bluuebunny/crossref_metadata_2025 huggingface dataset:
Remaining useful life prediction of rolling bearing using adaptive sparsest narrow-band decomposition and locality preserving projections
Authors: Peng Yanfeng , Liu Yanfei , Cheng Junsheng , Yang Yu , He Kuanfang , Wang Guangbin , Liu Yi
Published: December 2019

There are two difficulties in the remaining useful life prediction of rolling bearings. First, the vibration signals are always interfered by noise signals. Second, some of the extracted features include useless information which may decrease the prediction accuracy. In order to solve the problems above, corresponding methods are employed in this article. First, adaptive sparsest narrow-band decomposition is utilized for extracting the degradation information from noise. Compared with the commonly used empirical mode decomposition method, problems including mode mixture and boundary effect caused by the calculation of extremas is not required. Second, locality-preserving projection is applied for merging the meaningful information from the original data and reduces the dimension of features. Based on adaptive sparsest narrow-band decomposition and locality preserving projection, a novel approach is employed for the remaining useful life prediction. The prediction procedure is as follows. First, the signals are analyzed by adaptive sparsest narrow-band decomposition and the feature vectors are constructed. Afterwards, the features are fused by locality preserving projection to merge useful information from the features. Least squares support vector machine is applied for the remaining useful life prediction in the end. The analysis results indicate that the proposed approach is reliable for rolling bearing remaining useful life prediction.
A parallel-machine scheduling with periodic constraints under uncertainty
Authors: Shen Jiayu , Zhu Yuanguo
Published: December 2019

Most studies on scheduling problem have assumed that the machine is continuously available. However, the machine is likely to be unavailable for many practical reasons (e.g. breakdown and planned preventive maintenance). Once a machine is not available, the optimal scheme in the deterministic scenario may not be the optimal choice. To address the actual scenario, a scheduling problem with two identical parallel machines, one of which requires periodic maintenance, is considered in this article. For uncertainties in reality, the processing and maintenance time are considered as uncertain variables. A novel method to study the worst-case ratio in an uncertain scenario is proposed. It is shown that the worst-case ratio of the longest processing time algorithm is 3/2 at a high confidence level. Given theoretical analysis results, an modified algorithm is proposed. Finally, numerical experiments are used to verify the feasibility of the modified algorithm.
Where Does the Patient Fit? An Analysis of Word Use Within the Context of Interprofessional Collaborative Care
Authors: Engel Joyce , Prentice Dawn , Hicks Rachel
Published: December 2019

Patient-centeredness is considered central to interprofessional collaborative patient care as a participatory, partnered approach between health care professionals and patients. Content analysis of 501 articles from the 1986, 1987, 1988, 1996, 2006, 2013, 2014, and 2018 volumes of a selected journal was undertaken. The purposes were to identify contexts in which the term patient was used in articles with a primary focus on interprofessional care and to identify trends in its usage. With Dilthey’s ideas on language as a framework, patient and its variations in the articles were coded under five categories. Findings suggest that the term patient appears predominantly as a modifier for activities enacted by experts and a platform for the discussion of relationships among professionals. There is limited evidence that use of the term patient fits within the context of partnership, suggesting that the language in published interprofessional collaborative research and discussion is currently largely expert, not patient-centered.
Factors versus Composites: Guidelines for Choosing the Right Structural Equation Modeling Method
Authors: Hair Joseph F. , Sarstedt Marko
Published: December 2019

Structural equation modeling (SEM) is a widely applied and useful tool for project management scholars. In this Thoughtlet article, we critically reflect on the measurement philosophy underlying the two streams of SEM and their adequacy for estimating relationships among concepts commonly encountered in the field (e.g., team performance). We also discuss considerations to ponder when making the choice between the two types of SEM as well as between SEM and regression analysis.
Minimal residual disease and stem cell transplantation outcomes
Authors: Cloos Jacqueline , Ossenkoppele Gert J. , Dillon Richard
Published: December 2019

Risk classification and tailoring of treatment are essential for improving outcome for patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. Both patient and leukemia-specific characteristics assessed using morphology, cytogenetics, molecular biology, and multicolor flow cytometry are relevant at diagnosis and during induction, consolidation, and maintenance phases of the treatment. In particular, minimal residual disease (MRD) during therapy has potential as a prognostic factor of outcome, determination of response to therapy, and direction of targeted therapy. MRD can be determined by cell surface markers using multicolor flow cytometry, whereas leukemia-specific translocations and mutations are measured using polymerase chain reaction–based techniques and recently using next-generation sequencing. All these methods of MRD detection have their (dis)advantages, and all need to be standardized, prospectively validated, and improved to be used for uniform clinical decision making and a potential surrogate end point for clinical trials testing novel treatment strategies. Important issues to be solved are time point of MRD measurement and threshold for MRD positivity. MRD is used for stem cell transplantation (SCT) selection in the large subgroup of patients with an intermediate risk profile. Patients who are MRD positive will benefit from allo-SCT. However, MRD-negative patients have a better chance of survival after SCT. Therefore, it is debated whether MRD-positive patients should be extensively treated to become MRD negative before SCT. Either way, accurate monitoring of potential residual or upcoming disease is mandatory. Tailoring therapy according to MRD monitoring may be the most successful way to provide appropriate specifically targeted, personalized treatment.
Prognostication with circulating tumor DNA: is it ready for prime time?
Authors: Kurtz David M.
Published: December 2019

