bluuebunny/crossref_metadata_2025 huggingface dataset:
Red Blood Cell Transfusion and the Use of Intravenous Iron in Iron Deficient Patients Presenting to the Emergency Department
Authors: Barghi Arvand , Balshaw Robert , Rimmer Emily , Leeies Murdoch , Garland Allan , Houston Brett L. , Houston Donald S. , Zarychanski Ryan
Published: November 2020

Background: Red blood cell (RBC) transfusions are often used to treat patients with iron deficiency who present to the emergency department (ED) with symptomatic anemia. Intravenous (IV) iron is the preferred treatment in this setting, as it has been shown to increase hemoglobin concentration rapidly and durably. We aim to determine the incidence of iron deficiency anemia (IDA) and the management of these patients in the ED setting.

Objectives: To evaluate the incidence of IDA, the frequency of RBC transfusion and iron supplementation, and factors associated with RBC transfusion.

Study Design: Retrospective cohort study of all adult patients presenting to the St Boniface Hospital (Winnipeg, CAN) ED from January 2014 to January 2019.

Methods: We used electronic data from the Emergency Department Information System (EDIS) and Laboratory Information Services (LIS) databases to identify patients presenting with IDA, defined as anemia (hemoglobin <120 g/L) with either a transferrin saturation less than 20% or ferritin less than 30 umol/L, or mean corpuscular volume (MCV) of < 75 fL. A ferritin greater than 100 umol was used to exclude IDA, regardless of MCV. We extracted patient demographics, diagnoses, markers of iron storage, RBC transfusion and use of IV iron. Multivariate logistic regression analysis was used to evaluate factors associated with RBC transfusion.

Results: Of 39222 patients, 17945 (45%) were anemic. Of the anemic patients, iron parameters were ordered in 1848 (10.3%) patients, and IDA was present in 910 (5.1 %). In the IDA population, 95 patients (10.4 %) received 1 RBC unit, and 197 patients (21.6 %) received 2 or more units. Oral iron and IV iron were prescribed for 64 (7 %) and 14 (1.5 %) patients, respectively. Our logistic regression model demonstrated that hemoglobin concentration was the main determinant of whether patients received RBC transfusion. Other variables including patient age, cardiac symptoms, heart rate, blood pressure, and CTAS score were not associated with increased likelihood of receiving RBC transfusion.

Conclusion: Iron parameters were infrequently ordered in the evaluation of anemia in the ED, with limited use of oral and IV iron. The decision to transfuse RBCs was primarily influenced by hemoglobin concentration, but not other surrogates of hemodynamic instability. An interventional study to improve education and access to oral and IV iron is planned to reduce unnecessary RBC transfusions and their associated risks in patients with IDA.

Disclosures

No relevant conflicts of interest to declare.
Association between Cancer and Anatomical Site of Venous Thromboembolic Disease
Authors: Froehling David A , Houghton Damon E. , Wysokinski Waldemar E. , McBane Robert D. , Vlazny Danielle , Hodge David , Peterson Lisa , Casanegra Ana I
Published: November 2020

Background:There is limited published data on the association between malignancy and the location of venous thromboembolism (VTE) in the body.

Aims:Assess the location of VTE in the body in patients with active cancer and compare these results in patients without malignancy.

Methods:Consecutive patients enrolled in the Mayo Clinic VTE Registry between March 1, 2013 and November 30, 2019 for acute VTE were followed prospectively. Anatomical site of thrombosis and malignancy status were recorded. Patient outcomes were assessed in person, by mailed questionnaire, or by a scripted phone interview. Active cancer was defined as treatment for malignancy within the last six months or not yet in remission.

Results:During the study period there were 2,798 patients with acute VTE (1256 with and 1542 without active cancer). Pulmonary emboli were more common in patients with active cancer compared to patients without cancer (49.5% vs. 39.7%, p<0.001). Upper extremity deep vein thrombosis (11.4 % vs. 7.7%, p<0.001), renal vein thrombi (1.4% vs. 0.2%, p<0.001) and splanchnic vein thrombi (9.3% vs. 6.0%, p=0.001) were all more common in patients with active cancer compared to patients without cancer.

Conclusion:Compared to those without malignancy, patients with active cancer were more likely to have pulmonary emboli, upper extremity deep vein thrombosis, renal vein thrombi, and splanchnic vein thrombi.

Disclosures

No relevant conflicts of interest to declare.
Clinical Efficacy and Safety of TPO in Combination with Eltrombopag in Patients with Solid Tumor Chemotherapy-Induced Thrombocytopenia
Authors: Zhou Fuling , Liu Shuai , Liu Yin
Published: November 2020

Aim: To evaluate the efficacy and safty of TPO in combination with eltrombopag in the treatment of solid tumor chemotherapy-induced thrombocytopenia (CIT).

Methods: 7 patients with thrombocytopenia after standard solid tumor chemotherapy were enrolled in this study, including gastric cancer(n=1), breast cancer(n=1), lung cancer(n=3) and liver cancer(n=2). They were treated with TPO (15000IU q.i.d.) in combination with eltrombopag (25mg t.i.d.) until the platelet count was recovered to 100 × 109 / L or the medication time was up to 14 days. The time required for platelets to recover to > 50 × 109 / L and ≥ 100 × 109 / L, platelet transfusion times and adverse reactions were observed.

Results: After the treatment, the platelet counts of all patients were recovered to > 50 × 109 / L, and 3 of them ≥ 100 × 109 / L. The adverse reactions include muscle soreness(n=1), liver and kidney dysfunction(n=1), no case of them was above grade 3 according to WHO classification criteria for adverse reactions.

