Domain Receptor 1
Authors: Zumla Cader Fathima , Vockerodt Martina , Bose Shikha , Nagy Eszter , Brundler Marie-Anne , Kearns Pamela R , Murray Paul G 
Published: November 2019

Abstract
The malignant Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin lymphoma are surrounded by a tumour microenvironment which is composed of a variety of cell types, as well as non-cellular components such as collagen. Although HRS cells harbour oncogenic Epstein-Barr virus (EBV) in approximately 50% of cases, it is not known if the tumour microenvironment contributes to EBV-driven lymphomagenesis. We show that expression of the EBV-encoded latent membrane protein-1 (LMP1) in primary human germinal centre B cells, the presumed progenitors of HRS cells, up-regulates discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase activated by collagen. We show that HRS cells intimately associated with collagen frequently over-express DDR1 and that short-term exposure to collagen is sufficient to activate DDR1 in Hodgkin lymphoma-derived cell lines. We also show that ectopic expression of DDR1 significantly increased the survival of collagen-treated DG75, Burkitt lymphoma cells, following etoposide treatment. Conversely, inhibition of DDR1, by RNA interference, significantly decreased the survival of collagen-treated L428 Hodgkin lymphoma cells in the absence of specific apoptotic stimulus suggesting that DDR1 also influences baseline survival. Our results identify a hitherto unknown function for collagen in protecting Hodgkin lymphoma from apoptosis and suggest an important contribution of the tumour microenvironment in promoting the oncogenic effects of EBV.

Disclosures:
No relevant conflicts of interest to declare.
Significant Improvement In Quality Of Life (QoL) In Patients With Chronic Myeloproliferative Neoplasms and Myelofibrosis Treated With JAK-1 and JAK-2 Inhibitor Ruxolitinib. A Single Institution Experience In Mexico
Authors: Vargas-Viveros Pablo , Monroy Rafael Hurtado , Candelaria-Hernandez Myrna 
Published: November 2019

Abstract

Introduction
Myeloproliferative Neoplasms can shorten the life of patients and affect severely their quality of life as a result of constitutional symptoms mediated by cytokines and from massive splenomegaly characteristic of these diseases. The objective measurement of symptoms in Myelofibrosis is essential for the presence of general constitutional symptoms as fatigue and is considered adverse prognostic value for survival. The systematic measurement of symptoms in Myelofibrosis is essential for assessing the outcome of treatment with JAK-2 inhibitors.

Material and Methods
To assess the impact on quality of life in patients with Myeloproliferative Neoplasms treated with the inhibitor Ruxolitinib, there was applied the questionnaire Myelofibrosis Symptom Assessment Form (Mesa et al. Leukemia Research. 2009: 33; 1199-1203) to 16 patients included in the Compassionate Use of Ruxolitinib Program: 8 men and 8 women were included with a median age of 63 years; 4 patients with primary Myelofibrosis, 3 with Myelofibrosis post Polycitemia vera and 9 with Myelofibrosis post essential Thrombocythemia. The median patient follow-up was 9 months. The patients started with a dose of 20 mg Ruxolitinib orally every 12 hours.

Results
The questionnaire was administered to all patients at each visit and the results of the ratings of the patients were presented as median of each answer at baseline, 3, 6 and 12 months of follow-up (table 1). By comparing the differences of each parameter measured between the start and at 3, 6 and 12 months were statistically significant for all variables (P <0.001, CI: 95%). The most significant changes were observed when comparing data at baseline and follow-up to the maximum time, however were obvious from the first quarter of observation on fatigue and symptoms dependent splenomegaly in most general symptoms, which actually disappeared completely after 3 months of treatment and not relapsed during the track and in the perception of the quality of life of patients. The variables with lower proportional change recorded were general activity, mood, walking tolerance and everyday work.

Discussion and conclusions
The treatment of Myeloproliferative Neoplasms with Ruxolitinib represents a major advance in the management of malignant Myeloproliferative and achieved excellent improvement in overall constitutional symptom control, splenomegaly and the general perception of the quality of life of these patients. The objective measurement of symptoms of Myelofibrosis is essential, since the presence of general constitutional symptoms as fatigue is considered adverse prognostic value for survival and systematic measurement of symptoms in Myelofibrosis is essential for assessing the outcome of treatment with inhibitors JAK-2.

