bluuebunny/crossref_metadata_2025_split huggingface dataset:
Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency—Features of CT and 18F-FDG Positron Emission Tomography/CT in Clinically Progressive Disease
Authors: Fraz Mai Sasaki Aanensen , Moe Natasha , Revheim Mona-Elisabeth , Stavrinou Maria L. , Durheim Michael T. , Nordøy Ingvild , Macpherson Magnhild Eide , Aukrust Pål , Jørgensen Silje Fjellgård , Aaløkken Trond Mogens , Fevang Børre 
Published: January 2021

Common variable immunodeficiency (CVID) is characterized not only by recurrent bacterial infections, but also autoimmune and inflammatory complications including interstitial lung disease (ILD), referred to as granulomatous-lymphocytic interstitial lung disease (GLILD). Some patients with GLILD have waxing and waning radiologic findings, but preserved pulmonary function, while others progress to end-stage respiratory failure. We reviewed 32 patients with radiological features of GLILD from our Norwegian cohort of CVID patients, including four patients with possible monogenic defects. Nineteen had deteriorating lung function over time, and 13 had stable lung function, as determined by pulmonary function testing of forced vital capacity (FVC), and diffusion capacity of carbon monoxide (DLCO). The overall co-existence of other non-infectious complications was high in our cohort, but the prevalence of these was similar in the two groups. Laboratory findings such as immunoglobulin levels and T- and B-cell subpopulations were also similar in the progressive and stable GLILD patients. Thoracic computer tomography (CT) scans were systematically evaluated and scored for radiologic features of GLILD in all pulmonary segments. Pathologic features were seen in all pulmonary segments, with traction bronchiectasis as the most prominent finding. Patients with progressive disease had significantly higher overall score of pathologic features compared to patients with stable disease, most notably traction bronchiectasis and interlobular septal thickening. 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/CT (PET/CT) was performed in 17 (11 with progressive and six with stable clinical disease) of the 32 patients and analyzed by quantitative evaluation. Patients with progressive disease had significantly higher mean standardized uptake value (SUVmean), metabolic lung volume (MLV) and total lung glycolysis (TLG) as compared to patients with stable disease. Nine patients had received treatment with rituximab for GLILD. There was significant improvement in pathologic features on CT-scans after treatment while there was a variable effect on FVC and DLCO.ConclusionPatients with progressive GLILD as defined by deteriorating pulmonary function had significantly greater pathology on pulmonary CT and FDG-PET CT scans as compared to patients with stable disease, with traction bronchiectasis and interlobular septal thickening as prominent features.
nab-Paclitaxel/Carboplatin in Vulnerable Populations With Advanced Non-Small Cell Lung Cancer: Pooled Analysis
Authors: Langer Corey J. , Gajra Ajeet , Gridelli Cesare , Konduri Kartik , Morgensztern Daniel , Spigel David , Talbot Denis , Thomas Michael , Weiss Jared , Pilot Richard , Bhore Rafia , Wolfsteiner Marianne , Ong Teng Jin , Socinski Mark 
Published: January 2021