Conclusion: TPO in combination with eltrombopag is an effective and safe method for the treatment of solid tumor chemotherapy-induced thrombocytopenia (CIT).

Disclosures

No relevant conflicts of interest to declare.
A Rare Glanzmann Thrombasthenia Pedigree of C.1067T>C Heterozygous Mutation in ITGA2B Gene
Authors: Liu Jiaying , Shen Lijing , Zhuansun Shiya
Published: November 2020

Purpose

A 50-year-old female with excessive menstruation and severe epistaxis since childhood was studied by using phenotype and genetic diagnosis. She was diagnosed as Glanzmann thrombasthenia (GT), meanwhile, her family members with severe epistaxis were also studied. Mutation sites were detected in them. Bioinformatics software was used to explore the molecular pathogenesis which provide evidence for in vitro and in vivo experiments.

Methods

Platelet count and morphology, coagulation function and platelet aggregation were detected for phenotype diagnosis. Platelet membrane glycoproteins (GP) αIIb and β3 were measured by flow cytometry (FCM). Exons and their end 15bp introns of 89 genes associated with hemorrhage and thrombosis from proband were amplified by PCR and analyzed by direct DNA sequencing. Mutation site was measured by sanger sequencing in other family members. ClustalX-2.1-win software was used to analyze homology of nucleotide. PROVEAN and SIFT was used to analyze the risk of mutation site.

Results

The proband, along with her brother and nephew, had normal platelet account and morphology. Coagulation function showed normal while platelet aggregation in response to ADP and AA were reduced. However, they had normal platelet aggregation in response to ristocetin. FCM demonstrated that expression level of CD41 and CD61 were significantly reduced. ITGA2B c.1067T>C heterozygous missense mutation, which led to a Val356→Ala substitution in αIIb protein, existed in the three people. This mutation site was highly conserved among human, mouse, rat and zebrafish. PROVEAN prediction scored -3.48 and SIFT prediction scored 0.001. These results demonstrated ITGA2B p.Val356Ala was pathogenic.

Conclusion

Glanzmann thrombasthenia is a rare autosomal recessive bleeding disorder results from quantitative or qualitative defect of αIIbβ3 integrin which encoded by ITGA2B and ITGB3. The nature of GT mutations is highly variable and most cases are sporadic. In our study, ITGA2B c.1067T>C (Val356Ala) heterozygous missense mutation caused Glanzmann thrombasthenia and aroused obvious symptoms. And in general, homozygous mutation in ITGA2B were recognized to led to Glanzmann thrombasthenia while ITGA2B heterozygous mutation carriers showed mild symptoms. However, there are also some patients with gain-of-function in ITGA2B showed abnormal platelet function or amount. More experiments should be conducted to identify the function of this heterozygous mutation.

Disclosures

No relevant conflicts of interest to declare.
Cfi-400945 Induces Cytokinesis Failure By Activating Hippo Signaling Pathway in Diffuse Large B-Cell Lymphoma
Authors: Zhao Yi , Yang Juan , Liu Jiarui , Ren Shuai , Cai Yiqing , Hu Shunfeng , Zhou Xiangxiang , Wang Xin
Published: November 2020

Targeting mitosis has been found to be a therapeutic strategy for cancer since microtubule poisons have proved efficacy in a broad range of malignancies. Cytokinesis failure can increase chromosomal instability beyond a critical threshold that triggers tumor suppression. Thus, agents developed to block cytokinesis can stop proliferation of cancer cells. We previously demonstrated that the polo-like kinase 4 (PLK4) inhibitor, CFI-400945, triggers growth inhibition and apoptotic death in diffuse large B-cell lymphoma (DLBCL). Since PLK4 is involved in centrosome duplication for cell division, we aimed to explore the effects of CFI-400945 on cytokinesis in DLBCL cells.

Here, we demonstrated that CFI-400945 induces cytokinesis failure in DLBCL. CFI-400945-treated cells led to binucleated/multinucleated cells (Fig. 1a). Previous study showed that the Hippo signaling pathway played a critical role in cytokinesis. Consistent with this finding, we found that CFI-400945 led to phosphorylation of LATS1 and YAP (Fig. 1b). Confocal microscopy confirmed the reduced nuclear YAP upon treatment of CFI-400945 (Fig. 1c). These results show that reduced nuclear YAP levels and activities contribute to growth inhibition by CFI-400945 in DLBCL cells.

In addition, we further explored the synergy of CFI-400945 and doxorubicin (DOX) both in vitro and in vivo. A combined treatment of CFI-400945 and DOX significantly inhibited DLBCL cell survival and induced more apoptosis compared with CFI-400945 or DOX alone (Fig. 1d, Fig. 1e).In the mice xenograft model, the combination of CFI-400945 and DOX significantly delayed tumor progression compared to those treated with vehicle or DOX alone (Fig. 1f). Tumors from combination-treated mice displayed an increase in γ-H2AX staining and a reduction in Ki67 staining (Fig. 1g). Strikingly, tumor cells were generally larger, heterogeneous in size and frequently binucleated (Fig. 1h).

Combined, our results indicate for the first time that CFI-400945 treatment induces cytokinesis failure and activation of Hippo signaling pathway, leading to vulnerability to mitotic catastrophe. Moreover, this study proves an attractive combination treatment that simultaneous targeting PLK4 with CFI-400945 could exacerbate mitotic defects to improve response of anthracycline-based chemotherapy in DLBCL.

