bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of Pediatric Tracheostomy Outcomes in the United States
Authors: Friesen Tzyynong L. , Zamora Steven M. , Rahmanian Ronak , Bundogji Nour , Brigger Matthew T. 
Published: April 2020

ObjectivesTo investigate the outcomes of pediatric tracheostomy as influenced by demographics and comorbidities.Study DesignRetrospective national database review.SettingFifty‐two children’s hospitals across the United States.Subjects and MethodsHospitalization records from Pediatric Health Information System database dated 2010 to 2018 with patients younger than 18 years and procedure codes for tracheostomy were extracted. The primary outcome was total length of stay. The secondary outcomes were 30‐day readmission, mortality, and posttracheostomy length of stay.ResultsA total of 14,155 children were included in the analysis. The median total length of stay was 77 days and increased from 59 to 103 days between 2010 and 2018 (P <. 001). The median posttracheostomy length of stay was 34 days and also increased from 27 to 49 days (P <. 001). On multivariate regression analyses, the total and posttracheostomy lengths of stay were significantly increased in children younger than 1 year, patients of black race, hospitals in the non‐West regions, those discharged to home, and those with comorbidities. Socioeconomic indicators such as insurance type and estimated household income were associated with no difference or small effect sizes. Regions and comorbidities were associated with differences in 30‐day readmission (overall 26%), while in‐hospital mortality was primarily associated with age and comorbidities (overall 8.6%).ConclusionPediatric tracheostomy requires substantial health care resources with length of stay escalating over recent years. Age, race, region, discharge destination, and comorbidities were associated with differences in length of stay.
Impact of mandated prospectively reported apparent diffusion coefficient values on the rates of positivity for clinically significant prostate cancer by PI-RADS score
Authors: Shaish Hiram , Casals Randy , Ahmed Firas , Makkar Jasnit , Wenske Sven 
Published: April 2020

Background Prior research has shown that retrospectively measured apparent diffusion coefficient (ADC) of prostate magnetic resonance imaging (MRI) lesions is associated with clinically significant prostate cancer (csPCa) on targeted biopsy suggesting that ADC should be measured and reported prospectively. Purpose To assess the impact of mandatory prospective measurement of ADC on the rates of positivity across PI-RADS scores for csPCa. Material and Methods Consecutive patients who underwent ultrasound (US)-MRI fusion prostate biopsy from August 2018 to July 2019 and who had prospectively reported ADC were compared to control patients who did not. Rates of positivity by PI-RADS category were computed and compared using Chi-square. Multivariable regression was performed. Results In total, 126 patients (median age 65 years) with 165 prostate lesions (19, 51, 70, and 25 PI-RADS 2, 3, 4, and 5, respectively) and prospectively reported ADC values were compared to 113 control patients (median age 66 years) with 157 prostate lesions (17, 42, 64, and 34 PI-RADS 2, 3, 4, and 5, respectively). Rates of positivity across PI-RADS scores were similar between the two cohorts; 11%, 25%, 55%, and 76% and 0%, 21%, 56%, and 62% for PI-RADS 2, 3, 4, and 5 in the test and control cohorts, respectively (Chi-square P = 0.78). Multivariate logistic regression showed no significant association between the presence of prospectively measured ADC and csPCa (odds ratio 1.1, 95% confidence interval 0.7–1.7, P = 0.82). Conclusion Prospective ADC measurement may not impact PI-RADS category assignments or positivity rates for csPCa under current guidelines. Future versions of PI-RADS may need to incorporate ADC into scoring rules to realize their potential.
Effect of anesthetic technique on serum vascular endothelial growth factor C and prostaglandin E2 levels in women undergoing surgery for uterine leiomyomas
Authors: Zhang Yonghai , Yu Jingfang , Yang Fan , Zhao Liyan , Ma Ling , Zhang Huiwen , Chen Xuexin , Ma Hanxiang 
Published: April 2020