Disclosures:
No relevant conflicts of interest to declare.
Irish Hospitals Meet Proposed International Guidelines For Non-Hodgkin Lymphoma Management, But Areas For Improvement Remain
Authors: Crotty Rory , Crowley Maeve P , Cahill Mary R , Healey Bird Brian R 
Published: November 2019

Abstract

Introduction
High-grade non-Hodgkin lymphoma is an aggressive condition that requires equally aggressive management. Due to the possibility of curative treatment if the disease is effectively managed, rapid diagnosis, precise staging, and swift commencement of treatment are crucial. In Ireland there is little reliable data on how closely guidelines in non-Hodgkin lymphoma treatment are followed. In order to obtain better data, we replicated a recent study carried out in the Netherlands by Wennekes and colleagues (J Clin Oncol 2011 April 10;29(11): 1436-1444).

Methods
This study was carried out in two hospitals in Cork, Ireland. Ethical approval was obtained from the Cork Research Ethics Committee. We used the National Cancer Registry of Ireland and records of the Citywide Lymphoma Conference to identify high-grade non-Hodgkin lymphoma patients treated at the participating centers. 125 patient records were identified. This was similar to the sample size used by Wennekes. The quality markers used in the Dutch study were chosen as data points. This set was then slightly modified to account for local guideline differences. Data was obtained through a systematic, retrospective chart review.

Results
When analyzing the data, 90% adherence was set as a target. This was in keeping with previous research. Of our 22 quality markers, 11 reached the target level. Diagnosis and staging markers were generally well adhered to. 93% of non-CNS lymphoma patients received an RCHOP or DA-EPOCH-R regimen, 92.8% of patients were diagnosed with an appropriate biopsy, and 92% received a histological diagnosis before treatment was commenced. Scores regarding treatment were close to the target level. 83.5% of patients began chemotherapy within four weeks of diagnosis, and 74.1% of patients received a histological diagnosis within three weeks of presentation. Lower adherence was noted in areas relating to the communication of results. Use of the Cheson criteria to report radiological response was very limited. 12.8% of PET reports and 5% of CT reports used the Cheson criteria. In addition, the patient’s Ann Arbor staging was rarely included on CT and PET reports – 0% and 2.4% respectively.

Conclusion
This is the first replication of the Dutch study on non-Hodgkin lymphoma management. Irish hospitals are meeting non-Hodgkin lymphoma management guidelines in 11 of 22 areas. Adherence for the remaining areas ranges from 83.5% to 0%. Further studies in different Irish centers will provide important data to increase the external validity of this study.

Disclosures:
No relevant conflicts of interest to declare.
Sequential Treatment With Bendamustine, Rituximab, Chlorambucil and Fludarabine Leads To a Major Survival Improvement Of Patients With Chronic Lymphocytic Leukemia (CLL) In Routine Care
Authors: Weide Rudolf , Feiten Stefan , Friesenhahn Vera , Heymanns Jochen , Kleboth Kristina , Thomalla Jörg , van Roye Christoph , Köppler Hubert 
Published: November 2019

Abstract

Introduction
Progress has been made in diagnosis and treatment of patients with CLL who receive their treatment within prospective clinical trials. Due to necessary inclusion and exclusion criteria only a very limited number of patients are treated in studies. Therefore results from clinical trials can't be transferred into routine care. No clinical practice data are available how patients with CLL are diagnosed and treated in routine care and whether improvements in survival are achieved.

Methods
A retrospective analysis of all patients with CLL who were treated in an oncology group practice in Germany between 1995-2012. Relevant clinical data concerning diagnosis, treatment and survival were transferred from clinical files into a database and analyzed statistically using SPSS and SURVSOFT.

