bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in eyelid position after glaucoma filtering surgery
Authors: Salvá-Palomeque Teresa , Muñoz-Ramón Pablo , Rebolleda Gema , Aguado-Casanova Victor , Ye-Zhu Cristina , Muñoz-Negrete Francisco J. 
Published: November 2021

Background While ptosis is a well-known consequence of glaucoma surgery, some isolated case reports point to the possibility of upper eyelid retraction occurring after glaucoma surgery. This study aims to analyze the occurrence of ptosis and eyelid retraction after glaucoma surgery and to evaluate factors contributing to these palpebral fissure changes. Methods Cross-sectional study including 100 eyes of 100 patients that had undergone unilateral glaucoma surgery. Upper eyelid height in the operated eye was measured by digital photography and compared with the fellow, non-operated eye. The main outcome was to determine if ptosis or retraction occurred in the operated eye in comparison with the fellow eye. The secondary outcome was to determine if any variable was associated with ptosis or retraction. A clinically significant difference (either toward ptosis or retraction) was defined as a difference ≥1 mm between both eyes. Results Of 100 eyes included 81 (81%) showed no change in eyelid height (−0.133 mm ± 0.496), 11 (11%) showed ptosis (−1.348 mm ± 0.387) and 8 eyes (8%) showed retraction (1.705 ± 0.634). A statistically significant relation was found between ptosis and pseudoexfoliation glaucoma (p = 0.003). A trend toward lower postoperative IOP and higher conjunctival blebs was found in eyes with postoperative eyelid retraction. Conclusions Eyelid retraction was present in 8% of patients and ptosis in 11%. Patients with eyelid retraction showed around a 3 mmHg lower postoperative IOP than eyes without retraction. The presence of pseudoexfoliation may be a risk factor for this complication. A prospective study with a large number of patients would be required to confirm these results.
Validation of a shortened FAST-ED algorithm for smartphone app guided stroke triage
Authors: Frank Benedikt , Fabian Felix , Brune Bastian , Bozkurt Bessime , Deuschl Cornelius , Nogueira Raul G. , Kleinschnitz Christoph , Köhrmann Martin 
Published: November 2021

Background and Purpose: Large vessel occlusion (LVO) recognition scales were developed to identify patients with LVO-related acute ischemic stroke (AIS) on the scene of emergency. Thus, they may enable direct transport to a comprehensive stroke centre (CSC). In this study, we aim to validate a smartphone app-based stroke triage with a shortened form of the Field Assessment Stroke Triage for Emergency Destination (FAST-ED). Methods: This retrospective validation study included 2815 patients with confirmed acute stroke and suspected acute stroke but final diagnosis other than stroke (stroke mimics) who were admitted by emergency medical service (EMS) to the CSC of the Neurological University Hospital Essen, Germany. We analysed the predictive accuracy of a shortened digital app-based FAST-ED ( ‘FAST-ED App’) for LVO-related AIS and yield comparison to various other LVO recognition scales. Results: The shortened FAST-ED App had comparable test quality (Area under ROC = 0.887) to predict LVO-related AIS to the original FAST-ED (0.889) and RACE (0.883) and was superior to Cincinnati Prehospital Stroke Severity (CPSS), 3-Item Stroke Scale (3-ISS) and National Institute of Health Stroke Scale (NIHSS). A FAST-ED App ⩾ 4 revealed very good accuracy to detect LVO related AIS (sensitivity of 77% and a specificity 87%) with an area under the curve c-statistics of 0.89 (95% CI: 0.87–0.90). In a hypothetical triage model, the number needed to screen in order to avoid one secondary transportation in an urban setting would be five. Conclusion: This validation study of a shortened FAST-ED assessment for a smartphone-app guided stroke triage yields good quality to identify patients with LVO.
Understanding Anterior Shoulder Instability Through Machine Learning: New Models That Predict Recurrence, Progression to Surgery, and Development of Arthritis
Authors: Lu Yining , Pareek Ayoosh , Wilbur Ryan R. , Leland Devin P. , Krych Aaron J. , Camp Christopher L. 
Published: November 2021