Emerging methods to detect tumor-derived DNA in the blood plasma of patients with lymphomas—so-called “circulating tumor DNA” (ctDNA)—have the potential to change the way in which lymphoma is diagnosed and managed in the clinic. The possible applications for ctDNA are numerous, including mutation genotyping, response monitoring, and detection of minimal residual disease during a time of radiographic remission. This article discusses the methodology for detecting ctDNA in aggressive B-cell lymphomas, including digital polymerase chain reaction, targeted sequencing of immunoglobulin receptors, and targeted next-generation sequencing. The advantages of each of these methods are also compared, with a focus on promising clinical applications. These include identification of molecular subtypes (eg, cell-of-origin and double-hit lymphomas) from pretreatment plasma, molecular response prediction after an initial course of therapy, and early detection of relapsing disease prior to clinical relapse. Finally, this article discusses the challenges in implementing ctDNA assays in the clinic today, including possible solutions to these challenges.
Roundtable: How I treat a newly diagnosed patient with high-risk myeloma
Authors: Kaufman Jonathan L.
Published: December 2019

Initial management of high-risk myeloma remains a treatment challenge. Risk is defined by a combination of clinical and biological features, with fluorescence in situ hybridization detection of specific cytogenetic abnormalities driving categorization. High-risk abnormalities include t(4;14), t(14;16), t(14;20), del(17p), and +1q. Clinical features such as plasma cell leukemia, presence of 5% to 20% circulating plasma cells, and extramedullary disease all are factors in high-risk presentations. The driving principle of treatment of the high-risk patient is the use of a regimen with the greatest likelihood of a deep and prolonged remission, as defined by minimal residual disease negativity. I will describe prior and current treatment approaches, including induction, the role of autologous transplantation, and posttransplantation consolidation and maintenance therapy selection using the best available data to provide a rationale for these decisions. This case-based roundtable walks through treatment of a patient with newly diagnosed high-risk myeloma.
Idiopathic aplastic anemia vs hypocellular myelodysplastic syndrome
Authors: Durrani Jibran , Maciejewski Jaroslaw P.
Published: December 2019

Proper diagnostic distinction of bone marrow failure syndromes can often be challenging. In particular, for older patients with idiopathic aplastic anemia (AA), differential diagnosis includes myelodysplastic syndrome (MDS), which can atypically present in a hypocellular form. In addition to blasts and overt dysplasia, the presence of chromosomal abnormalities and a spectrum of somatic mutations may be revealing. Both clonal cytogenetic aberrations and somatic mutations most typically correspond to a clonal myelodysplasia, but clonal somatic mutations have also recently been found in AA. True driver myeloid mutations are uncommon in AA. Marrow hypocellularity in AA and occasionally in MDS patients points toward a similar immune mechanism responsible for deficient blood cell production and indicates that cytopenias in early hypocellular MDS might be treated with immunosuppressive modalities. Primary hypocellular MDS has to be distinguished from post-AA secondary MDS, most commonly associated with del7/7q. Post-AA MDS evolves at the rate of about 10% in 10 years, but recent observations suggest that widespread use of eltrombopag may influence the risk of progression to MDS. This complication likely represents a clonal escape, with founder hits occurring early on in the course of AA. A similar mechanism operates in the evolution of paroxysmal nocturnal hemoglobinuria (PNH) in AA patients, but PNH clones are rarely encountered in primary MDS.
Genetic predisposition to MDS: diagnosis and management
Authors: Furutani Elissa , Shimamura Akiko
Published: December 2019

Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by clonal hematopoiesis with a propensity to evolve into acute myeloid leukemia. MDS presenting in children and young adults is associated with features clinically and biologically distinct from MDS arising in older adults. MDS presenting in children and young adults is associated with a higher likelihood of an underlying genetic predisposition; however, genetic predisposition is increasingly recognized in a subset of older adults. The diagnosis of a genetic predisposition to MDS informs clinical care and treatment selection. Early diagnosis allows a tailored approach to management and surveillance. Genetic testing now offers a powerful diagnostic approach but also poses new challenges and caveats. Clinical expertise in these disorders together with scientific expertise regarding the affected genes is essential for diagnosis. Understanding the basic mechanisms of genetic predisposition to myeloid malignancies may inform surveillance strategies and lead to novel therapies. The cases presented in this article illustrate challenges to the diagnosis of germline genetic predisposition to MDS and how the diagnosis affects clinical management and treatment.
Is there a role for low-dose DOACs as prophylaxis?
Authors: Cohen Alexander T. , Hunt Beverley J.
Published: December 2019

