bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges in chronic transfusion for patients with thalassemia
Authors: Lal Ashutosh 
Published: December 2020

Abstract
The introduction of regular red cell transfusions 60 years ago transformed β-thalassemia major from a fatal childhood illness into a chronic disorder. Further advances in the prevention of transfusion-transmitted infections and management of iron overload have allowed survival and quality of life to approach normal. However, transfusion therapy for some other thalassemia syndromes continues to challenge clinical decision-making. Nearly one-half of the patients with E ß thalassemia are transfusion-dependent, yet the criteria for initiating transfusions or hemoglobin targets are not well defined. Patients with thalassemia intermedia who begin transfusions as adults are at very high risk for developing red cell alloimmunization and serious hemolytic transfusion reactions. In the growing number of survivors of Bart hydrops fetalis, the approach to transfusion therapy and iron chelation is rapidly evolving. A collaboration between hematology and transfusion medicine specialists will be essential to improving patient care and developing evidence-based guidelines.
Can pregnancy-adapted algorithms avoid diagnostic imaging for pulmonary embolism?
Authors: Chan Wee-Shian 
Published: December 2020

Abstract
The low prevalence of pulmonary embolism (PE) among pregnant patients presenting with suspected PE implies that most of these patients will be found not have the disease. Given this low prevalence, excluding PE in this population has necessitated the use of sensitive and specific diagnostic imaging, such as computed tomography pulmonary angiography or ventilation-perfusion scanning. Recent studies suggest that a clinical prediction rule with D-dimer testing can also be used to exclude a subset of pregnant patients with suspected PE without the need for diagnostic imaging. The YEARS criteria, which consist of clinical signs and symptoms of deep venous thrombosis, hemoptysis, and PE as the most likely diagnosis (a subjective variable), combined with selective D-dimer levels, seem to safely exclude up to one-third of these patients without imaging. The revised Geneva rule using objective variables, combined with nonpregnancy cutoffs for D-dimer levels, offers some promise, although fewer patients avoided imaging (14%). These recent studies provide evidence in support of radiation avoidance for some patients; however, for most, imaging remains the only option. Future studies should focus on improving the safety and techniques of imaging modalities, in addition to improving the specificity of D-dimer testing and objective prediction rules. Studies assessing patients’ and physicians’ values, preferences, and risk perceptions are also required to assist clinicians in shared decision making when counseling pregnant patients with suspected PE.
First-generation vs second-generation tyrosine kinase inhibitors: which is best at diagnosis of chronic phase chronic myeloid leukemia?
Authors: Oehler Vivian G. 
Published: December 2020

Abstract
In 2020, for the great majority of patients with chronic phase chronic myeloid leukemia (CML), life expectancy is unaffected by a diagnosis of CML because of the unparalleled efficacy of ABL-targeted tyrosine kinase inhibitors (TKIs) in halting disease progression. A wealth of choices exist for first-line treatment selection, including the first-generation TKI imatinib and the second-generation TKIs bosutinib, dasatinib, and nilotinib. How I select first-line therapy between first-generation and second-generation TKIs is discussed in the context of patient-specific CML disease risk, therapy-related risks, and treatment goals. Although rare, identifying patients with CML at higher risk for disease progression or resistance is important and influences first-line TKI selection. I review the impact of first-generation vs second-generation TKI selection on treatment response and outcomes; the ability to achieve, as well as the timing of, treatment-free remission; and the impact of specific TKIs on longer-term health.
Transformed lymphoma: what should I do now?
Authors: Smith Sonali 
Published: December 2020