Results
580 CLL patients with a median age of 67 (35-92) were identified. At initial diagnosis 446 patients (76.9 %) were in Binet stage A, 69 (11.9%) Binet stage B and 31 (5.3%) Binet stage C. Due to external diagnosis of 34 patients (5.9%) the stage at initial diagnosis couldn't be retrieved. 323 patients (55.7 %) never received any treatment. 257 patients (44.3%) needed therapy with a median of 2 therapy lines (1-11). Regimens most frequently applied were: Bendamustine-containig (66.9%), Rituximab-containing (62.3%), Chlorambucil-containing (61.5%), Bendamustine+Rituximab-combinations (48.2%) and Fludarabine-containing (40.9%). 21.0% of patients were treated within a clinical trial. 5 and 10 year absolute overall survival was 83.6% and 60.9%. Relative survival after 5 and 10 years was 96.1% and 82.3%. Median overall survival according to Binet stage was 16 years for Binet A, 9 years for Binet B and 8 years for Binet C. Median relative survival was 20.8 years for Binet A, 14.0 years for Binet B and 8.6 years for Binet C. Patients who needed therapy had a median overall survival of 11 years (0-41) compared to 18 years (0-23+) of patients who never needed any therapy.

Conclusions
55.7% of CLL-patients never needed any therapy. Patients who needed therapy had a much lower life expectancy compared to patients who never needed therapy. Treatment consisted mainly of Bendamustine, Rituximab, Chlorambucil, Bendamustine+Rituximab-combinations and Fludarabine leading to a marked prolongation of survival compared to historical controls and registry data.

Disclosures:
No relevant conflicts of interest to declare.
Correlation between kidney transplantation and colorectal cancer in hemodialysis patients: A nationwide, retrospective, population-based cohort study
Authors: Wang Han-En , Liao Yu-Chan , Hu Je-Ming , Wu Wen-Chih , Chou Wan-Yun , Chen Yong-Chen , Chou Yu-Ching , Hung Chi-Feng , Tian Yu-Feng , You San-Lin , Sun Chien-An 
Published: November 2019

Abstract
Background
Kidney transplantation (KT) correlates with an increased risk of developing several malignancies; however, the risk of colorectal cancer (CRC) after KT remains debatable and has been marginally explored. Hence, in this nationwide, retrospective, population-based cohort study, we aimed to examine the correlation between KT and CRC in a large-scale population-based Chinese cohort.

Methods
We identified a total of 3739 regular hemodialysis patients undergoing KT (exposed cohort) and 42,324 hemodialysis patients not undergoing KT (non-exposed cohort) between 2000 and 2008 from Taiwan’s National Health Insurance Research Database (NHIRD). Both cohorts were followed up from January 1, 2000, to the date of CRC diagnosis, death, or the end of 2013. Using Kaplan–Meier method, we measured the cumulative incidence of CRC in each cohort. Furthermore, Cox proportional hazards models were used to compute hazards ratios (HRs) and 95% confidence intervals (CIs) to estimate the correlation between KT and CRC in hemodialysis patients.

Results
The Kaplan–Meier analysis revealed that the cumulative incidence of CRC was significantly higher in the exposed cohort than in the non-exposed cohort (log-rank test, P < 0.001). After adjusting for potential confounders, the exposed cohort exhibited a significantly increased risk of CRC compared with the non-exposed cohort (adjusted HR, 1.34; 95% CI, 1.11–1.62).

Conclusions
Hemodialysis patients undergoing KT have a significantly higher risk of CRC than those not undergoing KT. Cancer should continue to be a primary focus of prevention during KT.
Noninvasive multimodal imaging in diagnosing polypoidal choroidal vasculopathy
Authors: Yang Jingyuan , Yuan Mingzhen , Wang Erqian , Xia Song , Chen Youxin 
Published: November 2019

Abstract
Purpose
To investigate the diagnostic accuracy of noninvasive multimodal imaging methods in diagnosing polypoidal choroidal vasculopathy (PCV) and distinguishing PCV from typical neovascular age-related macular degeneration (nvAMD).

Methods
Retrospective study. Imaging features of noninvasive multimodal imaging methods, including fundus photography (FP), B-scan optical coherence tomography (OCT), en face OCT, OCT angiography, and autofluorescence, of 103 eyes with PCV or typical nvAMD were reviewed. Diagnostic strategy was established based on imaging features and was validated in other 105 eyes with PCV or typical nvAMD.

Results
Features of subretinal orange nodule on FP, thumb-like PED on OCT, notched PED on OCT, bubble sign on OCT, and Bruch’s membrane depression under serosanguinous PED on OCT were more common. When the diagnostic strategy of using at least 2 of 5 features was performed, there is 0.88 sensitivity and 0.92 specificity for diagnosing PCV. The results of the validation test further confirmed the diagnostic strategy with 0.94 sensitivity and 0.93 specificity.