The direct oral anticoagulants (DOACs) have transformed the management of thrombotic disorders. Large clinical trials have demonstrated that DOACs can replace vitamin K antagonists (VKAs) in the 2 existing major indications for anticoagulation: the prevention of stroke in atrial fibrillation and the acute treatment and secondary prevention of venous thromboembolism (VTE); this literature is widely known. In this article, we will concentrate on the less well-discussed benefits of the use of DOACs—using low doses as primary and secondary prophylaxis in both venous and arterial thromboprophylaxis. The attractiveness of using a low-dose DOAC is that the bleeding risk seems to be slightly lower than with the standard dose and significantly lower than with VKAs so that they can be used safely for long periods, where previously, VKAs had risk/benefit ratios that did not permit this. We discuss in detail the extended use of low-dose DOACs in secondary VTE prevention. We also cover the utility of low-dose DOACs in the evolving fields of prevention of hospital-associated VTE in acutely ill medical patients, after total hip and knee replacement, and in cancer patients. To complete the indications, we briefly discuss the role of low-dose DOACs in the secondary prevention of arterial vascular events.
Direct oral anticoagulant monitoring: what laboratory tests are available to guide us?
Authors: Sarode Ravi
Published: December 2019

Direct oral anticoagulants (DOACs) are increasingly used in the treatment and prophylaxis of thromboembolism because of several advantages over vitamin K antagonists, including no need for laboratory monitoring. However, it has become increasingly important in certain clinical scenarios to know either actual DOAC concentration (quantitative) or presence of DOAC (qualitative). These clinical conditions include patients presenting with major bleeding or requiring urgent surgery who may need a reversal or hemostatic agent, extremes of body weight, failed therapy, etc. Prothrombin time and activated partial thromboplastin time are variably affected by factor Xa inhibitors (FXaIs) and direct thrombin inhibitor (DTI), respectively, depending on reagents’ sensitivity, and hence, they cannot be relied on confidently. Thrombin time is highly sensitive to very low amounts of DTI; thus, normal value rules out a clinically significant amount. Liquid chromatography mass spectrometry accurately measures DOAC levels but is clinically impractical. Dilute thrombin time and ecarin-based assays using appropriate calibrators/controls provide an accurate DTI level. Anti-Xa assay using corresponding FXaI calibrators/controls provides accurate drug levels. However, these assays are not readily available in the United States compared with some other parts of the world. Heparin assays using anti-Xa activity often have a linear relationship with calibrated FXaI assays, especially at the lower end of on-therapy levels, and they may provide rapid assessment of drug activity for clinical decision making. Currently, there is very limited knowledge of DOAC effect on viscoelastic measurements. Although there is uniformity in expression of DOAC concentrations in nanograms per milliliter, a universal FXaI DOAC assay is urgently needed.
Indolent lymphomas: pushing the pace with novel agents
Authors: Jacobson Caron A.
Published: December 2019

Chemoimmunotherapy has been a hallmark of treatment of indolent B-cell non-Hodgkin lymphomas for the past 2 decades, with high response rates seen but relapses nearly inevitable and patients spending, on average, 20 years on and off treatment. Treatment advances, then, should be aimed at maintaining efficacy while minimizing toxicity or at achieving cure. Improved understanding of the genetic and molecular features of these diseases, as well as of the interaction between the tumor cell and its immune microenvironment, has resulted in an accelerated expansion of tolerable treatment options for patients, with new combinations of therapy holding promise that definitive therapy in these diseases is possible. These drugs include immunomodulating agents such as lenalidomide, small-molecule inhibitors of the B-cell receptor signaling pathway such as ibrutinib and idelalisib, B-cell lymphoma 2 homology 3 mimetics such as venetoclax, and enhancer of zeste homolog 2 inhibitors such as tazemetostat. Therapies that improve the host immune response against the malignant B cell are also of great interest, given the durable remission seen after allogeneic stem cell transplant in these diseases, and immune checkpoint inhibitors, agonist antibodies against immunostimulatory T-cell receptors, antibody–drug conjugates, bispecific antibodies, and finally chimeric antigen receptor T cells are all being investigated, with promising early efficacy signals. These treatments may not necessarily replace chemotherapy but rather augment it in an attempt to improve quality of life and survival for these patients.
Where does transplant fit in the age of targeted therapies?
Authors: Chow Victor A. , Gopal Ajay K.
Published: December 2019

The role of hematopoietic cell transplantation (HCT) for indolent lymphoma has evolved over the last 5 years with the availability of novel low-toxicity therapies and a better understanding of the prognosis of these entities. However, despite numerous treatment options for patients with follicular lymphoma, none are thought to be curative, and many require ongoing therapy with chronic toxicity. Historical trials indicate that autologous HCT as initial consolidation leads to improved progression-free survival, but not overall survival (OS) and, thus, is not typically recommended. However, autologous HCT for chemosensitive relapse can be carried out with ∼1% early mortality risk, affording disease control lasting a median of 3 to 5 years and the potential to improve OS. These results may compare favorably in efficacy, toxicity, and cost vs multiple sequential novel therapies with shorter durations of benefit. Recent data indicate that autologous HCT in follicular lymphoma patients with early initial progression will result in more than one third being alive and without relapse at 5 years, leading to improved OS when used within a year of the first recurrence. Unlike other available therapies, allogeneic HCT has the potential to cure up to one half of those transplanted with indolent B-cell non-Hodgkin lymphoma, although the risks need to be recognized and appropriate patient and donor selection is critical to ensure the best outcomes. HCT continues to remain a viable option in the current era of multiple targeted agents.
New diagnostic tools for delineating iron status
Authors: Ginzburg Yelena Z.
Published: December 2019