Background: Management of anterior shoulder instability (ASI) aims to reduce risk of future recurrence and prevent complications via nonoperative and surgical management. Machine learning may be able to reliably provide predictions to improve decision making for this condition. Purpose: To develop and internally validate a machine-learning model to predict the following outcomes after ASI: (1) recurrent instability, (2) progression to surgery, and (3) the development of symptomatic osteoarthritis (OA) over long-term follow-up. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: An established geographic database of >500,000 patients was used to identify 654 patients aged <40 years with an initial diagnosis of ASI between 1994 and 2016; the mean follow-up was 11.1 years. Medical records were reviewed to obtain patient information, and models were generated to predict the outcomes of interest. Five candidate algorithms were trained in the development of each of the models, as well as an additional ensemble of the algorithms. Performance of the algorithms was assessed using discrimination, calibration, and decision curve analysis. Results: Of the 654 included patients, 443 (67.7%) experienced multiple instability events, 228 (34.9%) underwent surgery, and 39 (5.9%) developed symptomatic OA. The ensemble gradient-boosted machines achieved the best performances based on discrimination (via area under the receiver operating characteristic curve [AUC]: AUCrecurrence = 0.86), AUCsurgery = 0.76, AUCOA = 0.78), calibration, decision curve analysis, and Brier score (Brierrecurrence = 0.138, Briersurgery = 0.185, BrierOA = 0.05). For demonstration purposes, models were integrated into a single web-based open-access application able to provide predictions and explanations for practitioners and researchers. Conclusion: After identification of key features, including time from initial instability, age at initial instability, sports involvement, and radiographic findings, machine-learning models were developed that effectively and reliably predicted recurrent instability, progression to surgery, and the development of OA in patients with ASI. After careful external validation, these models can be incorporated into open-access digital applications to inform patients, clinicians, and researchers regarding quantifiable risks of relevant outcomes in the clinic.
Chimeric Antigen Receptor T Cell Targeting to CD19 and CD22 Combined with Anti-PD-1 Antibody Induce High Response in Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Authors: Zhang Ying , Li Jiaqi , Zong Xiangping , Zhou Jin , Jia Sixun , Geng Hongzhi , Lou Xiaoyan , Kang Liqing , Yu Lei , Wu Depei , Li Caixia 
Published: November 2021

Abstract
Objective: Despite the remarkable success of chimeric antigen receptor modified T (CAR-T) cell therapy for refractory or relapsed B cell non-Hodgkin lymphoma (R/R B-NHL), high rates of treatment failure and relapse after CAR-T cell therapy are considerable obstacles to overcome. Preclinical models have demonstrated that anti-PD-1 antibody is an attractive option following CAR-T therapy to reverse T cell exhaustion. Thus, we investigated their combination in R/R B-NHL.
Methods: We performed a prospective, single-arm study of CAR-T cell combined with anti-PD-1 antibody treatment in R/R B-NHL (NCT04539444). Anti-PD-1 antibody was administrated on day 1 after patients received sequential infusion of anti-CD19 and anti-CD22 second-generation CAR-T cells, and the efficacy and safety of the combination treatment were evaluated.
Results: From August 1, 2020 to June 30, 2021, a total of 11 patients were enrolled and completed at least 3 months follow-up. The median follow-up time is 5.8 months. Overall response was achieved in 9 of 11 patients (81.8%), and the complete response (CR) was achieved in 8 of 11 patients (72.7%). All 8 patients achieving CR still sustained remission at the last follow-up. The progression-free survival (PFS) and overall survival (OS) rates at 6 months were 80.8% and 100.0%, respectively. Cytokine release syndrome (CRS) occurred in only 4 patients (all were grade 1), and no neurotoxicity were observed.
Conclusion: This study suggests that CAR-T cells combined with anti-PD-1 antibody elicit a safe and durable response in R/R B-NHL.
Keywords: chimeric antigen receptor modified T cell, anti-PD-1 antibody, CD19/CD22, refractory or relapsed B cell non-Hodgkin lymphoma

Disclosures
No relevant conflicts of interest to declare.

