bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does surgical approach affect early outcomes following primary total hip replacement in obese patients?
Authors: Zhang John , Wyatt Michael C , Frampton Chris M , Anderson Geoffrey 
Published: October 2019

Aim: The aim of this study was to assess whether obese patients undergoing primary total hip replacement (THR) via a posterior approach had superior revision rates and Oxford Hip Scores (OHS) compared to those via a lateral approach. Patients and methods: This is a retrospective cohort study using prospective data from the New Zealand Joint Registry applying STROBE and RECORD guidelines. Patients undergoing THR since 2010 were stratified by body mass index (BMI) into obese (BMI 30–39 kg/m2), and morbidly obese (BMI ⩾40 kg/m2) groups. All-cause revision rates, and 6-month OHS post-surgery were compared between groups. Multivariate analysis was performed. Results: 12,109 unilateral THRs in obese patients were identified. The mean follow-up was 2.8 years (range 0.01–6.95 years). Univariate analysis in the BMI ⩾ 40 group showed the posterior approach had a significantly lower all-cause revision rate (0.99/100 observed component years (ocys); 95% CI, 0.65–1.44/100 ocys) than the lateral approach (1.71/100 ocys (95% CI, 0.98–2.77/100 ocys), p < 0.05). There was no significant difference in dislocation rates between the surgical approaches. OHS was statistically higher in the posterior approach group in BMI 30–39 patients ( p < 0.001) but not clinically significant. Multivariate analysis showed femoral head size significantly influenced all-cause revision rates and mitigated against the increased risk associated with the surgical approach. Conclusion: The choice of surgical approach in obese patients conveys no advantage in overall revision rates in the short-term. Choosing an appropriate size of femoral head may be of greater importance than choice of surgical approach for obese patients in primary THR.
The Bio-inspired Artificial Pancreas for Type 1 Diabetes Control in the Home: System Architecture and Preliminary Results
Authors: Herrero Pau , El-Sharkawy Mohamed , Daniels John , Jugnee Narvada , Uduku Chukwuma N. , Reddy Monika , Oliver Nick , Georgiou Pantelis 
Published: October 2019

Background: Artificial pancreas (AP) technology has been proven to improve glucose and patient-centered outcomes for people with type 1 diabetes (T1D). Several approaches to implement the AP have been described, clinically evaluated, and in one case, commercialized. However, none of these approaches has shown a clear superiority with respect to others. In addition, several challenges still need to be solved before achieving a fully automated AP that fulfills the users’ expectations. We have introduced the Bio-inspired Artificial Pancreas (BiAP), a hybrid adaptive closed-loop control system based on beta-cell physiology and implemented directly in hardware to provide an embedded low-power solution in a dedicated handheld device. In coordination with the closed-loop controller, the BiAP system incorporates a novel adaptive bolus calculator which aims at improving postprandial glycemic control. This paper focuses on the latest developments of the BiAP system for its utilization in the home environment. Methods: The hardware and software architectures of the BiAP system designed to be used in the home environment are described. Then, the clinical trial design proposed to evaluate the BiAP system in an ambulatory setting is introduced. Finally, preliminary results corresponding to two participants enrolled in the trial are presented. Results: Apart from minor technical issues, mainly due to wireless communications between devices, the BiAP system performed well (~88% of the time in closed-loop) during the clinical trials conducted so far. Preliminary results show that the BiAP system might achieve comparable glycemic outcomes to the existing AP systems (~73% time in target range 70-180 mg/dL). Conclusion: The BiAP system is a viable platform to conduct ambulatory clinical trials and a potential solution for people with T1D to control their glucose control in a home environment.
Prevalence of and Risk Factors for Heterotopic Ossification After Cervical Total Disc Replacement: A Systematic Review and Meta-Analysis
Authors: Hui Nicholas , Phan Kevin , Kerferd Jack , Lee Meiyi , Mobbs Ralph J. 
Published: October 2019