Recent advances in our understanding of iron metabolism regulation and crosstalk with erythropoiesis have provided insight into the pathophysiology of multiple disease conditions. For instance, the peptide hormone hepcidin is central to the regulation of iron metabolism. Its effect on cellular iron concentration involves binding ferroportin, the main iron export protein, resulting in its internalization and degradation and leading to iron sequestration within ferroportin-expressing cells. Furthermore, hepcidin regulation by erythropoiesis is attributed in large part to a bone marrow–derived hormone erythroferrone. Erythroferrone-induced hepcidin suppression in diseases of expanded hematopoiesis results in iron overload. Conversely, diseases, such as iron refractory iron deficiency anemia and anemia of chronic inflammation, are characterized by aberrantly increased hepcidin, resulting in iron sequestration and decreased circulating iron and eventually leading to iron-restricted erythropoiesis. Lastly, because iron functions in concert with erythropoietin to promote erythroid precursor survival, proliferation, and differentiation, iron deficiency anemia is a consequence not only of decreased hemoglobin synthesis in each cell but also, a decrease in erythropoietin responsiveness in the bone marrow. How to translate this new information to the clinical setting has not been fully elucidated. The purpose of this manuscript is to summarize current standard tools for identifying iron deficiency in anemic patients; explore the tools and context for evaluating novel markers, such as hepcidin, erythroferrone, and markers of the iron restriction response; and assess available evidence for how their use could increase our understanding of health outcomes in clinically challenging cases.
Diagnostic workflow for hereditary erythrocytosis and thrombocytosis
Authors: McMullin Mary Frances
Published: December 2019

In the patient presenting with an elevated blood count who does not have an acquired clonal disorder causing a myeloproliferative neoplasm, hereditary erythrocytosis or hereditary thrombocytosis needs to be considered as a possible explanation. A young patient and/or those with a family history of myeloproliferative neoplasm should specifically raise this possibility. Among the causes of hereditary erythrocytosis are mutations in the genes in the oxygen sensing pathway and high-affinity hemoglobins. Hereditary thrombocytosis has been shown to be accounted for by mutations in THPO, MPL, and JAK2 genes. In those who have a possible hereditary erythrocytosis or thrombocytosis, the investigative pathway includes specific investigation to rule out the more common acquired clonal disorders, and, if indicated, other secondary causes, measurement of specific cytokines as indicated, and search for specific identified molecular lesions that have been shown to cause these hereditary disorders. There remain individuals who appear to have a hereditary disorder in whom a genetic lesion cannot currently be identified.
Treatment of primary immunodeficiency with allogeneic transplant and gene therapy
Authors: Pai Sung-Yun
Published: December 2019

The treatment of primary immunodeficiency disorders with allogeneic hematopoietic cell transplantation (HCT) has a history dating back to 1968 with the first successful transplant for a patient with severe combined immunodeficiency (SCID). The omission of conditioning for patients with SCID owing to their inability to reject allogeneic grafts and the increasing use of reduced intensity conditioning regimens often result in a state of mixed or split donor-recipient chimerism. The use of gene therapy (GT) via retroviral or lentiviral transduction of autologous CD34+ hematopoietic stem and progenitor cells is expected to correct only a portion of the hematopoietic stem cell compartment. The consequences of partial correction after either form of cellular therapy differ according to how the genetic deficiency affects immune cell development and function. Moreover, the conditioning regimen or lack thereof impacts the cell lineages at risk of partial correction. Advances in our understanding of immune reconstitution after HCT and GT for SCID, Wiskott–Aldrich syndrome, and chronic granulomatous disease are discussed.
Single-agent and combination biologics in acute myeloid leukemia
Authors: Richard-Carpentier Guillaume , DiNardo Courtney D.
Published: December 2019

Acute myeloid leukemia (AML) is a heterogeneous malignancy characterized by recurrent genetic, epigenetic, and metabolic abnormalities. As a result of our increasing knowledge of the underlying biology of AML leading to rational drug development, several new targeted agents have been recently added to our therapeutic arsenal. The BCL2 inhibitor venetoclax in combination with low-dose cytarabine (LDAC) or hypomethylating agents (HMAs) is safe and effective in older patients with newly diagnosed AML ineligible for intensive chemotherapy. Glasdegib, a hedgehog pathway inhibitor, may be used in combination with LDAC for the same indication and improves survival compared with LDAC alone. In newly diagnosed, fit, older patients with therapy-related AML or AML with myelodysplasia-related changes, the liposome-encapsulated combination of daunorubicin and cytarabine (CPX-351) has shown superiority over the 7 + 3 regimen. The presence of an IDH1 or IDH2 mutation can be effectively targeted by ivosidenib or enasidenib, respectively. Gemtuzumab ozogamicin improves event-free survival in CD33+ patients with favorable or intermediate-risk cytogenetics. With new targeted agents available, comprehensive genomic characterization of AML at diagnosis and relapse is increasingly necessary to select optimal treatment. Herein, we review the new single-agent and combination biologics (omitting FLT3 inhibitors, which are discussed separately) and provide recommendations on how to best use and manage patients on these regimens in clinical practice.
Patient blood management as the standard of care
Authors: Murphy Michael F. , Palmer Antony
Published: December 2019

