bluuebunny/crossref_metadata_2025_split huggingface dataset:
Erdafitinib treatment in Brazilian patients with metastatic urothelial carcinoma (mUC): real-world evidence from an Expanded Access Program
Authors: Monteiro Fernando Sabino M. , Silva Adriano Gonçalves e , Gomes Andrea Juliana P. de S. , Dutra Carolina , Ferreira Naira Oliveira , Mariano Rodrigo Coutinho , Schutz Fabio A. 
Published: May 2021

Background: Erdafitinib is the first targeted therapy approved for the treatment of patients with metastatic urothelial carcinoma (mUC). Approval was based on a phase II single-arm trial that demonstrated significant activity of erdafitinib in patients with tumors harboring FGFR2/3 alterations. In Brazil, an Expanded Access Program (EAP) provided patients with early access to erdafitinib prior to market authorization. The current report describes characteristics and outcomes of patients with mUC on erdafitinib therapy. Methods: Patients with mUC that failed first- and second-line systemic therapies were screened for FGFR2/3 alterations in primary or metastatic tumor tissues. Patients with FGFR2/3 alterations were selected to receive erdafitinib at the standard dosing schedule and were followed prospectively to evaluate the efficacy and safety outcomes. Results: From 19 April 2019, through 13 March 2020, 47 patients with mUC from 10 Brazilian centers were tested for FGFR2/3 alterations. Alterations in FGFR2/3 were found in 12 patients (25.5%) and all of them were eligible for the EAP. Four patients (33%) had partial response, while two patients (17%) had stable disease. Progressive disease, the best response, was observed in five patients (42%). At a median follow-up of 16.2 months, the median time to treatment failure (TTF) was 2.8 months. When considering only patients with objective response, the median TTF was 5.3 months. Adverse events (AEs) were reported for any grade and grade 3 or higher in 10 patients (83%) and 5 patients (42%), respectively. The most common AE was hyperphosphatemia. Conclusion: This first real-world evidence report of heavily treated patients with mUC confirms the efficacy and safety of erdafitinib in a disease setting with a lack of treatment options.
Determining the Number of Bariatric Beds Needed in a U.S. Acute Care Hospital
Authors: Magazine Michael , Murphy Matt , Schauer Daniel P. , Wiggermann Neal 
Published: May 2021

Aim: This project used historical hospital data to forecast demand for specialized bariatric beds. Models were evaluated that determined the relationship between the number of bariatric beds owned and service level for patients of size requiring these beds. A calculator was developed for minimizing the equipment costs of meeting demand. Background: Failing to provide enough bariatric beds may negatively affect outcomes for patients of size and healthcare workers, whereas owning more bariatric beds than required to meet demand means unnecessary cost. With rising rates of obesity increasing care costs, minimizing equipment costs is increasingly important. Method: One year of hospital admissions data were used to determine arrival rates and lengths of stay for patients of size. Two subsequent years verified the consistency of these rates. Simulations modeled the flow of patients of size through the hospital and the service level associated with the number of beds owned. A minimization function determined the optimal number of bariatric beds to be provided. A simplified, generalizable model was compared to the simulation. Results: The simplified model produced similar results to more complex simulation. The optimization was robust, or insensitive to small changes in inputs, and identified substantial opportunity for savings if demand for beds was substantially over- or underestimated. Conclusions: The simplified model and cost optimization could be used in many situations to prevent costly errors in equipment planning. However, hospitals should consider customized simulation to estimate demand for high-cost equipment or unique circumstances not fitting the assumptions of these models.
Pros and cons of eHealth: A systematic review of the literature and observations in Denmark
Authors: Svendsen Mathias T , Tiedemann Sylvia N , Andersen Klaus Ejner 
Published: May 2021

