bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of immune-mediated cytopenias in patients with primary immunodeficiencies and immune regulatory disorders (PIRDs)
Authors: Seidel Markus G. 
Published: December 2020

Abstract
Severe immune cytopenias (SICs) are rare acquired conditions characterized by immune-mediated blood cell destruction. They may necessitate emergency medical management and long-term immunosuppressive therapy, strongly compromising the quality of life. The initial diagnostic workup involves excluding malignancies, congenital cytopenias, bone marrow failure syndromes, infections, and rheumatologic diseases such as systemic lupus erythematosus. Causal factors for SIC such as primary immunodeficiencies or immune regulatory disorders, which are referred to as inborn errors of immunity (IEIs), should be diagnosed as early as possible to allow the initiation of a targeted therapy and avoid multiple lines of ineffective treatment. Ideally, this therapy is directed against an overexpressed or overactive gene product or substitutes a defective protein, restoring the impaired pathway; it can also act indirectly, enhancing a countermechanism against the disease-causing defect. Ultimately, the diagnosis of an underling IEI in patients with refractory SIC may lead to evaluation for hematopoietic stem cell transplantation or gene therapy as a definitive treatment. Interdisciplinary care is highly recommended in this complex patient cohort. This case-based educational review supports decision making for patients with immune-mediated cytopenias and suspected inborn errors of immunity.
How do I sequence therapy for follicular lymphoma?
Authors: Salles Gilles 
Published: December 2020

Abstract
In the past decade, many new agents have been introduced for the management of follicular lymphoma, and therapeutic strategies have evolved over time. The clinical benefits of the different treatments vary and, at the time of progression, are influenced by patient and disease characteristics, the duration of the interval from last treatment, and the nature of the treatments previously administered. Altogether, this results in a marked heterogeneity of clinical situations encountered during the treatment of these patients. Despite numerous trials performed in the field, there is no single standard of care for patients undergoing second-line treatment or beyond. Furthermore, patients recruited in these studies have characteristics that rarely represent the full spectrum of possible clinical presentations. Therefore, to optimally individualize treatment, all of the risks (short- and long-term) and benefits of the available options should be well known. Discussing the goals of therapy with the patient at each intervention is also critical in providing an optimal sequence of therapy.
Inherited microcytic anemias
Authors: Cappellini Maria Domenica , Russo Roberta , Andolfo Immacolata , Iolascon Achille 
Published: December 2020

Abstract
Inherited microcytic anemias can be broadly classified into 3 subgroups: (1) defects in globin chains (hemoglobinopathies or thalassemias), (2) defects in heme synthesis, and (3) defects in iron availability or iron acquisition by the erythroid precursors. These conditions are characterized by a decreased availability of hemoglobin (Hb) components (globins, iron, and heme) that in turn causes a reduced Hb content in red cell precursors with subsequent delayed erythroid differentiation. Iron metabolism alterations remain central to the diagnosis of microcytic anemia, and, in general, the iron status has to be evaluated in cases of microcytosis. Besides the very common microcytic anemia due to acquired iron deficiency, a range of hereditary abnormalities that result in actual or functional iron deficiency are now being recognized. Atransferrinemia, DMT1 deficiency, ferroportin disease, and iron-refractory iron deficiency anemia are hereditary disorders due to iron metabolism abnormalities, some of which are associated with iron overload. Because causes of microcytosis other than iron deficiency should be considered, it is important to evaluate several other red blood cell and iron parameters in patients with a reduced mean corpuscular volume (MCV), including mean corpuscular hemoglobin, red blood cell distribution width, reticulocyte hemoglobin content, serum iron and serum ferritin levels, total iron-binding capacity, transferrin saturation, hemoglobin electrophoresis, and sometimes reticulocyte count. From the epidemiological perspective, hemoglobinopathies/thalassemias are the most common forms of hereditary microcytic anemia, ranging from inconsequential changes in MCV to severe anemia syndromes.
Approaches for relapsed CLL after chemotherapy-free frontline regimens
Authors: Roeker Lindsey E. , Mato Anthony R. 
Published: December 2020

