bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatal adverse events associated with programmed cell death protein 1 or programmed cell death-ligand 1 monotherapy in cancer
Authors: Zhao Bin , Zhao Hong , Zhao Jiaxin 
Published: February 2020

Background: The introduction of antibodies targeting programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) into clinical practice has had a revolutionary effect on cancer treatment. However, the incidence and risk of fatal adverse events (FAEs) following PD-1/PD-L1 inhibitor administration are controversial. Methods: We performed a systematic search for randomized controlled trials (RCTs) of PD-1/PD-L1 inhibitors (atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab) in Embase, PubMed, the Cochrane database, and abstracts presented at American Society of Clinical Oncology and European Society of Medical Oncology from inception to July 2018. FAEs were extracted from each study and pooled to calculate overall incidence and odds ratios (ORs). Results: In total, 20 RCTs involving 12,398 patients with solid tumors were included in this study. The overall incidence of FAEs with PD-1/PD-L1 inhibitors was 0.43% [95% confidence interval (CI), 0.25–0.66%]. However, the incidences of FAEs varied significantly by tumor type and median follow-up time. Compared with conventional agents, the application of PD-1/PD-L1 inhibitors significantly reduced the risk of FAEs (OR, 0.56; 95% CI, 0.35–0.89; p = 0.015). Moreover, trial sequential analysis confirmed that our results were solid and reliable; further studies were unlikely to alter this conclusion. FAEs occurred dispersed in major organ systems, with the most common mortalities appearing in the respiratory system (46.2%). Conclusions: Compared with conventional treatment, PD-1/PD-L1 blockade monotherapy is associated with a significantly reduced risk of mortality in patients with solid tumors.
The Relationship Between Humeral Torsion and Arm Injury in Baseball Players: A Systematic Review and Meta-analysis
Authors: Helmkamp Joshua K. , Bullock Garrett S. , Rao Allison , Shanley Ellen , Thigpen Charles , Garrigues Grant E. 
Published: February 2020

Context: Humeral torsion (HT) has been linked to various injuries and benefits. However, the exact interplay between HT, shoulder range of motion (ROM), competition level differences, and injury risk is unclear. Objective: To determine the relationship between HT, ROM, and injury risk in baseball players. Secondarily, to determine HT based on competition level. Data Sources: PubMed, Embase, Web of Science, CINAHL, and Cochrane databases were searched from inception until November 4, 2018. Study Selection: Inclusion criteria consisted of (1) HT measurements and (2) arm injury or shoulder ROM. Study Design: Systematic review. Level of Evidence: Level 3. Data Extraction: Two reviewers recorded patient demographics, competition level, HT, shoulder ROM, and injury data. Results: A total of 32 studies were included. There was no difference between baseball players with shoulder and elbow injuries and noninjured players (side-to-side HT difference: mean difference [MD], 1.75 [95% CI, –1.83 to 2.18]; dominant arm: MD, 0.17 [95% CI, –1.83 to 2.18]). Meta-regression determined that for every 1° increase in shoulder internal rotation (IR), there was a subsequent increase of 0.65° in HT (95% CI, 0.28 to 1.02). HT did not explain external rotation (ER ROM: 0.19 [95% CI, –0.24 to 0.61]) or horizontal adduction (HA ROM: 0.18 [95% CI, –0.46 to 0.82]). There were no differences between HT at the high school, college, or professional levels. Conclusion: No relationship was found between HT and injury risk. However, HT explained 65% of IR ROM but did not explain ER ROM or HA ROM. There were no differences in HT pertaining to competition level. The majority of IR may be nonmodifiable. Treatment to restore and maintain clinical IR may be important, especially in players with naturally greater torsion. HT adaptation may occur prior to high school, which can assist in decisions regarding adolescent baseball participation.
Guideline-based flexible cystoscopy safely improves capacity, avoiding unnecessary intervention with cost savings
Authors: Habib A , Noel J , Batura D , Hellawell G 
Published: February 2020

