bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoregulatory networks in sickle cell alloimmunization
Authors: Yazdanbakhsh Karina 
Published: December 2016

Abstract
Red blood cell (RBC) transfusions are critical for treatment and prevention of complications of sickle cell disease (SCD), and most SCD patients will receive 1 or more transfusions by age 20. However, SCD alloimmunization remains a serious complication of transfusions that can lead to life-threatening acute and delayed transfusion reactions. Alloimmunization rates are higher in SCD patients most likely due to RBC antigenic differences between largely white donors vs mainly African-American recipients and frequency of transfusions. However, it remains unclear why some but not all SCD patients develop alloantibodies. Cellular immune responses that differ between alloimmunized and nonalloimmunized SCD patients are beginning to be characterized. Altered CD4+ T helper cell responses, known to control immunoglobulin G production, have been identified in alloimmunized SCD patients, including abnormalities in regulatory T cells, as well as helper type 1 (TH1), TH17, and follicular helper T cells. Furthermore, heightened innate immune cell responses to cell free heme with cell polarization toward proinflammatory T cell profiles were recently reported in SCD antibody responders, suggesting that the ongoing hemolytic state in SCD may impair the ability of innate immune cells in these already alloimmunized patients to counter alloimmunization. Identification of molecular pathways in key cellular components that differ between alloimmunized and nonalloimmunized SCD patients is likely to lead to identification of biomarkers of alloimmunization and future design of targeted therapies to prevent or even dampen alloantibody responses in these highly susceptible patients.
Checkpoint inhibition in myeloma
Authors: Benson Don M. 
Published: December 2016

Abstract
Historically, attempts at cancer immunotherapy have emphasized strategies designed to stimulate or augment the immune system into action. In the past decade, a complementary approach has developed, that of releasing immune cells from inhibitory restraint. Discoveries in the fundamental biology of how immunity is regulated, how the immune system interfaces with malignancy, and how cancer cells may exploit these processes to evade detection have all been translated into the rapidly growing field of therapeutic immune checkpoint inhibition for cancer. Myeloma is a malignancy associated with significant immune dysfunction imparted both by the disease itself as well as by many of the immunosuppressive therapies that have been used in the past. The growing body of preclinical data regarding immunoregulatory mechanisms that appear active in myeloma has begun to be translated to clinical trials targeting these signaling axes. This review will attempt to summarize the current understanding of the basic biology of several immune checkpoint pathways that may be important in myeloma and provide an up-to-date overview of recent and ongoing clinical trials of immune checkpoint inhibitors in myeloma. Finally, several current challenges and possible future directions of immune checkpoint blockade in myeloma will be reviewed.
Non-Hodgkin lymphoma across the pediatric and adolescent and young adult age spectrum
Authors: Sandlund John T. , Martin Mike G. 
Published: December 2016

Abstract
The non-Hodgkin lymphomas (NHLs) occurring in children and adolescents and young adults (AYA) are characterized by various age-related differences in tumor biology and survival. Children generally present with high-grade lymphomas, such as Burkitt lymphoma, diffuse large B-cell lymphoma, lymphoblastic lymphoma, and anaplastic large cell lymphoma, whereas low-grade histologic subtypes, such as follicular lymphoma, occur more frequently with increasing age. Treatment outcome for children with NHL is generally superior to that observed in adults. Factors contributing to this discrepancy include psychosocial factors, patient factors, and differences in tumor biology and therapy. These factors will be reviewed, with particular attention to the biological features of diffuse large B-cell lymphoma and anaplastic large cell lymphoma and corresponding therapeutic challenges. Novel targeting agents have been developed, which have been shown to be active in some patients. There is clearly a need for treatment protocols with eligibility criteria that cover the full span of the pediatric and AYA age range and that incorporate detailed molecular characterization of the tumors.
Sickle cell disease: when and how to transfuse
Authors: Howard Jo 
Published: December 2016