OffLabel Disclosure:
We use the T cells were transduced with a lentivirus encoding the CD19-4-1BB-CD3 z and CD22-4-1BB-CD3 ztransgene to produce CAR-T cells. The main purpose of our study is to improve the response rate in patients with R/R B-NHL.
Mesenchymal Stromal Cells Plus Anti-CD25 Antibody and Calcineurin Inhibitors for Steroid-Resistant Acute Graft-Versus-Host Disease: A Multicenter, Randomized, Phase 3 Trial
Authors: Zhao Ke , Lin Ren , Fan Zhiping , Chen Xiaoyong , Wang Yu , Huang Fen , Xu Na , Zhang Xi , Zhang Xin , Xuan Li , Wang Shunqing , Lin Dongjun , Deng Lan , Nie Danian , Weng Jianyu , Li Yonghua , Zhang Xiaohui , Li Yuhua , Xiang Andy Peng , Liu Qifa 
Published: November 2021

Abstract
INTRODUCTION Steroid-resistant (SR) acute graft-versus-host disease (aGVHD) lacks standard second-line treatment. Mesenchymal stromal cells (MSCs) have potential efficacy in SR aGVHD. To assess efficacy and safety of MSCs combined with anti-CD25 antibody and calcineurin inhibitors as second-line therapy for SR aGVHD.
METHORDS A randomized phase 3 trial involved 203 SR aGVHD patients at 10 centers in China (September 2014-March 2019). Final follow-up was on June 30, 2020. Participants were randomized in a 1:1 ratio to receive second-line therapy (anti-CD25 antibody combined with calcineurin inhibitors) with MSCs (n=101) or without MSCs (n=102). The primary endpoint was overall response (OR) at day 28 with a predefined threshold of -20%. Secondary and safety endpoints included durable OR at day 56, failure-free survival, overall survival (OS), chronic GVHD (cGVHD), infection, haematological toxicity and relapse.
RESULTS Of 203 patients, 198 (97.5%; mean age, 30.1years; 40.4% women) completed the study. OR at day 28 was higher in the MSCs group than in the control group (82.8% [82 patients] vs 70.7% [70]; odds ratio, 2.00; 95% confidence interval [CI], 1.01-3.94; P=.043). Durable OR at day 56 was also higher in the MSCs group (78.8% [78 patients] vs. 64.6% [64]; odds ratio, 2.02; 95% CI, 1.08-3.83; P=.027). The median failure-free survival was longer in the MSCs group compared with control group (11.3 months vs. 6.0 month; hazard ratio (HR) 0.68; 95% CI, 0.48-0.95, P=.024). The 2-year cumulative incidence of cGVHD was 39.5% (95% CI, 29.3%-49.4%) and 62.7% (51.4%-72.1%) in the MSCs and control groups (HR 0·55, 95% CI, 0·36-0·84; P=0·005). Within 180 days after study treatments, the most common grade 3 and 4 adverse events were infections (65 [65.7%] in the MSCs group vs 78 [78.8%] in the control group), haematological toxicity (37 [37.4%] vs 53 [53.5%]).
CONCLLUSIONS MSCs plus second-line treatments may increase the efficacy of SR aGVHD, decrease drug toxicity of second-line therapy and cGVHD development, and are well tolerated.

Disclosures
No relevant conflicts of interest to declare.
Decision Analysis of Allogeneic Stem Cell Transplantation for Primary Myelofibrosis
Authors: Cipkar Christopher , Kumar Srishti , Thavorn Kednapa , Kekre Natasha 
Published: November 2021