Figure 1

Disclosures

No relevant conflicts of interest to declare.
GADD45a Controls Self-Renewal in Acute Myeloid Leukemia Stem Cells
Authors: Hassan Nunki , Yi Hangyu , Gaspard-Boulinc Lucie , Chen Franklin , Datuin Jayvee , Yang Jonason , Wang Jenny Yingzi
Published: November 2020

Acute myeloid leukemia (AML) is a heterogenous malignancy, where the persistence of chemo-resistant leukemia stem cells (LSCs) contributes to disease relapse. We have previously demonstrated the clinical significance of WNT/β-catenin signaling in driving AML LSCs (Science, 327:1650-1653, 2010; Cancer Cell, 38:1-16, 2020). In this study, we uncover that GADD45a (growth arrest and DNA-damage inducible protein) is an essential regulator of β-catenin signaling pathway and its loss promotes LSC function and leukemia progression.

Transgenic knockout of Gadd45a led to a progressive increase in aberrant self-renewal and leukemogenesis in vivo. Gadd45a-/- leukemic cells developed a more aggressive leukemia with a shorter latency than Gadd45a+/+ cells in mice, indicating the involvement of Gadd45a loss in AML initiation and progression. Subsequent serial transplantation experiments showed that Gadd45a deletion enhanced LSC self-renewal in vivo. In agreement with our findings in murine LSCs, deletion of GADD45a by CRISPR/Cas9 in AML patient-derived xenograft (PDX) cells revealed increased engraftment and tumor burden in NSG mice. Consistent with our phenotypic observations, knockout of GADD45a increased βcatenin activity and key WNT/self-renewal target genes in human AML cells. In addition, our cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) data showed that GADD45a deletion in patient-derived LSCs was associated with cell metabolism, reactive oxygen species and tumor progression, as well as poor patient outcomes in AML. Further studies are being conducted to evaluate transcriptional mechanisms discovered by our single-cell sequencing.

Taken together, this study is the first to demonstrate that GADD45a loss promotes LSC potential and consequently enhances tumor growth in murine and PDX models of AML, thus showcasing GADD45a as a promising therapeutic target in AML.

References:

Wang Y, Krivtsov AV, Sinha AU, et al. The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML. Science. 2010;327:1650-1653.

Salik B, Yi H, Hassan N, et al. Targeting RSPO-LGR4 signaling for leukemia stem cell eradication in acute myeloid leukemia. Cancer Cell. 2020; 38:1-16.

Disclosures

No relevant conflicts of interest to declare.
Venetoclax and Posaconazole Plus Standard Dose Cytarabine or Azacytidine for Newly Diagnosed Acute Myeloid Leukemia
Authors: Tan Tran-Der , Chiou Lun-Wei
Published: November 2020

Background: The present standard induction treatment for newly diagnosed acute myeloid leukemia (ND AML) is three days' daunorubicin or idarubicin plus seven days' cytarabine chemotherapy (3+7). Venetoclax plus azacytidine or low dose cytarabine is effective and better than azacitidine or low dose cytarabine alone for ND AML in VIALE A and VIALE C trials, respectively and the outcome by Venetoclax dose levels was not different between 400 mg, 800 mg, or 1200 mg a day. As a strong CYP3A inhibitor, posaconazole can increase serum level of Venetoclax and the dosage could be reduced to 75~100mg a day.

Method: We treat ND AML patients with uninterrupted Venetoclax 100 mg plus posaconazole 300 mg daily and 7 days' standard dose of cytarabine (100 mg/m2/day) or 7 days' azacitidine (75 mg/m2/d), followed by 5 days' consolidation cytarabine (100 mg/m2/d) or another 7 days' azacitidine, and then followed by allogeneic hematopoietic stem cell transplantation.

Results: Eight patients have enrolled the treatment including 7 underwent venetoclax/posaconazole/cytarabine and one venetoclax/posaconazole/azacitidine patients and four patients are secondary AML (one myeloma, one MDS, and 2 breast cancer patients). All patients were hematologic complete remission achieved in one month and 6 patients underwent allogeneic hematopoietic stem cell transplantation including one from matched sibling, two from matched unrelated, and three from haplo-identical donors (sons). Febrile neutropenia rates were similar to 3+7 treatment patients on historical comparison but shorter period of febrile illness. There was no grade II or higher adverse effect of oral mucosa and gastrointestinal tract as compared with conventional 3+7 therapy. Two out of six allo-transplant patients got leukemia relapse then salvage treatment ensued and the other 2 non-transplant and 4 allo-transplant patients are persisted in complete remission.

Conclusion: Venetoclax plus posaconazole and standard dose cytarabine is a feasible choice of induction therapy in ND AML and high CR rate and transplant rate achieved and there was no detrimental effect upon the hematopoietic recovery during induction and transplant therapy.

Figure

Disclosures

No relevant conflicts of interest to declare.
Brentuximab Vedotin Plus Chemotherapy As Pre-Autologous Stem Cell Transplantation Salvage Treatment in Heavily Pretreated Relapsed/Refractory Hodgkin Lymphoma: Real-World Data from Peru
Authors: Quintana Shirley , Vasquez Jule F , Lopez Lourdes , Alcarraz Cindy , Flores Claudio , Samanez-Figari Cesar
Published: November 2020

Background:Brentuximab Vedotin (BV) is an active drug in patients with relapsed / refractory (R/R) Hodgkin Lymphoma (HL). Autologous stem cell transplantation (ASCT) remains standard of care for these patients and achieving a clinical response pre-ASCT predicts favorable outcomes. Pre-ASCT salvage chemotherapy combinations with BV have been explored in this setting.