Abstract
Blood transfusion remains an important therapeutic intervention in patients with sickle cell disease (SCD), aiming to both increase the oxygen carrying capacity of blood and to reduce the complications of vaso-occlusion. Simple, manual exchange and automated exchange can be effective in reducing the acute and chronic complications of SCD, and the advantages and disadvantages of each methodology mean they all have a role in different situations. Evidence for the role of emergency transfusion in the management of the acute complications of SCD, including acute pain and acute chest syndrome, comes from observational data. Several important randomized controlled trials have shown the efficacy of transfusion in primary and secondary stroke prevention in patients with SCD but, outside these areas, clinical practice lacks a clear evidence base. Evidence for the role of long-term transfusion in the prevention of the non-neurologic chronic complications of SCD comes from analysis of secondary outcomes of these randomized trials and from observational data. In view of the paucity of data, the risks and benefits of transfusion should be fully discussed with patients/families before a long-term transfusion program is commenced. Evidence is only available for the role of preoperative transfusion or for prophylactic transfusion through pregnancy in certain situations, and the role of transfusions outside these situations is discussed. Questions about when and how to transfuse in SCD remain and will need further randomized trials to provide answers.
Prevention of central nervous system sequelae in sickle cell disease without evidence from randomized controlled trials: the case for a team-based learning collaborative
Authors: DeBaun Michael R. , King Allison A. 
Published: December 2016

Abstract
Since 1998, the National Institutes of Health has funded 5 randomized controlled trials (RCTs) for primary and secondary prevention of strokes in children with sickle cell anemia (SCA). In a systematic fashion, these trials have significantly advanced the care of children with SCA. In the absence of an RCT, clinicians are often compelled to make decisions at the bedside, based on experience, observational studies, and principles of hematology. We will provide an initial example that describes how a team-based, learning collaborative developed a multisite standard care protocol with a low budget (<$10 000 per year) to overcome the intrinsic limitations of advancing the care of neurologic complications in sickle cell disease (SCD). The critical components of this approach include: (1) regular meetings with the multidisciplinary team from multiple sites; (2) consensus regarding the best evidence-based neurologic management in multiple SCD centers; (3) an Institutional Review Board-approved protocol based on consensus standard care; (4) minimizing and ensuring accurate data collection; and most importantly, (5) a spirit of collaboration to improve the care of individuals with SCD. Four common neurologic problems and strategies for management in children and adults with SCD will be discussed: (1) secondary stroke prevention in high-income countries; (2) primary stroke prevention in low- and middle-income countries (LMICs); (3) poor academic performance in students; and (4) cognitive disability in adults. With a commitment to a team-based learning collaborative, incremental advances are possible for the neurologic care of children and adults with SCD.
New therapies for hemophilia
Authors: Pipe Steven W. 
Published: December 2016

AbstractIndividuals with severe hemophilia have benefitted from 5 decades of advances that have led to widespread availability of safe and efficacious factors VIII and IX, a multidisciplinary integrated care model through a network of specialized hemophilia treatment centers, and aggressive introduction of prophylactic replacement therapy to prevent bleeding and preserve joint health. Yet, there are remaining challenges and treatment gaps which have prevented complete abrogation of all joint bleeding, and progressive joint deterioration may continue in some affected individuals over the course of a lifetime. Some of these challenges can now be addressed with recombinant clotting factors with extended half-life that may improve adherence to prophylaxis regimens through more convenient infusion schedules, maintain higher plasma levels for longer when clinically necessary, and allow for better adaptation to individual phenotypic and pharmacokinetic variability. Real-world case studies will be presented that illustrate practical application of these newly approved therapies in clinical practice and the clinical trial data that have demonstrated the potential for improved clinical outcomes by implementing these strategies.
What is the role of hydroxychloroquine in reducing thrombotic risk in patients with antiphospholipid antibodies?
Authors: Wang Tzu-Fei , Lim Wendy 
Published: December 2016