Introduction: Flexible cystoscopy (FC) is a common and useful diagnostic tool. Because of its broader applications, availability and simplicity, there has been criticism of its overuse with accompanying financial burden to the health system and unnecessary invasive intervention to the patient. Therefore, we reviewed our local practice against current guidelines to evaluate compliance, enhance patient safety and capacity utilisation. Patients and methodology: Data were collected retrospectively on all patients having FC over two months. The indications and findings of FC were gathered from the hospital electronic patient record system. Results: A total of 413 FCs were carried out over the study period. The most common indications were cancer surveillance 116 (28%) and visible haematuria 76 (18.4%). A total of 152 (37%) FCs were performed for non-recommended indications. The most common conditions that deviated from guidelines were lower urinary tract symptoms (LUTS) (72, 17.4%), urinary tract infection (UTI) (41, 9.9%) and asymptomatic non-visible haematuria (35, 8.5%). In all non-visible haematuria cases, 65 (90%) of LUTS and 39 (95%) of UTI patients, FC was non-contributory. Adherence to guidelines would have yielded 37% of FC slots. Based on current UK National Tariffs, cost savings would have been £352,032 annually in this trust. Conclusions: FC is a frequent investigation within urology departments for which referral guidelines exist. Protocol-driven practice enables appropriate use, ensures patient safety and leads to efficient utilisation of capacity with substantial cost savings. Level of evidence: Not applicable for this multicentre audit.
Effect of Baseline Symptom Manifestations on Retention in Care and Treatment among HIV-Infected Patients in Nigeria
Authors: Adeola Juliet , Badejo Okikiolu Abimbola , Ahonkhai Aimalohi , Okonkwo Prosper , Aboh Akande Patrick , Evans Charlesnika Tyon , McHugh Megan , Pierce Leslie , Ahmed Isah , Jolayemi Toyin , Ladi Akinyemi Babatunde , Onwuatuelo Ifeyinwa , Murphy Robert , Kyriacou Demetrious , Musa Jonah , Agaba Patricia 
Published: February 2020

Background: Symptom management is an important component of HIV care. But symptom patterns and how they affect engagement with HIV care and treatment services have not been adequately explored in the era of increased HIV treatment scale-up. We investigated the relationship between symptom patterns among people living with HIV (PLHIV) and 12 months retention in care, within the context of other clinical and demographic characteristics. Methods: Retrospective cohort analysis of 5114 PLHIV receiving care within a large HIV treatment program in Nigeria. We assessed the prevalence and burden of baseline symptoms reported during routine clinic visits from January 2015 to December 2017. Multivariable regression was used to identify relationships between 12-month retention and symptom dimensions (prevalence and burden) while controlling for demographic and other clinical variables. Results: Increasing symptom burden was associated with higher likelihood of retention at 12 months (adjusted odds ratio [aOR] = 1.19 [95% confidence interval, CI: 1.09-1.29]; P < .001) as was the reporting of skin rashes/itching symptom (aOR = 2.59 [95% CI: 1.65-4.09]; P < .001). Likelihood of retention reduced with increasing World Health Organization (WHO) Clinical staging, with CD4 ≥500 cells/mL and self-reported heterosexual mode of HIV transmission. Conclusions: Symptom dimensions and standardized clinical/immunological measures both predicted retention in care, but effects differed in magnitude and direction. Standardized clinical/immunological measures in HIV care (eg, WHO clinical staging and CD4 count categories) can mask important differences in how PLHIVs experience symptoms and, therefore, their engagement with HIV care and treatment. Symptom management strategies are required alongside antiretroviral treatment to improve outcomes among PLHIV, including retention in care.
Reduced–dose intensity therapy for pediatric lymphoblastic leukemia: long-term results of the Recife RELLA05 pilot study
Authors: Pedrosa Francisco , Coustan-Smith Elaine , Zhou Yinmei , Cheng Cheng , Pedrosa Arli , Lins Mecneide Mendes , Pedrosa Marcia , Lucena-Silva Norma , Ramos Alessandra Maria de Luna , Vinhas Ester , Rivera Gaston K. , Campana Dario , Ribeiro Raul C. 
Published: February 2020