Blood transfusion is one of the most common hospital procedures in developed countries. However, inappropriate use of blood transfusion is common, and this is of considerable concern because transfusion is known to be associated with adverse events and is costly. Reductions in blood use have resulted from recent evidence indicating that restrictive use of red blood cell transfusions is associated with similar patient outcomes to liberal strategies and from a focus on patient blood management (PBM), which recognizes the importance of conserving the patient’s own blood alongside the judicious use of transfusion. A recent Consensus Conference in Frankfurt developed practice and research recommendations for PBM but also indicated that additional studies are needed to provide better evidence for PBM interventions, including for improved patient outcomes and lower hospital costs as well as for reductions in blood utilization. In the meanwhile, it is of utmost importance to translate PBM guidelines into practical day-to-day recommendations and encourage their use to make PBM “the standard of care.”
Perioperative management of patients with von Willebrand disease
Authors: O’Donnell James S. , Lavin Michelle
Published: December 2019

Surgical procedures represent a serious hemostatic challenge for patients with von Willebrand disease (VWD), and careful perioperative management is required to minimize bleeding risk. Risk stratification includes not only the nature of the surgery to be performed but the baseline plasma von Willebrand factor (VWF) levels, bleeding history, and responses to previous challenges. Baseline bleeding scores (BSs) may assist in identification of patients with a higher risk of postsurgical bleeding. There remains a lack of consensus between best practice guidelines as to the therapeutic target and assays to be monitored in the postoperative period. Hemostatic levels are maintained until bleeding risk abates: usually 3 to 5 days for minor procedures and 7 to 14 days for major surgery. Hemostatic supplementation is more complex in VWD than in other bleeding disorders owing to the combined but variable deficiency of both plasma VWF and factor VIII (FVIII) levels. For emergency surgery, coadministration of VWF and FVIII is required to ensure hemostasis; however, for elective procedures, early infusion of VWF replacement therapy will stabilize endogenous FVIII. Because endogenous FVIII production is unaffected in patients with VWD, repeated VWF supplementation (particularly with plasma-derived FVIII-containing products) may lead to accumulation of FVIII. Frequent monitoring of plasma levels and access to hemostatic testing are, therefore, essential for patients undergoing major surgery, particularly with more severe forms of VWD.
Is there a role for immunosuppression in antiphospholipid syndrome?
Authors: Sevim Ecem , Willis Rohan , Erkan Doruk
Published: December 2019

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis, pregnancy morbidity, or nonthrombotic manifestations in patients with persistently positive antiphospholipid antibodies (aPL). Conventional APS treatment focuses on antithrombotic strategies, which are usually ineffective for the microvascular and nonthrombotic manifestations of aPL. Using a case-based presentation, this review focuses on the role of immunosuppression in nonobstetric APS, including B-cell inhibition (rituximab, belimumab, and bortezomib), complement inhibition (eculizumab), mechanistic target of rapamycin inhibition (sirolimus), vascular endothelial cell modulation (defibrotide), statins, and traditional rheumatologic disease–modifying agents (hydroxychloroquine, mycophenolate mofetil, azathioprine, and cyclophosphamide).
Evidence-Based Minireview: What is the optimal timing of anti–PD-1 antibodies in relapsed classical Hodgkin lymphoma?
Authors: Allen Pamela Blair , LaCasce Ann S.
Published: December 2019

A 26-year-old woman was initially diagnosed with stage III classical Hodgkin lymphoma (HL) treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for 6 cycles and relapsed 9 months after completing therapy. She was treated with salvage chemotherapy followed by an autologous transplantation and 1 year of brentuximab vedotin (BV) maintenance therapy. She now presents 1 year later with relapsed disease above and below the diaphragm. What treatment would you recommend for this patient?
How we perform haploidentical stem cell transplantation with posttransplant cyclophosphamide
Authors: McCurdy Shannon R. , Luznik Leo
Published: December 2019

HLA-haploidentical hematopoietic stem cell transplantation is now one of the most commonly employed alternative donor techniques, with most centers applying T-cell–replete strategies such as that developed by the Baltimore group using high-dose posttransplant cyclophosphamide. HLA-haploidentical hematopoietic stem cell transplantation using posttransplant cyclophosphamide is associated with low rates of severe graft-versus-host disease and nonrelapse mortality and does not require graft manipulation or storage, which results in a low graft acquisition cost. Its remarkable safety when used with reduced-intensity conditioning has been demonstrated in patients up to 75 years old with outcomes similar to those of patients in their 50s. Several large, registry-based retrospective studies have confirmed the efficacy of HLA-haploidentical hematopoietic stem cell transplantation with posttransplant cyclophosphamide, achieving results comparable to those of HLA-matched hematopoietic stem cell transplantation. In this article, we describe our approach to this rapidly available and clinically simple platform and address some of the key clinical questions associated with its use.
Platelets and cancer-associated thrombosis: focusing on the platelet activation receptor CLEC-2 and podoplanin
Authors: Suzuki-Inoue Katsue
Published: December 2019