Objective:To evaluate the efficacy and safety of the combination of BV and chemotherapy in heavily pretreated R/R HL patients eligible for ASCT.

Methods:We reviewed the clinical characteristics, treatment, response, safety, and survival of 21 heavily pretreated R/R HL patients in 2 Peruvian institutions between June 2018 and February 2020. Survival curves were estimated using the Kaplan-Meier method.

Results:A total of 21 patients (15 (71%) refractory and 6 (29%) relapsed) were included. The median age was 31 years (range, 19-55), 13 (62%) patients were female. The median of previous treatment lines was 3 (range, 1-4).

Patients received BV plus chemotherapy (CT) on day 1: Dexamethasone, Cytarabine and Cisplatin (DHAP) (43%), Gemcitabine-based CT (33%), Ifosfamide, Carboplatin and Etoposide (ICE) (14%), and other CT (ESHAP, Bendamustine) (10%).

After a median of 3 cycles of combination therapy (range, 2-7), the objective response rate was 81 %, with 8 (38%) patients achieving CR. 10 (48%) patients had successful peripheral blood stem cell (PBSC) collection. 7 (33%) patients underwent ASCT, the remaining responding patients had a delay in either collection or ASCT due to COVID-19 pandemic.

The most significant adverse events were thrombocytopenia (69%) (G3-4: 53%), neutropenia (47%) (G3-4: 28%), infections (37%), febrile neutropenia (33%) and G1-2 peripheral neuropathy (16%).

The Progression Free-Survival (PFS) at 1 year was 86% in ASCT patients.

Conclusion:The combination of Brentuximab and chemotherapy is active as a bridge for ASCT in heavily pretreated R/R HL patients. The CR rates were lower than previously reported and it could be related with the number of previous lines of treatment received; there was also a higher incidence of febrile neutropenia in our cohort. We could hypothesize that the combination of Brentuximab and chemotherapy provides greater benefit if it is administered earlier in patients with R/R HL.

Disclosures

No relevant conflicts of interest to declare.
Risk of Recurrent Venous Thromboembolism and Bleeding in Patients with Cancer Associated Thrombosis
Authors: Attia Doaa , Jia Xuefei , Wilks Mailey L , Tripp Barbara , D'Andrea Christopher , McCrae Keith R , Khorana Alok A , Angelini Dana E
Published: November 2020

Background: The treatment paradigm for cancer associated thrombosis (CAT) has evolved over recent years from using low molecular weight heparin (LMWH) to direct oral anticoagulants (DOACs). Some randomized trials suggest decreased rates of recurrent venous thromboembolism (VTE) in CAT patients treated with DOACs compared to LMWH but also reported increased rates of bleeding. The Cleveland Clinic Taussig Cancer Center has been treating cancer thrombosis in a centralized CAT clinic since 2014. Here we report our rates of bleeding and recurrent VTE in cancer patients treated with anticoagulation.

Methods: We prospectively followed cancer patients referred to our clinic from 8/2014-10/2019. A total of 1548 patients were referred to the clinic, of whom 462 were diagnosed with an acute VTE. VTE events, including deep venous thrombosis, pulmonary embolism, and visceral thrombosis, were noted. The comparison of bleeding rates (defined using ISTH criteria for major and clinically relevant non major bleeding, CRNMB) among treatment groups (LMWH vs DOACs) was examined using chi-square test. Rate of recurrent VTE was analyzed using a competing model in which death was treated as a competing risk.

Results: The study population comprised 462 patients with acute VTE with a mean age of 62.67±12.23 and 51.8 % males. Of these, 234 (52.9%) received LMWH, 161(36.4%) received DOACs, and 47 (10.6%) received other agents including warfarin for initial anticoagulation. Overall, the 6-month, 1 year, and 2-year VTE recurrence rate was 5.9%, 6.6%, 7.9%, respectively. Recurrent VTE rates were similar for LMWHs, DOACs and other agents (P>0.05). Of 368 patients for whom follow-up data was available, 74 (16.7%) had bleeding event , of which 25 (33.8%) had major bleeding and 49 (66.4%) had CRNMB at 6 month follow-up with no difference across three treatment groups (p=0.56).

Conclusion: In this real-world practice setting, rates of recurrent VTE and bleeding were similar for DOACs and LMWH suggesting that with careful patient selection the concern for higher bleeding with DOACs in cancer patients can be safely overcome.

Disclosures

McCrae: Momenta Pharmaceuticals: Consultancy; Novartis: Honoraria; Rigel: Consultancy; Dova: Consultancy. Khorana:Merck: Research Funding; Medscape: Honoraria; Leo Pharma: Honoraria; Seattle Genetics: Honoraria; Pharmacyte: Honoraria; Pharmacyclics: Honoraria; Array: Other: Research funding (to institution); Janssen: Honoraria; Bayer: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; BMS: Honoraria, Research Funding; Leap: Research Funding.
Clinical Outcomes in Relapsed/Refractory Multiple Myeloma Patients Receiving Sequential Elotuzumab and Daratumumab: A Single Center Experience
Authors: Basher Fahmin , Paul Yonette , Hoffman James E.
Published: November 2020

Daratumumab and elotuzumab are monoclonal antibodies approved by the FDA in November 2015 for the treatment of relapsed/refractory multiple myeloma (RRMM). Daratumumab was approved as a single therapy targeting plasma cell surface CD38, while elotuzumab was approved as part of combination therapy (with lenalidomide), targeting SLAMF7 to impact natural killer cell activation. While both therapies are involved in the recruitment of cellular cytotoxic mechanisms against multiple myeloma, the efficacy of each after a patient has relapsed on the other therapy is unclear.