Abstract
Novel agents, including Bruton’s tyrosine kinase inhibitors (BTKi; ibrutinib, acalabrutinib), venetoclax, and phosphatidylinositol 3-kinase inhibitors (PI3Ki; idelalisib, duvelisib), have fundamentally changed the chronic lymphocytic leukemia (CLL) treatment landscape, allowing for a chemotherapy-free paradigm for many. Randomized trials that demonstrated efficacy of these agents in the relapsed/refractory setting rarely included patients with prior novel agent exposure. Herein, we review available data, including single-arm prospective studies and retrospective cohorts, on outcomes for novel agent approaches after novel agent exposure. We examine data for subsequent treatment options in 3 specific scenarios: (1) progression of disease while receiving BTKi, (2) progression of disease after discontinuation of BTKi for intolerance, and (3) after treatment with venetoclax. Data are most robust for venetoclax-based regimens after progression on BTKi. For patients who experience progression of disease after discontinuation of BTKi for intolerance, venetoclax-based regimens and retreatment with BTKi (depending on severity of initial intolerance) are 2 data-driven options. After frontline venetoclax/obinutuzumab, subsequent treatment approaches depend on whether patients experience progression of disease during or after discontinuation of their fixed duration frontline regimen and whether venetoclax/obinutuzumab was discontinued for intolerance. After progression of disease while on venetoclax, we recommend BTKi as second-line therapy. For patients who experience progression after completion or premature discontinuation (because of intolerance) of fixed duration venetoclax/obinutuzumab, either BTKi or retreatment with venetoclax (with aggressive supportive care if prior intolerance) are reasonable considerations. Subsequent lines of therapy in these scenarios include PI3Ki and consideration of cellular therapies. Finally, clinical trial enrollment for interested patients in any line of therapy is recommended.
Extrahematopoietic manifestations of the short telomere syndromes
Authors: Schratz Kristen E. 
Published: December 2020

Abstract
The short telomere syndromes encompass a spectrum of clinical manifestations that present from infancy to late adulthood. They are caused by mutations in telomerase and other telomere maintenance genes and have a predominantly degenerative phenotype characterized by organ failure across multiple systems. They are collectively one of the most common inherited bone marrow failure syndromes; however, their most prevalent presentations are extrahematopoietic. This review focuses on these common nonhematologic complications, including pulmonary fibrosis, liver pathology, and immunodeficiency. The short telomere syndrome diagnosis informs clinical care, especially in guiding diagnostic evaluations as well as in the solid organ transplant setting. Early recognition allows an individualized approach to screening and management. This review illustrates a myriad of extrahematopoietic presentations of short telomere syndromes and how they impact clinical decisions.
CAR T cells vs allogeneic HSCT for poor-risk ALL
Authors: Diorio Caroline , Maude Shannon L. 
Published: December 2020

Abstract
For subgroups of children with B-cell acute lymphoblastic leukemia (B-ALL) at very high risk of relapse, intensive multiagent chemotherapy has failed. Traditionally, the field has turned to allogeneic hematopoietic stem cell transplantation (HSCT) for patients with poor outcomes. While HSCT confers a survival benefit for several B-ALL populations, often HSCT becomes standard-of-care in subsets of de novo ALL with poor risk features despite limited or no data showing a survival benefit in these populations, yet the additive morbidity and mortality can be substantial. With the advent of targeted immunotherapies and the transformative impact of CD19-directed chimeric antigen receptor (CAR)–modified T cells on relapsed or refractory B-ALL, this approach is currently under investigation in frontline therapy for a subset of patients with poor-risk B-ALL: high-risk B-ALL with persistent minimal residual disease at the end of consolidation, which has been designated very high risk. Comparisons of these 2 approaches are fraught with issues, including single-arm trials, differing eligibility criteria, comparisons to historical control populations, and vastly different toxicity profiles. Nevertheless, much can be learned from available data and ongoing trials. We will review data for HSCT for pediatric B-ALL in first remission and the efficacy of CD19 CAR T-cell therapy in relapsed or refractory B-ALL, and we will discuss an ongoing international phase 2 clinical trial of CD19 CAR T cells for very-high-risk B-ALL in first remission.
Fundamentals of immunology for understanding immunotherapy for lymphoma
Authors: Ansell Stephen M. 
Published: December 2020