Objectives: The main objectives of this article are to systematically review the recent literature on patient safety in relation to the use of eHealth and to investigate how the Danish authorities supervise private eHealth clinics with regard to patient safety. Methods: Original studies reporting the association between patient safety and the use of eHealth as a means of communication between patients and healthcare providers were included. Four literature databases were searched for English-language articles reporting results from cohort studies and clinical trials, published from 2015 until March 2021. Moreover, registered private eHealth clinics in Denmark were evaluated with reference to a recent national audit of patient safety issues in eHealth. Results: The literature search retrieved four intervention studies. The studies did not identify any particular patient safety risks associated with the use of eHealth. Many different authorized healthcare providers (preferably, doctors) apply eHealth in various contexts. eHealth is being used as the only form of contact between the healthcare provider and the patient, as a supplement to patient visitations in an outpatient clinic, or as a tool for communicating between two or more healthcare providers. The regulation of eHealth involves patient safety issues but also has interfaces to marketing, IT systems, and infrastructure. Supervision of eHealth includes the organization of clinics, handling patient charts, prescription medicine, patient legal rights, and patient transition. However, there are many interfaces in the division of responsibilities among the various governmental players. Conclusion: eHealth is being used increasingly and in many settings, although recently published intervention studies investigating patient safety issues by the use of eHealth are limited. A structured and continuous governmental control and regulation of patient safety in relation to the use of eHealth is warranted.
Expert Consensus on Clinical Application of Lateral Lumbar Interbody Fusion: Results From a Modified Delphi Study
Authors: Hai Yong , Liu Jingwei , Liu Yuzeng , Liu Tie , Zhang Xinuo , Pan Aixing , Zhang Yiqi , Ding Hongtao , Wu Yuxuan , Han Bo , Tang Xinli 
Published: May 2021

Study Design: Modified Delphi study. Objective: The objective of this study was to establish expert consensus on the application of lateral lumbar interbody fusion (LLIF) by using the modified Delphi study. Methods: From June 2019 to March 2020, Members of the Chinese Study Group for Lateral Lumbar Spine Surgery were selected to collect expert feedback using the modified Delphi method where 65 spine surgeons from all over China agreed to participate. Four rounds were performed: 1 face-to-face meeting and 3 subsequent survey rounds. The consensus was achieved with ≥a 70.0% agreement for each question. The recommendation of grade A was defined as ≥90.0% of the agreement for each question. The recommendation of grade B was defined as 80.0-89.9% of the agreement for each question. The recommendation of grade C was defined as 70.0-79.9% of the agreement for each question. Results: A total of 65 experts formed a panelist group, and the number of questionnaires collected was 63, 59, and 62 in the 3 rounds. In total, 5 sections, 71 questions, and 382 items achieved consensus after the Delphi rounds including summary; preoperative evaluation; application at the lumbar spinal stenosis, lumbar disc herniation, lumbar spondylolisthesis, adult degenerative scoliosis, postoperative adjacent segmental degeneration, and revision surgery; complications; and postoperative follow-up evaluation of LLIF. Conclusion: The modified Delphi method was utilized to ascertain an expert consensus from the Chinese Study Group for Lateral Lumbar Spine Surgery to inform clinical decision-making in the application of LLIF. The salient grade A recommendations of the survey are enumerated.
Effect of Irrigants and Irrigating Devices on Disinfection of Root Canal System: A Systematic Review
Authors: Attavar Shruthi H. , Hegde Mithra N. 
Published: May 2021

Aim: The effective delivery of irrigants into the inaccessible areas of the root canal system is the prerequisite for a proper disinfection of the root canal system. Numerous activation devices that can provide effective delivery of the irrigant and aid in the success of the root canal treatment are available. The activation of irrigants has claimed to be effective in in vitro and clinical trials. Hence, the present systematic review aims to analyze the effect of irrigants and irrigating devices in disinfecting the root canal system. Materials and Methods: A literature search was undertaken in PubMed, Cochrane, Web of Science, and Scopus databases. The inclusion criteria included clinical trials, both in vivo and ex vivo. The exclusion criteria included animal studies, textbooks, review articles, and case reports. The patients who required endodontic treatment along with the activation of irrigants were chosen as participants for the review. Result: The search strategy screened around 132 articles, out of which only 10 were selected for the present systematic review. The risk of bias was calculated based on the following scores: 3, high; 2, moderate; and 1, low. In the present systematic review, four articles were categorized into low-risk bias, three articles were classified as moderate risk, and three articles belonged to the high-risk category. Conclusion: The present systematic review concluded that the use of a mechanical activation device along with the irrigant will help in better removal of the smear layer and debris from the root canal system, improving the cleanliness and helping achieve more successful endodontic treatment.
Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21)
Authors: Han Se young , Mrózek Krzysztof , Voutsinas Jenna , Wu Qian , Morgan Elizabeth A. , Vestergaard Hanne , Ohgami Robert , Kluin Philip M. , Kristensen Thomas Kielsgaard , Pullarkat Sheeja , Møller Michael Boe , Schiefer Ana-Iris , Baughn Linda B. , Kim Young , Czuchlewski David , Hilberink Jacobien R. , Horny Hans-Peter , George Tracy I. , Dolan Michelle , Ku Nam K. , Arana Yi Cecilia , Pullarkat Vinod , Kohlschmidt Jessica , Salhotra Amandeep , Soma Lori , Bloomfield Clara D. , Chen Dong , Sperr Wolfgang R. , Marcucci Guido , Cho Christina , Akin Cem , Gotlib Jason , Broesby-Olsen Sigurd , Larson Melissa , Linden Michael A. , Deeg H. Joachim , Hoermann Gregor , Perales Miguel-Angel , Hornick Jason L. , Litzow Mark R. , Nakamura Ryotaro , Weisdorf Daniel , Borthakur Gautam , Huls Gerwin , Valent Peter , Ustun Celalettin , Yeung Cecilia C. S. 
Published: May 2021