We conducted a retrospective analysis of 26 patients with RRMM at the University of Miami Sylvester Comprehensive Cancer Center that received both elotuzumab and daratumumab between January 2016 and December 2018 to determine if progression-free survival (PFS) with each monoclonal antibody is affected by previous treatment with the other. Median age at time of treatment was 59.7 years, and 58% of patients were female. Median number of treatments prior to first monoclonal antibody was 4, and median time to first monoclonal antibody was 58 months. Seventeen patients received daratumumab prior to elotuzumab, while nine patients received elotuzumab prior to daratumumab. Patients that received daratumumab first received on average 2 treatments before receiving elotuzumab, while patients receiving elotuzumab first received 1 treatment on average before receiving daratumumab, and time between treatments was significantly shorter for patients receiving daratumumab first (3.7 months vs. 12.4 months, p = 0.0009). Overall survival (OS) and cumulative PFS trended higher in patients receiving elotuzumab first but did not reach significance (OS 37 months vs. 21.7 months, p = 0.07, and PFS 15.5 months vs. 7.6 months, p = 0.09). PFS with initial elotuzumab was higher than with initial daratumumab (11.9 months vs. 3.5 months, p = 0.0124). PFS on daratumumab trended favorably when elotuzumab was administered first (9.4 months vs. 3.0 months), although not significant (p = 0.19). In patients receiving daratumumab, 47% initially demonstrated response, all with eventual progression, with 40% responding to later elotuzumab therapy. Conversely, 56% of patients receiving elotuzumab first demonstrated a response, with 44% eventually progressing over time, and 56% responding to subsequent daratumumab therapy.

These results generate a plausible hypothesis related to a possible potentiating effect of elotuzumab that extends after therapy regimen has changed and warrants further investigation into the sequencing of these two therapies in RRMM and the interplay of their different immunologic impact.

Disclosures

Hoffman: Seattle Genetics: Research Funding; Loxo: Current equity holder in publicly-traded company; Celgene: Honoraria, Speakers Bureau.
Inpatient Outcomes and 60-Day Unplanned Readmissions after Hip Arthroplasty in Sickle Cell Patients with Avascular Necrosis
Authors: Lingamaneni Prasanth , Moturi Krishna , Ba Aqeel Sheeba , Upadhyay Banskota Shristi , Baral Binav , Zia Maryam
Published: November 2020

Background: Avascular necrosis (AVN) afflicts up to 10% of patients with sickle cell disease (SCD), and results in significant impairment in mobility and quality of life. The femoral head is the most common site for involvement of AVN in SCD patients. Total hip arthroplasty has a higher rate of perioperative complications in SCD patients, when compared to the general population. In this study, we aimed to evaluate the rates of readmissions in SCD patients undergoing hip arthroplasty as well as examine the causes behind these readmissions.

Methods: The Nationwide Readmissions Database (NRD) was queried to include all adults who underwent hip arthroplasty in the years 2016 and 2017. SCD patients with AVN of the hip were compared to those undergoing hip arthroplasty for other reasons. T-test was used to compare means of continuous variables and Chi-square test to compare proportions of categorical variables. Multivariable logistic regression was used to evaluate risk factors for inpatient mortality, increased length of hospital stays, and hospitalization charges. We also examined risk factors for readmissions and the most common causes of readmissions in both sickle cell and non-sickle cell cohorts.

Results: A total of 1,167,675 hip arthroplasties were performed in 2016 and 2017, of which 0.1% were for SCD patients with AVN. As expected, those with SCD were younger (mean age 40.6 vs 68.2 years, p<0.0001), with an equal gender distribution (57.8% female) in the two groups. Sickle cell patients were more likely to be from lower income neighborhoods and were also more likely to be treated at teaching hospitals. After adjusting for demographic variables and comorbidity burden, sickle cell disease was associated with higher risk of inpatient mortality (aOR 9.50, 95% CI 2.39-37.77, p<0.01), longer length of hospital stay by 3.2 days (95% CI 2.5-3.9 days, p<0.001), and higher hospitalization costs by roughly 20,000 USD per admission (95% CI 12,000-29,000 USD, p<0.001).

On multivariate analysis, sickle cell patients were more likely to be readmitted within 60 days (aOR 5.25, 95% CI 4.01-6.87, p<0.001). 65% of these readmissions were due to SCD itself. Procedural complications resulted in a 60-day readmission rate of 3% in both the SCD and non-SCD groups, whereas, infectious complications accounted for a higher rate of readmission in those with SCD (2.4% vs 1.3%).

Conclusions: Hip arthroplasty is associated with inferior inpatient outcomes and higher resource utilization in those with sickle cell disease. This can be attributed to high incidence of sickle cell crises post-procedure, as well as, intraoperative surgical complications (femoral fractures and perforations) and high rates of postoperative infections in the functionally asplenic sickle cell disease population.

Disclosures

No relevant conflicts of interest to declare.
Development and evaluation of an online education tool on attention deficit hyperactivity disorder for general practitioners: the important contribution of co-production
Authors: French B. , Daley D. , Perez Vallejos E. , Sayal K. , Hall C. L.
Published: November 2020

Background

Attention deficit hyperactivity disorder (ADHD) is underdiagnosed in the UK and the assessment and diagnosis pathway often involves a general practitioner (GP) referral to secondary care services. GPs’ levels of knowledge and understanding about ADHD is often a significant barrier in patients accessing care. The development of an online education resource could improve GPs knowledge of ADHD and optimise appropriate referrals. Involving end-users in co-creating interventions may enhance their clinical utility and impact routine clinical practice. However, there is limited published evidence describing how to meaningfully involve stakeholders in both the design and development components of co-production.