Abstract
An effective antitumor immune response in patients with lymphoma would eradicate the malignant B cells and cure the patient of the disease. This, however, does not occur, and a suboptimal antitumor response results in persistence and subsequent progression of the patient’s disease. The goals of immunotherapy are therefore to restore an effective antitumor immune response by promoting immune recognition, optimizing immune activation, and supporting persistence of the immune response resulting in subsequent immunological memory. Multiple mechanisms, however, are present within the tumor microenvironment that account for an inadequate immune response. These include loss of major histocompatibility complex expression on tumor cells and subsequent inadequate antigen presentation, increased expression of immunosuppressive ligands on malignant cells, populations of immune cells with suppressive function present in the tumor, and cytokines secreted by the malignant cell or other cells in the microenvironment that promote immune exhaustion or suppress the immune response. Successful immunotherapeutic strategies are specifically addressing these issues by promoting antigen presentation, improving recognition of the malignant cell, directly activating T cells and natural killer cells, and blocking immune checkpoint signaling that would suppress the immune response. Many of these approaches have proven highly successful in patients with various subtypes of lymphoma and are now being incorporated into standard clinical practice.
Handling challenging questions in the management of chronic myeloid leukemia: when is it safe to stop tyrosine kinase inhibitors?
Authors: Rea Delphine 
Published: December 2020

AbstractThe paradigm for managing patients with chronic myeloid leukemia is evolving. In the recent past, restoring a normal life expectancy while patients are receiving never-ending targeted therapy with BCR–ABL1 tyrosine kinase inhibitors through prevention of progression to blast phase and mitigation of iatrogenic risks was considered the best achievable outcome. Now, long-term treatment-free remission with continued response off tyrosine kinase inhibitor therapy is recognized as the most optimal benefit of treatment. Indeed, numerous independent clinical trials provided solid proof that tyrosine kinase inhibitor discontinuation was feasible in patients with deep and sustained molecular responses. This article discusses when tyrosine kinase inhibitors may be safely stopped in clinical practice on the basis of the best and latest available evidence.
Lack of association between multiple polymorphisms in aryl hydrocarbon receptor (AhR) gene and cancer susceptibility
Authors: Li He , Luo Li , Wang Dan , Duan Jun , Zhang Rui 
Published: December 2020

Abstract
Background
The aryl hydrocarbon receptor (AhR) is commonly known as an environmental sensor. Polymorphisms in AhR gene have been implicated in susceptibility to cancer. However, the results were controversial. This study was conducted to quantitatively summarize the association between AhR polymorphisms and cancer risk by meta-analysis.

Methods
Relevant reports were searched in four databases (Embase, PubMed, Wanfang, and China National Knowledge Infrastructure). We used pooled odds ratio (OR) and 95% confidence interval (95% CI) to evaluate the strength of the association in both standard and cumulative meta-analysis. Subgroup and sensitivity analysis was also performed, and between-study heterogeneity and publication bias were checked.

Results
A total of seventeen studies referring to three AhR polymorphisms (rs2066853, rs7796976, and rs2074113) were identified, and 9557 cases and 10038 controls were included. There was no statistically significant association of AhR rs2066853 polymorphism with cancer risk in the overall population, and the negative results were repeated in subgroup analysis by the ethnicity and cancer type. Concerning AhR rs7796976 or rs2074113 polymorphism, no significant correlation was detected. Moreover, these non-significant findings were stable in sensitivity analysis, and the cumulative meta-analysis indicated a trend of no significant link between this three AhR polymorphisms and cancer risk as more data accumulated over time.