Abstract
Although the majority of indolent lymphomas (focusing on follicular lymphoma [FL]) have a prolonged waxing and waning course, a portion of patients experience histologic transformation (HT) to either diffuse large B-cell lymphoma or a higher-grade morphology, often with acquisition of MYC and BCL2 and/or BCL6 rearrangements (high-grade B-cell lymphoma–double-hit lymphoma/triple-hit lymphoma). The overall incidence of HT and transformed follicular lymphoma (tFL) may be declining, but outcomes remain inferior to those in simple indolent lymphoma progression. Recent data suggest that the majority of HT cases occur in higher-risk patients with FL, and they occur early after initial chemoimmunotherapy, comprising the majority of patients with progression of disease within 24 months. This latter point emphasizes the need for a sufficient biopsy at relapse in FL. Treatment options depend on the prior therapy for the indolent component as well as the histology at relapse, but they generally follow several principles discussed in this article. Anthracycline-naïve patients have the best outcomes if there is HT, and responses to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) are similar to those of patients with de novo diffuse large B-cell lymphoma. Patients with anthracycline exposure prior to transformation have the best outcomes with salvage chemotherapy and a consolidative autologous stem cell transplant. However, a major challenge is the management of patients with tFL who experience relapse early after bendamustine-based treatment, in whom the role of consolidative transplant after anthracycline-based treatment is unclear. In the past several years, cellular therapy has emerged as an important tool for some but not all patients with tFL. This review focuses on the nuances of managing tFL.
Preventing infections in children and adults with asplenia
Authors: Lee Grace M. 
Published: December 2020

Abstract
An estimated 1 million people in the United States have functional or anatomic asplenia or hyposplenia. Infectious complications due to encapsulated organisms such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae can lead to fulminant sepsis and death, particularly in young children, in the period shortly after splenectomy, and in immunocompromised patients. Patients with asplenia are also at risk for less common infections due to Capnocytophaga, Babesia, and malaria. Antibiotic prophylaxis, vaccines, and patient and family education are the mainstays of prevention in these at-risk patients. Recommendations for antibiotic prophylaxis typically target high-risk periods, such as 1 to 3 years after splenectomy, children ≤5 years of age, or patients with concomitant immunocompromise. However, the risk for sepsis is lifelong, with infections occurring as late as 40 years after splenectomy. Currently available vaccines recommended for patients with asplenia include pneumococcal vaccines (13-valent pneumococcal conjugate vaccine followed by the 23-valent pneumococcal polysaccharide vaccine), meningococcal vaccines (meningococcal conjugate vaccines for serogroups A, C, Y and W-135 and serogroup B meningococcal vaccines), H. influenzae type b vaccines, and inactivated influenza vaccines. Ongoing booster doses are also recommended for pneumococcal and meningococcal vaccines to maintain protection. Despite the availability of prevention tools, adherence is often a challenge. Dedicated teams or clinics focused on patient education and monitoring have demonstrated substantial improvements in vaccine coverage rates for individuals with asplenia and reduced risk of infection. Future efforts to monitor the quality of care in patients with asplenia may be important to bridge the know–do gap in this high-risk population.
Managing toxicities of Bruton tyrosine kinase inhibitors
Authors: Lipsky Andrew , Lamanna Nicole 
Published: December 2020

Abstract
Inhibition of Bruton’s tyrosine kinase (BTK) has revolutionized the treatment landscape for patients with chronic lymphocytic leukemia (CLL). By targeting this critical kinase in proximal B-cell receptor signaling, BTK inhibitors (BTKis) impair cell proliferation, migration, and activation of NF-κB. Clinically, because indefinite inhibition is a mainstay of therapy, there is an extended period of exposure in which adverse effects can develop. Given the impressive efficacy and activity of BTKis in the treatment of patients with CLL, appropriate management of treatment-emergent adverse events (AEs) is of paramount importance. Here we review the BTKi landscape and present the available toxicity and safety data for each agent. The long-term toxicity profile of ibrutinib, a first-in-class inhibitor, is well characterized and includes a clinically significant incidence of cardiac arrhythmias, bleeding, infection, diarrhea, arthralgias, and hypertension. Acalabrutinib, the initial second-generation BTKi to earn approval from the US Food and Drug Administration, demonstrates improved kinase selectivity for BTK, with commonly observed adverse reactions including infection, headache, and diarrhea. Mediated by both on-target inhibition of BTK and variable off-target inhibition of other kinases including interleukin-2–inducible T-cell kinase (ITK), tyrosine-protein kinase (TEC), and endothelial growth factor receptor (EGFR), the toxicity profile of BTKis is closely linked to their pattern of kinase binding. Other emerging BTKis include second-generation agents with variable degrees of kinase selectivity and third-generation agents that exhibit reversible noncovalent binding to BTK. We also highlight critical considerations for the prevention and monitoring of AEs and offer practical management strategies for treatment-emergent toxicities.
Applied genomics in MPN presentation
Authors: Moliterno Alison R. , Kaizer Hannah 
Published: December 2020