Study Design: A systematic review and meta-analysis. Objectives: The results from previous meta-analyses are limited by the small number of included studies. Moreover, the risk factors of heterotopic ossification (HO) have not been well studied. Therefore, this study aims to estimate the prevalence of HO after cervical total disc replacement (CTDR) at different follow-up time points and explore potential risk factors for HO. Methods: We searched databases to identify eligible studies that reported the rate of HO after CTDR. The pooled prevalence of HO, according to different grades of HO, length of follow-up and types of prosthesis, and 95% confidence intervals (CIs) were calculated. Multivariable meta-regression analyses were performed to identify factors that may contribute to the heterogeneity between estimates. Results: Of the 94 studies included, 82 studies reported an overall rate of HO, encompassing a total of 5861 cervical spinal levels that underwent CTDR. The overall pooled prevalence of HO was 32.5% (95% CI 26.7% to 38.4%). Single-level CTDR was associated with a higher overall rate of HO. When the rate of HO was stratified by McAfee/Mehren classification, the pooled prevalence of range of motion (ROM)–limiting HO was 11.0% (95% CI 9.2% to 12.8%). Latest publication, single-level CTDR, longer follow-up period, and studies published outside were associated with a higher rate of ROM-limiting HO. Conclusions: We provide a comprehensive overview of the prevalence of different grades of HO. This meta-analysis also identifies and rules out some risk factors for HO after CTDR.
Metabolic Dysregulation in Normal and Malignant Hematopoiesis
Authors: Mak Tak Wah 
Published: October 2019

Abstract
Over the past decade, the metabolic alterations that occur during tumorigenesis have been recognized as a key feature required for the transformation and maintenance of malignant cells. In order to meet the demands of unrestrained growth, tumor cells must adopt metabolic phenotypes that provide sufficient energy generation, biosynthetic precursor molecules, maintenance of redox/oxidative stress balance and intracellular biochemical homeostasis for growth and survival. Many of these deregulated pathways may predispose premalignant cells to genomic instability resulting to aneuploidy. These phenotypes allow tumor cells to cease functioning as part of an integrated tissue, and evolve independently along a trajectory ultimately leading to malignant disease. During this process, cells must adapt to abnormal microenvironmental conditions that develop after tissue architecture and homeostatic regulation are disrupted. Based on recent work, we will provide an overview of the metabolic alterations, such as mutations in isocitrate dehydrogenase genes that occur in malignancies of the myeloid an lymphoid system. Although the importance of these metabolic alterations to specific disease states, including Acute Myeloid Leukemia and T cell lymphomas, remains to be determined, there may be opportunities for novel therapeutic intervention. Recent advances based on these molecular changes will be discussed.

Disclosures
No relevant conflicts of interest to declare.
Targeting Autophagy as a Therapeutic Pathway in Diamond-Blackfan Anemia
Authors: Doulatov Sergei 
Published: October 2019

Abstract
Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. We previously used unbiased drug screens in induced pluripotent stem cells (iPSCs) which identified SMER28 as a potential therpauetic for DBA. SMER28 acts by selectively modulating autophagy, but has distinct effects from the mTOR inhibitor rapamycin, highlighting the need for further study. Autophagy and mitophagy are critical metabolic pathways that mediate turnover of damaged organelles and mitochondria. Autophagy has been linked to regulation of hematopoietic stem cell function and terminal erythroid differentiation. However, the mechanisms by which autophagy regulates hematopoiesis are still poorly understood. We utilize primary cord blood and adult human progenitors and iPSCs to circumvent the paucity of primary patient blood stem and progenitor cells. To understand the role of autophagy, we have developed a lentiviral LC3-based reporter which allows real-time quantitation of autophagic flux. Using this reporter, we show that autophagy is dynamically regulated during erythroid differentiation and closely parallels mitochondrial mass and levels of reactive oxygen species. In our model, oxidative stress in erythroid precursors drives a stress response which involves activation of autophagy and mitophagy pathways. The interplay between oxidative stress and autophagy regulates erythropoiesis in normal and multiple disease contexts, including DBA and myelodysplastic syndromes (MDS). SMER28 and mitochondrial uncouplers promote homeostasis by facilitating mitochondrial clearance. In summary, therpauetic modulation of autophagy may be a broadly applicable therpauetic strategy in both inherited and acquired anemias.