AbstractA 35-year-old man presents with an acute unprovoked deep vein thrombosis of the left lower extremity. He is treated with anticoagulation and elects to discontinue treatment after 6 months. He subsequently develops polyarthralgias, fatigue, and a malar rash, and a diagnosis of systemic lupus erythematosus is made based on laboratory and clinical findings. Additional laboratory testing reveals persistent triple positive antiphospholipid antibodies, including lupus anticoagulant, high titer anticardiolipin antibodies, and anti–β2-glycoprotein I antibodies. The patient is reinitiated on anticoagulation, and the patient’s rheumatologist inquires if the addition of hydroxychloroquine could help to prevent recurrent thrombosis.
Nontransplant therapy for bone marrow failure
Authors: Townsley Danielle M. , Winkler Thomas 
Published: December 2016

Abstract
Nontransplant therapeutic options for acquired and constitutional aplastic anemia have significantly expanded during the last 5 years. In the future, transplant may be required less frequently. That trilineage hematologic responses could be achieved with the single agent eltrombopag in refractory aplastic anemia promotes new interest in growth factors after years of failed trials using other growth factor agents. Preliminary results adding eltrombopag to immunosuppressive therapy are promising, but long-term follow-up data evaluating clonal evolution rates are required before promoting its standard use in treatment-naive disease. Danazol, which is traditionally less preferred for treating cytopenias, is capable of preventing telomere attrition associated with hematologic responses in constitutional bone marrow failure resulting from telomere disease.
Transplantation for bone marrow failure: current issues
Authors: Peffault de Latour Régis 
Published: December 2016

Abstract
The preferred treatment of idiopathic aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA)–identical sibling donor. Transplantation from a well-matched unrelated donor (MUD) may be considered for patients without a sibling donor after failure of immunosuppressive therapy, as may alternative transplantation (mismatched, cord blood or haplo-identical HSCT) for patients without a MUD. HSCT may also be contemplated for congenital disorders in cases of pancytopenia or severe isolated cytopenia. Currently, HSCT aims are not only to cure patients but also to avoid long-term complications, notably chronic graft-versus-host disease (GVHD), essential for a good quality of life long term. This paper summarizes recent advances in HSCT for idiopathic and inherited AA disorders. The effect of age on current transplantation outcomes, the role of transplantation in paroxysmal nocturnal hemoglobinuria, and the prevention of GVHD are also discussed. Emerging strategies regarding the role of up-front unrelated donor and alternative donor HSCT in idiopathic AA, along with advances in the treatment of clonal evolution in Fanconi anemia, are also examined.
Childhood maltreatment and characteristics of adult depression: Meta-analysis
Authors: Nelson Janna , Klumparendt Anne , Doebler Philipp , Ehring Thomas 
Published: December 2016

BackgroundChildhood maltreatment has been discussed as a risk factor for the development and maintenance of depression.AimsTo examine the relationship between childhood maltreatment and adult depression with regard to depression incidence, severity, age at onset, course of illness and treatment response.MethodWe conducted meta-analyses of original articles reporting an association between childhood maltreatment and depression outcomes in adult populations.ResultsIn total, 184 studies met inclusion criteria. Nearly half of patients with depression reported a history of childhood maltreatment. Maltreated individuals were 2.66 (95% CI 2.38–2.98) to 3.73 (95% CI 2.88–4.83) times more likely to develop depression in adulthood, had an earlier depression onset and were twice as likely to develop chronic or treatment-resistant depression. Depression severity was most prominently linked to childhood emotional maltreatment.ConclusionsChildhood maltreatment, especially emotional abuse and neglect, represents a risk factor for severe, early-onset, treatment-resistant depression with a chronic course.
Depression screening with patient-targeted feedback in cardiology: DEPSCREEN-INFO randomised clinical trial
Authors: Löwe Bernd , Blankenberg Stefan , Wegscheider Karl , König Hans-Helmut , Walter Dirk , Murray Alexandra M. , Gierk Benjamin , Kohlmann Sebastian 
Published: December 2016