Conclusion
This meta-analysis provides evidence that the rs2066853, rs7796976, or rs2074113 polymorphism in AhR gene is not a susceptible predictor of cancer. Further clinical and functional investigation between AhR polymorphisms and cancer susceptibility are needed.
Evidence based models of care for the treatment of alcohol use disorder in primary health care settings: a systematic review
Authors: Rombouts Susan A. , Conigrave James H. , Saitz Richard , Louie Eva , Haber Paul , Morley Kirsten C. 
Published: December 2020

Abstract
Background
Pharmacological and behavioural treatments for alcohol use disorders (AUDs) are effective but the uptake is limited. Primary care could be a key setting for identification and continuous care for AUD due to accessibility, low cost and acceptability to patients.
We aimed to synthesise the literature regarding differential models of care for the management of AUD in primary health care settings.

Methods
We conducted a systematic review of articles published worldwide (1998-present) using the following databases; Medline, PsycINFO, Cochrane database of systematic reviews, Cochrane Central Register of Controlled Trials and Embase. The Grey Matters Tool guided the grey literature search. We selected randomised controlled trials evaluating the effectiveness of a primary care model in the management of AUD. Two researchers independently assessed and then reached agreement on the included studies. We used the Cochrane risk of bias tool 2.0 for the critical appraisal.

Results
Eleven studies (4186 participants) were included. We categorised the studies into ‘lower’ versus ‘higher’ intensity given the varying intensity of clinical care evaluated across the studies. Significant differences in treatment uptake were reported by most studies. The uptake of AUD medication was reported in 5 out of 6 studies that offered AUD medication. Three studies reported a significantly higher uptake of AUD medication in the intervention group. A significant reduction in alcohol use was reported in two out of the five studies with lower intensity of care, and three out of six studies with higher intensity of care.

Conclusion
Our results suggest that models of care in primary care settings can increase treatment uptake (e.g. psychosocial and/or pharmacotherapy) although results for alcohol-related outcomes were mixed. More research is required to determine which specific patient groups are suitable for AUD treatment in primary health care settings and to identify which models and components are most effective.

Trial Registration
PROSPERO: CRD42019120293.
Factors affecting prehospital delay in rural and urban patients with stroke: a prospective survey-based study in Southwest Germany
Authors: Ungerer Matthias N. , Busetto Loraine , Begli Nima H. , Riehle Katharina , Regula Jens , Gumbinger Christoph 
Published: December 2020

Abstract
Background
Reducing prehospital delay plays an important role in increasing the thrombolysis rate in patients with stroke. Several studies have identified predictors for presentation ≤4.5 h, but few compared these predictors in urban and rural communities. We aimed to identify predictors of timely presentation to the hospital and identify possible differences between the urban and rural populations.

Methods
From January to June 2017, we conducted a prospective survey of patients with stroke admitted to an urban comprehensive stroke centre (CSC) and a rural primary care centre (PCC). Predictors were identified using binary logistical regression. Predictors and patient characteristics were then compared between the CSC and PCC.

Results
Overall, 459 patients were included in our study. We identified hesitation before seeking help, awareness of the existence of a time-window, type of admission and having talked about stroke symptoms with friends/relatives who had previously had a stroke as the strongest predictors for presentation to the emergency room ≤4.5 h. Patients admitted to the rural PCC were more hesitant to seek help and less likely to contact emergency services, even though patients had comparable knowledge pertaining to stroke care concepts.