Objective Angiogenesis is essential for growth and recurrence of uterine leiomyomas, and angiogenesis is mediated by vascular endothelial growth factor C (VEGF-C) and prostaglandin E2 (PGE2). This study investigated whether spinal anesthesia (SA) with continuous postoperative epidural analgesia attenuates postoperative changes in these angiogenic factors compared with general anesthesia (GA) with patient-controlled intravenous analgesia. Methods Forty-four women with uterine leiomyomas undergoing abdominal myomectomy were randomized to receive either standard SA or GA. Blood samples were taken before anesthesia and at 48 hours after surgery for measuring serum VEGF-C and PGE2 levels, which were analyzed by using enzyme-linked immunosorbent assays. Visual analog scale pain scores were used to evaluate postoperative pain. Results Serum VEGF-C and PGE2 levels were not significantly different preoperatively between the SA and GA groups, but they were decreased in each group at 48 hours after surgery compared with preoperatively. The change in pre- and postoperative VEGF-C levels was smaller in the GA group than in the SA group. Conclusions Removal of uterine leiomyomas by surgery can reduce serum VEGF-C and PGE2 levels. The anesthetic technique affects serum VEGF-C levels, which are associated with angiogenesis in surgery for leiomyomas.
Changes in Treg numbers and activity in papillary thyroid carcinoma with and without Hashimoto’s thyroiditis
Authors: Zhao Na , Liu Xin , Wu Chao , Liu Yuanchao , Zhao Xiangnan , He Xianghui 
Published: April 2020

Background Hashimoto’s thyroiditis (HT) is a common autoimmune disease, and an increasing number of papillary thyroid carcinoma (PTC) cases are being diagnosed in HT patients. The aim of this study was to investigate the proportion and function of different T cell subtypes in peripheral blood, especially CD4+Foxp3+ regulatory T cells (Tregs), in PTC with and without HT. We also studied the effect of HT on PTC. Methods Flow cytometry was used to detect the proportions of CD4+ T cells, CD8+ T cells, CD4+Foxp3+ Tregs, and the level of interleukin-10 (IL-10) secreted by CD4+ T cells in the peripheral blood of PTC patients with and without HT. AimPlex bead-based immunoassays were used to determine serum cytokine levels. Results No significant differences were observed in the proportion of CD4+ or CD8+ T cells in the two groups of PTC patients. The percentage of CD4+FoxP3+ Tregs and their levels of IL-10 were significantly lower in PTC patients with HT than in those without HT. Conclusions Our findings suggest that CD4+Foxp3+ Tregs have vital regulatory functions in the initiation and progression of PTC by secreting the inhibitory cytokine IL-10.
Factors Associated with Costs in Chimeric Antigen Receptor T-Cell Therapy for Patients with Relapsed/Refractory B-Cell Malignancies
Authors: Zhu Feng , Wei Guoqing , Zhang Mingming , Zhao Houli , Wu Wenjun , Yang Luxin , Hu Yongxian , Huang He 
Published: April 2020

Background: Chimeric antigen receptor T cells (CAR-Ts) constitute a novel therapeutic strategy for relapsed/refractory B-cell malignancies. CAR-T therapy has been extensively applied in the clinical setting; however, few systematic studies have evaluated the cost of CAR-T treatment. This study was conducted to evaluate the total cost and cost structure of CAR-T therapy and identify potential risk factors leading to increased costs. Methods: We identified the associated risk factors in 89 patients in a phase 1/2 study. The cohort included patients with acute lymphoblastic leukemia (ALL, n = 55) and non-Hodgkin’s lymphoma (NHL, n = 34). Results: Overall, the treatment of the ALL cohort was costlier than that of the NHL cohort ( P < 0.001). Furthermore, in the ALL cohort, it was costlier to treat patients with a high tumor burden ( P < 0.001), high cytokine release syndrome (CRS) grade ( P < 0.001), and complications of infection after CAR-T cell infusion (CTI) in the whole cohort ( P = 0.013) than patients with a low tumor burden, with low CRS grade, and without infection, respectively. CRS grade and length of stay ( P ≤ 0.005) were independent risk factors associated with the total cost in both the ALL and NHL cohorts during CAR-T therapy. A high tumor burden, duration of fever, and treatment with tocilizumab were independent risk factors associated with the total cost in the ALL cohort ( P < 0.05). Conclusions: CAR-T treatment should be extended to patients with a low tumor burden or patients in a state of complete remission, and a corticosteroid approach, as opposed to tocilizumab, may reduce costs.
Posterior reversible encephalopathy syndrome: A rare neurotoxicity after capecitabine
Authors: Monti Manlio , Barone Domenico , Amadori Elena , Bartolini Giulia , Ruscelli Silvia , Frassineti Giovanni Luca 
Published: April 2020