IntroductionDespite improvements in the treatment of advanced non-small cell lung cancer (NSCLC), certain patient populations remain underrepresented in clinical trials. Many patients have benefited from platinum doublets, including nab-paclitaxel–based regimens, but there are patients with comorbidities who particularly require careful balancing of efficacy and safety. Clinical trial data are limited for patients who are elderly or have renal impairment, diabetes, or impaired performance status.MethodsTo better understand outcomes in these patient populations, we performed a pooled analysis using data from the ABOUND clinical trial program (ABOUND.SQM, ABOUND.PS2, ABOUND.70+) and the key phase III trial of nab-paclitaxel/carboplatin in advanced NSCLC. The populations included in this pooled analysis consisted of elderly patients (≥ 70 years) and patients with renal impairment (eGFR &lt; 60 ml/min/1.73 m2), diabetes, or poor performance status (ECOG PS 2).ResultsMedian progression-free survival (PFS) ranged from 4.1 months in patients with ECOG PS 2 (95% CI, 2.04–5.09 months) to 7.7 months in patients with diabetes (95% CI, 5.88–10.12 months). PFS for elderly patients and patients with renal impairment was 6.9 months each (95% CI, 6.01–7.98 months and 4.47–9.79 months, respectively). Median overall survival (OS) was 18.2 months (95% CI, 10.94–28.22 months), 17.4 months (95% CI, 14.59–20.14 months), and 16.1 months (95% CI, 14.09–18.50 months) in patients with renal impairment, patients with diabetes, and elderly patients, respectively. Patients with ECOG PS 2 exhibited the shortest median OS: 5.6 months (95% CI, 3.98–11.37 months). Overall response rates were 56.9%, 54.6%, 45.9%, and 29.4% in patients with diabetes, elderly patients, patients with renal impairment, and patients with ECOG PS 2, respectively. Most treatment-related adverse events were hematologic. The most common grade 3/4 hematologic adverse events in patients with renal impairment, elderly patients, patients with diabetes, and patients with poor performance status included neutropenia, anemia, and thrombocytopenia.ConclusionsAlthough survival data in patients with ECOG PS 2 were notably inferior to the other cohorts, our findings are consistent with those previously reported in the population-specific studies of the ABOUND trials and lend additional support for the use of nab-paclitaxel–based regimens in historically understudied and vulnerable populations.
A Simulated Dosimetric Study of Contribution to Radiotherapy Accuracy by Fractional Image Guidance Protocol of Halcyon System
Authors: Wang Haiyang , Huang Yuliang , Hu Qiaoqiao , Li Chenguang , Liu Hongjia , Wang Xuejuan , Li Weibo , Ma Wenjun , Pu Yichen , Du Yixiao , Wu Hao , Zhang Yibao 
Published: January 2021

PurposeFrequency of conventional kV-image guidance is sometimes sacrificed to reduce concomitant risk, leaving deviations of unguided fractions unknown. MV-imaging and treatment dose can be collectively optimized on Halcyon, where fractional MVCBCT provides complete anatomic records for course-wide dose reconstruction. By retrospective dose accumulation, this work simulated the impact of imaging frequency on patient treatment dose on the platform of Halcyon.MethodsFour hundred and sixteen MVCBCT image sets from 16 patients of various tumor sites treated with radiotherapy on Halcyon were retrospectively selected. After applying the image-guided couch shifts of the clinical records, deformable image registration was performed using Velocity software, to deform the planning CTs to the corresponding MVCBCTs, generating pseudo CTs representing the actual anatomies on the treatment day. Fractional treatment dose was reconstructed on pseudo CTs for accumulation, representing the actual patient dose (Ddaily). To simulate weekly image guidance, fractional dose was reconstructed and accumulated by incorporating 1 CBCT-guided corrections and 4 laser-guided setups of each week (Dweekly). Limited by partially imaged volumes and different organs-at-risk of various sites, only target dose-volume parameters were evaluated across all patients.ResultsGTV_D98%, CTV_D98%, PTV_D90%, PTV_D95%, PGTV_D90%, and PGTV_D95% were evaluated, where Dx% means the minimal dose received by x% volume. Pairwise comparisons were made between plan dose and Ddaily, Ddaily and Dweekly respectively. PGTV_D95% of accumulated Dweekly were significantly lower than those of accumulated Ddaily by up to 32.90% of prescription dose, suggesting that weekly-guidance may result in unacceptable under dose to the target. The broad distribution of fractional differences between Ddaily and Dweekly suggested unreliable patient positioning based on aligning surface markers to laser beams, as a popular approach broadly used on conventional Linac systems. Slight target under-dose was observed on daily reconstructed results compared with planned dose, which provided quantitative data to guide clinical decisions such as the necessity of adaptive radiotherapy.ConclusionFractional image guided radiotherapy on Halcyon provides more reliable treatment accuracy than using sacrificed imaging frequency, which also provides complete anatomic records for deformable dose reconstruction supporting more informed clinical decisions.
Correlation of HPV16 Gene Status and Gene Expression With Antibody Seropositivity and TIL Status in OPSCC
Authors: von Witzleben Adrian , Currall Eve , Wood Oliver , Chudley Lindsey , Akinyegun Oluyemisi , Thomas Jaya , Bendjama Kaïdre , Thomas Gareth J. , Friedmann Peter S. , King Emma V. , Laban Simon , Ottensmeier Christian H. 
Published: January 2021