Patients with cancer have an increased risk of thromboembolism, which is the second leading cause of death in these patients. Several mechanisms of the prothrombotic state in these patients have been proposed. Among them are a platelet activation receptor, C-type lectin-like receptor 2 (CLEC-2), and its endogenous ligand podoplanin, which are the focus of this review. CLEC-2 is almost specifically expressed in platelets/megakaryocytes in humans. A membrane protein, podoplanin is expressed in certain types of cancer cells, including squamous cell carcinoma, brain tumor, and osteosarcoma, in addition to several normal tissues, including kidney podocytes and lymphatic endothelial cells but not vascular endothelial cells. In the bloodstream, podoplanin induces platelet activation by binding to CLEC-2 and facilitates hematogenous cancer metastasis and cancer-associated thrombosis. In an experimental lung metastasis model, the pharmacological depletion of CLEC-2 from platelets in mice resulted in a marked reduction of lung metastasis of podoplanin-expressing B16F10 cells. Control mice with B16F10 orthotopically inoculated in the back skin showed massive thrombus formation in the lungs, but the cancer-associated thrombus formation in CLEC-2–depleted mice was significantly inhibited, suggesting that CLEC-2–podoplanin interaction stimulates cancer-associated thrombosis. Thromboinflammation induced ectopic podoplanin expression in vascular endothelial cells or macrophages, which may also contribute to cancer-associated thrombosis. CLEC-2 depletion in cancer-bearing mice resulted in not only reduced cancer-associated thrombosis but also reduced levels of plasma inflammatory cytokines, anemia, and sarcopenia, suggesting that cancer-associated thrombosis may cause thromboinflammation and cancer cachexia. Blocking CLEC-2–podoplanin interaction may be a novel therapeutic strategy in patients with podoplanin-expressing cancer.
Pancreaticoduodenectomy following surgery for esophageal cancer with gastric tube reconstruction: a case report and literature review
Authors: Izumi Hideki , Yoshii Hisamichi , Abe Rin , Yamamoto Soichiro , Mukai Masaya , Nomura Eiji , Sugiyama Tomoko , Tajiri Takuma , Makuuchi Hiroyasu
Published: December 2019

Background

Synchronous and asynchronous multiple cancers have become more pervasive in recent years despite advances in medical technologies. However, there have been only six cases (including the present case) that underwent pancreaticoduodenectomy (PD) for pancreas head cancer following surgery for esophageal cancer. PD for treating pancreas head cancer is extremely challenging; thus, the confirmation of vessel variation and selection of surgical procedures are vital.

Case presentation

The patient was a 78-year-old Japanese male who was synchronously diagnosed with esophageal and cecal cancer 7 years previously at our hospital. He was admitted with densely stained and jaundiced urine and presented no remarkable family medical history. Following various examinations, surgery was performed due to the diagnosis of distal cholangiocarcinoma (pancreatic head cancer). Since the tumor was located far from the gastroduodenal artery (GDA) and no significant lymph node metastases could be found, subtotal stomach-preserving PD was performed instead of the resection of GDA with the right gastroepiploic artery (RGEA) for gastric tube blood flow preservation. The common hepatic artery (CHA) and GDA were confirmed, and RGEA diverged from GDA was identified. Subsequently, their respective tapings were preserved. The right gastric artery (RGA) was identified, taped, and preserved considering the gastric tube blood flow. The inflow area of the right gastroepiploic vein (RGEV) through gastric colic vein trunk in the superior mesenteric vein was exposed and preserved as the outflow of gastric tube blood flow. PD was completed without any complications on the shade of the gastric tube.

Conclusions

This case report describes successfully preserved gastric blood flow without the resection of GDA, RGEA, RGEV, or RGA. To preserve the gastric tube, GDA inflow, RGEA, RGA, and RGEV outflow should be preserved if possible. When performing PD after tube reconstruction, it is essential to confirm the relative positions of the blood vessel, blood flow, and tumor through three-dimensional computed tomography angiography before surgery and to consider the balance between the invasiveness and optimal curability of the surgery.
Phase II Feasibility and Biomarker Study of Neoadjuvant Trastuzumab and Pertuzumab With Chemoradiotherapy for Resectable Human Epidermal Growth Factor Receptor 2–Positive Esophageal Adenocarcinoma: TRAP Study
Authors: Stroes Charlotte I. , Schokker Sandor , Creemers Aafke , Molenaar Remco J. , Hulshof Maarten C.C.M. , van der Woude Stephanie O. , Bennink Roel J. , Mathôt Ron A.A. , Krishnadath Kausilia K. , Punt Cornelis J.A. , Verhoeven Rob H.A. , van Oijen Martijn G.H. , Creemers Geert-Jan , Nieuwenhuijzen Grard A.P. , van der Sangen Maurice J.C. , Beerepoot Laurens V. , Heisterkamp Joos , Los Maartje , Slingerland Marije , Cats Annemieke , Hospers Geke A.P. , Bijlsma Maarten F. , van Berge Henegouwen Mark I. , Meijer Sybren L. , van Laarhoven Hanneke W.M.
Published: December 2019

PURPOSE

Approximately 15% to 43% of esophageal adenocarcinomas (EACs) are human epidermal growth factor receptor 2 (HER2) positive. Because dual-agent HER2 blockade demonstrated a survival benefit in breast cancer, we conducted a phase II feasibility study of trastuzumab and pertuzumab added to neoadjuvant chemoradiotherapy (nCRT) in patients with EAC.

