bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence-Based Minireview: Abnormal uterine bleeding in users of rivaroxaban and apixaban
Authors: Jacobson-Kelly Amanda E. , Samuelson Bannow Bethany T. 
Published: December 2020

Abstract
Up to two-thirds of menstruating women experience abnormal uterine bleeding (AUB) when treated with oral anticoagulants. However, the true prevalence of AUB for specific agents remains uncertain, as many of these episodes, while interfering significantly with quality of life and overall health, are not captured by definitions of major bleeding (MB) or clinically relevant nonmajor bleeding (CRNMB) used in clinical trials. A 2017 systematic review determined that women taking rivaroxaban, but not edoxaban or apixaban, had a twofold higher risk of AUB than women taking warfarin. Since then, new data have become available from extension trials, cancer-associated venous thromboembolism trials, pediatric trials, and a few observational studies specifically examining AUB as an outcome. Reported rates of uterine CRNMB were low (around 1%) and similar for rivaroxaban and apixaban in all these studies, and no episodes of uterine bleeding meeting MB criteria were reported. Rates of AUB not meeting MB or CRNMB criteria were much higher, affecting up to 50% of women on rivaroxaban. Only 1 such study included women on apixaban, and no AUB was reported. In pediatric trials, 19% of girls experienced menorrhagia when treated with rivaroxaban. In conclusion, rates of uterine MB and CRNMB were low in all studies, but rates of other types of AUB not meeting these criteria ranged from 15.8% to 50%. We conclude that AUB is underreported due to the limitations of MB/CRNMB criteria despite its substantial impact on quality of life. We urge future investigators to include broader definitions of AUB to better capture the impact of this outcome in menstruating women treated with oral anticoagulants.
Identifying potential germline variants from sequencing hematopoietic malignancies
Authors: Kraft Ira L. , Godley Lucy A. 
Published: December 2020

Abstract
Next-generation sequencing (NGS) of bone marrow and peripheral blood increasingly guides clinical care in hematological malignancies. NGS data may help to identify single nucleotide variants, insertions/deletions, copy number variations, and translocations at a single time point, and repeated NGS testing allows tracking of dynamic changes in variants during the course of a patient’s disease. Tumor cells used for NGS may contain germline, somatic, and clonal hematopoietic DNA alterations, and distinguishing the etiology of a variant may be challenging. We describe an approach using patient history, individual variant characteristics, and sequential NGS assays to identify potential germline variants. Our current criteria for identifying an individual likely to have a deleterious germline variant include a strong family history or multiple cancers in a single patient, diagnosis of a hematopoietic malignancy at a younger age than seen in the general population, variant allele frequency &gt; 0.3 of a deleterious allele in a known germline predisposition gene, and variant persistence identified on clinical NGS panels, despite a change in disease state. Sequential molecular testing of hematopoietic specimens may provide insight into disease pathology, impact patient and family members’ care, and potentially identify new cancer-predisposing risk alleles. Ideally, individuals should give consent at the time of NGS testing to receive information about potential germline variants and to allow future contact as research advances.
How to manage CML patients with comorbidities
Authors: Cortes Jorge 
Published: December 2020

Abstract
Patients with chronic myeloid leukemia (CML) often have comorbidities, at an incidence that might be higher than in the general population. Because of the favorable outcome of most patients with CML treated with tyrosine kinase inhibitors (TKIs), a greater number of comorbidities might be the most significant adverse feature for long-term survival. The presence of comorbidities may also affect the risk of developing adverse events with TKIs. This effect is perhaps best exemplified by the risk of developing arterio-occlusive events, which is greatest for patients who have other risk factors for such events, with the risk increasing with higher numbers of comorbidities. The coexistence of comorbidities in patients with CML not only may affect TKI selection but also demands close monitoring of the overall health condition of the patient to optimize safety and provide the opportunity for an optimal outcome to such patients. With optimal, holistic management of leukemia and all other conditions afflicting them, patients with CML and comorbidities may aim for a near-normal life expectancy, just as the more select patients enrolled in clinical trials now enjoy.
Management of AL amyloidosis in 2020
Authors: Palladini Giovanni , Milani Paolo , Merlini Giampaolo 
Published: December 2020