IntroductionHuman papillomavirus 16 (HPV16) is the main cause of oropharyngeal squamous cell carcinoma (OPSCC). To date, the links between HPV16 gene expression and adaptive immune responses have not been investigated. We evaluated the correlation of HPV16 DNA, RNA transcripts and features of adaptive immune response by evaluating antibody isotypes against E2, E7 antigens and density of tumor-infiltrating lymphocytes (TIL).Material and MethodsFFPE-tissue from 27/77 p16-positive OPSCC patients was available. DNA and RNA were extracted and quantified using qPCR for all HPV16 genes. The TIL status was assessed. Immune responses against E2 and E7 were quantified by ELISA (IgG, IgA, and IgM; 77 serum samples pre-treatment, 36 matched post-treatment).ResultsAmounts of HPV16 genes were highly correlated at DNA and RNA levels. RNA co-expression of all genes was detected in 37% (7/19). E7 qPCR results were correlated with higher anti-E7 antibody (IgG, IgA) level in the blood. Patients with high anti-E2 IgG antibody (&gt;median) had better overall survival (p=0.0311); anti-E2 and anti-E7 IgA levels had no detectable effect. During the first 6 months after treatment, IgA but not IgG increased significantly, and &gt;6 months both antibody classes declined over time. Patients with immune cell-rich tumors had higher levels of circulating antibodies against HPV antigens.ConclusionWe describe an HPV16 qPCR assay to quantify genomic and transcriptomic expression and correlate this with serum antibody levels against HPV16 oncoproteins. Understanding DNA/RNA expression, relationship to the antibody response in patients regarding treatment and outcome offers an attractive tool to improve patient care.
Everolimus in Invasive Malignant Renal Epithelioid Angiomyolipoma
Authors: Guo Gang , Gu Liangyou , Zhang Xu 
Published: January 2021

BackgroundTo evaluate the efficacy and safety of everolimus, a mTOR inhibitor, on invasive malignant renal epithelioid angiomyolipoma (EAML).Materials and MethodsFrom Oct 2014 to May 2019, we collected data from seven patients with a definite (clinical and pathological) diagnosis of EAML received everolimus in our hospital. Targeted sequence capture array technique with next-generation of high throughput sequencing (NGS) were performed to detect mutations of TSC1/2 genes. All patients had received surgery and everolimus. The clinical efficacy and safety of the therapy were evaluated.ResultsMutations of TSC1 and TSC2 were detected in two and three patients though targeted sequence capture array technique with NGS, respectively. Among seven patients, three had missense mutations, one had nonsense mutation, and one had the large fragment deletion mutation. Five patients accompanied with tuberous sclerosis complex (TSC) were identified. All patients were administered 10mg everolimus once daily, the treatment duration lasted for 3 to 28 months. The objective response was assessed 3 months later, five partial response, two stable disease (SD), the mean greatest tumor diameter of all patients decreased from 9.6 to 5.2cm. Six patients stayed SD and one patient died during follow up. Patients accompanying with TSC had better responses to everolimus compared with non-TSC.ConclusionThe mTOR inhibitor can be an effective treatment for patients with invasive malignant renal EAML. Patients with TSC may benefit more from the therapy.
Low Pretreatment Albumin-to-Globulin Ratio Predicts Poor Prognosis in Gastric Cancer: Insight From a Meta-Analysis
Authors: Wei Chengzhi , Yu Zhu , Wang Gonghe , Zhou Yiming , Tian Lei 
Published: January 2021

BackgroundIn recent five years, reports regarding albumin-to-globulin ratio (AGR) and the survival of gastric cancer (GC) have emerged rapidly, yet their association remains controversial. This meta-analysis was aimed to provide an insight into the prognostic significance of pretreatment AGR in GC.MethodsPubMed, Embase, Cochrane library, Web of Science, WanFang, China National Knowledge Infrastructure (CNKI) and VIP databases were searched for relevant studies, from inception to September 30, 2020. Individual hazard ratios (HRs) with their 95% confidence intervals (CIs) were combined by Stata 12.0 software to evaluate the association between pretreatment AGR and overall survival (OS) and disease-free survival/progression-free survival (DFS/PFS).ResultsA total of 8,305 patients with GC from 12 studies were included for further analysis. Pooled analyses indicated that low AGR was closely associated with worse OS (HR = 1.531, 95% CI: 1.300–1.803, P &lt; 0.001) and worse DFS/PFS (HR = 2.008, 95% CI: 1.162–3.470, P = 0.012) in GC patients. Moreover, subgroup analyses demonstrated that the association between low AGR and worse OS remained constant despite variations in country, tumor stage, cut-off value, cut-off selection and treatment method.ConclusionAGR could act as an efficient prognostic indicator for GC, and that low pretreatment AGR predicts poor prognosis in GC.
Upregulation of Long Non-Coding RNA GCC2-AS1 Facilitates Malignant Phenotypes and Correlated With Unfavorable Prognosis for Lung Adenocarcinoma
Authors: Yu Fengqiang , Liang Mingqiang , Wu Weidong , Huang Yu , Zheng Jiantao , Zheng Bin , Chen Chun 
Published: January 2021