Conclusions
Patients from rural areas were more likely to be hesitant to seek help and contacted the EMS less frequently, despite similar self-awareness of having a stroke.
Educational campaigns should focus on addressing these disparities in rural populations. Affected patients should also be encouraged to talk about their symptoms and take part in educational campaigns.
A study of medication errors during the prescription stage in the pediatric critical care services of a secondary-tertiary level public hospital
Authors: Brennan-Bourdon Lorena Michele , Vázquez-Alvarez Alan O. , Gallegos-Llamas Jahaira , Koninckx-Cañada Manuel , Marco-Garbayo José Luis , Huerta-Olvera Selene G. 
Published: December 2020

Abstract
Background
Medication Errors (MEs) are considered the most common type of error in pediatric critical care services. Moreover, the ME rate in pediatric patients is up to three times higher than the rate for adults. Nevertheless, information in pediatric population is still limited, particularly in emergency/critical care practice. The purpose of this study was to describe and analyze MEs in the pediatric critical care services during the prescription stage in a Mexican secondary-tertiary level public hospital.

Methods
A cross-sectional study to detect MEs was performed in all pediatric critical care services [pediatric emergency care (PEC), pediatric intensive care unit (PICU), neonatal intensive care unit (NICU), and neonatal intermediate care unit (NIMCU)] of a public teaching hospital. A pharmacist identified MEs by direct observation as the error detection method and MEs were classified according to the updated classification for medication errors by the Ruíz-Jarabo 2000 working group. Thereafter, these were subclassified in clinically relevant MEs.

Results
In 2347 prescriptions from 301 patients from all critical care services, a total of 1252 potential MEs (72%) were identified, and of these 379 were considered as clinically relevant due to their potential harm. The area with the highest number of MEs was PICU (n = 867). The ME rate was > 50% in all pediatric critical care services and PICU had the highest ME/patient index (13.1). The most frequent MEs were use of abbreviations (50.9%) and wrong speed rate of administration (11.4%), and only 11.7% of the total drugs were considered as ideal medication orders.

Conclusion
Clinically relevant medication errors can range from mild skin reactions to severe conditions that place the patient’s life at risk. The role of pharmacists through the detection and timely intervention during the prescription and other stages of the medication use process can improve drug safety in pediatric critical care services.
The forehead is a better site than the sternum to check transcutaneous bilirubin during phototherapy in sick infants
Authors: Jeon Jaesung , Lim Gina , Oh Ki Won , Lee Na Mi , Park Hye Won , Chung Mi Lim 
Published: December 2020

Abstract
Background
To confirm the accuracy of transcutaneous bilirubin (TcB) in the neonatal intensive care unit both with and without phototherapy, and compare forehead and sternum as the TcB assessment site.

Methods
We simultaneously assessed the total serum bilirubin (TSB) and TcB at the forehead and sternum, using a JM-103 bilirubinometer. We analyzed the correlation between the TSB and TcB assessed at the forehead and sternum, with measurements classified as ‘without phototherapy’ (before phototherapy and > 24 hours after phototherapy discontinuation) and ‘with phototherapy’ (after 24 hours of phototherapy).

Results
There were 1,084 paired forehead and sternum TcB measurements, with the corresponding TSB measurement, from 384 infants. Their mean gestational age of 35.4 ± 3.2 weeks (62% were preterm) and a mean birth weight of 2434 ± 768 grams, and TSB was 6.61 ± 3.56 mg/dL. Without phototherapy, TcB values at the forehead and sternum were correlated well to the TSB value (r = 0.925 and 0.915, respectively). With phototherapy, TcB values at the forehead and sternum were significantly correlated with the TSB value, but TcB at the forehead (r = 0.751) was a better match to the TSB than was TcB at the sternum (r = 0.668). Additionally, Bland-Altman plots showed a greater degree of underestimation of the TSB by TcB at the sternum with phototherapy.

Conclusions
TcB was more accurate in infants not receiving phototherapy. During phototherapy, it is better to assess TcB at the forehead rather than at the sternum.