Conclusions
Noninvasive multimodal imaging, especially FP and B-scan OCT, provide high sensitivity and specificity for diagnosing PCV and distinguishing PCV from typical nvAMD, when at least 2 of 5 suggestive imaging features are present.
The prevalence and clinical characteristics of pertussis-associated pneumonia among infants in Botswana
Authors: Abu-Raya Bahaa , Goldfarb David M. , Smieja Marek , Luinstra Kathy , Richard-Greenblatt Melissa , Steenhoff Andrew P. , Feemster Kristen A. , Arscott-Mills Tonya , Cunningham Coleen K. , Shah Samir S. , Patel Mohamed Zaakir , Kelly Matthew S. , Sadarangani Manish 
Published: November 2019

Abstract
Background
There are scant data on the prevalence and clinical course of pertussis disease among infants with pneumonia in low- and middle-income countries. While pertussis vaccination coverage is high (≥90%) among infants in Botswana, human immunodeficiency virus (HIV) infection affects nearly one-third of pregnancies.
We aimed to evaluate the prevalence and clinical course of pertussis disease in a cohort of HIV-unexposed uninfected (HUU), HIV-exposed uninfected (HEU), and HIV-infected infants with pneumonia in Botswana.

Methods
We recruited children 1–23 months of age with clinical pneumonia at a tertiary care hospital in Gaborone, Botswana between April 2012 and June 2016. We obtained nasopharyngeal swab specimens at enrollment and tested these samples using a previously validated in-house real-time PCR assay that detects a unique sequence of the porin gene of Bordetella pertussis.

Results
B. pertussis was identified in 1/248 (0.4%) HUU, 3/110 (2.7%) HEU, and 0/33 (0.0%) HIV-infected children. All pertussis-associated pneumonia cases occurred in infants 1–5 months of age (prevalence, 1.0% [1/103] in HUU and 4.8% [3/62] in HEU infants). No HEU infants with pertussis-associated pneumonia were taking cotrimoxazole prophylaxis at the time of hospital presentation. One HUU infant with pertussis-associated pneumonia required intensive care unit admission for mechanical ventilation, but there were no deaths.

Conclusions
The prevalence of pertussis was low among infants and young children with pneumonia in Botswana. Although vaccination against pertussis in pregnancy is designed to prevent classical pertussis disease, reduction of pertussis-associated pneumonia might be an important additional benefit.
Seasonal variations in the occurrence of acute appendicitis and their relationship with the presence of fecaliths in children
Authors: Hsu Yao-Jen , Fu Yu-Wei , Chin Taiwai 
Published: November 2019

Abstract
Background
Acute appendicitis (AA) is the most common surgical condition in children. Although a higher incidence of AA in summer has been reported, the reason for this observation remains unclear. The purpose of this study was to compare the clinical findings of AA patients who underwent appendectomies during the summer months with those who underwent the procedure during the non-summer months.

Methods
The clinical data of 171 patients who underwent appendectomy from January 2013 to December 2016 were reviewed. The patients were divided into a summer group (from May to October) and a non-summer group (from November to April) based on the month when appendectomy was performed. All patients were under 18 years of age at the time of surgery. The medical records including laboratory data, computed tomography scans, pathology reports and operative notes were reviewed.

Results
The number of patients with AA was higher in the summer group than in the non-summer group (101 vs. 70 patients). No significant differences in the laboratory results between the two groups of patients were observed. The percentage of AA patients who presented with a fecalith was significantly lower in the summer group (33.6%) than in the non-summer group (55.7%). No significant differences in the incidence of appendiceal perforations and abscesses, as well as postoperative complications were observed between the two groups.

Conclusions
The percentage of AA patients with fecaliths in summer was lower than that in the non-summer months. The increase in the number of AA patients in summer may be due to the increased occurrence of lymphoid hyperplasia, which may be correlated with the yearly outbreak of enterovirus infection during this period.
The long-term efficacy of one-shot neoadjuvant intra-arterial chemotherapy combined with radical cystectomy versus radical cystectomy alone for bladder cancer: a propensity-score matching study
Authors: Wahafu Wasilijiang , Liu Sai , Xu Wenbin , Wang Mengtong , He Qingbao , Song Liming , Wang Mingshuai , Yang Feiya , Hua Lin , Niu Yinong , Xing Nianzeng 
Published: November 2019

Abstract
Background
Bladder cancer is a complex disease associated with high morbidity and mortality. Management of bladder cancer before radical cystectomy continues to be controversial. We compared the long-term efficacy of one-shot neoadjuvant intra-arterial chemotherapy (IAC) versus no IAC (NIAC) before radical cystectomy (RC) for bladder cancer.