Abstract
In amyloid light chain (AL) amyloidosis, a small B-cell clone, most commonly a plasma cell clone, produces monoclonal light chains that exert organ toxicity and deposit in tissue in the form of amyloid fibrils. Organ involvement determines the clinical manifestations, but symptoms are usually recognized late. Patients with disease diagnosed at advanced stages, particularly when heart involvement is present, are at high risk of death within a few months. However, symptoms are always preceded by a detectable monoclonal gammopathy and by elevated biomarkers of organ involvement, and hematologists can screen subjects who have known monoclonal gammopathy for amyloid organ dysfunction and damage, allowing for a presymptomatic diagnosis. Discriminating patients with other forms of amyloidosis is difficult but necessary, and tissue typing with adequate technology available at referral centers, is mandatory to confirm AL amyloidosis. Treatment targets the underlying clone and should be risk adapted to rapidly administer the most effective therapy patients can safely tolerate. In approximately one-fifth of patients, autologous stem cell transplantation can be considered up front or after bortezomib-based conditioning. Bortezomib can improve the depth of response after transplantation and is the backbone of treatment of patients who are not eligible for transplantation. The daratumumab+bortezomib combination is emerging as a novel standard of care in AL amyloidosis. Treatment should be aimed at achieving early and profound hematologic response and organ response in the long term. Close monitoring of hematologic response is vital to shifting nonresponders to rescue treatments. Patients with relapsed/refractory disease are generally treated with immune-modulatory drugs, but daratumumab is also an effective option.
GP’s perspectives on laboratory test use for monitoring long-term conditions: an audit of current testing practice
Authors: Elwenspoek Martha M. C. , Mann Ed , Alsop Katharine , Clark Hannah , Patel Rita , Watson Jessica C. , Whiting Penny 
Published: December 2020

Abstract
Background
We have shown previously that current recommendations in UK guidelines for monitoring long-term conditions are largely based on expert opinion. Due to a lack of robust evidence on optimal monitoring strategies and testing intervals, the guidelines are unclear and incomplete. This uncertainty may underly variation in testing that has been observed across the UK between GP practices and regions.

Methods
Our objective was to audit current testing practices of GPs in the UK; in particular, perspectives on laboratory tests for monitoring long-term conditions, the workload, and how confident GPs are in ordering and interpreting these tests. We designed an online survey consisting of multiple-choice and open-ended questions that was promoted on social media and in newsletters targeting GPs practicing in UK. The survey was live between October–November 2019. The results were analysed using a mixed-methods approach.

Results
The survey was completed by 550 GPs, of whom 69% had more than 10 years of experience. The majority spent more than 30 min per day on testing (78%), but only half of the respondents felt confident in dealing with abnormal results (53%). There was a high level of disagreement for whether liver function tests and full blood counts should be done ‘routinely’, ‘sometimes’, or ‘never’ in patients with a certain long-term condition.
The free text comments revealed three common themes: (1) pressures that promote over-testing, i.e. guidelines or protocols, workload from secondary care, fear of missing something, patient expectations; (2) negative consequences of over-testing, i.e. increased workload and patient harm; and (3) uncertainties due to lack of evidence and unclear guidelines.

Conclusion
These results confirm the variation that has been observed in test ordering data. The results also show that most GPs spent a significant part of their day ordering and interpreting monitoring tests. The lack of confidence in knowing how to act on abnormal test results underlines the urgent need for robust evidence on optimal testing and the development of clear and unambiguous testing recommendations. Uncertainties surrounding optimal testing has resulted in an over-use of tests, which leads to a waste of resources, increased GP workload and potential patient harm.
Severe hypercalcemia and a pelvic brown tumor in an adolescent with primary hyperparathyroidism: a case report
Authors: Legault O. , Inman M. , Moolman N. , Wiebe S. , Poulin A. , Nour M. A. 
Published: December 2020

Abstract
Background
Primary hyperparathyroidism may present in a myriad of manners, varying from an incidental asymptomatic biochemical finding to gastrointestinal, psychiatric, renal, and bone manifestations. While hyperparathyroidism remains a rare diagnosis in the pediatric population, the initial approach to diagnosis and management of hypercalcemia in children is imperative for the general pediatrician. Herein, we describe an adolescent who presented with a lytic bone lesion and severe, symptomatic hypercalcemia due to primary hyperparathyroidism.