BackgroundInternational guidelines advocate depression screening in patients with coronary heart disease (CHD) and other chronic illnesses, but evidence is lacking.AimsTo test the differential efficacy of written patient-targeted feedback v. no written patient feedback after depression screening.MethodPatients with CHD or hypertension from three cardiology settings were randomised and screened for depression (ClinicalTrials.gov Identifier: NCT01879111). Compared with the control group, where only cardiologists received written feedback, in the intervention group both cardiologists and patients received written feedback regarding depression status. Depression severity was measured 1 month (primary outcome) and 6 months after screening.ResultsThe control group (n = 220) and the patient-feedback group (n = 155) did not differ in depression severity 1 month after screening. Six months after screening, the patient-feedback group showed significantly greater improvements in depression severity and was twice as likely to seek information about depression compared with the control group.ConclusionsPatient-targeted feedback in addition to screening has a significant but small effect on depression severity after 6 months and may encourage patients to take an active role in the self-management of depression.
Preoperative Echocardiographic Indices of Diastolic Dysfunction and Brain Natriuretic Peptide in Predicting Postoperative Atrial Fibrillation After Noncardiac Surgery
Authors: Brecher Oren , Gulati Harleena , Roistacher Nancy , Zhang Hao , Shi Weiji , Thaler Howard T. , Amar David 
Published: December 2016

BACKGROUND:
We have shown previously that either echocardiographic indices of diastolic dysfunction or increased preoperative brain natriuretic peptide (BNP) predict postoperative atrial fibrillation (POAF). Because these 2 predictors of POAF have not been evaluated together, our goal was to further elucidate their concurrent role in patients undergoing noncardiac thoracic surgery.

METHODS:
We retrospectively identified 191 patients who had a preoperative transthoracic echocardiogram and serum BNP level collected as part of routine care before major lung or esophageal resection. Clinical and echocardiographic data were compared between patients who did or did not develop POAF (>5 minutes), and prognostic factors for POAF were identified.

RESULTS:
Univariate associations with POAF (41 of 191; 22% patients) included older age (P = .04), male sex (P = .01), hypertension (P = .03), increased body mass index (P = .01), and prolonged transmitral flow deceleration time (P < .0001), whereas BNP was not statistically significant (P = .07). Stepwise logistic regression analysis showed that both increasing transmitral flow deceleration time (continuous data log base 2 transformed; odds ratio, 16.05; 95% confidence interval, 3.74–68.96; P = .0002) and left atrial diastolic volume index (continuous data log base 2 transformed; odds ratio, 3.29; 95% confidence interval, 1.22–8.91; P = .02) were independent risk factors of POAF (area under the receiver operating characteristic curve = 0.73). There was no significant interaction between BNP and the 2 independent variables (P = .60, and P = .90), respectively.

CONCLUSIONS:
In a cohort of patients who had echocardiography and BNP measurements before undergoing major thoracic surgery, this study showed that when evaluated together greater preoperative left atrial diastolic volume index and transmitral flow deceleration time but not BNP levels were independent predictors for POAF.
Resident Physicians Improve Nontechnical Skills When on Operating Room Management and Leadership Rotation
Authors: Cole Devon C. , Giordano Christopher R. , Vasilopoulos Terrie , Fahy Brenda G. 
Published: December 2016

BACKGROUND:
Anesthesiology residency primarily emphasizes the development of medical knowledge and technical skills. Yet, nontechnical skills (NTS) are also vital to successful clinical practice. Elements of NTS are communication, teamwork, situational awareness, and decision making.