Abstract
Treatment-related mortality is common among children with acute lymphoblastic leukemia (ALL) treated in poor-resource settings. We applied a simplified flow cytometric assay to identify patients with precursor B-cell ALL (B-ALL) at very low risk (VLR) of relapse and treated them with a reduced-intensity treatment plan (RELLA05). VLR criteria include favorable presenting features (age ≥ 1 and &lt; 10 years), white blood cell count of &lt;50 ×109/L, lack of extramedullary leukemia, and minimal residual disease level of &lt;0.01% on remission induction day 19. Except for 2 doses of daunorubicin, treatment of patients with VLR B-ALL consisted of a combination of agents with relatively low myelotoxicity profiles, including corticosteroids, vincristine, L-asparaginase, methotrexate, and 6-mercaptopurine. Cyclophosphamide, systemic cytarabine, and central nervous system radiotherapy were not used. Of 454 patients with ALL treated at the Instituto de Medicina Integral Professor Fernando Figueira in Recife, Brazil, between December 2005 and June 2015, 101 were classified as having VLR B-ALL. There were no cases of death resulting from toxicity or treatment abandonment during remission induction. At a median follow-up of 6.6 years, there were 8 major adverse events: 6 relapses, 1 treatment-related death (from septicemia) during remission, and 1 secondary myeloid leukemia. The estimated 5-year event-free and overall survival rates were 92.0% ± 3.9% and 96.0% ± 2.8%, respectively. The 5-year cumulative risk of relapse was 4.24% ± 2.0%. The treatment was well tolerated. Episodes of neutropenia were of short duration. Patients with B-ALL selected by a combination of presenting features and degree of early response can be successfully treated with a mildly myelosuppressive chemotherapy regimen.
Propranolol inhibits molecular risk markers in HCT recipients: a phase 2 randomized controlled biomarker trial
Authors: Knight Jennifer M. , Rizzo J. Douglas , Hari Parameswaran , Pasquini Marcelo C. , Giles Karen E. , D’Souza Anita , Logan Brent R. , Hamadani Mehdi , Chhabra Saurabh , Dhakal Binod , Shah Nirav , Sriram Deepika , Horowitz Mary M. , Cole Steve W. 
Published: February 2020

Abstract
Preclinical research shows that stress-induced activation of the sympathetic nervous system can promote hematopoietic malignancies via β-adrenoreceptor–mediated molecular pathways. Hematopoietic cell transplant (HCT) recipients exposed to conditions of chronic stress show activation of a conserved transcriptional response to adversity (CTRA) gene expression profile, which in turn is associated with increased relapse and decreased disease-free survival. We conducted a randomized controlled phase 2 biomarker trial testing the impact of the nonselective β-antagonist propranolol on CTRA-related gene expression of 25 individuals receiving an autologous HCT for multiple myeloma. Propranolol was administered for 1 week prior to and 4 weeks following HCT. Blood was collected at baseline, day −2, and day +28. Intention-to-treat analyses controlling for demographic characteristics, high-risk disease (International Myeloma Working Group risk score), and tumor stage tested effects on a 53-gene CTRA indicator profile and measures of CTRA-related cellular processes in peripheral blood mononuclear cells. Twelve participants were randomized to the intervention and 13 to the control. Relative to the control group, propranolol-treated patients showed greater decreases from baseline to HCT day −2 and day +28 for both CTRA gene expression (P = .017) and bioinformatic measures of CD16− classical monocyte activation (P = .005). Propranolol-treated patients also showed relative upregulation of CD34+ cell–associated gene transcripts (P = .011) and relative downregulation of myeloid progenitor–containing CD33+ cell–associated gene transcripts (P = .001). Ancillary analyses identified nonsignificant trends toward accelerated engraftment and reduced posttransplant infections in propranolol-treated patients. Peri-HCT propranolol inhibits cellular and molecular pathways associated with adverse outcomes. Changes in these pathways make propranolol a potential candidate for adjunctive therapy in cancer-related HCT.
Genomic context and TP53 allele frequency define clinical outcomes in TP53-mutated myelodysplastic syndromes
Authors: Montalban-Bravo Guillermo , Kanagal-Shamanna Rashmi , Benton Christopher B. , Class Caleb A. , Chien Kelly S. , Sasaki Koji , Naqvi Kiran , Alvarado Yesid , Kadia Tapan M. , Ravandi Farhad , Daver Naval , Takahashi Koichi , Jabbour Elias , Borthakur Gautham , Pemmaraju Naveen , Konopleva Marina , Soltysiak Kelly A. , Pierce Sherry R. , Bueso-Ramos Carlos E. , Patel Keyur P. , Kantarjian Hagop , Garcia-Manero Guillermo 
Published: February 2020