PATIENTS AND METHODS

Patients with resectable HER2-positive EAC received standard nCRT with carboplatin and paclitaxel and 41.4 Gy of radiotherapy, with 4 mg/kg of trastuzumab on day 1, 2 mg/kg per week during weeks 2 to 6, and 6 mg/kg per week during weeks 7, 10, and 13 and 840 mg of pertuzumab every 3 weeks. The primary end point was feasibility, defined as ≥ 80% completion of treatment with both trastuzumab and pertuzumab. An exploratory comparison of survival with a propensity score–matched cohort receiving standard nCRT was performed, as were exploratory pharmacokinetic and biomarker analyses.

RESULTS

Of the 40 enrolled patients (78% men; median age, 63 years), 33 (83%) completed treatment with trastuzumab and pertuzumab. No unexpected safety events were observed. R0 resection was achieved in all patients undergoing surgery, with pathologic complete response in 13 patients (34%). Three-year progression-free and overall survival (OS) were 57% and 71%, respectively (median follow-up, 32.1 months). Compared with the propensity score–matched cohort, a significantly longer OS was observed with HER2 blockade (hazard ratio, 0.58; 95% CI, 0.34 to 0.97). Results of pharmacokinetic analysis and activity on [18F]fluorodeoxyglucose positron emission tomography scans did not correlate with survival or pathologic response. Patients with HER2 3+ overexpression or growth factor receptor–bound protein 7 (Grb7) –positive tumors at baseline demonstrated significantly better survival ( P = .007) or treatment response ( P = .016), respectively.

CONCLUSION

Addition of trastuzumab and pertuzumab to nCRT in patients with HER2-positive EAC is feasible and demonstrates potentially promising activity compared with historical controls. HER2 3+ overexpression and Grb7 positivity are potentially predictive for survival and treatment response, respectively.
Treatment versus Punishment: Understanding Racial Inequalities in Drug Policy
Authors: Kim Jin Woo , Morgan Evan , Nyhan Brendan
Published: December 2019

Context: Many observers believe that the policy response to the opioid crisis is less punitive than the crack scare and that the reason is that victims are (stereotypically) white.

Methods: To assess this conjecture, we compile new longitudinal data on district-level drug-related deaths and (co)sponsorship of legislation on drug abuse in the House of Representatives over the past four decades. Using legislator fixed effects models, we then test how changes in drug-related death rates in legislators' districts predict changes in (co)sponsorship of treatment-oriented or punitive legislation in the subsequent year and assess whether these relationships vary by race of victim or drug type.

Findings: Policy makers were more likely to introduce punitive drug-related bills during the crack scare and are more likely to introduce treatment-oriented bills during the current opioid crisis. The relationship between district-level drug deaths and subsequent sponsorship of treatment-oriented legislation is greater for opioid deaths than for cocaine-related deaths and for white victims than for black victims. By contrast, district-level drug deaths are not significantly related to sponsorship of punishment-oriented bills.

Conclusions: These results suggest that the racial inequalities and double standards of drug policy still persist but in different forms.
Framing the Opioid Crisis: Do Racial Frames Shape Beliefs of Whites Losing Ground?
Authors: Gollust Sarah E. , Miller Joanne M.
Published: December 2019

Context: Although research has begun to examine perceptions of being on the losing side of politics, it has been confined to electoral politics. The context of health disparities, and particularly the opioid crisis, offers a case to explore whether frames that emphasize racial disadvantage activate loser perceptions and the political consequences of such beliefs.

Methods: White survey participants (N = 1,549) were randomized into three groups: a control which saw no news article, or one of two treatment groups which saw a news article about the opioid crisis framed to emphasize either the absolute rates of opioid mortality among whites or the comparative rates of opioid mortality among whites compared to blacks.

Findings: Among control group participants, perceiving oneself a political loser was unrelated to attitudes about addressing opioids, whereas those who perceived whites to be on the losing side of public health had a less empathetic response to the opioid crisis. The comparative frame led to greater beliefs that whites are on the losing side of public health, whereas the absolute frame led to more empathetic policy opinions.

Conclusions: Perceptions that one's racial group has lost ground in the public health context could have political consequences that future research should explore.
Are Policy Strategies for Addressing the Opioid Epidemic Partisan? A View from the States
Authors: Grogan Colleen M. , Bersamira Clifford S. , Singer Phillip M. , Smith Bikki Tran , Pollack Harold A. , Andrews Christina M. , Abraham Amanda J.
Published: December 2019

Context: In contrast to the Affordable Care Act, some have suggested the opioid epidemic represents an area of bipartisanship. This raises an important question: to what extent are Democrat-led and Republican-led states different or similar in their policy responses to the opioid epidemic?