METHODS:
The first 10 consecutive senior residents who chose to participate in this 2-week elective rotation of operating room (OR) management and leadership training were enrolled in this study, which spanned from March 2013 to March 2015. Each resident served as the anesthesiology officer of the day (AOD) and was tasked with coordinating OR assignments, managing care for 2 to 4 ORs, and being on call for the trauma OR; all residents were supervised by an attending AOD. Leadership and NTS techniques were taught via a standardized curriculum consisting of leadership and team training articles, crisis management text, and daily debriefings. Resident self-ratings and attending AOD and charge nurse raters used the Anaesthetists’ Non-Technical Skills (ANTS) scoring system, which involved task management, situational awareness, teamwork, and decision making. For each of the 10 residents in their third year of clinical anesthesiology training (CA-3) who participated in this elective rotation, there were 14 items that required feedback from resident self-assessment and OR raters, including the daily attending AOD and charge nurse. Results for each of the items on the questionnaire were compared between the beginning and the end of the rotation with the Wilcoxon signed-rank test for matched samples. Comparisons were run separately for attending AOD and charge nurse assessments and resident self-assessments. Scaled rankings were analyzed for the Kendall coefficient of concordance (ω) for rater agreement with associated χ2 and P value.

RESULTS:
Common themes identified by the residents during debriefings were recurrence of challenging situations and the skills residents needed to instruct and manage clinical teams. For attending AOD and charge nurse assessments, resident performance of NTS improved from the beginning to the end of the rotation on 12 of the 14 NTS items (P < .05), whereas resident self-assessment improved on 3 NTS items (P < .05). Interrater reliability (across the charge nurse, resident, and AOD raters) ranged from ω = .36 to .61 at the beginning of the rotation and ω = .27 to .70 at the end of the rotation.

CONCLUSIONS:
This rotation allowed for teaching and resident assessment to occur in a way that facilitated resident education in several of the skills required to meet specific milestones. Resident physicians are able to foster NTS and build a framework for clinical leadership when completing a 2-week senior elective as an OR manager.
Effectiveness of Epidural Analgesia, Continuous Surgical Site Analgesia, and Patient-Controlled Analgesic Morphine for Postoperative Pain Management and Hyperalgesia, Rehabilitation, and Health-Related Quality of Life After Open Nephrectomy: A Prospective, Randomized, Controlled Study
Authors: Capdevila Xavier , Moulard Sebastien , Plasse Christian , Peshaud Jean-Luc , Molinari Nicolas , Dadure Christophe , Bringuier Sophie 
Published: December 2016

BACKGROUND:
There is no widely recognized effective technique to optimally reduce pain scores and prevent persistent postoperative pain after nephrectomy. We compared continuous surgical site analgesia (CSSA), epidural analgesia (EA), and a control group (patient-controlled analgesic morphine) in patients undergoing open nephrectomy.

METHODS:
Sixty consecutive patients were randomized to be part of EA, CSSA, or control groups postoperatively for 72 hours. All patients received patient-controlled analgesic morphine, if needed. Hyperalgesia was assessed on the first, second, and third postoperative days. Chronic pain characteristics and quality of life were analyzed at 1 and 3 months. The primary outcome was the pain score at 24 hours. Secondary outcomes were morphine consumption, postoperative rehabilitation, hyperalgesia, chronic pain incidence, and quality-of-life parameters.

RESULTS:
At 24 hours, mean ± standard deviation pain values at rest (2.4 ± 1.7, 2.2 ± 1.2, and 4.2 ± 1.2, respectively, in EA, CSSA, and control groups, P <.001) and during coughing was lower in the EA and CSSA groups. Total morphine consumption was higher in the control group. Rehabilitation parameters improved sooner in the EA and CSSA groups. Median values of area of hyperalgesia differed at 48 hours between the EA group and the control group (36.4 cm2) and (52 cm2) (P = .01) and at 72 hours among the EA group, CSSA group, and the control group (40 cm2, 39.5 cm2, and 59 cm2, respectively; P = .002). CSSA reduced the severity of pain and hyperalgesia at 1 month and optimized quality of life 3 months after surgery (role physical scores, P = .005).

CONCLUSIONS:
CSSA and EA significantly improve postoperative analgesia, reduce postoperative morphine consumption, area of wound hyperalgesia, and accelerate patient rehabilitation after open nephrectomy. CSSA significantly reduces the severity of residual pain 1 month after surgery and optimizes quality-of-life parameters 3 months after surgery.