Abstract
Polycythemia vera, essential thrombocytosis (ET), and primary myelofibrosis (PMF) are grouped together as myeloproliferative neoplasms (MPNs) because of shared clinical, pathologic, and molecular features. The 2005 discovery of the driver mutation JAK2V617F, found in more than 70% of individuals with MPNs and 98% of those with PV, has transformed the diagnosis and management of MPNs. Although PV is the most common phenotype associated with JAK2V617F, roughly 60% of individuals with ET or PMF also have the mutation, and JAK2V617F is now recognized as a common lesion in clonal hematopoiesis (CH). JAK2V617F+ CH and MPN are indolent disorders that evolve over time, with transitions to different disease phases, transformation to bone marrow failure or leukemia, and high thrombosis rates. Genomic assessment has taken center stage as an important tool to define disease phenotype, disease burden, prognosis, and even thrombosis risk of MPNs. Genomics has also unveiled the causes and factors that modify the risk of acquiring and expanding CH and MPNs and points to new pathways for targeted therapies to treat and ultimately prevent them. Genomic assessment of patients with MPNs, like other cancers, enables the clinician to capitalize on large population data sets to inform the individual patient of risk, identify treatment, and improve outcomes.
Genomics of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes
Authors: Patnaik Mrinal M. , Lasho Terra L. 
Published: December 2020

Abstract
Myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes are uniquely classified neoplasms occurring in both children and adults. This category consists of 5 neoplastic subtypes: chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), BCR-ABL1–negative atypical chronic myeloid leukemia (aCML), MDS/MPN-ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), and MDS/MPN-unclassifiable (U). Cytogenetic abnormalities and somatic copy number variations are uncommon; however, &gt;90% patients harbor gene mutations. Although no single gene mutation is specific to a disease subtype, certain mutational signatures in the context of appropriate clinical and morphological features can be used to establish a diagnosis. In CMML, mutated coexpression of TET2 and SRSF2 results in clonal hematopoiesis skewed toward monocytosis, and the ensuing acquisition of driver mutations including ASXL1, NRAS, and CBL results in overt disease. MDS/MPN-RS-T demonstrates features of SF3B1-mutant MDS with ring sideroblasts (MDS-RS), with the development of thrombocytosis secondary to the acquisition of signaling mutations, most commonly JAK2V617F. JMML, the only pediatric entity, is a bona fide RASopathy, with germline and somatic mutations occurring in the oncogenic RAS pathway giving rise to disease. BCR-ABL1–negative aCML is characterized by dysplastic neutrophilia and is enriched in SETBP1 and ETNK1 mutations, whereas MDS/MPN-U is the least defined and lacks a characteristic mutational signature. Molecular profiling also provides prognostic information, with truncating ASXL1 mutations being universally detrimental and germline CBL mutations in JMML showing spontaneous regression. Sequencing information in certain cases can help identify potential targeted therapies (IDH1, IDH2, and splicing mutations) and should be a mainstay in the diagnosis and management of these neoplasms.
Evidence-Based Minireview: Myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes: a focused review
Authors: Patnaik Mrinal M. , Lasho Terra 
Published: December 2020

AbstractMyelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes are unique myeloid neoplasms, with overlapping features of MDS and MPN. They consist of four adult onset entities including chronic myelomonocytic leukemia (CMML), MDS/MPN-ring sideroblasts-thrombocytosis (MDS/MPN-RS-T), BCR-ABL1 negative atypical chronic myeloid leukemia (aCML) and MDS/MPN-unclassifiable (MDS/MPN-U); with juvenile myelomonocytic leukemia (JMML) being the only pediatric onset entity. Among these overlap neoplasms, CMML is the most frequent and is hallmarked by the presence of sustained peripheral blood monocytosis with recurrent mutations involving TET2 (60%), SRSF2 (50%) and ASXL1 (40%); with RAS pathway mutations and JAK2V617F being relatively enriched in proliferative CMML subtypes (WBC ≥13 × 109/L). CMML usually presents in the 7th decade of life, with a male preponderance and is associated with a median overall survival of &lt;36 months. Adverse prognosticators in CMML include increasing age, high WBC, presence of circulating immature myeloid cells, anemia, thrombocytopenia and truncating ASXL1 mutations. While allogeneic stem cell transplantation remains the only curative option, given the late onset of this neoplasm and high frequency of comorbidities, most patients remain ineligible. Hypomethylating agents such as azacitidine, decitabine and oral decitabine/cedazuridine have been US FDA approved for the management of CMML, with overall response rates of 40-50% and complete remission rates of &lt;20%. While these agents epigenetically restore hematopoiesis in a subset of responding patients, they do not impact mutational allele burdens and eventual disease progression to AML remains inevitable. Newer treatment modalities exploiting epigenetic, signaling and splicing abnormalities commonly seen in CMML are much needed.
Immunotherapy with cells (article not eligible for CME credit)
Authors: Chong Elise A. , Porter David L. 
Published: December 2020

Abstract
Both older and newer cell therapies have demonstrated impressive responses in otherwise poor-prognosis lymphomas. Consequently, cellular therapy now plays a major role in the management of many non-Hodgkin lymphomas. In this article, we examine the role of chimeric antigen receptor (CAR) T cells, allogeneic stem cell transplantation, and virus-directed T cells for treatment of lymphomas. We review the current indications for CAR T cells and discuss our clinical approach to selecting and treating patients with aggressive B-cell lymphomas to receive CD19-directed CAR T cells. In addition, we highlight newer cell therapies and provide an overview of promising future approaches that have the potential to transform immunotherapy with cells to treat lymphomas.
The impact of COVID-19 on chronic care according to providers: a qualitative study among primary care practices in Belgium
Authors: Danhieux Katrien , Buffel Veerle , Pairon Anthony , Benkheil Asma , Remmen Roy , Wouters Edwin , van Olmen Josefien 
Published: December 2020

Abstract
Background
The COVID-19 pandemic affects the processes of routine care for chronic patients. A better understanding helps to increase resilience of the health system and prepare adequately for next waves of the pandemic.

Methods
A qualitative study was conducted in 16 primary care practices: 6 solo working, 4 monodisciplinary and 7 multidisciplinary. Twenty-one people (doctors, nurses, dieticians) were interviewed, using semi-structured video interviews. A thematic analysis was done using the domains of the Chronic Care Model (CCM).

Results
Three themes emerged: changes in health care organization, risk stratification and self-management support. All participating practices reported drastic changes in organization with a collective shift towards COVID-19 care, and reduction of chronic care activities, less consultations, and staff responsible for self-management support put on hold. A transition to digital support did not occur. Few practitioners had a systematic approach to identify and contact high-risk patients for early follow-up. A practice with a pre-established structured team collaboration managed to continue most chronic care elements. Generally, practitioners expected no effects of the temporary disruption for patients, although they expressed concern about patients already poorly regulated.

Conclusion
Our findings show a disruption of the delivery of chronic care in the Belgium prim care context. In such contexts, the establishment of the CCM can facilitate continuity of care in crisis times. Short term actions should be directed to facilitate identifying high-risk patients and to develop a practice organization plan to organize chronic care and use digital channels for support, especially to vulnerable patients, during next waves of the epidemic.
An implementation history of primary health care transformation: Alberta’s primary care networks and the people, time and culture of change
Authors: Leslie Myles , Khayatzadeh-Mahani Akram , Birdsell Judy , Forest P. G. , Henderson Rita , Gray Robin Patricia , Schraeder Kyleigh , Seidel Judy , Zwicker Jennifer , Green Lee A. 
Published: December 2020