Method

We report a step wise, co-production approach towards developing an online ADHD education intervention for GPs. Preparatory work highlighted the relevant topics to be included in the intervention, from which educational videos were then developed. Workshops were then conducted with GPs, leading to further refinement of the video content and subsequently the final intervention. A pilot usability study (n = 10 GPs) was then conducted to assess the intervention’s acceptability, feasibility and accessibility.

Results

The development of the online intervention was greatly facilitated by the involvement of GPs. Having a co-production development process ensured the consistent adaptation of the intervention to meet GPs’ needs. The usability study showed that the content of the intervention was suitable, easily accessible, engaging and delivered at an acceptable level of intensity, validating the development approach taken.

Conclusion

While further studies are needed to evaluate the efficacy of the developed intervention, preliminary findings demonstrated that it was acceptable and well received. The importance of co-development was highlighted in developing an intervention that addresses specific needs for GPs. This development approach may be useful for other researchers and developers of clinical interventions.
Barriers and facilitators of videoconferencing psychotherapy implementation in veteran mental health care environments: a systematic review
Authors: Muir Samuel D. , de Boer Kathleen , Nedeljkovic Maja , Meyer Denny
Published: November 2020

Background

Whilst treatment for mental health issues has traditionally been conducted in-person, advances in technology has seen a recent growth in the use of online video therapy services to help overcome access-to-care barriers faced by those living in rural locations and those unable to travel. These barriers are particularly apparent in the case of veteran populations, which is the focus of this review. Whilst the research investigating the efficacy of online video therapy to treat mental health issues among veterans is promising, widespread adoption and utilisation of this modality remains low with efforts often failing to progress past the pilot phase to implementation. This review focuses on the implementation of online video therapy in veteran mental health care settings and aims to identify the potential barriers and facilitators relevant to implementing the modality in military organisations.

Methods

A systematic search of three databases (PsycInfo, PubMed, and Web of Science) was conducted. To be eligible for inclusion, studies had to investigate the challenges, lessons learnt, or factors operating as barriers and/or facilitators to the implementation of online video therapy in veteran health care systems.

Results

The initial search revealed a total of 202 articles. This was reduced to 133 when duplicates were removed. After screening the titles and abstracts a further 70 articles were excluded leaving 63 to be retrieved for full review. A total of 10 studies were included in this review. The most commonly reported barriers were related to clinician concerns, logistical problems, and technology. Other barriers included access to resources as well as challenges posed by collaborations, policy and recruitment. Facilitators included experience using the modality and having dedicated staff responsible for promoting and managing the new service (e.g., on-site champions and telehealth technicians).

Conclusions

This review suggests that numerous barriers must be identified and addressed before attempting to implement an online video therapy service in veteran organisations. Further research is needed to establish best practice for implementation, particularly across geographically dispersed sites. It is hoped that the findings of this review will be used to help inform future implementation efforts and research initiatives in this space.
β-lactamase-mediated resistance in MDR-Pseudomonas aeruginosa from Qatar
Authors: Sid Ahmed Mazen A. , Khan Faisal Ahmad , Sultan Ali A. , Söderquist Bo , Ibrahim Emad Bashir , Jass Jana , Omrani Ali S.
Published: November 2020

Background

The distribution of β-lactam resistance genes in P. aeruginosa is often closely related to the distribution of certain high-risk international clones. We used whole-genome sequencing (WGS) to identify the predominant sequence types (ST) and β-lactamase genes in clinical isolates of multidrug-resistant (MDR)-P. aeruginosa from Qatar

Methods

Microbiological identification and susceptibility tests were performed by automated BD Phoenix™ system and manual Liofilchem MIC Test Strips.

Results

Among 75 MDR-P. aeruginosa isolates; the largest proportions of susceptibility were to ceftazidime-avibactam (n = 36, 48%), followed by ceftolozane-tazobactam (30, 40%), ceftazidime (n = 21, 28%) and aztreonam (n = 16, 21.3%). All isolates possessed Class C and/or Class D β-lactamases (n = 72, 96% each), while metallo-β-lactamases were detected in 20 (26.7%) isolates. Eight (40%) metallo-β-lactamase producers were susceptible to aztreonam and did not produce any concomitant extended-spectrum β-lactamases. High risk ST235 (n = 16, 21.3%), ST357 (n = 8, 10.7%), ST389 and ST1284 (6, 8% each) were most frequent. Nearly all ST235 isolates (15/16; 93.8%) were resistant to all tested β-lactams.