Background Posterior reversible encephalopathy syndrome (PRES) is a condition characterized by seizures, headache, visual disturbances, paresis, nausea and altered mental status. Risk factors include hypertension, eclampsia/pre-eclampsia, infection/sepsis, transplantation (allograft, bone marrow and solid organ) and immunosuppression, especially in association with autoimmune disorders and use of cyclosporine or chemotherapy. Case report A few days after starting the first cycle of treatment with capecitabine, a 50-year-old female with metastatic breast cancer experienced serious adverse events consisting of severe hematological, gastrointestinal and neurological toxicity. A brain magnetic resonance imaging, performed because of the severe state of confusion of the patient, confirmed PRES. Management and outcome The patient was admitted to the hospital; capecitabine was stopped and treatment was started with antibiotics, growth factor therapy and blood and platelet transfusions. Her clinical conditions slowly improved and the PRES resolved. A dihydropyrimidine dehydrogenase deficiency was identified. Discussion The patient had previously been treated with another fluoropyrimidine, 5-fluorouracil, but without toxicity. A literature search was performed, and only six cases of PRES associated with capecitabine were found. Our case suggests that capecitabine differs from 5-fluorouracil in its mechanism of action and that at least one of the metabolites of capecitabine has the ability to cross the blood–brain barrier, causing neurotoxicity. We believe that it is useful to test for dihydropyrimidine dehydrogenase deficiency before using fluoropyrimidines and would encourage the reporting of such cases of PRES to gain a better overall picture of its incidence in this setting. Naranjo score 7
Atlas Sampling for Prone Breast Automatic Segmentation of Organs at Risk: The Importance of Patients’ Body Mass Index and Breast Cup Size for an Optimized Contouring of the Heart and the Coronary Vessels
Authors: Wang Xinzhuo , Miralbell Raymond , Fargier-Bochaton Odile , Bulling Shelley , Vallée Jean Paul , Dipasquale Giovanna 
Published: April 2020

Objective: Delineation of organs at risk is a time-consuming task. This study evaluates the benefits of using single-subject atlas-based automatic segmentation of organs at risk in patients with breast cancer treated in prone position, with 2 different criteria for choosing the atlas subject. Together with laterality (left/right), the criteria used were either (1) breast volume or (2) body mass index and breast cup size. Methods: An atlas supporting different selection criteria for automatic segmentation was generated from contours drawn by a senior radiation oncologist (RO_A). Atlas organs at risk included heart, left anterior descending artery, and right coronary artery. Manual contours drawn by RO_A and automatic segmentation contours of organs at risk and breast clinical target volume were created for 27 nonatlas patients. A second radiation oncologist (RO_B) manually contoured (M_B) the breast clinical target volume and the heart. Contouring times were recorded and the reliability of the automatic segmentation was assessed in the context of 3-D planning. Results: Accounting for body mass index and breast cup size improved automatic segmentation results compared to breast volume-based sampling, especially for the heart (mean similarity indexes >0.9 for automatic segmentation organs at risk and clinical target volume after RO_A editing). Mean similarity indexes for the left anterior descending artery and the right coronary artery edited by RO_A expanded by 1 cm were ≥0.8. Using automatic segmentation reduced contouring time by 40%. For each parameter analyzed (eg, D2%), the difference in dose, averaged over all patients, between automatic segmentation structures edited by RO_A and the same structure manually drawn by RO_A was <1.5% of the prescribed dose. The mean heart dose was reliable for the unedited heart segmentation, and for right-sided treatments, automatic segmentation was adequate for treatment planning with 3-D conformal tangential fields. Conclusions: Automatic segmentation for prone breast radiotherapy stratified by body mass index and breast cup size improved segmentation accuracy for the heart and coronary vessels compared to breast volume sampling. A significant reduction in contouring time can be achieved by using automatic segmentation.
Short- to Midterm Follow-up of Cemented Total Ankle Replacement Using the INBONE II: A Retrospective Chart Review
Authors: Berlet Gregory C. , Brandão Roberto A. , Consul Devon , Ebaugh Pierce , Hyer Christopher F. 
Published: April 2020