Case presentation
A 14-year-old male presented with vomiting, constipation, abdominal pain, and lethargy. He had an elevated total corrected calcium of 4.3 mmol/L. He was found to have a large pelvic lytic tumor consistent with a brown tumor due to primary hyperparathyroidism. He received pharmacologic therapy for stabilization of his hypercalcemia, including intravenous saline, intravenous bisphosphonates, and calcitonin. He subsequently received definitive therapy via parathyroidectomy and his post-operative course was complicated by hungry bone syndrome. Long-term follow-up has found full resolution of the lytic lesion and restored calcium homeostasis.

Conclusions
We present this case to highlight the possible presentations of hypercalcemia and hyperparathyroidism that are essential for a general pediatrician to recognize to ensure prompt diagnosis and management. Evaluation for hypercalcemia should be considered in patients with suggestive symptoms and physical exam findings. To our knowledge, this patient represents the first reported pediatric case of a pelvic brown tumor in an adolescent. While the multi-systemic complications of hyperparathyroidism may be quite severe, swift and appropriate management may mitigate these clinical outcomes.
Instrumented Posterolateral fusion versus instrumented Interbody fusion for degenerative lumbar diseases in uremic patients under hemodialysis
Authors: Ho Chia-Ning , Liao Jen-Chung , Chen Wen-Jer 
Published: December 2020

Abstract
Background
Advances in hemodialysis have facilitated longer lifespan and better quality of life for patients with end stage renal disease (ESRD). Symptomatic degenerative lumbar diseases (DLD) becomes more common in patients with ESRD. Posterior instrumented fusion remains popular for spinal stenosis combining instability. Only a few sporadic studies mentioned about surgical outcomes in patients with ESRD underwent spine surgeries, but no one discussed about which fusion method was optimal for this kind of patients. In this study, we compared the differences between lumbar posterolateral fusion (PLF) and lumbar interbody fusion (IBF) in uremic patients underwent instrumented lumbar surgeries.

Methods
Between January 2005 and December 2017, ESRD patients under maintenance hemodialysis underwent posterior instrumented fusion for DLD were reviewed. A PLF group and an IBF group were identified. The demographic data was collected using their medical records. Clinical outcomes were evaluated by Oswestry Disability Index (ODI) and the visual analogue scale (VAS); radiographic results were assessed using final fusion rates. Any surgical or implant-related complication was documented.

Results
A total of 34 patients (22 women and 12 men, mean age of 65.4 years) in PLF group and 45 patients (26 women and 19 men, mean age of 65.1 years) in IBF group were enrolled. Both groups had similar surgical levels. The operation time was longer (200.9 vs 178.3 min, p = 0.029) and the amount of blood loss was higher (780.0 vs 428.4 ml, p = 0.001) in the IBF group. The radiographic fusion rate was better in the PLF group but without significant difference (65.2% vs 58.8%, p = 0.356). Seven in the PLF group and ten in the IBF group developed surgical complications (20.5% vs. 22.2%, p = 0.788); three patients in the PLF group (8.8%) and five patients in the IBF group (11.1%) received revision surgeries because of implant-related or wound complications. Comparing to preoperative ODI and VAS, postoperative ODI and VAS obtained significant improvement in both groups.

Conclusions
Successful fusion rates and clinical improvement (VAS, ODI) were similar in IBF and PLF group. Uremic patients underwent IBF for DLD had longer length of operation and higher operative blood loss than underwent PLF.
Comparison of oral glucose tolerance test and HbA1c in detection of disorders of glucose metabolism in patients with acute stroke
Authors: Matz Karl , Tuomilehto Jaakko , Teuschl Yvonne , Dachenhausen Alexandra , Brainin Michael 
Published: December 2020

Abstract
Background
Diabetes is an increasingly important risk factor for ischemic stroke and worsens stroke prognosis. Yet a large proportion of stroke patients who are eventually diabetic are undiagnosed. Therefore, it is important to have sensitive assessment of unrecognized hyperglycaemia in stroke patients.