Abstract
Patients with core-binding factor (CBF) acute myeloid leukemia (AML), caused by either t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), have higher complete remission rates and longer survival than patients with other subtypes of AML. However, ∼40% of patients relapse, and the literature suggests that patients with inv(16) fare differently from those with t(8;21). We retrospectively analyzed 537 patients with CBF-AML, focusing on additional cytogenetic aberrations to examine their impact on clinical outcomes. Trisomies of chromosomes 8, 21, or 22 were significantly more common in patients with inv(16)/t(16;16): 16% vs 7%, 6% vs 0%, and 17% vs 0%, respectively. In contrast, del(9q) and loss of a sex chromosome were more frequent in patients with t(8;21): 15% vs 0.4% for del(9q), 37% vs 0% for loss of X in females, and 44% vs 5% for loss of Y in males. Hyperdiploidy was more frequent in patients with inv(16) (25% vs 9%, whereas hypodiploidy was more frequent in patients with t(8;21) (37% vs 3%. In multivariable analyses (adjusted for age, white blood counts at diagnosis, and KIT mutation status), trisomy 8 was associated with improved overall survival (OS) in inv(16), whereas the presence of other chromosomal abnormalities (not trisomy 8) was associated with decreased OS. In patients with t(8;21), hypodiploidy was associated with improved disease-free survival; hyperdiploidy and del(9q) were associated with improved OS. KIT mutation (either positive or not tested, compared with negative) conferred poor prognoses in univariate analysis only in patients with t(8;21).
Burden and attitude to resistant and refractory migraine: a survey from the European Headache Federation with the endorsement of the European Migraine & Headache Alliance
Authors:   On behalf of the Burden and Attitude to Resistant and Refractory (BARR) Study Group, Sacco Simona , Lampl Christian , Maassen van den Brink Antoinette , Caponnetto Valeria , Braschinsky Mark , Ducros Anne , Little Patrick , Pozo-Rosich Patricia , Reuter Uwe , Ruiz de la Torre Elena , Sanchez Del Rio Margarita , Sinclair Alexandra J. , Martelletti Paolo , Katsarava Zaza 
Published: May 2021

Abstract
Background
New treatments are currently offering new opportunities and challenges in clinical management and research in the migraine field. There is the need of homogenous criteria to identify candidates for treatment escalation as well as of reliable criteria to identify refractoriness to treatment. To overcome those issues, the European Headache Federation (EHF) issued a Consensus document to propose criteria to approach difficult-to-treat migraine patients in a standardized way. The Consensus proposed well-defined criteria for resistant migraine (i.e., patients who do not respond to some treatment but who have residual therapeutic opportunities) and refractory migraine (i.e., patients who still have debilitating migraine despite maximal treatment efforts).
The aim of this study was to better understand the perceived impact of resistant and refractory migraine and the attitude of physicians involved in migraine care toward those conditions.

Methods
We conducted a web-questionnaire-based cross-sectional international study involving physicians with interest in headache care.

Results
There were 277 questionnaires available for analysis. A relevant proportion of participants reported that patients with resistant and refractory migraine were frequently seen in their clinical practice (49.5% for resistant and 28.9% for refractory migraine); percentages were higher when considering only those working in specialized headache centers (75% and 46% respectively). However, many physicians reported low or moderate confidence in managing resistant (8.1% and 43.3%, respectively) and refractory (20.7% and 48.4%, respectively) migraine patients; confidence in treating resistant and refractory migraine patients was different according to the level of care and to the number of patients visited per week. Patients with resistant and refractory migraine were infrequently referred to more specialized centers (12% and 19%, respectively); also in this case, figures were different according to the level of care.