Abstract
Introduction: Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm characterized by cytopenias, splenomegaly and a risk of leukemic transformation. In light of newer therapies such as ruxolitinib that are not curative but can improve quality of life, the timing of transplant needs more in-depth analysis to determine which patients would benefit from an early versus delayed transplant strategy.
Methods: We developed a Markov cohort model to simulate the long-term disease trajectory in patients with PMF and predict the optimal timing of transplant stratified by a Dynamic International Prognostic Scoring System (DIPSS) risk. Our model consisted of five health states including alive with PMF, alive after leukemic transformation, alive after transplant, alive after relapse and death. Transition probabilities between health states were acquired from published literature on the natural history of the disease and outcomes following transplantation. The model was run over a patient's lifetime until all patients transitioned to the death state. We used a cycle length of one-month to represent the natural progression of PMF. The structure of the Markov model is delineated in Figure 1. In this decision model, a hypothetical cohort of patients begins in the Alive-PMF state and can transition after each monthly cycle to other health states. Patients could remain in an alive state for any number of cycles without transitioning to another health state, indicated by the arrow wheels. We performed probabilistic analyses by jointly varying all model parameters over 1000 simulations and calculated 95% confidence intervals (CI) for the model outcome.
Results: Regardless of DIPSS risk, all patients with PMF benefited from a transplant with respect to life expectancy gained (Figure 2). Life expectancy gains from a transplant among patients with high-risk disease peak at 9.7 months (95% CI: 9.5-9.9) from diagnosis, while patients with intermediate-2 disease have a peak gain in life expectancy at 16.6 months (95% CI: 16.4-16.8). Intermediate-1 DIPSS risk patients have a more delayed time frame where the net gain in life expectancy from transplant begins to slow at 20.5 months (95% CI: 20.2-20.7). Patients with low risk DIPSS had greater net gain in life expectancy the longer transplant was delayed; this trend plateaued at 29 to 45 months, when thereafter net gain in life expectancy begins to be lost (Figure 1).
Conclusion: Our modeling suggests that transplant processes including donor selection and pre-transplant work-up are indicated upfront for patients diagnosed with intermediate-2 and high risk PMF, while this can be delayed for patients with low or intermediate-1 risk disease. This model should provide clinicians with guidance on when to refer eligible patients with PMF for transplantation.
Figure 1 Figure 1.

Disclosures
Kekre: Novartis: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.
Efficacy and Safety of Fecal Microbiota Transplantation in the Treatment of Acute and Chronic Steroid-Refractory Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation
Authors: Huang Fen , Lv Pinjing , Liu Qifa 
Published: November 2021

Abstract
Despite major improvements in allogeneic hematopoietic stem cell transplantation over the last decades, steroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. SR-GVHD is a therapeutic challenge. Increasing evidence reveals that gut microbiota play a significant role in GVHD. Several small sample clinical trials indicates fecal microbiota transplantation (FMT) is the viable solution for SR-GVHD.In this retrospective survey, we reported outcome data from 29 patients aged 16-61 years who had underwent a total of 44 FMTs (range, 1-3) as salvage-therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=18, all grade II or III, all gastrointestinal tract involvement) or SR-cGVHD (n=11, all moderate or severe, progressive involvement of the gastrointestinal tract, lungs, liver, skin and mouth). The median number of prior systemic GVHD-therapies was 3 for both SR-aGVHD (range, 1-4) and SR-cGVHD (range, 1-5). The overall response rate (ORR) was 55.6% (10/18) in SR-aGVHD including 7 CRs (38.9%), while for SR-cGVHD the ORR was 54.5% (6/11, all partial responses). Among the complications of FMT with a possible cause-effect relationship there were: 11 fever, 3 fecal bacterial culture positive, 2 constipation. No serious adverse events clearly related to FMT occurred.FMT may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.

Disclosures
No relevant conflicts of interest to declare.
A Systematic Literature Review and Meta-Analysis of the Incidence of Serious or Severe Hypersensitivity Reactions after Administration of Ferric Derisomaltose and Ferric Carboxymaltose
Authors: Biggar Patrick , Kennedy Nicholas , Pöhlmann Johannes , Pollock-Wilkins Richard F 
Published: November 2021