Conclusion

MDR-P. aeruginosa isolates from Qatar are highly resistant to antipseudomonal β-lactams. High-risk STs are predominant in Qatar and their associated MDR phenotypes are a cause for considerable concern.
Retrieving similar substructures on 3D neuron reconstructions
Authors: Yang Jian , He Yishan , Liu Xuefeng
Published: November 2020

Since manual tracing is time consuming and the performance of automatic tracing is unstable, it is still a challenging task to generate accurate neuron reconstruction efficiently and effectively. One strategy is generating a reconstruction automatically and then amending its inaccurate parts manually. Aiming at finding inaccurate substructures efficiently, we propose a pipeline to retrieve similar substructures on one or more neuron reconstructions, which are very similar to a marked problematic substructure. The pipeline consists of four steps: getting a marked substructure, constructing a query substructure, generating candidate substructures and retrieving most similar substructures. The retrieval procedure was tested on 163 gold standard reconstructions provided by the BigNeuron project and a reconstruction of a mouse’s large neuron. Experimental results showed that the implementation of the proposed methods is very efficient and all retrieved substructures are very similar to the marked one in numbers of nodes and branches, and degree of curvature.
Reconstruction of the middle hepatic vein using a vein graft from the resected portion of the liver
Authors: Yang ShiWei , Han DongDong , Wang Liang , Gong Lei , Xiang CanHong
Published: November 2020

Background

The middle hepatic veins are often infiltrated by intrahepatic cholangiocarcinoma. Reconstruction of the hepatic vein plays a critical role in preserving more of the residual liver volume and reducing the risk of postoperative liver failure in extreme hepatectomy. We here report a novel way to reconstruct middle hepatic vein by using vessel grafts from wasted liver.

Case presentation

Case 1: A 64-year-old man was diagnosed with intrahepatic cholangiocarcinoma. The bifurcation and left branch of the portal vein were stenosed, and the root of the middle hepatic vein was infiltrated by the tumor. An extended left hepatectomy was performed, the portal vein was resected and reconstructed, and the middle hepatic vein was reconstructed by anastomosing the proximal left hepatic vein to the distal middle hepatic vein. Case 2: A 69-year-old woman was diagnosed with intrahepatic cholangiocarcinoma. The tumor was located in the left lobe of the liver and the left and middle hepatic veins were infiltrated by the tumor. An extended left hepatectomy was performed, and the left portal vein was used as a vein graft to reconstruct the middle hepatic vein. Both of the two patients’ postoperative ultrasound showed vessel graft patency.

Conclusion

Using a vein graft from the resected portion of the liver to reconstruct the middle hepatic vein was a useful technique and showed good result.
Elective staged proctocolectomy and living donor liver transplantation for colon cancer with sclerosing cholangitis-related ulcerative colitis: a case report
Authors: Miyagi Yoshihiro , Kinjo Tatsuya , Yoshizumi Tomoharu , Harada Noboru , Arakaki Shingo , Kinjo Tetsu , Hokama Akira , Takatsuki Mitsuhisa
Published: November 2020

Background

Primary sclerosing cholangitis (PSC) is a well-known complication of ulcerative colitis (UC), but it is rare to encounter patients requiring both living donor liver transplantation (LDLT) and proctocolectomy. We report a case of elective two-stage surgery involving proctocolectomy performed after LDLT for a patient with early colon cancer concurrent with PSC-related UC. To our knowledge, this is the first report of concurrent cancer successfully treated with both LDLT and proctocolectomy.

Case presentation

A 32-year-old Japanese man with colon cancer associated with UC underwent restorative proctocolectomy at 3 months after living donor liver transplantation (LDLT) for PSC. He was diagnosed with PSC and UC when he was a teenager. Conservative therapy was initiated to treat both PSC and UC. He had experienced recurrent cholangitis for years; therefore, a biliary stent was placed endoscopically. However, his liver function progressively deteriorated. Colonoscopic surveillance revealed early colon cancer; hence, surgical treatment was considered. PSC progressed to cirrhosis and portal hypertension; hence, LDLT was performed before restorative proctocolectomy. Three months after LDLT, we performed restorative proctocolectomy with ileal pouch–anal anastomosis. The postoperative course was uneventful. The patient was well, with good liver and bowel functions and without tumor recurrence, more than 1 year after proctocolectomy.

Conclusions

With strict patient selection and careful patient management and follow-up, elective proctocolectomy may be performed safely and effectively after LDLT for concurrent early colon cancer with PSC-related UC. There are no previous reports of the use of both LDLT and proctocolectomy for the successful treatment of PSC-related UC and concurrent cancer.
But Who’s Counting? Plotting Age in Trollope
Authors: Markovits Stefanie
Published: November 2020

Anthony Trollope is unusually concerned with numbers: consider both the famous obsession with productivity and the figures that organize his serial fictions, what Mary Hamer has called his “writing by numbers.” Yet while such numerals control his narrative flow, forming the remarkable torrents of his romans fleuve, this essay focuses on ones that appear as such within his novels: those used to designate his characters’ ages. Age has long been recognized as a central Trollopian concern, but exploring formally Trollope’s habitual use of age-related integers reveals Trollope’s practice of counting the years to be another kind of “writing by numbers.” “X was now Y years of age” is a favorite locution, and all Trollope’s novels measure the gap between adjacent nows by watching characters grow older. Trollope’s now is thus crucially a sign of age, dependent upon its adjacent number for its force, coloring it and alerting us to its relationship with other numbers as with previous and future selves. This now should be distinguished both from what Mikhail Bakhtin calls the novel’s foundation in “maximal contact with the present” and from Jonathan Culler’s lyric “now.” Instead, it is a paradoxically durational present—a special generic marker of the roman fleuve. Trollope’s figures thus bear heavily on his form of plotting. Narrative generally depends on keeping track of numbers, but not all genres of narrative count in the same ways. Trollope’s age-related numbers show what happens when plot is not only subordinated to but also embodied in character.
Inducible nuclear import by TetR aptamer-controlled 3′ splice site selection
Authors: Mol Adam A. , Vogel Marc , Suess Beatrix
Published: November 2020