Background: Total ankle arthroplasty is a viable option for the treatment of end stage ankle arthritis. The purpose of this study is to report on the mid-term results with a cemented total ankle prosthesis, the Inbone™ II implant over a 5 year period. Methods: A retrospective, single-center chart and radiographic review of all patients with end stage ankle arthritis treated with Inbone™ II TAR) as the primary index procedure from 12/1/2012 to 3/1/2017. Clinical data were evaluated at 3 month, 6 month, 1 year and subsequent intervals for the study period. Preoperative diagnosis, pertinent patient demographics adjunctive procedures, implant associated complications, subsequent surgeries, and revisions were recorded. Results: 121 total ankles met our inclusion criteria. Patients had an INBONE™ II TAR implant placed with bone cement with a minimum of a 12 months follow up. Average age was 62.88 (range, 32-87) years, average body mass index was 32.74 (range, 21.8-56.04) kg/m2 and average follow up was 28.51(range, 12-69) months. Using the COFAS complication classification there were 14 minor, 11 moderate, and 5 major complications. 6/121 (5.0%) revisions which included: polyethylene exchange, device explant/fusion, and antibiotic spacer in situ. No complications over the course of this study ended in amputation. Conclusion: Total Ankle Arthroplasty utilizing the cemented INBONE™ II yielded good midterm results with regards to minor, moderate, and major complications. Rate of revision 6/121 (5.0%) was within the reported range with only 5 patients converted to fusion during the study period resulting in a 95% survivability at mid-term follow up. Levels of Evidence: Level IV: Retrospective case series
Risk of hepatotoxicity with trastuzumab emtansine in breast cancer patients: a systematic review and meta-analysis
Authors: Cobert Amani M. , Helms Catherine , Larck Chris , Moore Donald C. 
Published: April 2020

Background: Trastuzumab emtansine (T-DM1) is an anti-HER2 antibody-drug conjugate indicated for the treatment of HER2-positive breast cancer. One of the most severe adverse events reported with T-DM1 is hepatotoxicity. The objective of our meta-analysis is to investigate the risk of hepatic adverse events in patients with breast cancer receiving T-DM1 compared with controls. Methods: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) comparing T-DM1 with a control treatment in patients with HER2-positive breast cancer. Phase II/III RCTs with available event number or event rate of hepatic toxicity with an assessable sample size were included. Relative risk (RR) and corresponding 95% confidence intervals (CI) for all grade and high-grade (grade 3/4) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevations were calculated. Results: Seven RCTs were deemed eligible and were included in the meta-analysis. The RR for all-grade AST and ALT elevations were 3.24 (95% CI 2.16–4.86; p < 0.00001) and 2.90 (95% CI 1.98–4.23; p < 0.00001), respectively. The RR for high-grade AST and ALT elevations were 2.73 (95% CI 1.07–6.93; p = 0.03) and 2.17 (95% CI 1.34–3.50; p = 0.002), respectively. Conclusions: Our meta-analysis demonstrates that T-DM1-based therapy is associated with an increased risk of AST and ALT elevations.
Adverse events with sacubitril/valsartan in the real world: emerging signals to target preventive strategies from the FDA adverse event reporting system
Authors: Gatti Milo , Antonazzo Ippazio Cosimo , Diemberger Igor , De Ponti Fabrizio , Raschi Emanuel 
Published: April 2020

Abstract

Aims
The aim of this study was to characterise clinical priority of adverse events with sacubitril/valsartan for targeting preventive measures.

Methods
We used the US Food and Drug Administration adverse event reporting system (worldwide pharmacovigilance database) to compare adverse events recording sacubitril/valsartan as suspect with other cardiovascular drugs. Disproportionality analyses were performed by calculating the reporting odds ratios, deemed significant when the lower limit of the 95% confidence interval was greater than 1. Clinical priority was assigned to adverse events with significant disproportionality by scoring (range 0–10 points) five features (number of events, magnitude of the lower limit of the 95% confidence interval, mortality frequency, important/designated medical event, biological plausibility).

Results
Sacubitril/valsartan was recorded in 20,021 reports, with 178 adverse events associated with significant disproportionality: 71.9%, 25.9% and 2.2% were classified as weak, moderate and strong clinical priorities, respectively. Increased reporting emerged for several cardiovascular adverse events, including ‘renal failure’ (N = 388; lower limit of the 95% confidence interval 2.26), ‘hyperkalaemia’ (314; 2.42) and ‘angioedema’ (309; 1.56). Sudden cardiac death (priority score 9 points) was the only designated medical event with strong clinical priority. Notably, sudden cardiac death occurred early after sacubitril/valsartan administration (average onset 124 days), with concomitant drugs known for pro-arrhythmic potential (e.g. amiodarone, escitalopram, mirtazapine, loop diuretics) in 26.2% of records.