Abstract
Background and Aims
Intravenous (IV) iron is the preferred treatment for patients with iron deficiency (ID) and iron deficiency anemia (IDA) in a variety of clinical situations. Although uncommon, administration of modern IV iron formulations can result in hypersensitivity reactions and, very rarely, anaphylactic reactions. The objective of the present study was to systematically review the literature to identify and analyze data on the incidence of serious or severe hypersensitivity reactions (HSRs) after administration of different IV iron formulations.
Methods
A prospectively-registered systematic literature review (SLR) was conducted to identify prospective, active comparator randomized controlled trials (RCTs) comparing ferric derisomaltose (FDI) (also known as iron isomaltoside 1000) or ferric carboxymaltose (FCM) with other IV iron formulations or oral iron. The primary endpoint was the incidence of serious or severe hypersensitivity reactions occurring on the day or day after dosing of IV iron, based on pre-specified terms (MedDRA classification).
Results
Data were obtained from ten prospective, active comparator RCTs of FDI (N=3,474) and seven prospective, active comparator RCTs of FCM (N=2,683), two of which were head-to-head comparisons of FDI and FCM. The trials enrolled a total of 10,467 patients, of whom 6,157 were treated with either FDI or FCM. The number of patients experiencing any serious or severe hypersensitivity reactions was 5/3474 with FDI (0.14%) versus 29/2683 (1.08%) with FCM; Bayesian inference of proportions showed the reaction rates to be significantly lower with FDI relative to FCM (Figure).
Conclusions
To our knowledge, the present analysis represents the first SLR and meta-analysis of the incidence of serious or severe HSRs after administration of FDI vs FCM based on pre-specified MedDRA terms. The SLR conducted for the present meta-analysis, identified 15 prospective, head-to-head RCTs including 10,467 patients, of whom 3,474 and 2,683 were treated with FDI and FCM, respectively. The analysis demonstrated that serious or severe hypersensitivity reactions were uncommon with the newer high-dose IV iron formulations; and showed a significantly lower incidence of serious or severe hypersensitivity reactions with FDI compared to FCM.
Figure 1 Figure 1.

Disclosures
Biggar: Vifor-Fresenius: Consultancy; Pharmacosmos: Consultancy; Medice: Consultancy. Pöhlmann: Pharmacosmos A/S: Consultancy. Pollock-Wilkins: Pharmacosmos A/S: Consultancy.
A Retrospective Analysis of the Efficacy of Low-Dose Metronomic Cyclophosphamide for Treatment in Patients with Low Grade Non-Hodgkin Lymphoma
Authors: Han Boram , Kim Bum Jun , Kim Ho Young , Zang Dae Young , Lim Hyun , Kang Ho Suk , Soh Jae Seung , Kim Hyo Jung 
Published: November 2021

Abstract
Background
Low-dose metronomic cyclophosphamide chemotherapy is an emerging strategy offering a potentially less toxic yet effective treatment modality. We evaluated the efficacy and safety of low-dose metronomic cyclophosphamide in patients with low grade non-Hodgkin lymphoma (NHL) by retrospectively reviewing the data.
Method
The patients received oral cyclophosphamide (50 mg per day) and/or oral methotrexate (2.5 mg twice weekly) until disease progression or unacceptable toxicity was noted.
Results
Of the 36 patients, 17 (47.2%) were male, median age was 66.4 years (range, 37-91 years), and subtypes of NHL were mucosa associated lymphoid tissue lymphoma (55.6%), small lymphocytic lymphoma (13.9%), follicular lymphoma (11.1%), mantle cell lymphoma (8.3%), nodal marginal zone lymphoma (4.5%), splenic marginal zone lymphoma (2.8%), and lymphoplasmacytic lymphoma (2.8%). The stage I, II, III, IV were 38.9%, 13.9%, 11.1%, 36.1%, respectively and 55.6% of patients received this regimen as the first-line treatment, mainly due to frailty, refusal to standard chemotherapy.
The overall best response rate (ORR) was 73.5% (12 complete responses, CRs and 13 partial responses, PRs), with 29.1 months of the median duration of response and the disease control rate was 88.2%. The median treatment duration was 8.8 months (range, 0.1-38.4 months); the median progression-free survival (PFS) was 43.5 months, and the median overall survival (OS) was not yet reached. Especially, the ORR in patients who were treated with metronomic cyclophosphamide as the first line treatment and as more than the second line treatment were 78.9% (10 CRs, 5 PRs) and 66.6% (2 CRs, 9 PRs), respectively. The median PFS were not reached in the first line cyclophosphamide treatment group and 26.5 months (range, 5.7-47.2 months) in the other group (p=0.110), and similarly, the median OS were not reached and 64.4 months (0-135.7 months) (p=0.058), respectively.
The regimen was generally well tolerated, with small numbers of grade 3-4 toxicities; neutropenia (2%), anemia (3%), thrombocytopenia (3%), fatigue (4%), and anorexia (1%).
Conclusion
We concluded that low-dose metronomic cyclophosphamide represents efficacious and well-tolerated treatment for low-grade NHL patients.

Disclosures
No relevant conflicts of interest to declare.