Conclusions
This report highlights the clinical relevance of difficult-to-treat migraine and the presence of unmet needs in this field. There is the need of more evidence regarding the management of those patients and clear guidance referring to the organization of care and available opportunities.
ClearSight™ finger cuff versus invasive arterial pressure measurement in patients with body mass index above 45 kg/m2
Authors: Eley Victoria , Christensen Rebecca , Guy Louis , Wyssusek Kerstin , Pelecanos Anita , Dodd Benjamin , Stowasser Michael , van Zundert Andre 
Published: May 2021

Abstract
Background
Measuring blood pressure in patients with obesity is challenging. The ClearSight™ finger cuff (FC) uses the vascular unloading technique to provide continuous non-invasive blood pressure measurements. We aimed to test the agreement of the FC with invasive radial arterial monitoring (INV) in patients with obesity.

Methods
Participants had a body mass index (BMI) ≥45 kg/m2 and underwent laparoscopic bariatric surgery. FC and INV measurements were obtained simultaneously every 5 min on each patient, following induction of anesthesia. Agreement over time was assessed using modified Bland-Altman plots and error grid analysis permitted clinical interpretation of the results. Four-quadrant plots allowed assessment of concordance in blood pressure changes.

Results
The 30 participants had a median (IQR) BMI of 50.2 kg/m2 (IQR 48.3–55.3). The observed bias (SD, 95% limits of agreement) for systolic blood pressure (SBP) was 14.3 mmHg (14.1, -13.4 – 42.0), 5.2 mmHg (10.9, -16.0 – 26.5) for mean arterial pressure (MAP) and 2.6 mmHg (10.8, -18.6 – 23.8) for diastolic blood pressure (DBP). Error grid analysis showed that the proportion of readings in risk zones A-E were 90.8, 6.5, 2.7, 0 and 0% for SBP and 91.4, 4.3, 4.3, 0 and 0% for MAP, respectively. Discordance occurred in ≤8% of pairs for consecutive change in SBP, MAP and DBP.

Conclusions
The vascular unloading technique was not adequately in agreement with radial arterial monitoring. Evaluation in a larger sample is required before recommending this technique for intraoperative monitoring of patients with BMI ≥45 kg/m2.
Systemic immune-inflammation index predicts prognosis of sequential therapy with sorafenib and regorafenib in hepatocellular carcinoma
Authors: Hong Young Mi , Yoon K. T. , Cho Mong 
Published: May 2021

Abstract
Background
Regorafenib has shown promising results as a second-line therapy for patients with hepatocellular carcinoma (HCC) who progressed on sorafenib. Although there have been several data regarding the efficacy of sequential therapy with sorafenib and that of regorafenib in real-life, specific inflammation markers for predicting the prognosis have not been studied. This study aimed to investigate prognostic value of systemic inflammatory markers in patients with HCC who received sorafenib-regorafenib sequential therapy.

Methods
We retrospectively analyzed medical data of patients who received regorafenib for the treatment of HCC after sorafenib failure. Progression free survival (PFS) and overall survival (OS) were assessed using the Kaplan–Meier survival curves. Univariate and multivariate analyses were performed to analyze the factors associated with survival.

Results
A total of 58 patients who received at least one dose of regroafenib and fulfilled the eligibility criteria, good performance status (Eastern Cooperative Oncology Group [ECOG] 0–1) and preserved liver function (Child-Pugh-A), were included in the analysis. The median PFS was 3 months (95% confidence interval [CI] = 0.981–5.019) and the median OS was 8 months (95% CI = 5.761–10.239). Elevated systemic immune-inflammation index (SII ≥340) was independently associated with poor OS. In multivariate analysis, the SII (hazard ratio [HR] = 2.211, 95% CI = 1.089–4.489, P = 0.028) and alpha-fetoprotein (AFP) (HR = 2.750, 95% CI = 1.259–6.010, P = 0.011) were independent predictors of OS.