BackgroundThe role played by long noncoding RNA GCC2-AS1 in primary malignant tumors remains poorly understood. This study aimed to determine the expression levels and evaluate the clinical significance and biological effects of GCC2-AS1 in lung adenocarcinoma (LUAD).MethodsWe used data obtained from tissue samples and the TCGA database to determine the levels of GCC2-AS1 expression LUAD patients, and the prognostic value of those levels. Functional experiments were performed to investigate the effect of GCC2-AS1 on LUAD cells. Genes that were differentially expressed in GCC2-AS1-low and -high groups were analyzed by an enrichment analysis. Additionally, a nomogram model was created and subgroup analyses were performed to further determine the prognostic value of GCC2-AS1 in LUAD.ResultsGCC2-AS1 expression was significantly upregulated in lung adenocarcinoma tissues as compared with normal tissues. Depletion of GCC2-AS1 inhibited the proliferation and invasion of LUAD cells in vitro. An elevated level of GCC2-AS1 was strongly correlated with shorter overall survival time and was identified as an independent prognostic marker for LUAD patients. Enrichment analyses conducted using GO, KEGG, and GSEA databases were performed to identify biological pathways that might involve GCC2-AS1. Several subgroups were found to have a significant prognostic value for patients in the GCC2-AS1-low and -high groups.ConclusionsOur findings suggest that GCC2-AS1 can serve as a diagnostic and prognostic biomarker for LUAD patients.
Minimally Invasive Management of Bladder Stones in Children
Authors: Esposito Ciro , Autorino Giuseppe , Masieri Lorenzo , Castagnetti Marco , Del Conte Fulvia , Coppola Vincenzo , Cerulo Mariapina , Crocetto Felice , Escolino Maria 
Published: January 2021

Background: Bladder stones (BS) are rare in children. Minimally invasive surgery (MIS) seems to be nowadays the procedure of choice to treat pediatric patients with BS. This study aimed to analyze retrospectively our experience with percutaneous cystolithotomy, endourological treatment with Holmium laser and robotic cystolithotomy in children with BS.Methods: We retrospectively analyzed the data of 13 children (eight boys and five girls) with BS who were treated at our centers between July 2013 and July 2020. The patients received three different MIS procedures for stones removal: five underwent robotic cystolithotomy, five underwent endourological treatment and three received percutaneous cystolithotomy (PCCL). We preferentially adopted endourological approach for stones &lt;10 mm, percutaneous approach between 2014 and 2016 and robotic approach since 2016 for larger stones.Results: Mean patients' age at the time of diagnosis was 13 years (range 5–18). Ten/13 patients (76.9%) had primary BS and 3/13 patients (23.1%) had secondary BS. Mean stone size was 18.8 mm (range 7–50). In all cases the stones were removed successfully. One Clavien II post-operative complication occurred following PCCL (33.3%). All the procedures were completed without conversions. Operative time ranged between 40 and 90 min (mean 66) with no significant difference between the three methods (p = 0.8). Indwelling bladder catheter duration was significantly longer after PCCL (mean 72 h) compared with robotic and endourological approaches (mean 15.6 h) (p = 0.001). Hospitalization was significantly longer after PCCL (mean 7.6 days) compared with the other two approaches (mean 4.7 days) (p = 0.001). The endourological approach was the most cost-effective method compared with the other two approaches (p = 0.001).Conclusions: Minimally invasive management of bladder stones in children was safe and effective. Endourological management was the most cost-effective method, allowing a shorter hospital stay compared with the other procedures but it was mainly indicated for smaller stones with a diameter &lt; 10 mm. Based upon our preliminary results, robotic surgery seemed to be a feasible treatment option for BS larger than 15–20 mm. It allowed to remove the big stones without crushing them with a safe and easy closure of the bladder wall thanks to the easy suturing provided by the Robot technology.
Unraveling the Contribution of Fluid Therapy to the Development of Augmented Renal Clearance in a Piglet Model
Authors: Dhondt Laura , Croubels Siska , De Paepe Peter , Goethals Klara , De Cock Pieter , Devreese Mathias 
Published: January 2021