Disclosures
No relevant conflicts of interest to declare.
Epigenetic Heterogeneity in Non-Hodgkin Lymphoma
Authors: Landau Dan A. 
Published: October 2019

Abstract
In chronic lymphocytic leukemia (CLL) genetically distinct subpopulations are commonly observed and predict future evolutionary and clinical trajectories. Similar to the case of intra-tumoral genetic diversity, intra-tumoral epigenetic diversity occurs at the level of DNA methylation, leading to massive stochastic diversification in methylation patterns. Importantly, stochastic "epimutations" impact transcription, clonal evolution and clinical outcome.
To robustly differentiate "epidrivers" from the majority of random passenger DNA methylation changes, a novel statistical inference framework has been developed that accounts for the varying epimutation rate across the genome. This framework can also include histone modifications revealing a decrease in the coherence between different epigenetic marks in CLL and consistent with intra-leukemic epigenetic diversity. Finally, multi-omic single-cell sequencing techniques further allow for tracking of epimutations and inferring high-resolution lineage trees.

Disclosures
Landau: Pharmacylcics: Honoraria.
Mitochondrial Morphology Controls Hematopoietic Stem Cell (HSC) Self-Renewal and Confers HSC Divisional Memory
Authors: Filippi Marie-Dominique 
Published: October 2019

Abstract
Adult hematopoietic stem cell (HSC) have extensive regenerative capacity; but recent evidence strongly indicate that their actual capacity for self-renewal is limited. HSC attrition occurs with cumulative divisions and after acute stress, causing reduction in regenerative capacity of the progeny. The principal mechanism driving the loss of HSC potency with stress hematopoiesis is not completely understood. We will show and discuss the concept that regulatory programs that are activated with HSC activation and cell cycle entry cause a permanent remodeling of mitochondria. Mitochondria do not return to homeostasis after replicative stress despite HSC re-entry into quiescence and termination of the metabolic programs that were activated with HSC cell cycle entry. HSC keep dysfunctional mitochondria after replicative stress and this loss in mitochondrial fidelity drives the decline of the HSC pool after regenerative stress. The mitochondrial remodeling with replicative stress is at least in part due to a loss in mitochondrial quality control, notably Drp1-mediated mitochondrial dynamics. Further, single cell RNA-seq data indicate that HSC carrying dysfunctional mitochondria fail to synchronize the transcriptional control of core cell cycle and metabolic components in subsequent division providing unexpected mechanism of why HSC that have divided are less potent than HSC that have never divided in similar microenvironment. Thus, the loss of fidelity of mitochondria homeostasis drives HSC attrition and serves as one source of cellular memory of hematopoietic stem cell replicative history.

Disclosures
No relevant conflicts of interest to declare.
Long-Term Follow-up of Myeloablative Haploidentical (HID) Peripheral Blood Stem Cell Transplantation and Post-Transplant Cyclophosphamide (PTCy) Following Fludarabine and Total Body Irradiation (TBI)
Authors: Solomon Scott R , Zhang Xu , Solh Melhem , Morris Lawrence E , Holland H. Kent , Bashey Asad 
Published: October 2019

Abstract

Haploidentical donor (HID) transplant with post-transplant cyclophosphamide (PTCy) is being increasingly utilized worldwide. Although the original "Baltimore" protocol employed nonmyeloablative conditioning, there has been increasing interest in the use of myeloablative conditioning (MAC) in an attempt to decrease the risk of disease recurrence and graft failure. We present the long-term follow-up results of 82 consecutive patients receiving a MAC HID transplant at a single institution between 2011-2017, following a uniform protocol of Fludarabine/total body irradiation (TBI) 1200cGy conditioning, PTCy, tacrolimus and mycophenolate mofetil. PBSC was utilized as the graft source for all transplants and graft CD34 dose was capped at 5 x 106/kg. Median patient age was 42 (range 19-61) years. The most common diagnoses were AML (51%) and ALL (33%), and 39% were high/very high disease risk index (DRI). Donor was a child, sibling or parent in 35%, 43% and 22% respectively. Median follow-up time for surviving patients was 37 months. Primary engraftment occurred in all patients, with all patients achieving complete donor T cell and myeloid chimerism by day +30. There were no cases of late graft failure. The cumulative incidence of grade 3-4 acute graft-versus-host disease (GVHD) and moderate-to-severe chronic GVHD was 17% and 22%, respectively. Non-relapse mortality (NRM) was 7% at one year and 12% at three years post-transplant. Overall survival at 1, 2, and 3 years post-transplant was 85%, 72% and 66% respectively (figure 1). Estimated 3-year DFS, current GVHD-, relapse-free survival (CGRFS), conventional GRFS, and relapse was 67%, 62%, 43%, and 21% respectively. DFS at 3-yr was significantly improved in patients with low/intermediate vs high/very high DRI (79% vs. 48%, figure 2) due to a lower risk of relapse (12% vs. 36%). Infectious complications included CMV reactivation in 55% of patients (CMV disease - 2%) and BK virus infection in 38% (severe - 2%). There were no reported cases of EBV lymphoproliferative disease. This large single institution analysis with long-term follow-up confirms the feasibility of Fludarabine/TBI-based MAC HID transplant with PBSC/PTCy in younger adult patients. This is supported by both the high rate of engraftment, low NRM and a 3-yr CGRFS of 62% (suggesting freedom from relapse and need for long-term systemic immunosuppression for GVHD). The achievement of long term DFS in approximately 80% of low/intermediate DRI and half of high/very high DRI patients is promising.