Conclusion
Elevated SII is associated with poor OS in patients with HCC who received sequential therapy with sorafenib and regorafenib. In addition, when selecting a treatment strategy, the SII can be used in combination with the AFP level as a promising prognostic tool for HCC.
Development of a nomogram model to predict survival outcomes in patients with primary hepatic neuroendocrine tumors based on SEER database
Authors: Zhang Ziteng , Zhao Xin , Li Zhiyan , Wu Youchun , Liu Yao , Li Zhiwei , Li Guobao 
Published: May 2021

Abstract
Background
Primary hepatic neuroendocrine tumors (PH-NETs) are extremely rare and unknown. Because of its rarity, its prognosis features and influencing factors are not well established.

Methods
Data of 140 patients with PH-NETs diagnosed in the SEER database from 1975 to 2016 were collected. The demographics and clinic-pathological features were described. By using propensity-score matching (PSM) analysis, three associated cohorts were selected to describe the malignancy of PH-NETs and univariate analysis was conducted. Then, multivariate Cox analyses were performed and a predicting nomograph was constructed. C-index, receiver operating characteristic (ROC) curve and calibration curves were used to evaluate the predictive value of nomogram.

Results
The overall survival outcomes of PH-NETs were superior to hepatocellular carcinoma (HCC) with a mean survival time 30.64 vs 25.11 months (p = 0.052), but inferior to gastrointestinal tract neuroendocrine tumors in situ (GI-NETs in situ) with a mean survival time 30.64 vs 41.62 months (p = 0.017). With reference to gastrointestinal neuroendocrine tumors with liver metastasis (GI-NETs-LM), GI-NETs-LM had better outcomes in short time (1-year survival rate: 64.75% vs 56.43%) but was worse in long time (5-year survival rate: 8. 63% vs 18.57%). Multivariate Cox analyses showed that tumor grade and surgery were two independent factors for prognosis of the patients (p < 0.00). Tumor grade and surgery were used to construct the predicting nomogram. The C-index was 0.79 (95%CI = 0.75–0.83). The area under curve (AUC) values in ROC were 0.868 in 1-year and 0.917 in 3-year survival and the calibration curves showed good consistency.

Conclusions
The overall prognosis PH-NETs is generally favorable, better than HCC and GI-NETs-LM in long term. Preoperative biopsy and complete pathological diagnosis were recommended. Radical surgical intervention including transplantation was the first choice in PH-NETs therapy.
Medication-related osteonecrosis of the jaw (MRONJ) and eNOS Polymorphisms in multiple myeloma patients: a single center experience
Authors: Taş Ozyurtseven Betul , Serin Istemi , Nursal Ayse Feyda , Pehlivan Sacide , Pehlivan Mustafa 
Published: May 2021

Abstract
Background
Multiple myeloma (MM) constitutes approximately 10% of hematological malignancies. Bisphosphonates have established themselves in solid organ metastasis and multiple myeloma lytic bone lesions by inhibiting osteoclast activation. Medication-related osteonecrosis of the jaw (MRONJ) emerges as an important complication. Investigating host-based factors, and developing personal risk factors gain importance in the development mechanism of MRONJ. We aimed to reveal the different genotype polymorphisms, and clinical effects of eNOS in patients with a diagnosis of MRONJ in MM patients.

Methods
Medical records and blood samples were collected from 60 MRONJ patients with MM and 60 healthy controls. Inclusion criteria was having an exposed maxillofacial bone for more than eight weeks, a history of bisphosphonates, and no history of radiation therapy for the jaws. eNOS G894T and intron 4 VNTR were calculated by polymerase chain reaction and/or restriction fragment length polymorphism.

Results
eNOS G894T and VNTR genotypes and alleles were compared statistically with the healthy control group. There was no significant difference between the two groups. In comparison between G894T and clinical parameters, aphthous stomatitis was more common in TT genotype, while DMFT > 3 was more common in TG-GG genotype (p = 0.035, 0.023).

Conclusions
eNOS induces osteogenesis in bone metabolism, with its regulatory effects on bone remodeling and also NO induced angiogenesis takes place indirectly with its protective effect on endothelial functions. We see that these polymorphisms affecting the entire process of bone remodeling and angiogenesis, especially mucosal damage, which is the triggering factor of MRONJ pathology, have been revealed in the MM patient group. Considering the MRONJ initiating factors, it is necessary to emphasize the importance of our study results. It should be seen as an important step for new studies towards MRONJ and its treatment.