Abstract
TP53 mutations are associated with adverse outcomes and shorter response to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS). Limited data have evaluated the impact of the type, number, and patterns of TP53 mutations in response outcomes and prognosis of MDS. We evaluated the clinicopathologic characteristics, outcomes, and response to therapy of 261 patients with MDS and TP53 mutations. Median age was 68 years (range, 18-80 years). A total of 217 patients (83%) had a complex karyotype. TP53 mutations were detected at a median variant allele frequency (VAF) of 0.39 (range, 0.01-0.94). TP53 deletion was associated with lower overall response rate (ORR) (odds ratio, 0.3; P = .021), and lower TP53 VAF correlated with higher ORR to HMAs. Increase in TP53 VAF at the time of transformation was observed in 13 patients (61%), and previously undetectable mutations were observed in 15 patients (65%). TP53 VAF was associated with worse prognosis (hazard ratio, 1.02 per 1% VAF increase; 95% confidence interval, 1.01-1.03; P &lt; .001). Integration of TP53 VAF and karyotypic complexity identified prognostic subgroups within TP53-mutant MDS. We developed a multivariable model for overall survival that included the revised International Prognostic Scoring System (IPSS-R) categories and TP53 VAF. Total score for each patient was calculated as follows: VAF TP53 + 13 × IPSS-R blast score + 16 × IPSS-R cytogenetic score + 28 × IPSS-R hemoglobin score + 46 × IPSS-R platelet score. Use of this model identified 4 prognostic subgroups with median survival times of not reached, 42.2, 21.9, and 9.2 months. These data suggest that outcomes of patients with TP53-mutated MDS are heterogeneous and that transformation may be driven not only by TP53 but also by other factors.
Patient preferences for symptom-driven or regular preventer treatment in mild to moderate asthma: findings from the PRACTICAL study, a randomised clinical trial
Authors: Baggott Christina , Reddel Helen K. , Hardy Jo , Sparks Jenny , Holliday Mark , Corin Andrew , Montgomery Barney , Reid Jim , Sheahan Davitt , Hancox Robert J. , Weatherall Mark , Beasley Richard , Fingleton James 
Published: February 2020

Symptom-driven low-dose inhaled corticosteroid–formoterol is safe and effective in mild asthma and has been recommended as one of the preferred treatment regimens at steps 1 and 2 in the 2019 update of the Global Initiative for Asthma. However, there are no data on patient preferences for this regimen.A subgroup of participants in the PRACTICAL study (ACTRN12616000377437), a randomised controlled trial comparing symptom-driven budesonide–formoterol with maintenance budesonide plus as-needed terbutaline completed a survey on treatment preferences, satisfaction, beliefs and experience at their final study visit.306 (75%) out of 407 eligible participants completed the survey. Regimen preference was strongly associated with randomised treatment, as were preferences for and beliefs about preventer inhaler use. Combination preventer and reliever as-needed therapy was preferred by 135 (90%, 95% CI 85.2–94.8%) out of 150 who were randomised to as-needed budesonide–formoterol, and by 63 (40%, 95% CI 32.7–48.1%) out of 156 who were randomised to maintenance budesonide. By contrast, twice-daily preventer inhaler with a reliever inhaler as required was preferred by 15 (10%) out of 150 of those randomised to as-needed budesonide–formoterol and 93 (60%) out of 156 of those randomised to maintenance budesonide. Satisfaction with all study inhalers was high. Of patients randomised to as-needed budesonide–formoterol 92% (n=138) were confident using it as a reliever at the end of the study.Although most participants preferred the regimen to which they had been randomised, this association was much stronger for those randomised to budesonide–formoterol as needed, indicating that most patients preferred as-needed corticosteroid–formoterol therapy if they had experienced it.
PANEV: an R package for a pathway-based network visualization
Authors: Palombo Valentino , Milanesi Marco , Sferra Gabriella , Capomaccio Stefano , Sgorlon Sandy , D’Andrea Mariasilvia 
Published: February 2020

Abstract
Background
During the last decade, with the aim to solve the challenge of post-genomic and transcriptomic data mining, a plethora of tools have been developed to create, edit and analyze metabolic pathways. In particular, when a complex phenomenon is considered, the creation of a network of multiple interconnected pathways of interest could be useful to investigate the underlying biology and ultimately identify functional candidate genes affecting the trait under investigation.

Results
PANEV (PAthway NEtwork Visualizer) is an R package set for gene/pathway-based network visualization. Based on information available on KEGG, it visualizes genes within a network of multiple levels (from 1 to n) of interconnected upstream and downstream pathways. The network graph visualization helps to interpret functional profiles of a cluster of genes.