Augmented renal clearance (ARC) observed in the critically ill pediatric population has received an increased attention over the last years due to its major impact on the disposition and pharmacokinetics of mainly renally excreted drugs. Apart from an important inflammatory trigger, fluid administration has been suggested to contribute to the development of ARC. Therefore, the primary objective of this study was to evaluate the effect of continuous intravenous fluid administration on renal function using a conventional piglet animal model and to quantify the impact of fluid administration on the pharmacokinetics of renally excreted drugs. At baseline, twenty-four piglets (12 treatment/12 control; 7 weeks old, all ♂) received the marker drugs iohexol (64.7 mg/kg body weight (BW)) and para-aminohippuric acid (10 mg/kg BW) to quantify glomerular filtration rate and effective renal plasma flow, respectively. In addition, the hydrophilic antibiotic amikacin (7.5 mg/kg BW) was administered. Following this baseline measurement, the treatment group received fluid therapy as a constant rate infusion of 0.9% saline at 6 mL/kg/h over 36 h. After 24 h of fluid administration, the marker drugs and amikacin were administered again. When comparing both groups, a significant effect of fluid administration on the total body clearances of iohexol (p= 0.032) and amikacin (p= 0.0014) was observed. Clearances of iohexol and amikacin increased with on average 15 and 14%, although large interindividual variability was observed. This led to decreased systemic exposure to amikacin, which was manifested as decrease in area under the plasma concentration-time curve from time 0 h to infinity from 34,807 to 30,804 ng.h/mL. These results suggest that fluid therapy is a key factor involved in the development of ARC and should be taken into account when administering mainly renally excreted drugs. However, further research is necessary to confirm these results in children.
Cost-Effectiveness of Genomic Test-Directed Olaparib for Metastatic Castration-Resistant Prostate Cancer
Authors: Su Dan , Wu Bin , Shi Lizheng 
Published: January 2021

Purpose: The effectiveness of poly (adenosine diphosphate–ribose) polymerase (PARP) inhibitor olaparib for metastatic castration-resistant prostate cancer (MCRPC) with multiple loss-of-function alterations in genes that are involved in DNA repair has been demonstrated. We aimed to evaluate the cost-effectiveness of genomic test-directed olaparib on MCRPC from the US payer perspective.Methods: A partitioned survival model was adopted to project the disease course of MCRPC had at least one gene alteration in BRCA1, BRCA2 and ATM (Scenario A) and has alterations in any of all 15 prespecified genes (Scenario B) after next-generation sequencing test. The efficacy and toxicity data were gathered from the PROfound trial. Clinical probabilities related to survival were estimated from the reported survival probabilities in each PROfound group. Cost and health preference data were derived from the literature. The incremental cost-effectiveness ratio (ICER) was measured. Subgroup analysis and sensitivity analysis were performed for exploring the model uncertainties.Results: Olaparib yielded an additional 0.063 and 0.068 of quality-adjusted life year (QALY) with the augmented cost of $7,382 and saved the cost of $ 1,980 compared to standard care in scenario A and B, respectively, which yielded an ICER of $116,903/QALY and a cost-saving option. The lower weekly cost related to olaparib treatment led to the dominant findings in scenario B. The varied results between scenario A and B could be partly explained by different the number need to screen for identifying eligible patients who could be administered with olaparib, which sharply augmented the costs of the olaparib arm in scenario A. Subgroup analysis and sensitivity analysis revealed the results were generally robust in both of two scenarios.Conclusion: The genomic test-directed olaparib is a preferred option compared with standard care strategy for men with MCRPC who had any of all 15 prespecified genes.