Disclosures
Solh: ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Amgen: Speakers Bureau.
The Role of Hydroxyurea to Prevent Silent Stroke in Sickle Cell Disease: Systematic Review and Meta-Analysis
Authors: Hasson Carla , Veling Lisa , Rico Juan Felipe , Mhaskar Rahul 
Published: October 2019

Abstract
Chronic blood transfusions are standard of care for stroke prevention in sickle cell disease. We evaluated hydroxyurea's efficacy in preventing silent stroke. We searched for randomized controlled trials (RCTs) and observational studies on Pubmed, CENTRAL, Embase, and Web of Science without using language/time limits. Eligible studies compared hydroxyurea with transfusions or observation to prevent silent stroke. This systematic review adheres to the Cochrane guidelines. Data were pooled using random effects model using STATA to perform meta-analysis. Methodological quality of RCTs was investigated using the Cochrane risk of bias assessment tool, while observational studies were assessed using the Downs & Black Checklist for Study Quality. One RCT enrolling 121 participants was included. There were no strokes, silent strokes, or deaths reported in either arm. There was no difference between hydroxyurea versus chronic blood transfusions (RR 1.52, 95% CI 0.57 to 4.02, P = 0.39) for adverse events. We included 10 observational studies, with 361 participants receiving hydroxyurea. There were no deaths attributed to hydroxyurea. Approximately 1% (I2 = 48.67%, 95% CI 0.0 to 0.05, 314 participants, seven comparisons) of patients receiving hydroxyurea had stroke. Approximately 18% (I2 = 91.37%, 95% CI 0.03 to 0.4, 266 participants, six comparisons) of the hydroxyurea patients had silent stroke. Approximately 24% (I2 = 88.54%, 95% CI 0.02 to 0.57, 91 participants, four comparisons) of the hydroxyurea patients had adverse events attributed to hydroxyurea. Our findings suggest that hydroxyurea is safe and may prevent silent stroke and stroke. More high-quality studies are needed.

Disclosures
No relevant conflicts of interest to declare.
Predictors Factors of Death during Induction Therapy of Acute Myeloblastic Leukemias (Western Algeria, multicenter experience)
Authors: Benzineb Brahim , Naima Mesli , Ahmed Fouad Bendahmane , Ismahane Chekkaf , Bensmail Faiza , Nadjia Benkhira , Krim Amina , Bekadja Mohammed Amine , Zouani Samira , Saidi Djamel , Touhami Hadj , Aberkane Mohamed , Bachiri Aissa , Hadjeb Asma , Zahia Zouaoui , Mehalhal Nemra , Ibraheem Othman 
Published: October 2019