Methods: Three main methodological approaches were used to assess state-level policy responses to the opioid epidemic: a legislative analysis across all 50 states, an online survey of 50 state Medicaid agencies, and in-depth case studies with policy stakeholders in five states.

Findings: Conservative states pursue hidden and targeted Medicaid expansions, and a number of legislative initiatives, to address the opioid crisis. However, the total fiscal commitment among these Republican-led states pales in comparison to states that adopt the ACA Medicaid expansion. Because the state legislative initiatives do not provide treatment, these states spend substantially less than states with Democratic control.

Conclusions: Rather than persistently working to retrench all programs, conservatives have relied on policy designs that emphasize devolution, fragmentation, and inequality to both expand and retrench benefits. This strategy, which allocates benefits differentially to different social groups and obfuscates responsibility, allows conservatives to avoid political blame typically associated with retrenchment.
INOVAÇÃO SOCIAL E DESENVOLVIMENTO TERRITORIAL
Authors: Sarate João Alberto , Carolina Piccinini Valmíria
Published: December 2019

Este estudo investiga a relação entre as ações empreendedoras coletivas em territórios específicos e a criação de inovação social. Trata-se de um estudo qualitativo empírico, baseado no método de estudo de caso. Os atores sociais locais foram entrevistados e os dados analisados por meio do software NVivo©. Os resultados indicam que o processo de inovação social está relacionado ao modo de habitar coletivo local e ao contexto social e econômico. O estudo identifica aspectos positivos e negativos do processo de desenvolvimento territorial por meio das ações coletivas empreendedoras. O modelo teórico de seis elementos é original e propõe uma contribuição para a pesquisa em desenvolvimento territorial e a emergência da inovação social.
EFEITO DO EXERCÍCIO FÍSICO SOBRE A DISLIPIDEMIA
Authors: Soares Bianca Tostes , Amaral Luila Vianna Rodrigues , Correia Cardozo Diogo , Duarte Emerson Rodrigues
Published: December 2019

Introdução: A dislipidemia é um fator de risco para o desenvolvimento de aterosclerose e doenças vasculares. Em contra partida, o exercício físico é considerado uma terapia contra a dislipidemia. Objetivo: Analisar os efeitos de um programa de exercícios físicos no perfil lipídico de indivíduos dislipidêmicos de ambos os sexos participantes de um programa multidisciplinar de reabilitação cardiopulmonar e metabólica (RCPM). Métodos: Foi feito uma análise retrospectiva de um banco de dados de pacientes atendidos na RCPM. O treinamento físico realizado consistia de uma combinação entre exercícios de força e aeróbicos realizados duas vezes por semana durante 10 meses. Resultados: Após o período de intervenção foi observado melhora em todos os parâmetros metabólicos investigados (P?0,05). Conclusão: A adesão em um programa de RCPM para portadores de dislipidemia, por aproximadamente 10 meses, praticado duas vezes na semana, mostrou melhora no perfil de colesterol total, HDL, LDL e triglicérides.
A INFLUÊNCIA DA GINÁSTICA LABORAL NOS DISTÚRBIOS OSTEOMUSCULARES RELACIONADOS AO TRABALHO
Authors: Oliveira Souza Juliana de , Teixeira Matins Marcela , Muniz de Souza Carine , Coelho Baptista Isabela , Pereira Cardoso Lauane , Braz de Medeiros Geisiane , Torres Cruz Ariela , Oliveira Januário Priscila de
Published: December 2019

Introdução: A ginástica laboral (GL) são exercícios diários que tem o intuido de promover benefícios à saúde dos trabalhadores. Objetivos: Analisar os efeitos da GL nos distúrbios osteomusculares relacionados ao trabalho em funcionários de um setor administrativo do ramo siderúrgico. Materiais e Métodos: Participaram deste estudo 31 funcionários, divididos em dois grupos: grupo experimental (GE n=16) e grupo controle (GC n=15). Ambos foram avaliados antes e após as sessões de GL através do Questionário Nórdico de Sintomas Osteomusculares.  Após a avaliação, os funcionários do GE foram submetidos a 16 sessões de GL, realizadas 2 vezes por semana, com duração média de 15 minutos. Resultados: No GE houve uma diminuição das queixas de dor/formigamento principalmente na parte superior das costas, enquanto no GC houve um aumento dessas queixas na parte inferior das costas e nos punhos/mãos. Quanto à realização das atividades laborativas, domésticas e de lazer observou-se no GE uma diminuição das queixas na parte inferior das costas, enquanto houve um aumento no GC. Em ambos os grupos houve diminuição na procura por médico/fisioterapeuta, principalmente por problemas na parte inferior das costas. No GE observou-se redução das queixas por algum problema principalmente na parte inferior das costas, porém no GC houve aumento das queixas nesta região. Conclusões: As sessões de GL mostraram-se eficazes sobre os distúrbios osteomusculares dos funcionários do GE, diminuindo os relatos de queixas de dor/formigamento para a realização das atividades laborativas, domésticas e de lazer, bem como diminuição das consultas com profissionais de saúde.