AbstractBackgroundPrimary care, and its transformation into Primary Health Care (PHC), has become an area of intense policy interest around the world. As part of this trend Alberta, Canada, has implemented Primary Care Networks (PCNs). These are decentralized organizations, mandated with supporting the delivery of PHC, funded through capitation, and operating as partnerships between the province’s healthcare administration system and family physicians. This paper provides an implementation history of the PCNs, giving a detailed account of howpeople,time, andculturehave interacted to implement bottom up, incremental change in a predominantly Fee-For-Service (FFS) environment.MethodsOur implementation history is built out of an analysis of policy documents and qualitative interviews. We conducted an interpretive analysis of relevant policy documents (n = 20) published since the first PCN was established. We then grounded 12 semi-structured interviews in that initial policy analysis. These interviews explored 11 key stakeholders’ perceptions of PHC transformation in Alberta generally, and the formation and evolution of the PCNs specifically. The data from the policy review and the interviews were coded inductively, with participants checking our emerging analyses.ResultsOver time, the PCNs have shifted from an initial Frontier Era that emphasized local solutions to local problems and featured few rules, to a present Era of Accountability that features central demands for standardized measures, governance, and co-planning with other elements of the health system. Across both eras, the PCNs have been first and foremost instruments and supporters of family physician authority and autonomy. A core group ofpeopleemerged to create the PCNs and, overtime,to develop a long-term Quality Improvement (QI) vision and governance plan for them as organizations. The continuing willingness of both these groups to work at understanding and aligning one another’sculturesto achieve the transformation towards PHC has been central to the PCNs’ survival and success.ConclusionsGeneralizable lessons from the implementation history of this emerging policy experiment include: The need for flexibility within a broad commitment to improving quality. The importance of time for individuals and organizations to learn about: quality improvement; one another’s cultures; and how best to support the transformation of a system while delivering care locally.
Maternal iodine status in a multi-ethnic UK birth cohort: associations with autism spectrum disorder
Authors: Cromie Kirsten Jade , Threapleton Diane Erin , Snart Charles Jonathan Peter , Taylor Elizabeth , Mason Dan , Wright Barry , Kelly Brian , Reid Stephen , Azad Rafaq , Keeble Claire , Waterman Amanda H. , Meadows Sarah , McKillion Amanda , Alwan Nisreen A. , Cade Janet Elizabeth , Simpson Nigel A. B. , Stewart Paul M. , Zimmermann Michael , Wright John , Waiblinger Dagmar , Mon-Williams Mark , Hardie Laura J. , Greenwood Darren Charles 
Published: December 2020

Abstract
Background
Maternal iodine requirements increase during pregnancy to supply thyroid hormones essential for fetal brain development. Maternal iodine deficiency can lead to hypothyroxinemia, a reduced fetal supply of thyroid hormones which, in the first trimester, has been linked to an increased risk of autism spectrum disorder (ASD) in the child. No study to date has explored the direct link between maternal iodine deficiency and diagnosis of ASD in offspring.

Methods
Urinary iodine concentrations (UIC) and iodine/creatinine ratios (I:Cr) were measured in 6955 mothers at 26–28 weeks gestation participating in the Born in Bradford (BiB) cohort. Maternal iodine status was examined in relation to the probability of a Read (CTV3) code for autism being present in a child’s primary care records through a series of logistic regression models with restricted cubic splines.

Results
Median (inter-quartile range) UIC was 76 μg/L (46, 120) and I:Cr was 83 μg/g (59, 121) indicating a deficient population according to WHO guidelines. Ninety two children (1·3%) in our cohort had received a diagnosis of ASD by the census date. Overall, there was no evidence to support an association between I:Cr or UIC and ASD risk in children aged 8–12 years (p = 0·3).

Conclusions
There was no evidence of an increased clinical ASD risk in children born to mothers with mild-to-moderate iodine deficiency at 26 weeks gestation. Alternative functional biomarkers of exposure and a wider range of conditions may provide further insight.