Conclusion
The increased cardiovascular reporting of sacubitril/valsartan in the real world was largely predictable from pre-approval evidence, underlying disease and likely patients’ comorbidities. The unexpected reporting of sudden cardiac death occurred well before the complete development of positive electrical remodelling induced by sacubitril/valsartan, and calls for stringent clinical monitoring (to reduce the pro-arrhythmic burden related to co-medications), and further investigation on appropriate combination with other preventive measures.
Protocol: The Lacunar Intervention Trial 2 (LACI-2). A trial of two repurposed licenced drugs to prevent progression of cerebral small vessel disease
Authors: Wardlaw Joanna , Bath Philip M W , Doubal Fergus , Heye Anna , Sprigg Nikola , Woodhouse Lisa J , Blair Gordon , Appleton Jason , Cvoro Vera , England Timothy , Hassan Ahamad , John Werring David , Montgomery Alan ,   The LACI-2 Trial Investigators
Published: April 2020

Background Small vessel disease causes a quarter of ischaemic strokes (lacunar subtype), up to 45% of dementia either as vascular or mixed types, cognitive impairment and physical frailty. However, there is no specific treatment to prevent progression of small vessel disease. Aim We designed the LACunar Intervention Trial-2 (LACI-2) to test feasibility of a large trial testing cilostazol and/or isosorbide mononitrate (ISMN) by demonstrating adequate participant recruitment and retention in follow-up, drug tolerability, safety and confirm outcome event rates required to power a phase 3 trial. Methods and design LACI-2 is an investigator-initiated, prospective randomised open label blinded endpoint (PROBE) trial aiming to recruit 400 patients with prior lacunar syndrome due to a small subcortical infarct. We randomise participants to cilostazol v no cilostazol and ISMN or no ISMN, minimising on key prognostic factors. All patients receive guideline-based best medical therapy. Patients commence trial drug at low dose, increment to full dose over 2–4 weeks, continuing on full dose for a year. We follow-up participants to one year for symptoms, tablet compliance, safety, recurrent vascular events, cognition and functional outcomes, Trails B and brain MRI. LACI-2 is registered ISRCTN 14911850, EudraCT 2016–002277-35. Trial outcome: Primary outcome is feasibility of recruitment and compliance; secondary outcomes include safety (cerebral or systemic bleeding, falls, death), efficacy (recurrent cerebral and cardiac vascular events, cognition on TICS, Trails B) and tolerability. Summary LACI-2 will determine feasibility, tolerability and provide outcome rates to power a large phase 3 trial to prevent progression of cerebral small vessel disease.
Low-cost, easy-to-build noninvasive pressure support ventilator for under-resourced regions: open source hardware description, performance and feasibility testing
Authors: Garmendia Onintza , Rodríguez-Lazaro Miguel A. , Otero Jorge , Phan Phuong , Stoyanova Alexandrina , Dinh-Xuan Anh Tuan , Gozal David , Navajas Daniel , Montserrat Josep M. , Farré Ramon 
Published: April 2020

AimCurrent pricing of commercial mechanical ventilators in low-/middle-income countries (LMICs) markedly restricts their availability, and consequently a considerable number of patients with acute/chronic respiratory failure cannot be adequately treated. Our aim was to design and test an affordable and easy-to-build noninvasive bilevel pressure ventilator to allow a reduction in the serious shortage of ventilators in LMICs.MethodsThe ventilator was built using off-the-shelf materials availableviae-commerce and was based on a high-pressure blower, two pressure transducers and an Arduino Nano controller with a digital display (total retail cost <75 USD), with construction details provided open source for free replication. The ventilator was evaluated, and compared with a commercially available device (Lumis 150 ventilator; Resmed, San Diego, CA, USA): 1) in the bench setting using an actively breathing patient simulator mimicking a range of obstructive/restrictive diseases; and b) in 12 healthy volunteers wearing high airway resistance and thoracic/abdominal bands to mimic obstructive/restrictive patients.ResultsThe designed ventilator provided inspiratory/expiratory pressures up to 20/10 cmH2O, respectively, with no faulty triggering or cycling; both in the bench test and in volunteers. The breathing difficulty score rated (1–10 scale) by the loaded breathing subjects was significantly (p<0.005) decreased from 5.45±1.68 without support to 2.83±1.66 when using the prototype ventilator, which showed no difference with the commercial device (2.80±1.48; p=1.000).ConclusionThe low-cost, easy-to-build noninvasive ventilator performs similarly to a high-quality commercial device, with its open-source hardware description, which will allow for free replication and use in LMICs, facilitating application of this life-saving therapy to patients who otherwise could not be treated.