Abstract
Introduction:
Death during induction therapy remains a problem in the management of acute myeloid leukemia (AML). An estimated 6.1% in adult patients and between 19.3% and 27% in subjects of all ages have died of AML during induction therapy. The purpose of this study is to identify the factors that can lead to death during induction therapy.
Patient and methods:
In this multicenter retrospective study, including the Hematology Services of CHU Tlemcen, EHU of Oran, CHU of Oran, CHU of SBA, EPH of Mascara and HMRU of Oran, from 01/01/2007 to 31/12 / 2017. We have included de novo and secondary AML adult patients and have benefited from conventional chemotherapy (regardless of the type and doses of anthracyclin). However, we have excluded patients with a contraindication to treatment, acute promyelocytic leukemias. The evaluation criterion was the death or the survival during the induction therapy (3 + 7 or 3 + 10 regimens).
A variable was considerated statistically significant if the p value was ≤ 0.05. The measurement of a relationship between a possible variable and the occurrence of death was estimated by the Odds-ratio. The associations were evaluated first by a bi-variate analysis followed by a multivariate analysis using logistic regression, including statistically significant variables at the value ≤ 0.1 in bi-variate analysis. If a continuous variable was statistically significant, the receiver operating characteristic curve ROC was constructed.
Results:
Over the past 11 years, 316 patients were included. These patients received either the 3 + 7 or 3 + 10 regimens. The death rate has been estimated at 11.4% (36 patients). We found that age (p: 0.17), PS ≥2 (p: 0.36), clinical symptoms at diagnosis, secondary AML (p: 0.86), FAB classification, white blood cell count (p: 0.34), anthracyclines doses (Daunorubicin 90 mg / m2 and Doxorubicin 45 mg / m2 VS Daunorubicin 60 mg / m2) and antibiotic prophylaxis (p: 0, 95) do not affect the mortality rate Table 1. In contrast, the creatinin level ≥ 12 mg / dL (p: 0.02), the LDH level> 700 U / L (p: 0.038) and the albumin level ≤ 35 g / L (p: 0.046), increase the risk of death during induction therapy. Table 1
Conclusion:
Conventional induction therapy can be used in patients over 60 years of age. On the other hand, renal failure, hypoalbuminemia and elevated LDH levels increase the risk of mortality during induction therapy.

Disclosures
No relevant conflicts of interest to declare.
Patient Adherence and Persistence to Oral Targeted Therapies for Hematologic Malignancies: A Retrospective Cohort Study Among Managed Care Enrollees
Authors: Patel Krish , Sudhir Vinjamuri Sai , Kabadi Shaum , Huang Joanna C , Porwal Sanchita , Thakkar Kushan , Pagel John M. 
Published: October 2019

Abstract
Existing studies evaluating patient adherence to oral targeted therapies such as tyrosine kinase inhibitors focus on small populations with single malignancies. This study evaluated patterns of use of oral agents in a larger population across multiple hematologic malignancies.
Adult patients diagnosed with a hematologic malignancy and prescribed oral targeted therapy between 2011 and 2016 (N = 18,976) were identified from the MarketScan Commercial Claims and Encounters, and Medicare Supplemental databases. Eligible patients were enrolled in monthly prescription plans 6 months before and 12 months after index date (date of first prescription claim) (n = 2,442). Multivariable logistic regressions were used to determine predictors of adherence using the medication possession ratio (MPR), and persistence through prescription refill gaps.
The overall median adherence was 0.9 (MPR ≥ 80%) and was comparable between once-daily (QD) and twice-daily (BID) groups (Table). Overall, 59% of patients were persistent at 12 months (Table). Patients on QD and BID products did not have significant differences in adherence (fixed interval MPR, odds ratio, 0.94; 95% CI, 0.75 to 1.18) or persistence (odds ratio, 0.93; 95% CI, 0.75 to 1.17) 12 months from index (Figure). Significant predictors of adherence and persistence included patient age, total inpatient admissions, number of adverse events and total hospital visits (Figure).
Patient-specific clinical factors, rather than regimen-specific factors, were the main predictors of oral targeted therapy adherence and persistence. Adherence to oral targeted therapies appears to be similar for patients on QD and BID regimens in the real-world setting.

Disclosures
Patel: Sunesis Pharmaceuticals: Consultancy; Pharmacyclics/Janssen: Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; Juno Therapeutics: Consultancy; Celgene: Consultancy. Sudhir:ZS Associates: Employment. Kabadi:AstraZeneca: Employment. Huang:ZS Associates: Employment; Novo Nordisk Inc: Equity Ownership; AstraZeneca: Research Funding. Porwal:ZS Associates: Employment. Thakkar:ZS Associates: Employment. Pagel:Gilead: Consultancy; Pharmacyclics, an AbbVie Company: Consultancy.