Methods
We performed a retrospective review of patients who underwent either one-shot IAC or NIAC before RC between October 2006 and November 2015. A propensity-score matching (1:3) was performed based on key characters. The Kaplan-Meier method was utilized to estimate survival probabilities, and the log-rank test was used to compare survival outcomes between different groups. A multivariable Cox proportional hazard model was used to estimate survival outcomes.

Results
Twenty-six patients were treated using IAC before RC, and 123 NIAC patients also underwent RC. After matching, there was no significant difference between groups in baseline characteristics, perioperative variables, complication outcomes or tumor characteristics. Compared with clinical tumor stages, pathological tumor stages demonstrated a significant decrease (P = 0.002) in the IAC group. There was no significant difference in overall survival (OS, p = 0.354) or cancer-specific survival (CSS, p = 0.439) between the groups. Among all patients, BMI significantly affected OS (p = 0.004), and positive lymph nodes (PLN) significantly affected both OS (p<0.001) and CSS (p = 0.010).

Conclusions
One-shot neoadjuvant IAC before RC shows safety and tolerability and provides a significant advantage in pathological downstaging but not in OS or CSS. Further study of neoadjuvant combination therapeutic strategies with RC is needed.
Risk of early mortality and cardiovascular disease in type 1 diabetes: a comparison with type 2 diabetes, a nationwide study
Authors: Lee You-Bin , Han Kyungdo , Kim Bongsung , Lee Seung-Eun , Jun Ji Eun , Ahn Jiyeon , Kim Gyuri , Jin Sang-Man , Kim Jae Hyeon 
Published: November 2019

Abstract
Background
Both type 1 and type 2 diabetes are well-established risk factors for cardiovascular disease and early mortality. However, few studies have directly compared the hazards of cardiovascular outcomes and premature death among people with type 1 diabetes to those among people with type 2 diabetes and subjects without diabetes. Furthermore, information about the hazard of cardiovascular disease and early mortality among Asians with type 1 diabetes is sparse, although the clinical and epidemiological characteristics of Asians with type 1 diabetes are unlike those of Europeans. We estimated the hazard of myocardial infarction (MI), hospitalization for heart failure (HF), atrial fibrillation (AF), and mortality during follow-up in Korean adults with type 1 diabetes compared with those without diabetes and those with type 2 diabetes.

Methods
We used Korean National Health Insurance Service datasets of preventive health check-ups from 2009 to 2016 in this retrospective longitudinal study. The hazard ratios of MI, HF, AF, and mortality during follow-up were analyzed using the Cox regression analyses according to the presence and type of diabetes in ≥ 20-year-old individuals without baseline cardiovascular disease (N = 20,423,051). The presence and type of diabetes was determined based on the presence of type 1 or type 2 diabetes at baseline.

Results
During more than 93,300,000 person-years of follow-up, there were 116,649 MIs, 135,532 AF cases, 125,997 hospitalizations for HF, and 344,516 deaths. The fully-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MI, hospitalized HF, AF, and all-cause death within the mean follow-up of 4.6 years were higher in the type 1 diabetes group than the type 2 diabetes [HR (95% CI) 1.679 (1.490–1.893) for MI; 2.105 (1.901–2.330) for HF; 1.608 (1.411–1.833) for AF; 1.884 (1.762–2.013) for death] and non-diabetes groups [HR (95% CI) 2.411 (2.138–2.718) for MI; 3.024 (2.730–3.350) for HF; 1.748 (1.534–1.993) for AF; 2.874 (2.689–3.073) for death].

Conclusions
In Korea, the presence of diabetes was associated with a higher hazard of cardiovascular disease and all-cause death. Specifically, people with type 1 diabetes had a higher hazard of cardiovascular disease and all-cause mortality compared to people with type 2 diabetes.