Design
Secondary outcome analysis of a randomized controlled trial focussing on parameters of glucose metabolism and detection of diabetes and prediabetes in patients with acute ischemic stroke (AIS).

Methods
A total of 130 consecutively admitted patients with AIS without previously known type 2 diabetes mellitus (T2DM) were screened for diabetes or prediabetes as part of secondary outcome analysis of a randomized controlled trial that tested lifestyle intervention to prevent post-stroke cognitive decline. Patients had the oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) measurements in the second week after stroke onset and after 1 year. The detection rates of diabetes and prediabetes based on the OGTT or HbA1c values were compared.

Results
By any of the applied tests at the second week after stroke onset 62 of 130 patients (48%) had prediabetes or T2DM. Seventy-five patients had results from both tests available, the OGTT and HbA1c; according to the OGTT 40 (53.3%) patients had normal glucose metabolism, 33 (44%) had prediabetes, two (2.7%) T2DM. In 50 (66.7%) patients the HbA1c results were normal, 24 (32%) in the prediabetic and one (1.3%) in the diabetic range. The detection rate for disorders of glucose metabolism was 10% higher (absolute difference; relative difference 29%) with the OGTT compared with HbA1c. After 1 year the detection rate for prediabetes or T2DM was 7% higher with the OGTT (26% relative difference).
The study intervention led to a more favourable evolution of glycemic status after 1 year.

Conclusion
The OGTT is a more sensitive screening tool than HbA1c for the detection of previously unrecognized glycemic disorders in patients with acute stroke with an at least a 25% relative difference in detection rate. Therefore, an OGTT should be performed in all patients with stroke with no history of diabetes.
Trial registrationhttp://clinicaltrials.gov. Unique identifier: NCT01109836.
Diabetes and Covid-19 among hospitalized patients in Saudi Arabia: a single-centre retrospective study
Authors: Alguwaihes Abdullah M. , Al-Sofiani Mohammed E. , Megdad Maram , Albader Sakhar S. , Alsari Mohammad H. , Alelayan Ali , Alzahrani Saad H. , Sabico Shaun , Al-Daghri Nasser M. , Jammah Anwar A. 
Published: December 2020

Abstract
Background
Information on the clinical characteristics and outcomes of hospitalized Covid-19 patients with or without diabetes mellitus (DM) is limited in the Arab region. This study aims to fill this gap.

Methods
In this single-center retrospective study, medical records of hospitalized adults with confirmed Covid-19 [RT-PCR positive for SARS-CoV2] at King Saud University Medical City (KSUMC)-King Khaled University Hospital (KKUH), Riyadh, Saudi Arabia from May to July 2020 were analyzed. Clinical, radiological and serological information, as well as outcomes were recorded and analyzed.

Results
A total of 439 patients were included (median age 55 years; 68.3% men). The most prevalent comorbidities were vitamin D deficiency (74.7%), DM (68.3%), hypertension (42.6%) and obesity (42.2%). During hospitalization, 77 out of the 439 patients (17.5%) died. DM patients have a significantly higher death rate (20.5% versus 12.3%; p = 0.04) and lower survival time (p = 0.016) than non-DM. Multivariate cox proportional hazards regression model revealed that age [Hazards ratio, HR 3.0 (95% confidence interval, CI 1.7–5.3); p < 0.001], congestive heart failure [adjusted HR 3.5 (CI 1.4–8.3); p = 0.006], smoking [adjusted HR 5.8 (CI 2.0–17.2); p < 0.001], β-blocker use [adjusted HR 1.7 (CI 1.0–2.9); p = 0.04], bilateral lung infiltrates [adjusted HR 1.9 (CI 1.1–3.3); p = 0.02], creatinine > 90 µmol/l [adjusted HR 2.1 (CI 1.3–3.5); p = 0.004] and 25(OH)D < 12.5 nmol/l [adjusted HR 7.0 (CI 1.7–28.2); p = 0.007] were significant predictors of mortality among hospitalized Covid-19 patients. Random blood glucose ≥ 11.1 mmol/l was significantly associated with intensive care admission [adjusted HR 1.5 (CI 1.0–2.2); p = 0.04], as well as smoking, β-blocker use, neutrophil > 7.5, creatinine > 90 µmol/l and alanine aminotransferase > 65U/l.