Correct cellular localization is essential for the function of many eukaryotic proteins and hence cell physiology. Here, we present a synthetic genetic device that allows the control of nuclear and cytosolic localization based on controlled alternative splicing in human cells. The device is based on the fact that an alternative 3′ splice site is located within a TetR aptamer that in turn is positioned between the branch point and the canonical splice site. The novel splice site is only recognized when the TetR repressor is bound. Addition of doxycycline prevents TetR aptamer binding and leads to recognition of the canonical 3′ splice site. It is thus possible to produce two independent splice isoforms. Since the terminal loop of the aptamer may be replaced with any sequence of choice, one of the two isoforms may be extended by the respective sequence of choice depending on the presence of doxycycline. In a proof-of-concept study, we fused a nuclear localization sequence to a cytosolic target protein, thus directing the protein into the nucleus. However, the system is not limited to the control of nuclear localization. In principle, any target sequence can be integrated into the aptamer, allowing not only the production of a variety of different isoforms on demand, but also to study the function of mislocalized proteins. Moreover, it also provides a valuable tool for investigating the mechanism of alternative splicing in human cells.
Apoptosis of Lymphocytes and Polymorphisms of Apoptosis Regulation Genes in Individuals Exposed to Chronic Radiation Exposure
Authors: Blinova E. , Kotikova A. , Yanishevskaya M. , Akleev A.
Published: November 2020

Purpose: Study the apoptotic death of peripheral blood lymphocytes in long-term period in persons exposed to chronic radiation exposure, and analysis of association of the polymorphic regions rs4645878, rs2279115, rs28362491, rs664677, rs1042522, rs1801270, rs2279744 of the BAX, BCL2, NFkB, ATM, TP53, CDKN1A, MDM2 genes with apoptotic lymphocytes frequency in residents of the coastal villages of the Techa River.

Material and methods: The study of apoptosis and genotyping was conducted in 390 persons exposed to chronic radiation exposure as a result of Mayak PA radioactive waste releases into the Techa–Iset–Tobol river system. The early stage of apoptosis was assessed on a flow cytometer by the presence of phosphatidylserine on the surface of the cell membranes using the Annexin V Apoptosis Detection Kit I and the late stage of apoptosis using the TUNEL method. Real-time PCR genotyping was performed of allelic variations of rs4645878, rs2279115, rs28362491, rs664677, rs1042522, rs1801270, rs2279744 of BAX, BCL2, NFkB, ATM, TP53, CDKN1A, MDM2 genes in a group of irradiated individuals.

Results: The number of cells at the early stage of apoptosis is statistically significantly increased in individuals whose irradiation began during the period of intrauterine development and continued in the postnatal period compared to individuals exposed only in the postnatal period. At the same time, the number of lymphocytes at the stage of DNA fragmentation in the group irradiated in utero is lower than in the group irradiated postnatally and non-irradiated individuals. Also, a weak negative correlation between intrauterine doses of RBM irradiation and the doses of thymus and peripheral lymphoid organs with the number of cells in the late stage of apoptosis in individuals irradiated in utero. The influence of allelic variation rs4645878 of the BAX gene was established on the number of lymphocytes at the early stage of apoptosis in residents of coastal villages of the Techa River. A statistically significant decrease in the number of cells at an early stage of apoptosis is observed in C/C genotype carriers according to the allelic variation rs4645878 of the BAX gene compared with carriers of the T/T and T/C genotypes.

Conclusion: Residents of coastal villages of the Techa River exposed to radiation during the period of prenatal development, there are differences in the frequency of apoptotic death of peripheral blood lymphocytes compared with non-irradiated persons and persons who were irradiated in the postnatal period. SNPs of apoptosis-regulating genes can modify the response of blood lymphocytes to radiation in a wide range of doses RBM.
Risk of Various Types of Cataracts in a Cohort of Mayak Workers Following Chronic Occupational Exposure to Ionizing Radiation
Authors: Azizova T. , Hamada N. , Grigor'eva E. , Bragin E.
Published: November 2020

Purpose: To assess cataract type specific risks in a cohort of workers occupationally exposed to ionizing radiation over prolonged periods.

Material and methods: The present retrospective cohort study included 22,377 workers first employed at a nuclear production facility in 1948–1982 and followed up till the end of 2008. By the end of the follow-up period in the study worker cohort 3123 cases of cortical cataract, 1239 cases of posterior subcapsular cataract (PSC) and 2033 cases of nuclear cataracts were registered over 486,245, 489,162, 492,004 person-years of follow-up, respectively.

Results: The incidence of PSC, cortical and nuclear cataracts was significantly linearly associated with the cumulative radiation dose. The excess relative risk per unit dose of external gamma-ray exposure (ERR/Sv) was 0.91 (95 % CI: 0.67–1.20) for PSC, 0.63 (95 % CI: 0.49–0.76) for cortical cataracts and 0.47 (95 % CI: 0.35–0.60) for nuclear cataracts. Exclusion of an adjustment for neutron dose and inclusion of additional adjustments for body mass index and smoking index reduced ERRs/Sv for all types of cataracts. However, an additional adjustment for glaucoma increased the incidence risks of cortical and nuclear cataracts just modestly (but not for PSC). Inclusion of an adjustment for diabetes mellitus reduced the ERR/Sv of external gamma-ray exposure only for PSC incidence. Increased incidence risks of all cataract types were observed in both males and females of the study cohort, but ERR/Sv was significantly higher in females (p < 0.001), especially for PSC.

Conclusion: The incidence of various types of cataracts in the cohort of workers occupationally chronically exposed to ionizing radiation was associated with the cumulative dose of external gamma-ray exposure.