Conclusions
The suite has no species constraints and it is ready to analyze genomic or transcriptomic outcomes. Users need to supply the list of candidate genes, specify the target pathway(s) and the number of interconnected downstream and upstream pathways (levels) required for the investigation. The package is available at https://github.com/vpalombo/PANEV.
Motor, cognitive and mobility deficits in 1000 geriatric patients: protocol of a quantitative observational study before and after routine clinical geriatric treatment – the ComOn-study
Authors: Geritz Johanna , Maetzold Sara , Steffen Maren , Pilotto Andrea , Corrà Marta F. , Moscovich Mariana , Rizzetti Maria C. , Borroni Barbara , Padovani Alessandro , Alpes Annekathrin , Bang Corinna , Barcellos Igor , Baron Ralf , Bartsch Thorsten , Becktepe Jos S. , Berg Daniela , Bergeest Lu M. , Bergmann Philipp , Bouça-Machado Raquel , Drey Michael , Elshehabi Morad , Farahmandi Susan , Ferreira Joaquim J. , Franke Andre , Friederich Anja , Geisler Corinna , Hüllemann Philipp , Gierthmühlen Janne , Granert Oliver , Heinzel Sebastian , Heller Maren K. , Hobert Markus A. , Hofmann Marc , Jemlich Björn , Kerkmann Laura , Knüpfer Stephanie , Krause Katharina , Kress Maximilian , Krupp Sonja , Kudelka Jennifer , Kuhlenbäumer Gregor , Kurth Roland , Leypoldt Frank , Maetzler Corina , Maia Luis F. , Moewius Andreas , Neumann Patricia , Niemann Katharina , Ortlieb Christian T. , Paschen Steffen , Pham Minh H. , Puehler Thomas , Radloff Franziska , Riedel Christian , Rogalski Marten , Sablowsky Simone , Schanz Elena M. , Schebesta Linda , Schicketmüller Andreas , Studt Simone , Thieves Martina , Tönges Lars , Ullrich Sebastian , Urban Peter P. , Vila-Chã Nuno , Wiegard Anna , Warmerdam Elke , Warnecke Tobias , Weiss Michael , Welzel Julius , Hansen Clint , Maetzler Walter 
Published: February 2020

Abstract
Background
Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany).

Methods
This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week’s inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters.

Discussion
This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.
Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma
Authors: Su Yan , Wang Lijun , Jiang Chiyi , Yue Zhixia , Fan Hongjun , Hong Huimin , Duan Chao , Jin Mei , Zhang Dawei , Qiu Lihua , Cheng Xianfeng , Xu Zhong , Ma Xiaoli 
Published: February 2020

Abstract
Background
Neuroblastoma is the most common extracranial solid tumor of childhood. The high rate of recurrence is associated with a low survival rate for patients with high-risk neuroblastoma. There is thus an urgent need to identify effective predictive biomarkers of disease recurrence.

Methods
A total of 116 patients with high-risk neuroblastoma were recruited at Beijing Children’s Hospital between February 2015 and December 2017. All patients received multidisciplinary treatment, were evaluated for the therapeutic response, and then initiated on maintenance treatment. Blood samples were collected at the beginning of maintenance treatment, every 3 months thereafter, and at the time of disease recurrence. Plasma levels of cell-free DNA (cfDNA) were quantified by qPCR. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of plasma cfDNA concentration to predict recurrence.

Results
Of the 116 patients, 36 (31.0%) developed recurrence during maintenance treatment. The median time to recurrence was 19.00, 9.00, and 8.00 months for patients who had achieved complete response (n = 6), partial response (n = 25), and stable disease (n = 5), respectively, after multidisciplinary treatment. The median plasma cfDNA concentration at the time of recurrence was significantly higher than the concentration in recurrence-free patients throughout maintenance treatment (29.34 ng/mL vs 10.32 ng/mL). Patients recorded a plasma cfDNA level ≥ 29 ng/mL an average of 0.55 months before diagnosis of disease recurrence. ROC analysis of the power of plasma cfDNA to distinguish between patients with or without recurrence yielded an area under the curve of 0.825, with optimal sensitivity and specificity of 80.6 and 71.3%, respectively, at a cfDNA level of 12.93 ng/mL.

Conclusions
High plasma cfDNA concentration is a potential molecular marker to signal disease recurrence in patients with high-risk neuroblastoma.