Conclusion
The prevalence of DM is high among hospitalized Covid-19 patients in Riyadh, Saudi Arabia. While DM patients have a higher mortality rate than their non-DM counterparts, other factors such as old age, congestive heart failure, smoking, β-blocker use, presence of bilateral lung infiltrates, elevated creatinine and severe vitamin D deficiency, appear to be more significant predictors of fatal outcome. Patients with acute metabolic dysfunctions, including hyperglycemia on admission are more likely to receive intensive care.
Characterization of novel neutralizing mouse monoclonal antibody JM1-24-3 developed against MUC18 in metastatic melanoma
Authors: Feng Runhua , Wang Yuling , Ramachandran Vijaya , Ma Qinhong , May Matthew M. , Li Ming , Zhou Joe X. , Xu Xiang , Xu Kejing , Fang Shenying , Xia Weiya , Sui Dawen , Liu Huey , Gao Xiaolian , Prieto Victor , Blacklow Stephen C. , Lu Mason , Lee Jeffrey E. 
Published: December 2020

Abstract
Background
MUC18 is a glycoprotein highly expressed on the surface of melanoma and other cancers which promotes tumor progression and metastasis. However, its mechanism of action and suitability as a therapeutic target are unknown.

Methods
A monoclonal antibody (mAb) (JM1-24-3) was generated from metastatic melanoma tumor live cell immunization, and high-throughput screening identified MUC18 as the target.

Results
Analysis of molecular interactions between MUC18 and JM1-24-3 revealed that the downstream signaling events depended on binding of the mAb to a conformational epitope on the extracellular domain of MUC18. JM1-24-3 inhibited melanoma cell proliferation, migration and invasion in vitro and reduced tumor growth and metastasis in vivo.

Conclusion
These results confirm that MUC18 is mechanistically important in melanoma growth and metastasis, suggest that the MUC18 epitope identified is a promising therapeutic target, and that the JM1-24-3 mAb may serve as the basis for a potential therapeutic agent.
Teaching professionalism in medical residency programs: a scoping review protocol
Authors: Ghaffarifar Saeideh , Asghari-Khatooni Azam , Akbarzadeh Amirhossein , Pourabbas Ahmad , Farshad Mehran Seif , Masoomi Rasoul , Akbarzadeh Fariborz 
Published: December 2020

Abstract
Background
Professionalism is a core competency of medical residents in residency programs. Unprofessional behavior has a negative influence on patient safety, quality of care, and interpersonal relationships. The objective of this scoping review is to map the range of teaching methods of professionalism in medical residency programs (in all specialties and in any setting, whether in secondary, primary, or community care settings). For doing so, all articles which are written in English in any country, regardless of their research design and regardless of the residents’ gender, year of study, and ethnic group will be reviewed.

Methods
This proposed scoping review will be directed in agreement with the methodology of the Joanna Briggs Institute for scoping reviews. The six steps of Arksey and O’Malley methodological framework for conducting scoping reviews, updated by Levac et al. (Implement. Sci. 5(1): 69, 2010) will be followed. The findings from this study will be merged with those of the previous Best Evidence Medical Education (BEME) systematic review. All published and unpublished studies from 1980 until the end of 2019 will be reviewed, and the previous BEME review will be updated by the findings of the articles from the beginning of 2010 until the end of 2019. All research designs and all credible evidence will be included in this review.

Conclusions
Conducting this scoping review will map the teaching methods of professionalism and will provide an inclusive evidence base to help the medical teachers in the choosing for proper teaching methods for use in their teaching practice.

Systematic review registration
Not registered.